bluuebunny/crossref_metadata_2025 huggingface dataset:
THE RELEVANCE OF THE COOPERATIVE MODEL IN THE FIELD OF RENEWABLE ENERGY
Authors: HUYBRECHTS Benjamin , MERTENS Sybille
Published: May 2014

While ‘traditional’ cooperatives operating for a long time in fields such as banking, agriculture, or retail, have received important attention in the cooperative literature, much work still needs to be done to understand why and how cooperatives emerge either in fields in which they have not traditionally been widespread (such as health and care, services, etc.), or in ‘new’ fields or sub‐fields (such as fair trade, microfinance or renewable energy). Research is even more needed insofar as ‘new’ cooperatives tend to differ from traditional ones in several ways, for instance through the involvement of multiple stakeholders (rather than a dominant one such as producers, consumers or workers) or through a stronger orientation towards general interest goals (beyond traditional mutual interest at the basis of most cooperatives). In this article, we analyze the emergence of cooperatives in the field of renewable energy. This emergence has raised a lot of enthusiasm among the supporters of cooperatives and citizen‐based renewable energy as well as questions regarding the viability and the replicability of this model. On the one hand, the assets of the cooperative model enable us to understand why this form has been adopted by citizen groups and has developed, although to varying extents, in many countries. On the other hand, the limits or weaknesses of the model enable us to explain why cooperatives are still a minority in the field of renewable energy and why their development is constrained by several obstacles.
The eunuch phenomenon: adaptive evolution of genital emasculation in sexually dimorphic spiders
Authors: Kuntner Matjaž , Agnarsson Ingi , Li Daiqin
Published: May 2014

Under natural and sexual selection traits often evolve that secure paternity or maternity through self‐sacrifice to predators, rivals, offspring, or partners. Emasculation—males removing their genitals—is an unusual example of such behaviours. Known only in insects and spiders, the phenomenon's adaptiveness is difficult to explain, yet its repeated origins and association with sexual size dimorphism (SSD) and sexual cannibalism suggest an adaptive significance. In spiders, emasculation of paired male sperm‐transferring organs — secondary genitals — (hereafter, palps), results in ‘eunuchs’. This behaviour has been hypothesized to be adaptive because (i) males plug female genitals with their severed palps (plugging hypothesis), (ii) males remove their palps to become better fighters in male–male contests (better‐fighter hypothesis), perhaps reaching higher agility due to reduced total body mass (gloves‐off hypothesis), and (iii) males achieve prolonged sperm transfer through severed genitals (remote‐copulation hypothesis). Prior research has provided evidence in support of these hypotheses in some orb‐weaving spiders but these explanations are far from general. Seeking broad macroevolutionary patterns of spider emasculation, we review the known occurrences, weigh the evidence in support of the hypotheses in each known case, and redefine more precisely the particular cases of emasculation depending on its timing in relation to maturation and mating: ‘pre‐maturation’, ‘mating’, and ‘post‐mating’. We use a genus‐level spider phylogeny to explore emasculation evolution and to investigate potential evolutionary linkage between emasculation,SSD, lesser genital damage (embolic breakage), and sexual cannibalism (females consuming their mates). We find a complex pattern of spider emasculation evolution, all cases confined to Araneoidea: emasculation evolved at least five and up to 11 times, was lost at least four times, and became further modified at least once. We also find emasculation, as well as lesser genital damage and sexual cannibalism, to be significantly associated withSSD. These behavioural and morphological traits thus likely co‐evolve in spiders. Emasculation can be seen as an extreme form of genital mutilation, or even a terminal investment strategy linked to the evolution of monogyny. However, as different emasculation cases in araneoid spiders are neither homologous nor biologically identical, and may or may not serve as paternity protection, the direct link to monogyny is not clear cut. Understanding better the phylogenetic patterns of emasculation and its constituent morphologies and behaviours, a clearer picture of the intricate interplay of natural and sexual selection may arise. With the here improved evolutionary resolution of spider eunuch behaviour, we can more specifically tie the evidence from adaptive hypotheses to independent cases, and propose promising avenues for further research of spider eunuchs, and of the evolution of monogyny.
What have studies of non‐industrialized countries told us about the cause of allergic disease?
Authors: Fogarty A.W.
Published: May 2014

The increase in allergic diseases that was observed in countries that had experienced rapid economic growth since the mid‐20th century initiated a search for environmental exposures that may explain these phenomena that continues to the present day. Societies that are in the earlier stages of the process of industrialization provide an opportunity to compare the initial stages of economic development and the lifestyle changes that may accompany this, with other communities whose way of life may not have changed appreciably for centuries. These studies have consistently demonstrated higher levels of allergic disease in the relatively affluent populations compared with those who maintain a more traditional lifestyle. Environmental changes that have emerged from these studies that may modify the risk of allergic disease include microbial exposures including parasite infection, pollution, diet and obesity. In addition, food and drug allergies represent a neglected area of research in these countries that may be causing a relatively high burden of disease.
Determination of the allelic frequency in Smith–Lemli–Opitz syndrome by analysis of massively parallel sequencing data sets
Authors: Cross J.L. , Iben J. , Simpson C.L. , Thurm A. , Swedo S. , Tierney E. , Bailey‐Wilson J.E. , Biesecker L.G. , Porter F.D. , Wassif C.A.
Published: May 2014

