An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Development of an extensible dual-core wireless sensing node for cyber-physical systems

The introduction of wireless telemetry into the design of monitoring and control systems has been shown to reduce system costs while simplifying installations. To date, wireless nodes proposed for sensing and actuation in cyberphysical systems have been designed using microcontrollers with one computational pipeline (i.e., single-core microcontrollers). While concurrent code execution can be implemented on single-core microcontrollers, concurrency is emulated by splitting the pipeline\u27s resources to support multiple threads of code execution. For many applications, this approach to multi-threading is acceptable in terms of speed and function. However, some applications such as feedback controls demand deterministic timing of code execution and maximum computational throughput. For these applications, the adoption of multi-core processor architectures represents one effective solution. Multi-core microcontrollers have multiple computational pipelines that can execute embedded code in parallel and can be interrupted independent of one another. In this study, a new wireless platform named Martlet is introduced with a dual-core microcontroller adopted in its design. The dual-core microcontroller design allows Martlet to dedicate one core to standard wireless sensor operations while the other core is reserved for embedded data processing and real-time feedback control law execution. Another distinct feature of Martlet is a standardized hardware interface that allows specialized daughter boards (termed wing boards) to be interfaced to the Martlet baseboard. This extensibility opens opportunity to encapsulate specialized sensing and actuation functions in a wing board without altering the design of Martlet. In addition to describing the design of Martlet, a few example wings are detailed, along with experiments showing the Martlet\u27s ability to monitor and control physical systems such as wind turbines and buildings. © 2014 SPIE

Understanding Treatment Preferences for Patients with Tricuspid Regurgitation

Background. Tricuspid regurgitation (TR) is a high-prevalence disease associated with poor quality of life and mortality. This quantitative patient preference study aims to identify TR patients’ perspectives on risk-benefit tradeoffs. Methods. A discrete-choice experiment was developed to explore TR treatment risk-benefit tradeoffs. Attributes (levels) tested were treatment (procedure, medical management), reintervention risk (0%, 1%, 5%, 10%), medications over 2 y (none, reduce, same, increase), shortness of breath (none/mild, moderate, severe), and swelling (never, 3× per week, daily). A mixed logit regression model estimated preferences and calculated predicted probabilities. Relative attribute importance was calculated. Subgroup analyses were performed. Results. An online survey was completed by 150 TR patients. Shortness of breath was the most important attribute and accounted for 65.8% of treatment decision making. The average patients’ predicted probability of preferring a “procedure-like” profile over a “medical management-like” profile was 99.7%. This decreased to 78.9% for a level change from severe to moderate in shortness of breath in the “medical management-like” profile. Subgroup analysis confirmed that patients older than 64 y had a stronger preference to avoid severe shortness of breath compared with younger patients ( P  < 0.02), as did severe or worse TR patients relative to moderate. New York Heart Association class I/II patients more strongly preferred to avoid procedural reintervention risk relative to class III/IV patients ( P  < 0.03). Conclusion. TR patients are willing to accept higher procedural reintervention risk if shortness of breath is alleviated. This risk tolerance is higher for older and more symptomatic patients. These results emphasize the appropriateness of developing TR therapies and the importance of addressing symptom burden. Highlights This study provides quantitative patient preference data from clinically confirmed tricuspid regurgitation (TR) patients to understand their treatment preferences. Using a targeted literature search and patient, physician, and Food and Drug Administration feedback, a cross-sectional survey with a discrete-choice experiment that focused on 5 of the most important attributes to TR patients was developed and administered online. TR patients are willing to accept higher procedural reintervention risk if shortness of breath is alleviated, and this risk tolerance is higher for older and more symptomatic patients

The major surface protein of malaria sporozoites is GPI-anchored to the plasma membrane

Glycosylphosphatidylinositol (GPI) anchor protein modification in Plasmodium species is well known and represents the principal form of glycosylation in these organisms. The structure and biosynthesis of GPI anchors of Plasmodium spp. has been primarily studied in the asexual blood stage of P. falciparum and is known to contain the typical conserved GPI structure of EtN-P-Man3GlcN-PI. Here, we have investigated the circumsporozoite protein (CSP) for the presence of a GPI-anchor. CSP is the major surface protein of Plasmodium sporozoites, the infective stage of the malaria parasite. While it is widely assumed that CSP is a GPI-anchored cell surface protein, compelling biochemical evidence for this supposition is absent. Here, we employed metabolic labeling and mass-spectrometry based approaches to confirm the presence of a GPI anchor in CSP. Biosynthetic radiolabeling of CSP with [3H]-palmitic acid and [3H]-ethanolamine, with the former being base-labile and therefore ester-linked, provided strong evidence for the presence of a GPI anchor on CSP, but these data alone were not definitive. To provide further evidence, immunoprecipitated CSP was analyzed for presence of myo-inositol (a characteristic component of GPI anchor) using strong acid hydrolysis and GC-MS for a highly sensitive and quantitative detection. The single ion monitoring (SIM) method for GC-MS analysis confirmed the presence of the myo-inositol component in CSP. Taken together, these data provide confidence that the long-assumed presence of a GPI anchor on this important parasite protein is correct

Spatiotemporal incidence of Zika and associated environmental drivers for the 2015-2016 epidemic in Colombia

