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The lack of regulation of child labor in the Province of Santa Fe has filled with gaps and uncertainties the scheme of participation of children and adolescents. The research carried out analyzes the claims and opinions of the legal community and the answers provided by the parliamentary initiatives in debate to inquire about the formation, function and performance of this figure. This article aims, through reflections, criticisms and proposals, at making a contribution to the construction of a model that guarantees the full and effective exercise of the rights of children and adolescents. [ABSTRACT FROM AUTHOR]

An experimental technique for the estimation of the temporal-averaged vapour volume fraction within high-speed cavitating flow orifices is presented. The scientific instrument is designed to employ X-ray micro computed tomography (microCT) as a quantitative 3D measuring technique applied to custom designed, large-scale, orifice-type flow channels made from Polyether-ether-ketone (PEEK). The attenuation of the ionising electromagnetic radiation by the fluid under examination depends on its local density; the transmitted radiation through the cavitation volume is compared to the incident radiation, and combination of radiographies from sufficient number of angles leads to the reconstruction of attenuation coefficients versus the spatial position. This results to a 3D volume fraction distribution measurement of the developing multiphase flow. The experimental results obtained are compared against the high speed shadowgraph visualisation images obtained in an optically transparent nozzle with identical injection geometry; comparison between the temporal mean image and the microCT reconstruction shows excellent agreement. At the same time, the real 3D internal channel geometry (possibly eroded) has been measured and compared to the nominal manufacturing CAD drawing of the test nozzle. [ABSTRACT FROM AUTHOR]

In this study we introduce the regional flux analysis , a novel approach to deformation based morphometry based on the Helmholtz decomposition of deformations parameterized by stationary velocity fields. We use the scalar pressure map associated to the irrotational component of the deformation to discover the critical regions of volume change. These regions are used to consistently quantify the associated measure of volume change by the probabilistic integration of the flux of the longitudinal deformations across the boundaries. The presented framework unifies voxel-based and regional approaches, and robustly describes the volume changes at both group-wise and subject-specific level as a spatial process governed by consistently defined regions. Our experiments on the large cohorts of the ADNI dataset show that the regional flux analysis is a powerful and flexible instrument for the study of Alzheimer's disease in a wide range of scenarios: cross-sectional deformation based morphometry, longitudinal discovery and quantification of group-wise volume changes, and statistically powered and robust quantification of hippocampal and ventricular atrophy. [ABSTRACT FROM AUTHOR]

Aim: To conduct a network meta-analysis (NMA) to determine the comparative efficacy, as measured by sustained virological response (SVR), between boceprevir (BOC), telaprevir (TEL), faldaprevir (FAL), simeprevir (SIM) and sofosbuvir (SOF) in combination with peginterferon–ribavirin (PR) against a control of PR. Design: A literature search was conducted to identify randomized controlled trials (RCTs) including adult patients with hepatitis C virus genotype 1 who were naive to any prior therapy. RCTs assessing standard duration therapy (SDT) or response-guided therapy (RGT) BOC, TEL, FAL, SIM or SOF in combination with PR against a control of PR were eligible for inclusion. All RCTs must have provided SVR at either 12 or 24 weeks post-therapy cessation. Results: We included nine RCTs. All direct-acting antivirals (DAAs) were found to perform better than PR. Additionally, SDT FAL was found to be better than the 240 mg RGT FAL regimen with the PR lead-in. A sensitivity analysis excluding RCTs with only SVR at 12 weeks was consistent with the results of the primary analysis. A sensitivity analysis removing an RCT assessing SIM that reported SVR of >60% in the PR control group additionally found that RGT SIM was superior to the 240 mg RGT FAL regimen with the PR lead-in. Discussion: Our analyses indicate that SDT and RGT regimens of DAAs plus PR do not differ greatly in terms of SVR among treatment-naive hepatitis C genotype 1 patients. More advanced Bayesian network meta-analyses are likely needed to incorporate a comprehensive evidence base, expanding beyond randomized clinical trials. [ABSTRACT FROM AUTHOR]

Several types of muscle abnormalities are present in the poultry industry as a result of genetic selection, leading to decreased quality of meat and consequent economic loss. The appearance of thin (moderate) to thick (severe) white striping (WS) striations parallel to muscle fibers on the surface of broiler breast fillets is one of the most troubling issues in the poultry industry. White striping also has unfavorable implications on visual acceptance, nutritional value, and processing traits of breast meat. The aim of this survey was to assess the influence of market class (medium and heavy birds) and genotype (standard- and high-breast yield hybrids) on the incidence of WS in broiler chickens raised under commercial conditions in Italy. The incidence of WS for both medium and heavy broilers was high (43.0%), with 6.2% of samples considered severe. Heavy flocks had significantly higher percentages of both moderate (46.9 vs. 25.8%; P ≤ 0.001) and severe (9.5 vs. 2.7%; P ≤ 0.001) WS than medium flocks. Considering the effect of genotype, high-breast yield hybrids exhibited a higher incidence of both moderate (40.2 vs. 33.2%; P ≤ 0.001) and severe WS (7.2 vs. 5.0%; P ≤ 0.001) compared with standard-breast yield birds. In addition, within the medium class, the occurrence of WS reached higher levels in flocks of males. The heavy class consisted of male flocks separated into 2 slaughter weight categories. Birds that reached higher slaughtering weights (3.8–4.2 kg) exhibited higher incidence of WS than flocks slaughtered at lower weights (3.0–3.8 kg) at a similar age. In conclusion, the main broiler genotypes used for commercial production were affected by a high rate of WS; hybrids selected for higher breast yields were more prone to the WS abnormality. In addition, severe cases of WS are even more prevalent at higher slaughter age and weight, although reduced growth rate is associated with a lower incidence and severity of WS. [ABSTRACT FROM AUTHOR]

