bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic Nitric Oxide Production by Azospirillum brasilense Sp245 and Its Influence on Root Architecture in Tomato
Authors: Molina-Favero Celeste , Creus Cecilia Mónica , Simontacchi Marcela , Puntarulo Susana , Lamattina Lorenzo
Published: June 2008

The major feature of the plant-growth-promoting bacteria Azospirillum brasilense is its ability to modify plant root architecture. In plants, nitric oxide (NO) mediates indole-3-acetic acid (IAA)-signaling pathways leading to both lateral (LR) and adventitious (AR) root formation. Here, we analyzed aerobic NO production by A. brasilense Sp245 wild type (wt) and its mutants Faj009 (IAA-attenuated) and Faj164 (periplasmic nitrate reductase negative), and its correlation with tomato root-growth-promoting effects. The wt and Faj009 strains produced 120 nmol NO per gram of bacteria in aerated nitrate-containing medium. In contrast, Faj164 produced 5.6 nmol NO per gram of bacteria, indicating that aerobic denitrification could be considered an important source of NO. Inoculation of tomato (Solanum lycopersicum Mill.) seedlings with both wt and Faj009 induced LR and AR development. In contrast, Faj164 mutant was not able to promote LR or AR when seedlings grew in nitrate. When NO was removed with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), both LR and AR formation were inhibited, providing evidence that NO mediated Azospirillum-induced root branching. These results show that aerobic NO synthesis in A. brasilense could be achieved by different pathways and give evidence for an NO-dependent promoting activity on tomato root branching regardless of bacterial capacity for IAA synthesis.
Kin in space: social viscosity in a spatially and genetically substructured network
Authors: Wolf Jochen B.W , Trillmich Fritz
Published: June 2008

Population substructuring is a fundamental aspect of animal societies. A growing number of theoretical studies recognize that who-meets-whom is not random, but rather determined by spatial relationships or illustrated by social networks. Structural properties of large highly dynamic social systems are notoriously difficult to unravel. Network approaches provide powerful ways to analyse the intricate relationships between social behaviour, dispersal strategies and genetic structure. Applying network analytical tools to a colony of the highly gregarious Galápagos sea lion (
Zalophus wollebaeki
), we find several genetic clusters that correspond to spatially determined ‘network communities’. Overall relatedness was low, and genetic structure in the network can be interpreted as an emergent property of philopatry and seems not to be primarily driven by targeted interactions among highly related individuals in family groups. Nevertheless, social relationships between directly adjacent individuals in the network were stronger among genetically more similar individuals. Taken together, these results suggest that even small differences in the degree of relatedness can influence behavioural decisions. This raises the fascinating prospect that kin selection may also apply to low levels of relatedness within densely packed animal groups where less obvious co-operative interactions such as increased tolerance and stress reduction are important.
Individual differences, density dependence and offspring birth traits in a population of red deer
Authors: Stopher Katie V , Pemberton Josephine M , Clutton-Brock Tim H , Coulson Tim
Published: June 2008

Variation between individuals is an essential component of natural selection and evolutionary change, but it is only recently that the consequences of persistent differences between individuals on population dynamics have been considered. In particular, few authors have addressed whether interactions exist between individual quality and environmental variation. In part, this is due to the difficulties of collecting sufficient data, but also the challenge of defining individual quality. Using a long-established study population of red deer,
Cervus elaphus,
inhabiting the North Block of the Isle of Rum, and three quality measures, this paper investigates how differences in maternal quality affect variation in birth body mass and date, as population density varies, and how this differs depending on the sex of the offspring and the maternal quality measure used. Significant interactions between maternal quality, measured as a hind's total contribution to population growth, and population density are reported for birth mass, but only for male calves. Analyses using dominance or age at primiparity to define maternal quality showed no significant interactions with population density, highlighting the difficulties of defining a consistent measure of individual quality.
Reciprocal-space imaging of a real quasicrystal. A feasibility study with PILATUS 6M
Authors: Weber Thomas , Deloudi Sofia , Kobas Miroslav , Yokoyama Yoshihiko , Inoue Akihisa , Steurer Walter
Published: June 2008

How many of the theoretically densely distributed Bragg reflections of a quasicrystal can be observed employing an area detector and synchrotron radiation? How does the reflection density of a real quasicrystal change as a function of exposure time, and what is the minimum distance between reflections? What does the distribution of diffuse scattering look like? To answer these questions, the Bragg reflection density of a perfect icosahedral quasicrystal with composition Al64Cu23Fe13was measured employing a novel type of single-photon-counting X-ray pixel detector, PILATUS 6M, which allows noise-free data collection with the extraordinarily large dynamic range of 20 bit. The reflection density was found to be two orders of magnitude lower than expected for a strictly quasiperiodic structure. Moreover, diffuse scattering reflects significant structural disorder, breaking six-dimensionalF-lattice symmetry. These findings have some implications for the interpretation of physical properties.
A method for merging of ultra-small-angle X-ray scattering and smeared small-angle X-ray scattering patterns of fibers
Authors: Stribeck Norbert , Nöchel Ulrich
Published: June 2008

