Evaluation of Midodrine Utilization in Patients with Cancer and Heart Failure.

PURPOSE: The purpose of this study was to evaluate safety and cardiovascular outcomes as well as overall survival of cancer patients with concomitant heart failure (HF) treated with midodrine for hypotension. METHODS: Adult patients diagnosed with cancer and HF who were treated with midodrine at a tertiary cancer center from 03/2013 to 08/2021 were identified. Demographic and clinical parameters were collected retrospectively. RESULTS: A total of 85 patients were included with a median age of 68 years (IQR: 60, 74; 33% female and 85% White). Of those, 31% had HFpEF (EF ≥ 50%), 42% HF with mildly reduced EF (HFmrEF; EF 41-49%), and 27% HFrEF (EF ≤ 40%). The most common indication for midodrine use was orthostatic hypotension (49%). Midodrine was continued for at least one month in 57% of the patients. Supine hypertension was the only side effect reported in 6% of patients. No statistically significant changes in NYHA class, guideline-directed medical therapy, cardiac biomarkers (NT-proBNP or troponin T), echocardiographic findings or cardiovascular hospitalizations were observed between patients who continued treatment with midodrine compared to those who stopped using midodrine over a median follow-up of 38 months. In the multivariable cox regression analysis, continuation of midodrine, compared to discontinuation, and use of midodrine for orthostatic hypotension, as opposed to other causes of hypotension, were not associated with an increased risk of mortality (HR 0.41, 95% CI 0.24-0.69, p < .0001; HR 0.34, 95% CI 0.18-0.64, p < .001, respectively). In contrast, elevated creatinine (> 1.3 for males and > 1.1 for females) was associated with an increased risk of mortality (HR 1.83, 95% CI 1.07-3.14). LVEF was not significantly associated with lower or higher risk of mortality. CONCLUSIONS: In our study, midodrine use in patients with cancer and HF was not associated with significant adverse effects, worse cardiovascular outcomes, or increased risk of mortality. Larger, prospective studies are needed to confirm these findings.

Scribl: an HTML5 Canvas-based graphics library for visualizing genomic data over the web.

MOTIVATION: High-throughput biological research requires simultaneous visualization as well as analysis of genomic data, e.g. read alignments, variant calls and genomic annotations. Traditionally, such integrative analysis required desktop applications operating on locally stored data. Many current terabyte-size datasets generated by large public consortia projects, however, are already only feasibly stored at specialist genome analysis centers. As even small laboratories can afford very large datasets, local storage and analysis are becoming increasingly limiting, and it is likely that most such datasets will soon be stored remotely, e.g. in the cloud. These developments will require web-based tools that enable users to access, analyze and view vast remotely stored data with a level of sophistication and interactivity that approximates desktop applications. As rapidly dropping cost enables researchers to collect data intended to answer questions in very specialized contexts, developers must also provide software libraries that empower users to implement customized data analyses and data views for their particular application. Such specialized, yet lightweight, applications would empower scientists to better answer specific biological questions than possible with general-purpose genome browsers currently available. RESULTS: Using recent advances in core web technologies (HTML5), we developed Scribl, a flexible genomic visualization library specifically targeting coordinate-based data such as genomic features, DNA sequence and genetic variants. Scribl simplifies the development of sophisticated web-based graphical tools that approach the dynamism and interactivity of desktop applications. AVAILABILITY AND IMPLEMENTATION: Software is freely available online at http://chmille4.github.com/Scribl/ and is implemented in JavaScript with all modern browsers supported.

Scotty: a web tool for designing RNA-Seq experiments to measure differential gene expression.

MOTIVATION: A common question arises at the beginning of every experiment where RNA-Seq is used to detect differential gene expression between two conditions: How many reads should we sequence? RESULTS: Scotty is an interactive web-based application that assists biologists to design an experiment with an appropriate sample size and read depth to satisfy the user-defined experimental objectives. This design can be based on data available from either pilot samples or publicly available datasets. AVAILABILITY: Scotty can be freely accessed on the web at http://euler.bc.edu/marthlab/scotty/scotty.php

Inpatient Corridor Visibility and Care Team Communication.

