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Multiple small supernumerary marker chromosomes (sSMCs) are among the rarest cytogenetic abnormalities as they represent roughly 1.4% of cases with sSMCs. We report on a prenatal case presenting de novo multiple sSMCs; these sSMCs were characterized by array CGH and FISH and resulted deriving from three different chromosomes: a der(13), a der(15) and a der(20). The co-presence of der(13), der(20), and der(15) have not been reported yet. The clinical consequences of this marker combination cannot be precisely predicted. However, according to the publicly available databases, the partial trisomies of chromosome 13 and 20 have probably a pathogenic effect. It is worth noting that a cooperative effect, due to interactions among genes harbored on the three derivatives, cannot be excluded, making the genetic counseling challenging.

Introduction Distance learning efficacy on physician performances and patient health outcomes has been demonstrated. This study explored the participation and evaluation of CME e-learning courses for Italian health care professionals addressing leading causes of maternal mortality identified by the Italian Obstetric Surveillance System (ItOSS) at the Italian National Health Institute, namely postpartum hemorrhage and pregnancy hypertensive disorders. Methods A model for two online free 12-hour case-based training courses was used. Data on participants were collected, anonymized, and transferred to the Italian National Health Institute for later analysis. Participants were requested to sign an online informed consent form. Results Twenty-one thousand five hundred thirty-two health care professionals enrolled to the courses from 2014 to 2017 as follows: midwives (14,187, 65.9%); obstetricians (3,716, 17.2%); anesthesiologists (1,896, 8.8%); and other medical specialists (1,733, 8.0%). Overall, 85% of participants acquired CME credits. Participants' satisfaction on quality, efficacy, and relevance was very high. Discussion ItOSS courses were able to reach a substantial number of different professional profiles involved in perinatal care all over the country; ItOSS courses can be considered an effective way to spread evidence-based good clinical practices. Nevertheless, further studies are needed to verify the improvement in professional health care skills and patient outcomes.

Cyanide is one of the main reagents used in gold mining that can be recovered to reduce operational costs. Gas membrane technology is an attractive method for intensifying both the stripping and absorption processes of valuable compounds, such as cyanide. However, scaling-up this technology from laboratory to industry is an unsolved challenge because it requires the improvement of the experimental methodologies that replicate lab-scale results at a larger scale. With this purpose in mind, this study compares the performance of three different hollow fiber membrane contactor modules (1.7 &times, 5.5 Mini Module, 1.7 &times, 10 Mini Module, and 2.5 &times, 8 Extra Flow). These are used for recovering cyanide from aqueous solutions at laboratory scale, using identical operational conditions. For each experimental set-up, mass-transfer correlations at the ranges of feed flows assayed were determined. The modules with the smallest and largest area of mass transfer reached similar cyanide recoveries (&gt, 95% at 60 min), which demonstrate the impact of module configuration on their operating performance. The results obtained here are limited for scaling-up the membrane module performance only because operating modules with the largest area results in a low Re number. This fact limits the extrapolation of results from the mass-transfer correlation.

// Elena Ciabatti 1,3 , Angelo Valetto 2 , Veronica Bertini 2 , Maria Immacolata Ferreri 2 , Alice Guazzelli 2 , Susanna Grassi 1,3 , Francesca Guerrini 1 , Iacopo Petrini 4 , Maria Rita Metelli 1 , Maria Adelaide Caligo 2 , Simona Rossi 2 and Sara Galimberti 1 1 Department of Clinical and Experimental Medicine, Section of Hematology, University of Pisa, Pisa, Italy 2 Laboratory of Medical Genetics, Azienda Ospedaliero-Universitaria Pisana, S. Chiara Hospital, Pisa, Italy 3 GenOMec, University of Siena, Siena, Italy 4 Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy Correspondence to: Elena Ciabatti, email: // Keywords : myelodysplastic syndromes, aCGH, cytogenetics, TP53, SF3B1 Received : August 23, 2016 Accepted : March 14, 2017 Published : March 25, 2017 Abstract In this study we present a new diagnostic workup for the myelodysplastic syndromes (MDS) including FISH, aCGH, and somatic mutation assays in addition to the conventional cytogenetics (CC). We analyzed 61 patients by CC, FISH for chromosome 5, 7, 8 and PDGFR rearrangements, aCGH, and PCR for ASXL1, EZH2, TP53, TET2, RUNX1, DNMT3A, SF3B1 somatic mutations. Moreover, we quantified WT1 and RPS14 gene expression levels, in order to find their possible adjunctive value and their possible clinical impact. CC analysis showed 32% of patients with at least one aberration. FISH analysis detected chromosomal aberrations in 24% of patients and recovered 5 cases (13.5%) at normal karyotype (two 5q- syndromes, one del(7) case, two cases with PDGFR rearrangement). The aGCH detected 10 “new” unbalanced cases in respect of the CC, including one with alteration of the ETV6 gene. After mutational analysis, 33 patients (54%) presented at least one mutation and represented the only marker of clonality in 36% of all patients. The statistical analysis confirmed the prognostic role of CC either on overall or on progression-free-survival. In addition, deletions detected by aCGH and WT1 over-expression negatively conditioned survival. In conclusion, our work showed that 1) the addition of FISH (at least for chr. 5 and 7) can improve the definition of the risk score; 2) mutational analysis, especially for the TP53 and SF3B1, could better define the type of MDS and represent a “clinical warning”; 3) the aCGH use could be probably applied to selected cases (with suboptimal response or failure).

