bluuebunny/crossref_metadata_2025 huggingface dataset:
How I manage patients with atypical microcytic anaemia
Authors: Camaschella Clara
Published: October 2012

Microcytic hypochromic anaemias are a result of defective iron handling by erythroblasts that decrease the haemoglobin content per red cell. Recent advances in our knowledge of iron metabolism and its homeostasis have led to the discovery of novel inherited anaemias that need to be distinguished from common iron deficiency or other causes of microcytosis. These atypical microcytic anaemias can be classified as: (i) defects of intestinal iron absorption (ii) disorders of the transferrin receptor cycle that impair erythroblast iron uptake (iii) defects of mitochondrial iron utilization for haem or iron sulphur cluster synthesis and (iv) defects of iron recycling. A careful patient history and evaluation of laboratory tests may enable these rare conditions to be distinguished from the more common iron deficiency anaemia. Molecular studies allow distinction of the different types, a prerequisite for differentiated therapy.
Social and emotional aspects of learning (SEAL) for secondary schools: implementation difficulties and their implications for school‐based mental health promotion
Authors: Lendrum Ann , Humphrey Neil , Wigelsworth Michael
Published: October 2012

Background

Increasing concern about adolescent mental health problems has resulted in schools being identified as central sites for their prevention (PsycInfo; ERIC 2000–2012). In this context, SEAL for secondary schools was launched in 2007.

Method

The implementation strand of the national evaluation of secondary SEAL comprised longitudinal case studies of nine schools and used multiple methods and data sources, including interviews, observations and document review.

Results

Implementation was variable, both within and between schools; barriers were identified at programme, teacher and school levels.

Conclusions

Implementation issues identified have implications for SEAL and school‐based mental health prevention and promotion interventions more generally.
An unfolded variant of the major peanut allergen Ara h 2 with decreased anaphylactic potential
Authors: Starkl P. , Felix F. , Krishnamurthy D. , Stremnitzer C. , Roth‐Walter F. , Prickett S. R. , Voskamp A. L. , Willensdorfer A. , Szalai K. , Weichselbaumer M. , O'Hehir R. E. , Jensen‐Jarolim E.
Published: October 2012

Background

Peanut allergy causes severe type 1 hypersensitivity reactions and conventional immunotherapy against peanut allergy is associated with a high risk of anaphylaxis.

Objective

Our current study reports proof of concept experiments on the safety of a stably denatured variant of the major peanut allergen Ara h 2 for immunotherapy. We determined the impact of structure loss of Ara h 2 on its IgE binding and basophil degranulation capacity, T cell reactivity as well as anaphylactic potential.

Methods

The secondary structure of untreated and reduced/alkylated Ara h 2 variants was determined by circular dichroism spectroscopy. We addressed human patient IgE binding to Ara h 2 by ELISA and Western blot experiments. RBL‐SX38 cells were used to test the degranulation induced by untreated and reduced/alkylated Ara h 2. We assessed the anaphylactic potential of Ara h 2 variants by challenge of sensitized BALB/c mice. T cell reactivity was investigated using human Ara h 2‐specific T cell lines and splenocytes isolated from sensitized mice.

Results

Reduction/alkylation of Ara h 2 caused a decrease in IgE binding capacity, basophil degranulation and anaphylactic potential in vivo. However, the human T cell response to reduced/alkylated and untreated Ara h 2 was comparable. Mouse splenocytes showed higher metabolic activity upon stimulation with reduced/alkylated Ara h 2 and released similar IL‐4, IL‐13 and IFNγ levels upon treatment with either Ara h 2 variant.

Conclusions and Clinical Relevance

Reduced/alkylated Ara h 2 might be a safer alternative than native Ara h 2 for immunotherapeutic treatment of peanut allergic patients.
House dust mite sublingual immunotherapy: a double‐blind, placebo‐controlled study in elderly patients with allergic rhinitis
Authors: Bozek A. , Ignasiak B. , Filipowska B. , Jarzab J.
Published: October 2012

Background

Immunotherapy in elderly patients is controversial, and there is still no evidence supporting this treatment's safety and efficacy in this population. This study was performed to evaluate the safety and efficacy of specific sublingual immunotherapy for house dust mite (HDM) allergens in patients over 60 years of age with allergic rhinitis and a confirmed allergy to HDM.

Objective

This study sought to assess nasal symptoms during HDM season, reduce medication use and monitor for adverse reactions during immunotherapy.

Methods

One hundred and eleven 60‐ to 75‐year‐old patients with allergic rhinitis and a confirmed Dermatophagoides pteronyssinus and Dermatophagoides farinae allergy were included in the study. The patients were individually randomized to active or placebo groups using a double‐blind method (NCTO01605760 ClinicalTrials.gov). A total of 51 subjects in the sublingual allergen‐specific immunotherapy (SLIT) group (Staloral 300R, Stallergenes, France) and 57 subjects in the placebo group were monitored for 3 years.

Results

Forty‐seven patients completed 3 years of SLIT, and 48 subjects finished the placebo treatment in the same time period. The total nasal symptom score decreased by 44% in the active group and 6% in the placebo group after 3 years of SLIT. This difference was only significant in the active group (P < 0.05). At the end of therapy, the total medication score of the active group decreased significantly by a maximum of 51% (P < 0.05), whereas the total medication score of the placebo control group showed an insignificant decrease (P = 0.56). There were no systemic adverse reactions during the study.

