BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Servizi Sociali Territoriali e Università: Esempi di Sinergie Possibili per un Percorso di Qualità

Although – or because – social work education in Italy has for some 15 years now been exclusively in the domain of the university the relationship between the academic world and that of practice has been highly tenuous. Research is indeed being conducted by universities, but rarely on issues that are of immediate practice relevance. This means that forms of practice develop and become established habitually which are not checked against rigorous standards of research and that the creation of knowledge at academic level pays scant attention to the practice implications of social changes. This situation has been made even worse by the dwindling resources both in social services and at the level of the universities which means that bureaucratic procedures or imports of specialisations from other disciplines frequently dominate the development of practice instead of a theory-based approach to methodology. This development does not do justice to the actual requirements of Italian society faced with ever increasing post-modern complexity which is reflected also in the nature of social problems because it implies a continuation of a faith in modernity with its idea of technical, clear-cut solutions while social relations have decidedly moved beyond that belief. This discrepancy puts even greater strain on the personnel of welfare agencies and does ultimately not satisfy the ever increasing demands for quality and accountability of services on the part of users and the general public. Social workers badly lack fundamental theoretical reference points which could guide them in their difficult work to arrive at autonomous, situation-specific methodological answers not based on procedures but on analytical knowledge. Thirty years ago, in 1977, a Presidential Decree created the legal basis for the establishment of social service departments at the level of municipalities which created opportunities for the direct involvement of the community in the fight against exclusion. For this potential to be fully utilized it would have required the bringing together of three dimensions, the organizational structure, the opportunities for learning and research in the territory and the contribution by the professional community. As this did not occur social services in Italy still often retain the character of charity which does not concern itself with the actual causes of poverty and exclusion. This in turn affects the relationship with citizens in general who cannot develop trust in those services. Through uncritical processes of interaction Edgar Morin’s dictum manifests itself which is that without resorting to critical reflection on complexity interventions can often have an effect that totally the opposite to the original intention. An important element in setting up a dynamic interchange between academia and practice is the placement on professional social work courses. Here the looping of theory to practice and back to theory etc. can actually take place under the right organizational and conceptual conditions, more so than in abstract, and for practitioners often useless debates about the theory-practice connection. Furthermore, research projects at the University of Florence Social Work Department for instance aim at fostering theoretical reflection at the level of and with the involvement of municipal social service agencies. With a general constructive disposition towards research and some financial investment students were facilitated to undertake social service practice related research for their degree theses for instance in the city of Pistoia. In this way it was also possible to strengthen the confidence and professional identity of social workers as they became aware of the contribution their own discipline can make to practice-relevant research instead of having to move over to disciplines like psychology for those purposes. Examples of this fruitful collaboration were presented at a conference in Pistoia on 25 June 2007. One example is a thesis entitled ‘The object of social work’ and examines the difficult development of definitions of social work and comes to the conclusion that ‘nothing is more practical than a theory’. Another is on coping abilities as a necessary precondition for the utilization of resources supplied by social services in exceptional circumstances. Others deal with the actual sequence of interventions in crisis situations, and one very interestingly looks at time and how it is being constructed often differently by professionals and clients. At the same time as this collaboration on research gathers momentum in the Toscana, supervision is also being demanded more forcefully as complementary to research and with the same aim of profiling more strongly the professional identity of social work. Collaboration between university and social service filed is for mutual benefit. At a time when professional practice is under threat of being defined from the outside through bureaucratic prescriptions a sound grounding in theory is a necessary precondition for competent practice.

Virtual Reality as a Support Tool for Ergonomic-Style Convergence

The competitive industrial context compels companies to speed-up every new product design. In order to keep designing products that meet the needs of the end user, a human centered concurrent product design methodology has been proposed. Its setting up is complicated by the difficulties of collaboration between experts involved inthe design process. In order to ease this collaboration, we propose the use of virtual reality as an intermediate design representation in the form of light and specialized immersive convergence support applications. In this paper, we present the As Soon As Possible (ASAP) methodology making possible the development of these tools while ensuring their usefulness and usability. The relevance oft his approach is validated by an industrial use case through the design of an ergonomic-style convergence support tool.

The European Modern Pollen Database (EMPD) project

Modern pollen samples provide an invaluable research tool for helping to interpret the quaternary fossil pollen record, allowing investigation of the relationship between pollen as the proxy and the environmental parameters such as vegetation, land-use, and climate that the pollen proxy represents. The European Modern Pollen Database (EMPD) is a new initiative within the European Pollen Database (EPD) to establish a publicly accessible repository of modern (surface sample) pollen data. This new database will complement the EPD, which at present holds only fossil sedimentary pollen data. The EMPD is freely available online to the scientific community and currently has information on almost 5,000 pollen samples from throughout the Euro-Siberian and Mediterranean regions, contributed by over 40 individuals and research groups. Here we describe how the EMPD was constructed, the various tables and their fields, problems and errors, quality controls, and continuing efforts to improve the available data.

Erratum to: The European Modern Pollen Database (EMPD) project

Unfortunately, the list of authors contains a number of duplications, omissions and other errors in the original publication of the article. The correct list appears in this erratum.

