bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals
Authors: CHAFFIN M. K. , FAJT V. , MARTENS R. J. , ARNOLD C. E. , COHEN N. D. , O’CONOR M. , TAYLOR R. J. , BERNSTEIN L. R.
Published: March 2010

Chaffin, M. K., Fajt, V., Martens, R. J., Arnold, C. E., Cohen, N. D., O’Conor, M., Taylor, R. J., Bernstein, L. R. Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals.J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01150.x.

Gallium is a trivalent semi‐metal with anti‐microbial effects because of its incorporation into crucial iron‐dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM againstRhodococcus equipneumonia in foals, we developed a methylcellulose formulation of GaM (GaM‐MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and another six foals received 40 mg/kg of GaM‐MCF orally. Serial serum samples were collected and serum gallium concentrations were determined using inductively coupled plasma mass spectroscopy. Gallium was rapidly absorbed (Tmaxof 4 h), and a meanCmaxof 0.90 or 1.8 μg/mL was achieved in foals receiving 20 or 40 mg/kg respectively. Marked variability existed inCmaxamong foals: only half of the foals receiving 20 mg/kg attained serum concentrations of >0.7 μg/mL, a level suggested to be therapeutic againstR. equiby previous studies. Mean elimination half‐life was 32.8 or 32.4 h for foals receiving 20 or 40 mg/kg respectively. The results of this study suggest that at least 30 mg/kg orally every 24 h should be considered in future pharmacodynamic and efficacy studies.
Modelling the effect of light intensity and duration of exposure on seed germination of Phalaris minor and Poa annua
Authors: OHADI S , RAHIMIAN MASHHADI H , TAVAKKOL‐AFSHARI R , BEHESHTIAN MESGARAN M
Published: March 2010

Ohadi S, Rahimian Mashhadi H, Tavakkol‐Afshari R & Beheshtian Mesgaran M (2010). Modelling the effect of light intensity and duration of exposure on seed germination of Phalaris minor and Poa annua. Weed Research50, 209–217.

Photocontrol of weeds requires a better understanding of the effect of light on seed germination. Therefore, the effect of light intensity and exposure duration was tested on seed germination of two winter annual weeds, Phalaris minor and Poa annua. Photo‐sensitised seeds of both species were subjected to four light intensities, including 130, 250, 500 and 1000 μmol m−2 s−1, each at six exposure durations of 0.1, 1, 10, 100, 1000 and 10 000 s. Light stimulated the germination of both weeds. A modelling approach was used to describe the relationship between light intensity and exposure duration with the germination of weed seeds. A combination of logistic and Gaussian models provided good fits to P. minor percentage germination data, whereas in the case of P. annua, the incorporation of logistic and quadratic models better described the relationships. According to the model, increasing light intensity from 0 (full darkness) to 1000 μmol m−2 s−1 increased the germination of P. minor and P. annua from 28% to 57% and from 0% to 35% respectively. The seed germination of both weed species increased with exposure duration, but declined at duration periods longer than 100 s in P. minor or 1000 s in P. annua. The model predicted a trade‐off between light intensity and light duration for both weeds. That is, a high light intensity irradiated for a short time exposure may result in the same percentage germination as one with a low light intensity, but at longer exposure duration.
Outcome of hematopoietic stem cell transplant in children with congenital heart disease*
Authors: Guinan Eva C. , Hewett Elizabeth K. , Domaney Nicholas M. , Margossian Renee
Published: March 2010

Guinan EC, Hewett EK, Domaney NM, Margossian R. Outcome of hematopoietic stem cell transplant in children with congenital heart disease. Pediatr Transplantation 2011: 15:75–80. © 2010 John Wiley & Sons A/S.

Abstract:  CHD is the most commonly occurring birth defect in the United States. Improvements in supportive care for CHD result in increasing numbers of survivors who may develop benign or malignant conditions for which HSCT is indicated. However, the ability of individuals with CHD to tolerate HSCT is unknown. Retrospective medical record review of 1031 patients who underwent HSCT at Children’s Hospital Boston between 1989 and 2007 identified those with CHD. Ten patients with CHD that required repair or palliation before or after HSCT, or with CHD that would have required repair had they survived HSCT, were identified. These patients tolerated chemotherapy and/or radiation therapy uneventfully. Although half experienced febrile neutropenia and two had documented bacteremia, no endocarditis was observed. During the first 100 days post‐HSCT, combined rates of grade 3, 4, and 5 cardiac, renal, and pulmonary toxicity for these patients were 10%, 0%, and 10%, respectively. In children with underlying CHD, there was no clinical evidence of impaired ability to tolerate febrile neutropenia, volume challenge, or other regimen‐related toxicities that might require significant cardiac reserve. CHD alone should not be considered an absolute contraindication for indicated HSCT.
Hamsters Use Predator Odors as Indirect Cues of Predation Risk
Authors: McPhee M. Elsbeth , Segal Andrea , Johnston Robert E.
Published: March 2010