Ophryotrocha diademais an outcrossing, simultaneous hermaphroditic polychaete with external fertilization. In isolated pairs, mature worms take turn contributing eggs upon the condition that their partners reciprocate egg donation. In dense populations, these worms do not reciprocate. Instead, they strongly compete for mating in their preferred male role and produce few eggs. This plastic sex allocation may result in an overall different reproductive performance: mean individual reproductive output will be larger in sparse than in dense populations. We tested this hypothesis by measuring the individual reproductive output (paternal and maternal offspring) of worms in sparse and dense replicated populations. In dense populations, mean individual reproductive output was fourfold lower than that in sparse populations. We hypothesise that such dramatic demographic costs are potentially widespread in outcrossing simultaneous hermaphrodites with external fertilization and plastic sex allocation. The reproductive output of hermaphroditic organisms is a function of population density (i.e. the number of conspecifics) and studies on population growth and reproductive performance should take this effect into account. [ABSTRACT FROM PUBLISHER]

Abstract: Non-linear registration is a key instrument for computational anatomy to study the morphology of organs and tissues. However, in order to be an effective instrument for the clinical practice, registration algorithms must be computationally efficient, accurate and most importantly robust to the multiple biases affecting medical images. In this work we propose a fast and robust registration framework based on the log-Demons diffeomorphic registration algorithm. The transformation is parameterized by stationary velocity fields (SVFs), and the similarity metric implements a symmetric local correlation coefficient (LCC). Moreover, we show how the SVF setting provides a stable and consistent numerical scheme for the computation of the Jacobian determinant and the flux of the deformation across the boundaries of a given region. Thus, it provides a robust evaluation of spatial changes. We tested the LCC-Demons in the inter-subject registration setting, by comparing with state-of-the-art registration algorithms on public available datasets, and in the intra-subject longitudinal registration problem, for the statistically powered measurements of the longitudinal atrophy in Alzheimer's disease. Experimental results show that LCC-Demons is a generic, flexible, efficient and robust algorithm for the accurate non-linear registration of images, which can find several applications in the field of medical imaging. Without any additional optimization, it solves equally well intra & inter-subject registration problems, and compares favorably to state-of-the-art methods. [Copyright &y& Elsevier]

Related species share genetic and developmental backgrounds. Therefore, separate-sex species that share recent common ancestors with hermaphroditic species may have hidden genetic variation for sex determination that causes some level of lability of expression of gender. Worms of the polychaete species Ophryotrocha labronica have separate, dimorphic sexes and their ancestor was hermaphroditic. Ophryotrocha labronica has a worldwide distribution and populations may differ in the degree of gender specialization. We analyzed the extent to which O. labronica had fixed or labile expression of gender. We found that there were up to four different sexual phenotypes, namely, pure males, males with oocytes, pure females, and females with sperm; the relative frequency of these sexual phenotypes varied in three geographically-distant populations. These sexual morphs had either male or female morphology. However, populations differed in the extent to which worms were sexually dimorphic. In the less dioecious-like population (in which pure males and females were virtually absent, all worms had both oocytes and sperm and sexual dimorphism was relatively weak), males with oocytes had slightly plastic female allocation that depended on mating opportunities—a clearly hermaphroditic trait. Males with oocytes and females with sperm were not functional hermaphrodites. They only used one type of gametes to reproduce and in this respect they probably differed from many cases of inconstancy of gender described in the literature. We consider these populations as novel examples of intermediate states between androdioecy and dioecy. This study contributes to our understanding of breeding systems as continuous gradients rather than as distinct clear-cut alternatives. [ABSTRACT FROM PUBLISHER]

Social insect colonies are attractive for many arthropods. The rare velvet ant, Mutilla europaea, visit colonies of Polistes wasps, but to date it was unclear which resources it targeted therein. Our field observations and bioassays showed that velvet ants visit the colonies of the social wasp Polistes biglumis almost undisturbed and may feed on larval wasp saliva. Chemical insignificance and resistance are the characteristics that allow velvet ants to visit unharmed wasp colonies and gain such a nutritious reward. [ABSTRACT FROM AUTHOR]

Social parasites exploit societies, rather than organisms, and rear their brood in social insect colonies at the expense of their hosts, triggering a coevolutionary process that may affect host social structure. The resulting coevolutionary trajectories may be further altered by selection imposed by predators, which exploit the abundant resources concentrated in these nests. Here, we show that geographic differences in selection imposed by predators affects the structure of selection on coevolving hosts and their social parasites. In a multiyear study, we monitored the fate of the annual breeding attempts of the solitary nesting foundresses of Polistes biglumis wasps in four geographically distinct populations that varied in levels of attack by the congeneric social parasite, P. atrimandibularis. Foundress fitness depended mostly on whether, during the long founding phase, a colony was invaded by social parasites or attacked by predators. Foundresses from each population differed in morphological traits and reproductive tactics that were consistent with selection imposed by their natural enemies and in ways that may affect host sociality. In turn, parasite traits were consistent with selection imposed locally by hosts, implying a geographic mosaic of coevolution in this brood parasitic interaction. [ABSTRACT FROM AUTHOR]

