Quantitative evaluation of the effect of attenuation correction in SPECT images with CT-derived attenuation

In this study, we assessed the importance of attenuation correction by quantitative evaluation of errors associated with attenuation in myocardial SPECT in a phantom study. To do attenuation correction we use an attenuation map derived from X-ray CT data. The succession of attenuation correction highly depends on high quality of attenuation maps. CT derived attenuation map in related to non-uniform attenuation correction is used to do transmission dependent scatter correction. The OSEM algorithm with attenuation model was developed and used for attenuation correction during image reconstruction. Finally a comparison was done between reconstructed images using our OSEM code and analytical FBP method. The results of measurements show that: Our programs are capable to reconstruct SPECT images and correct the attenuation effects. Moreover to evaluate reconstructed image quality before and after attenuation correction we applied a famous approach using Image Quality Index. Attenuation correction increases the quality and quantity factors in both methods. This increasing is independent of activity in quantity factor and decrease with activity in quality factor. Both quantitative and qualitative of SPECT images were improved by attenuation correction. In both OSEM and FBP the activity ratio of heart phantom in comparison with the markers was very increased. So the attenuation correction in fat patients and low activity is recommended. Attenuation correction with CT images and OSEM reconstruction in the condition of complete registration yields superior results

Obesity, Type 2 Diabetes, Lifestyle Factors, and Risk of Gallstone Disease: A Mendelian Randomization Investigation.

BACKGROUND & AIMS: Obesity, type 2 diabetes, and lifestyle factors (cigarette smoking, alcohol drinking, and coffee consumption) have been associated with the risk of developing gallstone disease in observational studies, but whether these associations are causal is undetermined. We conducted a Mendelian randomization study to assess these associations. METHODS: Genetic instruments associated with the exposures at the genome-wide significance (p < 5×10-8) level were selected from corresponding genome-wide associations studies (n=224 459 to 1 232 091 individuals). Summary-level data for gallstone disease were obtained from the UK Biobank (10 520 cases and 350 674 non-cases) and FinnGen consortium (11 675 cases and 121 348 non-cases). Univariable and multivariable Mendelian randomization analyses were conducted. Results from UK Biobank and FinnGen were combined using fixed-effects meta-analysis. RESULTS: The odds ratios were 1.63 (95% confidence interval (CI), 1.49, 1.79) for one standard deviation (SD) increase in body mass index, 1.81 (95% CI, 1.60, 2.05) for one SD increase in waist circumference, 1.13 (95% CI, 1.09, 1.17) for one unit increase in the log-odds ratio of type 2 diabetes and 1.25 (95% CI, 1.16, 1.34) for one SD increase in prevalence of smoking initiation. The associations for body mass index and type 2 diabetes persisted after mutual adjustment. Genetically predicted coffee consumption was inversely associated with gallstone disease after adjustment for body mass index and smoking (odds ratio per 50% increase 0.44, 95% CI, 0.21, 0.91). There was no association with alcohol consumption. CONCLUSIONS: This study supports independent causal roles of obesity, type 2 diabetes, and smoking in gallstone disease

Mitochondria directly influence fertilisation outcome in the pig

The mitochondrion is explicitly involved in cytoplasmic regulation and is the cell's major generator of ATP. Our aim was to determine whether mitochondria alone could influence fertilisation outcome. In vitro, oocyte competence can be assessed through the presence of glucose-6-phosphate dehydrogenase (G6PD) as indicated by the dye, brilliant cresyl blue (BCB). Using porcine in vitro fertilisation (IVF), we have assessed oocyte maturation, cytoplasmic volume, fertilisation outcome, mitochondrial number as determined by mtDNA copy number, and whether mitochondria are uniformly distributed between blastomeres of each embryo. After staining with BCB, we observed a significant difference in cytoplasmic volume between BCB positive (BCB+) and BCB negative (BCB-) oocytes. There was also a significant difference in mtDNA copy number between fertilised and unfertilised oocytes and unequal mitochondrial segregation between blastomeres during early cleavage stages. Furthermore, we have supplemented BCB- oocytes with mitochondria from maternal relatives and observed a significant difference in fertilisation outcomes following both IVF and intracytoplasmic sperm injection (ICSI) between supplemented, sham-injected and non-treated BCB- oocytes. We have therefore demonstrated a relationship between oocyte maturity, cytoplasmic volume, and fertilisation outcome and mitochondrial content. These data suggest that mitochondrial number is important for fertilisation outcome and embryonic development. Furthermore, a mitochondrial pre-fertilisation threshold may ensure that, as mitochondria are diluted out during post-fertilisation cleavage, there are sufficient copies of mtDNA per blastomere to allow transmission of mtDNA to each cell of the post-implantation embryo after the initiation of mtDNA replication during the early postimplantation stages