Conclusions & Clinical Relevance

Sublingual allergen‐specific immunotherapy in elderly patients with a HDM allergy to D. pteronyssinus and D. farinae generated a significant clinical improvement in the active group compared with the placebo group, particularly during the heating season. This therapy was well tolerated.
CCMG statement on gene patents
Authors: Richer J , Nelson TN , Evans J , Armstrong L , Lauzon J , McGillivray B
Published: October 2012

Richer J, Nelson TN, Evans J, Armstrong L, Lauzon J, McGillivray B. CCMG statement on gene patents.
Increased cardiovascular risk after pre‐eclampsia in women with dysglycaemia
Authors: McDonald S. D. , Yusuf S. , Walsh M. W. , Lonn E. , Teo K. , Anand S. S. , Pogue J. , Islam S. , Devereaux P. J. , Gerstein H. C.
Published: October 2012

Aims

Compared with women with uncomplicated pregnancies, women with a history of pre‐eclampsia have two to five times the risk of cardiovascular disease. It is not known whether this risk is related to albuminuria, a known cardiovascular risk factor that is part of the definition of pre‐eclampsia and that often persists after delivery. Our objective was to determine if the high risk of cardiovascular disease in women with pre‐eclampsia is accounted for by known cardiovascular risk factors including albuminuria.

Methods

We performed a cross‐sectional analysis of 4080 dysglycaemic women enrolled in a large randomized controlled trial who provided an obstetric history and had at least one delivery. Blood pressure, height, weight, waist circumference and hip circumference were measured. An oral glucose tolerance test, lipids, an electrocardiogram and an albumin/creatinine ratio from a first morning urine sample were obtained.

Results

There were 3613 women with no history of pre‐eclampsia during their pregnancies, 108 with severe pre‐eclampsia and 359 with non‐severe pre‐eclampsia. Women with a history of severe pre‐eclampsia had higher rates of previous cardiovascular disease than women with non‐severe pre‐eclampsia or women without pre‐eclampsia (87, 72 and 72%, P = 0.0019). The high risk of previous cardiovascular disease in women with a history of severe pre‐eclampsia (odds ratio 2.67, 95% CI 1.52–4.70) persisted after adjustment for albuminuria (odds ratio 2.74, 95% CI 1.55–4.83) and also after adjusting for other covariates including albuminuria (odds ratio 3.03, 95% CI 1.69–5.44).

Conclusion

Even after accounting for cardiovascular risk factors including albuminuria, a history of severe pre‐eclampsia is independently associated with a threefold higher risk of cardiovascular disease.
Mating failures as a consequence of sexual selection on females
Authors: Gwynne Darryl T. , Lorch Patrick D.
Published: October 2012

Multiple mating by individuals successful in sexual competition results in other individuals failing to mate. This leads to sexual selection within a sex, typically the males. However, more species are coming to light in which females are subject to sexual selection. We review the contexts for and nature of sexual selection on females in several insect species where female mating failures have been noted. We then examine evidence of mating failures in two groups of insects, empidid flies (Diptera) and tettigoniid Orthoptera (katydids), in which sexual selection is expected to be relatively stronger on females. Using data from the field, we show for two species of katydids that, as predicted, there are mating failures by females in populations in which the direction of sexual selection appears to be reversed, but not in populations where sexual selection appears to be stronger on males.
Modelling female mating success during mass trapping and natural competitive attraction of searching males or females
Authors: Byers John A.
Published: October 2012

Simulation models of insects encountering sex pheromone with or without mass trapping in which the searching sex is either male (moths and many insect species) or female (some true bugs, beetles, and flies) were developed. The searching sex moved as a correlated random walk, while the opposite sex remained stationary (calling) and released an attractive sex pheromone. The searching sex was caught when encountering a pheromone‐baited trap, and females mated when encountering a male. An encounter with pheromone was defined by the searcher's interception of a circle termed the effective attraction radius (EARc). Parameters of movement (speed and duration), initial numbers of calling sex and searching sex, number of traps, area, and EARc of traps and calling sex were varied individually to evaluate effects on the percentage of females mating. In the natural condition without traps, female mating success in both models was identical. Increasing the EARc of the calling sex caused diminishing increases in female mating success, suggesting that evolution of larger pheromone release and EARc is limited by increasing costs (production/sensitivity) relative to diminishing increases and benefits of mating encounters. With mass trapping, increasing the EARc of traps or density of traps caused similar declines in female mating in both models, but the female‐searching model predicted slightly lower mating success than the male‐searching model. Increasing the EARc of calling insects or the initial density of insects caused similar increases in female mating in both models, but again the female‐searching model had slightly lower mating success than the male‐searching model. The models have implications for mating lek formation and for understanding the variables affecting the success of mass trapping programs for insect pests with either male or female sex pheromones.
Sex ratio dynamics of Gonatocerus ashmeadi, a parasitoid of the glassy‐winged sharpshooter in California
Authors: Lytle John , Kapranas A. , Morgan D.J.W. , Nichols J.M. , Morse J.G.
Published: October 2012