Data from massively parallel sequencing or ‘Next Generation Sequencing’ of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single nucleotide polymorphism (SNP) or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes, we analyzed the causative gene for the disorder Smith–Lemli–Opitz Syndrome (SLOS), the 7‐dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening.
Systematic Temporal Patterns in the Relationship Between Housing Development and Forest Bird Biodiversity
Authors: PIDGEON ANNA M. , FLATHER CURTIS H. , RADELOFF VOLKER C. , LEPCZYK CHRISTOPHER A. , KEULER NICHOLAS S. , WOOD ERIC M. , STEWART SUSAN I. , HAMMER ROGER B.
Published: May 2014

As people encroach increasingly on natural areas, one question is how this affects avian biodiversity. The answer to this is partly scale‐dependent. At broad scales, human populations and biodiversity concentrate in the same areas and are positively associated, but at local scales people and biodiversity are negatively associated with biodiversity. We investigated whether there is also a systematic temporal trend in the relationship between bird biodiversity and housing development. We used linear regression to examine associations between forest bird species richness and housing growth in the conterminous United States over 30 years. Our data sources were the North American Breeding Bird Survey and the 2000 decennial U.S. Census. In the 9 largest forested ecoregions, housing density increased continually over time. Across the conterminous United States, the association between bird species richness and housing density was positive for virtually all guilds except ground nesting birds. We found a systematic trajectory of declining bird species richness as housing increased through time. In more recently developed ecoregions, where housing density was still low, the association with bird species richness was neutral or positive. In ecoregions that were developed earlier and where housing density was highest, the association of housing density with bird species richness for most guilds was negative and grew stronger with advancing decades. We propose that in general the relationship between human settlement and biodiversity over time unfolds as a 2‐phase process. The first phase is apparently innocuous; associations are positive due to coincidence of low‐density housing with high biodiversity. The second phase is highly detrimental to biodiversity, and increases in housing density are associated with biodiversity losses. The long‐term effect on biodiversity depends on the final housing density. This general pattern can help unify our understanding of the relationship of human encroachment and biodiversity response.

Patrones Sistemáticos Temporales en la Relación entre Desarrollos Urbanos y la Biodiversidad de Aves de Bosque
Swarm Intelligent Compressive Routing in Wireless Sensor Networks
Authors: Mehrjoo Saeed , Sarrafzadeh Abdolhossein , Mehrjoo Mehrdad
Published: May 2014

This article proposes a novel algorithm to improve the lifetime of a wireless sensor network. This algorithm employs swarm intelligence algorithms in conjunction with compressive sensing theory to build up the routing trees and to decrease the communication rate. The main contribution of this article is to extend swarm intelligence algorithms to build a routing tree in such a way that it can be utilized to maximize efficiency, thereby rectifying the delay problem of compressive sensing theory and improving the network lifetime. In addition, our approach offers accurate data recovery from small amounts of compressed data. Simulation results show that our approach can effectively extend the network lifetime of a large‐scale wireless sensor network.
Deconstructing alcohol use on a night out in England: Promotions, preloading and consumption
Authors: McClatchley Kirstie , Shorter Gillian W. , Chalmers Jenny
Published: May 2014

Introduction and Aims

To examine alcohol consumed during a drinking event (a single drinking occasion) by those attending public house/on‐trade establishments on nights with standard pricing and nights with promotional prices.

Design and Methods

Data (n = 425) were collected in an ecological momentary assessment over eight nights in two locations (Midlands and London) on both promotional and standard (Saturday) nights. Multiple regression was used to predict event alcohol consumption by sex, age, type of night, alcohol preloading behaviour, marital and employment status, education, Alcohol Use Disorders Identification Test alcohol consumption questions separately or total AUDIT‐C and social group size.

Results

Mean (UK) units consumed were 11.8 (London) and 14.4 (Midlands). In London, consumption was similar on promotional and standard nights, but in the Midlands, standard night consumption was three units higher. Preloading was reported by 30%; more common on standard nights. Regression analyses revealed being male, preloading and past‐year total AUDIT‐C were associated with higher event consumption. However, when AUDIT‐C questions were added separately, being a standard night was associated with increased event consumption and different AUDIT‐C questions were significantly associated with event consumption in each location.

