Does ocular treatment of uveal melanoma influence survival?

Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision. About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour. The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways. Treatment is therefore based on intuition and varies greatly between centres. Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive. Strategies for coping with uncertainty are needed to avoid unethical care

Links between Metabolic Syndrome and Cardiovascular Autonomic Dysfunction

Background. Type 2 diabetes (T2D) might occur within metabolic syndrome (MbS). One of the complications of T2D is an impaired (imp) cardiovascular autonomic function (CAF). Aims. In subjects with T2D and age ≤ 55 years, the prevalence of impCAF and its relationship with BMI, waist, HbA1c values, MbS, hypertension, and family history of T2D and/or hypertension were analysed. Methods. 180 subjects consecutively undergoing a day hospital for T2D were studied. The IDF criteria were used to diagnose MbS. To detect impCAF, 5 tests for the evaluation of CAF were performed with Cardionomic (Meteda, Italy). Univariate and multivariate analyses were performed. Results. The prevalence of impCAF and MbS were 33.9% and 67.8%, respectively. Among diabetics with impCAF, 86.9% had MbS. ImpCAF was significantly associated with MbS, overweight, and HbA1c > 7%. Both logistic (P = 0.0009) and Poisson (P = 0.0113) models showed a positive association between impCAF and MbS. The degree of ImpCAF showed a positive linear correlation with BMI and HbA1c values. Conclusions. The study demonstrates that glycaemic control and overweight influence CAF and that T2D + MbS is more strongly associated with impCAF than isolated T2D. We suggest that MbS not only increases the cardiovascular risk of relatively young subjects with T2D but is also associated with impCAF

Isocitrate dehydrogenase 1 mutations (IDH1) and p16/CDKN2A copy number change in conventional chondrosarcomas.

To determine whether IDH1 mutations are present in primary and relapsed (local and distal) conventional central chondrosarcomas; and secondly, to assess if loss of p16/CDKN2A is associated with tumour grade progression, 102 tumour samples from 37 patients, including material from presenting and relapse events, were assessed. All wild-type cases for IDH1 R132 substitutions were also tested for IDH2 R172 and R140 alterations. The primary tumour and the most recent relapse sample were tested for p16/CDKN2A by interphase fluorescence in situ hybridisation. An additional 120 central cartilaginous tumours from different patients were also tested for p16/CDKN2A copy number. The study shows that if an IDH1 mutation were detected in a primary central chondrosarcoma, it is always detected at the time of presentation, and the same mutation is detected in local recurrences and metastatic events. We show that p16/CDKN2A copy number variation occurs subsequent to the IDH1 mutation, and confirm that p16/CDKN2A copy number variation occurs in 75 % of high grade central chondrosarcomas, and not in low grade cartilaginous tumours. Finally, p16/CDKN2A copy number variation is seen in both the IDH1 wild-type and mutant cartilaginous central tumours