Golden hamsters (Mesocricetus auratus) use olfactory cues to assess traits of conspecifics such as kinship, individual identity, and reproductive status. The environment, however, is full of a wide variety of other olfactory information such as signals emitted by some of the hamster’s primary predators. Given this, we hypothesized that hamsters use odors from predators as an indirect sign of increased predation risk in the environment. In addition, based on data that show that wild hamsters are diurnal while laboratory hamsters are nocturnal, we hypothesized that if golden hamsters did respond to the predator odors, perceived predator risk might influence daily activity patterns in hamsters. We tested male and female hamsters over 5 d with scent gland secretion from domestic ferrets (Mustela putorius furo) and compared their behavior to that observed when they were exposed to a clean arena. In response to the predator odor, subjects significantly decreased the amount of time active outside of their burrow, returned to their burrow more quickly, and spent less time near the predator odor than the clean control stimulus. These results strongly support our hypothesis that hamsters, like other species of small mammals, avoid predator odors. The results did not, however, support our second hypothesis that exposure to predator odors during the dark phase of the light cycle would elicit a switch to a more diurnal pattern of activity. More work is needed to understand how environmental cues and internal mechanisms interact to shape activity patterns.
Female Control of Offspring Sex Ratios Based on Male Attractiveness in the Guppy
Authors: Sato Aya , Karino Kenji
Published: March 2010

The sex allocation hypothesis predicts that females manipulate the offspring sex ratios according to mate attractiveness. Although there is increasing evidence to support this prediction, it is possible that paternal effects may often obscure the relationship between female control of offspring sex ratios and male attractiveness. In the present study, we examined whether females played a primary role in the manipulation their offspring sex ratios based on male attractiveness, in the guppy Poecilia reticulata, a live‐bearing fish. We excluded the paternal effects by controlling the relative sexual attractiveness of the male by presenting them to the females along with a more attractive or less attractive stimulus male. The test male was perceived to be relatively more attractive by females when it was presented along with a less attractive stimulus male, or vice versa. Subsequently, test male was mated in two different roles (relatively more and less attractive) with two females. If females were responsible for offspring sex ratio manipulation, the sex ratio of the brood would be altered on the basis of the relative attractiveness of the test male. On the other hand, if males play a primary role in offspring sex ratio manipulation, the sex ratios would not differ with the relative attractiveness of the test male. We found that females gave birth to more male‐biased broods when they mated with test males in the attractive role than when they mated with males in the less attractive role. This finding suggests that females are responsible for the manipulation of offspring sex ratios based on the attractiveness of their mates.
Home Range Analysis in the Study of Spatial Organization on the Comb in the Paper Wasp Polistes Dominulus
Authors: Baracchi David , Zaccaroni Marco , Cervo Rita , Turillazzi Stefano
Published: March 2010

In order to understand how the apparent freedom of individual movements can concur with social order in a colony, we investigated spatial relationships between foundresses, workers and immature brood in a paper wasp. This is the first time an ecological analytical approach (home range analysis) has been employed to describe small scale spatial use in a social context. In this study, home range was not used in its strictly ecological sense, but rather applied to the comb. Our results show that the positions individual wasps assumed on Polistes dominulus combs are spatially structured. Workers and foundresses do not occupy the comb in random distribution, but rather follow predictable spatial patterns. Each active wasp has its own spatial fidelity area, at least over a 1 d observation period, spending the majority of its time within a very small area averaging approx. 12% of the comb but occasionally it may cover an area of up to 50% of the comb surface. Dominant females occupied a significantly smaller area that either subordinate foundresses or workers. Areas patrolled by workers varied in shape and size, with no relation to time spent on the comb, wasp density or position of immature brood. All the wasps clumped around the dominant female, who proved to be the only individual affected by cell content. Nevertheless, although the wasps tended to clump together, average superimposition rates among nest‐mates was very low (higher in workers than foundresses), suggesting that the wasps limit each other’s individual spaces.
Comparison of the gene expression profiles of resistant and non‐resistant Japanese black pine inoculated with pine wood nematode using a modified LongSAGE technique
Authors: Nose M. , Shiraishi S.
Published: March 2010

The Japanese black pine (Pinus thunbergii) is highly susceptible to pine wilt disease caused by the pine wood nematode (PWN; Bursaphelenchus xylophilus). To cope with this disease, researchers and tree breeders selected PWN‐resistant individuals in a previous breeding program. In an attempt to understand the mechanisms of resistance in the Japanese black pine, we created four LongSAGE (serial analysis of gene expression) libraries. A total of 20 818 tags were studied, including 5194 tags from a PWN inoculated resistant pine, 5218 a non‐inoculated resistant pine, 5194 an inoculated non‐resistant pine, and 5212 a non‐inoculated non‐resistant pine. The analysis of the libraries indicated that 14 tag species were significantly up‐regulated (e.g., pathogenesis‐related proteins 2 and 4, osmotin, lipoxygenase, and chalcone synthase), and nine were down‐regulated (eukaryotic translation initiation factor SUI1, translationally controlled tumor protein, and xyloglucan endotransglycosylase) by the PWN inoculation in both the resistant and non‐resistant pines. On the other hand, 38 tag species were significantly expressed at a higher level only in the resistant pine (catalase, dienelactone hydrolase family protein) and 25 were expressed at a higher level in the non‐resistant pine (pathogenesis‐related proteins 1, 2, and 3, and leucoanthocyanidin dioxygenase). These differentially expressed genes are presumed to reflect some of the differences between the resistant and non‐resistant pines. Our results provide valuable information on the complex responses induced in the resistant and non‐resistant pine trees in response to PWN invasion.
A Universal Index of Uterine Discharge Symptoms from Calving to 6 Weeks Postpartum
Authors: Gorzecka J , Friggens NC , Ridder C , Callesen H
Published: March 2010