We examined whether Gonatocerus ashmeadi Girault (Hymenoptera: Mymaridae), a quasi‐gregarious egg parasitoid of Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae), produces precise sex ratios under a field setting. Under laboratory conditions, previous studies have shown that G. ashmeadi exhibits strongly female‐biased sex ratios with low variance in the number of males produced per host. Field‐collected G. ashmeadi tend to produce much less female‐biased sex ratios with high variance in male numbers. We found significant positive effects of proportion parasitism and host density on sex ratio. Proportion parasitism also had a positive effect on sex ratio variance. The findings of this study are discussed in the context of theoretical predictions.
Latitudinally structured variation in the temperature dependence of damselfly growth rates
Authors: Nilsson‐Örtman Viktor , Stoks Robby , De Block Marjan , Johansson Helena , Johansson Frank
Published: October 2012

The Metabolic Theory of Ecology predicts that the slope of the rate–temperature relationship, E, remains consistent across traits and organisms, acting as a major determinant of large‐scale ecological patterns. Although E has recently been shown to vary systematically, we have a poor understanding of its ecological significance. To address this question, we conducted a common‐garden experiment involving six damselfly species differing in distribution, estimating E at the level of full‐sib families. Each species was sampled throughout its latitudinal range, allowing us to characterise variation in E along a latitudinal gradient spanning 3600 km. We show that E differs among populations and increases with latitude. E was right‐skewness across species, but this was largely an artefact of the latitudinal trend. Increased seasonality towards higher latitude may contribute to the latitudinal trend in E. We conclude that E should be seen as a trait involved in local adaptation.
Optimal temperature for malaria transmission is dramatically lower than previously predicted
Authors: Mordecai Erin A. , Paaijmans Krijn P. , Johnson Leah R. , Balzer Christian , Ben‐Horin Tal , de Moor Emily , McNally Amy , Pawar Samraat , Ryan Sadie J. , Smith Thomas C. , Lafferty Kevin D.
Published: October 2012

The ecology of mosquito vectors and malaria parasites affect the incidence, seasonal transmission and geographical range of malaria. Most malaria models to date assume constant or linear responses of mosquito and parasite life‐history traits to temperature, predicting optimal transmission at 31 °C. These models are at odds with field observations of transmission dating back nearly a century. We build a model with more realistic ecological assumptions about the thermal physiology of insects. Our model, which includes empirically derived nonlinear thermal responses, predicts optimal malaria transmission at 25 °C (6 °C lower than previous models). Moreover, the model predicts that transmission decreases dramatically at temperatures > 28 °C, altering predictions about how climate change will affect malaria. A large data set on malaria transmission risk in Africa validates both the 25 °C optimum and the decline above 28 °C. Using these more accurate nonlinear thermal‐response models will aid in understanding the effects of current and future temperature regimes on disease transmission.
Lactoferrin and its hydrolysate bind directly to the oleate‐activated form of the lipolysis stimulated lipoprotein receptor
Authors: Ahmad Nazir , Girardet Jean‐Michel , Akbar Samina , Lanhers Marie‐Claire , Paris Cédric , Yen Frances T. , Corbier Catherine
Published: October 2012

The hepatic removal of triglyceride‐rich chylomicrons during the postprandial phase represents an important step towards determining the bioavailability of dietary lipids amongst the peripheral tissues. Indeed, elevated postprandial lipemia is often associated with obesity and increased risk of coronary heart disease. The milk protein, lactoferrin, has been shown to inhibit hepatic chylomicron remnant removal by the liver, resulting in increased postprandial lipemia. Despite numerous studies on potential targets for lactoferrin, the molecular mechanisms underlying the effect of lactoferrin remain unclear. We recently demonstrated that the lipolysis stimulated lipoprotein receptor (LSR) contributes to the removal of triglyceride‐rich lipoproteins during the postprandial phase. Here, we report that while lactoferrin does not have any significant effect on LSR protein levels in mouse Hepa1–6 cells, this protein colocalizes with LSR in cells but only in the presence of oleate, which is needed to obtain LSR in its active form as lipoprotein receptor. Ligand blotting using purified LSR revealed that lactoferrin binds directly to the receptor in the presence of oleate and prevents the binding of triglyceride‐rich lipoproteins. Both C‐ and N‐lobes of lactoferrin as well as a mixture of peptides derived from its hydrolysis retained the ability to bind LSR in its active form. We propose then that the elevated postprandial lipemia observed upon lactoferrin treatment in vivo is mediated in part by its direct interaction with free fatty acid activated LSR, thus preventing clearance of chylomicrons and their remnants through the LSR pathway.

Structured digital abstract

• Lsr and Lsr bind by comigration in gel electrophoresis (View interaction)

• Lsr binds to Lf by filter binding (View interaction)

• Lf and Lsr colocalize by fluorescence microscopy (View interaction)

• Lsr physically interacts with VLDL by filter binding (View interaction)
Increased amounts of von Willebrand factor are bound to microparticles after infusion of desmopressin
Authors: Trummer A. , Haarmeijer B. , Werwitzke S. , Wermes C. , Ganser A. , Budde U. , Tiede A.
Published: October 2012

