The use of the likelihood ratio for evaluative and investigative purposes in comparative forensic handwriting examination

This paper extends previous research and discussion on the use of multivariate continuous data, which are about to become more prevalent in forensic science. As an illustrative example, attention is drawn here on the area of comparative handwriting examinations. Multivariate continuous data can be obtained in this field by analysing the contour shape of loop characters through Fourier analysis. This methodology, based on existing research in this area, allows one describe in detail the morphology of character contours throughout a set of variables. This paper uses data collected from female and male writers to conduct a comparative analysis of likelihood ratio based evidence assessment procedures in both, evaluative and investigative proceedings. While the use of likelihood ratios in the former situation is now rather well established (typically, in order to discriminate between propositions of authorship of a given individual versus another, unknown individual), focus on the investigative setting still remains rather beyond considerations in practice. This paper seeks to highlight that investigative settings, too, can represent an area of application for which the likelihood ratio can offer a logical support. As an example, the inference of gender of the writer of an incriminated handwritten text is forwarded, analysed and discussed in this paper. The more general viewpoint according to which likelihood ratio analyses can be helpful for investigative proceedings is supported here through various simulations. These offer a characterisation of the robustness of the proposed likelihood ratio methodology.

Bayes factor for investigative assessment of selected handwriting features

This paper extends previous research [1] on the use of multivariate continuous data in comparative handwriting examinations, notably for gender classification. A database has been constructed by analyzing the contour shape of loop characters of type a and d by means of Fourier analysis, which allows characters to be described in a global way by a set of variables (e.g., Fourier descriptors). Sample handwritings were collected from right- and left-handed female and male writers. The results reported in this paper provide further arguments in support of the view that investigative settings in forensic science represent an area of application for which the Bayesian approach offers a logical framework. In particular, the Bayes factor is computed for settings that focus on inference of gender and handedness of the author of an incriminated handwritten text. An emphasis is placed on comparing the efficiency for investigative purposes of characters a and d.

Stem Cell Transplantation for Retinal Degenerations

Within the last few years, several reports have revealed that cell transplantation can be an effective way to replace lost neurons in the central nervous system (CNS) of patients affected with neurodegenerative diseases. Concerning the retina, the concept that newborn photoreceptors can integrate the retina and restore some visual functions was univocally demonstrated recently in the mouse eye (MacLaren et al. 2006) and remains to be achieved in human. These results pave the way to a standard approach in regenerative medicine aiming to replace lost photoreceptors. With the discovery of stem cells a great hope has appeared towards elaborating protocols to generate adequate cells to restore visual function in different retinal degeneration processes. Retinal stem cells (RSCs) are good candidates to repair the retina and are present throughout the retina development, including adulthood. However, neonatal mouse RSCs derived from the radial glia population have a different potential to proliferate and differentiate in comparison to adult RSCs. Moreover, we observed that adult mouse RSCs, depending on the culture conditions, have a marked tendency to transform, whereas neonatal RSCs show subtle chromosome abnormalities only after extensive expansion. These characteristics should help to identify the optimal cell source and culture conditions for cell transplantation studies. These results will be discussed in light of other studies using RSCs as well as embryonic stem cells. Another important factor to consider is the host environment, which plays a crucial role for cell integration and which was poorly studied in the normal and the diseased retina. Nonetheless, important results were recently generated to reconsider cell transplantation strategy. Perspectives to enhance cell integration by manipulating the environment will also be presented.