A method for collimation correction and combination of anisotropic scattering patterns recorded in tandem experiments is proposed. It includes both an advanced two-dimensional extrapolation procedure for the center of the pattern and (compared with the `blind deconvolution' method) a more justified procedure for desmearing from an unknown broad primary beam profile. This semi-blind deconvolution rests on the availability of unsmeared data in a region of the smeared image. Materials exhibiting both ultra-small-angle X-ray scattering (USAXS) and small-angle X-ray scattering (SAXS) must be studied in both angular bands (tandem experiment), in order to collect the complete range of discrete scattering for nanostructure analysis. Merging of the patterns requires desmearing of at least the SAXS pattern from its point-spread function,i.e.the primary beam profile. The distorting effect of single-band experiments on the reconstructed nanostructure of polymer materials is demonstrated.
Current caveats and further directions in the analysis of density‐dependent population regulation
Authors: Carrete Martina , Tella José L. , Sánchez‐Zapata José A. , Moleón Marcos , Gil‐Sánchez José M.
Published: June 2008

An important issue in population ecology is to disentangle different density‐dependent mechanisms that may limit or regulate animal populations. This goal is further complicated when studying long‐lived species for which experimental approaches are not feasible, in whose cases density‐dependence hypotheses are tested using long‐term monitored populations. Here we respond to some criticisms and identify additional problems associated with these kinds of observational studies. Current caveats are related to the temporal and spatial scales covered by population monitoring data, which may question its suitability for density‐dependence tests, and to statistical flaws such as the incorrect control for confounding variables, low statistical power, the distribution of demographic variables, the interpretation of spurious correlations, and the often used stepwise series of univariate analyses. Generalised linear mixed models are recommended over other more traditional approaches, since they help to solve the above statistical problems and, more importantly, allow to properly test several hypotheses simultaneously. Finally, several management actions aimed to recover endangered species, such as supplementary feeding, might be considered as field experiments for further testing density‐dependence hypotheses in long‐lived study models. We expect these opportunities, together with the most adequate statistical tools now available, will help to better our understanding of density‐dependent effects in wild populations.
Quantifying the randomness of extinctions
Authors: De Boeck Hans J. , Visscher Alain , Milbau Ann , Nijs Ivan
Published: June 2008

Extinctions occur either randomly or in a more deterministic and predictable manner, with certain characteristics making some species more vulnerable to (local) extinction than others. Although the quantification of extinction randomness would better our understanding of the extinction causes and increase the predictability of future species losses, few quantification methods are currently available. To this purpose, we propose two indices based on a comparison of an a priori (expected) extinction series with an observed one. Whereas the first index requires data on the order of extinctions, the second index is only concerned with which species went extinct and which did not. Using a model for generating extinction data, we tested both indices successfully for accordance with the robustness prerequisites. Index outputs were furthermore unaffected by species richness, apart from decreased variation with rising species numbers. Because of its independence of non‐extinct species and its focus on extinction sequences, the first randomness index seems especially useful for use in paleontological and paleo‐ecological research. The second index is likely a good tool to study shorter term extinctions, for which the extinction order is often not known and for which the comparison with species that did persist is of greater interest. We use a real dataset to illustrate this. Finally, we discuss how it is possible to expand the use of this index toward identifying previously unknown extinction‐promoting species characteristics, and toward a credible assessment of the extinction risk posed by global change.
Importance of estimating matrix quality for modeling species distribution in complex tropical landscapes: a test with Atlantic forest small mammals
Authors: Umetsu Fabiana , Paul Metzger Jean , Pardini Renata
Published: June 2008

Information to guide decision making is especially urgent in human dominated landscapes in the tropics, where urban and agricultural frontiers are still expanding in an unplanned manner. Nevertheless, most studies that have investigated the influence of landscape structure on species distribution have not considered the heterogeneity of altered habitats of the matrix, which is usually high in human dominated landscapes. Using the distribution of small mammals in forest remnants and in the four main altered habitats in an Atlantic forest landscape, we investigated 1) how explanatory power of models describing species distribution in forest remnants varies between landscape structure variables that do or do not incorporate matrix quality and 2) the importance of spatial scale for analyzing the influence of landscape structure. We used standardized sampling in remnants and altered habitats to generate two indices of habitat quality, corresponding to the abundance and to the occurrence of small mammals. For each remnant, we calculated habitat quantity and connectivity in different spatial scales, considering or not the quality of surrounding habitats. The incorporation of matrix quality increased model explanatory power across all spatial scales for half the species that occurred in the matrix, but only when taking into account the distance between habitat patches (connectivity). These connectivity models were also less affected by spatial scale than habitat quantity models. The few consistent responses to the variation in spatial scales indicate that despite their small size, small mammals perceive landscape features at large spatial scales. Matrix quality index corresponding to species occurrence presented a better or similar performance compared to that of species abundance. Results indicate the importance of the matrix for the dynamics of fragmented landscapes and suggest that relatively simple indices can improve our understanding of species distribution, and could be applied in modeling, monitoring and managing complex tropical landscapes.
Why do mountains support so many species of birds?
Authors: Ruggiero Adriana , Hawkins Bradford A.
Published: June 2008