Effects of desmopressin (DDAVP) in platelet disorders and primary haemostasis cannot be attributed solely to the increase in FVIII/VWF (von Willebrand factor), as VWF/FVIII concentrates have no effect in these circumstances. Microparticles (MP) can support haemostasis by expression of phospholipids, tissue factor and VWF on their surface. We hypothesized that significant amounts of VWF are bound to MP after DDAVP administration and that consequently depletion of MP should influence VWF:Ag and VWF:RCo plasma levels. Platelet‐poor plasma was either obtained well from healthy controls or before and after DDAVP administration from patients with von Willebrand's disease (type 1 or possible type 1) or patients with other bleeding disorders as controls. Concentrations of MP and VWF parameters were determined before and after MP depletion by different methods (magnetic bead selection, plasma microfiltration, ultracentrifugation). Platelet MP and VWF‐bearing MP were significantly increased after DDAVP. MP depletion by magnetic bead selection led to a significant reduction in VWF:Ag (−18.0%) and VWF:RCo (−27.7%) plasma levels without changes in VWF multimer composition. As results were similar for DDAVP control subjects, the amount of VWF bound to circulating microparticles was significantly higher after DDAVP administration compared with healthy controls (reduction −11.7%). DDAVP leads to a release of microparticles and increases the amount of VWF bound to microparticles which might explain the clinical efficacy of DDAVP in platelet disorders.
Quadriceps strength, inter‐extremity difference (IED) and joint status in adult persons with severe haemophilia in different age stages
Authors: Brunner A. , Stäuber F. , Göhler S. , Czepa D. , Krüger S. , Wendel M. , Seuser A. , Hilberg T.
Published: October 2012

Quadriceps weakness seems to be a hallmark in adult persons with severe haemophilia (PWH). The purpose of this study was to compare PWH and non‐haemophilic controls in different age stages with reference to joint status and quadriceps strength. Further aims were to examine the extent of strength‐specific inter‐extremity‐difference (IED) and the prevalence of abnormal IED (AIED). A total of 106 adults with severe haemophilia (H) and 80 controls (C) had undergone an orthopaedic examination for classification of knee and ankle status using the WFH score. Quadriceps strength was evaluated unilaterally as well as bilaterally with a knee extensor device. Each group was divided into four age‐related subgroups (HA/CA: 18–29, HB/CB: 30–39, HC/CC: 40–49, HD/CD: 50–70; in years). H presented a worse knee and ankle status than C indicated by higher WFH scores (P < 0.01). Regarding the age‐matched subgroups only HB showed higher knee scores than CB (P < 0.05). The ankles were clinically more affected in HB‐HD compared with those in age‐matched controls (P < 0.05). H showed lower quadriceps strength than C (P < 0.05). In addition, all subgroups of H presented lower strength (HA: 10–17, HB: 19–23, HC: 35–36, HD: 53–61; in%, P < 0.05). IED was higher in H than in C [H: 12.0 (5.3/32.2) vs. C: 7.1 (2.9/10.9); Median (quartiles) in%, P < 0.001] and increased with age in H. We discovered an AIED in 35% of H. These findings highlight the importance for the early implementation of preventive and rehabilitative muscle training programmes in the comprehensive treatment of PWH.
Information needs of public health practitioners: a review of the literature
Authors: Ford Jennifer , Korjonen Helena
Published: October 2012

Objective

To review published literature covering the information needs of public health practitioners and papers highlighting gaps and potential solutions in order to summarise what is already known about this population and models tested to support them.

Methods

The search strategy included bibliographic databases LISTA, LISA, PubMed and Web of Knowledge. The results of this literature review were used to create two tables displaying published literature.

Findings

The literature highlighted that some research has taken place into different public health subgroups with consistent findings. Gaps in information provision have also been identified by looking at the information services provided.

Conclusion

There is a need for further research into information needs in subgroups of public health practitioners as this group is diverse, has different needs and needs varying information. Models of informatics that can support public health must be developed and published so that the public health information community can share experiences and solutions and begin to build an evidence‐base to produce superior information systems for the goal of a healthier society.
Quantitative trait loci for resistance to Haemonchus contortus artificial challenge in Red Maasai and Dorper sheep of East Africa
Authors: Marshall K. , Mugambi J. M. , Nagda S. , Sonstegard T. S. , Van Tassell C. P. , Baker R. L. , Gibson J. P.
Published: October 2012

A genome‐wide scan was performed to detect quantitative trait loci (QTL) for resistance to the gastrointestinal nematode Haemonchus contortus in a double backcross population of Red Maasai and Dorper sheep. The mapping population comprised six sire families, with 1026 lambs in total. The lambs were artificially challenged with H. contortus at about 6.5 months of age, and nine phenotypes were measured: fecal egg count, packed cell volume decline, two weight traits and five worm traits. A subset of the population (342 lambs) was selectively genotyped for 172 microsatellite loci covering 25 of the 26 autosomes. QTL mapping was performed for models which assumed that the QTL alleles were either fixed or segregating within each breed, combined with models with only an additive QTL effect fitted or both additive and dominance QTL effects fitted. Overall, QTL significant at the 1% chromosome‐wide level were identified for 22 combinations of trait and chromosome. Of particular interest are a region of chromosome 26 with putative QTL for all nine traits and a region of chromosome 2 with putative QTL for three traits. Favorable QTL alleles for disease resistance originated in both the Red Maasai and Dorper breeds, were not always fixed within breed and had significant dominance effects in some cases. We anticipate that this study, in combination with follow‐up work and other relevant studies, will help elucidate the biology of disease resistance.
Economic burden of acute pesticide poisoning in South Korea
Authors: Choi Yeongchull , Kim Younhee , Ko Yousun , Cha Eun S. , Kim Jaeyoung , Lee Won J.
Published: October 2012

Objectives  To investigate the magnitude and characteristics of the economic burden resulting from acute pesticide poisoning (APP) in South Korea.