Case Survey Studies in Software Engineering Research

Background: Given the social aspects of Software Engineering (SE), in the last twenty years, researchers from the field started using research methods common in social sciences such as case study, ethnography, and grounded theory. More recently, case survey, another imported research method, has seen its increasing use in SE studies. It is based on existing case studies reported in the literature and intends to harness the generalizability of survey and the depth of case study. However, little is known on how case survey has been applied in SE research, let alone guidelines on how to employ it properly. Aims: This article aims to provide a better understanding of how case survey has been applied in Software Engineering research. Method: To address this knowledge gap, we performed a systematic mapping study and analyzed 12 Software Engineering studies that used the case survey method. Results: Our findings show that these studies presented a heterogeneous understanding of the approach ranging from secondary studies to primary inquiries focused on a large number of instances of a research phenomenon. They have not applied the case survey method consistently as defined in the seminal methodological papers. Conclusions: We conclude that a set of clearly defined guidelines are needed on how to use case survey in SE research, to ensure the quality of the studies employing this approach and to provide a set of clearly defined criteria to evaluate such work.Comment: Accepted for presentation at ACM / IEEE International Symposium on Empirical Software Engineering and Measurement (ESEM) (ESEM '20

Transmission of mitochondrial DNA following assisted reproduction and nuclear transfer

Review of the articleMitochondria are the organelles responsible for producing the majority of a cell's ATP and also play an essential role in gamete maturation and embryo development. ATP production within the mitochondria is dependent on proteins encoded by both the nuclear and the mitochondrial genomes, therefore co-ordination between the two genomes is vital for cell survival. To assist with this co-ordination, cells normally contain only one type of mitochondrial DNA (mtDNA) termed homoplasmy. Occasionally, however, two or more types of mtDNA are present termed heteroplasmy. This can result from a combination of mutant and wild-type mtDNA molecules or from a combination of wild-type mtDNA variants. As heteroplasmy can result in mitochondrial disease, various mechanisms exist in the natural fertilization process to ensure the maternal-only transmission of mtDNA and the maintenance of homoplasmy in future generations. However, there is now an increasing use of invasive oocyte reconstruction protocols, which tend to bypass mechanisms for the maintenance of homoplasmy, potentially resulting in the transmission of either form of mtDNA heteroplasmy. Indeed, heteroplasmy caused by combinations of wild-type variants has been reported following cytoplasmic transfer (CT) in the human and following nuclear transfer (NT) in various animal species. Other techniques, such as germinal vesicle transfer and pronuclei transfer, have been proposed as methods of preventing transmission of mitochondrial diseases to future generations. However, resulting embryos and offspring may contain mtDNA heteroplasmy, which itself could result in mitochondrial disease. It is therefore essential that uniparental transmission of mtDNA is ensured before these techniques are used therapeutically

A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: results of a multicentre analysis.

New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines

Can mutations in ELA2, neutrophil elastase expression or differential cell toxicity explain sulphasalazine-induced agranulocytosis?