Although topographic complexity is often associated with high bird diversity at broad geographic scales, little is known about the relative contributions of geomorphologic heterogeneity and altitudinal climatic gradients found in mountains. We analysed the birds in the western mountains of the New World to examine the two‐fold effect of topography on species richness patterns, using two grains at the intercontinental extent and within temperate and tropical latitudes. Birds were also classified as montane or lowland, based on their overall distributions in the hemisphere. We estimated range in temperature within each cell and the standard deviation in elevation (topographic roughness) based on all pixels within each cell. We used path analysis to test for the independent effects of topographic roughness and temperature range on species richness while controlling for the collinearity between topographic variables. At the intercontinental extent, actual evapotranspiration (AET) was the primary driver of species richness patterns of all species taken together and of lowland species considered separately. In contrast, within‐cell temperature gradients strongly influenced the richness of montane species. Regional partitioning of the data also suggested that range in temperature either by itself or acting in combination with AET had the strongest “effect” on montane bird species richness everywhere. Topographic roughness had weaker “effects” on richness variation throughout, although its positive relationship with richness increased slightly in the tropics. We conclude that bird diversity gradients in mountains primarily reflect local climatic gradients. Widespread (lowland) species and narrow‐ranged (montane) species respond similarly to changes in the environment, differing only in that the richness of lowland species correlates better with broad‐scale climatic effects (AET), whereas mesoscale climatic variation accounts for richness patterns of montane species. Thus, latitudinal and altitudinal gradients in species richness can be explained through similar climatic‐based processes, as has long been argued.
Caterpillars on the run – induced defences create spatial patterns in host plant damage
Authors: Roslin Tomas , Syrjälä Heidi , Roland Jens , Harrison Philip J. , Fownes Sherri , Matter Stephen F.
Published: June 2008

Herbivores usually consume a mere fraction of available plant biomass. Spatial patterns in feeding damage may be attributable to induced defences by the host plant; a damaged plant reacts by lowering its nutritional value, thereby forcing herbivores to move on before food gets worse. In this study, we test this general hypothesis on a specific model system: caterpillars of the alpine butterfly Parnassius smintheus feeding on lance‐leaved stonecrop Sedum lanceolatum. We first describe spatial patterns in host distribution and feeding damage within alpine meadows. We then use laboratory experiments to test a key assumption behind the proposed mechanisms: that the host plant exhibits an induced response with a negative impact on larval performance, and that this response is activated with a delay. Finally, we relate the patterns observed to the actual behaviour of Parnassius larvae.

Overall, we found the level of feeding damage to be low (on damaged plants, only 5% of all leaves were fed upon). Within meadows, both host plants and feeding damage were clumped at a small spatial scale. This pattern seemed directly explicable by the timing of the host's induced defence. Laboratory experiments revealed a delay of 1–2 d before the defence reached a level affecting larval performance, and wild larvae switch plants more quickly than this. A simulation model demonstrated that the spatial distribution of host plant damage can be generated by a simple random walk, based on the empirically observed step frequency, length and turning angles. Hence, as the most parsimonious explanation for the observed level and pattern of host plant damage, we offer a scenario where induced changes in host‐plant quality limits the time spent per plant, but the herbivore moves throughout the landscape without any particular directionality.
Likely responses of the Antarctic benthos to climate‐related changes in physical disturbance during the 21st century, based primarily on evidence from the West Antarctic Peninsula region
Authors: Smale Dan A. , Barnes David K. A.
Published: June 2008

Disturbance has always shaped the evolution and ecology of organisms and nowhere is this more apparent that on the iceberg gouged continental shelves of the Antarctic Peninsula (AP). The vast majority of currently described polar biodiversity occurs on the Southern Ocean shelf but current and projected climate change is rapidly altering disturbance intensities in some regions. The AP is now amongst the fastest warming and changing regions on earth. Seasonal sea ice has decreased in time and extent, most glaciers in the region have retreated, a number of ice shelves have collapsed, and the surface waters of the seas west of the AP have warmed. Here, we review the influences of disturbance from ice, sedimentation, freshening events, wave action and humans on shallow water benthic assemblages, and suggest how disturbance pressures will change during the 21st century in the West Antarctic Peninsula (WAP) and Scotia Arc region. We suggest that the intensity of ice scouring will increase in the region over the next few decades as a result of decreased winter sea ice periods and increased ice loading into coastal waters. Thus, the most frequently disturbed environment on earth will become more so, which will lead to considerable changes in community structure and species distributions. However, as ice fronts retreat past their respective grounding lines, sedimentation and freshening events will become relatively more important. Human presence in the region is increasing, through research, tourism, and resource exploitation, which represents a considerable threat to polar biodiversity over the next century. Adapting to or tolerating multiple, changing environmental stressors will be difficult for a fauna with typically slow generation turnovers that has evolved largely in isolation. We suggest that intensifying acute and chronic disturbances are likely to cause significant changes in ecosystem structure, and probably a considerable loss of polar marine biodiversity, over relatively short timescales.
Galectin‐1 supports the survival of CD45RA(−) primary myeloma cells in vitro
Authors: Abroun Saeid , Otsuyama Ken‐ichiro , Shamsasenjan Karim , Islam Abul , Amin Jakia , Iqbal Mohd S. , Gondo Toshikazu , Asaoku Hideki , Kawano Michio M.
Published: June 2008