Methods  The total costs of APP from a societal perspective were estimated by summing the direct medical and non‐medical costs together with the indirect costs. Direct medical costs for patients assigned a disease code of pesticide poisoning were extracted from the Korean National Health Insurance Reimbursement Data. Direct non‐medical costs were estimated using the average transportation and caregiving costs from the Korea Health Panel Survey. Indirect costs, incurred by pre‐mature deaths and work loss, were obtained using 2009 Life Tables for Korea and other relevant literature.

Results  In 2009, a total of 11 453 patients were treated for APP and 1311 died, corresponding to an incidence of 23.1 per 100 000 population and a mortality rate of 2.6 per 100 000 population in South Korea. The total costs of APP were estimated at approximately US$ 150 million, 0.3% of the costs of total diseases. Costs due to pre‐mature mortality accounted for 90.6% of the total costs, whereas the contribution of direct medical costs was relatively small.

Conclusion  Costs from APP demonstrate a unique characteristic of a large proportion of the indirect costs originating from pre‐mature mortality. This finding suggests policy implications for restrictions on lethal pesticides and safe storage to reduce fatality and cost due to APP.
Factors affecting seed germination and emergence of Gomphrena perennis
Authors: ACOSTA J M , BENTIVEGNA D J , PANIGO E S , DELLAFERRERA I , PERRETA M G
Published: October 2012

Controlled growth chamber experiments were conducted to determine factors affecting seed germination and emergence of the troublesome weed Gomphrena perennis. The objective of this research was to examine the effects of temperature, light, moist chilling, osmotic potential, dry storage and depth of seed burial on G. perennis germination and emergence. The optimum temperature for germination was around 15–20°C. Seeds showed germination rates above 90% under 20/10 and 25/15°C temperature regimes. The minimum exposure to light needed to stimulate germination was 1 min. However, the light requirement was reduced after a long storage period. Furthermore, germination was high (>90%) in all moist‐chilling treatments tested. Germination was highly sensitive to increasing osmotic stress. The highest germination percentage (94%) was achieved at 0 MPa, and decreasing osmotic potential from 0 to −0.3 MPa reduced germination to 11%. The highest seedling emergence occurred for seeds placed from 0 to 1 cm deep, and no seedlings emerged from a 5‐cm burial depth. Gomphrena perennis has a suitable environment in a no‐till soybean field, where seeds remaining on the surface have the required temperature, light and depth needed for germination.
MicroRNA‐155 is a predictive marker for survival in patients with clear cell renal cell carcinoma
Authors: Shinmei Shunsuke , Sakamoto Naoya , Goto Keisuke , Sentani Kazuhiro , Anami Katsuhiro , Hayashi Tetsutaro , Teishima Jun , Matsubara Akio , Oue Naohide , Kitadai Yasuhiko , Yasui Wataru
Published: October 2012

Objectives

To investigate the clinical significance of micro‐ribonucleic acid‐155 in clear cell renal cell carcinoma, in particular focusing on the association of expression levels of micro‐ribonucleic acid‐155 with clinicopathological factors, cancer‐specific survival and therapeutic outcomes in clear cell renal cell carcinoma patients.

Methods

Quantitative reverse transcription polymerase chain reaction of micro‐ribonucleic acid‐155 was carried out on 137 clear cell renal cell carcinoma cases, containing 77 matched pairs of clear cell renal cell carcinoma and normal adjacent kidney tissues from the same patients.

Results

Significant overexpression of micro‐ribonucleic acid‐155 was found in clear cell renal cell carcinoma compared with normal kidney tissue. Expression of micro‐ribonucleic acid‐155 was not associated with prognosis in all stage groups. However, in 43 patients with stage III and IV clear cell renal cell carcinoma, low expression levels of micro‐ribonucleic acid‐155 correlated with a poor prognosis. Regarding cancer‐free survival of 26 patients with stage III and IV clear cell renal cell carcinoma who received curative resection and cancer‐specific survival of 31 patients who received postoperative therapy with interferon‐α after radical nephrectomy, low expression levels of micro‐ribonucleic acid‐155 correlated with poor clinical outcomes in these two groups.

Conclusions

Low expression of micro‐ribonucleic acid‐155 represents a valuable marker of poor clinical outcomes in patients with stage III and IV clear cell renal cell carcinoma.
Single versus multiple doses of antibiotic prophylaxis in limb fracture surgery
Authors: Morrison Stewart , White Nathan , Asadollahi Saeed , Lade Justin
Published: October 2012

Background

There is no consensus with regard to optimum prophylactic antibiotic regimen in orthopaedic fracture surgery.

Objective

A systematic review and meta‐analysis were performed to determine if multiple‐dose perioperative antibiotic prophylaxis is more effective than a single preoperative dose in the prevention of surgical wound infection in patients undergoing operative treatment of low‐energy closed fractures.

Data resources

Medline, Medline in Process and other non‐indexed citations, Embase, Cochrane database of systematic reviews and conference proceedings were searched.

Review methods

Studies were included if they were randomized or quasi‐randomized trials comparing the results of a single antibiotic prophylaxis versus multiple doses of the same antibiotic in patients undergoing surgical fixation of closed fractures.

Results

Four studies were found to meet the searching criteria. The mean score for quality assessment of these studies was 16 (8–24 points). Only two out of four studies had detailed analysable data and therefore were included in the final analysis. 921 patients were pooled using a random‐effects model. Compared to multiple‐dose prophylaxis, administration of a single preoperative dose demonstrated no significant difference regarding the overall surgical site infection rate (risk ratio (RR) = 0.3, 95% confidence interval (CI): 0.07–1.25). Multiple‐dose antibiotic prophylaxis is marginally more effective than single dose in reducing the incidence of deep surgical wound infection (risk ratio: 0.13, 95% CI: 0.02 to 0.99).

