Diritti sociali e obblighi giuridici

Molti interpreti attribuiscono ai diritti sociali uno status giuridico incerto, fino ad escluderli dal novero dei diritti fondamentali. In particolare, si sostiene che ai diritti sociali non corrispondano adeguate garanzie e che di conseguenza non si possa agire in giudizio per la loro tutela. Questa impostazione trova ulteriori argomenti basati sulla nota tesi della correlatività che, sulla scorta della tipologia di Wesley N. Hohfeld, identifica il contenuto dei diritti con quello dei doveri correlativi. Luigi Ferrajoli aderisce alla tesi della correlatività ma introduce una variazione che dovrebbe permettere di “salvare” i diritti sociali: fra diritti e garanzie (obblighi e divieti correlativi) vi è un nesso non ontico ma deontico; se l’ordinamento non prevede tali garanzie, esse devono venire introdotte, ma ciò non significa che i diritti non esistano. Tuttavia anche Ferrajoli esclude il “cosiddetto” diritto al lavoro – storicamente, il progenitore dei diritti sociali – dalla sua teoria assiomatizzata. Nell’articolo si suggerisce che per “prendere sul serio” i diritti sociali occorre ricostruire una diversa visione dei diritti come nozione non riducibile al correlativo dei doveri, espressione dei processi sociali di rivendicazione

Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder.

Abstract OBJECTIVE: To study rituximab in pediatric neuromyelitis optica (NMO)/NMO spectrum disorders (NMOSD) and the relationship between rituximab, B cell repopulation, and relapses in order to improve rituximab monitoring and redosing. METHODS: Multicenter retrospective study of 16 children with NMO/NMOSD receiving 652 rituximab courses. According to CD19 counts, events during rituximab were categorized as "repopulation," "depletion," or "depletion failure" relapses (repopulation threshold CD19 6510 7 10(6) cells/L). RESULTS: The 16 patients (14 girls; mean age 9.6 years, range 1.8-15.3) had a mean of 6.1 events (range 1-11) during a mean follow-up of 6.1 years (range 1.6-13.6) and received a total of 76 rituximab courses (mean 4.7, range 2-9) in 42.6-year cohort treatment. Before rituximab, 62.5% had received azathioprine, mycophenolate mofetil, or cyclophosphamide. Mean time from rituximab to last documented B cell depletion and first repopulation was 4.5 and 6.8 months, respectively, with large interpatient variability. Earliest repopulations occurred with the lowest doses. Significant reduction between pre- and post-rituximab annualized relapse rate (ARR) was observed (p = 0.003). During rituximab, 6 patients were relapse-free, although 21 relapses occurred in 10 patients, including 13 "repopulation," 3 "depletion," and 4 "depletion failure" relapses. Of the 13 "repopulation" relapses, 4 had CD19 10-50 7 10(6) cells/L, 10 had inadequate monitoring ( 641 CD19 in the 4 months before relapses), and 5 had delayed redosing after repopulation detection. CONCLUSION: Rituximab is effective in relapse prevention, but B cell repopulation creates a risk of relapse. Redosing before B cell repopulation could reduce the relapse risk further. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab significantly reduces ARR in pediatric NMO/NMOSD. This study also demonstrates a relationship between B cell repopulation and relapses

Mechanical Stimulation Modulates Osteocyte Regulation of Cancer Cell Phenotype

Breast and prostate cancers preferentially metastasise to bone tissue, with metastatic lesions forming in the skeletons of most patients. On arriving in bone tissue, disseminated tumour cells enter a mechanical microenvironment that is substantially different to that of the primary tumour and is largely regulated by bone cells. Osteocytes, the most ubiquitous bone cell type, orchestrate healthy bone remodelling in response to physical exercise. However, the effects of mechanical loading of osteocytes on cancer cell behaviour is still poorly understood. The aim of this study was to characterise the effects of osteocyte mechanical stimulation on the behaviour of breast and prostate cancer cells. To replicate an osteocyte-controlled environment, this study treated breast (MDA-MB-231 and MCF-7) and prostate (PC-3 and LNCaP) cancer cell lines with conditioned media from MLO-Y4 osteocyte-like cells exposed to mechanical stimulation in the form of fluid shear stress. We found that osteocyte paracrine signalling acted to inhibit metastatic breast and prostate tumour growth, characterised by reduced proliferation and invasion and increased migration. In breast cancer cells, these effects were largely reversed by mechanical stimulation of osteocytes. In contrast, conditioned media from mechanically stimulated osteocytes had no effect on prostate cancer cells. To further investigate these interactions, we developed a microfluidic organ-chip model using the Emulate platform. This new organ-chip model enabled analysis of cancer cell migration, proliferation and invasion in the presence of mechanical stimulation of osteocytes by fluid shear stress, resulting in increased invasion of breast and prostate cancer cells. These findings demonstrate the importance of osteocytes and mechanical loading in regulating cancer cell behaviour and the need to incorporate these factors into predictive in vitro models of bone metastasis