The survival and proliferation of human myeloma cells are considered to be heavily dependent on the microenvironment of bone marrow (BM). This study confirmed that galectin‐1 (Gal‐1) and SDF‐1α were produced by bone marrow mononuclear cells of myeloma patients. The addition of Gal‐1 and SDF‐1α to a serum‐free synthetic medium, maintained the viability of primary myeloma cells for 2 weeks similar to that before culture. While Gal‐1 reduced the viable cell number in CD45RA(+) B cell lines, it maintained the viability of CD45(−) U266 and CD45RA(−)RO(+) ILKM3 myeloma cell lines in the synthetic medium. This was confirmed with the transfection of the PTPRC (CD45) RA, ‐RB, or ‐RO gene into CD45(−) U266 cells. The combination of Gal‐1 and SDF‐1α significantly induced phosphorylation of Akt and IkB, while the phosphorylation of ERK1/2 was significantly reduced in CD45RA(+) U266 and Raji cells but not CD45(−) or CD45RA(−) U266 cells. Furthermore, we confirmed that Gal‐1 bound to CD45RA in CD45RA(+) Raji cells, and also physically interacted with β1‐integrin by immunoprecipitation followed by Western blotting and confocal microscopy. The results suggest that Gal‐1 has two different actions depending on its binding partner, and supports the survival of CD45RA(−) myeloma cells.
The HMG‐CoA inhibitor, simvastatin, triggers in vitro anti‐tumour effect and decreases IgM secretion in Waldenstrom macroglobulinaemia
Authors: Moreau Anne‐Sophie , Jia Xiaoying , Patterson Christopher J. , Roccaro Aldo M. , Xu Lian , Sacco Antonio , O’Connor Kelly , Soumerai Jacob , Ngo Hai T. , Hatjiharissi Evdoxia , Hunter Zachary R. , Ciccarelli Bryan , Manning Robert , Ghobrial Irene M. , Leleu Xavier , Treon Steven P.
Published: June 2008

Waldenstrom macroglobulinaemia (WM) is an incurable lymphoplasmacytic lymphoma with secretion of serum monoclonal immunoglobulin M (IgM). We previously showed that patients receiving cholesterol‐lowering statins, had the lowest IgM value in a large cohort of patients with WM. Simvastatin, a 3‐hydroxy‐3‐methyl‐glutaryl‐CoA reductase inhibitor, induced inhibition of proliferation, cytotoxic effect and apoptosis in IgM secreting cell lines as well as in primary CD19+ WM cells. Interestingly, those effects were reversed by addition of mevalonate and geranylgeranylpyrophosphate, demonstrating that simvastatin inhibited cell growth, survival and IgM secretion on BCWM.1 WM cells by inhibition of geranylgeranylated proteins. Furthermore, simvastatin overcame tumour cell growth induced by co‐culture of WM cells with bone‐marrow stromal cells. Simvastatin also decreased IgM secretion by BCWM.1 cells at an early time‐point that had not affected cell survival. Simvastatin‐induced cytotoxicity was preceded by a decrease in Akt (protein kinase B, PKB) and extracellular signal‐regulated kinase (ERK) mitogen‐activated protein kinase (MAPK) pathways at 18 h. In addition, simvastatin induced an increase in stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) MAPK followed by caspase‐8, ‐9, ‐3 and poly(ADP‐ribose) polymerase (PARP) cleavages at 18 h, leading to apoptosis. Furthermore, simvastatin enhanced the cytotoxicity induced by bortezomib, fludarabine and dexamethasone. Our studies therefore support our earlier observation of statin‐mediated anti‐WM activity and provide the framework for future clinical trials testing simvastatin in WM.
Planning for the end of children's lives – the lifetime framework
Authors: Finlay F. , Lewis M. , Lenton S. , Poon M.
Published: June 2008

Aim  This paper describes the development of ‘a best practice framework’, following review of a sample of notes of children known to the Lifetime Service, where the child has a non‐malignant life limiting condition, to improve child and family engagement in the planning process at the end of life.

Background  There is very little literature about how to engage with families to decide end of life plans for children with life limiting conditions.

Method  An audit of clinical case notes was followed by the development of ‘a best practice framework’ through a Delphi process involving clinical practitioners.

Results  The 3 × 3 framework is presented to aid communication with parents and children at this difficult time of decision‐making.

Conclusion  This new framework has been well received by both parents and practitioners, and its use will be audited in the future.
The Millennium Cohort Study Child Health Group Factors associated with uptake of measles, mumps, and rubella vaccine (MMR) and use of single antigen vaccines in a contemporary UK cohort: prospective cohort study
Authors: Reading Richard
Published: June 2008

.
 
Pearce A.,
Law C.,
Elliman D.,
Cole T. J. &
Bedford H.
(
2008
)

,
336
,
754
–
757
.
 
DOI: 10.1136/bmj.39489.590671.25
.

Objectives  To estimate uptake of the combined measles, mumps, and rubella vaccine (MMR) and single antigen vaccines and explore factors associated with uptake and reasons for not using MMR.

Design  Nationally representative cohort study.

Setting  Children born in the UK, 2000–2002.

Participants  A total of 14 578 children for whom data on immunization were available.

Main outcome measures  Immunization status at 3 years defined as ‘immunized with MMR’, ‘immunized with at least one single antigen vaccine’, and ‘unimmunized’.