Conclusion

There is lack of definite evidence that multiple‐dose antibiotic prophylaxis is superior to single preoperative dose in low‐energy closed fracture surgery.
Agent‐Based Modeling of Behavioral Housing Recovery Following Disasters
Authors: Nejat Ali , Damnjanovic Ivan
Published: October 2012

Abstract: In the context of postdisaster recovery, housing reestablishment has been known to be a critical factor as it has ripple effects on the overall timing of recovery. This reestablishment is based on the dynamic behavior of homeowners in the aftermath of disasters. Therefore, to have an effective disaster planning it is essential that policy makers recognize this dynamic aspect of disaster recovery to effectively enhance the recovery process. This entails a thorough understanding of how homeowners react to recovery signals. One of the main sources of these signals comes from neighbors’ activities including reconstruction and relocation. The goal of this research is to develop a preliminary temporospatial agent‐based model that can account for homeowners’ dynamic interactions with their neighbors. These interactions are based on homeowners’ equilibrium strategy derived from a game‐theoretical approach, which is modeled in a multiagent system framework. The results highlight the significant impact of discount factor and the accuracy of the signals on homeowners’ reconstruction decisions as well as formation clusters by reconstructed properties.
Marital fertility and wealth during the fertility transition: ruralFrance, 1750–1850
Authors: Cummins Neil
Published: October 2012

It has been long established that the demographic transition began in eighteenth‐centuryFrance, yet there is no consensus on exactly why fertility declined. This analysis links fertility life histories to wealth at death data for four rural villages inFrance, 1750–1850. For the first time, the wealth–fertility relationship during the onset of theFrench fertility decline can be analysed. Where fertility is declining, wealth is a powerful predictor of smaller family size. This article argues that fertility decline inFrance was a result of changing levels of economic inequality, associated with the 1789Revolution. In cross‐section, the data support this hypothesis: where fertility is declining, economic inequality is lower than where fertility is high.
Natalizumab may reduce cognitive changes and brain atrophy rate in relapsing–remitting multiple sclerosis: a prospective,  non‐randomized pilot study
Authors: Portaccio E. , Stromillo M. L. , Goretti B. , Hakiki B. , Giorgio A. , Rossi F. , De Leucio A. , De Stefano N. , Amato M. P.
Published: October 2012

Background and purpose

The development of treatment strategies for cognitive impairment in multiple sclerosis (MS) is still in its infancy. The objective of this prospective, non‐randomized, pilot study was to assess the possible efficacy of treatment with natalizumab in comparison with interferon beta (IFNB) in a group of relapsing–remitting patients with MS.

Methods

We included 12 patients treated with natalizumab and 14 with IFNB. At baseline and at follow‐up, cognitive functioning was assessed through Rao's Brief Repeatable Battery. All the patients underwent brain MR study with the assessment of T2 lesion volumes, neocortical volume, normalized brain volume and percentage brain volume change (PBVC). Evolution of cognitive performance was assessed using available normative data for the Italian population. Treatment comparisons were assessed through the Mann–Whitney U‐test, anova for repeated measures and linear multivariate regression analyses.

Results

After a mean follow‐up of 1.5 years, the mean number of neuropsychological tests with a deteriorating performance was significantly lower in patients treated with natalizumab (0.7 ± 0.7 vs. 1.7 ± 1.4; P = 0.031). Likewise, PBVC was significantly lower in natalizumab‐treated subjects than that observed in patients treated with IFNB (−0.51% ± 0.47% vs. −1.18% ± 0.98%; P = 0.050).

Concluion

Our results suggest a potential beneficial effect of natalizumab therapy on cognitive functioning in MS, possibly mediated by a reduction of brain atrophy.
Suppression of Ku70/80 or Lig4 leads to decreased stable transformation and enhanced homologous recombination in rice
Authors: Nishizawa‐Yokoi Ayako , Nonaka Satoko , Saika Hiroaki , Kwon Yong‐Ik , Osakabe Keishi , Toki Seiichi
Published: October 2012

Evidence for the involvement of the nonhomologous end joining (NHEJ) pathway in Agrobacterium‐mediated transferred DNA (T‐DNA) integration into the genome of the model plant Arabidopsis remains inconclusive.

Having established a rapid and highly efficient Agrobacterium‐mediated transformation system in rice (Oryza sativa) using scutellum‐derived calli, we examined here the involvement of the NHEJ pathway in Agrobacterium‐mediated stable transformation in rice. Rice calli from OsKu70, OsKu80 and OsLig4 knockdown (KD) plants were infected with Agrobacterium harboring a sensitive emerald luciferase (LUC) reporter construct to evaluate stable expression and a green fluorescent protein (GFP) construct to monitor transient expression of T‐DNA.

Transient expression was not suppressed, but stable expression was reduced significantly, in KD plants. Furthermore, KD‐Ku70 and KD‐Lig4 calli exhibited an increase in the frequency of homologous recombination (HR) compared with control calli. In addition, suppression of OsKu70, OsKu80 and OsLig4 induced the expression of HR‐related genes on treatment with DNA‐damaging agents.

