EMMA - A New Underground Cosmic-Ray Experiment

A new type of cosmic-ray experiment is under construction in the Pyh\"asalmi mine in the underground laboratory of the University of Oulu, Finland. It aims to study the composition of cosmic rays at and above the knee region. The experiment, called EMMA, will cover approximately 150 square-metres of detector area. The array is capable of measuring the multiplicity and the lateral distribution of underground muons, and the arrival direction of the air shower. The full-size detector is expected to run by the end of 2007.Comment: Extended and updated TAUP2005 Proceedings contribution. 8 pages, 5 figures (part in colour). Preprint not submitte

Second primary malignancies in patients with male breast cancer

An international multicentre study of first and second primary neoplasms associated with male breast cancer was carried out by pooling data from 13 cancer registries. Among a total of 3409 men with primary breast cancer, 426 (12.5%) developed a second neoplasia; other than breast cancer, a 34% overall excess risk of second primary neoplasia, affecting the small intestine (standardised incidence ratio, 4.95, 95% confidence interval, 1.35–12.7), rectum (1.78, 1.20–2.54), pancreas (1.93, 1.14–3.05), skin (nonmelanoma, 1.65, 1.16–2.29), prostate (1.61, 1.34–1.93) and lymphohaematopoietic system (1.63, 1.12–2.29). A total of 225 male breast cancers was recorded after cancers other than breast cancer, but an increase was found only after lymphohaematopoietic neoplasms. BRCA2 (and to some extent BRCA1) mutations may explain the findings for pancreatic and prostate cancers. Increases at other sites may be related to unknown factors or to chance. This large study shows that the risks for second discordant tumours after male breast cancer pose only a moderate excess risk

Separate and combined analysis of successive dependent outcomes after breast-conservation surgery: recurrence, metastases, second cancer and death

<p>Abstract</p> <p>Background</p> <p>In the setting of recurrent events, research studies commonly count only the first occurrence of an outcome in a subject. However this approach does not correctly reflect the natural history of the disease. The objective is to jointly identify prognostic factors associated with locoregional recurrences (LRR), contralateral breast cancer, distant metastases (DM), other primary cancer than breast and breast cancer death and to evaluate the correlation between these events.</p> <p>Methods</p> <p>Patients (n = 919) with a primary invasive breast cancer and treated in a cancer center in South-Western France with breast-conserving surgery from 1990 to 1994 and followed up to January 2006 were included. Several types of non-independent events could be observed for the same patient: a LRR, a contralateral breast cancer, DM, other primary cancer than breast and breast cancer death. Data were analyzed separately and together using a random-effects survival model.</p> <p>Results</p> <p>LRR represent the most frequent type of first failure (14.6%). The risk of any event is higher for young women (less than 40 years old) and in the first 10 years of follow-up after the surgery. In the combined analysis histological tumor size, grade, number of positive nodes, progesterone receptor status and treatment combination are prognostic factors of any event. The results show a significant dependence between these events with a successively increasing risk of a new event after the first and second event. The risk of developing a new failure is greatly increased (RR = 4.25; 95%CI: 2.51-7.21) after developing a LRR, but also after developing DM (RR = 3.94; 95%CI: 2.23-6.96) as compared to patients who did not develop a first event.</p> <p>Conclusion</p> <p>We illustrated that the random effects survival model is a more satisfactory method to evaluate the natural history of a disease with multiple type of events.</p

A metrological approach to improve accuracy and reliability of ammonia measurements in ambient air

The environmental impacts of ammonia (NH$_3$) in ambient air have become more evident in the recent decades, leading to intensifying research in this field. A number of novel analytical techniques and monitoring instruments have been developed, and the quality and availability of reference gas mixtures used for the calibration of measuring instruments has also increased significantly. However, recent inter-comparison measurements show significant discrepancies, indicating that the majority of the newly developed devices and reference materials require further thorough validation. There is a clear need for more intensive metrological research focusing on quality assurance, intercomparability and validations. MetNH3 (Metrology for ammonia in ambient air) is a three-year project within the framework of the European Metrology Research Programme (EMRP), which aims to bring metrological traceability to ambient ammonia measurements in the 0.5–500 nmol mol$^{−1}$ amount fraction range. This is addressed by working in three areas: (1) improving accuracy and stability of static and dynamic reference gas mixtures, (2) developing an optical transfer standard and (3) establishing the link between high-accuracy metrological standards and field measurements. In this article we describe the concept, aims and first results of the project.EMRP MetNH3 (EURAMET

A metrological approach to improve accuracy and reliability of ammonia measurements in ambient air

The environmental impacts of ammonia (NH$_3$) in ambient air have become more evident in the recent decades, leading to intensifying research in this field. A number of novel analytical techniques and monitoring instruments have been developed, and the quality and availability of reference gas mixtures used for the calibration of measuring instruments has also increased significantly. However, recent inter-comparison measurements show significant discrepancies, indicating that the majority of the newly developed devices and reference materials require further thorough validation. There is a clear need for more intensive metrological research focusing on quality assurance, intercomparability and validations. MetNH3 (Metrology for ammonia in ambient air) is a three-year project within the framework of the European Metrology Research Programme (EMRP), which aims to bring metrological traceability to ambient ammonia measurements in the 0.5–500 nmol mol$^{−1}$ amount fraction range. This is addressed by working in three areas: (1) improving accuracy and stability of static and dynamic reference gas mixtures, (2) developing an optical transfer standard and (3) establishing the link between high-accuracy metrological standards and field measurements. In this article we describe the concept, aims and first results of the project.EMRP MetNH3 (EURAMET