OBJECTIVE: This article aims to investigate the impact of fine-grained differences in unit layout on care staff corridor communication. BACKGROUND: Corridor design can be undertaken with greater emphasis on space and cost efficiency or with greater emphasis on affording quality knowledge workspace. Building on prior research on care team communication and inpatient unit design, this study aims to gain a better understanding of how corridor layout properties affect care team communication. METHOD: This study used space syntax analysis to characterize inpatient unit design, specifically floor-plan layout. Two approaches were used to capture care team communication: behavior mapping with recording of care team member locations and whether they were communicating and the HDR CARE Scale, Inpatient Version. The two units were part of a vertical tower expansion project, and, though constructed at separate times, they maintain the same organizational culture, floor plate, and location of key vertical elements. RESULTS: The newer unit was found to be more visually open using three measures from space syntax. More nursing staff verbal communication was observed on this unit. Across both units, nursing staff were more likely to be observed verbally communicating in locations that were more visually connected (i.e., at locations with larger viewsheds). There were no significant differences between nursing staff self-report on work using the HDR CARE Scale, Inpatient Version. CONCLUSION: We conclude that care team communication may tend to be encouraged by visual connectivity that can be promoted through floor-plan layout.

Racial Disparities in Opioid Use and Lumbar Spine Surgery for Chronic Pain and in Pain and Function Over 3 Years: A Retrospective Cohort Study.

This study aims to compare treatments and outcomes among Black and White patients with chronic low back pain in the United States. A retrospective cohort study was conducted within a pain research registry, including 1,443 participants with up to 3 years of follow-up. Pain treatments were measured at quarterly research encounters using reported current opioid use and prior lumbar spine surgery. Pain intensity and functional disability were also measured quarterly with a numerical rating scale and the Roland-Morris Disability Questionnaire, respectively. Longitudinal data were analyzed with generalized estimating equations, including multivariable models to measure temporal trends and adjust for potential confounders. The mean baseline age of participants was 53.5 years (SD, 13.1 years); 1,074 (74.4%) were female, and 260 (18.0%) were Black. In longitudinal multivariable analyses, Black participants reported more frequent current opioid use (odds ratio, 1.40; 95% confidence interval [CI], 1.03-1.91; P = .03) and less frequent lumbar spine surgery (odds ratio, .45; 95% CI, .28-.72; P < .001). Black participants also reported greater pain intensity (mean, 6.6; 95% CI, 6.3-6.9 vs mean, 5.6; 95% CI, 5.4-5.8; P < .001) and functional disability (mean, 15.3; 95% CI, 14.6-16.0 vs mean, 13.8; 95% CI, 13.2-14.3; P = .002). Racial disparities were clinically important (risk ratio = 1.28 and risk ratio = .49, respectively, for opioid use and surgery; and d = .46 and d = .24, respectively, for pain and function). Racial disparities in pain and function also widened over time. Thus, barriers to guideline-adherent and specialized pain care among Black patients may affect pain and function outcomes. Greater efforts are needed to address the observed racial disparities. PERSPECTIVE: Widening racial disparities in pain and function over time indicate that new approaches to chronic pain management are needed in the United States. Considering race as a social framework represents an emerging strategy for planning and improving pain treatment services for Black patients.

Childhood vision impairment and blindness in West Africa: public health measures and implications for systemic health.

Childhood blindness is an issue of global health impact, affecting approximately 2 million children worldwide. Vision 2020 and the United Nations Sustainable Development Goals previously identified childhood blindness as a key issue in the twentieth century, and while public health measures are underway, the precise etiologies and management require ongoing investigation and care, particularly within resource-limited settings such as sub-Saharan Africa. We systematically reviewed the literature on childhood blindness in West Africa to identify the anatomic classification and etiologies, particularly those causes of childhood blindness with systemic health implications. Treatable causes included cataract, refractive error, and corneal disease. Systemic etiologies identified included measles, rubella, vitamin A deficiency, and Ebola virus disease. While prior public health measures including vitamin A supplementation and vaccination programs have been deployed in most countries with reported data, multiple studies reported preventable or reversible etiologies of blindness and vision impairment. Ongoing research is necessary to standardize reporting for anatomies and/or etiologies of childhood blindness to determine the necessity of further development and implementation of public health measures that would ameliorate childhood blindness and vision impairment.

