Capture Of Events Research Articles

Ultrafast laser-scanning time-stretch imaging at visible wavelengths

Optical time-stretch imaging enables the continuous capture of non-repetitive events in real time at a line-scan rate of tens of MHz—a distinct advantage for the ultrafast dynamics monitoring and high-throughput screening that are widely needed in biological microscopy. However, its potential is limited by the technical challenge of achieving significant pulse stretching (that is, high temporal dispersion) and low optical loss, which are the critical factors influencing imaging quality, in the visible spectrum demanded in many of these applications. We present a new pulse-stretching technique, termed free-space angular-chirp-enhanced delay (FACED), with three distinguishing features absent in the prevailing dispersive-fiber-based implementations: (1) it generates substantial, reconfigurable temporal dispersion in free space (>1 ns nm−1) with low intrinsic loss (<6 dB) at visible wavelengths; (2) its wavelength-invariant pulse-stretching operation introduces a new paradigm in time-stretch imaging, which can now be implemented both with and without spectral encoding; and (3) pulse stretching in FACED inherently provides an ultrafast all-optical laser-beam scanning mechanism at a line-scan rate of tens of MHz. Using FACED, we demonstrate not only ultrafast laser-scanning time-stretch imaging with superior bright-field image quality compared with previous work but also, for the first time, MHz fluorescence and colorized time-stretch microscopy. Our results show that this technique could enable a wider scope of applications in high-speed and high-throughput biological microscopy that were once out of reach.

The validation of electronic health records in accurately identifying patients eligible for colorectal cancer screening in safety net clinics.

While electronic health records (EHRs) play a key role in increasing colorectal cancer (CRC) screening by identifying individuals who are overdue, important shortfalls remain. As part of the Strategies and Opportunities to STOP Colon Cancer (STOP CRC) study, we assessed the accuracy of EHR codes in identifying patients eligible for CRC screening. We selected a stratified random sample of 800 study participants from 26 participating clinics, in the Pacific Northwest region of the USA. We compared data obtained through codes in the EHR to conduct a manual chart audit. A trained chart abstractor completed the abstraction of eligible and ineligible patients. Of 520 individuals in need of CRC screening, identified via the EHR, 459 were confirmed through chart review (positive predictive value = 88%). Of 280 individuals flagged as up-to-date in their screening per EHR data, 269 were confirmed through chart review (negative predictive value = 96%). Among the 61 patients incorrectly classified as eligible, 83.6% of disagreements were due to evidence of a prior colonoscopy or referral that was not captured in recognizable fields in the EHR. Our findings highlight importance of better capture of past screening events in the EHR. While the need for better population-based data is not unique to CRC screening, it provides an important example of the use of population-based data not only for tracking care, but also for delivering interventions.

Spread-Spectrum Beamforming and Clutter Filtering for Plane-Wave Color Doppler Imaging.

Plane-wave imaging is desirable for its ability to achieve high frame rates, allowing the capture of fast dynamic events and continuous Doppler data. In most implementations of plane-wave imaging, multiple low-resolution images from different plane wave tilt angles are compounded to form a single high-resolution image, thereby reducing the frame rate. Compounding improves the lateral beam profile in the high-resolution image, but it also acts as a low-pass filter in slow time that causes attenuation and aliasing of signals with high Doppler shifts. This paper introduces a spread-spectrum color Doppler imaging method that produces high-resolution images without the use of compounding, thereby eliminating the tradeoff between beam quality, maximum unaliased Doppler frequency, and frame rate. The method uses a long, random sequence of transmit angles rather than a linear sweep of plane wave directions. The random angle sequence randomizes the phase of off-focus (clutter) signals, thereby spreading the clutter power in the Doppler spectrum, while keeping the spectrum of the in-focus signal intact. The ensemble of randomly tilted low-resolution frames also acts as the Doppler ensemble, so it can be much longer than a conventional linear sweep, thereby improving beam formation while also making the slow-time Doppler sampling frequency equal to the pulse repetition frequency. Experiments performed using a carotid artery phantom with constant flow demonstrate that the spread-spectrum method more accurately measures the parabolic flow profile of the vessel and outperforms conventional plane-wave Doppler in both contrast resolution and estimation of high flow velocities. The spread-spectrum method is expected to be valuable for Doppler applications that require measurement of high velocities at high frame rates.

Abstract 3376: Molecular drivers of endothelial hypoxic adaption during angiogenesis deciphered using the Berg Interrogative Biology® platform

