The likelihood approach to compare populations : a study on DNA evidence and pitfalls of intuitions

The paper follows on from earlier work [Taroni F and Aitken CGG. Probabilistic reasoning in the law, Part 1: assessment of probabilities and explanation of the value of DNA evidence. Science & Justice 1998; 38: 165-177]. Different explanations of the value of DNA evidence were presented to students from two schools of forensic science and to members of fifteen laboratories all around the world. The responses were divided into two groups; those which came from a school or laboratory identified as Bayesian and those which came from a school or laboratory identified as non-Bayesian. The paper analyses these responses using a likelihood approach. This approach is more consistent with a Bayesian analysis than one based on a frequentist approach, as was reported by Taroni F and Aitken CGG. [Probabilistic reasoning in the law, Part 1: assessment of probabilities and explanation of the value of DNA evidence] in Science & Justice 1998.

Helical tomotherapy or intensity-modulated radiation therapy in the treatment of anal cancer: experience of Geneva and Lausanne

Background: To assess the early clinical outcomes and toxicities in patients treated with high precision radiation therapy (RT) consisting of helical tomotherapy (HT) or intensity-modulated radiation therapy (IMRT) for anal cancer. Materials and Methods: Since March 2006, 30 patients with stage I-IIIB anal squamous-cell carcinoma were treated curatively by IMRT or HT alone (n = 2) or by concomitant chemotherapy and IMRT or HT (n = 28). Median age was 59 years (range, 36−83 years) and the female/male ratio was 2.3 (21/9). Primary tumor site was anal canal, anal margin, or both in 26, 1, and 3 patients, respectively. Anal tumor, pelvic and inguinal nodes were irradiated with a median dose of 36 Gy using HT, or 5- or 7-field IMRT in 18 and 12 patients, respectively; After a planned gap of 1−2 weeks (median 1 week), a median boost dose of 23.4 Gwas delivered to the tumor and/or involved nodes using 3DRT (n = 24) or HT/IMRT (n = 6). The total delivered dose ranged between 59.4 and 64.8 Gy (median, 59.4 Gy). Concomitant chemotherapy consisted of mitomycin C alone (n = 1), mitomycin C and 5-fluorouracil (n = 17) or capecitabin (n = 10) in 28 patients. Common Terminology Criteria for Adverse Events v3.0 scale was used to score acute and late toxicities. Results: All but one patient, who developed progressive local and distant disease at the end of RT, achieved a complete response. Twelve months following RT, one patient had a recurrence at the primary tumor site, salvaged with brachytherapy. After a median follow-up of 7.5 months (range, 1−35 months), no deaths were observed. The 2-year actuarial locoregional control and probability of disease control without colostomy rates were 82% and 79%, respectively. RT was well tolerated without any unplanned treatment interruptions. Grade 1 or 2 acute adverse events consisted of skin toxicity in 8 and 22 patients, diarrhea in 18 and 3 patients, and cystitis in 9 and 2 patients; respectively. Only one patient developed grade 3 mucosal necrosis at the end of the treatment, requiring diverting colostomy. No difference in terms of acute toxicity was observed between patients treated with HT or IMRT. None of the 22 patients with a follow-up of more than 3 months developed grade 3 or more late toxicity. Conclusions: Our preliminary results suggest that HT or IMRT combined with concomitant chemotherapy for anal cancer is effective, and associated with favorable rates of toxicity compared with historical series. Further follow-up is warranted to assess late toxicity.

Repeat Gamma Knife surgery for recurrent trigeminal neuralgia: long-term outcomes and systematic review.

