Distributed Cognition and Process Management Enabling Individualized Translational Research: The NIH Undiagnosed Diseases Program Experience.

The National Institutes of Health Undiagnosed Diseases Program (NIH UDP) applies translational research systematically to diagnose patients with undiagnosed diseases. The challenge is to implement an information system enabling scalable translational research. The authors hypothesized that similar complex problems are resolvable through process management and the distributed cognition of communities.

Collaboratively charting the gene-to-phenotype network of human congenital heart defects.

Background: How to efficiently integrate the daily practice of molecular biologists, geneticists, and clinicians with the emerging computational strategies from systems biology is still much of an open question.

Description: We built on the recent advances in Wiki-based technologies to develop a collaborative knowledge base and gene prioritization portal aimed at mapping genes and genomic regions, and untangling their relations with corresponding human phenotypes, congenital heart defects (CHDs). This portal is not only an evolving community repository of current knowledge on the genetic basis of CHDs, but also a collaborative environment for the study of candidate genes potentially implicated in CHDs - in particular by integrating recent strategies for the statistical prioritization of candidate genes.

ENDEAVOUR update: a web resource for gene prioritization in multiple species.

Endeavour (http://www.esat.kuleuven.

Array comparative genomic hybridization and computational genome annotation in constitutional cytogenetics: suggesting candidate genes for novel submicroscopic chromosomal imbalance syndromes.

Genome-wide array comparative genomic hybridization screening is uncovering pathogenic submicroscopic chromosomal imbalances in patients with developmental disorders. In those patients, imbalances appear now to be scattered across the whole genome, and most patients carry different chromosomal anomalies. Screening patients with developmental disorders can be considered a forward functional genome screen.

Gene prioritization through genomic data fusion.

The identification of genes involved in health and disease remains a challenge. We describe a bioinformatics approach, together with a freely accessible, interactive and flexible software termed Endeavour, to prioritize candidate genes underlying biological processes or diseases, based on their similarity to known genes involved in these phenomena. Unlike previous approaches, ours generates distinct prioritizations for multiple heterogeneous data sources, which are then integrated, or fused, into a global ranking using order statistics.

TXTGate: profiling gene groups with text-based information.

We implemented a framework called TXTGate that combines literature indices of selected public biological resources in a flexible text-mining system designed towards the analysis of groups of genes. By means of tailored vocabularies, term- as well as gene-centric views are offered on selected textual fields and MEDLINE abstracts used in LocusLink and the Saccharomyces Genome Database. Subclustering and links to external resources allow for in-depth analysis of the resulting term profiles.

INCLUSive: A web portal and service registry for microarray and regulatory sequence analysis.

INCLUSive is a suite of algorithms and tools for the analysis of gene expression data and the discovery of cis-regulatory sequence elements. The tools allow normalization, filtering and clustering of microarray data, functional scoring of gene clusters, sequence retrieval, and detection of known and unknown regulatory elements using probabilistic sequence models and Gibbs sampling. All tools are available via different web pages and as web services.

The vertical mammaplasty: a reappraisal of the technique and its complications.

Since 1989, superior pedicle vertical scar mammaplasty as described by Lejour has been used in the authors' department as the only technique for breast reduction. From 1991 through 1994, a series of 170 consecutive patients (330 breasts) underwent an operation. In these patients, minor complications were observed in 30 percent of the patients and major complications in 15 percent.

MARAN: normalizing micro-array data.

Summary: MARAN is a web-based application for normalizing microarray data. MARAN comprises a generic ANOVA model, an option for Loess fitting prior to ANOVA analysis, and a module for selecting genes with significantly changing expression.

Availability: http://www.

Toucan: deciphering the cis-regulatory logic of coregulated genes.

TOUCAN is a Java application for the rapid discovery of significant cis-regulatory elements from sets of coexpressed or coregulated genes. Biologists can automatically (i) retrieve genes and intergenic regions, (ii) identify putative regulatory regions, (iii) score sequences for known transcription factor binding sites, (iv) identify candidate motifs for unknown binding sites, and (v) detect those statistically over-represented sites that are characteristic for a gene set. Genes or intergenic regions are retrieved from Ensembl or EMBL, together with orthologs and supporting information.

Do multiple consecutive head and neck reconstructions improve the patients functional outcome?

Background: The purpose of this study was to determined the functional outcome of surgically treated head and neck cancer patients who required more than "standard" microsurgical reconstruction.

Methods: Data concerning all patients with head and neck cancers, who underwent free-tissue transfers in our institution between January 1, 1994 and August 31, 1999 were reviewed. The cases of tumor recurrences and those with micro-surgical complications were excluded.

One-stage elbow interposition arthroplasty with a fasciocutaneous distally planned lateral arm flap.

We report a case of severe posttraumatic ankylosis of the elbow with chronic osteomyelitis of the lateral condyle of the humerus. The triple problem of restoring elbow mobility, providing for coverage, and controlling infection was treated in a one-stage procedure. A distally planned fasciocutaneous lateral arm flap was used for elbow interposition arthroplasty.

