Shortest Path Problems on a Polyhedral Surface

We develop algorithms to compute shortest path edge sequences, Voronoi diagrams, the Fréchet distance, and the diameter for a polyhedral surface

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Iloperidone: a new benzisoxazole atypical antipsychotic drug: is it nove enough to impact the crowded atypical antipsychotic market?

Iloperidone (Zomaril\uae) is a new generation atypical antipsychotic agent, acting as a 5-HT2A/D2 antagonist, currently under development by Vanda Pharmaceuticals for the treatment of schizophrenia, bipolar disorder and other psychiatric conditions. Chemically Iloperidone is a benzisoxazole, like Risperidone, and shows a multiple receptor binding profile, sharing this feature with the other atypical antipsychotic agents. Administered orally, the drug is highly bound to plasma proteins and extensively metabolised; reduced Iloperidone is the main active metabolite. Several clinical trials were carried out, to check efficacy, safety and side effects. In order to introduce Iloperidone as an agent for the treatment of schizophrenia, a short overview of the disease and of the most important available or under development antipsychotic drugs will be reported as well. Iloperidone pharmacokinetics and pharmacodynamics are presented herein, together with an evaluation of clinical safety and efficacy results

Therapeutic drug monitoring (TDM) of the recent antipsychotic ziprasidone in dried blood spots (DBS) and plasma

Introduction: Ziprasidone (5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazin-yl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one) is the most recent atypical antipsychotic introduced onto the market. It probably has the highest selectivity of any antipsychotic agent toward 5-HT2A receptors relative to D2 and 5-HT2C receptors. The main clinical advantage of ziprasidone with respect to other atypical antipsychotics seems to be its low incidence of metabolic side effects. However, the drug can cause severe undesired effects, mainly QTc prolongation and orthostatic hypotension. For this reason, an accurate TDM of patients is advised during ziprasidone therapy. Aim of this study is the development of an original analytical method for the determination of ziprasidone in dried blood spots (DBS) and plasma of psychotic patients, based on HPLC with spectrofluorimetric and spectrophotometric detection. DBS testing has the advantage of being a minimally invasive procedure; moreover, DBS can be easily stored and transported without the need for refrigeration. Methods: The analysis is carried out on a C8 reversed phase column, using a phosphate buffer / acetonitrile mixture as the mobile phase. Ziprasidone is natively fluorescent under the chromatographic conditions used, therefore fluorimetric detection is suitable for its dosage, granting satisfactory sensitivity and selectivity to the assay. The sample pre-treatment of DBS is based on a very fast and feasible solvent extraction procedure, while plasma sample cleaning is achieved by solid phase extraction. Results: The results obtained until now are satisfactory in terms of precision and extraction yield on both matrices. Conclusions: Method validation is currently in progress. From preliminary assays, the method seems to be suitable for the TDM of ziprasidone in DBS and plasma

Analisi simultanea di quetiapina e fluvoxamina in plasma di pazienti schizofrenici mediante cromatografia liquida

La schizofrenia \ue8 spesso associata ad altre turbe psichiatriche, come depressione, aggressivit\ue0, asocialit\ue0. La terapia della malattia prevede che i farmaci antipsicotici siano spesso affiancati da altri farmaci, come gli antidepressivi. I pazienti in terapia con il recente antipsicotico quetiapina (2-(2-[4-(dibenzo[b,f]tiazepin-11-il)piperazin-1-il]-etossi)etanolo) sono a volte sottoposti a trattamento anche con fluvoxamina, un antidepressivo SSRI. La fluvoxamina, (E)-O-(2-aminoetil)ossima-5-metossi-1-[4-(trifluorometil)fenil]-1-pentanone, esiste come coppia di isomeri geometrici, dei quali solo quello (E)- presenta attivit\ue0 terapeutica. Scopo di questo studio \ue8 la determinazione della quetiapina e degli isomeri della fluvoxamina nel plasma di pazienti schizofrenici sottoposti a polifarmacoterapia. Le analisi sono effettuate mediante HPLC-UV, utilizzando una colonna C8 ed una fase mobile composta da acetonitrile e tampone fosfato a pH 3,5 contenente trietilammina; lambda = 245 nm. Per il pretrattamento del campione \ue8 stata sviluppata un'originale procedura d'estrazione in fase solida mediante l'impiego di cartucce Discovery\uae DSC-MCAX. La procedura permetteva di ottenere un purificazione ottimale dalla matrice biologica con una buona resa d'estrazione degli analiti. Si \ue8 ottenuta linearit\ue0 nei range di concentrazioni: 2-400 ng/mL per la quetiapina; 5-160 ng/mL per ciascun isomero della fluvoxamina. Il metodo sembra essere idoneo all'analisi di quetiapina e fluvoxamina in plasma umano

Visualising improved peritoneal perfusion at lower intra-abdominal pressure by fluorescent imaging during laparoscopic surgery: A randomised controlled study

Contains fulltext : 221721.pdf (Publisher’s version ) (Closed access)BACKGROUND: Laparoscopy is the gold standard for many surgical procedures and is embraced as minimally invasive surgery in the enhanced recovery after surgery programme. Lowering intra-abdominal pressure during laparoscopy may decrease the degree of surgical injury and further enhance patient outcomes. This study aims to assess the effect of low pressure pneumoperitoneum on peritoneal perfusion during laparoscopic surgery. MATERIALS AND METHODS: We performed a prospective randomized intervention study in 30 adults undergoing colorectal robot assisted laparoscopic surgery at a secondary care medical center in the Netherlands between June and December 2018. A 3 min video recording of the parietal peritoneum was made with the Da Vinci® Firefly mode following intravenous injection of 0.2 mg/kg indocyanine green at a pneumoperitoneum pressure of 8, 12 or 16 mmHg. Observers were blinded for the level of intra-abdominal pressure that was used. Fluorescent intensity in [-] over time was extracted from each video in MATLAB. Time to reach maximal fluorescent intensity (TMFI) and maximum fluorescent intensity (MFI) were compared among groups. The study was registered at clinicaltrials.gov (NCT03928171). RESULTS: Mean TMFI was shorter at low pressure (8 mmHg) than standard pressure (12 and 16 mmHg): 44 ± 12 versus 58 ± 18 s (p = 0.032), respectively. Mean MFI was higher at 8 mmHg than 12 and 16 mmHg (222 ± 25 versus 188 ± 54, p = 0.033). Regression analysis identified intra-abdominal pressure, mean arterial pressure and female gender as significant predictors of peritoneal perfusion. CONCLUSION: Low pressure pneumoperitoneum was associated with improved perfusion of the parietal peritoneum. Current available evidence supported feasibility and enhanced postoperative recovery. Future investigations should focus on optimizing factors that facilitate lower intra-abdominal pressure and explore effects on other clinically relevant patient outcomes such as anastomotic leakage and immune homeostasis