Octopus Standard Automated Perimetry, Pulsar Perimetry, Moorfields Motion Displacement Test and Heidelberg Retinal Tomography in Glaucoma Detection - A Comparison of Diagnostic Accuracy

Purpose: To investigate the accuracy of 4 clinical instruments in the detection of glaucomatous damage. Methods: 102 eyes of 55 test subjects (Age mean = 66.5yrs, range = [39; 89]) underwent Heidelberg Retinal Tomography (HRTIII), (disc area<2.43); and standard automated perimetry (SAP) using Octopus (Dynamic); Pulsar (TOP); and Moorfields Motion Displacement Test (MDT) (ESTA strategy). Eyes were separated into three groups 1) Healthy (H): IOP<21mmHg and healthy discs (clinical examination), 39 subjects, 78 eyes; 2) Glaucoma suspect (GS): Suspicious discs (clinical examination), 12 subjects, 15 eyes; 3) Glaucoma (G): progressive structural or functional loss, 14 subjects, 20 eyes. Clinical diagnostic precision was examined using the cut-off associated with the p<5% normative limit of MD (Octopus/Pulsar), PTD (MDT) and MRA (HRT) analysis. The sensitivity, specificity and accuracy were calculated for each instrument. Results: See table Conclusions: Despite the advantage of defining glaucoma suspects using clinical optic disc examination, the HRT did not yield significantly higher accuracy than functional measures. HRT, MDT and Octopus SAP yielded higher accuracy than Pulsar perimetry, although results did not reach statistical significance. Further studies are required to investigate the structure-function correlations between these instruments.

Differential regulations of AQP4 and Kir4.1 by triamcinolone acetonide and dexamethasone in the healthy and inflamed retina.

PURPOSE: Glucocorticoids are used to treat macular edema, although the mechanisms underlying this effect remain largely unknown. The authors have evaluated in the normal and endotoxin-induced uveitis (EIU) rats, the effects of dexamethasone (dex) and triamcinolone acetonide (TA) on potassium channel Kir4.1 and aquaporin-4 (AQP4), the two main retinal Müller glial (RMG) channels controlling retinal fluid movement. METHODS: Clinical as well as relatively low doses of dex and TA were injected in the vitreous of normal rats to evaluate their influence on Kir4.1 and AQP4 expression 24 hours later. The dose-dependent effects of the two glucocorticoids were investigated using rat neuroretinal organotypic cultures. EIU was induced by footpad lipopolysaccharide injection, without or with 100 nM intraocular dex or TA. Glucocorticoid receptor and channel expression levels were measured by quantitative PCR, Western blot, and immunohistochemistry. RESULTS: The authors found that dex and TA exert distinct and specific channel regulations at 24 hours after intravitreous injection. Dex selectively upregulated Kir4.1 (not AQP4) in healthy and inflamed retinas, whereas TA induced AQP4 (not Kir4.1) downregulation in normal retina and upregulation in EIU. The lower concentration (100 nM) efficiently regulated the channels. Moreover, in EIU, an inflammatory condition, the glucocorticoid receptor was downregulated in the retina, which was prevented by intravitreous injections of the low concentration of dex or TA. CONCLUSIONS: The results show that dex and TA are far from being equivalent to modulate RMG channels. Furthermore, the authors suggest that low doses of glucocorticoids may have antiedematous effects on the retina with reduced toxicity.

Evaluating sampling strategies and logistic regression methods for modelling complex land cover changes

The role of land cover change as a significant component of global change has become increasingly recognized in recent decades. Large databases measuring land cover change, and the data which can potentially be used to explain the observed changes, are also becoming more commonly available. When developing statistical models to investigate observed changes, it is important to be aware that the chosen sampling strategy and modelling techniques can influence results. We present a comparison of three sampling strategies and two forms of grouped logistic regression models (multinomial and ordinal) in the investigation of patterns of successional change after agricultural land abandonment in Switzerland. Results indicated that both ordinal and nominal transitional change occurs in the landscape and that the use of different sampling regimes and modelling techniques as investigative tools yield different results. Synthesis and applications. Our multimodel inference identified successfully a set of consistently selected indicators of land cover change, which can be used to predict further change, including annual average temperature, the number of already overgrown neighbouring areas of land and distance to historically destructive avalanche sites. This allows for more reliable decision making and planning with respect to landscape management. Although both model approaches gave similar results, ordinal regression yielded more parsimonious models that identified the important predictors of land cover change more efficiently. Thus, this approach is favourable where land cover change pattern can be interpreted as an ordinal process. Otherwise, multinomial logistic regression is a viable alternative.