Our findings suggest strongly that NHEJ is involved in Agrobacterium‐mediated stable transformation in rice, and that there is a competitive and complementary relationship between the NHEJ and HR pathways for DNA double‐strand break repair in rice.
Biogeographical patterns and determinants of invasion by forest pathogens in Europe
Authors: Santini A. , Ghelardini L. , De Pace C. , Desprez‐Loustau M. L. , Capretti P. , Chandelier A. , Cech T. , Chira D. , Diamandis S. , Gaitniekis T. , Hantula J. , Holdenrieder O. , Jankovsky L. , Jung T. , Jurc D. , Kirisits T. , Kunca A. , Lygis V. , Malecka M. , Marcais B. , Schmitz S. , Schumacher J. , Solheim H. , Solla A. , Szabò I. , Tsopelas P. , Vannini A. , Vettraino A. M. , Webber J. , Woodward S. , Stenlid J.
Published: October 2012

A large database of invasive forest pathogens (IFPs) was developed to investigate the patterns and determinants of invasion in Europe.

Detailed taxonomic and biological information on the invasive species was combined with country‐specific data on land use, climate, and the time since invasion to identify the determinants of invasiveness, and to differentiate the class of environments which share territorial and climate features associated with a susceptibility to invasion.

IFPs increased exponentially in the last four decades. Until 1919, IFPs already present moved across Europe. Then, new IFPs were introduced mainly from North America, and recently from Asia. Hybrid pathogens also appeared. Countries with a wider range of environments, higher human impact or international trade hosted more IFPs. Rainfall influenced the diffusion rates. Environmental conditions of the new and original ranges and systematic and ecological attributes affected invasiveness.

Further spread of established IFPs is expected in countries that have experienced commercial isolation in the recent past. Densely populated countries with high environmental diversity may be the weakest links in attempts to prevent new arrivals. Tight coordination of actions against new arrivals is needed. Eradication seems impossible, and prevention seems the only reliable measure, although this will be difficult in the face of global mobility.
The role of MRI as a prognostic tool in ischemic stroke
Authors: Arsava Ethem Murat
Published: October 2012

Magnetic resonance imaging (MRI) is an invaluable tool used in the diagnosis of ischemic stroke. Ongoing technological advances in MRI technology and advent of new imaging sequences has now made it possible to use MRI as a prognostic tool both in the acute and chronic stages of cerebral ischemia. This review summarizes the role of MRI in estimating final tissue outcome, specifically by providing information on severity and location of ischemic insult, cerebral blood flow dynamics, vascular status, and cerebral reserve. All of these predictions can then be used to make projections regarding clinical outcome, and can be refined by other prognostic models to estimate recovery and risk of further ischemic events. These algorithms, in the end, can ultimately help the clinician in tailoring therapies on an individual basis and optimize the risk–benefit ratio of therapeutic approaches used in the acute and chronic stages of ischemic stroke. The implementation of such prognostic algorithms to clinical imaging workstations and calculation of all the possible projections within minutes after completion of imaging are likely to become an integral part of clinical practice in the near future.
Vascular neuroprotection via TrkB‐ and Akt‐dependent cell survival signaling
Authors: Guo Shuzhen , Som Angel T. , Waeber Christian , Lo Eng H.
Published: October 2012

The cerebral endothelium can be a vital source of signaling factors such as brain‐derived neurotrophic factor that defends the neuronal parenchyma against stress and injury. But the underlying mechanisms remain to be fully defined. Here, we use cell models to ask how vascular neuroprotection is sustained. Human brain endothelial cells were grown in culture, and conditioned media were transferred to primary rat cortical neurons. Brain endothelial cell‐conditioned media activated neuronal Akt signaling and protected neurons against hypoxia and oxygen‐glucose deprivation. Blockade of Akt phosphorylation with the PI3‐kinase inhibitor LY294002 negated this vascular neuroprotective effect. Upstream of Akt signaling, the brain‐derived neurotrophic factor receptor TrkB (neurotrophic tyrosine kinase receptor, type 2) was involved because depletion with TrkB/Fc eliminated the ability of endothelial‐conditioned media to protect neurons against hypoxia. Downstream of Akt signaling, activation of GSK‐3β (glycogen synthase kinase 3 beta), caspase 9, caspase 3 and Bad pathways were detected. Taken together, these findings suggest that the molecular basis for vascular neuroprotection involves TrkB‐Akt signaling that ameliorates neuronal apoptosis. Further investigation of these mechanisms may reveal new approaches for augmenting endogenous vascular neuroprotection in stroke, brain injury, and neurodegeneration.
Poly‐ICLC preconditioning protects the blood–brain barrier against ischemic injury in vitro through type I interferon signaling
Authors: Gesuete Raffaella , Packard Amy E. B. , Vartanian Keri B. , Conrad Valerie K. , Stevens Susan L. , Bahjat Frances R. , Yang Tao , Stenzel‐Poore Mary P.
Published: October 2012