The chemical integration strategies of facultative social parasites of social insects have not received the scientific attention they deserve, even though there is considerable research being done on the strategies of obligate social parasites. We simulated intraspecific nest usurpations in the social paper wasp, Polistes biglumis, by dividing each nest into two parts and putting one half in the care of the original foundress and the other half in the care of a usurper. After 8days, we removed and killed foundresses and usurpers, and later tested the responses of naïve, sister-offspring to them. In each half-colony, the offspring were more tolerant to the female that was last on the nest, regardless of whether she was the foundress or a usurper. This suggested that usurpers had the chemical means to be tolerated by the host offspring. Comparisons between the epicuticular hydrocarbon profiles of foundresses and usurpers showed that usurpers were neither chemically insignificant nor transparent, nor were they mimetic, as obligate parasites often are. Instead, usurpers had chemical profiles richer in methyl-branched hydrocarbons than those of the foundresses. Analyses of the hydrocarbon profiles of nest paper revealed that usurpers supplemented host nests with their own hydrocarbons, a sort of nest marking. As a result, the chemical profiles of the host nests became qualitatively more similar to those of the usurpers. These chemical strategies illustrate that branched hydrocarbons play a role as semiochemicals and that facultative parasites may not all be on the main pathway to obligate parasitism. [ABSTRACT FROM AUTHOR]

Hermaphroditism and gonochorism are two contrasting forms of sexuality. Hermaphroditic species are generally seen as species adapted to conditions of low density, stabilized by poor mate search efficiency and high costs of searching. They can adjust allocation of reproductive resources to each sex function in response to current social conditions, making reproduction more efficient, at least in principle. By contrast, gonochorism (separate sexes) is advantageous when mates are frequent, making it ineffective to maintain two sex functions in a single individual. This, however, also rules out the need for a flexible response to mating opportunities as known for hermaphrodites. In the hermaphroditic marine polychaete worm Ophryotrocha d!adema we showed earlier that group size is assessed through a chemical cue. In this study we verified the accuracy of the response to gradients of the chemical cue used to assess group size by O. diadema by checking reduction in egg production as the group of partners increases, as expected according to sex allocation theory. Furthermore we compared the effect of such a gradient with a similar gradient in a closely related gonochoric species (O. labronica). Here sex allocation adjustment is not predicted, thus an adaptive change in egg production in response to group-size cues is not expected. In fact, our results show that the group-size effect only occurs in O. diadema and not in O. labronica. Moreover, our study provides evidence of high perceptual abilities of chemical cues in O. diadema, suggesting that perceiving social cues and adjusting sex allocation appropriately are special properties of hermaphrodites. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to map metabolic compensation and depression in Alzheimer's disease (AD) on a voxel-by-voxel basis. Methods: Twenty-one healthy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. Results: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity. Significant metabolic compensation was found in the amygdala, while exceeding hypometabolism was mainly located in the posterior cingulate cortex. Conclusion: Metabolic depression can be due to both distant effects of atrophy and to additional hypometabolism-inducing factors, such as amyloid deposition. Conversely, metabolic compensation could reflect spared synaptic plasticity of the surviving neurons. The investigation of the metabolic compensation mechanism could help in the comprehension of the AD underlying pathology. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this study was to map metabolic compensation and depression in Alzheimer’s disease (AD) on a voxel-by-voxel basis. Methods: Twenty-one healthy elderly subjects and 25 AD patients underwent cerebral MR and FDG-PET imaging. All images were processed with SPM2, and whole-brain gray matter (GM) atrophy and hypometabolism maps were computed. Metabolic compensation and depression were assessed using Biological Parametric Mapping software. Results: GM atrophy and hypometabolism mapped to similar regions, with varying degrees of severity. Significant metabolic compensation was found in the amygdala, while exceeding hypometabolism was mainly located in the posterior cingulate cortex. Conclusion: Metabolic depression can be due to both distant effects of atrophy and to additional hypometabolism-inducing factors, such as amyloid deposition. Conversely, metabolic compensation could reflect spared synaptic plasticity of the surviving neurons. The investigation of the metabolic compensation mechanism could help in the comprehension of the AD underlying pathology. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. The International Classification of Disease, ninth revision (ICD-9) is designed to code disease into categories which are placed into administrative databases. These databases have been used for epidemiological studies. However, the categories used in the ICD9-codes are not always the most effective for evaluating specific diseases or their outcomes, such as the outcomes of cancer treatment. Therefore a re-classification of the ICD-9 codes into new categories specific to cancer outcomes is needed. Methods. An expert panel comprised of two physicians created broad categories that would be most useful to researchers investigating outcomes and morbidities associated with the treatment of cancer. A Senior Data Coordinator with expertise in ICD-9 coding, then joined this panel and each code was re-classified into the new categories. Results. Consensus was achieved for the categories to go from the 17 categories in ICD-9 to 39 categories. The ICD-9 Codes were placed into new categories, and subcategories were also created for more specific outcomes. The results of this re-classification is available in tabular form. Conclusions. ICD-9 codes were re-classified by group consensus into categories that are designed for oncology survivorship research. The novel re-classification system can be used by those involved in cancer survivorship research. [ABSTRACT FROM AUTHOR]