Results  In total, 88.6% (13 013) were immunized with MMR and 5.2% (634) had received at least one single antigen vaccine. Children were more likely to be unimmunized if they lived in a household with other children (risk ratio 1.74, 95% confidence interval 1.35 to 2.25, for those living with three or more) or a lone parent (1.31, 1.07 to 1.60) or if their mother was under 20 (1.41, 1.08 to 1.85) or over 34 at cohort child's birth (reaching 2.34, 1.20 to 3.23, for ≥40), more highly educated (1.41, 1.05 to 1.89, for a degree), not employed (1.43, 1.12 to 1.82), or self‐employed (1.71, 1.18 to 2.47). Use of single vaccines increased with household income (reaching 2.98, 2.05 to 4.32, for incomes of ≥£52 000 (€69 750, $102 190)), maternal age (reaching 3.04, 2.05 to 4.50, for ≥40) and education (reaching 3.15, 1.78 to 5.58, for a degree). Children were less likely to have received single vaccines if they lived with other children (reaching 0.14, 0.07 to 0.29, for three or more), had mothers who were Indian (0.50, 0.25 to 0.99), Pakistani or Bangladeshi (0.13, 0.04 to 0.39), or black (0.31, 0.14 to 0.64), or aged under 25 years (reaching 0.14, 0.05 to 0.36, for 14–19). Nearly three‐quarters (74.4%, 1110) of parents who did not immunize with MMR made a ‘conscious decision’ not to immunize.

Conclusions  Although MMR uptake in this cohort is high, a substantial proportion of children remain susceptible to avoidable infection, largely because parents consciously decide not to immunize. Social differentials in uptake could be used to inform targeted interventions to promote uptake.
Ambiguous abbreviations: an audit of abbreviations in paediatric note keeping
Authors: Reading Richard
Published: June 2008

.
 
Sheppard J. E.,
Weidner L. C. E.,
Zakai S.,
Fountain‐Polley S. &
Williams J.
(
2008
)

,
93
,
204
–
206
.
 
DOI: 10.1136/adc.2007.128132
.

Objective  To assess the frequency, nature and understanding of abbreviations in medical records.

Design  Audit of abbreviation use and meaning in paediatric handover sheets and medical notes compared with two standards, the Trust Intranet Medical Dictionary (TID) and Mosby's Medical Dictionary (MMD). A selection of abbreviations was shown to healthcare professionals to examine interpretation of abbreviations.

Setting  Large inner‐city district general hospital, Birmingham, UK.

Main outcome measures  Frequency, nature and understanding of abbreviations in paediatric medical records.

Results  On 25 handover sheets, a total of 2286 abbreviations were used, with 221 different abbreviations; the standards recognized 14% (TID) and 20% (MMD) of these abbreviations. In 168 sets of medical notes, a total of 3668 abbreviations were used, with 479 different abbreviations; the standards recognized 15% (TID) and 17% (MMD). Some words were shortened in different forms; for example, normal (N, Nl, NAD) and some abbreviations had multiple interpretations that differed from those intended, for example, TOF (tetralogy of Fallot, tracheo‐oesophageal fistula). When presented with a selection of abbreviations, paediatric doctors recognized 56–94% and other healthcare professionals recognized 31–63%.

Conclusion  Abbreviation use was widespread in paediatric note keeping. There was no systematic approach to this and difficulties in interpretation were demonstrated. The use of standardized abbreviations to avoid confusion is suggested.
Interventions to improve medication adherence in people with multiple chronic conditions: a systematic review
Authors: Williams Allison , Manias Elizabeth , Walker Rowan
Published: June 2008

Aim.  This paper is a report of a literature review to identify research involving interventions to improve medication adherence in people with multiple co‐existing chronic conditions.

Title.  Interventions to improve medication adherence in people with multiple chronic conditions: a systematic review.

Background.  The importance of managing co‐existing, chronic conditions in people of all ages is critical to prevent adverse health outcomes.

Data sources.  Databases, including Cumulative Index of Nursing and Allied Health Literature, Medline, PubMed and Web of Science were searched for the period January 1997–2007 using the combined keywords adherence, compliance, drug therapy, medication, clinical trial, randomized controlled trial, intervention, chronic condition, chronic disease, multiple morbidity and comorbidity. References of retrieved papers were also considered.

Methods.  The inclusion criteria were: English language, oral medication adherence, self‐administered medications, multiple prescribed medications for three or more chronic conditions and randomized controlled trials lasting at least 3 months.

Results.  Studies examining medication adherence in people with multiple chronic conditions targeted people over 70 years of age, and were primarily focused on the management of polypharmacy and reducing healthcare costs. Adherence was measured using different tools and estimates of adherence, and interventions were predominantly delivered by pharmacists. The evidence for effective interventions to enhance medication adherence in multiple chronic conditions was weak, and psychosocial interventions were absent.

Conclusion.  Interventions that improve medication adherence for people with multiple chronic conditions are essential, given the increased prevalence of these conditions in people of all ages. Outcomes of improved adherence, such as disease control and quality of life, require investigation. Psychosocial interventions engaging people in medication self‐management offer potential for improved patient outcomes in complex diseases.
Local adaptation to biotic factors: reciprocal transplants of four species associated with aromatic Thymus pulegioides and T. serpyllum
Authors: Grøndahl Eva , Ehlers Bodil K.
Published: June 2008

A plant producing secondary compounds may affect the fitness of other plants in the vicinity, and, likewise, associated plants may evolve adaptation to the presence of their ‘chemical neighbour’. Species of the genus Thymus are aromatic plants, well known for their production of aromatic oils whose constitution is dominated by mono‐ or sesquiterpenes. A polymorphism for the production of the dominant terpene in the oil exists both within and between thyme species.