BACKGROUND: Drug-induced agranulocytosis, a severe side effect marked by a deficit or absolute lack of granulocytic white blood cells, is a rare side-effect of the anti-inflammatory drug sulphasalazine. Mutations in the human neutrophil elastase gene (ELA2), causing increased intracellular concentration of this serine protease, inhibits neutrophil differentiation in severe congenital neutropenia (SCN). Since the clinical symptoms of agranulocytosis and SCN are similar, we hypothesized that it may origin from a common genetic variation in ELA2 or that sulphasalazine may affect human neutrophil elastase activity and protein expression. METHODS: We screened for genetic differences in ELA2 in DNA from 36 patients who had suffered from sulphasalazine-induced agranulocytosis, and compared them with 72 patients treated with sulphasalazine without blood reactions. We also performed in vitro studies of the blood cell lines HL60 and U937 after sulphasalazine exposure with respect to cell survival index, neutrophil elastase protein expression and activity. RESULTS: None of the mutations in ELA2, which previously have been reported to be associated with SCN, was found in this material. Protein expression of human neutrophil elastase in lymphoma U937 cells was not affected by treatment with concentrations equivalent to therapeutic doses. Cell survival of lymphoma U937 and promyelocytic leukemia HL-60 cells was not affected in this concentration range, but exhibited a decreased proliferative capacity with higher sulphasalazine concentrations. Interestingly the promyelocytic cells were more sensitive to sulphasalazine than the lymphoma cell line. CONCLUSION: Neutrophil elastase expression and ELA2 mutations do, however, not seem to be involved in the etilogy of sulphasalazine-induced agranulocytosis. Why sulphasalazine is more toxic to promyelocytes than to lymphocytes remains to be explained

The bashful and the boastful : prestigious leaders and social change in Mesolithic Societies

The creation and maintenance of influential leaders and authorities is one of the key themes of archaeological and historical enquiry. However the social dynamics of authorities and leaders in the Mesolithic remains a largely unexplored area of study. The role and influence of authorities can be remarkably different in different situations yet they exist in all societies and in almost all social contexts from playgrounds to parliaments. Here we explore the literature on the dynamics of authority creation, maintenance and contestation in egalitarian societies, and discuss the implications for our interpretation and understanding of the formation of authorities and leaders and changing social relationships within the Mesolithic

Responsibility for managing musculoskeletal disorders – A cross-sectional postal survey of attitudes

Background: Musculoskeletal disorders are a major burden on individuals, health systems and social care systems and rehabilitation efforts in these disorders are considerable. Self-care is often considered a cost effective treatment alternative owing to limited health care resources. But what are the expectations and attitudes in this question in the general population? The purpose of this study was to describe general attitudes to responsibility for the management of musculoskeletal disorders and to explore associations between attitudes and background variables. Methods: A cross-sectional, postal questionnaire survey was carried out with a random sample of a general adult Swedish population of 1770 persons. Sixty-one percent (n = 1082) responded to the questionnaire and was included for the description of general attitudes towards responsibility for the management of musculoskeletal disorders. For the further analyses of associations to background variables 683–693 individuals could be included. Attitudes were measured by the &quot;Attitudes regarding Responsibility for Musculoskeletal disorders&quot; (ARM) instrument, where responsibility is attributed on four dimensions; to myself, as being out of my hands, to employers or to (medical) professionals. Multiple logistic regression was used to explore associations between attitudes to musculoskeletal disorders and the background variables age, sex, education, physical activity, presence of musculoskeletal disorders, sick leave and whether the person had visited a care provider. Results: A majority of participants had internal views, i.e. showed an attitude of taking personal responsibility for musculoskeletal disorders, and did not place responsibility for the management out of their own hands or to employers. However, attributing shared responsibility between self and medical professionals was also found.The main associations found between attitude towards responsibility for musculoskeletal disorders and investigated background variables were that physical inactivity (OR 2.92–9.20), musculoskeletal disorder related sick leave (OR 2.31–3.07) and no education beyond the compulsory level (OR 3.12–4.76) increased the odds of attributing responsibility externally, i.e placing responsibility on someone or something else.Conclusion: Respondents in this study mainly saw themselves as responsible for managing musculoskeletal disorders. The associated background variables refined this finding and one conclusion is that, to optimise outcome when planning the prevention, treatment and management of these disorders, people&apos;s attitudes should be taken into account