Object The purpose of this study was to establish the safety and efficacy of repeat Gamma Knife surgery (GKS) for recurrent trigeminal neuralgia (TN). Methods Using the prospective database of TN patients treated with GKS in Timone University Hospital (Marseille, France), data were analyzed for 737 patients undergoing GKS for TN Type 1 from July 1992 to November 2010. Among the 497 patients with initial pain cessation, 34.4% (157/456 with ≥ 1-year follow-up) experienced at least 1 recurrence. Thirteen patients (1.8%) were considered for a second GKS, proposed only if the patients had good and prolonged initial pain cessation after the first GKS, with no other treatment alternative at the moment of recurrence. As for the first GKS, a single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4-14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 90 Gy (range 70-90 Gy) was delivered. Data for 9 patients with at least 1-year followup were analyzed. A systematic review of literature was also performed, and results are compared with those of the Marseille study. Results The median time to retreatment in the Marseille study was 72 months (range 12-125 months) and in the literature it was 17 months (range 3-146 months). In the Marseille study, the median follow-up period was 33.9 months (range 12-96 months), and 8 of 9 patients (88.9%) had initial pain cessation with a median of 6.5 days (range 1-180 days). The actuarial rate for new hypesthesia was 33.3% at 6 months and 50% at 1 year, which remained stable for 7 years. The actuarial probabilities of maintaining pain relief without medication at 6 months and 1 year were 100% and 75%, respectively, and remained stable for 7 years. The systematic review analyzed 20 peer-reviewed studies reporting outcomes for repeat GKS for recurrent TN, with a total of 626 patients. Both the selection of the cases for retreatment and the way of reporting outcomes vary widely among studies, with a median rate for initial pain cessation of 88% (range 60%-100%) and for new hypesthesia of 33% (range 11%-80%). Conclusions Results from the Marseille study raise the question of surgical alternatives after failed GKS for TN. The rates of initial pain cessation and recurrence seem comparable to, or even better than, those of the first GKS, according to different studies, but toxicity is much higher, both in the Marseille study and in the published data. Neither the Marseille study data nor literature data answer the 3 cardinal questions regarding repeat radiosurgery in recurrent TN: which patients to retreat, which target is optimal, and which dose to use.

Reducing the learning curve for the treatment of morphoeic (sclerosing) basal cell carcinoma of the face.

The treatment of morphoeic (or sclerosing) basal cell carcinoma (mBCC) of the face is associated with high rates of incomplete excision and recurrence. A principal risk factor for incomplete resection is the grade of surgeon. We did a prospective, randomised study of 40 consecutive patients with mBCC of the face. The extent of the tumour was assessed under standard conditions by consultant surgeons and compared with assessments by resident surgeons with the help of the Varioscope, a combination of microscope and loupe glasses with strong illumination and a maximal magnification of 7x. The data from a former retrospective study of all excisions of mBCC of the face during a five-year period at the hospital served as control. Residents with the support of the Varioscope achieved a rate of incomplete excisions similar to that of consultants under standard conditions. There was a significant reduction of the rate of incomplete resections by resident surgeons thanks to high magnification and good lighting (p=0.02). High magnification and good lighting were useful in learning how to recognise skin changes associated with mBCC of the face and achieving a low rate of incomplete excisions.

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in Colombian patients with acute and chronic ocular toxoplasmosis

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35%) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10%). In group 2 (recurrences) in 1/7 (14%) we found IgM and IgA test positives and in 1/7 (14%) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18%). These results show that serum IgM or IgA or IgE can be present during recurrences.

Partial cricotracheal resection for pediatric subglottic stenosis: long-term outcome in 57 patients.

OBJECTIVE: We sought to assess the long-term outcome of 57 pediatric patients who underwent partial cricotracheal resection for subglottic stenosis. METHODS: Eighty-one pediatric partial cricotracheal resections were performed in our tertiary care institution between 1978 and 2004. Fifty-seven patients had a minimal follow-up time of 1 year and were included in this study. Evaluation was based on the last laryngotracheal endoscopy, the responses to a questionnaire, and a retrospective review of the patient's data. The following parameters were analyzed: decannulation rates, breathing, voice quality, and deglutition. RESULTS: A single-stage partial cricotracheal resection was performed in 38 patients, and a double-stage procedure was performed in 19 patients. Sixteen patients underwent an extended partial cricotracheal resection (ie, partial cricotracheal resection combined with another open procedure). At a median follow-up time of 5.1 years, the decannulation rates after a single- or double-stage procedure were 97.4% and 95%, respectively. Two patients remained tracheotomy dependent. One patient had moderate exertional dyspnea, and all other patients had no exertional dyspnea. Voice quality was found to improve after surgical intervention for 1 +/- 1.34 grade dysphonia (P < .0001) according to the adapted GRBAS grading system (Grade, Roughness, Breathiness, Asthenia, and Strain). CONCLUSIONS: Partial cricotracheal resection provides good results for grades III and IV subglottic stenosis as primary or salvage operations. The procedure has no deleterious effects on laryngeal growth and function. The quality of voice significantly improves after surgical intervention but largely depends on the preoperative condition.