Here we examine the effects of two different terpenes produced by Thymus pulegioides and T. serpyllum on the performance of four associated plant species: Achillea millefolium, Agrostis capillaris, Galium verum and Plantago lanceolata. In a reciprocal transplant experiment we studied how plants naturally occurring together with thyme producing either carvacrol or b‐caryophyllene perform on soil treated with these compounds.

We found evidence of local adaptation to the ‘home’ terpene. Plants originating from sites where they grow together with carvacrol‐producing thyme plants also perform better on soil treated with carvacrol. One of the associated species (A. millefolium) also showed evidence of local adaptation to the sesquiterpene b‐caryophyllene .

Seed germination and root biomass showed an adaptive response to soil treatment. Vegetation analysis supported the results of the reciprocal transplant experiment. When the associated species performed best on ‘home’ soil, thyme and the associated species also showed a positive spatial association at natural sites of origin. Moreover, coefficients of variation in plant traits were significantly lower on ‘home’ soil compared to other soils for both A. capillaris and A. millefolium, but higher for G. verum.

Synthesis. Our results show that plant species can adapt to the presence of neighbour plants that produce specific chemical compounds. This supports the idea that local plant communities may be a lot more co‐evolved than was previously thought.
The effect of sesame and sunflower oils on the plasma disposition of ivermectin in goats
Authors: GOKBULUT C. , KARADEMIR U. , BOYACIOGLU M. , McKELLAR Q. A.
Published: June 2008

The effect of sesame oil (SSO) and sunflower oil (SFO) (the excipients) on the plasma disposition of ivermectin (IVM) following intravenous (i.v.) and subcutaneous (s.c.) administration at a dosage of 200 μg/kg was investigated in goats. Ten clinically healthy crossbred goats were used in the study. The animals were allocated by weight and sex into two groups of five animals each. Group 1 (n = 5) received the drug and excipient by the i.v. route only and group 2 received drug and excipient by the s.c. route only. The study was designed according to a two‐phase crossover design protocol. In the first phase three animals in group 1 were i.v. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. In group 2 during the first phase, three animals were s.c. administered IVM (0.2 mg/kg) + SSO (1 mL) and the other two animals were received IVM (0.2 mg/kg) + SFO (1 mL). In the second phase animals were crossed over and received the alternate excipient with IVM at the same dosages. A 4‐week washout period was allowed between the two phases. In group 2 significantly increased dermal thickness was observed at the s.c. injection site of the all animals which received IVM during phase I regardless of the excipient. There was almost no change observed at the injection site of any animal during the second phase of the study following s.c. administration. In group 2 the plasma concentrations of IVM in the second phase for both excipient combinations were much higher than the plasma concentrations following first administration and appeared to be related with the dermal changes. The mean plasma disposition of IVM in combination with SSO or SFO was similar following i.v. administration. Longer terminal elimination half‐lives and resultant longer mean resident time were observed after s.c. administration of the both combinations compared with i.v. administration.
Intermediate dose cidofovir does not cause additive nephrotoxicity in BK virus allograft nephropathy
Authors: Araya Carlos E. , Lew Judy F. , Fennell Robert S. , Neiberger Richard E. , Dharnidharka Vikas R.
Published: June 2008

Abstract:  BKVAN has emerged as a major morbidity in kidney transplant recipients. Among treatment options is cidofovir, which can be nephrotoxic. We previously reported that intermediate dose cidofovir could be used without significant nephrotoxicity. We present extended results of the same treatment protocol in a larger cohort and with longer follow up. Diagnosis of BKVAN was based on detection of BK viral DNA from plasma and renal allograft biopsy tissue. All patients received cidofovir (0.25–1 mg/kg/dose) every 2–3 wk. Total number of cidofovir doses ranged from 1 to 18 (mean 8). This report includes eight patients, aged 5–21 yr, treated with intermediate dose cidofovir. Median follow‐up was 11 months (range 4–32). Mean fall in reciprocal of serum creatinine (1/sCr) from baseline at BKVAN diagnosis was 64% (range 28–120%). A time‐series plot of plasma BK virus PCR and 1/sCr showed marked reduction in viral loads without significant deterioration in 1/sCr from the initial value at BKVAN diagnosis. In this larger series with extended follow up, intermediate dose cidofovir without probenecid for the treatment of BKVAN continues to show stabilization of renal function without progression to renal failure.
Hyperuricemia after liver transplantation in children
Authors: Harambat Jérôme , Dubourg Laurence , Ranchin Bruno , Hadj‐Aïssa Aoumeur , Fargue Sonia , Rivet Christine , Boillot Olivier , Lachaux Alain , Cochat Pierre
Published: June 2008