The role of sexual selection in shaping the mating system of hermaphrodites is currently widely accepted. However, a quantification of the intensity of sexual selection in hermaphroditic animals has never been accomplished. We evaluated the opportunity for sexual selection for both the female and the male functions in the simultaneous outcrossing hermaphrodite Ophryotrocha diadema by measuring focal hermaphrodites’ paternal and maternal offspring in experimental replicated monogamous and promiscuous populations, using genetic markers to estimate paternity. Opportunity for sexual selection for each of the two sexual functions was quantified by means of the Crow’s index, i.e. the ratio of variance in progeny number to the squared mean number of progeny. In addition, the extent to which the reproductive success was shared among competing individuals was estimated by means of the Nonacs’s B index. We documented that the strength of selection on the male and female function in hermaphrodites with external fertilization depends on the reproductive context. Under a promiscuous regime, hermaphrodites have higher opportunities for selection for both the male and the female function than under the monogamous regime. Moreover, the reproductive skew for the female function becomes greater than that for the male function, moving from monogamy to promiscuity. In our model system, allocation to one sexual function is opposed by any degree of allocation to the other, indicating that sex-specific patterns of selection operate in this model species. [ABSTRACT FROM AUTHOR]

Because of their double sex functions, hermaphrodites are selected to optimize their investment in the two sex functions. Sex allocation (SA) theory predicts that, in promiscuous mating conditions, simultaneous hermaphrodites should adjust their reproductive investment so as to invest an amount of resources into the male relatively larger than that invested into the female function. In contrast, in monogamy, individuals should invest relatively larger amount of resources into the female function at the expenses of the male function. In the study of SA patterns of simultaneous hermaphrodites little attention has been paid to allocate adjustments costs, which may play an important role in determining variations in SA pattern among species. Indeed, the costs paid for such adjustments may constrain sex investment resulting in suboptimal allocation. We evaluated the costs of SA adjustments on individual fitness in each sexual function in the simultaneous, outcrossing hermaphrodite Ophryotrocha diadema. Following a crossover design, we compared the reproductive success in paternal and maternal offspring of focal hermaphrodites, which were put in replicated monogamous and promiscuous regimes. We document that those hermaphrodites that switched mating regimes and altered their sex investment accordingly did not entail large short-term fitness costs in any sexual function compared to those that were in stable mating regimes. Indeed, individuals changed their sex investment quickly and appropriately to current mating conditions. Hermaphrodites, which had to adjust their SA, did not decrease their maternal or paternal reproductive output with respect to those which did not change their SA. Time needed to shift resources from one to the other sex function is 5 days (the time interval between successive egg layings is of 3 days) indicating that selective pressures for SA adjustments may favour great plasticity and quick adjustments of sex investments in simultaneous hermaphrodites. [ABSTRACT FROM AUTHOR]

Sex allocation theory predicts that, in hermaphroditic organisms, individuals allocate a fixed amount of resources divided among male and female functions to reproduction and that the proportion devoted to each sex depends on the mating group size. As the mating group size increases, hermaphrodites are predicted to allocate proportionally more resources to the male and less resources to the female function (approaching equal allocation to both sexes) to face increased sperm competition. Up to now little experimental evidence has been provided to support the theory in hermaphroditic animals. Facultative shift between male and female allocation in response to variation in local group size does occur in several tax a but not always in the expected direction and not with similar patterns. In the protandric and then simultaneously hermaphroditic polychaete worm Ophryotrocha diadema reproductive resources are flexibly allocated in the protandrous and the hermaphroditic phase. The cost of male reproduction during adolescence is spread over the whole energy budget of the animal as shown by the shortening of lifespan and the lowering of growth rate in individuals with enhanced male expenditure during the protandrous phase. Moreover, in this species, short term sex allocation adjustments differ from those described in other taxa. Individuals regulate their reproductive output so that where reproductive competitors are present, the number of female gametes is strongly reduced but the number of male gametes (although it changes) is not significantly increased. Resources subtracted from the female function are not directly allocated to sperm production, but to expensive male behaviors that are likely to enhance male reproductive success. These results are discussed in the light of the relevance of sexual selection in large populations of hermaphrodites. [ABSTRACT FROM AUTHOR]

Sex allocation theory predicts that simultaneous hermaphrodites shift sex allocation facultatively in response to variation in local group size. This study was performed to evaluate the relative investment in each sex function by the simultaneously hermaphroditic polychaete worm Ophryotrocha diadema and to test whether allocation to each sex depends on the number of reproductive competitors. Four experimental groups were set up (in a 2 × 2 factorial design) with small or large group size and with small or large enclosures to control for potential confounding effects of density. We measured the proportion of female and male investment in focal individuals. Results revealed that individuals regulated their reproductive output so that when reproductive competitors were present, the number of female gametes was strongly reduced and the male function increased. In contrast, under monogamy, individuals in small groups produced lower numbers of sperm but had a higher egg output than worms in large groups. Density did not affect sex allocation in our experiment. Our findings provide qualitative support for Local Mate Competition theory, but also show that the pattern of sex allocation specific to this species is more complex than expected by current theory. [ABSTRACT FROM AUTHOR]