Biogem: an effective tool-based approach for scaling up open source software development in bioinformatics.

SUMMARY: Biogem provides a software development environment for the Ruby programming language, which encourages community-based software development for bioinformatics while lowering the barrier to entry and encouraging best practices. Biogem, with its targeted modular and decentralized approach, software generator, tools and tight web integration, is an improved general model for scaling up collaborative open source software development in bioinformatics. AVAILABILITY: Biogem and modules are free and are OSS. Biogem runs on all systems that support recent versions of Ruby, including Linux, Mac OS X and Windows. Further information at http://www.biogems.info. A tutorial is available at http://www.biogems.info/howto.html CONTACT: bonnal@ingm.org.

Mobile ELISA with a Transparent Incubator.

Enzyme-linked immunosorbent assay (ELISA) is one of the most important technologies for biochemical testing critical for diagnosis and monitoring of many diseases. Traditional systems for ELISA incubation and reading are expensive and bulky, thus cannot be used at point-of-care or in the field. Here, we designed and demonstrated a new miniature mobile phone-based system for ELISA. This mHealth system can be used to complete all steps of the assay, including incubation and reading. It can be fabricated at low cost, it is portable, and can transfer test results via mobile phone. We have designed incubation chamber, imaging enclosure, and data processing algorithm. We demonstrate how mobile ELISA can be calibrated for accurate measurements of cortisol and show successful measurements with the calibrated system. We show that the results acquired with our prototype match well the results obtained with the gold standard.

The effectiveness of reducing endotracheal cuff pressure after retractor placement to decrease postoperative laryngeal dysfunction in anterior cervical surgery: a meta-analysis.

OBJECTIVE: The authors sought to determine if a consensus could be reached regarding the effectiveness of endotracheal tube cuff pressure (ETTCP) reduction after retractor placement in reducing postoperative laryngeal dysfunction after anterior cervical fusion surgery. METHODS: A literature search of MEDLINE (PubMed), EMBASE, Cochrane Central, Google Scholar, and Scopus databases was performed. Quantitative analysis was performed on data from articles comparing groups of patients with either reduced or unadjusted ETTCP after retractor placement in the context of anterior cervical surgery. The incidence and severity of postoperative recurrent laryngeal nerve palsy (RLNP), dysphagia, and dysphonia were compared at several postsurgical time points, ranging from 24 hours to 3 months. Heterogeneity was assessed using the chi-square test, I2 statistics, and inverted funnel plots. A random-effects model was used to provide a conservative estimate of the level of effect. RESULTS: Nine studies (7 randomized, 1 prospective, and 1 retrospective) were included in the analysis. A total of 1671 patients were included (1073 [64.2%] in the reduced ETTCP group and 598 [35.8%] in the unadjusted ETTCP group). In the reduced ETTCP group, the severity of dysphagia, measured by the Bazaz-Yoo system in 3 randomized studies at 24 hours and at 4-8 weeks, was significantly lower (24 hours [standardized mean difference: -1.83, p = 0.04] and 4-8 weeks [standardized mean difference: -0.40, p = 0.05]). At 24 hours, the odds of developing dysphonia were significantly lower (OR 0.51, p = 0.002). The odds of dysphagia (24 hours: OR 0.77, p = 0.24; 1 week: OR 0.70, p = 0.47; 12 weeks: OR 0.58, p = 0.20) were lower, although not significantly, in the reduced ETTCP group. The odds of a patient having RLNP were significantly lower at all time points (24 hours: OR 0.38, p = 0.01; 12 weeks: OR 0.26, p = 0.03) when 3 randomized and 2 observational studies were analyzed. A subgroup analysis using only randomized studies demonstrated a similar trend in odds of having RLNP, yet without statistical significance (24 hours: OR 0.79, p = 0.60). All other statistically significant findings persisted with removal of any observational data. CONCLUSIONS: Based on the current best available evidence, reduction of ETTCP after retractor placement in anterior cervical surgery may be a protective measure to decrease the severity of dysphagia and the odds of developing RLNP or dysphonia.