Streamlined variational inference for higher level group-specific curve models

© 2020 Statistical Modeling Society. A two-level group-specific curve model is such that the mean response of each member of a group is a separate smooth function of a predictor of interest. The three-level extension is such that one grouping variable is nested within another one, and higher level extensions are analogous. Streamlined variational inference for higher level group-specific curve models is a challenging problem. We confront it by systematically working through two-level and then three-level cases and making use of the higher level sparse matrix infrastructure laid down in (Nolan and Wand (2020), ANZIAM Journal, doi: 10.1017/S1446181120000061). A motivation is analysis of data from ultrasound technology for which three-level group-specific curve models are appropriate. Whilst extension to the number of levels exceeding three is not covered explicitly, the pattern established by our systematic approach sheds light on what is required for even higher level group-specific curve models

Can the Revised UK Code Direct Practice?

The Nursing and Midwifery Council, the United Kingdom regulator of nursing and midwifery has recently revised its professional code of practice. This paper begins by arguing that a professional code must be capable of sustaining close reading and of action guidance. Using four exemplar clauses it is argued that the new revised code does not met this purpose. First, I show that in setting out requirements for consent and documentation, the meaning of the relevant clause has changed significantly during the editing process so that a literal reading of the final document bears little relation to established professional practice. Second, I argue that the clause concerning the nature of professional relationships has also been altered during the editing process so that it is inconsistent with other professional groups and established accounts of the professional nurse-patient relationship. Third, I argue that the clause concerning disclosure of confidential information, which survived revision and editing with its meaning intact is nevertheless factually incorrect and inconsistent with UK law and authoritative guidance. Finally, fourth, I argue that use of the word ‘inappropriate’ is inappropriate as it amounts to meaningless circularity, discussed in relation to a clause on expressing personal beliefs. Taken together, these examples demonstrate that the Code is seriously flawed and does not fulfil its purpose. One way that simple prescriptive clauses in the Code can be usefully understood is through the provision of detailed guidance. I argue that the NMC has changed its position on its view of the value of guidance and has significantly reduced the amount of written guidance and advice is provides. The paper concludes by arguing that in order to meet its action directing function, further clarifying revision and the provision of detailed guidance is required

Self-organization of bacterial biofilms is facilitated by extracellular DNA

Twitching motility-mediated biofilm expansion is a complex, multicellular behavior that enables the active colonization of surfaces by many species of bacteria. In this study we have explored the emergence of intricate network patterns of interconnected trails that form in actively expanding biofilms of Pseudomonas aeruginosa. We have used high-resolution, phase-contrast time-lapse microscopy and developed sophisticated computer vision algorithms to track and analyze individual cell movements during expansion of P. aeruginosa biofilms. We have also used atomic force microscopy to examine the topography of the substrate underneath the expanding biofilm. Our analyses reveal that at the leading edge of the biofilm, highly coherent groups of bacteria migrate across the surface of the semisolid media and in doing so create furrows along which following cells preferentially migrate. This leads to the emergence of a network of trails that guide mass transit toward the leading edges of the biofilm. We have also determined that extracellular DNA (eDNA) facilitates efficient traffic flow throughout the furrow network by maintaining coherent cell alignments, thereby avoiding traffic jams and ensuring an efficient supply of cells to the migrating front. Our analyses reveal that eDNA also coordinates the movements of cells in the leading edge vanguard rafts and is required for the assembly of cells into the "bulldozer" aggregates that forge the interconnecting furrows. Our observations have revealed that large-scale self-organization of cells in actively expanding biofilms of P. aeruginosa occurs through construction of an intricate network of furrows that is facilitated by eDNA

Troubling "understanding mathematics-in-depth": Its role in the identity work of student-teachers in England

Copyright @ The Author(s) 2013. This article is published with open access at Springerlink.comThis article has been made available through the Brunel Open Access Publishing Fund.In this paper, we focus on an initiative in England devised to prepare non-mathematics graduates to train as secondary mathematics teachers through a 6-month Mathematics Enhancement Course (MEC) to boost their subject knowledge. The course documentation focuses on the need to develop “understanding mathematics in-depth” in students in order for them to become successful mathematics teachers. We take a poststructural approach, so we are not interested in asking what such an understanding is, about the value of this approach or about the effectiveness of the MECs in developing this understanding in their participants. Instead we explore what positions this discourse of “understanding mathematics in-depth” makes available to MEC students. We do this by looking in detail at the “identity work” of two students, analysing how they use and are used by this discourse to position themselves as future mathematics teachers. In doing so, we show how even benign-looking social practices such as “understanding mathematics in-depth” are implicated in practices of inclusion and exclusion. We show this through detailed readings of interviews with two participants, one of whom fits with the dominant discourses in the MEC and the other who, despite passing the MEC, experiences tensions between her national identity work and MEC discourses. We argue that it is vital to explore “identity work” within teacher education contexts to ensure that becoming a successful mathematics teacher is equally available to all.King’s College Londo

Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss

Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is known about genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium- and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P < 0.05). In order to confirm our quantitative findings, we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function