Discrete time Non-homogeneous Semi-Markov Processes applied to Models for Disability Insurance

In this paper, we present a stochastic model for disability insurance contracts. The model is based on a discrete time non-homogeneous semi-Markov process (DTNHSMP) to which the backward recurrence time process is introduced. This permits a more exhaustive study of disability evolution and a more efficient approach to the duration problem. The use of semi-Markov reward processes facilitates the possibility of deriving equations of the prospective and retrospective mathematical reserves. The model is applied to a sample of contracts drawn at random from a mutual insurance company.

Characterization of metabolites in infiltrating gliomas using ex vivo &supl;H high-resolution magic angle spinning spectroscopy.

Gliomas are routinely graded according to histopathological criteria established by the World Health Organization. Although this classification can be used to understand some of the variance in the clinical outcome of patients, there is still substantial heterogeneity within and between lesions of the same grade. This study evaluated image-guided tissue samples acquired from a large cohort of patients presenting with either new or recurrent gliomas of grades II-IV using ex vivo proton high-resolution magic angle spinning spectroscopy. The quantification of metabolite levels revealed several discrete profiles associated with primary glioma subtypes, as well as secondary subtypes that had undergone transformation to a higher grade at the time of recurrence. Statistical modeling further demonstrated that these metabolomic profiles could be differentially classified with respect to pathological grading and inter-grade conversions. Importantly, the myo-inositol to total choline index allowed for a separation of recurrent low-grade gliomas on different pathological trajectories, the heightened ratio of phosphocholine to glycerophosphocholine uniformly characterized several forms of glioblastoma multiforme, and the onco-metabolite D-2-hydroxyglutarate was shown to help distinguish secondary from primary grade IV glioma, as well as grade II and III from grade IV glioma. These data provide evidence that metabolite levels are of interest in the assessment of both intra-grade and intra-lesional malignancy. Such information could be used to enhance the diagnostic specificity of in vivo spectroscopy and to aid in the selection of the most appropriate therapy for individual patients.

L'angioplastie coronaire chez le patient âgé [Coronary angioplasty in elderly patients]

Percutaneous transluminal coronary angioplasty (PTCA) is a widely accepted treatment of symptomatic coronary heart disease providing prompt and prolonged clinical, improvement in most patients. We have examined the value of this therapy in a group of 91 patients in their eighth decade treated by 133 consecutive angioplasties. Most patients had refractory or instable angor in spite of optimal pharmacotherapy. Multivessel disease was present in 67% and maintained left-ventricular function in 92% of the patients. The angiographic success rate of PTCA was 84%; technical failures occurred in 12% and adverse events in 14%. Two patients died. The rate of symptomatic restenosis was 24%. Survival and patients free of myocardial events were at 89% and 60%, respectively, estimated by Kaplan-Meier analysis. PTCA is an efficient and acceptable treatment for the elderly patient with severe and drug-resistant angina. Two years after PTCA the majority of patients was asymptomatic.

Schistosomal myeloradiculopathy due to Schistosoma mansoni: report on 23 cases

Schistosoma mansoni infection is likely to be responsible for a significant proportion of cases of myelopathy occurring in areas where schistosomiasis is endemic. The aim of this study is to describe the clinical, laboratory and therapeutic data of 23 patients with schistosomal myeloradiculopathy. The medical records of 23 patients with schistosomal myelopathy admitted to two general hospitals of Belo Horizonte (MG), in Brazil, from 1995 to 1999, were reviewed retrospectively. Seventeen patients were male (74%). The mean age for the whole group was 27 years. Lower limb weakness and associated lumbar and/or lower limb pain were reported by 20 patients (87%), and 16 (70%) were unable to walk. All individuals presented urinary retention and 19 (83%) complained of intestinal dysfunction. The treatment was based on the association of antischistosomal drugs and corticosteroids. Five patients (22%) presented a full response to treatment, 13 (57%) partial response without functional limitations and 4 (17%) partial improvement with limitations or no response. Three out of the 4 patients who stopped steroids before 45 days of treatment developed recurrence of the symptoms and signs of myelopathy. Our cases demonstrate the severe presentation of the disease and the data disclosed here suggest that treatment with steroids should be kept for months after clinical improvement.

