Predicting clinical scores from magnetic resonance scans in Alzheimer's disease.

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome.

Quantitative distribution of parvalbumin, calretinin, and calbindin D-28k immunoreactive neurons in the visual cortex of normal and Alzheimer cases.

The distribution of parvalbumin (PV), calretinin (CR), and calbindin (CB) immunoreactive neurons was studied with the help of an image analysis system (Vidas/Zeiss) in the primary visual area 17 and associative area 18 (Brodmann) of Alzheimer and control brains. In neither of these areas was there a significant difference between Alzheimer and control groups in the mean number of PV, CR, or CB immunoreactive neuronal profiles, counted in a cortical column going from pia to white matter. Significant differences in the mean densities (numbers per square millimeter of cortex) of PV, CR, and CB immunoreactive neuronal profiles were not observed either between groups or areas, but only between superficial, middle, and deep layers within areas 17 and 18. The optical density of the immunoreactive neuropil was also similar in Alzheimer and controls, correlating with the numerical density of immunoreactive profiles in superficial, middle, and deep layers. The frequency distribution of neuronal areas indicated significant differences between PV, CR, and CB immunoreactive neuronal profiles in both areas 17 and 18, with more large PV than CR and CB positive profiles. There were also significantly more small and less large PV and CR immunoreactive neuronal profiles in Alzheimer than in controls. Our data show that, although the brain pathology is moderate to severe, there is no prominent decrease of PV, CR and CB positive neurons in the visual cortex of Alzheimer brains, but only selective changes in neuronal perikarya.

Como os trabalhadores de um Centro Obstétrico justificam a utilização de práticas prejudiciais ao parto normal

Este estudo busca entender as justificativas dos trabalhadores de um Centro Obstétrico do Sul do Brasil para a utilização de práticas do parto normal consideradas prejudiciais pela Organização Mundial da Saúde. A pesquisa é do tipo exploratória, desenvolvida em julho de 2009, por meio de entrevista com 23 trabalhadores. Na análise, houve a conformação de três núcleos temáticos: Ações e condutas na dependência do trabalhador de saúde; Práticas rotineiras como facilitadoras do trabalho e Restrição da participação da parturiente no processo decisório. Algumas justificativas para o emprego das práticas: perpetuação de modelos inadequados, facilitação para a assistência no momento do parto e autoritarismo que alguns trabalhadores exercem sobre a parturiente por acreditarem serem detentores do conhecimento.

Alpha1-adrenoceptors are required for normal male sexual function.

BACKGROUND AND PURPOSE: Alpha(1)-adrenoceptor antagonists are extensively used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia. Among the side effects, ejaculatory dysfunction occurs more frequently with drugs that are relatively selective for alpha(1A)-adrenoceptors compared with other drugs of this class. This suggests that alpha(1A)-adrenoceptors may contribute to ejaculation. However, this has not been studied at the molecular level. EXPERIMENTAL APPROACH: The physiological contribution of each alpha(1)-adrenoceptor subtype was characterized using alpha(1)-adrenoceptor subtype-selective knockout (KO) mice (alpha(1A)-, alpha(1B)- and alpha(1D)-AR KO mice) since the subtype-specific drugs available are only moderately selective. We analysed the role of alpha(1)-adrenoceptors in the blood pressure and vascular response as well as ejaculation by determining these variables in alpha(1)-adrenoceptor subtype-selective KO mice and in mice with all their alpha(1)-adrenoceptor subtypes deleted (alpha(1)-AR triple-KO mice). KEY RESULTS: The pregnancy rate was reduced by 50% in alpha(1A)-adrenoceptor KO mice, and this reduction was dramatically enhanced in alpha(1)-adrenoceptor triple-KO mice. Contractile tension of the vas deferens in response to noradrenaline was markedly decreased in alpha(1A)-adrenoceptor KO mice, and this contraction was completely abolished in alpha(1)-adrenoceptor triple-KO mice. This attenuation of contractility was also observed in the electrically stimulated vas deferens. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that alpha(1)-adrenoceptors, particularly alpha(1A)-adrenoceptors, are required for normal contractility of the vas deferens and consequent sperm ejaculation as well as having a function in fertility.

Detection of Optimal Models in Parameter Space with Support Vector Machines

The paper proposes an approach aimed at detecting optimal model parameter combinations to achieve the most representative description of uncertainty in the model performance. A classification problem is posed to find the regions of good fitting models according to the values of a cost function. Support Vector Machine (SVM) classification in the parameter space is applied to decide if a forward model simulation is to be computed for a particular generated model. SVM is particularly designed to tackle classification problems in high-dimensional space in a non-parametric and non-linear way. SVM decision boundaries determine the regions that are subject to the largest uncertainty in the cost function classification, and, therefore, provide guidelines for further iterative exploration of the model space. The proposed approach is illustrated by a synthetic example of fluid flow through porous media, which features highly variable response due to the parameter values' combination.