“Multidimensional child sex rings”: a systematic review of the literature

Background: In 1983 Kennet Lanning began his studies dealing with sexual rituals, and in 1985 there calls “Multidimensional Child Sex Rings” identifying features and modes (Lanning, 1992). In his studies Lanning (1992), describes the types of offences related to the dimension of ritual abuse by claiming that there is no clear evidence about some of these crimes. On the basis of those statements Weir and Wheatcroft (1995) list as possible by declaring a false ritual abuse and then of false memories, the suggestion of special interest about the growing psychotherapists induced ritual abuse and who believe in the existence of these crimes.This systematic review of the literature, in the light of subsequent events and subsequent updates of methodology aims to analyze the relationship between “Ritual Abuse” and the false memory that can appear during psychotherapy. Materials and Methods: This study was carried out using the PRISMA guidelines, by conducting a systematic search of the literature on PubMed, Scopus, ISI Web of Science, EBSCO, Google Scholar, and ScienceDirect. The following keywords used were “ritual abuse” “AND” (i.e., Boolean operator) “psychotherapy” combined with “AND” Boolean operator and “false memory”.Results: The initial search identified n = 167 citations. Only one research report met the predefined inclusion criteria and was analysed.Conclusion: In case of false memories in ritual abuse, it is necessary to implement the research activities to avoid that results obtained can be rejected by health professionals or by theories not scientifically validated.Background: Nel 1983 Kennet Lanning inizia i suoi studi occupandosi di abusi sessuali rituali, e nel 1985 lì definisce “Multidimensional Child Sex Rings” identificandone caratteristiche e modalità (Lanning, 1992). Nei suoi studi Lanning (1992), descrive le tipologie di reato connesse alla dimensione dell’abuso rituale sostenendo che non esistono prove certe in merito ad alcuni di questi reati. Sulla base di tali affermazioni Weir and Wheatcroft (1995) elencano come possibili ipotesi di generazione di falsi abusi rituali e quindi di falsi ricordi, la suggestione indotta di psicoterapeuti che coltivano speciali interessi circa gli abusi rituali e che credono nell’esistenza di questi crimini. La presente analisi sistematica della letteratura, alla luce dei successivi accadimenti e di successivi aggiornamenti metodologici ha lo scopo di analizzare la relazione tra “Abuso Rituale” ed il falso ricordo che può manifestarsi durante la psicoterapia. Materiali e Metodi: Tale studio è stato effettuato utilizzando le linee guida per l’utilizzo della metodología PRISMA, effettuando una ricerca sistematica su PubMed, Scopus, ISI Web of Science, EBSCO, Google Scholar e ScienceDirect. Le parole chiave utilizzate per la ricerca sono state “ritual abuse” “AND” (i.e. operatore Boleano) “psychotherapy” “AND” “false memory”.Risultati: Sono stati inizialmente trovati n = 167 records. Un solo articolo ha poi soddisfatto i criteri di inclusione ed è stato analizzati.Conclusioni: Nel caso delle false memorie negli abusi rituali, sembra necessario implementare l’attività di ricerca per evitare che qualsiasi risultato ottenuto possa essere contrastato dai professionisti della salute o da teorie non validate scientificamente

Il minore vittima di abusi sessuali e le garanzie del giusto processo penale

Criminal proceedings concerning the assessment of sexual abusive behaviour affecting minors includes, among its most delicate stages, the collection of the young victim’s statements, especially if the victims are in their earliest years.The collection of a minor’s testimony must follow rules and procedures whose main goal is to safeguard the minor.Up to now, Italian Criminal Justice System does not provide an organic system for the Young victim’s protection; on the part of the legislator, there is a lack of specific rules and regolations for the minor’s testimony.According to Article 196, paragraph 1 and 2 of the Italian Code of Criminal Procedures, “every person is competent to testify,” but “in order to evaluate the witness’ statement, the judge can order appropriate verifications using all lawful means, even ex officio.”More effectively, Article 10 of the Carta of Noto recommend, for children under 12 and apart from exceptional cases, “that a valuation must always occur in order to verify the victim’s fitness to testify about the matters,” unless the judge can evaluate the reliability of the testimony.Therefore, is it possible for the judge to establish the truthfulness of the minor’s testimony apart from a technical advice of an expert, that is without making a psychological evaluation of the child first?” The prevailing jurisprudential orientation in recent years confirms the prevalence of the so-called principle of the all-encompassing evaluation, whereby “on the subject of sexual offenses against young children, it is illegal, for violation of the principle of the formation of evidence in contradictory, the refusal of judge to arrange a psychological examination, in order to ascertain the adherence to the reality or not of the narration of the facts, depending on possible fanciful elaborations of the age or of the personological structure of the minor2”.Nei procedimenti penali aventi ad oggetto l’accertamento della condotta di abuso sessuale a danno di minore, fra le fasi più delicate, vi è quella inerente l’acquisizione delle dichiarazioni della giovane vittima specie se in tenera età.E’ pacifico che l’assunzione della testimonianza di un minore, perché tale, deve avvenire con criteri e modalità che abbiano quale obiettivo principale, quello della tutela del minore stesso. Il sistema penale italiano a tutt’oggi rileva l’assenza di un organico sistema di protezione del minore vittima di abusi; manca una specifica disciplina da parte del legislatore, della testimonianza del soggetto minore di età.Secondo quanto disposto dall’art. 196, comma 1 e 2 c.p.p.“Ogni persona ha la capacità di testimoniare” tuttavia “qualora, al fine di valutare le dichiarazioni del testimone, sia necessario verificarne l’idoneità física o mentale a rendere testimonianza, il giudice anche di ufficio può ordinare gli accertamenti opportuni con i mezzi consentiti dalla legge”.Più efficacemente la Carta di Noto all’art. 10 raccomanda per i minori di anni dodici e salvo casi eccezionali “che sia sempre disposta perizia al fine di verificarne la idoneità a testimoniare sui fatti oggetto d’indagine”, salvo al giudice valutare l’attendibilità della testimonianza resa.E’ possibile allora per il decidente, accertare la veridicità della condotta abusante dal racconto del minore, prescindendo dall’ausilio del parere tecnico di un perito, ovvero senza aver prima disposto una perizia psicologica sul bambino?L’orientamento giurisprudenziale prevalente negli ultimi anni, conferma il prevalere del principio cosiddetto della valutazione onnicomprensiva, per cui “in tema di reati sessuali su minori in tenera età, è illegittimo, per violazione del principio della formazione della prova in contraddittorio, il rifiu to dei giudice di disporre una perizia psicologica, al fine di accertare l’aderenza alla realtà o meno della narrazione dei fatti, in dipendenza di eventuali elaborazioni fantasiose proprie dell’età o della struttura personologica del minore”1