Contents

In this paper, a new uterine discharge index (D‐index) was created and tested. It was based on a principal component analysis (PCA) of clinical findings of classical uterine discharge symptoms and rectal temperature during the postpartum period of dairy cattle. The PCA analysis revealed how uterine discharge features relate to each other and how they cluster together possibly representing different degrees of uterine inflammation. The D‐index was the result of the multivariate PCA‐analysis, and the D‐index gives a continuous value between 0 and 10. It was demonstrated that the same scale, i.e. the D‐index, can be used without any adjustment from 1 to 6 weeks post‐calving. It is valid for any type of uterine discharge without defining the type of infection or differentiating between infection and contamination. The D‐index was tested using the uterine involution data. Uterine involution was significantly delayed in the high‐D‐index group of cows. Similarly, in the test with all cows, involution was progressively delayed and the rate of involution of the pregnant horn was slowed down with the increase of the D‐index values. It is concluded that the D‐index can be a new practical, universal, tool for improved management of dairy cows in the postpartum period under commercial conditions.
Association of IRF5 gene polymorphisms and lupus nephritis in a Chinese population
Authors: QIN LIANXIANG , LV JICHENG , ZHOU XUJIE , HOU PING , YANG HAIZHEN , ZHANG HONG
Published: March 2010

Aim:  Recently, several studies have provided convincing evidence that polymorphisms in the interferon regulatory factor 5 (IRF5) gene were significantly associated with systemic lupus erythematosus (SLE) in several populations. The aim of this study was to investigate the association between IRF5 and lupus nephritis in a Chinese cohort and analyze the relationship between the rs2004640 genotype and the clinical and pathological phenotypes of lupus nephritis.

Methods:  The IRF5 rs2004640 polymorphism in a cohort of 190 Chinese lupus nephritis patients and 182 healthy Chinese blood donors was analyzed. The polymorphism examined was genotyped using the TaqMan assay.

Results:  The IRF5 rs2004640 T allele was associated with the susceptibility to lupus nephritis (rs2004640 T, 41.6% in patients, 30.8% in healthy controls, odds ratio = 1.6, P = 0.002). It was also found that the Chinese population had a much lower minor allele frequency of rs2004640 than Western populations studied to date. In the present cohort, 30.8% individuals in the control group had the detrimental T allele, compared to frequencies in the range of 44–56% that exist in Western populations. No association was found between IRF5 rs2004640 and pathology, or clinical presentation of lupus nephritis in the Chinese cohort examined.

Conclusion:  The results suggested that the rs2004640 T allele was associated with susceptibility to lupus nephritis and that the IRF5 polymorphism analyzed did not seem to be implicated in the pathology and clinical manifestation of lupus nephritis in the Chinese population.
Review: Metformin: Potential benefits and use in chronic kidney disease
Authors: PILMORE HELEN L
Published: March 2010

Diabetes mellitus is the commonest cause of end‐stage renal failure in both Australia and New Zealand. In addition, the burden of diabetes is prominent in those with chronic kidney disease who have not yet reached the requirement for renal replacement therapy. While diabetes is associated with a higher incidence of mortality and morbidity in all populations studied with kidney disease, little is known about optimal treatment strategies for hyperglycaemia and the effects of glycaemic treatment in this large group of patients. Metformin is recommended as the drug of first choice in patients diagnosed with type 2 diabetes in the USA, Europe and Australia. There are potential survival benefits associated with the use of metformin in additional to recent studies suggesting benefits in respect to cardiovascular outcomes and metabolic parameters. The use of metformin has been limited in patients with renal disease because of the perceived risk of lactic acidosis; however, it is likely that use of this drug would be beneficial in many with chronic kidney disease. Thus the potential benefits and harms of metformin are outlined in this review with suggestions for its clinical use in those with kidney disease.
Pre‐zygotic parental environment modulates seed longevity
Authors: KOCHANEK JITKA , BUCKLEY YVONNE M. , PROBERT ROBIN J. , ADKINS STEVE W. , STEADMAN KATHRYN J.
Published: March 2010

The potential for the pre‐zygotic plant growth environment to play a role in determining seed longevity was investigated for a species that inhabits arid to semi‐arid Australia. Seed longevity is particularly important for wild populations in fluctuating environments because the longer a seed‐lot is able to survive in the soil seed bank the more likely it is to buffer the population from unpredictable environments. Thus Wahlenbergia tumidifructa plants received wet or dry soil moisture within a warm or cool glasshouse until flowering. Seeds subsequently produced by flowers that opened on the day that plants were moved to a common environment were collected at maturity and longevity assessed by controlled ageing at 60% relative humidity and 45°C. Mean seed longevity was similar for seeds produced by plants that grew in warm‐wet, warm‐dry and cool‐dry conditions (P50 of about 20 days), but extended for plants in cool‐wet conditions (P50 = 41.7 days). Cool temperatures resulted in seeds with a wider distribution of lifespans (σ = 20 days) than warm conditions (σ = 12 days); the large σ caused the extended P50 for cool‐wet plants, but not cool‐dry as a result of a concomitant reduction in initial seed germination (Ki). After moving to the common environment, all plants generated new vegetative material, which went on to produce seeds with similar longevity (P50 approx. 20 days) irrespective of original environment. Visible phenotypic responses of the parent to environmental conditions correlated with longevity and quality parameters of the progeny seeds, suggesting that a parental effect modified seed longevity. Our study provides novel empirical data showing that environmental conditions expected under climate change scenarios may potentially cause seed longevity to decline for a species that inhabits arid to semi‐arid Australia. These negative impacts on population buffering may weaken the storage effect mechanism of species coexistence in fluctuating environments.
Attitudes of physicians and public to pharmaceutical industry ‘gifts’
Authors: Macneill P. U. , Kerridge I. H. , Newby D. , Stokes B. J. , Doran E. , Henry D. A.
Published: March 2010