In social insects, cuticular hydrocarbons (CHCs) play an important role in nestmate discrimination processes, but young individuals are usually not discriminated. We studied CHC changes in young workers of the social wasp Polistes dominulus. A quantitative estimation demonstrated that total quantities of CHCs increased after emergence, with branched alkanes increasing drastically when compared with other classes of hydrocarbons. The relative quantity of longer-chain compounds increased with respect to shorter ones; unsaturated compounds decreased. These changes might reduce the capacity of the cuticle to acquire compounds of environmental origin. We then tested whether individuals acquire hydrocarbons from the environment, and whether this capability equally characterises newly emerged and mature wasps. We exposed wasps of two age classes (adults younger or older than 24h) to four linear hydrocarbons in turn, and observed how nestmates reacted to their re-introduction into the natal colony. Exposed young wasps elicited significantly more aggressive responses than control sisters; but treated wasps older than 24h were generally accepted by nestmates. Chemical assays showed that exposed young wasps readily absorbed hydrocarbons; older ones did not incorporate hydrocarbons, suggesting that the chemical profiles of mature wasps are less prone to chemical shifts than those of newly emerged wasps. [Copyright &y& Elsevier]

The phytotoxic protein PcF (Phytophthora cactorum-Fragaria) is a 5.6-kDa cysteine-rich, hydroxyproline- containing protein that is secreted in limited amounts by P. cactorum, an oomycete pathogen of tomato, strawberry and other relevant crop plants. Although we have shown that pure PcF triggers plant reactivity, its mechanism of action is not yet understood. Here we show that PcF, like other known fungal protein elicitors involved in pathogen-plant interaction, stimulates the activity of the defense enzyme phenylalanine ammonia a key step in understanding the mechanism of action of PcF at a molecular level is knowledge of its three-dimensional structure, we overexpressed this protein extracellularly in Pichia pastoris. The preliminary structural and functional characterization of a recombinant PcF homologue, N4-rPcF, is reported. Interestingly, although N4-rPcF is devoid of proline hydroxylation and has four additional amino acid residues attached to its N terminus, its secondary structure and biological activity are indistinguishable from wild-type PcF. [ABSTRACT FROM AUTHOR]

Background: Selective re-creation of a new internal anal sphincter could be indicated when the natural one is irreversibly damaged or excised. Methods: In this preliminary experimental work, surgical techniques of internal anal sphincter replacement in pigs were investigated. After preoperative anorectal manometry, surgical procedure was done in two phases: abdominal, mobilization of the colon-rectum to the pelvic floor; and perianal, dissection of the anal canal from the external anal sphincter through the intersphincteric space. The fully mobilized anorectal segment, including the internal anal sphincter, was pulled down through the anus and resected. The distal colonic stump was then demucosated and two types of plications of the demucosated segment were accomplished, each type in three animals. The plicated segment was then returned into the anal canal, inside the external sphincter. Short-term follow-up with clinical and manometric evaluations was performed and, subsequently, histological analysis of the plicated segment, after the animals were sacrificied. Results: None of the animals became incontinent. Anal manometry identified a high-pressure zone and relaxation reflex in the new anal canal. Histologic studies showed hypertrophy of smooth muscle layers without degenerative changes. Conclusion: This study indicates that a plication of colonic smooth muscle wall can re-create a high-pressure zone in the anal canal after the internal anal sphincter has been excised. [ABSTRACT FROM AUTHOR]

Meniere's disease (MD) is still controversial in several aspects. The vestibular aqueduct, the osseous channel that carries the endolymphatic duct and sac, has previously been studied by tomography and computed tomography, with shortening and narrowing of this structure observed. These findings are apparently correlated to the development of the endolymphatic hydrops present in MD and related to its episodic symptoms. In studying the endolymphatic duct, the key structure in the pathology of this disease, magnetic resonance imaging (MRI) studies of the temporal bone were performed in 12 patients with unilateral MD and in 9 bilateral cases; the results were compared with images obtained from 30 normal ears. The endolymphatic duct appeared to be statistically less visible in MD patients, with no difference between symptomatic and asymptomatic ears in the presence of unilateral disease. No relationship was found between visualization of the endolymphatic duct and time of evolution or response to clinical treatment in these cases. The distance from the posterior semicircular canal to the posterior temporal border was found to be bilaterally reduced in MD. The authors conclude that although the demonstration of endolymphatic hydrops “in vivo” is not yet possible by MRI, some features can be observed that can support a clinical hypothesis of MD. [ABSTRACT FROM AUTHOR]

The mating system of the simultaneously hermaphroditic polychaete worm Ophryotrocha diadema consists of a regular egg exchange between partners of a pair. Such reciprocal egg exchange has been considered a form of cooperation, where one partner cooperates by offering its eggs to be fertilized and expects to receive partner's eggs to fertilize. Frequency of cases in which hermaphrodites cheated (i.e., failed to give up eggs at their turn) and responses to cheating were estimated by analyzing the behavior of 38 triplets of ovigerous hermaphrodites over a 2-week period. The partner did not reciprocate 8% of egg layings. The cheated partner did not detect most cases of cheating (16 out of 25). Such a low frequency of cheating can explain why no retaliation mechanism evolved in this species. Sixty-eight percent of the individuals from the original pairs deserted even if their partners never cheated them; therefore, cheating cannot be considered the cause of desertion. Rather, desertion appeared to be a consequence of availability of a new partner whose oocytes were riper than those of the old partner. It occurred because the opportunity arose for an immediate reward, indicating that O. diadema egg exchange differs from that originally described in some serranid fish as egg trading. The relationship between costs of desertion and population size is discussed. [ABSTRACT FROM PUBLISHER]