Progressive Myoclonus Epilepsies (PMEs) are a group of uncommon clinically and genetically heterogeneous disorders characterised by myoclonus, generalized epilepsy, and neurological deterioration, including dementia and ataxia. PMEs may have infancy, childhood, juvenile or adult onset, but usually present in late childhood or adolescence, at variance from epileptic encephalopathies, which start with polymorphic seizures in early infancy. Neurophysiologic recordings are suited to describe faithfully the time course of the shock-like muscle contractions which characterize myoclonus. A combination of positive and negative myoclonus is typical of PMEs. The gene defects for most PMEs (Unverricht-Lundborg disease, Lafora disease, several forms of neuronal ceroid lipofuscinoses, myoclonus epilepsy with ragged-red fibers [MERRF], and type 1 and 2 sialidoses) have been identified. PMEs are uncommon disorders, difficult to diagnose in the absence of extensive experience. Thus, aetiology is undetermined in many patients, despite the advance in molecular medicine. Treatment of PMEs remains essentially symptomaticof seizures and myoclonus, together with palliative, supportive, and rehabilitative measures. The response to therapy may initially be relatively favourable, afterwards however, seizures may become more frequent, and progressive neurologic decline occurs. The prognosis of a PME depends on the specific disease. The history of PMEs revealed that the international collaboration and sharing experience is the right way to proceed. This emerging picture and biological insights will allow us to find ways to provide the patients with meaningful treatment.

The Polycomb gene BMI1 expression exerts a negative predictive impact on several hematological malignancies, such as acute and chronic myeloid leukemia (CML), myelofibrosis, and follicular lymphoma. As already demonstrated in CML, BMI1 is responsible for the resistance to the tyrosine kinase inhibitors (TKIs) in a BCR-ABL1-independent way. Even if, it is unknown where BMI1 in CML is expressed (in progenitors or more mature cells). We decided, therefore, to evaluate if and where the BMI1 protein is located, focusing mainly on the CD34+/CD38-/CD26+ CML progenitors. To begin we measured, by flow cytometry, the proportion of CD34+/CD26+ cells in 31 bone marrow samples from 20 CML patients, at diagnosis and during treatment with imatinib. After that the bone marrow blood smears were stained with antibodies anti-CD26, BCR-ABL1, and BMI1. These smears were observed by a confocal laser microscope and a 3D reconstruction was then performed. At diagnosis, CD34+/CD26+ cells median value/μL was 0.48; this number increased from diagnosis to the third month of therapy and then reduced during treatment with imatinib. The number and behavior of the CD26+ progenitors were independent from the BCR-ABL1 expression, but they summed up what previously observed about the BMI1 expression modulation. In this work we demonstrate for the first time that in CML the BMI1 protein is co-expressed with BCR-ABL1 only in the cytoplasm of the CD26+ precursors; on the contrary, in other hematological malignancies where BMI1 is commonly expressed (follicular lymphoma, essential thrombocytemia, acute myeloid leukemia), it was not co-localized with CD26 or, obviously, with BCR-ABL1. Once translated into the clinical context, if BMI1 is a marker of stemness, our results would suggest the combination of the BMI1 inhibitors with TKIs as an interesting object of research, and, probably, as a promising way to overcome resistance in CML patients.

We report on a patient with a 6.5 Mb interstitial de novo deletion in 3q24q25.2, characterized by array CGH. The patient is a 4-year and 2-month-old girl, who presented to us with mild developmental delay, absence of language, facial dysmorphism, hirsutism, strabismus, and Dandy-Walker Malformation. The main clinical signs typical of WS (Wisconsin syndrome) are evident in the patient. The molecular mapping of WS in 3q23q25 allowed geneticists to define the syndrome more accurately. Comparing the present patient's phenotype with that of cases with a molecular characterization so far reported, it was possible to narrow the critical region for WS to an interval of 750 Kb, where two genes (MBNL1 and TMEM14E) are harbored. The potential role of MBNL1 in causing the WS phenotype is discussed. © 2016 Wiley Periodicals, Inc.