Background: Few studies have reported the attitudes of both individual doctors and members of the public toward the appropriateness of ‘gifts’ from pharmaceutical companies.

Aims: To investigate the attitudes of both doctors and members of the public toward the appropriateness of receiving particular ‘gifts’ from pharmaceutical companies, and to consider whether public acceptability is a suitable criterion for determining the ethical appropriateness of ‘gifts’.

Methods: A survey questionnaire of medical specialists in Australia and a survey questionnaire of members of the public itemised 23 ‘gifts’ (valued between AU$10 and AU$2500) and asked whether or not each was appropriate.

Results: Both medical specialists and members of the public believe certain ‘gifts’ from pharmaceutical companies are appropriate but not others. There was a tendency for members of the public to be more permissive than medical specialists.

Conclusion: Although some professional guidelines place importance on the attitudes of the general public to ‘gift’ giving, and other guidelines give importance to a need for transparency and public accountability, we question whether public acceptability is a suitable criterion for determining the ethical appropriateness of ‘gifts’. We suggest that more weight be given to the need for independence of clinical decision making, with empirical evidence indicating that even small ‘gifts’ can bias clinicians’ judgments, and to important values such as the primacy of patient welfare, autonomy and social justice. We conclude that it is time to eliminate giving and receiving of promotional items between the pharmaceutical industry and members of health professions.
Escherichia coli K‐12 possesses multiple cryptic but functional chaperone–usher fimbriae with distinct surface specificities
Authors: Korea Charalampia‐Georgia , Badouraly Réana , Prevost Marie‐Christine , Ghigo Jean‐Marc , Beloin Christophe
Published: March 2010

Commensal and pathogenic Escherichia coli adherence to host and environmental surfaces is mediated by a variety of adhesins. Although extensively studied as a model bacterium, 34% of the genes in the E. coli K‐12 genome have no known function. We hypothesized that some of them may correspond to functional adhesins. We characterized E. coli K‐12 ycb, ybg, yfc, yad, yra, sfm and yeh operons, which display sequence and organizational homologies to type 1 fimbriae exported by the chaperone/usher pathway. We showed that, although these operons are poorly expressed under laboratory conditions, six of them are nevertheless functional when expressed, and promote adhesion to abiotic and/or epithelial cell surfaces. While the studied fimbriae display different binding specificities, we obtained evidence of synergy/interference with other adhesins such as Ag43 or type 1 fimbriae. We showed that their expression is under the negative control of H‐NS and, except for yad, subjected to cAMP receptor protein‐mediated activation and carbon catabolite repression. These results therefore demonstrate that ycb, yfc, yad, yra, sfm and yeh operons encode cryptic but functional fimbriae adhesins whose expression following environmental modifications could contribute to E. coli's ability to adhere to and colonize a wide diversity of surfaces in its various ecological niches.
Activity, abundance and diversity of nitrifying archaea and bacteria in the central California Current
Authors: Santoro Alyson E. , Casciotti Karen L. , Francis Christopher A.
Published: March 2010

A combination of stable isotope and molecular biological approaches was used to determine the activity, abundance and diversity of nitrifying organisms in the central California Current. Using 15NH4+ incubations, nitrification was detectable in the upper water column down to 500 m; maximal rates were observed just below the euphotic zone. Crenarchaeal and betaproteobacterial ammonia monooxygenase subunit A genes (amoA), and 16S ribosomal RNA (rRNA) genes of Marine Group I Crenarchaeota and a putative nitrite‐oxidizing genus, Nitrospina, were quantified using quantitative PCR. Crenarchaeal amoA abundance ranged from three to six genes ml−1 in oligotrophic surface waters to > 8.7 × 104 genes ml−1 just below the core of the California Current at 200 m depth. Bacterial amoA abundance was lower than archaeal amoA and ranged from below detection levels to 400 genes ml−1. Nitrification rates were not directly correlated to bacterial or archaeal amoA abundance. Archaeal amoA and Marine Group I crenarchaeal 16S rRNA gene abundances were correlated with Nitrospina 16S rRNA gene abundance at all stations, indicating that similar factors may control the distribution of these two groups. Putatively shallow water‐associated archaeal amoA types (‘Cluster A’) decreased in relative abundance with depth, while a deep water‐associated amoA type (‘Cluster B’) increased with depth. Although some Cluster B amoA sequences were found in surface waters, expressed amoA gene sequences were predominantly from Cluster A. Cluster B amoA transcripts were detected between 100 and 500 m depths, suggesting an active role in ammonia oxidation in the mesopelagic. Expression of marine Nitrosospira‐like bacterial amoA genes was detected throughout the euphotic zone down to 200 m. Natural abundance stable isotope ratios (δ15N and δ18O) in nitrate (NO3‐) and nitrous oxide (N2O) were used to evaluate the importance of nitrification over longer time scales. Using an isotope mass balance model, we calculate that nitrification could produce between 0.45 and 2.93 µmol m−2 day−1 N2O in the central California Current, or approximately 1.5–4 times the local N2O flux from deep water.
Rosiglitazone and pioglitazone increase fracture risk in women and men with type 2 diabetes
Authors: Aubert R. E. , Herrera V. , Chen W. , Haffner S. M. , Pendergrass M.
Published: March 2010