Abstract: Clinical trials of disease modifying drugs for Alzheimer''s disease (AD) in patients with mild cognitive impairment (MCI) might benefit from enrichment with true AD cases. Four hundred five MCI patients (143 converters and 262 nonconverters to AD within 2 years) of the Alzheimer''s disease Neuroimaging Initative (ADNI) were used. Markers for enrichment were hippocampal atrophy on magnetic resonance (MRI), temporoparietal hypometabolism on FDG PET, cerebrospinal fluid (CSF) biomarkers (Abeta42, tau, and phospho-tau), and cortical amyloid deposition (11C–PIB positron emission tomography (PET)). Two separate enrichment strategies were tested to A) maximize the proportion of MCI converters screened in, and B) minimize the proportion of MCI converters screened out. Based on strategy A, when compared with no enrichment and ADAS-Cog as an outcome measure (sample size of 834), enrichment with 18F-FDG PET and hippocampal volume lowered samples size to 260 and 277 cases per arm, but at the cost of screening out 1,597 and 434 cases per arm. When compared with no enrichment and clinical dementia rating (CDR-SOB) as an outcome measure (sample size of 674), enrichment with hippocampal volume and Abeta42 lowered sample sizes to 191 and 291 cases per arm, with 639 and 157 screened out cases. Strategy B reduced the number of screened out cases (740 for [11C]-PIB PET, 101 hippocampal volume, 82 ADAS-COG and 330 for [18F]-FDG PET) but at the expense of decreased power and a relative increase size (740 for [11C]-PIB PET, 676 for hippocampal volume, 744 for ADAS-Cog, and 517 for [18F]-FDG PET). Enrichment comes at the price of an often relevant proportion of screened out cases, and in clinical trial settings, the balance between enrichment of screened in and loss of screened out patients should be critically discussed. [Copyright &y& Elsevier]

In primitively eusocial insects, air temperature is the environmental factor that primarily affects colony cycle. Several studies demonstrated interspecific differences in the adaptation of eusocial insects to local air temperature. Nevertheless, studies on intraspecific adaptations are rare. In this study, we investigate the influence of air temperature on local adaptations in behavior and colony productivity of Polistes biglumis foundresses living in warm and cold temperate zones. We hypothesized that foundresses from warm temperate zones would show a higher activity level compared to those from cold temperate zones before brood emergence, based on differences in air temperature between the two zones. After brood emergence, we expected a reduced foundress activity level in the warm climate zone, due to workers' help. In contrast, foundresses living in the cold-climate zone, which do not produce workers, were expected to remain active throughout the nesting season. We also hypothesized that colony productivity was higher in warm-climate colonies. As expected, warm-climate foundresses reduced their activity level after brood emergence and, with their relatively large number of workers, continued egg production throughout the nesting season. Further studies are necessary to assess if these intraspecific differences are attributable to phenotypic plasticity or genetic divergence. [ABSTRACT FROM AUTHOR]

Local Mate Competition theory (LMC) predicts female-biased offspring sex ratios when mate competition occurs locally between siblings. The mating system of the marine polychaete wormDinophilus gyrociliatusapparently fits LMC theory well. Females lay egg capsules with 3–6 large eggs (which produce females), and 1–2 small eggs (which produce males), resulting in female-biased sex ratios. However, mating occurs between larvae, inside egg capsules, and brothers fertilize sisters, possibly preventing any competition between unrelated males and obviating the need for sex ratio adjustments to local population size. Therefore, we tested whether mothers adjusted their offspring sex ratio to local population size, controlling for density. As predicted by LMC theory, sex ratios of single females were less male-biased than those of populations of multiple females, suggesting that males also compete with unrelated males. Sex ratio adjustments occurred irrespective of density, revealing sophisticated perception of the social environment in these worms. [ABSTRACT FROM AUTHOR]

Phenotypic plasticity is the environment-induced change in the phenotype of an organism. Natural selection operates for the ability of individuals to adjust their phenotype to the current environmental conditions when environmental conditions fluctuate. Simultaneous hermaphrodites may exhibit plasticity in sex allocation according to the availability of mates at any particular time. The plasticity in sex allocation has probably evolved under fluctuating mating opportunities, which are usually low but increase when hermaphrodites incur sudden demographic expansion. Here we compare the plasticity in sex allocation in two different populations of the hermaphroditic polychaete wormOphryotrocha diadema– a laboratory population and a wild one. Worms from the laboratory population were kept under constant crowded conditions for about 200 generations (i.e. they were exposed to high mating opportunities). Worms from the wild population were kept under crowded conditions for 20 generations only. Worms from the laboratory population showed significantly less plasticity in sex allocation than worms from the wild population. Although we cannot rule out the hypotheses that genetic drift or local adaptation played a role in the differences between the two populations, the most likely explanation for our results is that worms of the laboratory population underwent a loss of plasticity in sex allocation because they were kept under constant mating opportunities. In fact, the sensory and regulatory machinery that worms use for exhibiting plastic sex allocation responses is likely to be the same as the machinery that is required for mate searching and sex role synchronization between mating partners. The need to maintain this machinery can explain why worms from the laboratory population diminished their plasticity in sex allocation but did not lose it completely. Therefore our results give some clues as to how plasticity in sex allocation evolves or is constrained. [ABSTRACT FROM PUBLISHER]