Sustaining large open source development efforts requires recruiting new participants; however, a lack of architectural documentation might inhibit new participants since large amounts of project knowledge are unavailable to newcomers. We present the results of a multitrait, multimethod analysis of the effects of introducing architectural documentation into a substantial open source project—the Hadoop Distributed File System (HDFS). HDFS had only minimal architectural documentation, and we wanted to discover whether the putative benefits of architectural documentation could be observed over time. To do this, we created and publicized an architecture document and then monitored its usage and effects on the project. The results were somewhat ambiguous: by some measures the architecture documentation appeared to effect the project but not by others. Perhaps of equal importance is our discovery that the project maintained, in its web-accessible JIRA archive of software issues and fixes, enough architectural discussion to support architectural thinking and reasoning. This “emergent” architecture documentation served an important purpose in recording core project members’ architectural concerns and resolutions. However, this emergent architecture documentation did not serve all project members equally well; it appears that those on the periphery of the project—newcomers and adopters—still require explicit architecture documentation, as we will show.

Background In adult studies the MTHFR C677T polymorphism has been associated with an increased risk of migraine, but little research has been done in this area in children. Methods A retrospective study of children referred with headache to a tertiary level Paediatric Neurology Service between 2008 and 2012. This study included only patients who had been genotyped for the MTHFR C677T polymorphism. An evaluation of homocysteine serum levels was necessary to exclude other types of migraine. Conclusion Compared with the wild-type genotype, the T/T genotype was associated with an increased risk of any type of migraine, though the statistical significance was greatest in migraine with aura. The homocysteine serum levels were significantly higher in migraine with aura compared to migraine without aura. In a pediatric population MTHFR T/T homozygosity influences susceptibility to migraine.

Terminal deletions of long arm of chromosome 13 are rare and poorly characterized by cytogenetic studies, making for difficult genotype-phenotype correlations. We report two siblings presenting generalized epilepsy, intellectual disability, and genitourinary tract defects. Array CGH detected a 1.3 Mb deletion at 13q34; it contains two protein-coding genes, SOX1 and ARHGEF7, whose haploinsufficiency can contribute to the epileptic phenotype.

When software developers fail to coordinate, build failures, duplication of work, schedule slips and software defects can result. However, developers are often unaware of when they need to coordinate, and existing methods and tools that help make developers aware of their coordination needs do not provide timely or efficient recommendations. We describe our techniques to identify timely and efficient coordination recommendations, which we developed and evaluated in a study of coordination needs in the Mylyn software project. We describe how data obtained from tools that capture developer actions within their Integrated Development Environment (IDE) as they occur can be used to timely identify coordination needs; we also describe how properties of tasks coupled with machine learning can focus coordination recommendations to those that are more critical to the developers to reduce information overload and provide more efficient recommendations. We motivate our techniques through developer interviews and report on our quantitative analysis of coordination needs in the Mylyn project. Our results suggest that by leveraging IDE logging facilities, properties of tasks and machine learning techniques awareness tools could make developers aware of critical coordination needs in a timely way. We conclude by discussing implications for software engineering research and tool design.

Gamification has been successfully applied in several application domains to persuade people to reach to a certain goal. However, such persuasive technologies have concerns to keep players engaged and to sustain newly acquired behaviors for a long term. One option to tackle this issue is personalizing the gamified experience for each individual player. To this end, we developed a framework that can personalize the game content by proposing to players challenges that are tailored to their profiles and game histories. In this paper we present a Machine Learning module that optimizes the challenge selection process and the evaluation results within an on-the-field game promoting sustainable mobility habits.

Maternal uniparental disomy of chromosome 14 (upd(14)mat) or Temple syndrome is an imprinting disorder associated with a relatively mild phenotype. The absence of specific congenital malformations makes this condition underdiagnosed in clinical practice. A boy with a de novo robertsonian translocation 45,XY,rob(13;14)(q10;q10) is reported; a CGH/SNP array showed a loss of heterozygosity in 14q11.2q13.1. The final diagnosis of upd(14)mat was made by microsatellite analysis, which showed a combination of heterodisomy and isodisomy for different regions of chromosome 14. Obesity after initial failure to thrive developed, while compulsive eating habits were not present, which was helpful for the clinical differential diagnosis of Prader-Willi syndrome. In addition, the boy presented with many phenotypic features associated with upd(14)mat along with hypoesthesia to pain, previously unreported in this disorder, and bilateral cryptorchidism, also rarely described. These features, as well as other clinical manifestations (i.e., truncal obesity, altered pubertal timing), may suggest a hypothalamic-pituitary involvement. A detailed cytogenetic and molecular characterization of the genomic rearrangement is presented. Early genetic diagnosis permits a specific follow-up of children with upd(14)mat in order to optimize the long-term outcome.