Discussion and Conclusions

Event consumption reflected heavy episodic drinking and was influenced by price. Promotional night consumption either matched standard Saturday night consumption or was slightly lower. In London, there was a significant preference for drinking at least one promotional beverage on promotional nights. On standard nights, consumption was over a wider range of venues, and preloading with off‐trade alcohol was more likely. [McClatchley K, Shorter GW, Chalmers J. Deconstructing alcohol use on a night out in England: Promotions, preloading and consumption. Drug Alcohol Rev 2014;33:367–375]
RISING R&D INTENSITY AND ECONOMIC GROWTH
Authors: POLLAK ANDREAS
Published: May 2014

Over the past decades, private R&D spending in the United States and other developed countries has been growing faster than gross domestic product. At the same time, the growth rates of per-capita and aggregate output have been rather stable, possibly declining slightly. This article proposes a growth model that can account for the observed phenomenon by explicitly describing competition among technological leaders and followers in individual markets in a way that is consistent with existing studies on firms' motivation to invest in R&D. The model shows the possibility that the unsustainable trend of rising R&D intensity persists for a very long time. (JEL O3, O4, L1)
Effects of altered precipitation on insect community composition and structure in a meadow steppe
Authors: ZHU HUI , WANG DELI , WANG LING , FANG JIAN , SUN WEI , REN BINGZHONG
Published: May 2014

Precipitation can be a key driver of ecosystem functioning in semi‐arid and arid grasslands. Altered precipitation patterns had significant impacts on plant community dynamics, which in turn influenced the community composition and structure of higher trophic levels, especially insects, in grasslands.

A field experiment was conducted by manipulating the amount of natural precipitation (control, +30% rainfall, and −30% rainfall) to examine the effects of altered precipitation patterns on insect diversity, abundance, and trophic structure in a meadow steppe over 3 years (2007–2009).

The results showed that the increased precipitation treatment significantly enhanced above‐ground biomass of the entire plant community and particularly grasses, whereas the decreased precipitation treatment significantly reduced them. There were year‐to‐year changes in species richness, Shannon–Wiener index, and abundance of the whole insect community. Both increased and decreased precipitation caused declines in insect species richness and abundance owing to potentially complex vegetation‐mediated effects and direct habitat effects. The abundance of each trophic guild in the insect community responded differently to altered precipitation patterns, with lower herbivore abundance and unchanged abundance of predators and parasitoids. Thus changes in precipitation may generate an insect community that is increasingly dominated by secondary consumers.

The present results suggest that altered precipitation causes a declines in insect diversity and shifts in trophic structure, potentially influencing ecosystem functioning in grasslands. Additionally, the inter‐annual variation in the insect community under altered precipitation highlights the importance of long‐term experiments for drawing correct conclusions about the impacts of climate change on grassland ecosystems.
The importance of individual developmental variation in stage‐structured population models
Authors: de Valpine Perry , Scranton Katherine , Knape Jonas , Ram Karthik , Mills Nicholas J.
Published: May 2014

Population stage structure is fundamental to ecology, and models of this structure have proven useful in many different systems. Many ecological variables other than stage, such as habitat type, site occupancy and metapopulation status are also modelled using transitions among discrete states. Transitions among life stages can be characterised by the distribution of time spent in each stage, including the mean and variance of each stage duration and within‐individual correlations among multiple stage durations. Three modelling traditions represent stage durations differently. Matrix models can be derived as a long‐run approximation from any distribution of stage durations, but they are often interpreted directly as a Markov model for stage transitions. Statistical stage‐duration distribution models accommodate the variation typical of cohort development data, but such realism has rarely been incorporated in population theory or statistical population models. Delay‐differential equation models include lags but no variation, except in limited cases. We synthesise these models in one framework and illustrate how individual variation and correlations in development can impact population growth. Furthermore, different development models can yield the same long‐term matrix transition rates but different sensitivities and elasticities. Finally, we discuss future directions for estimating realistic stage duration models from data.
Community ecology theory predicts the effects of agrochemical mixtures on aquatic biodiversity and ecosystem properties
Authors: Halstead Neal T. , McMahon Taegan A. , Johnson Steve A. , Raffel Thomas R. , Romansic John M. , Crumrine Patrick W. , Rohr Jason R.
Published: May 2014

Ecosystems are often exposed to mixtures of chemical contaminants, but the scientific community lacks a theoretical framework to predict the effects of mixtures on biodiversity and ecosystem properties. We conducted a freshwater mesocosm experiment to examine the effects of pairwise agrochemical mixtures [fertiliser, herbicide (atrazine), insecticide (malathion) and fungicide (chlorothalonil)] on 24 species‐ and seven ecosystem‐level responses. As postulated, the responses of biodiversity and ecosystem properties to agrochemicals alone and in mixtures was predictable by integrating information on each functional group's (1) sensitivity to the chemicals (direct effects), (2) reproductive rates (recovery rates), (3) interaction strength with other functional groups (indirect effects) and (4) links to ecosystem properties. These results show that community ecology theory holds promise for predicting the effects of contaminant mixtures on biodiversity and ecosystem services and yields recommendations on which types of agrochemicals to apply together and separately to reduce their impacts on aquatic ecosystems.
Cortical cartography reveals political and physical maps
Authors: Loring David W. , Gaillard William Davis , Bookheimer Susan Y. , Meador Kimford J. , Ojemann Jeffrey G.
Published: May 2014

