The immunogenetic basis of severe infections caused by bacille Calmette-Guérin vaccine and environmental mycobacteria in humans remains largely unknown. We describe 18 patients from several generations of 12 unrelated families who were heterozygous for 1 to 5 overlapping IFNGR1 frameshift small deletions and a wild-type IFNGR1 allele. There were 12 independent mutation events at a single mutation site, defining a small deletion hotspot. Neighbouring sequence analysis favours a small deletion model of slipped mispairing events during replication. The mutant alleles encode cell-surface IFNgamma receptors that lack the intra-cytoplasmic domain, which, through a combination of impaired recycling, abrogated signalling and normal binding to IFNgamma exert a dominant-negative effect. We thus report a hotspot for human IFNGR1 small deletions that confer dominant susceptibility to infections caused by poorly virulent mycobacteria.

In recent years many papers about diagnostic applications of diffusion tensor imaging (DTI) have been published. This is because DTI allows to evaluate in vivo and in a non-invasive way the process of diffusion of water molecules in biological tissues. However, the simplified description of the diffusion process assumed in DTI does not permit to completely map the complex underlying cellular components and structures, which hinder and restrict the diffusion of water molecules. These limitations can be partially overcome by means of diffusion kurtosis imaging (DKI). The aim of this paper is the description of the theory of DKI, a new topic of growing interest in radiology. DKI is a higher order diffusion model that is a straightforward extension of the DTI model. Here, we analyze the physics underlying this method, we report our MRI acquisition protocol with the preprocessing pipeline used and the DKI parametric maps obtained on a 1.5 T scanner, and we review the most relevant clinical applications of this technique in various neurological diseases.

Three of four children in a family have homozygous (less than 1% of normal) deficiency of factor H of the complement system and both parents, who are first cousins, are heterozygous for the same defect. The father and two of the H-deficient siblings also have a partial C2 deficiency. One of the children with combined deficiencies is affected by systemic lupus erythematosus with nephritis. No increased susceptibility to infections has been observed in the family. H deficiency is inherited in an autosomal codominant manner and is independently transmitted from C2 deficiency and HLA haplotypes. In the homozygous state it is associated with very low serum concentrations of B and C3, barely demonstrable as activated molecules. C5 is greatly reduced (less than 5%). Also, properdin and C6-9 are decreased. The findings in this family demonstrate that the occurrence of systemic lupus erythematosus in one of the children affected by a combined deficiency of factor H and C2 raises the question whether this pathology is related to the complete factor H or to the heterozygous C2 deficiency. Complete H deficiency is not necessarily accompanied by overt illness.

A total of 100 Chinese blood donors (50 from Shen-Zhen and 50 from Taiwan) were studied by the participants in addition to 9 reference samples. A new nomenclature for the CR1 structural alleles was recommended by the participants which would use a numbering system, e.g. CR1*1. The structural allele frequencies in the Chinese were: CR1*1 (190 kD) 0.96, CR1*2 (220 kD) 0.03, CR1*3 (160 kD) 0.01 and CR1*4 (250 kD) 0.00. The HindIII expression polymorphism was also studied and the high expressing allele had a gene frequency of 0.71 while the low expressor gene frequency was 0.28. Erythrocyte copy numbers were quantified and compared between laboratories with good correlation (R = 0.55–0.88). The mean (± SD) erythrocyte copy number was 463 (± 229) in the Taiwan donors and 446 (± 207) in the Mainland Chinese.

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New generation spectroscopy systems have advanced towards digital pulse processing (DPP) approaches. DPP systems, based on direct digitizing and processing of detector signals, have recently been favoured over analog pulse processing electronics, ensuring higher flexibility, stability, lower dead time, higher throughput and better spectroscopic performance. In this work, we present the performance of a new real time DPP system for X-ray and gamma ray semiconductor detectors. The system is based on a commercial digitizer equipped with a custom DPP firmware, developed by our group, for on-line pulse shape and height analysis. X-ray and gamma ray spectra measurements with cadmium telluride (CdTe) and germanium (Ge) detectors, coupled to resistivefeedback preamplifiers, highlight the excellent performance of the system both at low and high rate environments (up to 800 kcps). A comparison with a conventional analog electronics showed the better high-rate capabilities of the digital approach, in terms of energy resolution and throughput. These results make the proposed DPP system a very attractive tool for both laboratory research and for the development of advanced detection systems for high-rate-resolution spectroscopic imaging, recently proposed in diagnostic medicine, industrial imaging and security screening.

The wavelet analysis is a powerful tool for analyzing and detecting features of signals characterized by time-dependent statistical properties, as biomedical signals. The identification and the analysis of the components of these signals in the time-frequency domain, give meaningful information about the physiological mechanisms that govern them. This article presents the results of the wavelet analysis applied to the a-wave component of the human electroretinogram. In order to deepen and improve our knowledge about the behavior of the early photoreceptoral response, including the possible activation of interactions and correlations among the photoreceptors, we have detected and identified the stable time-frequency components of the a-wave, using six representative values of luminance. The results indicate the occurrence of three frequencies lying in the range 20-200 Hz. The lowest one is attributed to the summed activities of the photoreceptors. The others are weaker and at low luminance one of them does not occur. We relate them to the response of the rods and the cones whose aggregate activities are non-linear and typically exhibit self-organization under selective stimuli. The identification of the stable frequency components and of their times of occurrence helps us to shine light about the complex mechanisms governing the a-wave. The present results are promising toward the assessment of more refined model concerning the photoreceptoral activities.

Feature detection in biomedical signals is crucial for deepening our knowledge about the involved physiological processes. To achieve this aim, many analytic approaches can be applied but only few are able to deal with signals whose time dependent features provide useful clinical information. Among the biomedical signals, the electroretinogram (ERG), that records the retinal response to a light flash, can improve our comprehension of the complex photoreceptoral activities. The present study is focused on the analysis of the early response of the photoreceptoral human system, known as a-wave ERG-component. This wave reflects the functional integrity of the photoreceptors, rods and cones, whose activation dynamics are not yet completely understood. Moreover, since in incipient photoreceptoral pathologies eventual anomalies in a-wave are not always detectable with a "naked eye" analysis of the traces, the possibility to discriminate pathologic from healthy traces, by means of appropriate analytical techniques, could help in clinical diagnosis. In the present paper, we discuss and compare the efficiency of various techniques of signal processing, such as Fourier analysis (FA), Principal Component Analysis (PCA), Wavelet Analysis (WA) in recognising pathological traces from the healthy ones. The investigated retinal pathologies are Achromatopsia, a cone disease and Congenital Stationary Night Blindness, affecting the photoreceptoral signal transmission. Our findings prove that both PCA and FA of conventional ERGs, don't add clinical information useful for the diagnosis of ocular pathologies, whereas the use of a more sophisticated analysis, based on the wavelet transform, provides a powerful tool for routine clinical examinations of patients.