We present a methodological approach, called Group Informatics, for understanding the social connections that are created between members of technologically mediated groups. Our methodological approach supports focused thinking about how online groups differ from each other, and diverge from their face-to-face counterparts. Group Informatics is grounded in 5 years of empirical studies of technologically mediated groups in online learning, software engineering, online political discourse, crisis informatics, and other domains. We describe the Group Informatics model and the related, 2-phase methodological approach in detail. Phase one of the methodological approach centers on a set of guiding research questions aimed at directing the application of Group Informatics to new corpora of integrated electronic trace data and qualitative research data. Phase 2 of the methodological approach is a systematic set of steps for transforming electronic trace data into weighted social networks.

Service evolution is a critical ingredient of the service life-cycle. The more our society depends on large-scale, complex service environments including cloud and mobile services, the more pressing becomes the question of how to evolve a service on the fly at runtime, without bringing whole systems to a halt, due to unintended percolation of evolution effects through service inter–dependency chains. Thus, there is an urgent need for coordinated service evolution (co-evolution). This paper contributes a conceptual solution for dynamic, on-the-fly co-evolution of services, as well as a framework that supports the engineering of such co-evolution support. Our solution is built on top of the Domain Objects architectural concept and service-oriented computing model. We also analyze the types of changes that might happen in a service and their potential impact on dependent clients and servers, and discuss the benefits of our approach on those service co-evolution scenarios.

BACKGROUND: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. \ud \ud METHODS: Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in science communication. We searched for, and evaluated, relevant existing materials and developed additional materials and tools, making them freely available under a Creative Commons licence. \ud \ud RESULTS: The principal communication materials developed were: 1. A website ( http://ecranproject.eu ) in six languages, including a Media centre section to help journalists to disseminate information about the ECRAN project 2. An animated film about clinical trials, dubbed in the 23 official languages of the European Community, and an interactive tutorial 3. An inventory of resources, available in 23 languages, searchable by topic, author, and media type 4. Two educational games for young people, developed in six languages 5. Testing Treatments interactive in a dozen languages, including five official European Community languages 6. An interactive tutorial slide presentation testing viewers' knowledge about clinical trials \ud \ud CONCLUSIONS: Over a 2-year project, our multidisciplinary and multinational consortium was able to produce, and make freely available in many languages, new materials to promote public knowledge about the importance of independent and international clinical trials. Sustained funding for the ECRAN information platform could help to promote successful recruitment to independent clinical trials supported through the European Clinical Research Infrastructure Network.

Individuals participating in technologically mediated forms of organization often have difficulty recognizing when groups emerge, and how the groups they take part in evolve. This paper contributes an analytical framework that improves awareness of these virtual group dynamics through analysis of electronic trace data from tasks and interactions carried out by individuals in systems not explicitly designed for context adaptivity, user modeling or user personalization. We discuss two distinct cases to which we have applied our analytical framework. These two cases provide a useful contrast of two prevalent ways for analyzing social relations starting from electronic trace data: either artifact-mediated or direct person-to-person interactions. Our case study integrates electronic trace data analysis with analysis of other, triangulating data specific to each application. We show how our techniques fit in a general model of group informatics, which can serve to construct group context, and be leveraged by future tool development aimed at augmenting context adaptivity with group context and a social dimension. We describe our methods, data management strategies and technical architecture to support the analysis of individual user task context, increased awareness of group membership, and an integrated view of social, information and coordination contexts.

Adams-Oliver Syndrome (AOS) is a rare genetic disease characterized by combination of aplasia cutis congenita (ACC) and terminal transverse limb defects (TTLD), often accompanied by defects in scalp and skull ossification. Different clinical phenotypes may be related to variable severity both of aplasia cutis and TTLD, and of minor clinical features as cutis marmorata telangiectatica congenita (CMTC), congenital cardiac defect and vascular anomalies. The treatment is multidisciplinary: dermatologic, orthopedic and surgical consult should be required. It still remains unclear how to treat patients with a large skin defect that can‘t be closed primarly and may require both surgical and conservative management. We report two cases of AOS with typical limb defects and an area of aplasia cutis over vertex of the scalp managed conservatively with two different dermatologic devices.

