Sperm protein 17 is expressed in human nervous system tumours

BACKGROUND: Human sperm protein 17 (Sp17) is a highly conserved protein that was originally isolated from a rabbit epididymal sperm membrane and testis membrane pellet. It has recently been included in the cancer/testis (CT) antigen family, and shown to be expressed in multiple myeloma and ovarian cancer. We investigated its immunolocalisation in specimens of nervous system (NS) malignancies, in order to establish its usefulness as a target for tumour-vaccine strategies. METHODS: The expression of Sp17 was assessed by means of a standardised immunohistochemical procedure [(mAb/antigen) MF1/Sp17] in formalin-fixed and paraffin embedded surgical specimens of NS malignancies, including 28 neuroectodermal primary tumours (6 astrocytomas, 16 glioblastoma multiforme, 5 oligodendrogliomas, and 1 ependymoma), 25 meningeal tumours, and five peripheral nerve sheath tumours (4 schwannomas, and 1 neurofibroma),. RESULTS: A number of neuroectodermal (21%) and meningeal tumours (4%) were found heterogeneously immunopositive for Sp17. None of the peripheral nerve sheath tumours was immunopositive for Sp17. The expression pattern was heterogeneous in all of the positive samples, and did not correlate with the degree of malignancy. CONCLUSION: The frequency of expression and non-uniform cell distribution of Sp17 suggest that it cannot be used as a unique immunotherapeutic target in NS cancer. However, our results do show the immunolocalisation of Sp17 in a proportion of NS tumour cells, but not in their non-pathological counterparts. The emerging complex function of Sp17 makes further studies necessary to clarify the link between it and immunopositive cells

Spatial sensory organization and body representation in pain perception

Pain is a subjective experience that protects the body. This function implies a special relation between the brain mechanisms underlying pain perception and representation of the body. All sensory systems involve the body for the trivial reason that sensory receptors are located in the body. The nociceptive system of detecting noxious stimuli comprises two classes of peripheral afferents, Aδ and C nociceptors, that cover almost the entire body surface. We review evidence from experimental studies of pain in humans and other animals suggesting that Aδ skin nociceptors project to a spatially-organised, somatotopic map in the primary somatosensory cortex. While the relation between pain perception and homeostatic regulation of bodily systems is widely acknowledged, the organization of nociceptive information into spatial maps of the body has received little attention. Importantly, the somatotopic neural organization of pain systems can shed light on pain-related plasticity and pain modulation. Finally, we show that the neural coding of noxious stimuli, and consequent experience of pain, are both strongly influenced when cognitive representations of the body are activated by viewing the body, as opposed to viewing another object — an effect we term ‘visual analgesia’. We argue that pain perception involves some of the representational properties of exteroceptive senses, such as vision and touch. Pain, however, has the unique feature that the content of representation is the body itself, rather than any external object of perception. We end with some suggestions regarding how linking pain to body representation could shed light on clinical conditions, notably chronic pain

A realist analysis of hospital patient safety in Wales:Applied learning for alternative contexts from a multisite case study

Background: Hospital patient safety is a major social problem. In the UK, policy responses focus on the introduction of improvement programmes that seek to implement evidence-based clinical practices using the Model for Improvement, Plan-Do-Study-Act cycle. Empirical evidence that the outcomes of such programmes vary across hospitals demonstrates that the context of their implementation matters. However, the relationships between features of context and the implementation of safety programmes are both undertheorised and poorly understood in empirical terms. Objectives: This study is designed to address gaps in conceptual, methodological and empirical knowledge about the influence of context on the local implementation of patient safety programmes. Design: We used concepts from critical realism and institutional analysis to conduct a qualitative comparative-intensive case study involving 21 hospitals across all seven Welsh health boards. We focused on the local implementation of three focal interventions from the 1000 Lives+ patient safety programme: Improving Leadership for Quality Improvement, Reducing Surgical Complications and Reducing Health-care Associated Infection. Our main sources of data were 160 semistructured interviews, observation and 1700 health policy and organisational documents. These data were analysed using the realist approaches of abstraction, abduction and retroduction. Setting: Welsh Government and NHS Wales. Participants: Interviews were conducted with 160 participants including government policy leads, health managers and professionals, partner agencies with strategic oversight of patient safety, advocacy groups and academics with expertise in patient safety. Main outcome measures: Identification of the contextual factors pertinent to the local implementation of the 1000 Lives+ patient safety programme in Welsh NHS hospitals. Results: An innovative conceptual framework harnessing realist social theory and institutional theory was produced to address challenges identified within previous applications of realist inquiry in patient safety research. This involved the development and use of an explanatory intervention–context–mechanism–agency–outcome (I-CMAO) configuration to illustrate the processes behind implementation of a change programme. Our findings, illustrated by multiple nested I-CMAO configurations, show how local implementation of patient safety interventions are impacted and modified by particular aspects of context: specifically, isomorphism, by which an intervention becomes adapted to the environment in which it is implemented; institutional logics, the beliefs and values underpinning the intervention and its source, and their perceived legitimacy among different groups of health-care professionals; and the relational structure and power dynamics of the functional group, that is, those tasked with implementing the initiative. This dynamic interplay shapes and guides actions leading to the normalisation or the rejection of the patient safety programme. Conclusions: Heightened awareness of the influence of context on the local implementation of patient safety programmes is required to inform the design of such interventions and to ensure their effective implementation and operationalisation in the day-to-day practice of health-care teams. Future work is required to elaborate our conceptual model and findings in similar settings where different interventions are introduced, and in different settings where similar innovations are implemented. Funding: The National Institute for Health Research Health Services and Delivery Research programme