Background and Objectives Patient Blood Management ( PBM) in Europe is a working group of the European Blood Alliance with the initial objective to identify the starting position of the participating hospitals regarding PBM for benchmarking purposes, and to derive good practices in PBM from the experience and expertise in the participating teams with the further aim of implementing and strengthening these practices in the participating hospitals. Methods We conducted two surveys in seven university hospitals in Europe: Survey on top indications for red blood cell use regarding usage of red blood cells during 1 week and Survey on PBM organization and activities. Results A total of 3320 units of red blood cells were transfused in 1 week at the seven hospitals. Overall, 61% of red cell units were transfused to medical patients and 36% to surgical patients, although there was much variation between hospitals. The organization and activities of PBM in the seven hospitals were variable, but there was a common focus on optimizing the treatment of bleeding patients, monitoring the use of blood components and treatment of preoperative anaemia. Conclusion Although the seven hospitals provide a similar range of clinical services, there was variation in transfusion rates between them. Further, there was variable implementation of PBM activities and monitoring of transfusion practice. These findings provide a baseline to develop joint action plans to further implement and strengthen PBM across a number of hospitals in Europe. [ABSTRACT FROM AUTHOR]

An experimental study about the anisotropic wetting behavior of a surface patterned with parallel grooves is presented as an application example of a novel technique for investigation of complete and partial anisotropic wetting on structured surface by X-ray microtomography. Shape of glycerin droplets on such surface is investigated by X-ray micro computed tomography (microCT) acting as a non-intrusive, full volume 3D microscope with micrometric spatial resolution. The reconstructed drop volumes enable to estimate the exact volumes of the drops, their base contours, and 3D static contact angles, based on true cross-sections of the drop-surface couple. Droplet base contours are compared to approximate geometrical contour shapes proposed in the literature. Contact angles along slices parallel and perpendicular to the grooves direction are compared with each other. The effect of the sessile drop volume on the wetting behavior is discussed. The proposed technique, which is applicable for any structured surface, enables the direct measure of Wenzel ratio based on the microCT scan in the wetted region usually inapproachable by any others. Comparisons with simplified models are presented and congruence of results with respect to the minimum resolution needed is evaluated and commented. [ABSTRACT FROM AUTHOR]

We previously reported that STAT1 expression is frequently abrogated in human estrogen receptor-α-positive (ERα+) breast cancers and mice lacking STAT1 spontaneously develop ERα+ mammary tumors. However, the precise mechanism by which STAT1 suppresses mammary gland tumorigenesis has not been fully elucidated. Here we show that STAT1-deficient mammary epithelial cells (MECs) display persistent prolactin receptor (PrlR) signaling, resulting in activation of JAK2, STAT3 and STAT5A/5B, expansion of CD61+ luminal progenitor cells and development of ERα+ mammary tumors. A failure to upregulate SOCS1, a STAT1-induced inhibitor of JAK2, leads to unopposed oncogenic PrlR signaling in STAT1−/− MECs. Prophylactic use of a pharmacological JAK2 inhibitor restrains the proportion of luminal progenitors and prevents disease induction. Systemic inhibition of activated JAK2 induces tumor cell death and produces therapeutic regression of pre-existing endocrine-sensitive and refractory mammary tumors. Thus, STAT1 suppresses tumor formation in mammary glands by preventing the natural developmental function of a growth factor signaling pathway from becoming pro-oncogenic. In addition, targeted inhibition of JAK2 may have significant therapeutic potential in controlling ERα+ breast cancer in humans. [ABSTRACT FROM AUTHOR]

Background Over the last 15 years, many studies demonstrated the myogenic regenerative potential of bone marrow mesenchymal stem cells ( BM- MSC), making them an attractive tool for the regeneration of damaged tissues. In this study, we have developed an animal model of esophagogastric myotomy ( MY) aimed at determining the role of autologous MSC in the regeneration of the lower esophageal sphincter ( LES) after surgery. Methods Syngeneic BM- MSC were locally injected at the site of MY. Histological and functional analysis were performed to evaluate muscle regeneration, contractive capacity, and the presence of green fluorescent protein-positive BM- MSC ( BM- MSC- GFP+) in the damaged area at different time points from implantation. Key Results Treatment with syngeneic BM- MSC improved muscle regeneration and increased contractile function of damaged LES. Transplanted BM- MSC- GFP+ remained on site up to 30 days post injection. Immunohistochemical analysis demonstrated that MSC maintain their phenotype and no differentiation toward smooth or striated muscle was shown at any time point. Conclusions & Inferences Our data support the use of autologous BM- MSC to both improve sphincter regeneration of LES and to control the gastro-esophageal reflux after MY. [ABSTRACT FROM AUTHOR]

Background:MEK is activated in ∼40% colorectal cancer (CRC) and 20-30% non-small cell lung cancer (NSCLC). Selumetinib is a selective inhibitor of MEK1/2, which is currently in clinical development.Methods:We evaluated the effects of selumetinib in vitro and in vivo in CRC and NSCLC cell lines to identify cancer cell characteristics correlating with sensitivity to MEK inhibition.Results:Five NSCLC and six CRC cell lines were treated with selumetinib and classified according to the median inhibitory concentration (IC50) values as sensitive (1 μM) or resistant (>1 μM). In selumetinib-sensitive cancer cell lines, selumetinib treatment induced G1 cell-cycle arrest and apoptosis and suppression of tumour growth as xenografts in immunodeficient mice. Evaluation of intracellular effector proteins and analysis of gene mutations showed no correlation with selumetinib sensitivity. Microarray gene expression profiles revealed that the activation of cAMP-dependent protein kinase A (PKA) was associated with MEK inhibitor resistance. Combined targeting of both MEK and PKA resulted in cancer cell growth inhibition of MEK inhibitor-resistant cancer cell lines in vitro and in vivo.Conclusion:This study provides molecular insights to explain resistance to an MEK inhibitor in human cancer cell lines. [ABSTRACT FROM AUTHOR]