Whole-genome microarray detects deletions and loss of heterozygosity of chromosome 3 occurring exclusively in metastasizing uveal melanoma

PURPOSE. To detect deletions and loss of heterozygosity of chromosome 3 in a rare subset of fatal, disomy 3 uveal melanoma (UM), undetectable by fluorescence in situ hybridization (FISH). METHODS. Multiplex ligation-dependent probe amplification (MLPA) with the P027 UM assay was performed on formalinfixed, paraffin-embedded (FFPE) whole tumor sections from 19 disomy 3 metastasizing UMs. Whole-genome microarray analyses using a single-nucleotide polymorphism microarray (aSNP) were performed on frozen tissue samples from four fatal disomy 3 metastasizing UMs and three disomy 3 tumors with Ͼ5 years' metastasis-free survival. RESULTS. Two metastasizing UMs that had been classified as disomy 3 by FISH analysis of a small tumor sample were found on MLPA analysis to show monosomy 3. No ubiquitous gene deletions of chromosome 3 were seen in the remaining 17 metastasizing disomy 3 UMs by MLPA. aSNP analysis revealed 95 deleted genes and 16 genes with loss of heterozygosity (LOH) on chromosome 3 in the disomy 3 metastasizing UMs that were not deleted or showing LOH in the nonmetastatic tumors. CONCLUSIONS. MLPA can detect monosomy 3 cell populations in FFPE whole tumor sections previously missed by FISH performed on small tumor samples. Consistent deletion and LOH of genes on chromosome 3 occur in metastasizing disomy 3 UM and are detectable by aSNP analysis. Ninety-five genes were found to be deleted, and 16 genes showed LOH exclusively in disomy 3 metastasizing UM, suggesting a potential role for these genes in UM metastasis. (Invest Ophthalmol Vis Sci. 2010;51:4884 -4891) DOI:10.1167/iovs.09-5083 U veal melanoma (UM), the most common primary intraocular cancer in adults, is fatal in almost 50% of patients, because of metastatic spread often involving the liver. Chemotherapy of metastases has limited success 1,2 and disseminated disease is fatal in 92% of patients within 2 years of diagnosis. Clinical and histopathologic risk factors for UM metastasis include large basal tumor diameter (LBD), ciliary body involvement, epithelioid cytomorphology, extracellular matrix periodic acid-Schiff-positive (PAS ϩ ) loops, and high mitotic count. 3,4 Prescher et al. 3,6 -10 Consequently, fluorescence in situ hybridization (FISH) detection of chromosome 3 using a centromeric probe became routine practice for UM prognostication; however, 5% to 20% of disomy 3 UM patients unexpectedly develop metastases. We hypothesize that disomy 3 UMs that metastasize do so by the same mechanisms as metastasizing monosomy 3 UMs. However, instead of loss of a single copy of chromosome 3 facilitating this process, specific genes are deleted on chromosome 3 that are essential to an early progression to metastasis, not commonly seen in disomy 3 UM. The purpose of our study was to identify key MSGs that are deleted exclusively in a rare subset of UMs that metastasized despite apparent disomy 3 on FISH testing. We investigated whether deletions of chromosome 3 could be detected using either multiplex ligationdependent probe amplification (MLPA) or a single-nucleotide polymorphism microarray (aSNP; SNP 6.0; Affymetrix, Santa Clara, CA). Knowledge of such deletions on chromosome 3 may allow more accurate prognostication, increase understanding of the natural history of UM, and help identify aberrant cell signaling pathways that may be amenable to therapy. MATERIALS AND METHODS Tumor Samples Fresh primary UM samples were routinely obtained at the Royal Liverpool University Hospital between 2001 and 2007 and analyzed by FISH for chromosome 3 copy number. Of these UMs, formalin-fixed, paraffin-embedded (FFPE) tumor samples were available in our archive for 34 disomy 3 UMs that were known to have metastasized (Di3M-UM). Nineteen of these samples were selected for MLPA studies, as they provided sufficient extracted DNA (700 ng) for quality control PCR and analysis by MLPA in triplicate. Four snap-frozen Di3M-UM samples from patients with fatal metastasis within 5 years of diagnosis and samples from three disomy 3 surviving UM (Di3S-UM) patients with no detectable metastases after a minimum of 5 years since diagnosis were used for aSNP analysis. Personalized survival curves were generated for all three patients with disomy 3 nonmetastasizing UM using the Cox proportional hazards model. The model predicts survival up to 8 years after diagnosis and specifies 95% CI based on the following information: age at treatment, sex, ciliary body involvement, largest basal From th