Analysis of urgent follow up visits and complications after intravitreal injections: a retrospective cohort study.

BACKGROUND: Intravitreal injections (IVIs), a common treatment in ophthalmology, result in acute complications and urgent follow-up visits causing significant burden to both patient and physician. We evaluated the incidence of acute complications following IVIs which occurred within seven days of injection. METHODS: A retrospective cohort study conducted at a private retinal practice, in Cleveland, Ohio. Using the practice management software database, we examined 73,286 injections of patients with unscheduled or urgent visits within 7 days of an injection from August 1st,2018 to August 1st,2020. Data collected included: age, gender, eye, medication injected, diagnosis, reason for urgent follow-up, time between injection and urgent follow-up, and type of anesthesia administered. Data was analyzed using SPSS v.28 (SPSS Inc., Chicago IL). RESULTS: Study included 73,286 injections, with 441 injections (n = 441) resulting in urgent follow-up visits (0.60%). Mean patient age was 72.1 (± 30.4) years, with 187 male (42.4%) and 254 female (57.6%) patients. IVI medications included: aflibercept (60.3%), ranibizumab (22.4%), bevacizumab (13.4%), dexamethasone intravitreal implant (2%), triamcinolone acetonide (1.6%) brolucizumab (1.59%), fluocinolone acetonide intravitreal implant 0.19 mg (0.2%), and fluocinolone acetonide intravitreal implant 0.18 mg (0.03%) (Table 1). Medications associated with urgent visits included: aflibercept (42.9%), bevacizumab (37.4%), ranibizumab (7.9%), dexamethasone intravitreal implant (6.8%), brolucizumab (2.7%), and triamcinolone acetonide (2.3%) (Table 2). Days between injection and urgent follow-up was on average 3.96 ± 2.14 days. Urgent follow-ups included blurred vision in 164 patients (37.2% of urgent visits), flashes, floaters or posterior vitreous detachment (PVD) in 55 (12.5%), pain in 42 (9.5%), 43 (9.8%) corneal abrasions, 33 (7.5%) subconjunctival hemorrhages, corneal dryness or foreign body sensation in 30 (6.6%), endophthalmitis in 20 (4.5%), 18 (4.1%)vitreous hemorrhages, iritis or uveitis in 11 (2.5%), miscellaneous complications in 9 (2.0%), 7 (1.6%) elevated intraocular pressures, choroidal neovascular membrane in 4 (0.9%), 4 (0.9%) retinal detachments or tears, and 2 (0.45%) traumatic cataracts (Table 3). CONCLUSION: IVIs resulted in 0.60% urgent/unscheduled follow-up visits within 7 days of injection. Most common causes were blurred vision and symptoms of PVD.

Frequency and Symptoms of Intravitreal Silicone Oil Droplets Following Becton Dickinson and Norm-Ject Bevacizumab Injections.

BACKGROUND AND OBJECTIVE: To determine silicone oil droplet frequency and symptomatic impact in patients injected with Norm-Ject (NJ) and/or Becton Dickinson (BD) intravitreal bevacizumab. PATIENTS AND METHODS: This was a retrospective cohort study of 426 patients with prior bevacizumab injection(s). Symptomatic floaters questionnaire responses were compiled and statistical analysis was performed using Fisher's exact t test with 95% CI calculated via the modified Wald method. RESULTS: Patients who received BD intravitreal bevacizumab showed more droplets (67.2%) than those who received NJ intravitreal bevacizumab (7.8%), and droplets increased with injection quantity. However, the symptomatic patients reporting new floaters were similar (NJ: 39.22%, BD: 39.47%). [Ophthalmic Surg Lasers Imaging Retina. 2022;53:108-112.].