Free deepithelialized anterolateral thigh myocutaneous flaps for chronic intractable empyema with bronchopleural fistula.

Background: Free deepithelialized anterolateral thigh (DALT) flaps have been used for treatment of chronic intractable empyema with bronchopleural fistula at Chang Gung Memorial Hospital since 1997.

Methods: Twelve patients with chronic empyema were treated at Chang Gung Memorial Hospital from January 1997 to January 2001. Their age ranged from 31 to 70 years (mean age 48.

Arteriovenous malformation involving the thumb and hand: radical excision and reconstruction of multiple components.

Arteriovenous malformation of the fingers is not an uncommon presentation in daily practice. The lesions may or may not become clinically evident from birth to adulthood. Treatment of the arteriovenous malformation includes conservative treatment, selective embolization, partial excision, and radical excision.

Dorsal carpometarcarpal dislocation of ulnar fingers. A case report.

Multiple dorsal dislocations of the carpometacarpal joints are rare. Diagnosis requires a high index of suspicion, careful examination and good radiography. Treatment is controversial and is based on the presence or not of associated fractures.

The nerve supply of the trapeziometacarpal joint.

Ten forearm and hand specimens from fresh cadavers were dissected and examined under magnification for articular branches to the trapeziometacarpal joint arising from the thenar and palmar cutaneous branches of the median nerve, the superficial branch of the radial nerve and the lateral cutaneous nerve of forearm. In all but one specimen the thenar branch of the median nerve sent an articular branch to the trapeziometacarpal joint. Multiple branches from the palmar cutaneous branch of the median nerve, the superficial branch of the radial nerve and the lateral cutaneous nerve of forearm were also found.

[Thenar branch of the median nerve and innervation of the trapeziometacarpal joint].

Introduction: Denervation has been proposed successfully for chronic wrist pain. This procedure is not commonly performed for degenerative osteoarthritis of the trapeziometacarpal joint. According to the classic anatomical descriptions of the wrist innervation, it seems that the thenar branch of the median nerve (TBMN) is the only nerve of the wrist for which no articular branches are clearly defined.

Use of gracilis muscle free flap for reconstruction of chronic osteomyelitis of foot and ankle.

Despite low donor-site morbidity and a straightforward dissection, the gracilis muscle flap is still for many surgeons a second choice in microsurgical reconstruction of the lower extremity in cases of osteomyelitis. They underscore the difficulty of the procedure, and the problems of insufficient muscle volume and a small sized vascular pedicle. The aim of this study was to assess the reliability of the gracilis muscle free flap in the treatment of osteomyelitis of the foot and ankle.

Congenital syndactyly: defatting facilitates closure without skin graft.

We attempted to correct 24 syndactylies without skin grafts in 16 consecutive patients. Digital volume was decreased by defatting the full length of the fingers and the interdigital space. Closure of the zigzag incisions on both fingers could then be achieved with minimal tension and did not seem to be related to the type of flap used for commissure resurfacing.

The distally planned lateral arm flap in hand reconstruction.

The lateral arm flap is a versatile free flap with straightforward dissection and low donor site morbidity. However, it presents some drawbacks: the vascular pedicle is relatively short (2-6 cm), and the flap is rather thick. Further surgery is often needed to decrease flap volume.

Evaluation of the donor site morbidity after lateral arm flap with skin paddle extending over the elbow joint.

The free lateral arm flap may be extended to include the skin over the lateral aspect of the elbow and the forearm. However, extending the flap beyond the lateral condyle has been thought to interfere with the elbow function. The aim of this study was to assess the donor site morbidity after placement of the skin paddle across the lateral aspect of the elbow joint.

An unusual case of squamous cell carcinoma of the nose.

A 49-year-old man presented with a tumoral lesion of the tip of the nose which had been manifest for 2 months. Within a few weeks, the tumour increased in size and became infiltrated. The biopsy showed a squamous cell carcinoma.

One-stage reconstruction of an infected skin and Achilles tendon defect with a composite distally planned lateral arm flap.

In this paper, the treatment of a complicated Achilles tendon defect with a composite lateral arm flap with distal design of the skin paddle has been presented. The extended portion of the flap was sufficient to restore adequate contour to the posterior aspect of the ankle, and reinervation showed good protective sensation at 1 year. In terms of resurfacing, the use of the reinervated lateral arm flap with a distal design of the skin paddle seems advantageous.

Preoperative ultrasound Doppler study and clinical correlation of free posterior interosseous flap.

Background: Conventional pedicled posterior interosseous flap has a relatively high rate of partial flap loss which may result in ultimate failure to provide coverage of this important structure. The goal of this study was to delineate the posterior interosseous flap as a reliable free tissue transfer.

Methods: From 1991 to 1995, 34 patients undergoing free posterior interosseous flap had preoperative Doppler mapping to determine the point of emergence of the skin perforators of the posterior interosseous artery.