HapTree: A Novel Bayesian Framework for Single Individual Polyplotyping Using NGS Data

As the more recent next-generation sequencing (NGS) technologies provide longer read sequences, the use of sequencing datasets for complete haplotype phasing is fast becoming a reality, allowing haplotype reconstruction of a single sequenced genome. Nearly all previous haplotype reconstruction studies have focused on diploid genomes and are rarely scalable to genomes with higher ploidy. Yet computational investigations into polyploid genomes carry great importance, impacting plant, yeast and fish genomics, as well as the studies of the evolution of modern-day eukaryotes and (epi)genetic interactions between copies of genes. In this paper, we describe a novel maximum-likelihood estimation framework, HapTree, for polyploid haplotype assembly of an individual genome using NGS read datasets. We evaluate the performance of HapTree on simulated polyploid sequencing read data modeled after Illumina sequencing technologies. For triploid and higher ploidy genomes, we demonstrate that HapTree substantially improves haplotype assembly accuracy and efficiency over the state-of-the-art; moreover, HapTree is the first scalable polyplotyping method for higher ploidy. As a proof of concept, we also test our method on real sequencing data from NA12878 (1000 Genomes Project) and evaluate the quality of assembled haplotypes with respect to trio-based diplotype annotation as the ground truth. The results indicate that HapTree significantly improves the switch accuracy within phased haplotype blocks as compared to existing haplotype assembly methods, while producing comparable minimum error correction (MEC) values. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2–5.National Science Foundation (U.S.) (NSF/NIH BIGDATA Grant R01GM108348-01)National Science Foundation (U.S.) (Graduate Research Fellowship)Simons Foundatio

Parenting and child adjustment: a comparison of Turkish and English families

The links between parenting and child behaviour in cultural context have received increasing research attention. We investigated the effect of parenting on child adjustment using a multi-method design, comparing English and Turkish families. The socioeconomically diverse samples included 118 English and 100 Turkish families, each with two children aged 4–8 years. Mothers completed questionnaires as well as parent–child interaction being assessed using a structured Etch-a-Sketch task with each child separately. Children were interviewed about their relationships with their mothers using the Berkeley Puppet Interview. Multiple-group Confirmatory Analysis was used to test Measurement Invariance across groups, and a multi-informant approach was used to assess parenting. We found partial cross-cultural measurement invariance for parenting and child adjustment. Strikingly, the association between parenting and child adjustment was stronger among English families than Turkish families. Culturally distinct meanings of both parenting and child behaviour must be considered when interpreting their association

Diagnostic algorithm for papillary urothelial tumors in the urinary bladder

Papillary urothelial neoplasms with deceptively bland cytology cannot be easily classified. We aimed to design a new algorithm that could differentiate between these neoplasms based on a scoring system. We proposed a new scoring system that enables to reproducibly diagnose non-invasive papillary urothelial tumors. In this system, each lesion was given individual scores from 0 to 3 for mitosis and cellular thickness, from 0 to 2 for cellular atypia, and an additional score for papillary fusion. These scores were combined to form a summed score allowing the tumors to be ranked as follows: 0–1 = UP, 2–4 = low malignant potential (LMP), 5–7 = low-grade transitional cell carcinoma (TCC), and 8–9 = high-grade TCC. In addition to the scoring system, ancillary studies of MIB and p53 indexes with CK20 expression pattern analyses were compared together with clinical parameters. The MIB index was strongly correlated with disease progression. Four of the 22 LMP patients (18.2%) had late recurrences, two of these four (9.1%) had progression to low-grade carcinoma. The MIB index for LMP patients was strongly associated with recurrence (recurrence vs. non-recurrence, 16.5 vs. 8.1, p < 0.001). The proposed scoring system could enhance the reproducibility to distinguish papillary urothelial neoplasms

Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan

<p>Abstract</p> <p>Background</p> <p>This study assessed the effectiveness and safety of bosentan when administered to thromboangiitis obliterans (Buerger's disease) patients.</p> <p>Methods</p> <p>A clinical pilot study was designed in which patients with ulcer and/or pain at rest were treated with bosentan p.o. at a dose of 62.5 mg twice daily during the first month, which was thereafter up-titrated to 125 mg twice daily. The study endpoints were clinical improvement rate, major or minor amputation rate, haemodynamic changes, changes in endothelial function and angiographic changes.</p> <p>Results</p> <p>Seven out of 12 patients were male (58%). Median age was 39 years (range 29-49). The median follow-up was 20 months (range 11-40). All patients were smokers. With bosentan treatment, new ischaemic lesions were observed in only one patient. Overall, clinical improvement was observed in 12 of the 13 extremities (92%). Only two out of 13 extremities underwent amputation (one major and one minor) after bosentan treatment. After being assessed by digital arteriography with subtraction or angio-magnetic resonance imaging, an increase of distal flow was observed in 10 out of the 12 patients. All patients experienced a statistically significant improvement in their BAFMD values (mean: 1.8 at baseline; 6.6 at the end of the treatment; 12.7 three months after the end of the treatment; p < 0.01).</p> <p>Conclusion</p> <p>Bosentan treatment may result in an improvement of clinical, angiographic and endothelial function outcomes. Bosentan should be investigated further in the management of TAO patients. Larger studies are required to confirm these results.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01447550">NCT01447550</a></p

Suture granuloma after orchiectomy: sonography, doppler and elastography features

ABSTRACTSuture granuloma is a mass forming benign lesion that develops at the site of surgery as a foreign body reaction to non-absorbable suture material. We present a case of suture granuloma that developed at the inguinal region after orchiectomy, and define the sonography, color Doppler sonography and real-time ultrasound elastography findings in correlation with the histopathological findings

VIRCHOWS ARCHIV

Objectives. This study assessed the diagnostic agreement and intra- and inter-observer reproducibility of the World Health Organization/International Society of Urologic Pathology Consensus Classification of Urothelial Neoplasms (1998 WHO/ISUP classification) and the 1973 WHO classification. Methods. A teaching set with 5 slides of each papillary neoplasm of low malignant potential, low-grade papillary carcinoma, high-grade papillary carcinoma, and a guideline, as well as a study set of 30 slides containing ten cases of each category, were sent to participants. Six pathologists expert in urological pathology reviewed the 30 slides of non-invasive papillary urothelial tumors in the study set. Diagnostic accuracy and reproducibility were evaluated using intra- and inter-rater techniques (kappa statistic). Results. A moderate to substantial intra- and inter-observer reproducibility was achieved for both the 1998 WHO/ISUP and 1973 WHO classification. The results of the two classification systems were not different statistically (P>0.05). Reproducibility was lower in low-grade tumors for both classifications. Conclusions. The new proposed classification system for non-invasive urothelial neoplasms does not increase the reproducibility. There is still a need for uniformity in grading in order to compare the different studies and therapies and to provide more accurate information for management

Osteonecrosis of the accessory navicular bone

A case of osteonecrosis of the accessory navicular bone is reported. This entity should be kept in mind in the differential diagnosis of painful accessory navicular

Tumor volume estimation by the percentage carcinoma method in uterine cervix carcinoma

OBJECTIVE: To assess the capacity of the percentage carcinoma method to predict tumor volume in cervical carcinoma and generate a mathematical equation for calculation of tumor volume

Ganglion cells in the human prostate

Prostate carcinoma infiltrating around ganglion cells is claimed to be diagnostic of extracapsular extension because ganglion cells are only found in periprostatic soft tissue. However, the presence of autonomic ganglion cells in the fibrous capsule of the prostate has been reported. In this study, we aimed to define the exact localization of the ganglion cells in radical prostatectomy specimens. Slides of 64 totally embedded radical prostatectomies were reviewed. The ganglion cells were noted as outside the gland if no relation could be defined with prostate capsule or prostatic glands. They were noted as in the capsule when ganglion cells were observed inside the capsule, which was easily and definitely discerned. Ganglion cells were noted as ill the prostate when ganglion cells were observed beneath the capsule and in close proximity to the prostatic glands. Also, the ganglion cells were noted as in the capsule if they were observed inside the capsule but not adjacent to the prostatic glands, and as outside the prostate when the capsule could not be easily defined and distant from the prostatic glands. Ganglion cells were observed ill the prostate in 12 cases (18.75%). There was no relationship of these ganglion cells with the tumor in the prostatectomy specimens. Ganglion cells were located in the capsule in 14 cases (21.9%). The ganglion cells were observed outside the prostate in the other 38 cases (59.4%). These results show that there may be ganglion cells the prostate. Therefore, defining ganglion cell invasion by the tumor as extracapsular invasion may lead to staging error and cause erroneous management of the disease. Presence of carcinoma in ganglion cells should be recorded by defining whether these structures are within or outside the prostate gland