Prevalence of normal weight obesity in Switzerland: effects of various definitions

Background: normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI<25 kg/m2), but its prevalence in the general population is unknown. Objective: to assess the prevalence of NWO in Switzerland according to different cut points used to define excess body fat. Design: cross-sectional study including 3,213 women and 2,912 men aged 35-75 years. Body fat was assessed by bioimpedance and prevalence of NWO was assessed using four previously published definitions for excess body fat. Results: % body fat increased with age: in men, the values (mean SD) were 20.2 5.4, 23.0 5.4, 26.3 5.2 and 28.2 4.6 for age groups [35 - 44], [45 - 54], [55 - 64] and [65 - 75] years, respectively; the corresponding values for women were 29.9 7.8, 33.1 7.4, 36.7 7.5 and 39.6 6.9. In men, prevalence of NWO was <1% irrespective of the definition used. Conversely, in women, a one to twenty fold difference (from 1.4% to 27.8%) in NWO prevalence was found. The prevalence of NWO increased with age when age-independent cut points were used in women, but not in men. Conclusions: prevalence of NWO is low in the general population and higher in women than in men. The prevalence is highly dependent on the criteria used to define excess body fat, namely in women. The use of gender- and age-specific cut points to define excess body fat is better than fixed or gender-specific only cut points.

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice.

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤ 500 ms) of radiation delivered at ultrahigh dose rate (≥ 40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤ 0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc(+) orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor-β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor-α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.

Adherence to best care practices in normal birth: construction and validation of an instrument

Abstract OBJECTIVE To describe the stages of construction and validation of an instrument in order to analyze the adherence to best care practices during labour and birth. METHOD Methodological research, carried out in three steps: construction of dimensions and items, face and content validity and semantic analysis of the items. RESULTS The face and content validity was carried out by 10 judges working in healthcare, teaching and research. Items with Content Validity Index (CVI) ≥ 0.9 were kept in full or undergone revisions as suggested by the judges. Semantic analysis, performed twice, indicated that there was no difficulty in understanding the items. CONCLUSION The instrument with three dimensions (organization of healthcare network to pregnancy and childbirth, evidence-based practices and work processes) followed the steps recommended in the literature, concluded with 50 items and total CVI of 0.98.

Prevalence of normal weight obesity in the general population

Background and Aims: normal weight obesity (NWO) has been defined as an excessive body fat (BF) associated with a normal body mass index (BMI). Little is known regarding its prevalence in the general population or which cut-offs for BF should be used. Methods: convenience sample of 1,523 Portuguese adults. BF was measured by validated hand-held bioimpedance. NWO was defined as a BMI<25 kg/m2 and a %BF mass>30%, along other published criteria. Results: prevalence of NWO was 10.1% in women and 3.2% in men. In women, prevalence of NWO increased considerably with age, and virtually all women aged over 55 with a BMI<25 kg/m2 were actually considered as NWO. Using gender specific cut-offs for BF (29.1% in men and 37.2% in women) led to moderately lower of NWO in women. Using gender- and age-specific cut-points for %BF considerably decreased the prevalence of NWO in women (0.5 to 2.5% depending on the criterion) but not in men (1.9 to 3.4%). Conclusions: gender- and age- specific or at least gender-specific, instead of single cut-offs for %BF, should be used to characterize and study NWO.

Individual Classification of Mild Cognitive Impairment Subtypes by Support Vector Machine Analysis of White Matter DTI.

BACKGROUND AND PURPOSE: MCI was recently subdivided into sd-aMCI, sd-fMCI, and md-aMCI. The current investigation aimed to discriminate between MCI subtypes by using DTI. MATERIALS AND METHODS: Sixty-six prospective participants were included: 18 with sd-aMCI, 13 with sd-fMCI, and 35 with md-aMCI. Statistics included group comparisons using TBSS and individual classification using SVMs. RESULTS: The group-level analysis revealed a decrease in FA in md-aMCI versus sd-aMCI in an extensive bilateral, right-dominant network, and a more pronounced reduction of FA in md-aMCI compared with sd-fMCI in right inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The comparison between sd-fMCI and sd-aMCI, as well as the analysis of the other diffusion parameters, yielded no significant group differences. The individual-level SVM analysis provided discrimination between the MCI subtypes with accuracies around 97%. The major limitation is the relatively small number of cases of MCI. CONCLUSIONS: Our data show that, at the group level, the md-aMCI subgroup has the most pronounced damage in white matter integrity. Individually, SVM analysis of white matter FA provided highly accurate classification of MCI subtypes.

The algebraic equality of two asymptotic tests for the hypothesis that a normal distribution has a specified correlation matrix

It is proved the algebraic equality between Jennrich's (1970) asymptotic$X^2$ test for equality of correlation matrices, and a Wald test statisticderived from Neudecker and Wesselman's (1990) expression of theasymptoticvariance matrix of the sample correlation matrix.