Advances in functional imaging have provided noninvasive techniques to probe brain organization of multiple constructs including language and memory. Because of high overall rates of agreements with older techniques, including Wada testing and cortical stimulation mapping (CSM), some have proposed that those approaches should be largely abandoned because of their invasiveness, and replaced with noninvasive functional imaging methods. High overall agreement, however, is based largely on concordant language lateralization in series dominated by cases of typical cerebral dominance. Advocating a universal switch from Wada testing and cortical stimulation mapping to functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG) ignores the differences in specific expertise across epilepsy centers, many of which often have greater skill with one approach rather than the other, and that Wada, CSM, fMRI, and MEG protocols vary across institutions resulting in different outcomes and reliability. Specific patient characteristics also affect whether Wada or CSM might influence surgical management, making it difficult to accept broad recommendations against currently useful clinical tools. Although the development of noninvasive techniques has diminished the frequency of more invasive approaches, advocating their use to replace Wada testing and CSM across all epilepsy surgery programs without consideration of the different skills, protocols, and expertise at any given center site is ill‐advised.

A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Diversity anomalies and spatial climate heterogeneity
Authors: Jiménez Iván , Ricklefs Robert E.
Published: May 2014

Aim

Diversity anomalies are differences in species richness between areas that belong to different regions but have similar environments. Some hypotheses addressing the origin of well‐known anomalies in plant diversity propose that regions with higher environmental spatial heterogeneity have higher diversity because heterogeneity fosters diversification or coexistence. Arguments supporting these hypotheses emphasize inter‐regional comparisons of diversity and assume that spatial environmental heterogeneity is higher in: (1) easternAsia (EA) than in easternNorthAmerica (ENA), (2) westernNorthAmerica (WNA) than inENA, and (3) theCapeFloristicRegion in southernAfrica (CFR) than in theSouthwestAustralian Floristic Region (SWA). Here, we evaluate these assumptions by measuring two kinds of environmental heterogeneity – spatially implicit and explicit – each thought to affect diversity via different mechanisms. The former refers to environmental variation among sites within a region, regardless of site location. The latter refers to the spatial pattern of environmental variation across a region (e.g., monotonic or undulating).

Location

EA,ENA,WNA,CFRandSWA.

Methods

Multivariate and univariate analyses of spatially implicit and explicit heterogeneity in 17 climatic variables describing central tendency, variation and extremes of temperature and precipitation.

Results

Multivariate (spatially implicit and explicit) climate heterogeneity is higher in: (1)EAthan inENA, (2)WNAthan inENA, and (3)CFRthan inSWA. However, univariate analysis revealed that the regions thought to be most homogeneous (ENAandSWA) were actually most heterogeneous in three or four climatic variables, including precipitation during the driest (ENA) or wettest (SWA) seasons.

Main conclusions

The overall inter‐regional pattern of spatially implicit and explicit heterogeneity in climate supports the three assumptions listed in the Aim. However, particular climate variables deviate from this overall pattern, implying that hypotheses linking diversity to regional heterogeneity can yield more precise predictions, and thus can be more stringently tested, than previously recognized.
Multiple drivers of plant diversity in forest ecosystems
Authors: Zhang Yu , Chen Han Y. H. , Taylor Anthony
Published: May 2014

Aim

Theoretical and empirical studies have shown that climate is a major determinant of species richness, yet the importance of climate relative to local site conditions remains unclear in forest ecosystems across large regions. Furthermore, little is known about how climate and local site conditions affect species evenness and understorey plant diversity.

Location

Canadian forest (42°37′ to 68°14′ N; 53°25′ to 134°46′ W; 4 to 2170 m elevation).

Methods

Using national, broad‐scale forest inventory data, we tested the influence of growing degree days (GDD), climate moisture index (CMI), soil drainage class (SDC) and stand age (SA) on plant diversity across Canada's forests. Diversity was assessed on variable plot sizes from 125 to 500 m2 for canopy tree and total plant species, and from 100 to 400 m2 for understorey plants.

Results

Our models accounted for 47, 30 and 49% of total variation in canopy tree species richness, Simpson's dominance index and total plant species richness, respectively. After accounting for the effects of plot size and management history, canopy richness increased with GDD and CMI and peaked at intermediate SDC and SA. Simpson's dominance index decreased with increasing GDD and CMI and was lowest at intermediate SDC and SA. Total species richness was most strongly related to SDC and was highest on imperfectly drained soils. Climatic controls on species richness of understorey strata were generally weaker than those on canopy richness.