Sexual selection is often quantified using Bateman gradients, which represent sex-specific regression slopes of reproductive success on mating success and thus describe the expected fitness returns from mating more often. Although the analytical framework for Batenian gradients aimed at covering all sexual systems, empirical studies are biased toward separate-sex organisms, probably because important characteristics of other systems remain incompletely treated. Our synthesis complements the existing Bateman gradient approach with three essential reproductive features of simultaneous hermaphrodites. First, mating in one sex may affect fitness via the opposite sex, for example, through energetic trade-offs. We integrate cross-sex selection effects and show how they help characterizing sexually mutualistic versus antagonistic selection. Second, male and female mating successes may be correlated, complicating the interpretation of Bateman gradients. We show how to quantify the impact of this correlation on sexual selection and propose a principal component analysis on male and female mating success to facilitate interpretation. Third, self-fertilization is accounted for by adding selfed progeny as a separate category of reproductive success to analyses of Bateman gradients. Finally, using a worked example from the snail Biomphalaria glabrata, we illustrate how the extended analytical framework can enhance our understanding of sexual selection in hermaphroditic animals and plants. [ABSTRACT FROM AUTHOR]

Objective: Prevention of diabetic retinopathy would benefit from availability of drugs that preempt the effects of hyperglycemia on retinal vessels. We aimed to identify candidate drug targets by investigating the molecular effects of drugs that prevent retinal capillary demise in the diabetic rat.Research Design and Methods: We examined the gene expression profile of retinal vessels isolated from rats with 6 months of streptozotocin-induced diabetes and compared it with that of control rats. We then tested whether the aldose reductase inhibitor sorbinil and aspirin, which have different mechanisms of action, prevented common molecular abnormalities induced by diabetes. The Affymetrix GeneChip Rat Genome 230 2.0 array was complemented by real-time RT-PCR, immunoblotting, and immunohistochemistry.Results: The retinal vessels of diabetic rats showed differential expression of 20 genes of the transforming growth factor (TGF)-beta pathway, in addition to genes involved in oxidative stress, inflammation, vascular remodeling, and apoptosis. The complete loop of TGF-beta signaling, including Smad2 phosphorylation, was enhanced in the retinal vessels, but not in the neural retina. Sorbinil normalized the expression of 71% of the genes related to oxidative stress and 62% of those related to inflammation. Aspirin had minimal or no effect on these two categories. The two drugs were instead concordant in reducing the upregulation of genes of the TGF-beta pathway (55% for sorbinil and 40% for aspirin) and apoptosis (74 and 42%, respectively).Conclusions: Oxidative and inflammatory stress is the distinct signature that the polyol pathway leaves on retinal vessels. TGF-beta and apoptosis are, however, the ultimate targets to prevent the capillary demise in diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Myeloproliferative disorders (MPDs) are clonal malignancies that arise from hematopoietic progenitors and characterized by overproduction of mature, functional blood cells. These disorders can be broadly characterized into Philadelphia chromosome-positive (Ph(+)) or negative (Ph(−)) genetic groupings. Chronic myeloid leukemia (CML) is a Ph(+) MPD that is defined on the basis of its molecular lesion, the BCR-ABL fusion gene. Inhibitors directed at the constitutive kinase activity of BCR-ABL have been shown to be disease modifying in CML and have dramatically altered the standard of care for this leukemia. The three main Ph(−) MPDs are polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The key features of these Ph(−) MPDs are an increased red blood cell mass in PV, a high platelet count in ET and bone marrow fibrosis in PMF, respectively. These disorders also share many clinical features such as long clinical course, increased risk for thrombosis, hemorrhage and elevated risk of leukemic transformation. Interest in these disorders has been ignited by the recent discovery of activating mutations in the tyrosine kinase gene, JAK2, in the predominance of Ph(−) MPD patients and has highlighted JAK2 as a therapeutic intervention point for drug discovery efforts with selective kinase inhibitors. This review will focus on the comparison of Ph(+) and Ph(−) MPDs, drug discovery and development efforts targeting these disorders, and will assess the new opportunities for targeted therapies for these diseases.Oncogene (2009) 28, 2305–2313; doi:10.1038/onc.2009.107; published online 4 May 2009 [ABSTRACT FROM AUTHOR]

The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy. Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m2 i.v. only on day 1, with leucovorin 100 mg/m2 i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m2/day and a 22-h infusion of 5-FU 600 mg/m2/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion. The percentage of patients presenting with grade ≥2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade ≥2 neurotoxicity in group A (6.1%) than in group B (18.5%) ( P < 0.001). This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment. [ABSTRACT FROM AUTHOR]

A total of 41 metastatic colorectal cancer (CRC) patients received tegafur/uracil (UFT)+leucovorin (LV)+oxaliplatin alternated with UFT/LV+irinotecan. The overall response rate was 58.5% (95% confidence interval, 42.2-73.3%), and the median progression-free survival was 8.8 months. There were no grade 4 toxicities; 12 patients (29%) experienced grade 3 diarrhoea. There were no cases of hand-foot syndrome. This alternating regimen seems to be effective and well tolerated in the first-line treatment of patients with metastatic CRC. [ABSTRACT FROM AUTHOR]