Aim: The objectives of the study were to determine whether thiazolidinedione (TZD) use is associated with an increased risk of fracture in men and women with type 2 diabetes mellitus and to compare the effects of pioglitazone and rosiglitazone.

Materials and Methods: A research database of integrated pharmacy and medical claims was analysed using Cox models adjusted for age, gender, chronic obstructive pulmonary disease, asthma, osteoporosis, stroke, prior fracture and chronic disease score. Patients were followed for 540 days.

Results: There was a 39% higher [adjusted hazard ratio (HR), 1.39; 95% confidence interval (CI), 1.32–1.46] incidence of fractures in men and women exposed to a TZD (n = 69047; age = 56 ± 5 years; 59% men; 48% rosiglitazone) compared with that in control patients (n = 75352; age = 56 ± 5 years; 51% men). Men treated with a TZD had a higher likelihood of fracture than control patients (adjusted HR rosiglitazone, 1.47; 95% CI, 1.38–1.56; adjusted HR pioglitazone, 1.43; 95% CI, 1.34–1.52). The HRs associated with pioglitazone (adjusted HR, 1.43; 95% CI, 1.34–1.52) and rosiglitazone (adjusted HR, 1.47; 95% CI, 1.38–1.56) were almost identical. TZD use was associated with a higher fracture risk in women aged above and below 50 years and in men aged above 50 years.

Conclusions: Our findings add support to the growing literature that TZD treatment is associated with an increased risk of fractures in both men and women, that effects of rosiglitazone and pioglitazone are similar and that fracture risk is increased even in younger women.
Vitamin E (α‐tocopherol) supplementation enhances nitric oxide production in penile tissue of diabetic rats
Authors: Tronchini Eleandro A. , De Miranda Neto Marcilio H. , Zanoni Jacqueline N.
Published: March 2010

OBJECTIVE

To investigate the effects of 0.1% and 2% vitamin E (α‐tocopherol) supplementation on the expression of nitric oxide (NO) in penile tissue of rats with experimentally induced diabetes mellitus (DM).

MATERIALS AND METHODS

In all, 30 male rats were divided into six groups: normoglycaemic (NG), NG treated with 0.1% vitamin E (NGE1), NG treated with 2% vitamin E (NGE2), DM, DM treated with 0.1% vitamin E (DME1), and DM treated with 2% vitamin E (DME2). After 120 days the rats were killed, and penile tissue was collected and processed for neuronal NO synthase (nNOS) immunohistochemistry to determine areas of nNOS‐immunoreactive varicosities.

RESULTS

nNOS‐immunoreactive varicosities in DME2 rats were similar to those of controls (NG) and controls supplemented with vitamin E (NGE1 and NGE2). Varicosity sizes in the NGE1 group were similar to the DM rats with no vitamin E supplementation.

CONCLUSION

Supplementation with 2% vitamin E had a positive effect on areas of nNOS‐immunoreactive varicosities of penile tissue in DM rats.
Association of percentage of tumour burden removed with debulking nephrectomy and progression‐free survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor‐targeted therapy
Authors: Barbastefano Juan , Garcia Jorge A. , Elson Paul , Wood Laura S. , Lane Brian R. , Dreicer Robert , Campbell Steven C. , Rini Brian I.
Published: March 2010

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

To determine if the fractional percentage of tumour volume (FPTV) removed with debulking nephrectomy was associated with progression‐free survival (PFS) after subsequent targeted therapy, as a debulking nephrectomy is the standard of care in metastatic renal cell carcinoma (mRCC), but there are few data.

PATIENTS AND METHODS

The Cleveland Clinic Taussig Cancer Institute Urologic Oncology database was retrospectively reviewed from 2005 to 2008 to identify patients with mRCC who had undergone debulking nephrectomy followed by vascular endothelial growth factor (VEGF)‐targeted therapy, defined as sunitinib‐, sorafenib‐ or bevacizumab‐based therapy. FPTV was calculated as the largest diameter of the primary tumour divided by the total tumour burden (as per the Response Evaluation Criteria in Solid Tumors, RECIST) through investigator re‐review of imaging. PFS was defined from the start date of systemic therapy to disease progression per RECIST criteria.

RESULTS

Forty‐six patients were identified (80% men, median age 61 years, all clear cell histology and 67% with an Eastern Cooperative Oncology Group performance status of 0). Patients received treatment with bevacizumab ± interleukin‐2 (18), sunitinib (14), sorafenib (11) or sunitinib + bevacizumab (three). The median diameter of the primary tumour was 10.0 cm. The median (range) FPTV removed was 95 (80–99)%. In univariable analysis, the FPTV removed (P= 0.002) and normal haemoglobin level (P= 0.04) were associated with improved PFS. In multivariable analysis, the FPTV removed (P < 0.001), male gender (P= 0.001) and corrected calcium (P= 0.05) were independent predictors of PFS.