Main conclusions

Our results for canopy richness along a mainly longitudinal gradient demonstrate the positive effects of energy on tree species diversity and show evidence for the effects of local site conditions and secondary succession on diversity. Furthermore, our results show that the extent of the influence of climate and local site conditions on plant species diversity can strongly differ between vegetation strata.
Is the grass always greener? Making sense of convergence and divergence in regeneration policies in England and Scotland
Authors: McGuinness David , Greenhalgh Paul , Pugalis Lee
Published: May 2014

This paper is concerned with the trajectories of regeneration policy discourse and practice in a devolved UK context. Over recent years the asymmetrical nature of devolved governance has intensified, exemplified by a policy of political containment in Scotland and a reconfiguration of sub‐national institutional architecture in England. Against a backdrop of the transfusion of Holyrood's devolution agenda and Westminster's localism programme, an empirical analysis of contemporary English and Scottish regeneration policy is provided. We investigate the extent to which perceived divergences in government policy resonate with those at the sharp end of regeneration practice, informed by concepts derived from the policy convergence/divergence literature. The key finding is the coexistence of ideological divergence, replete in political discourse and policy documentation, but growing convergence in actual existing practice, evidenced in the nature, extent and scale of initiatives. The enveloping fiscal context and austere politics, producing what is anticipated to be a protracted period of financial retrenchment, appears to be a defining factor in contemporary urban regeneration policy convergence.
Workfare and resistance in the US: the quietude and ineffectiveness of progressive welfare politics post 1996
Authors: MacLeavy Julie
Published: May 2014

This paper focuses on the implementation of workfare in the US, with the aim of understanding the passive response of the unions and other progressive groups to the restructuring and retrenchment of the American welfare system. In particular, it considers the disparate efforts to organise welfare recipients and low‐wage workers around the restructuring of social benefits towards work in the District of Columbia. Although the convergence of welfare recipients and low‐wage workers through ‘work‐first’ initiatives has the potential to spur political mobilisation and protest against the reform of welfare, it is found that at the local level campaigns against workfare are diverse and changeable, producing very little – it could be argued – in terms of long‐term resistance. Identifying forms of dissidence in Washington DC as constitutive of the broader liberal regime of governance and re‐regulation, this paper probes the forms, possibilities and problems of organising workfare subjects. This allows for consideration of the extent to which workfare programmes are being re‐inscribed within emerging patterns of political‐economic development and the potential for future action.
Changes in fluid pathways in a calcite vein mesh (Natih Formation, Oman Mountains): insights from stable isotopes
Authors: Arndt M. , Virgo S. , Cox S. F. , Urai J. L.
Published: May 2014

We present a structural, microstructural, and stable isotope study of a calcite vein mesh within the Cretaceous Natih Formation in the Oman Mountains to explore changes in fluid pathways during vein formation. Stage 1 veins form a mesh of steeply dipping crack‐seal extension veins confined to a 3.5‐m‐thick stratigraphic interval. Different strike orientations of Stage 1 veins show mutually crosscutting relationships. Stage 2 veins occur in the dilatant parts of a younger normal fault interpreted to penetrate the stratigraphy below. The δ18O composition of the host rock ranges from 21.8‰ to 23.7‰. The δ13C composition ranges from 1.5‰ to 2.3‰. This range is consistent with regionally developed diagenetic alteration at top of the Natih Formation. The δ18O composition of vein calcite varies from 22.5‰ to 26.2‰, whereas δ13C composition ranges from −0.8‰ to 2.1‰. A first trend observed in Stage 1 veins involves a decrease of δ13C to compositions nearly 1.3‰ lower than the host rock, whereas δ18O remains constant. A second trend observed in Stage 2 calcite has δ18O values up to 3.3‰ higher than the host rock, whereas the δ13C composition is similar. Stable isotope data and microstructures indicate an episodic flow regime for both stages. During Stage 1, formation of a stratabound vein mesh involved bedding‐parallel flow, under near‐lithostatic fluid pressures. The 18O fluid composition was host rock‐buffered, whereas 13C composition was relatively depleted. This may reflect reaction of low 13C CO2 derived by fluid interaction with organic matter in the limestones. Stage 2 vein formation is associated with fault‐controlled fluid flow accessing fluids in equilibrium with limestones about 50 m beneath. We highlight how evolution of effective stress states and the growth of faults influence the hydraulic connectivity in fracture networks and we demonstrate the value of stable isotopes in tracking changes in fluid pathways.
Validation of the manufacturing process used to produce long‐acting recombinant factor IX Fc fusion protein
Authors: McCue J. , Osborne D. , Dumont J. , Peters R. , Mei B. , Pierce G. F. , Kobayashi K. , Euwart D.
Published: May 2014

Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long‐acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human‐ and animal‐derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi‐step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process‐related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non‐human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc.
Climbazole increases expression of cornified envelope proteins in primary keratinocytes
Authors: Pople J. E. , Moore A. E. , Talbot D. C. S. , Barrett K. E. , Jones D. A. , Lim F. L.
Published: May 2014

Objective

Dandruff is a troubling consumer problem characterized by flaking and pruritus of the scalp and is considered a multifactorial condition with sebum, individual susceptibility and the fungus Malassezia all thought to play a part. The condition is commonly treated with shampoo products containing antifungal ingredients such as zinc pyrithione and climbazole. It is hypothesized that these ingredients may be delivering additional scalp skin benefits besides their antifungal activity helping to relieve dandruff effectively. The objective of this study was to evaluate the anti‐dandruff ingredient climbazole for potential skin benefits using genomics and in vitro assays.

Methods

Microarray analysis was performed to profile gene expression changes in climbazole‐treated primary human keratinocyte cells. Results were independently validated using qPCR and analysis of protein expression using ELISA and immunocytochemistry.

Results

Microarray analysis of climbazole‐treated keratinocytes showed statistically significant expression changes in genes associated with the gene ontology groups encompassing epidermal differentiation, keratinization, cholesterol biosynthesis and immune response. Upregulated genes included a number encoding cornified envelope proteins such as group 3 late‐cornified envelope proteins, LCE3 and group 2 small‐proline‐rich proteins, SPRR2. Protein analysis studies of climbazole‐treated primary keratinocytes using ELISA and immunocytochemistry were able to demonstrate that the increase in gene transcripts translated into increased protein expression of these cornified envelope markers.

Conclusion

Climbazole treatment of primary keratinocytes results in an upregulation in expression of a number of genes including those encoding proteins involved in cornified envelope formation with further studies demonstrating this did translate into increased protein expression. A climbazole‐driven increase in cornified envelope proteins may improve the scalp skin barrier, which is known to be weaker in dandruff. These studies suggest climbazole, besides its antifungal activity, is delivering positive skin benefits helping to relive dandruff symptoms effectively.
Mechanisms of pain from urinary tract infection
Authors: Rosen John M , Klumpp David J
Published: May 2014

The pain response to urinary tract infection is largely uncharacterized, but the symptomatic response to urinary tract infection contrasts with the lack of pain response among individuals with asymptomatic bacteriuria. Quantifying pelvic pain in a murine urinary tract infection model, uropathogenic Escerichia coli induces transient pelvic pain, whereas an asymptomatic bacteriuria E. coli isolate causes no pain, thus recapitulating the spectrum of clinical responses to intravesical E. coli. These differential pain responses are not correlated with bladder colonization or inflammation, but instead are intrinsic to E. coli lipopolysaccharide and dependent on the lipopolysaccharide receptor, TLR4. Epidemiological data suggest a link between interstitial cystitis and a history of urinary tract infection, so it was evaluated whether repetitive uropathogenic E. coli instillation would result in chronic pain through central sensitization. Although repeated infection with wild type uropathogenic E. coli results in only transient episodes of acute pain, a uropathogenic E. coli mutant lacking O‐antigen causes chronic, post‐urinary tract infection pelvic pain. Similarly, a K‐12 E. coli strain lacking O‐antigen induces chronic pain that persisted long after bacterial clearance, and expressing O‐antigen nullified the pain phenotype. Spinal cords isolated from mice with post‐urinary tract infection chronic pain showed deficits in short‐term depression consistent with central sensitization. Deleting O‐antigen gene complex from a uropathogenic E. coli strain and subsequent heterologous expression of O‐antigen gene clusters shows that a single bacterial isolate can exhibit pain phenotypes ranging from a null phenotype, an acute pain phenotype, to a chronic pain phenotype. Post‐urinary tract infection chronic pain is also associated with voiding dysfunction and anxious/depressive behavior. These effects are also mediated by TRPV1 at the level of pain establishment and CCR2 at the level of pain maintenance. Together, these findings show that transient infection with E. coli might result in chronic visceral pain with the hallmarks of neuropathic pain. This pattern of behaviors mimics the spectrum of interstitial cystitis symptoms, thus supporting the possibility of an infectious etiology of interstitial cystitis.
Hypersensitive bladder: A solution to confused terminology and ignorance concerning interstitial cystitis
Authors: Homma Yukio
Published: May 2014