BIO::Phylo-phyloinformatic analysis using perl.

BACKGROUND: Phyloinformatic analyses involve large amounts of data and metadata of complex structure. Collecting, processing, analyzing, visualizing and summarizing these data and metadata should be done in steps that can be automated and reproduced. This requires flexible, modular toolkits that can represent, manipulate and persist phylogenetic data and metadata as objects with programmable interfaces. RESULTS: This paper presents Bio::Phylo, a Perl5 toolkit for phyloinformatic analysis. It implements classes and methods that are compatible with the well-known BioPerl toolkit, but is independent from it (making it easy to install) and features a richer API and a data model that is better able to manage the complex relationships between different fundamental data and metadata objects in phylogenetics. It supports commonly used file formats for phylogenetic data including the novel NeXML standard, which allows rich annotations of phylogenetic data to be stored and shared. Bio::Phylo can interact with BioPerl, thereby giving access to the file formats that BioPerl supports. Many methods for data simulation, transformation and manipulation, the analysis of tree shape, and tree visualization are provided. CONCLUSIONS: Bio::Phylo is composed of 59 richly documented Perl5 modules. It has been deployed successfully on a variety of computer architectures (including various Linux distributions, Mac OS X versions, Windows, Cygwin and UNIX-like systems). It is available as open source (GPL) software from http://search.cpan.org/dist/Bio-Phylo.

Comparison of Visual Outcome After Hyperopic LASIK Using a Wavefront-Optimized Platform Versus Other Excimer Lasers in the Past Two Decades.

INTRODUCTION: Laser-assisted in-situ keratomileusis (LASIK) for the correction of hyperopia and hyperopic astigmatism is challenging and has been less studied than for the correction of myopia and myopic astigmatism. The aim of this study was to analyze the refractive outcomes of LASIK in hyperopia and hyperopic astigmatic eyes using a wave-front optimized laser platform (the Allegretto EX500 laser) and perform a historical comparison with other excimer lasers within the past two decades. METHODS: A one-center (Tertiary Refractive Center, Draper, Utah), retrospective, non-comparative study was conducted on 379 eyes treated with LASIK for hyperopia and hyperopic astigmatism. The data retrieved on these eyes were analyzed using uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalents. A literature search of excimer platforms in use in the past 20 years and a comparison of US Federal Drug Administration-approved platforms for hyperopia were performed. RESULTS: At 3 and 12 months postoperatively, 142 (66%) and 81 (69%) eyes had a UDVA of 20/20 or better and 207 (96%) and 114 (97%) eyes had a UDVA of 20/40 or better, respectively. The mean refractive spherical equivalent was - 0.52 ± 0.78 D at 3 months and - 0.46 ± 0.79 D at 12 months. At 12 months, 181 (96%) eyes achieved a spherical equivalent within ± 1.00 D of the intended target. Studies published before 2005 reported lower rates of UDVA 20/20 or better (32%) compared to those published after (68%); however, this discrepancy was less evident for UDVA 20/40 or better. A similar trend towards improved accuracy was noted in the literature with postoperative manifest refractive spherical equivalent within ± 0.50 D before and after 2005. CONCLUSION: There has been significant improvement in safety, efficacy, stability, and accuracy of LASIK treatment for hyperopia and hyperopic astigmatism within the past two decades. Newer excimer lasers meet industry standards and in particular, the Allegretto EX500 used in this study exceeded industry standards.

Five-Year Occurrence and Management of Central Toxic Keratopathy After Femtosecond Laser-Assisted LASIK.