Entrance pupil size predicts retinal illumination in darkly pigmented eyes, but not lightly pigmented eyes.

PURPOSE: We determined the effect of entrance pupil size on retinal illumination. The influence of unilateral miosis on the magnitude of the pupil light reflex was studied to ascertain how a clinically significant anisocoria influences the relative afferent pupil defect (RAPD). METHODS: Miosis was induced by topical 1% pilocarpine in the right eye of 14 healthy subjects with normal eyes. The interocular difference in retinal illumination was assessed by computerized pupillometry from the stimulus response curve of the right and left eyes. The main outcome measure was the RAPD, determined by computerized pupillography, at baseline and after pilocarpine-induced anisocoria. RESULTS: Induced anisocoria produced a significant change in RAPD from baseline (mean = 1.60 dB in the miotic eye, P = 0.007). However, anisocoria correlated with RAPD only in subjects with darkly pigmented irides (Pearson correlation coefficient 0.793, P = 0.05). CONCLUSIONS: In darkly pigmented eyes, entrance pupil size significantly influenced the retinal illumination. However, retinal illumination of lightly pigmented eyes is relatively independent of entrance pupil size, presumably due to extrapupillary transmission of light through the iris and sclera. This has important implications in understanding the potential influence of anisocoria on the RAPD and also greater susceptibility of lightly pigmented eyes to light toxicity.

Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNF-alpha single-chain antibody, upon topical administration to the rabbit eye.

PURPOSE: The purpose of this study was to characterize local distribution and systemic absorption of the tumor necrosis factor (TNF)-alpha inhibitory single-chain antibody fragment (scFv) ESBA105 following topical administration to the eye in vivo. METHODS: Rabbits received ESBA105 as topical eye drops in two dosing regimens. First, pharmacokinetics after the topical route of administration was compared to the intravenous (i.v.) route by means of applying the identical cumulative daily dose of ESBA105. In a second study rabbits received five eye drops daily for six consecutive days in a lower frequency topical dosing regimen. Kinetics and biodistribution of ESBA105 in ocular tissues and fluids as well as in sera were determined in all animals. RESULTS: After topical administration to the eye, ESBA105 quickly reaches therapeutic concentrations in all ocular compartments. Systemic exposure after topical administration is 25,000-fold lower than exposure after i.v. injection of the identical cumulative daily dose. ESBA105 levels in vitreous humor and neuroretina are significantly higher on topical administration than after i.v. injection. Absolute and relative intraocular biodistribution of ESBA105 is different with topical and systemic delivery routes. Compared to its terminal half-life in circulation (7 hours), the vitreal half-life of ESBA105 is significantly enhanced (16-24 hours). CONCLUSIONS: On topical administration, ESBA105 is efficiently absorbed and distributed to all compartments of the eye, whereby systemic drug exposure is very low. Based on its unique intraocular biodistribution and pharmacokinetics and the absolute intraocular levels reached, topical ESBA105 appears highly attractive for treatment of various ophthalmological disorders.

A collaborative approach for incorporating forensic case data into crime investigation using criminal intelligence analysis and visualisation

There is an increasing awareness that the articulation of forensic science and criminal investigation is critical to the resolution of crimes. However, models and methods to support an effective collaboration between these partners are still poorly expressed or even lacking. Three propositions are borrowed from crime intelligence methods in order to bridge this gap: (a) the general intelligence process, (b) the analyses of investigative problems along principal perspectives: entities and their relationships, time and space, quantitative aspects and (c) visualisation methods as a mode of expression of a problem in these dimensions. Indeed, in a collaborative framework, different kinds of visualisations integrating forensic case data can play a central role for supporting decisions. Among them, link-charts are scrutinised for their abilities to structure and ease the analysis of a case by describing how relevant entities are connected. However, designing an informative chart that does not bias the reasoning process is not straightforward. Using visualisation as a catalyser for a collaborative approach integrating forensic data thus calls for better specifications.