Routine phenotypic identification of bacterial species of the family Pasteurellaceae isolated from animals

Pasteurellaceae are bacteria with an important role as primary or opportunistic, mainly respiratory, pathogens in domestic and wild animals. Some species of Pasteurellaceae cause severe diseases with high economic losses in commercial animal husbandry and are of great diagnostic concern. Because of new data on the phylogeny of Pasteurellaceae, their taxonomy has recently been revised profoundly, thus requiring an improved phenotypic differentiation procedure to identify the individual species of this family. A new and simplified procedure to identify species of Actinobacillus, Avibacterium, Gallibacterium, Haemophilus, Mannheimia, Nicoletella, and Pasteurella, which are most commonly isolated from clinical samples of diseased animals in veterinary diagnostic laboratories, is presented in the current study. The identification procedure was evaluated with 40 type and reference strains and with 267 strains from routine diagnostic analysis of various animal species, including 28 different bacterial species. Type, reference, and field strains were analyzed by 16S ribosomal RNA (rrs) and rpoB gene sequencing for unambiguous species determination as a basis to evaluate the phenotypic differentiation schema. Primary phenotypic differentiation is based on beta-nicotinamide adenine dinucleotide (beta-NAD) dependence and hemolysis, which are readily determined on the isolation medium. The procedure divides the 28 species into 4 groups for which particular biochemical reactions were chosen to identify the bacterial species. The phenotypic identification procedure allowed researchers to determine the species of 240 out of 267 field strains. The procedure is an easy and cost-effective system for the rapid identification of species of the Pasteurellaceae family isolated from clinical specimens of animals.

Addressing micropollution by linking problem characteristics to policy instruments

What characterizes micropollution as a policy problem and which policy instruments are adequate to regulate micropollution, given the specific problem features? In this article, problem characteristics of micropollution are systematically analyzed and linked to potential policy solutions.

Detection of Leishmania RNA virus in Leishmania parasites.

BACKGROUND Patients suffering from cutaneous leishmaniasis (CL) caused by New World Leishmania (Viannia) species are at high risk of developing mucosal (ML) or disseminated cutaneous leishmaniasis (DCL). After the formation of a primary skin lesion at the site of the bite by a Leishmania-infected sand fly, the infection can disseminate to form secondary lesions. This metastatic phenotype causes significant morbidity and is often associated with a hyper-inflammatory immune response leading to the destruction of nasopharyngeal tissues in ML, and appearance of nodules or numerous ulcerated skin lesions in DCL. Recently, we connected this aggressive phenotype to the presence of Leishmania RNA virus (LRV) in strains of L. guyanensis, showing that LRV is responsible for elevated parasitaemia, destructive hyper-inflammation and an overall exacerbation of the disease. Further studies of this relationship and the distribution of LRVs in other Leishmania strains and species would benefit from improved methods of viral detection and quantitation, especially ones not dependent on prior knowledge of the viral sequence as LRVs show significant evolutionary divergence. METHODOLOGY/PRINCIPAL FINDINGS This study reports various techniques, among which, the use of an anti-dsRNA monoclonal antibody (J2) stands out for its specific and quantitative recognition of dsRNA in a sequence-independent fashion. Applications of J2 include immunofluorescence, ELISA and dot blot: techniques complementing an arsenal of other detection tools, such as nucleic acid purification and quantitative real-time-PCR. We evaluate each method as well as demonstrate a successful LRV detection by the J2 antibody in several parasite strains, a freshly isolated patient sample and lesion biopsies of infected mice. CONCLUSIONS/SIGNIFICANCE We propose that refinements of these methods could be transferred to the field for use as a diagnostic tool in detecting the presence of LRV, and potentially assessing the LRV-related risk of complications in cutaneous leishmaniasis.

Cost-benefit analysis: The ``gold standard'' re-examined

The dissertation reviews the recommendations of the Panel on Cost Effectiveness in Health and Medicine (Panel) convened by the US Public Health Service in 1993 in four areas: aggregation of costs and benefits, methods of estimating resources used, definition of population impacted and perspective used in cost benefit analysis. Financial data from a clinical trial was used to test whether different approaches in each of the above four areas would change the net benefit resulting from a cost benefit analysis. Differences in aggregation of cost and benefit resulted in the same net benefit, but not the same cost/benefit ratios. Differences in resource use estimation methods, population subgroups definitions and perspectives all produced different net benefits. Difference in perspective resulted in different and often opposing decisions as to whether the proposed intervention from the clinical trial should be implemented. ^

Disorganization and timing of motor behavior : insight from gesture impairments and movement patterns in schizophrenia

Background: Motor symptoms are frequent phenomena across the entire course of schizophrenia1. Some have argued that disorganized behavior was associated with aberrant motor behavior. We have studied the association of motor disturbances and disorganization in two projects focusing on the timing of movements. Method: In two studies, we assessed motor behavior and psychopathology. The first study applied a validated test of upper limb apraxia in 30 schizophrenia patients2,3. We used standardized video assessments of hand gestures by a blinded rater. The second study tested the stability of movement patterns using time series analysis in actigraphy data of 100 schizophrenia patients4. Both stability of movement patterns and the overall amount of movement were calculated from data of two hours with high degrees of social interaction comparable across the 100 subjects. Results: In total, 67% of the patients had gesture performance deficits3. Most frequently, they made spatial, temporal and body-part-as-object errors. Gesture performance relied on frontal lobe function2. Poor gesture performance was associated with increased disorganization scores. In the second study, we found disorganization to be predicted only by more irregular movement patterns irrespective of the overall amount of movement4. Conclusion : Both studies provide evidence for a link between aberrant timing of motor behavior and disorganization. Disturbed movement control seems critical for disorganized behavior in schizophrenia.