CONCLUSION

A greater percentage of tumour burden removed at debulking nephrectomy is significantly associated with improved PFS on subsequent VEGF‐targeted systemic therapy.
Two solitudes: post‐tsunami and post‐conflict Aceh
Authors: Waizenegger Arno , Hyndman Jennifer
Published: March 2010

In August 2005, after the devastating tsunami in the Indian Ocean Basin, a Memorandum of Understanding (MoU) for the cessation of hostilities was signed by Aceh's longstanding adversaries—the Government of Indonesia and the Free Aceh Movement (GAM). The tsunami was a major catalyst for ‘disaster diplomacy’—international political pressure, which, this paper argues, was an important ingredient in creating conditions for the MoU, although the situation within Aceh also shaped the peace process. Based on interviews conducted in 2006 and 2007 with government officials, GAM representatives and fighters, and non‐governmental organization staff in Aceh, this paper finds that assistance for tsunami survivors far exceeds that available for conflict survivors and ex‐combatants. The formation of these two solitudes—the tsunami‐affected and the conflict‐affected—compounds challenges for sustaining peace in Aceh. This research points to an enduring lack of livelihoods for former fighters and conflict victims that may threaten a sustainable peace.
Symptomatic profile and health‐related quality of life of persons affected by the Prestige catastrophe
Authors: Sabucedo José M. , Arce Constantino , Senra Carmen , Seoane Gloria , Vázquez Isabel
Published: March 2010

This study analyses the impact of the Prestige oil spill on the mental health and the perception of physical health and functional capacity in the affected population. The sample comprised 926 residents from the section of the Spanish coast affected by the oil spill. The data was collected slightly more than one year after the accident. Scales referring to clinical symptoms (SCL‐36) and health‐related quality of life (SF‐36) were administered. The results suggest that individuals with higher degrees of exposure or residing in areas closest to the spill show lower levels of mental health in comparison to those with lower levels of exposure or living in areas farther away from the spill. This study also finds that women and fishermen tend to suffer more from the consequences of these types of disaster.
Optimizing hurricane disaster relief goods distribution: model development and application with respect to planning strategies
Authors: Horner Mark W. , Downs Joni A.
Published: March 2010

Over the last few years, hurricane emergencies have been among the most pervasive major disruptions in the United States, particularly in the south‐east region of the country. A key aspect of managing hurricane disasters involves logistical planning to facilitate the distribution and transportation of relief goods to populations in need. This study shows how a variant of the capacitated warehouse location model can be used to manage the flow of goods shipments to people in need. In this application, the model is used with protocols set forth in Florida's Comprehensive Emergency Plan and tested in a smaller city in north Florida. Scenarios explore the effects of alternate goods distribution strategies on the provision of disaster relief. Results show that measures describing people's accessibility to relief goods are affected by the distribution infrastructure used to provide relief, as well as assumptions made regarding the population(s) assumed to be in need of aid.
Minimization of socioeconomic disruption for displaced populations following disasters
Authors: El‐Anwar Omar , El‐Rayes Khaled , Elnashai Amr
Published: March 2010

In the aftermath of catastrophic natural disasters such as hurricanes, tsunamis and earthquakes, emergency management agencies come under intense pressure to provide temporary housing to address the large‐scale displacement of the vulnerable population. Temporary housing is essential to enable displaced families to reestablish their normal daily activities until permanent housing solutions can be provided. Temporary housing decisions, however, have often been criticized for their failure to fulfil the socioeconomic needs of the displaced families within acceptable budgets. This paper presents the development of (1) socioeconomic disruption metrics that are capable of quantifying the socioeconomic impacts of temporary housing decisions on displaced populations; and (2) a robust multi‐objective optimization model for temporary housing that is capable of simultaneously minimizing socioeconomic disruptions and public expenditures in an effective and efficient manner. A large‐scale application example is optimized to illustrate the use of the model and demonstrate its capabilities ingenerating optimal plans for realistic temporary housing problems.
MRI verified STN stimulation site – gait improvement and clinical outcome
Authors: Johnsen E. L. , Sunde N. , Mogensen P. H. , Østergaard K.
Published: March 2010

Background:  Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in alleviating Parkinson’s disease (PD) symptoms (tremor, rigidity and bradykinesia) and may improve gait and postural impairment associated with the disease. However, improvement of gait is not always as predictable as the clinical outcome. This may relate to the type of gait impairment or localization of the active DBS contact.

Methods:  The active contact was visualized on peri‐operative magnetic resonance imaging in 22 patients with idiopathic PD, consecutively treated with bilateral STN DBS. Stimulation site was grouped as either in the dorsal/ventral STN or medial/lateral hereof and anterior/posterior STN or medial/lateral hereof. The localization was compared with relative improvement of clinical outcome (UPDRS‐III). In 10 patients, quantitative gait analyses were performed, and the improvement in gait performance was compared with stimulation site in the STN.

Results:  Of 44 active contacts, 77% were inside the nucleus, 23% were medial hereof. Stimulation of the dorsal half improved UPDRS‐III significantly more than ventral STN DBS (P = 0.02). However, there were no differences between anterior and posterior stimulation in the dorsal STN. Step velocity and length improved significantly more with dorsal stimulation compared with ventral stimulation (P = 0.03 and P = 0.02). Balance during gait was also more improved with dorsal stimulation compared with ventral stimulation.