Converting simulated total dry matter to fresh marketable yield for field vegetables at a range of nitrogen supply levels

Simultaneous analysis of economic and environmental performance of horticultural crop production requires qualified assumptions on the effect of management options, and particularly of nitrogen (N) fertilisation, on the net returns of the farm. Dynamic soil-plant-environment simulation models for agro-ecosystems are frequently applied to predict crop yield, generally as dry matter per area, and the environmental impact of production. Economic analysis requires conversion of yields to fresh marketable weight, which is not easy to calculate for vegetables, since different species have different properties and special market requirements. Furthermore, the marketable part of many vegetables is dependent on N availability during growth, which may lead to complete crop failure under sub-optimal N supply in tightly calculated N fertiliser regimes or low-input systems. In this paper we present two methods for converting simulated total dry matter to marketable fresh matter yield for various vegetables and European growth conditions, taking into consideration the effect of N supply: (i) a regression based function for vegetables sold as bulk or bunching ware and (ii) a population approach for piecewise sold row crops. For both methods, to be used in the context of a dynamic simulation model, parameter values were compiled from a literature survey. Implemented in such a model, both algorithms were tested against experimental field data, yielding an Index of Agreement of 0.80 for the regression strategy and 0.90 for the population strategy. Furthermore, the population strategy was capable of reflecting rather well the effect of crop spacing on yield and the effect of N supply on product grading