Unstructured superpeer overlays are an approach to peer-to-peer systems that enables collective organization and ensures the efficient participation and use of divers peers with heterogenous capabilities and resources. Such overlays are, however, vulnerable to failures and attacks that target the superpeers in an attempt to disrupt the overlay. In this paper, we present SODAP (Self-Organized Degree Adaptation Protection), a self-organized strategy for the self-protection of the overlay, based on the local adaptation of a peer's degree in response to disconnections, whether directly detected, or indirectly discovered with the assistance of neighbor peers. When network conditions deteriorate, the SODAP mechanism induces the creation of redundant connections to superpeers, which leads to the adjustment of the entire overlay to a topology that is more resilient to disconnection, while still allowing the system to continue exploiting heterogeneous peer capabilities. When network conditions improve, SODAP responds by reducing peer degrees to reduce redundancy and streamline the topology. We demonstrate this mechanism and evaluate its effectiveness as an extension to Myconet, a self-organized superpeer overlay for unstructured peer-to-peer networks.

© 2015 IEEE.In this position paper, we argue that a new methodological paradigm and software platform is required for developing citizen-oriented social computing applications. The platform that we propose is based on the idea of Collective Intelligence as a Service, and is grounded in the formalisation of computational models derived from an empirical analysis of psychological processes and social practices. This in turn provides the enablers for developing radically innovative tools for computational sustainability and computer-supported collective action in smart communities (e.g. Smart cities). Our vision is illustrated with two exemplars, one a healthcare application for patients with peripheral arterial disease, and the other an application for collaborative energy conservation to meet targets set out in a citys Sustainable Energy Action Plan.

We present Mycocloud, a fully self-organized approach to service placement. Mycocloud supports service elasticity within a network of hosts with heterogeneous computational capacity. Mycocloud proposes a completely decentralized algorithm that continuously calculates the dynamic placement of different services on the host nodes, in response to the varying demand for each service, the churn and dynamism of the node set contributing resources to the system, and the changes in the overlay topology. Our simulation results show how Mycocloud provides good performance in terms of convergence rate, response time, system load and network traffic overhead.

We report a case of DiGeorge-like syndrome in which immunodeficiency coexisting with juvenile idiopathic arthritis, congenital heart disease, delay in emergence of language and in motor milestones, feeding and growing problems, enamel hypoplasia, mild skeletal anomalies, and facial dysmorphisms are associated with no abnormalities found on genetic tests.

sec:abstractnak Autonomic computing--self-configuring, self-healing, self-managing applications, systems and networks--is a promising solution to ever-increasing system complexity and the spiraling costs of human management as systems scale to global proportions. Most results to date, however, suggest ways to architect new software designed from the ground up as autonomic systems, whereas in the real world organizations continue to use stovepipe legacy systems and/or build "systems of systems" that draw from a gamut of disparate technologies from numerous vendors. Our goal is to retrofit autonomic computing onto such systems, externally, without any need to understand, modify or even recompile the target system's code. We present an autonomic infrastructure that operates similarly to active middleware, to explicitly add autonomic services to pre-existing systems via continual monitoring and a feedback loop that performs reconfiguration and/or repair as needed. Our lightweight design and separation of concerns enables easy adoption of individual components for use with a variety of target systems, independent of the rest of the full infrastructure. This work has been validated by several case studies spanning multiple real-world application domains.

A collective adaptive system is composed of a set of heterogeneous, autonomous and self-adaptive entities that come into a collaboration with one another in order to improve the effectiveness with which they can accomplish their individual goals. In this paper, we offer a characterization of ensembles, as the main concept around which systems that exhibit collective adaptability can be built. Our conceptualization of ensembles enables to define a collective adaptive system as an emergent aggregation of autonomous and self-adaptive process-based elements. To elucidate our approach to ensembles and collective adaptation, we draw an example from a scenario in the urban mobility domain, we describe an architecture that enables that approach, and we show how our approach can address the problems posed by the motivating scenario.

A major advantage of Virtual Organizations (VOs) is flexible membership and participation. VO members are able to join and leave VOs at will, and can change whom they collaborate with at any point in time. Such flexibility may make VOs more efficient in the completion of collaborative work than traditional organizations. However, efficiency is only one of several measures of organizational performance; and flexibility in a virtual organization includes both how VO structures may be more fluid and adaptive, and how VO leadership emerges and evolves throughout the VO lifecycle. The aim of this chapter is to: (1) define and quantitatively assess the actual flexibility of participation in VOs, through a social network index that we call structural fluidity; and (2) measure the relationship between fluidity and performance in the work carried out within the VO. These are essential insights for the development of theories to guide the formation, development and dissolution of VOs, and teams that emerge around VO work. To accomplish these aims, we will apply a methodological approach and ontology for the study of VOs that we have used in over a dozen published studies, and refer to as Group Informatics. Our approach enables a comprehensive, interdisciplinary inquiry into the relationship between structural fluidity and performance in diverse VOs. Specifically, we will examine VOs in software engineering, disaster relief, online learning and public discourse communities that emerge through social media. We will apply Group Informatics to the design, development and testing of empirically and theoretically grounded algorithms for measuring VO fluidity and performance in each context, which will result in new theoretical advances that enable sophisticated analysis of the resulting data.