Despite a long history of mosquito-borne virus epidemics in the Americas, the impact of the Zika virus (ZIKV) epidemic of 2015–2016 was unexpected. The need for scientifically informed decision-making is driving research to understand the emergence and spread of ZIKV. To support that research, we assembled a data set of key covariates for modeling ZIKV transmission dynamics in Colombia, where ZIKV transmission was widespread and the government made incidence data publically available. On a weekly basis between January 1, 2014 and October 1, 2016 at three administrative levels, we collated spatiotemporal Zika incidence data, nine environmental variables, and demographic data into a single downloadable database. These new datasets and those we identified, processed, and assembled at comparable spatial and temporal resolutions will save future researchers considerable time and effort in performing these data processing steps, enabling them to focus instead on extracting epidemiological insights from this important data set. Similar approaches could prove useful for filling data gaps to enable epidemiological analyses of future disease emergence events

Demo hour: Lichtsuchende

NordiCHI'14 conference attendees got hands-on experience with a number of great new interactive systems. Among the accepted poster, video, and demo submissions, we selected the following four prototypes to illustrate the high-quality design research displayed during the conference, which was held in Helsinki, Finland, October 26--30, 2014

Evaluating the Significance of Paleophylogeographic Species Distribution Models in Reconstructing Quaternary Range-Shifts of Nearctic Chelonians

<div><p>The climatic cycles of the Quaternary, during which global mean annual temperatures have regularly changed by 5–10°C, provide a special opportunity for studying the rate, magnitude, and effects of geographic responses to changing climates. During the Quaternary, high- and mid-latitude species were extirpated from regions that were covered by ice or otherwise became unsuitable, persisting in refugial retreats where the environment was compatible with their tolerances. In this study we combine modern geographic range data, phylogeny, Pleistocene paleoclimatic models, and isotopic records of changes in global mean annual temperature, to produce a temporally continuous model of geographic changes in potential habitat for 59 species of North American turtles over the past 320 Ka (three full glacial-interglacial cycles). These paleophylogeographic models indicate the areas where past climates were compatible with the modern ranges of the species and serve as hypotheses for how their geographic ranges would have changed in response to Quaternary climate cycles. We test these hypotheses against physiological, genetic, taxonomic and fossil evidence, and we then use them to measure the effects of Quaternary climate cycles on species distributions. Patterns of range expansion, contraction, and fragmentation in the models are strongly congruent with (i) phylogeographic differentiation; (ii) morphological variation; (iii) physiological tolerances; and (iv) intraspecific genetic variability. Modern species with significant interspecific differentiation have geographic ranges that strongly fluctuated and repeatedly fragmented throughout the Quaternary. Modern species with low genetic diversity have geographic distributions that were highly variable and at times exceedingly small in the past. Our results reveal the potential for paleophylogeographic models to (i) reconstruct past geographic range modifications, (ii) identify geographic processes that result in genetic bottlenecks; and (iii) predict threats due to anthropogenic climate change in the future.</p></div

Association of COVID-19 Versus COVID-19 Vaccination With Kidney Function and Disease Activity in Primary Glomerular Disease: A Report of the Cure Glomerulonephropathy Study

Patients with glomerular disease (GN) may be at increased risk of severe COVID-19, yet concerns over vaccines causing disease relapse may lead to vaccine hesitancy. We examined the associations of COVID-19 with longitudinal kidney function and proteinuria and compared these to similar associations with COVID-19 vaccination. Observational cohort study from July 1, 2021 to Jan. 1, 2023. & Participants: A prospective observational study network of 71 centers from North America and Europe (CureGN) with children and adults with primary minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy. COVID-19 and COVID-19 vaccination. Repeated measure of estimated glomerular filtration rate (eGFR); recurrent time-to-event outcome of GN disease worsening as defined by doubling of UPCR to at least 1.5g/g or increase in dipstick urine protein by two ordinal levels to 3+ (300mg/dL) or above. Interrupted time series analysis for eGFR. Prognostic matched sequential stratification recurrent event analysis for GN disease worsening. Among 2,055 participants, 722 (35%) reported COVID-19; of these, 92 (13%) were hospitalized and 3 died (<1%). eGFR slope pre-COVID-19 was -1.40ml/min/1.73m2 (SD 0.29), and -4.26ml/min/1.73m2 (SD 3.02) within 6 months post-COVID-19, which were not significantly different (p=0.34). COVID-19 was associated with increased risk of worsening GN disease activity (HR 1.35, 95% CI 1.01-1.80). Vaccination was not associated with change in eGFR (-1.34ml/min/1.73m2, SD 0.15 vs -2.16ml/min/1.73m2, SD 1.74; p=0.6) or subsequent GN disease worsening (HR 1.02, 95% CI 0.79–1.33) in this cohort. Infrequent or short follow-up. Among patients with primary GN, COVID-19 was severe for 1 in 8 cases and was associated with subsequent worsening of GN disease activity, as defined by proteinuria. In contrast, vaccination against COVID-19 was not associated with change in disease activity or kidney function decline. These results support COVID-19 vaccination for patients with GN. In this cohort study of 2,055 patients with minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy, COVID-19 resulted in hospitalization or death for 1 in 8 cases and was associated with a 35% increase in risk for worsening proteinuria. In contrast, vaccination did not appear to adversely affect kidney function or proteinuria. Our data support vaccination for COVID-19 in patients with glomerular disease