New standards of absorbed dose to water under reference conditions by graphite calorimetry for 60^{60}Co and high-energy x-rays at LNE-LNHB

article id. 552International audienceThe LNE-LNHB has developed two primary standards to determine the absorbed dose to water under reference conditions (for 10 cm × 10 cm) in $^{60}$Co, 6 MV, 12 MV and 20 MV photon beams: a new graphite calorimeter and a water calorimeter. This first paper presents the results obtained with the graphite calorimeter and the new associated methodology. The associated relative standard uncertainty ($k$ = 1) of absorbed dose to water is 0.25% for $^{60}$Co and lies between 0.32% to 0.35% for MV x-ray beams

Key comparison BIPM.RI(I)-K6 of the standards for absorbed dose to water of the LNE–LNHB, France and the BIPM in accelerator photon beams

Technical SupplementInternational audienceA comparison of the dosimetry for accelerator photon beams was carried out between the Laboratoire National de Métrologie et d'Essais–Laboratoire National Henri Becquerel (LNE–LNHB) and the Bureau International des Poids et Mesures (BIPM) in March 2012. The comparison was based on the determination of absorbed dose to water for three radiation qualities at the LNE–LNHB. The comparison result, reported as a ratio of the LNE–LNHB and the BIPM evaluations, is 0.995 at 6 MV and 12 MV; 0.994 at 20 MV, with a combined standard uncertainty of 5 parts in 103 at all three energies. This result is the fourth in the on-going BIPM.RI(I)-K6 series of comparisons

Using a dose-area product for absolute measurements in small fields: a feasibility study

International audienceTo extend the dosimetric reference system to field sizes smaller than 2 cm x 2 cm, the LNE-LNHB laboratory is studying an approach based on a new dosimetric quantity named the dose-area product instead of the commonly used absorbed dose at a point. A graphite calorimeter and a plane parallel ion chamber with a sensitive surface of 3 cm diameter were designed and built for measurements in fields of 2, 1 and 0.75 cm diameter. The detector surface being larger than the beam section, most of the issues linked with absolute dose measurements at a point could be avoided. Calibration factors of the plane parallel ionization chamber were established in terms of dose-area product in water for small fields with an uncertainty smaller than 0.9%

A new single crystal diamond dosimeter for small beam: comparison with different commercial active detectors

International audienceRecent developments of new therapy techniques using small photon beams, such as stereotactic radiotherapy, require suitable detectors to determine the delivered dose with a high accuracy. The dosimeter has to be as close as possible to tissue equivalence and to exhibit a small detection volume compared to the size of the irradiation field, because of the lack of lateral electronic equilibrium in small beam. Characteristics of single crystal diamond (tissue equivalent material Z = 6, high density) make it an ideal candidate to fulfil most of small beam dosimetry requirements. A commercially available Element Six electronic grade synthetic diamond was used to develop a single crystal diamond dosimeter (SCDDo) with a small detection volume (0.165 mm3).Long term stability was studied by irradiating the SCDDo in a 60Co beam over 14 h. A good stability (deviation less than ± 0.1%) was observed. Repeatability, dose linearity, dose rate dependence and energy dependence were studied in a 10 × 10 cm2 beam produced by a Varian Clinac 2100 C linear accelerator. SCDDo lateral dose profile, depth dose curve and outputfactor (OF) measurements were performed for small photon beams with a micro multileaf collimator m3 (BrainLab) attached to the linac. This study is focused on the comparison of SCDDo measurements to those obtained with different commercially available active detectors: an unshielded silicon diode (PTW 60017), a shielded silicon diode (Sun Nuclear EDGE), a PinPoint ionization chamber (PTW 31014) and two natural diamond detectors (PTW 60003). SCDDo presents an excellent spatial resolution for dose profile measurements, due to its small detection volume. Low energy dependence (variation of 1.2% between 6 and 18 MV photon beam) and low dose rate dependence of the SCDDo (variation of 1% between 0.53 and 2.64 Gy min−1) are obtained, explaining the good agreement between the SCDDo and the efficient unshielded diode (PTW 60017) in depth dose curve measurements. For field sizes ranging from 0.6 × 0.6 to 10 × 10 cm2 , OFs obtained with the SCDDo are between the OFs measured with the PinPoint ionization chamber and the Sun Nuclear EDGE diode that are known to respectively underestimate and overestimate OF values in small beam, due to the large detection volume of the chamber and the non-water equivalence of both detector