PURPOSE: To report the 5-year occurrence, management, and outcomes of 12 eyes diagnosed as having central toxic keratopathy (CTK) after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A retrospective chart review was conducted on 20,622 FS-LASIK procedures performed at a single site from January 2015 to December 2019 to identify patients diagnosed as having central toxic keratopathy. Preoperative and postoperative visual acuity, refraction, and imaging were recorded and analyzed. RESULTS: CTK occurred in 12 eyes of 8 patients after FSLASIK. A total of 75% of eyes were diagnosed during an outbreak that happened over 2 months and the remaining 25% were considered sporadic. Five eyes were treated with flap lift and irrigation and 7 eyes were treated non-surgically. The average time to resolution of CTK in eyes that underwent flap lift and irrigation was 53 days compared to 33 days in eyes treated non-surgically. All 5 eyes treated with flap lift and irrigation ultimately achieved uncorrected distance visual acuity of 0.1 logMAR or better, whereas only 3 of 7 eyes treated non-surgically achieved the same. At the final postoperative visit, the eyes treated with flap lift and irrigation measured on average 14 µm thinner and 1.60 diopters (D) flatter than the expected postoperative pachymetry and keratometry, respectively. Those treated non-surgically were on average 28 µm thinner and 1.70 D flatter than expected. CONCLUSIONS: CTK is a rare complication of FS-LASIK but can occur in clusters. Although management of CTK is debated, flap lift and irrigation may lead to better visual acuity and refractive and anatomic outcomes in some cases. [J Refract Surg. 2021;37(1):25-31.].

Incidence, Risk, and Visual Outcomes after Repositioning of Acute Non-Traumatic Flap Dislocations Following Femtosecond-Assisted LASIK.

Although the use of femtosecond lasers instead of mechanical devices has decreased the incidence of flap complications following laser-assisted in situ keratomileusis (LASIK), dislocations and striae still occur. Flap repositioning is an effective intervention to improve visual outcomes after acute flap complications in both microkeratome-assisted and femtosecond-assisted LASIK. This retrospective case series included patients undergoing flap repositioning secondary to acute flap dislocation and/or visually significant striae within the first two weeks following femtosecond LASIK (FS-LASIK) from 2015 to 2020 at a single institution. Preoperative, intraoperative, and postoperative de-identified data were analyzed for incidence, risk factors, and visual acuity outcomes. The incidence of flap repositioning was 0.35% in 21,536 eyes (n = 70). Indications for repositioning included acute flap dislocation (35.7%) and visually significant striae (64.3%). High myopia (OR = 3.04, p = 0.001) and patient age over 50 years (OR = 3.69, p = 0.001) were the strongest risk factors for these complications. Prior to flap repositioning, uncorrected distance visual acuity (UDVA) of 20/20 or better and 20/40 or better occurred in 19% and 57% of eyes, respectively. After repositioning, a final UDVA of 20/20 or better and 20/40 or better occurred in 78% and 98% of eyes, respectively. After repositioning, one line of UDVA was lost in two eyes (2.8%) and two lines were lost in one eye (1.4%). Risk factors for acute flap dislocation included high myopia and age over 50 years. Flap repositioning was effective in salvaging visual outcomes.

Gene.iobio: an interactive web tool for versatile, clinically-driven variant interrogation and prioritization.

With increasing utilization of comprehensive genomic data to guide clinical care, anticipated to become the standard of care in many clinical settings, the practice of diagnostic medicine is undergoing a notable shift. However, the move from single-gene or panel-based genetic testing to exome and genome sequencing has not been matched by the development of tools to enable diagnosticians to interpret increasingly complex or uncertain genomic findings. Here, we present gene.iobio, a real-time, intuitive and interactive web application for clinically-driven variant interrogation and prioritization. We show gene.iobio is a novel and effective approach that significantly improves upon and reimagines existing methods. In a radical departure from existing methods that present variants and genomic data in text and table formats, gene.iobio provides an interactive, intuitive and visually-driven analysis environment. We demonstrate that adoption of gene.iobio in clinical and research settings empowers clinical care providers to interact directly with patient genomic data both for establishing clinical diagnoses and informing patient care, using sophisticated genomic analyses that previously were only accessible via complex command line tools.

Five-Year Incidence, Management, and Visual Outcomes of Diffuse Lamellar Keratitis after Femtosecond-Assisted LASIK.