Taxonomy or nomenclature concerning interstitial cystitis and its related symptom syndromes is in a state of confusion. After analyzing the reasons for confusion in regard to three components (disease name, symptoms, Hunner's lesion), I would like to propose a new term, “hypersensitive bladder”, taking after overactive bladder, as a solution. Hypersensitive bladder symptoms are defined as “increased bladder sensation, usually associated with urinary frequency and nocturia, with or without bladder pain.” The proposal of hypersensitive bladder is based on: (i) it does not appear a symptom syndrome, but a disease by ending with an organ name, “bladder”; (ii) it does not contain confusable symptom terms (pain and urgency), but indicates irritative symptoms including pain and urgency; and (iii) it suggests pathophysiological hyperactivity of sensory nerves. Interstitial cystitis is defined by three requirements: (i) hypersensitive bladder symptoms; (ii) bladder pathology; and (iii) no other diseases, where bladder pathology should be clearly stated either as Hunner's lesion or glomerulations after hydrodistention. Hypersensitive bladder can be used for the condition with hypersensitive bladder symptoms, but no obvious disease explaining hypersensitive bladder symptoms identified. Interstitial cystitis is a representative disease causing hypersensitive bladder symptoms, most typically with pain, but might be painless and indistinguishable from overactive bladder. Introducing hypersensitive bladder as a counter concept of overactive bladder into bladder dysfunction taxonomy will facilitate clinical practice and research progress, and attract considerable attention from the medical world.
Efficacy and safety of augmentation ileocystoplasty combined with supratrigonal cystectomy for the treatment of refractory bladder pain syndrome/interstitial cystitis with Hunner's lesion
Authors: Kim Hyung Joon , Lee Jae Seong , Cho Won Jin , Lee Hyo Serk , Lee Ha Na , You Hyun Wook , Jung Wonho , Lee Kyu‐Sung
Published: May 2014

Objective

To evaluate the efficacy and safety of augmentation ileocystoplasty with supratrigonal cystectomy for the treatment of refractory bladder pain syndrome/interstitial cystitis patients with Hunner's lesion.

Methods

Of 45 patients who underwent augmentation ileocystoplasty with supratrigonal cystectomy between July 2006 and June 2012, 40 patients (33 women, 7 men) were included in the analysis. Primary outcome was the change in the O'Leary–Sant interstitial cystitis symptoms/problem index from baseline to 1, 3 and 6 months. Changes in pain, urgency, frequency, functional bladder capacity and maximal cystometric capacity were also assessed. Intraoperative and postoperative complications were evaluated.

Results

Median preoperative symptom duration was 5.0 years (range 3.0–6.0 years). Pain decreased significantly after surgery (8.3 vs 1.3, P < 0.001). Functional bladder capacity and maximal cystometric capacity increased, whereas frequency, urgency and nocturia decreased significantly after surgery (all P < 0.001). At 6 months, significant improvements in the interstitial cystitis symptom index (17.8 vs 9.9, P < 0.001) and interstitial cystitis problem index (14.6 vs 6.5, P < 0.001) compared with baseline were noted. Seven patients developed vesicoureteral reflux and seven patients had acute pyelonephritis that resolved with antibiotic treatment. Five patients required clean intermittent self‐catheterization. None of the preoperative factors were significant predictors of treatment failure.

Conclusions

Augmentation ileocystoplasty with supratrigonal cystecomy decreased pain and frequency, and increased bladder capacity significantly. There were no severe complications related to surgery during follow up. Augmentation ileocystoplasty with supratrigonal cystectomy is therefore an appropriate final treatment strategy for refractory bladder pain syndrome/interstitial cystitis patients with Hunner's lesion.
Development and evaluation of an E‐health system to care for patients with bladder pain syndrome/interstitial cystitis
Authors: Lee Ming‐Huei , Wu Huei‐Ching , Lin Jen‐Yung , Tan Tan‐Hsu , Chan Po‐Chou , Chen Yung‐Fu
Published: May 2014

Objectives

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a chronic disease that highly degrades the quality of life for patients. In the present study, Internet intervention was used to care for bladder pain syndrome/interstitial cystitis patients to alleviate their pain and bothering symptoms.

Methods

Healthcare education was carried out through the Internet by asking the patients, who were randomly divided into study (40 patients) and control (40 patients) groups, to check possible sensitive foods, habits, and behaviors weekly to remind and consolidate important rules for promoting quality of life. The symptom flares consultation through short message service with the Internet used to elevate healthcare efficiency was undertaken. Questionnaires, including Short Form 36 health survey, O'Leary–Sant symptom and problem indices, as well as visual analog scales pain and urgency scales, were used to evaluate quality of life and disease severity improvements before and after information and communication technology intervention. The outcome was evaluated at week 8.

Results

The quality of life of both the control and study groups was significantly improved. The quality of life and visual analog scales for the patients in the study group with information and communication technology intervention showed a much greater improvement compared with the patients in the control group (P < 0.05).