New perspectives in the use of ink evidence in forensic science

Resume : L'utilisation de l'encre comme indice en sciences forensiques est décrite et encadrée par une littérature abondante, comprenant entre autres deux standards de l'American Society for Testing and Materials (ASTM). La grande majorité de cette littérature se préoccupe de l'analyse des caractéristiques physiques ou chimiques des encres. Les standards ASTM proposent quelques principes de base qui concernent la comparaison et l'interprétation de la valeur d'indice des encres en sciences forensiques. L'étude de cette littérature et plus particulièrement des standards ASTM, en ayant a l'esprit les développements intervenus dans le domaine de l'interprétation de l'indice forensique, montre qu'il existe un potentiel certain pour l'amélioration de l'utilisation de l'indice encre et de son impact dans l'enquête criminelle. Cette thèse propose d'interpréter l'indice encre en se basant sur le cadre défini par le théorème de Bayes. Cette proposition a nécessité le développement d'un système d'assurance qualité pour l'analyse et la comparaison d'échantillons d'encre. Ce système d'assurance qualité tire parti d'un cadre théorique nouvellement défini. La méthodologie qui est proposée dans ce travail a été testée de manière compréhensive, en tirant parti d'un set de données spécialement créer pour l'occasion et d'outils importés de la biométrie. Cette recherche répond de manière convaincante à un problème concret généralement rencontré en sciences forensiques. L'information fournie par le criminaliste, lors de l'examen de traces, est souvent bridée, car celui-ci essaie de répondre à la mauvaise question. L'utilisation d'un cadre théorique explicite qui définit et formalise le goal de l'examen criminaliste, permet de déterminer les besoins technologiques et en matière de données. Le développement de cette technologie et la collection des données pertinentes peut être justifiées économiquement et achevée de manière scientifique. Abstract : The contribution of ink evidence to forensic science is described and supported by an abundant literature and by two standards from the American Society for Testing and Materials (ASTM). The vast majority of the available literature is concerned with the physical and chemical analysis of ink evidence. The relevant ASTM standards mention some principles regarding the comparison of pairs of ink samples and the evaluation of their evidential value. The review of this literature and, more specifically, of the ASTM standards in the light of recent developments in the interpretation of forensic evidence has shown some potential improvements, which would maximise the benefits of the use of ink evidence in forensic science. This thesis proposes to interpret ink evidence using the widely accepted and recommended Bayesian theorem. This proposition has required the development of a new quality assurance process for the analysis and comparison of ink samples, as well as of the definition of a theoretical framework for ink evidence. The proposed technology has been extensively tested using a large dataset of ink samples and state of the art tools, commonly used in biometry. Overall, this research successfully answers to a concrete problem generally encountered in forensic science, where scientists tend to self-limit the usefulness of the information that is present in various types of evidence, by trying to answer to the wrong questions. The declaration of an explicit framework, which defines and formalises their goals and expected contributions to the criminal and civil justice system, enables the determination of their needs in terms of technology and data. The development of this technology and the collection of the data is then justified economically, structured scientifically and can be proceeded efficiently.

Preliminary Experience in Treatment of Papillary and Macular Retinoblastoma: Evaluation of Local Control and Local Complications After Treatment with Linear Accelerator-Based Stereotactic Radiotherapy with Micromultileaf Collimator as Second-Line or Salvage Treatment after chemotherapy.