Abstract:  Uric acid may be involved in the development and progression of kidney diseases. Hyperuricemia is a common feature in adult liver transplant recipients but there is limited information in children. In order to estimate the incidence, predictors of hyperuricemia in pediatric liver transplant recipients, and to assess whether hyperuricemia may impact long‐term renal function determined by measured GFR, we reviewed data of 70 children who received a first liver transplant between 1991 and 2005 (median follow‐up 7.1 yr). Renal function tests performed annually included uric acid concentration, inulin and uric acid clearances. The cumulative incidence of hyperuricemia was 32% at 10‐yr post‐transplantation, mainly because of decreased urate excretion. The only factor significantly associated with an increased risk of hyperuricemia was older age. After adjustment for donor and recipient age, gender, primary liver disease, immunosuppression, and post‐operative acute renal failure, hyperuricemia as time dependent variable tended to predict (p = 0.05) subsequent CRI. The control of serum urate concentration in eight of the 21 hyperuricemic patients either by nutritional management or by allopurinol was not followed by a significant GFR improvement. Hyperuricemia after liver transplantation in children is a frequent problem which needs further investigation.
Natural spread of Cryphonectria parasitica and persistence of hypovirulence in three Italian coppiced chestnut stands
Authors: Turchetti T. , Ferretti F. , Maresi G.
Published: June 2008

Three coppiced chestnut stands near Florence (Tuscany, Italy) were monitored for 15 years. Presence of blight, damage, evaluation of different types of cankers and their relationship with stand structure were assessed. Disease incidence ranged from 67% to 99% of infected shoots, and mortality caused by blight was between 6% and 12%. Canker types were defined in the study sites; healing and healed cankers represented 70–88% of the total infections recorded, whereas normal cankers represented 9–12.5%. In general, more than one infection was detected for each shoot, and on some trunks up to nine cankers were observed. During the entire investigation period, a constant trend of hypovirulence spread was observed that was symptomatic of a substantial stability of the phenomenon: most (63.5%) undifferentiated new infections evolved into healing and healed cankers, compared with 6.5% that developed into normal infections. Isolations confirmed that a mixed inoculum (normal, intermediate and white strains) of the pathogen was spreading in the coppices. Inocula produced by pycnidia from healing cankers were examined and tested in an artificial inoculation trial. dsRNA was detected in white strains isolated from healing cankers. In this natural condition and in the complete absence of silvicultural treatments, this inoculum seems capable of ensuring both the spread of hypovirulence and its persistence over the years. Data suggest that hypovirulence and its spread are complex phenomena based on the interaction between fungal inoculum, host resistance and site conditions.
Effect of Polymorphisms in the Genes for LIF and RBP4 on Litter Size in Two German Pig Lines
Authors: Spötter A , Müller S , Hamann H , Distl O
Published: June 2008

Contents

The association of two diallelic polymorphisms in the porcine genes for leukaemia inhibitory factor (LIF) and retinol‐binding protein 4 (RBP4) with number of piglets born alive (NBA) in two German pig lines was studied. The investigated single nucleotide polymorphism (SNP) in the porcine LIF gene has been located in the 3′‐untranslated region of its third exon, whereas the SNP in the RBP4 gene genotyped in this study is intronic. At the LIF locus the allele frequencies were 0.613 for the A allele and 0.387 for the B allele in German Landrace (GL) and 0.276 for A and 0.724 for B in German Large White (GW). At the RBP4 locus, the allele frequencies were 0.586 for the A allele and 0.414 for the B allele in GL and 0.733 for A and 0.267 for B in GW. There was a significant additive effect of the LIF B allele on NBA in GW over all parities (p ≤ 0.05) and a significant positive dominance effect of 0.69 ± 0.22 (p = 0.002) was observed for first parity on NBA in GL. For RBP4, no association of genotypes and NBA was detected in GW but a significant additive effect of the A allele of 0.24 ± 0.11 (p = 0.027) and a significant dominance effect of 0.31 ± 0.13 (p = 0.020) were found in GL over all parities and confirmed through the evaluations by parity.
Ultra‐slow oscillatory neuronal activity in the rat olivary pretectal nucleus: comparison with oscillations within the intergeniculate leaflet
Authors: Szkudlarek Hanna J. , Herdzina Olga , Lewandowski Marian H.
Published: June 2008

Oscillations with a period between 1 and 4 min have been previously observed in many visual system structures. To determine whether similar oscillations in neuronal firing also exist in rat pretectum, recordings of neuronal activity were made with standard extracellular recording methodsin vivo. Oscillations with a mean period of ∼140 s were identified in 127 recording sites in olivary pretectal nucleus (OPT). Prolonged iontophoretical current ejection of bicuculline, an antagonist of GABAAreceptors, increased the firing rate but did not disrupt the oscillatory pattern of activity. This suggests that rhythmic activity of OPT neurons is either intrinsic to the nucleus or driven by rhythmic excitatory input. It is worth noting that oscillations within OPT were synchronized with the above‐described oscillatory activity in the ipsilateral intergeniculate leaflet (IGL). In the case of simultaneous double recordings from OPT and contralateral OPT or IGL, oscillations were uncorrelated. Our findings suggest functional coupling of the OPT with ipsilateral IGL, and imply that OPT, besides its well established role in pupil constriction, might be involved in modulation of the neuronal mechanism of the circadian timing system, as was suggested previously. Alternatively, IGL might be involved in pupil diameter regulation.
Postnatal changes in somatic γ‐aminobutyric acid signalling in the rat hippocampus
Authors: Tyzio Roman , Minlebaev Marat , Rheims Sylvain , Ivanov Anton , Jorquera Isabelle , Holmes Gregory L. , Zilberter Yuri , Ben‐Ari Yehezkiel , Khazipov Rustem
Published: June 2008