Femtosecond (FS) lasers initially had a higher incidence of diffuse lamellar keratitis (DLK) compared with microkeratome flap creation. It has been theorized that higher-frequency lower-energy (HFLE) FS lasers would reduce the incidence of DLK. Our study sought to evaluate the incidence of newer HFLE FS lasers with pulse frequencies above 60 kHz. It was a retrospective case-control study evaluating the incidence of DLK following flap creation with one of three FS lasers (AMO iFs, WaveLight FS200, Zeiss VisuMax). Uncomplicated LASIK cases were included as the control group (14,348 eyes) and cases of DLK were recorded in the study group (637 eyes). Of the 637 cases of DLK, 76 developed stage II, 25 progressed to stage III, and only three developed stage IV DLK. The overall incidence rate of DLK was 4.3%; it has fallen with the invention of newer HFLE FS lasers and is approaching the DLK incidence rates of DLK with microkeratome.

An Sp185/333 gene cluster from the purple sea urchin and putative microsatellite-mediated gene diversification.

BACKGROUND: The immune system of the purple sea urchin, Strongylocentrotus purpuratus, is complex and sophisticated. An important component of sea urchin immunity is the Sp185/333 gene family, which is significantly upregulated in immunologically challenged animals. The Sp185/333 genes are less than 2 kb with two exons and are members of a large diverse family composed of greater than 40 genes. The S. purpuratus genome assembly, however, contains only six Sp185/333 genes. This underrepresentation could be due to the difficulties that large gene families present in shotgun assembly, where multiple similar genes can be collapsed into a single consensus gene. RESULTS: To understand the genomic organization of the Sp185/333 gene family, a BAC insert containing Sp185/333 genes was assembled, with careful attention to avoiding artifacts resulting from collapse or artificial duplication/expansion of very similar genes. Twelve candidate BAC assemblies were generated with varying parameters and the optimal assembly was identified by PCR, restriction digests, and subclone sequencing. The validated assembly contained six Sp185/333 genes that were clustered in a 34 kb region at one end of the BAC with five of the six genes tightly clustered within 20 kb. The Sp185/333 genes in this cluster were no more similar to each other than to previously sequenced Sp185/333 genes isolated from three different animals. This was unexpected given their proximity and putative effects of gene homogenization in closely linked, similar genes. All six genes displayed significant similarity including both 5' and 3' flanking regions, which were bounded by microsatellites. Three of the Sp185/333 genes and their flanking regions were tandemly duplicated such that each repeated segment consisted of a gene plus 0.7 kb 5' and 2.4 kb 3' of the gene (4.5 kb total). Both edges of the segmental duplications were bounded by different microsatellites. CONCLUSIONS: The high sequence similarity of the Sp185/333 genes and flanking regions, suggests that the microsatellites may promote genomic instability and are involved with gene duplication and/or gene conversion and the extraordinary sequence diversity of this family.

gene.iobio: an interactive web tool for versatile, clinically-driven variant interrogation and prioritization.

With increasing utilization of comprehensive genomic data to guide clinical care, anticipated to become the standard of care in many clinical settings, the practice of diagnostic medicine is undergoing a notable shift. However, the move from single-gene or panel-based genetic testing to exome and genome sequencing has not been matched by the development of tools to enable diagnosticians to interpret increasingly complex genomic findings. A new paradigm has emerged, where genome-based tests are often evaluated by a large multi-disciplinary collaborative team, typically including a diagnostic pathologist, a bioinformatician, a genetic counselor, and often a subspeciality clinician. This team-based approach calls for new computational tools to allow every member of the clinical care provider team, at varying levels of genetic knowledge and diagnostic expertise, to quickly and easily analyze and interpret complex genomic data. Here, we present gene.iobio , a real-time, intuitive and interactive web application for clinically-driven variant interrogation and prioritization. We show gene.iobio is a novel and effective approach that significantly improves upon and reimagines existing methods. In a radical departure from existing methods that present variants and genomic data in text and table formats, gene.iobio provides an interactive, intuitive and visually-driven analysis environment. We demonstrate that adoption of gene.iobio in clinical and research settings empowers clinical care providers to interact directly with patient genomic data both for establishing clinical diagnoses and informing patient care, using sophisticated genomic analyses that previously were only accessible via complex command line tools.