Variable phenotypic expressivity in a Swiss family with autosomal dominant retinitis pigmentosa due to mutation T494m in the Prpf3 gene

Purpose:to describe the clinical features in a five generations family segregating autosomal dominant retinitis pigmentosa and to identify the causative gene Patient and Methods:Twenty five individuals of a large five-generation family originating from Western Switzerland were ascertained for phenotypic and genotypic characterization. Ophthalmologic evaluations included color vision testing, Goldman perimetry and digital fundus photography. Some patients had autofluorescence (AF) imaging, ocular coherence tomography (OCT) and ISCEV-standard full-field electroretinography (ERG). Blood samples were collected from 10 affected (4 to 70 years of age) and 15 unaffected members after informed consent. DNA was isolated and exons and intron-exons junctions of known adRP genes were sequenced using a Big Dye sequencing kit 1.1. Results:Age of onset of nightblindness and severity of progression of the disease was variable between members of the family. Some patients had early onset of nightblindess aged 3, others at mid-twenties. Most patients had visual acuity above 0.6 for the first 4 decades. Two older patients still had good vision (0.4) in their seventies. Myopia (range: -2 to -5) was noticed in most affected subjects. Fundus findings showed areas of atrophy along the arcades. The AF imaging showed a large high density ring bilaterally. A T494M change was found in exon 11 of PRPF3 gene. The change segregates with the disease in the family. Conclusion: A mutation in the PRPF3 gene is rare compared with other genes causing ADRP. Although a T494M change has been reported, our family is the first one with a variable expressivity. Mutations in PRPF3 gene can cause a variable phenotype of ADRP unlike the previously described Danish and English families. Our report gives a better understanding as to the phenotype/genotype description of ADRP due to PRPF3 mutation.

L'espace partisan marocain : un microcosme polarisé ?

Cet article s'interroge sur les caractéristiques du personnel partisan marocain, à partir d'un protocole d'enquête inédit et d'une base de données sur 4 127 congressistes de dix organisations politiques marocaines, sondées entre 2008 et 2012. D'après les premiers traitements, l'espace partisan marocain est un petit monde dominé par les citadins, les hommes d'âge mûr, les plus dotés scolairement et économiquement ; mais, loin d'être coupé des citoyens ordinaires, il est travaillé par les dynamiques en oeuvre dans la société. Irréductible à une clientèle segmentée, il n'en demeure pas moins façonné par une opposition idéal-typique entre partis de notables et partis de militants. Using an original investigative protocol and a data base of 4,127 national delegates from ten Moroccan political organizations, surveyed between 2008 and 2012, this article examines the characteristics of party members in Morocco. Initial results indicate that the field of Moroccan political parties is a small world dominated by city dwellers, mature men, and the most highly educated, wealthiest individuals. However, far from being isolated from ordinary citizens, there are social dynamics at work. While it cannot be reduced to a segmented clientele, it is, nonetheless, shaped by an ideal-typical opposition between parties of notables and parties of activists.

EIU in the rat promotes the potential of syngeneic retinal cells injected into the vitreous cavity to induce PVR.

PURPOSE: To determine whether syngeneic retinal cells injected in the vitreous cavity of the rat are able to initiate a proliferative process and whether the ocular inflammation induced in rats by lipopolysaccharide (LPS) promotes this proliferative vitreoretinopathy (PVR). METHODS: Primary cultured differentiated retinal Müller glial (RMG) and retinal pigmented epithelial (RPE) cells isolated from 8 to 12 postnatal Lewis rats were injected into the vitreous cavity of 8- to 10-week-old Lewis rats (10(5) cells/eye in 2 microlieter sterile saline), with or without the systemic injection of 150 microgram LPS to cause endotoxin-induced uveitis (EIU). Control groups received an intravitreal injection of 2 microliter saline. At 5, 15, and 28 days after cell injections, PVR was clinically quantified, and immunohistochemistry for OX42, ED1, vimentin (VIM), glial fibrillary acidic protein (GFAP), and cytokeratin was performed. RESULTS: The injection of RMG cells, alone or in combination with RPE cells, induced the preretinal proliferation of a GFAP-positive tissue, that was enhanced by the systemic injection of LPS. Indeed, when EIU was induced at the time of RMG cell injection into the vitreous cavity, the proliferation led to retinal folds and localized tractional detachments. In contrast, PVR enhanced the infiltration of inflammatory cells in the anterior segment of the eye. CONCLUSIONS: In the rat, syngeneic retinal cells of glial origin induce PVR that is enhanced by the coinduction of EIU. In return, vitreoretinal glial proliferation enhanced the intensity and duration of EIU.

