Music in minor activates limbic structures: a relationship with dissonance?

Using functional magnetic resonance imaging, we contrasted major and minor mode melodies controlled for liking to study the neural basis of musical mode perception. To examine the influence of the larger dissonance in minor melodies on neural activation differences, we further introduced a strongly dissonant stimulus, in the form of a chromatic scale. Minor mode melodies were evaluated as sadder than major melodies, and in comparison they caused increased activity in limbic structures, namely left parahippocampal gyrus, bilateral ventral anterior cingulate, and in left medial prefrontal cortex. Dissonance explained some, but not all, of the heightened activity in the limbic structures when listening to minor mode music.     

Embryo selection with artificial intelligence: how to evaluate and compare methods?

Journal of Assisted Reproduction and Genetics - Embryo selection within in vitro fertilization (IVF) is the process of evaluating qualities of fertilized oocytes (embryos) and selecting the best...     

Male sexual dysfunction and infertility associated with neurological disorders

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate.     

Newborn survival: a multi-country analysis of a decade of change

Neonatal deaths account for 40% of global under-five mortality and are ever more important if we are to achieve the Millennium Development Goal 4 (MDG 4) on child survival. We applied a results framework to evaluate global and national changes for neonatal mortality rates (NMR), healthy behaviours, intervention coverage, health system change, and inputs including funding, while considering contextual changes. The average annual rate of reduction of NMR globally accelerated between 2000 and 2010 (2.1% per year) compared with the 1990s, but was slower than the reduction in mortality of children aged 1-59 months (2.9% per year) and maternal mortality (4.2% per year). Regional variation of NMR change ranged from 3.0% per year in developed countries to 1.5% per year in sub-Saharan Africa. Some countries have made remarkable progress despite major challenges. Our statistical analysis identifies inter-country predictors of NMR reduction including high baseline NMR, and changes in income or fertility. Changes in intervention or package coverage did not appear to be important predictors in any region, but coverage data are lacking for several neonatal-specific interventions. Mortality due to neonatal infection deaths, notably tetanus, decreased, and deaths from complications of preterm birth are increasingly important. Official development assistance for maternal, newborn and child health doubled from 2003 to 2008, yet by 2008 only 6% of this aid mentioned newborns, and a mere 0.1% (US$4.56m) exclusively targeted newborn care. The amount of newborn survival data and the evidence based increased, as did recognition in donor funding. Over this decade, NMR reduction seems more related to change in context, such as socio-economic factors, than to increasing intervention coverage. High impact cost-effective interventions hold great potential to save newborn lives especially in the highest burden countries. Accelerating progress requires data-driven investments and addressing context-specific implementation realities.     

CTL epitopes for influenza A including the H5N1 bird flu; genome-, pathogen-, and HLA-wide screening

The purpose of the present study is to perform a global screening for new immunogenic HLA class I (HLA-I) restricted cytotoxic T cell (CTL) epitopes of potential utility as candidates of influenza A-virus diagnostics and vaccines. We used predictions of antigen processing and presentation, the latter encompassing 12 different HLA class I supertypes with >99% population coverage, and searched for conserved epitopes from available influenza A viral protein sequences. Peptides corresponding to 167 predicted peptide-HLA-I interactions were synthesized, tested for peptide-HLA-I interactions in a biochemical assay and for influenza-specific, HLA-I-restricted CTL responses in an IFN-gamma ELISPOT assay. Eighty-nine peptides could be confirmed as HLA-I binders, and 13 could be confirmed as CTL targets. The 13 epitopes, are highly conserved among human influenza A pathogens, and all of these epitopes are present in the emerging bird flu isolates. Our study demonstrates that present technology enables a fast global screening for T cell immune epitopes of potential diagnostics and vaccine interest. This technology includes immuno-bioinformatics predictors with the capacity to perform fast genome-, pathogen-, and HLA-wide searches for immune targets. To exploit this new potential, a coordinated international effort to analyze the precious source of information represented by rare patients, such as the current victims of bird flu, would be essential.     

Scoring sacroiliac joints by magnetic resonance imaging. A multiple-reader reliability experiment

Magnetic resonance imaging (MRI) of the sacroiliac (SI) joints and the spine is increasingly important in the assessment of inflammatory activity and structural damage in clinical trials with patients with ankylosing spondylitis (AS). We investigated inter-reader reliability and sensitivity to change of several scoring systems to assess disease activity and change in disease activity in patients with AS. Twenty sets of consecutive MRI, derived from a randomized clinical trial comparing an active drug with placebo and selected on the basis of the presence of activity at baseline, were presented electronically to 7 experienced readers from different countries (Europe, Canada). Readers scored the MRI by 3 different methods including: a global score (grading activity per SI joint); a more comprehensive global score (grading activity per SI joint per quadrant); and a detailed scoring system [Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system], which scores 6 images, divided into quadrants, with additional scores for "depth" and "intensity." A fourth and a fifth scoring system were constructed afterwards. The fourth method included the SPARCC score minus the additional scores for "depth" and "intensity," and the fifth method included the SPARCC slice with the maximum score. Inter-reader reliability was investigated by calculating intraclass correlation coefficients (ICC) for all readers together and for all possible reader pairs. Sensitivity to change was investigated by calculating standardized response means (SRM) on change scores that were made positive. Overall inter-reader ICC per method were between 0.47 and 0.58 for scoring status, and between 0.40 and 0.53 for scoring change. ICC per possible reader pairs showed much more fluctuation per method, with lowest observed values close to zero (no agreement) and highest observed values over 0.80 (excellent agreement). In general, agreement of status scores was somewhat better than agreement of change scores, and agreement of the comprehensive SPARCC scoring system was somewhat better than agreement of the more condensed systems. Sensitivity to change differed per reader, but in general was somewhat better for the comprehensive SPARCC system. This experiment under "real life," far from optimal conditions demonstrates the feasibility of scoring exercises for method comparison, provides evidence for the reliability and sensitivity to change of scoring systems to be used in assessing activity of SI joints in clinical trials, and sets the conditions for further validation research in this field.