Calpain 3 is important for muscle regeneration: Evidence from patients with limb girdle muscular dystrophies

<p>Abstract</p> <p>Background</p> <p>Limb girdle muscular dystrophy (LGMD) type 2A is caused by mutations in the CAPN3 gene and complete lack of functional calpain 3 leads to the most severe muscle wasting. Calpain 3 is suggested to be involved in maturation of contractile elements after muscle degeneration. The aim of this study was to investigate how mutations in the four functional domains of calpain 3 affect muscle regeneration.</p> <p>Methods</p> <p>We studied muscle regeneration in 22 patients with LGMD2A with calpain 3 deficiency, in five patients with LGMD2I, with a secondary reduction in calpain 3, and in five patients with Becker muscular dystrophy (BMD) with normal calpain 3 levels. Regeneration was assessed by using the developmental markers neonatal myosin heavy chain (nMHC), vimentin, MyoD and myogenin and counting internally nucleated fibers.</p> <p>Results</p> <p>We found that the recent regeneration as determined by the number of nMHC/vimentin-positive fibers was greatly diminished in severely affected LGMD2A patients compared to similarly affected patients with LGMD2I and BMD. Whorled fibers, a sign of aberrant regeneration, was highly elevated in patients with a complete lack of calpain 3 compared to patients with residual calpain 3. Regeneration is not affected by location of the mutation in the <it>CAPN3 </it>gene.</p> <p>Conclusions</p> <p>Our findings suggest that calpain 3 is needed for the regenerative process probably during sarcomere remodeling as the complete lack of functional calpain 3 leads to the most severe phenotypes.</p

Understanding conflict-related sexual violence and the ‘everyday’ experience of conflict through witness testimonies.

The testimonies of witnesses who testify before criminal courts provide crucial insights into the situated experience of conflict-related sexual violence. Witness testimonies highlight the complex realities and everyday lives of individuals caught up in situations of armed conflict. The evidence presented by witnesses can provide vital insights into lived experiences of wartime violence, and reveal the seemingly mundane strategies and tactics adopted by victims to cope with, survive and resist the violent and coercive circumstances of war. This article foregrounds conflict-related sexual violence witness testimonies as highly significant sources of knowledge of the everyday experiences of conflict. It sets out a bottom-up, mixed-method approach for identifying and analysing the experiential accounts of those who lived through conflict-related sexual violence, while engaging with the opportunities and challenges of using witness testimony. Our approach unsettles existing notions of ‘the everyday’ in Peace & Conflict Studies as a synonym for narratives and practices of violence, justice and peacebuilding that are private, informal and largely hidden from view. Understanding witness testimonies requires conceptualising the everyday as an amalgam of formal and informal practices, as accessible through both elite and lay knowledges and as documented in both public and private (e.g. redacted) sources. It requires challenging taken-for-granted dichotomies that are frequently invoked to understand conflict and peace

Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

Background: Obesity is a complex metabolic condition in strong association with various diseases, like type 2 diabetes, resulting in major public health and economic implications. Obesity is the result of environmental and genetic factors and their interactions, including genome-wide genetic interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model for human obesity, offering the possibility to study in-depth organ-level transcriptomic regulations of obesity, unfeasible in humans. Our aim was to reveal adipose tissue co-expression networks, pathways and transcriptional regulations of obesity using RNA Sequencing based systems biology approaches in a porcine model. Methods: We selected 36 animals for RNA Sequencing from a previously created F2 pig population representing three extreme groups based on their predicted genetic risks for obesity. We applied Weighted Gene Co-expression Network Analysis (WGCNA) to detect clusters of highly co-expressed genes (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results: WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P <0.001). Functional annotation identified pathways enlightening the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E(-7)), and immune-related complications (e. g. Natural killer cell mediated cytotoxity, P = 3.8E(-5); B cell receptor signaling pathway, P = 7.2E(-5)). Lemon-Tree identified three potential regulator genes, using confident scores, for the WGCNA module which was associated with osteoclast differentiation: CCR1, MSR1 and SI1 (probability scores respectively 95.30, 62.28, and 34.58). Moreover, detection of differentially connected genes identified various genes previously identified to be associated with obesity in humans and rodents, e.g. CSF1R and MARC2. Conclusions: To our knowledge, this is the first study to apply systems biology approaches using porcine adipose tissue RNA-Sequencing data in a genetically characterized porcine model for obesity. We revealed complex networks, pathways, candidate and regulatory genes related to obesity, confirming the complexity of obesity and its association with immune-related disorders and osteoporosis

Laser spectroscopy for breath analysis : towards clinical implementation

Detection and analysis of volatile compounds in exhaled breath represents an attractive tool for monitoring the metabolic status of a patient and disease diagnosis, since it is non-invasive and fast. Numerous studies have already demonstrated the benefit of breath analysis in clinical settings/applications and encouraged multidisciplinary research to reveal new insights regarding the origins, pathways, and pathophysiological roles of breath components. Many breath analysis methods are currently available to help explore these directions, ranging from mass spectrometry to laser-based spectroscopy and sensor arrays. This review presents an update of the current status of optical methods, using near and mid-infrared sources, for clinical breath gas analysis over the last decade and describes recent technological developments and their applications. The review includes: tunable diode laser absorption spectroscopy, cavity ring-down spectroscopy, integrated cavity output spectroscopy, cavity-enhanced absorption spectroscopy, photoacoustic spectroscopy, quartz-enhanced photoacoustic spectroscopy, and optical frequency comb spectroscopy. A SWOT analysis (strengths, weaknesses, opportunities, and threats) is presented that describes the laser-based techniques within the clinical framework of breath research and their appealing features for clinical use.Peer reviewe