During postnatal development of the rat hippocampus, γ‐aminobutyric acid (GABA) switches its action on CA3 pyramidal cells from excitatory to inhibitory. To characterize the underlying changes in the GABA reversal potential, we used somatic cell‐attached recordings of GABA(A) and N‐methyl‐d‐aspartate channels to monitor the GABA driving force and resting membrane potential, respectively. We found that the GABA driving force is strongly depolarizing during the first postnatal week. The strength of this depolarization rapidly declines with age, although GABA remains slightly depolarizing, by a few millivolts, even in adult neurons. Reduction in the depolarizing GABA driving force was due to a progressive negative shift of the reversal potential of GABA currents. Similar postnatal changes in GABA signalling were also observed using the superfused hippocampus preparation in vivo, and in the hippocampal interneurons in vitro. We also found that in adult pyramidal cells, somatic GABA reversal potential is maintained at a slightly depolarizing level by bicarbonate conductance, chloride‐extrusion and chloride‐loading systems. Thus, the postnatal excitatory‐to‐inhibitory switch in somatic GABA signalling is associated with a negative shift of the GABA reversal potential but without a hyperpolarizing switch in the polarity of GABA responses. These results also suggest that in adult CA3 pyramidal cells, somatic GABAergic inhibition takes place essentially through shunting rather than hyperpolarization. Apparent hyperpolarizing GABA responses previously reported in the soma of CA3 pyramidal cells are probably due to cell depolarization during intracellular or whole‐cell recordings.
Foot infections in diabetes (DFIs) in the out‐patient setting: an Italian multicentre observational survey
Authors: Esposito S. , Leone S. , Noviello S. , Fiore M. , Ianniello F. , Felaco F. M. , Romagnoli F. , Sarli E.
Published: June 2008

Aims  To conduct a multicentre observational study to describe management of foot infections in diabetes in the out‐patient setting in Italy.

Patients and methods  Ten centres equally distributed nationwide were asked to collect, by means of a spreadsheet (Access/Excel Microsoft program), data concerning 30 consecutive diabetic patients with foot infections deemed suitable for antibiotic treatment in the out‐patient setting. Centres with ≥ 5 years’ experience of out‐patient management were selected. Data from 271 consecutive patients treated as out‐patients were collected and analysed by the central coordinator. Statistical analysis was performed using the SPSS statistical software package.

Results  Lesions were mainly located at the toes and midfoot (33.6 and 30.2%, respectively); 63 (23.2%) patients had multiple ulcers. Seventy (25.8%) patients also had concomitant osteomyelitis. Three hundred and four pathogens, including Gram‐positive and Gram‐negative aerobes and anaerobes, were isolated in 219/271 patients (80.8%) by culturing debrided tissue (71.2%) or purulent material (28.8%). Infections were polymicrobial in 33.8% of patients. The most common pathogens were Staphylococcus aureus (27.3%) and Pseudomonas spp. (20.4%); enterobacteriaceae, enterococci, streptococci and anaerobes accounted for 11.5, 7.6, 6.9 and 1.9%, respectively. Antibiotics were frequently administered by parenteral route and frequently in combination. Piperacillin/tazobactam was the parenteral antibiotic most frequently utilized (21.1%). Cure/improvement was observed in 93.4% of patients.

Conclusions  Foot ulcers in diabetes are common and serious; the aetiology is often polymicrobial, often including S. aureus and Pseudomonas spp. Treatment in the out‐patient setting is safe and effective, and penicillins together with β‐lactamase inhibitors and fluoroquinolones are the most frequent choice.
RD Lawrence Lecture 2008 Targeting GLP‐1 release as a potential strategy for the therapy of Type 2 diabetes
Authors: Gribble F. M.
Published: June 2008

Glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) are gastrointestinal hormones that play an important role in stimulating postprandial insulin release from pancreatic β‐cells. Agents that either mimic GLP‐1 or prevent its degradation are now available for the treatment of Type 2 diabetes, and strategies to enhance endogenous GLP‐1 release are under assessment. As intestinal peptides have a range of actions, including appetite regulation and coordination of fat metabolism, harnessing the enteric endocrine system is a promising new field for drug development.
Imperium in Imperioand the Political Origins of the American Labor Conspiracy Doctrine
Authors: KAHANA JEFFREY S.
Published: June 2008

Many political essayists and judges writing in the early republic sought to circumscribe actions deemed oppressive and otherwise interfering with civil liberty. Associations seeking to advance a set of narrow interests at the expense of the public posed a threat to civil liberty. The way that threat was interpreted in the specific case of labor associations is the subject of this article. It was not the economic power of such entities that gave rise to indictments. Rather the political significance of “private confederacies” acting as an“imperium in imperio”was cited as the key threat to the new political order. Thus, Judge Levy in granting legitimacy to the American labor conspiracy laws did not cite common law precedent but his concern that “a new legislature consisting of journeymen shoemakers” would usurp the legitimate power “of our state legislatures.”