Keratin degradation by dermatophytes relies on cysteine dioxygenase and a sulfite efflux pump.

Millions of people suffer from superficial infections caused by dermatophytes. Intriguingly, these filamentous fungi exclusively infect keratin-rich host structures such as hair, nails, and skin. Keratin is a hard, compact protein, and its utilization by dermatophytes for growth has long been discussed as a major virulence attribute. Here, we provide strong support for the hypothesis that keratin degradation is facilitated by the secretion of the reducing agent sulfite, which can cleave keratin-stabilizing cystine bonds. We discovered that sulfite is produced by dermatophytes from environmental cysteine, which at elevated concentrations is toxic for microbes and humans. We found that sulfite formation from cysteine relies on the key enzyme cysteine dioxygenase Cdo1. Sulfite secretion is supported by the sulfite efflux pump Ssu1. Targeted mutagenesis proved that dermatophyte mutants in either Cdo1 or Ssu1 were highly growth-sensitive to cysteine, and mutants in Ssu1 were specifically sensitive to sulfite. Most notably, dermatophyte mutants in Cdo1 and Ssu1 were specifically growth-defective on hair and nails. As keratin is rich in cysteine, our identified mechanism of cysteine conversion and sulfite efflux supports both cysteine and sulfite tolerance per se and progression of keratin degradation. These in vitro findings have implications for dermatophyte infection pathogenesis.

Three Generation Family With Pattern Dystrophy and a Successful Treatment of Subfoveal Cnv Related to Pattern Dystrophy With Anti-vegf Intravitreal Injections

Purpose: To phenotype a large 3 generation Swiss family with pattern dystrophy and to report a successful result of treatment with ranibizumab of a subfoveal choroidal neovascularisation (CNV) associated with pattern dystrophy in 1 patient Patients and methods: 4 affected and 3 unaffected patients (3 female 4 male, age range: 19 - 80 years) were assessed with a complete ophthalmologic examination. AF images were taken using Heidelberg Retina Angiograph and the digital color photos, fluorescein angiogragraphy (FFA) using the same TOPCON 501 camera. Electroretinogram (full-field and multifocal) was performed in 1 affected patient. One 48 years old patient developed a subfoveal CNV, which was treated with 2 injections of ranibizumab, at 3 months interval. Blood sample was taken for molecular analysis (screening of the gene RDS). Results: Two patients had a typical fundoscopic appearance of pattern dystrophy with butterfly shaped deposit at the fovea and some peripheral flecks, as shown with AF imaging.. Two others affected patients had a more unusual appearance with some macular atrophy in one or both eyes, surrounded by flecks. The visual acuity ranged from 1.0 to 0.1 according to Snellen EDTRS chart. The patient with subfoveal CNV presented a drop of vision form 1.0 to 0.6 within 10 days prior to the diagnosis and also reported some metamorphopsia. FFA and optical computerized tomography (OCT) confirmed a classic CNV. After the 1st injection her vision improved to 1.0 but persistent metamorphopsia and fluid on OCT motivated a second injection. One month after the second injection the OCT was flat and the patient had no symptoms. The results of RDS screening will be presented at the meeting. Conclusion: We present a family with pattern dystrophy, with some members having an unusual fundus appearance, which was mistaken for an early onset dry AMD. The AF imaging is a useful tool in diagnosing this condition. A CNV associated with pattern dystrophy a rare. This is the first report of a successful treatment of the CNV with anti-VEGF intravitreal injections.