Gastrointestinal toxicity from hepatic arterial infusion (HAI) of floxuridine in patients with liver metastases is probably due to extrahepatic perfusion or to partial escape of the drug from first-pass liver extraction. The aim of this study was to verify the role of technetium-99m-labelled macroaggregated albumin (99mTc-MAA) arterial catheter perfusion scintigraphy at the beginning of each chemotherapy cycle in decreasing or preventing gastrointestinal toxicity. We studied 167 consecutive patients. On the basis of the scintigraphic follow-up and the presence or absence of an intrahepatic arteriovenous shunt (IHAVS), we classified our patients into the following groups: (1) FU+ hepatic distribution pattern (DP), comprising 29 patients with regular scintigraphic follow-up who showed the expected distribution pattern at each control or a distribution pattern with transient alterations (extrahepatic escape) promptly reversed by the replacement of the catheter. Among these 29 patients there was one case of gastrointestinal toxicity. (2) FU- hepatic DP, comprising 128 patients who were evaluated with 99mTc-MAA only at the beginning of the first chemotherapy cycle, showed the expected distribution pattern and underwent HAI with no further scintigraphic evaluation. Among these 128 patients there were 28 cases of gastrointestinal toxicity. (3) FU+ pulmonary DP, comprising three patients with abnormally elevated pulmonary uptake (higher than 5%) and with regular scintigraphic follow-up. There were two cases of gastrointestinal toxicity among these three patients. (4) FU- pulmonary DP, comprising seven patients with abnormally elevated pulmonary uptake and without regular scintigraphic follow-up. There were four cases of gastrointestinal toxicity among these seven patients. The incidence of toxicity was significantly higher in group FU- hepatic DP than in group FU+ hepatic DP (21.9% vs 3.4%, P0.05). In both the FU+ pulmonary DP and FU- pulmonary DP groups, the incidence of gastrointestinal toxicity was higher than 50%, with no significant difference between them. We conclude that, when performing 99mTc-MAA perfusion scintigraphy, the presence of an abnormally elevated pulmonary uptake (IHAVS higher than 5%) is the most relevant positive prognostic index for the development of gastrointestinal toxicity. Furthermore, in the absence of abnormal pulmonary uptake (IHAVS lower than 5%), strict scintigraphic follow-up is useful since it is able to promptly diagnose the presence of extrahepatic abdominal perfusion and thus to prevent the occurrence of gastrointestinal toxicity.

We present a case study that aims at quantitative assessment of the impact of requirements changes, and quantitative estimation of costs of the development activities that must be carried out to accomplish those changes. Our approach is based on enhanced traceability and an integrated view of the process and product models. The elements in the process and product models are quantitatively characterised through proper measurement, thus achieving a sound basis for different kinds of sophisticated analysis concerning the impact of requirements changes and their costs. We present the results of the application of modeling and measurement to an industrial project dealing with real-time software development. The ability to predict the impact of changes in requirements and the cost of related activities is shown.

Reduced cardiac mass and performances are present in GH deficiency and are counteracted by rhGH replacement. GH and IGF-I possess specific myocardial receptors and have been reported able to exert an acute inotropic effect. Synthetic GH secretagogues (GHS) possess specific pituitary and hypothalamic but even myocardial receptors. In 7 male volunteers, we studied cardiac performance by radionuclide angiocardiography after iv administration of rhGH or hexarelin (HEX), a peptidyl GHS. The administration of rhGH or HEX increased circulating GH levels to the same extent (AUC: 1594.6+/-88.1 vs 1739.3+/-262.2 microg/l/min for 90 min) while aldosterone and catecholamine levels did not change; HEX, but not rhGH, significantly increased cortisol levels. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP) and heart rate (HR) were unaffected by rhGH (62.4+/-2.1 vs 62.1+/-2.3%, 90.6+/-3.4 vs 92.0+/-2.5 mm Hg, 62.3+/-1.8 vs 66.7+/-2.7 bpm). HEX increased LVEF (70.7+/-3.0 vs 64.0+/-1.5%, p

OBJECTIVE: IGF-I possesses specific myocardial receptors and is able to promote cardiac remodelling and even inotropic effects in both humans and other animals. In fact, reduced cardiac mass and performance are present in GH deficiency and these alterations are counteracted by recombinant human (rh) GH replacement, restoring IGF-I levels. Recently, the acute administration of 60 microg/kg rhIGF-I has also been reported to be able to improve cardiac performance evaluated by echocardiography or impedance cardiography in normal subjects. The aim of our study was to verify the effects of a subcutaneous low dose of rhIGF-I (20 microg/kg) on cardiac performance in humans. METHODS: In six healthy male adults (mean+/-S. e.m.: 35.7+/-4.3 years of age), the effects of rhIGF-I on left ventricular function evaluated by radionuclide angiocardiography and on circulating IGF-I, GH, insulin, glucose and catecholamines levels were studied. RESULTS: Administration of rhIGF-I increased circulating IGF-I (peak at +150 min vs baseline: 330.2+/- 9.6 vs 199. 7+/-8.7 microg/l, P

OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH deficiency. DESIGN: Stimulation with GHRH. (1 μg/kg iv) combined with arginine (ARG, 0.5 g/kg iv), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH+ARG was evaluated in a second session. SUBJECTS: Forty-five patients with simple obesity (OB 11 male and 34 female, age 40.5±1.8 y, BMI 38.8±1.1 kg/m2), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6±2.4 y, 24.7±0.7 kg/m2) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8±1.0 y, 21.6±0.3 kg/m2) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at −60 and 0 min, and than every 15 min up to +120 min. Basal IGF–I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF–I levels in OB were lower (P

In this paper, we describe a way to identify the critical coordination needs that exist in a software development project through post-mortem content analysis and manual coding of task pairs. Our coding scheme provides guidelines on how to score the strength of the relationship of task pairs based on four characteristics. Such a method and coding scheme has the potential to become a research tool that can be used within the community of researchers and practitioners interested in the socio- technical aspects of software development to identify coordination needs for their analysis in future studies. We seek community feedback to help improve the proposed coding scheme.

BAcKgroUNd: Mixed gonadal dysgenesis (Mgd) is a rare disorder. short stature is a well known feature of this condition. Although growth hormone ( gH) treatment has been suggested to treat growth impairment, conflicting data surround this issue. cAse rePorT: We report on long-term growth hormone ( gH) therapy at pharmacological doses (0.33 mg/kg/week) in a boy (age 4.6 years) with M gd [karyotype 45,X/46,X,idic( y p)]. An untreated boy of similar karyotype and growth delay served as control. The treated boy showed a progressive improve ment of stature during g H administration. His height completely normalized after 6.5 years of treatment and he reached his target height centile before puberty onset. In the untreated boy, no improvement of growth pattern was found. co NclUsIo Ns: We conclude that short boys with M gd and 45,X/46,X,idic( y p) karyotype may benefit from early gH therapy at pharmacological doses. e valuation of larger patient samples and additional follow-up till final height are needed to reach definitive conclusions as to the optimal growth-promoting therapy for this disorder of sex development.

Investigations of self-organizing mechanisms, often inspired by phenomena in natural or societal systems, have yielded a wealth of techniques for the self-adaptation of complex, large- and ultra-large-scale software systems. The principled design of self-adaptive software using principles of self-organization remains challenging. Several studies have approached this problem by proposing design patterns for self-organization. In this paper, we present the results of applying a catalog of biologically inspired design patterns to Mycoload, a self-organizing system for clustering and load balancing in decentralized service networks. We reverse-engineered Mycoload, obtaining a design that isolates instances of several patterns. This exercise allowed us to identify additional reusable self-organization mechanisms, which we have also abstracted out as design patterns: SPECIALIZATION, which we present here for the first time, and a generalized form of COLLECTIVE SORT. The pattern-based design also led to a better understanding of the relationships among the multiple self-organizing mechanisms that together determine the emegent dynamics of Mycoload.

It is estimated that hereditary hearing loss accounts for 60% of deafness in the developed countries. About 30% of hereditary hearing impairment is syndromic which involves other presenting abnormalities along with deafness. There are more than 400 syndromes which include various degrees of hearing impairment with different phenotypes. (Barlow Stewart et al., 2007; Berrettini et al., 2008). Abnormalities of different systems or suggestive clinical findings have been associated with syndromic hearing loss. These include craniofacial malformations, dental abnormalities, ocular abnormalities, renal defects, cardiac abnormalities, endocrine dysfunction, neurologic dysfunction, skeletal abnormalities, integumentary abnormalities, metabolic disease, chromosomal abnormalities.

We describe a method for determining coordination requirements in collaborative software development. Our method uses "live" data based on developer activity rather than relying on historical data such as source code commits which is prevalent in existing methods. We introduce proximity, a measure of the strength of the work dependencies that lead to coordination requirements among members of a software development organization. Our proximity measure relies on a tool which captures the interactions of a developer with her IDE. It quantifies the similarity between records of interactions of developers as they work on their assigned tasks. We describe an algorithm that measures proximity between pairs of tasks or pairs of developers. Through an empirical study on an open source project that routinely records environment interaction data, we show how proximity accurately determines coordination requirements. The proximity measure thus enables proactive detection of coordination requirements and makes possible real time intervention and coordination facilitation via management-, design- and team-related decisions.