PURPOSE: To determine the local control and complication rates for children with papillary and/or macular retinoblastoma progressing after chemotherapy and undergoing stereotactic radiotherapy (SRT) with a micromultileaf collimator. METHODS AND MATERIALS: Between 2004 and 2008, 11 children (15 eyes) with macular and/or papillary retinoblastoma were treated with SRT. The mean age was 19 months (range, 2-111). Of the 15 eyes, 7, 6, and 2 were classified as International Classification of Intraocular Retinoblastoma Group B, C, and E, respectively. The delivered dose of SRT was 50.4 Gy in 28 fractions using a dedicated micromultileaf collimator linear accelerator. RESULTS: The median follow-up was 20 months (range, 13-39). Local control was achieved in 13 eyes (87%). The actuarial 1- and 2-year local control rates were both 82%. SRT was well tolerated. Late adverse events were reported in 4 patients. Of the 4 patients, 2 had developed focal microangiopathy 20 months after SRT; 1 had developed a transient recurrence of retinal detachment; and 1 had developed bilateral cataracts. No optic neuropathy was observed. CONCLUSIONS: Linear accelerator-based SRT for papillary and/or macular retinoblastoma in children resulted in excellent tumor control rates with acceptable toxicity. Additional research regarding SRT and its intrinsic organ-at-risk sparing capability is justified in the framework of prospective trials.

Risk factors for repetitive ileocolic resection in patients with Crohn's disease: results of an observational cohort study.

BACKGROUND: Surgical recurrence rates among patients with Crohn's disease with ileocolic resection (ICR) remain high, and factors predicting surgical recurrence remain controversial. We aimed to identify risk and protective factors for repetitive ICRs among patients with Crohn's disease in a large cohort of patients. METHODS: Data on 305 patients after first ICR were retrieved from our cross-sectional and prospective database (median follow-up: 15 yr [0-52 yr]). Data were compared between patients with 1 (ICR = 1, n = 225) or more than 1 (ICR >1, n = 80) resection. Clinical phenotypes were classified according to the Montreal Classification. Gender, family history of inflammatory bowel disease, smoking status, type of surgery, immunomodulator, and biological therapy before, parallel to and after first ICR were analyzed. RESULTS: The mean duration from diagnosis until first ICR did not differ significantly between the groups, being 5.93 ± 7.65 years in the ICR = 1 group and 5.36 ± 6.35 years in the ICR >1 group (P = 0.05). Mean time to second ICR was 6.7 ± 5.74 years. In the multivariate logistic regression analysis, ileal disease location (odds ratio [OR], 2.42; 95% confidence interval [CI], 1.02-5.78; P = 0.05) was a significant risk factor. A therapy with immunomodulators at time of or within 1 year after first ICR (OR, 0.23; 95% CI, 0.09-0.63; P < 0.01) was a protective factor. Neither smoking (OR, 1.16; 95% CI, 0.66-2.06) nor gender (male OR, 0.85; 95% CI, 0.51-1.42) or family history (OR, 1.68; 95% CI, 0.84-3.36) had a significant impact on surgical recurrence. CONCLUSIONS: Immunomodulators have a protective impact regarding surgical recurrence after ICR. In contrast, ileal disease location constitutes a significant risk factor for a second ICR.

Le conseil génétique: aspects théoriques et pratique en prénatal [Genetic counselling: theoretical aspects and prenatal practice]

Le conseil génétique doit fournir aux individus une information médicale précise et un soutien psychologique. L'importance des principes d'autonomie et de confidentialité, dogmes du conseil génétique, est renforcée par la nouvelle loi suisse (LAGH). Dans certains pays, une grande partie du conseil génétique est assurée par des conseillers en génétique non médecins ayant une formation postgraduée spécifique. Le conseil génétique joue un rôle grandissant dans différents domaines de la médecine. En particulier, il est indispensable dans le contexte du prénatal où les couples reçoivent des informations complexes et doivent bénéficier d’un soutien pour prendre une décision. Genetic counselling provides families with accurate medical information and psychological support. Respect and concern for the emotional well-being should be taken into account while discussing genetics aspects and recurrence risks. The importance of autonomy and confidentiality, central to genetic counselling, is reinforced by the new Swiss law (LAGH). In many countries, most of the genetic counselling is provided by genetic counsellors who have a specialised post-graduate training. Genetic counselling plays an increasing role in different medical specialities. In particular, it is essential in the context of prenatal and pre-conceptual care, where couples are confronted to complex information and should have access to appropriate support during the decision-making process