Conclusions

The E‐health system was shown to be effective in improving quality of life of bladder pain syndrome/interstitial cystitis patients through intervention of Internet healthcare education and short message service for the consolidation of healthy behavior and lifestyle in the 8‐week follow up.
Urethral sensation: Basic mechanisms and clinical expressions
Authors: Birder Lori A , de Wachter Stefan , Gillespie James , Wyndaele Jean Jacques
Published: May 2014

A prerequisite for conscious bladder control is adequate sensory input to the central nervous system, and it is well established that changes in sensory mechanisms can give rise to disturbances in bladder function. Impulses related to the desire to void are believed to course through the pelvic nerves, and those for sensation of a full bladder course through the pudendal nerves. The sense of imminent micturition most probably resides in the urethra, and the desire to void comes from stretching the bladder wall. In addition, a variety of structures play an important role in terms of urethral closure (such as the urethral epithelium, vasculature and smooth muscle) that are necessary to maintain continence. This overview will discuss mechanisms related in part to the urethra involved in activation of bladder reflexes and sensation with a discussion on the mucosa (urothelium and underlying lamina propria) and underlying cellular structures.
A Review and Comparison of Bandwidth Selection Methods for Kernel Regression
Authors: Köhler Max , Schindler Anja , Sperlich Stefan
Published: May 2014

Over the last decades, several methods for selecting the bandwidth have been introduced in kernel regression. They differ quite a bit, and although there already exist more selection methods than for any other regression smoother, one can still observe coming up new ones. Given the need of automatic data‐driven bandwidth selectors for applied statistics, this review is intended to explain and, above all, compare these methods. About 20 different selection methods have been revised, implemented and compared in an extensive simulation study.
Unani treatment and leech therapy saved the diabetic foot of a patient from amputation
Authors: Zaidi SM Arif
Published: May 2014

Every 30 seconds, a lower limb amputation is carried out due to diabetes throughout the world. The mortality rate due to diabetic foot gangrene is just next to that of cancer. As tissue death cannot be reversed, surgical removal of the affected tissue (debridement) or amputation of the limb is the only treatment option left when gangrene has advanced. The present case study illustrates an option to treat poorly healing diabetic wounds with Unani medicine (blood purifier and deobstruent) besides hirudotherapy. The study was performed on a 60‐year‐old woman suffering from diabetic foot (on the left) grade 5 and facing the prospect of imminent amputation. The patient was having severe pain (80 mm on a 100 mm visual analogue scale) in the gangrenous foot and foul‐smelling with necrosed areas. Wound dressing was done with unripe papaya as it has a very good role in clearing necrotising area and hirudotherapy was also used in poorly healing wounds. The pain score decreased to 0–10 mm on a 100 mm visual analogue scale within 20 days and no further pain relieving medication was required. Over a time interval of nearly 3·5 months, necrotic areas disappeared and the wound was completely healed.
Evaluation of Potential Bleeding Problems in Dermatologic Surgery
Authors: Sharkey Irwin , Brughera‐Jones Antonella
Published: May 2014

Even minor dermatologic surgery can be complicated by severe hemorrhage if the surgeon fails to anticipate and recognize potential bleeding disorders.

How to detect and manage such problems is discussed. The most important consideration is a careful and thorough history prior to surgery in all patients.
New Instruments For Use in Hair Transplants Techniques
Authors: Baran Robert
Published: May 2014

This article will describe new instruments for use in hair transplants that have eliminated many complications and simplified the procedure for both the patient and the physician.
Basal‐Cell Carcinomas of the Eyelids: Pitfalls in Diagnosis and Therapy
Authors: Charles Norman C.
Published: May 2014

All eyelid lesions, because of their strategic proximity to the ocular and adnexal structures, should be considered as basal cell carcinomas until proved otherwise. The morphologic similarities of basal cell carcinomas to other common lid lesions are described. Following positive biopsy, successful therapy involves choice of an appropriate therapeutic modality for each individual patient and tumor.
Recurrent Basal Cell Carcinomas In Young Women
Authors: Robins Perry , Albom Michael J.
Published: May 2014

During a two year study at the New York University Medical Center, the authors found that basal‐cell carcinoma recurs in young women more frequently than in any other group. We offer three possible explanations, all relating to inadequate management during initial treatment.
Use of Skin Flaps in Dermatologic Surgery of the Face
Authors: Konz Birger
Published: May 2014

Surgical ablation of some cutaneous conditions often result in defects which are difficult to close by primary suture. Pedicle flaps are especially useful for closure of deep defects. They consist of skin and subcutaneous tissue which contain blood supply from the site from which they are raised. This paper discusses the specific use of these grafts.
Surgical Methods in the Treatment of Rhinophyma
Authors: Karge Hans‐Joachim , Konz Birger
Published: May 2014

Fifteen patients with rhinophyma were treated surgically by cutting off the hyperplasia nodules with a scalpel followed by shaving with a disposable shaving razor. The cosmetic results were good and no scar formation occurred.
Complications In The Treatment of Hemangiomas
Authors: Rees Thomas D. , Connors David
Published: May 2014

Occasionally the results of treatment can be worse than the disease. This has often been the case in unwarrented and aggressive early treatment of hemangiomata. This paper focuses on modern concepts of the management of hemangiomas.