Acro-cardio-facial syndrome (ACFS) is an infrequently reported, variable condition characterized by split-hand and split-foot malformation and congenital heart defect (CHD), along with cleft lip and palate, genital anomalies, unusual face and intellectual disability. An autosomal recessive pattern of inheritance has been suggested because of affected sibs born to unaffected parents and parental consanguinity; the cause is unknown. We describe a newborn with the clinical manifestations of ACFS in whom a deletion of the region 6q21-q22.3 was detected by array CGH. We compare the clinical features of the present patient with earlier reported patients with similar 6q deletions and patients diagnosed with ACFS. The similarities between these patient groups suggest that ACFS may be a microdeletion syndrome caused by loss of the 6q21-22.3 region. The recurrence in families may be explained by prenatal germline mosaicism. Alternatively, ACFS may be a genetically heterogeneous disorder which can also be caused by biallelic mutations of an autosomal recessive gene.

We present a bio-inspired mechanism that allows a peer-to-peer overlay network to adapt its topology in response to attacks that try to disrupt the overlay by targeting high-degree nodes. Our strategy is based on the diffusion of an “alert hormone” through the overlay network, in response to node failures. A high level of hormone concentration in a node induce that node to switch protocol. That leads to a self-organized modification of the entire overlay from a superpeer, scale-free layout, to a flatter network that is much less vulnerable to targeted attacks. As the hormone is metabolized with time, nodes switch back to the original protocol and reconstruct a superpeer overlay. We demonstrate and evaluate this mechanism on top of the peer-to-peer Myconet overlay, which is itself self-organized and bio-inspired.

Describing, understanding, and modeling the behavior of systems built upon self-organizing principles (such as many bio-inspired systems) is key to engineering self-organizing systems that can solve problems in real computing environments. Capturing the properties of the micro-macro linkage that connects local behaviors of system components to global emergent properties of the system as a whole is particularly important. Different kinds of models have been proposed, each focusing on a different aspect of the problem: descriptive models provide notations that support the design activity and the application of self-organzing principles; validation models allow formal examination of dynamic properties; and analytic models provide techniques for mathematical exploration of abstracted collective behaviors. Our goal is to identify and select the best tools available from these families, extend them where needed, and tie them together to support the creation and analysis of self-organized autonomic computing systems in an integrated way.

A service network with decentralized ownership is a system where nodes offering a variety of services are administered by different organizations -- or even by a set of individuals. In such a context, nodes hosting services can dynamically enter and exit the system without prior notice, and there is no centralized point of control. If one wants to build into such a system the ability to direct incoming requests for the various hosted services to those nodes that can efficiently fulfill them, one option is to introduce in the system an entity that serves as a gateway to accept service requests, and is an intermediary to re-direct requests as needed. That implies that this intermediary is able to acquire and maintain accurate and up-to-date information on where it can direct incoming requests. Another option, which is the one we pursue in this paper, is to build the system as an overlay network, in which the nodes hosting instances of each of many different types of services can self-organize as "virtual clusters", and efficiently load-balance incoming requests amongst themselves. We describe our design and evaluation of a decentralized computing framework of this kind. We leverage a resilient peer-to-peer overlay that automatically re-configures its topology, responding to the number of different service types executing on the peer nodes, the dynamics of the participation of those nodes (peer churn), and the traffic coming into the system for the various services.

Nineteen acromegalic patients (12 females and 7 males, aged 24–71 yr) were studied for 1–6 yr after radiotherapy (RT), administered by Xrays (18 MeV) by linear accelerator, with parallel opposite beams (doses 45–50.4 Gy, 1.8 Gy daily). Basal GH levels gradually decreased from 6.3–76.2 μg/L (mean±SE, 27.8±4.9) to 0.3–43.4 μg/L (11.7±3.6 μg/L; p

Although the quality of life for haemophiliacs has clearly improved in the last few years, haemophilia still remains a serious disorder justifying prenatal diagnosis (PD) and, if necessary, termination. Because chorionic villus sampling (CVS) is performed in the first trimester of pregnancy, an increasing number of carriers are interested in this test. It has been shown that waiting for the results is particularly distressing for pregnant women, therefore decreasing the diagnostic procedure time can be psychologically helpful. Here we report on PD in a sporadic haemophilia B family based on the direct identification of the pathogenic mutation in a CVS taken at the 12th gestational week. In order to hasten the results, we recovered DNA from a single villus fragment boiled in water and used it directly for PCR reaction. Conformation-sensitive gel electrophoresis (CSGE) was used to detect the mutation in the haemophilia carrier and in the foetus. This approach allowed us to obtain a diagnosis within 24 h of CVS, thus avoiding the long-term psychological effects on the pregnant woman.