ACTA OTORHINOLARYNGOLOGICA ITALICA

Le asimmetrie maxillo-mandibolari riconoscono numerose eziologie: congenita, traumatica, iatrogena e post resezione oncologica. I pazienti affetti da malformazioni congenite vengono generalmente sottoposti a chirurgia ortognatica con o senza procedure aggiuntive (genioplastica, impianti alloplastici) con risultati soddisfacenti. Tuttavia, nonostante il raggiungimento della simmetria scheletrica può esitare una asimmetria residua più o meno evidente. Lo studio presentato è stato effettuato su 45 pazienti (29 femmine e 16 maschi), trattati chirurgicamente tra Dicembre 2012 e Giugno 2014. Tutti i pazienti erano affetti da asimmetria maxillo-mandibolare e sono stati sottoposti a chirurgia ortognatica per la correzione ossea della deformità. Le alterazioni residue sono state trattate con lipofilling. In tutti i casi si è osservato un buon attecchimento del grasso a livello del sito ricevente. Lanalisi retrospettiva della documentazione fotografica ha dimostrato un progressivo decremento dei volumi raggiunti in seguito al trattamento con lipofilling fino a sei mesi dalla procedura, dopodiché i volumi sono rimasti invariati. Non sono state riportate complicanze significative sia a livello del sito donatore sia del ricevente. Un lieve edema ecchimotico è stato osservato frequentemente nella prima settimana post-operatoria, non sono stati riportati casi di ematoma, infezioni, danni nervosi o vascolari. 24 pazienti hanno avuto necessità di ulteriori applicazioni, una seconda applicazione si è resa necessaria in 22 pazienti ed una terza in 2 pazienti. (totale di 69 procedure). Sulla base dei risultati di questo studio la metodica del lipofilling si è dimostrata semplice, efficace e facilmente riproducibile, mostrando un alto indice di soddisfazione da parte dei pazienti e una scarsa incidenza di svantaggi e complicanze. Abbiamo inoltre dimostrato come il successo del riempimento con grasso autologo sia dipendente dalla subunità del viso che viene trattata. Le regioni malare e della guancia hanno mostrato i migliori risultati mentre le subunità corrispondenti al labbro inferiore e superiore hanno mostrato uno scarso attecchimento del grasso innestato, con una conseguente maggiore perdita di volume. In conclusione si può dire che le procedure composite, che prevedono lutilizzo congiunto della correzione chirurgica delle basi scheletriche e un successivo ritocco per mezzo di innesto di grasso autologo, costituiscono una opzione addizionale e personalizzabile per i pazienti affetti da malformazioni maxillo-mandibolari

Variability in MRI vs. ultrasound measures of prostate volume and its impact on treatment recommendations for favorable-risk prostate cancer patients: a case series

Background: Prostate volume can affect whether patients qualify for brachytherapy (desired size ≥20 mL and ≤60 mL) and/or active surveillance (desired PSA density ≤0.15 for very low risk disease). This study examines variability in prostate volume measurements depending on imaging modality used (ultrasound versus MRI) and volume calculation technique (contouring versus ellipsoid) and quantifies the impact of this variability on treatment recommendations for men with favorable-risk prostate cancer. Methods: We examined 70 patients who presented consecutively for consideration of brachytherapy for favorable-risk prostate cancer who had volume estimates by three methods: contoured axial ultrasound slices, ultrasound ellipsoid (height × width × length × 0.523) calculation, and endorectal coil MRI (erMRI) ellipsoid calculation. Results: Average gland size by the contoured ultrasound, ellipsoid ultrasound, and erMRI methods were 33.99, 37.16, and 39.62 mLs, respectively. All pairwise comparisons between methods were statistically significant (all p < 0.015). Of the 66 patients who volumetrically qualified for brachytherapy on ellipsoid ultrasound measures, 22 (33.33%) did not qualify on ellipsoid erMRI or contoured ultrasound measures. 38 patients (54.28%) had PSA density ≤0.15 ng/dl as calculated using ellipsoid ultrasound volumes, compared to 34 (48.57%) and 38 patients (54.28%) using contoured ultrasound and ellipsoid erMRI volumes, respectively. Conclusions: The ultrasound ellipsoid and erMRI ellipsoid methods appeared to overestimate ultrasound contoured volume by an average of 9.34% and 16.57% respectively. 33.33% of those who qualified for brachytherapy based on ellipsoid ultrasound volume would be disqualified based on ultrasound contoured and/or erMRI ellipsoid volume. As treatment recommendations increasingly rely on estimates of prostate size, clinicians must consider method of volume estimation