Preconditioning with a low dose of harmful stimulus prior to injury induces tolerance to a subsequent ischemic challenge resulting in neuroprotection against stroke. Experimental models of preconditioning primarily focus on neurons as the cellular target of cerebral protection, while less attention has been paid to the cerebrovascular compartment, whose role in the pathogenesis of ischemic brain injury is crucial. We have shown that preconditioning with polyinosinic polycytidylic acid (poly‐ICLC) protects against cerebral ischemic damage. To delineate the mechanism of poly‐ICLC protection, we investigated whether poly‐ICLC preconditioning preserves the function of the blood–brain barrier (BBB) in response to ischemic injury. Using an in vitro BBB model, we found that poly‐ICLC treatment prior to exposure to oxygen‐glucose deprivation maintained the paracellular and transcellular transport across the endothelium and attenuated the drop in transendothelial electric resistance. We found that poly‐ICLC treatment induced interferon (IFN) β mRNA expression in astrocytes and microglia and that type I IFN signaling in brain microvascular endothelial cells was required for protection. Importantly, this implicates a potential mechanism underlying neuroprotection in our in vivo experimental stroke model, where type I IFN signaling is required for poly‐ICLC‐induced neuroprotection against ischemic injury. In conclusion, we are the first to show that preconditioning with poly‐ICLC attenuates ischemia‐induced BBB dysfunction. This mechanism is likely an important feature of poly‐ICLC‐mediated neuroprotection and highlights the therapeutic potential of targeting BBB signaling pathways to protect the brain against stroke.
Suppression of the inflammatory response by diphenyleneiodonium after transient focal cerebral ischemia
Authors: Nagel Simon , Hadley Gina , Pfleger Karin , Grond‐Ginsbach Caesar , Buchan Alastair Mitchell , Wagner Simone , Papadakis Michalis
Published: October 2012

Diphenyleneiodonium (DPI), a NADPH oxidase inhibitor, reduces production of reactive oxygen species (ROS) and confers neuroprotection to focal cerebral ischemia. Our objective was to investigate whether the neuroprotective action of DPI extends to averting the immune response. DPI‐induced gene changes were analyzed by microarray analysis from rat brains subjected to 90 min of middle cerebral artery occlusion, treated with NaCl (ischemia), dimethylsulfoxide (DMSO), or DMSO and DPI (DPI), and reperfused for 48 h. The genomic expression profile was compared between groups using ingenuity pathway analysis at the pathway and network level. DPI selectively up‐regulated 23 genes and down‐regulated 75 genes more than twofold compared with both DMSO and ischemia. It significantly suppressed inducible nitric oxide synthase signaling and increased the expression of methionine adenosyltransferasesynthetase 2A and adenosylmethionine decarboxylase 1 genes, which are involved in increasing the production of the antioxidant glutathione. The most significantly affected gene network comprised genes implicated in the inflammatory response with an expression change indicating an overall suppression. Both integrin‐ and interleukin‐17A‐signaling pathways were also significantly associated and suppressed. In conclusion, the neuroprotective effects of DPI are mediated not only by suppressing ischemia‐triggered oxidative stress but also by limiting leukocyte migration and infiltration.
Post‐ischemic vascular adhesion protein‐1 inhibition provides neuroprotection in a rat temporary middle cerebral artery occlusion model
Authors: Watcharotayangul Jittiya , Mao Lizhen , Xu Haoliang , Vetri Francesco , Baughman Verna L. , Paisansathan Chanannait , Pelligrino Dale A.
Published: October 2012

We examined the neuroprotective efficacy associated with post‐ischemic vascular adhesion protein‐1 (VAP‐1) blockade in rats subjected to transient (1 h) middle cerebral artery occlusion (MCAo). We compared saline‐treated control rats to rats treated with a highly selective VAP‐1 inhibitor, LJP‐1586 [Z‐3‐fluoro‐2‐(4‐methoxybenzyl) allylamine hydrochloride]. Initial intraperitoneal LJP‐1586 (or saline control) treatments were delayed until 6 h or 12 h reperfusion. At 72‐h reperfusion, LJP‐1586‐treated rats displayed 51% and 33% smaller infarct volumes, relative to their controls, in the 6‐ and 12‐h treatment groups, respectively. However, only in the 6‐h treatment group was the infarct volume reduction significant (p < 0.05). On the other hand, we observed significantly improved neurologic functions in both 6‐ and 12‐h treatment groups, versus their matched controls (p < 0.05). Also, the effect of 6‐h LJP‐1586 treatment on post‐ischemic leukocyte trafficking in pial venules overlying the ischemic cortex was evaluated using intravital microscopy. These experiments revealed that: 1) LJP‐1586 did not affect intravascular leukocyte (largely neutrophil) adhesion, at least out to 12‐h reperfusion; and 2) the onset of neutrophil extravasation, which occurred between 6–8‐h reperfusion in control rats, was prevented by LJP‐1586‐treatment. In conclusion, in rats subjected to transient MCAo, selective VAP‐1 pharmacologic blockade provided neuroprotection, with a prolonged therapeutic window of 6–12‐h reperfusion.
SCIENTIFIC INVESTIGATION OF FAIENCE FRAGMENTS ATTRIBUTED TO THE TOWN MOSAIC AT KNOSSOS*
Authors: SPATARO M. , MEEKS N. , MEEK A. S. , SHAPLAND A. J.
Published: October 2012

We analysed a faience fragment from Bristol Museum and Art Gallery, to determine whether it belonged to the Town Mosaic, excavated at Knossos. Three Town Mosaic fragments from the Ashmolean Museum, Oxford were also examined. The objects were analysed using non‐destructive variable‐pressure scanning electron microscopy with energy‐dispersive X‐ray spectrometry. The Bristol object's composition and microstructures are similar to those of the Town Mosaic samples. Our results are also comparable to those from polished samples of Minoan faience (Tite et al. ), showing that VP SEM–EDX gives reliable results without invasive sampling. Silicaceous, copper‐rich microspheres were identified for the first time in two of the Ashmolean objects.