Conclusions:  Deep brain stimulation of the dorsal STN is superior to stimulation of the ventral STN. Possible different effects of stimulation inside the nucleus underline the need for exact knowledge of the active stimulation site position to target the most effective area.
Assisted Voluntary Return of Irregular Migrants: Policy and Practice in the Slovak Republic
Authors: Stančová Kateřina
Published: March 2010

Assisted voluntary return (AVR) is a new approach to return of irregular immigrants aiming at combating unlawful migration, and thus strengthening national immigration systems. AVR lowers risks of the violation of human rights and preserves migrants’ dignity and safety. In addition, it carries fewer political and financial costs. AVR of irregular immigrants is an integral part of migration management in some European countries, including the Slovak Republic. This paper provides a general understanding of the issue of irregular migration and an analysis of policies and practices in assisted voluntary return of irregular migrants in the Slovak Republic. The paper concludes with a discussion of the major issues that need to be addressed in order to achieve sustainable and effective AVR management.
Modelling species distribution at multiple spatial scales: gibbon habitat preferences in a fragmented landscape
Authors: Gray T. N. E. , Phan C. , Long B.
Published: March 2010

Conservation of Indochinese primates is hampered by a lack of knowledge of species ecology, habitat preferences and, locally, distribution. Predictive distribution and habitat suitability models, using predictors known to affect the distribution of similar species elsewhere, may, therefore be of great benefit to conservationists within the region. Yellow‐cheeked crested gibbon Nomascus gabriellae is an IUCN‐listed endangered primate distributed east of the Mekong River in Cambodia, southern Vietnam, and possibly southern Lao PDR. Within Cambodia, yellow‐cheeked crested gibbon are naturally restricted to evergreen forest fragments within a landscape matrix of deciduous dipterocarp and semi‐evergreen forests. During the 2008 dry season, auditory surveys for yellow‐cheeked crested gibbon were conducted within Phnom Prich Wildlife Sanctuary, Mondulkiri province, Cambodia. Predictive distribution models, in which variables were included at the scale at which they best explained gibbon occurrence (multi‐grain models), were constructed to examine the species' habitat associations and tolerance of habitat fragmentation within the wildlife sanctuary. Gibbon occupancy (ϕ) was higher in evergreen (0.43±0.26–0.62) than in semi‐evergreen forest (0.21±0.09–0.4), with gibbon presence constrained by a critical amount of evergreen forest within 5 km radius of listening posts. Three patches of optimal habitat within Phnom Prich Wildlife Sanctuary were identified. These, and connecting habitats, should be the target of increased enforcement effort to limit hunting and habitat conversion. Similar multi‐grain models are likely to be valuable for conservationists within mosaic habitats as they can facilitate identification of the minimum suitable fragment size for species of conservation concern.
Aβ promotes Alzheimer’s disease‐like cytoskeleton abnormalities with consequences to APP processing in neurons
Authors: Henriques Ana Gabriela , Vieira Sandra Isabel , Da Cruz e Silva Edgar F. , Da Cruz e Silva Odete A. B.
Published: March 2010

J. Neurochem. (2010) 113, 761–771.

Aβ is proteolytically produced from the Alzheimer’s amyloid precursor protein (APP). Major properties attributed to Aβ include neurotoxic effects that contribute to Alzheimer’s disease neurodegeneration. However, Aβ can also affect APP processing and trafficking that, in neurons, is anterogradelly transported via microtubules in a kinesin‐associated manner. Herein we show that Aβ can induce accumulation of intracellular sAPP in primary neuronal cultures. Subcellular fractionation studies and immunofluorescence analysis revealed that upon Aβ exposure sAPP retention was localized to cytoskeleton associated vesicular structures along the neurite processes, positive for an APP N‐terminal antibody and negative for an APP C‐terminal antibody. These vesicular structures were also positive for kinesin light chain 1 (KLC). We confirm that Aβ alters both actin and microtubule networks. It increases F‐actin polymerization and we report for the first time that Aβ decreases α‐tubulin acetylation. The use of cytoskeleton associated drugs partially reversed the Aβ‐induced effects on sAPP secretion. The data here presented show that Aβ causes intracellular sAPP retention by inducing alterations in the cytoskeleton network, thus contributing to impaired APP/sAPP vesicular transport. Moreover, the data strengthens the hypothesis that Aβ‐induces neurodegeneration and provides a potential mechanism of action, as impaired vesicular and axonal transport have been linked to Alzheimer’s disease pathology.
Spatially‐explicit sensitivity analysis for conservation management: exploring the influence of decisions in invasive alien plant management
Authors: Roura‐Pascual Núria , Krug Rainer M. , Richardson David M. , Hui Cang
Published: March 2010

Aim  Decision‐support models have considerable potential for guiding management strategies when problems are complex. The robustness of such decision‐making processes is rarely evaluated, and the influence of decision criteria (or factors) in management decisions is seldom considered. We present a framework for a spatially‐explicit sensitivity analysis by using a scheme developed to provide objective guidelines, in the form of static priority maps, for managing woody invasive alien plants (IAPs).

Location  The Cape Floristic Region, South Africa.

Methods  The model included seven factors related to management history, fire risk, and the age, identity, density and spread of IAPs. Each factor had a weight associated that reflected its relative importance in prioritizing areas for clearing. We changed these factor weights using three approaches of sensitivity analysis and assessed the effect of these changes on the spatial structure of the resulting priority maps in three different management regions.

Results  Different outcomes arose depending on the importance given to different factors. Priority maps were most sensitive to the fire‐related factors, suggesting that fire is both a crucial driver of invasion in fynbos and an overriding determinant of management options. The factor ‘area burnt recently’ provided crucial information for the effective clearing of IAPs. The sensitivity of the model to changes in other factors was more context specific: levels of sensitivity were highly dependent on different features of the landscape, especially the spatial heterogeneity of particular factors.

Main conclusions  By clarifying the importance of factors in shaping priority maps, the sensitivity analysis framework enabled us to identify the necessary factors to produce outcomes matching a pre‐selected management strategy. This is important for cost‐efficient management, as acquisition and curation of data is expensive. This spatially‐explicit sensitivity analysis is, thus, recommended to evaluate the robustness and generality of selected management strategies, and validate the assumptions derived from decision‐making protocols.
Structurally diverse amphiphiles exhibit biphasic modulation of GABAAreceptors: similarities and differences with neurosteroid actions
Authors: Chisari M , Shu H‐J , Taylor A , Steinbach JH , Zorumski CF , Mennerick S
Published: March 2010

Background and purpose: Some neurosteroids, notably 3α‐hydroxysteroids, positively modulate GABAAreceptors, but sulphated steroids negatively modulate these receptors. Recently, other lipophilic amphiphiles have been suggested to positively modulate GABA receptors. We examined whether there was similarity among the actions of these agents and the mechanisms of neurosteroids. Significant similarity would affect theories about the specificity of steroid actions.

Experimental approach: Xenopus laevisoocytes were challenged with Triton X‐100, octyl‐β‐glucoside, capsaicin, docosahexaenoic acid and sodium dodecyl sulphate (SDS), along with different GABA concentrations.

Key results: These compounds have both positive and negative effects on GABA currents, which can be accentuated according to the degree of receptor activation. A low GABA concentration (1 µM) promoted potentiation and a high concentration (20 µM) promoted inhibition of current, except for SDS that inhibited function even at low GABA concentrations. Amphiphile inhibition was characterized by enhanced apparent desensitization and by weak voltage dependence, similar to pregnenolone sulphate antagonism. We then tested amphiphile effects on mutated receptor subunits that are insensitive to negative (α1V256S) and positive (α1Q241L or α1N407A/Y410F) steroid modulation. Negative regulation by amphiphiles was nearly abolished in α1V256S‐mutated receptors, but potentiation was unaffected. In α1Q241L‐ or α1N407A/Y410F‐mutated receptors, potentiation by amphiphiles remained intact.

Conclusions and implications: Structurally diverse amphiphiles have antagonist actions at GABAAreceptors very similar to those of sulphated neurosteroids, while the potentiating mechanisms of these amphiphiles are distinct from those of neurosteroid‐positive modulators. Thus, such antagonism at GABAAreceptors does not have a clear pharmacophore requirement.
Effects of the calcium sensitizer OR‐1896, a metabolite of levosimendan, on post‐infarct heart failure and cardiac remodelling in diabetic Goto–Kakizaki rats
Authors: Louhelainen Marjut , Merasto Saara , Finckenberg Piet , Vahtola Erik , Kaheinen Petri , Levijoki Jouko , Mervaala Eero
Published: March 2010

Background and purpose: Levosimendan is a novel, short half‐life calcium sensitizer used as pharmacological inotropic support in acute decompensated heart failure. After oral administration, levosimendan is metabolized to OR‐1855, which, in rats, is further metabolized into OR‐1896. OR‐1896 is a long‐lasting metabolite of levosimendan sharing the pharmacological properties of the parent compound.

Experimental approach: Effects of oral OR‐1896 treatment on post‐infarct heart failure and cardiac remodelling were assessed in diabetic Goto–Kakizaki (GK) rats, an animal model of type II diabetes. Myocardial infarction (MI) was produced to GK rats by coronary ligation. Twenty‐four hours after MI or sham operation, the rats were randomized into four groups: (i) MI; (ii) MI + OR‐1896 treatment; (iii) sham; and (iv) sham + OR‐1896. Cardiac function and markers of cardiac remodelling were assessed 1, 4 and 12 weeks after MI.

Key results: OR‐1896 increased ejection fraction and fractional shortening in GK rats with MI. OR‐1896 ameliorated post‐infarct cardiac hypertrophy, and prevented the MI‐induced increase in cardiac mRNA for atrial natriuretic peptide, monocyte chemoattractant protein‐1 and connective tissue growth factor, markers of pressure/volume overload, inflammation and fibrosis respectively. OR‐1896 also suppressed mRNA for senescence‐associated p16INK4Aand p19ARF. The beneficial effects of OR‐1896 were more prominent at week 12 than at week 4. OR‐1896 did not influence systolic blood pressure, blood glucose level, myocardial infarct size or cardiovascular mortality.

Conclusions and implications: Oral treatment with calcium sensitizer OR‐1896 protects against post‐infarct heart failure and cardiac remodelling in experimental model of type II diabetes.