Abstract Angiogenesis is a key feature of tumor progression providing oxygen and nutrients required for tumor cell growth, hypoxia being a major driver of this phenomenon. A systems biology approach using the Berg Interrogative Biology® platform was implemented to identify drivers of the endothelial cell (EC) angiogenic response to hypoxia. To determine the proteomic profile of proliferating ECs and non-proliferating confluent ECs exposed to normoxia or hypoxia, a functional proteomic approach employing activity-based probes and phosphorylation analysis was utilized. Kinases and ATPases were labeled with ATP-binding domain enrichment probes and titanium dioxide enrichment of phosphopeptides was employed for capture of protein phosphorylation events. Phenotypic assays including proliferation rates, apoptosis, mitochondrial superoxide and ROS/NO signaling were included as a measure of EC phenotype. Comparative proteomics, kinase activity, phosphoproteomics and assay data were integrated using an AI based Bayesian Network Inference approach to investigate causal signaling networks in order to elucidate the complexity and dynamics of angiogenesis and more specifically, the role of hypoxia in driving intracellular signaling in response to changes in oxygen tension. High confidence causal networks identified novel proteins that modulate the EC hypoxic response, validation of which are in process. Previously characterized proteins that are responsive to hypoxia were also identified in the hypoxic, but not normoxic signaling networks, namely Aldoc, Rac1, mTor, Cav-1 and Bax. Endothelial proliferation rate is closely related to both hydrogen peroxide and nitric oxide signaling, as has previously been reported. Novel regulatory networks that determine these interactions were identified. Using the Berg Interrogative Biology® platform, we are deciphering both the effects of the hypoxic microenvironment, and the unique characteristics of proliferating ECs by applying integrated functional proteomic assays and a systems approach to determine global changes in intracellular signaling in response to hypoxia. Citation Format: Tony E. Walshe, Justin Bourdelais, Viatcheslav R. Akmaev, Leonardo O. Rodrigues, Socheata Lao, Stephane Gesta, Michael A. Kiebish, Vivek K. Vishnudas, Rangaprasad Sarangarajan, Niven R. Narain. Molecular drivers of endothelial hypoxic adaption during angiogenesis deciphered using the Berg Interrogative Biology® platform. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3376.

Photon-Counting Arrays for Time-Resolved Imaging.

The paper presents a camera comprising 512 × 128 pixels capable of single-photon detection and gating with a maximum frame rate of 156 kfps. The photon capture is performed through a gated single-photon avalanche diode that generates a digital pulse upon photon detection and through a digital one-bit counter. Gray levels are obtained through multiple counting and accumulation, while time-resolved imaging is achieved through a 4-ns gating window controlled with subnanosecond accuracy by a field-programmable gate array. The sensor, which is equipped with microlenses to enhance its effective fill factor, was electro-optically characterized in terms of sensitivity and uniformity. Several examples of capture of fast events are shown to demonstrate the suitability of the approach.

Integrative Phosphoproteomics Links IL-23R Signaling with Metabolic Adaptation in Lymphocytes.

Interleukin (IL)-23 mediated signal transduction represents a major molecular mechanism underlying the pathology of inflammatory bowel disease, Crohn’s disease and ulcerative colitis. In addition, emerging evidence supports the role of IL-23-driven Th17 cells in inflammation. Components of the IL-23 signaling pathway, such as IL-23R, JAK2 and STAT3, have been characterized, but elements unique to this network as compared to other interleukins have not been readily explored. In this study, we have undertaken an integrative phosphoproteomics approach to better characterise downstream signaling events. To this end, we performed and compared phosphopeptide and phosphoprotein enrichment methodologies after activation of T lymphocytes by IL-23. We demonstrate the complementary nature of the two phosphoenrichment approaches by maximizing the capture of phosphorylation events. A total of 8202 unique phosphopeptides, and 4317 unique proteins were identified, amongst which STAT3, PKM2, CDK6 and LASP-1 showed induction of specific phosphorylation not readily observed after IL-2 stimulation. Interestingly, quantitative analysis revealed predominant phosphorylation of pre-existing STAT3 nuclear subsets in addition to translocation of phosphorylated STAT3 within 30 min after IL-23 stimulation. After IL-23R activation, a small subset of PKM2 also translocates to the nucleus and may contribute to STAT3 phosphorylation, suggesting multiple cellular responses including metabolic adaptation.

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin)

The genome is the target of some of the most effective chemotherapeutics, but most of these drugs lack DNA sequence specificity, which leads to dose-limiting toxicity and many adverse side effects. Targeting the genome with sequence-specific small molecules may enable molecules with increased therapeutic index and fewer off-target effects. N-methylpyrrole/N-methylimidazole polyamides are molecules that can be rationally designed to target specific DNA sequences with exquisite precision. And unlike most natural transcription factors, polyamides can bind to methylated and chromatinized DNA without a loss in affinity. The sequence specificity of polyamides has been extensively studied in vitro with cognate site identification (CSI) and with traditional biochemical and biophysical approaches, but the study of polyamide binding to genomic targets in cells remains elusive. Here we report a method, the crosslinking of small molecules to isolate chromatin (COSMIC), that identifies polyamide binding sites across the genome. COSMIC is similar to chromatin immunoprecipitation (ChIP), but differs in two important ways: (1) a photocrosslinker is employed to enable selective, temporally-controlled capture of polyamide binding events, and (2) the biotin affinity handle is used to purify polyamide–DNA conjugates under semi-denaturing conditions to decrease DNA that is non-covalently bound. COSMIC is a general strategy that can be used to reveal the genome-wide binding events of polyamides and other genome-targeting chemotherapeutic agents.

Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC (Crosslinking of Small Molecules to Isolate Chromatin).

The genome is the target of some of the most effective chemotherapeutics, but most of these drugs lack DNA sequence specificity, which leads to dose-limiting toxicity and many adverse side effects. Targeting the genome with sequence-specific small molecules may enable molecules with increased therapeutic index and fewer off-target effects. N-methylpyrrole/N-methylimidazole polyamides are molecules that can be rationally designed to target specific DNA sequences with exquisite precision. And unlike most natural transcription factors, polyamides can bind to methylated and chromatinized DNA without a loss in affinity. The sequence specificity of polyamides has been extensively studied in vitro with cognate site identification (CSI) and with traditional biochemical and biophysical approaches, but the study of polyamide binding to genomic targets in cells remains elusive. Here we report a method, the crosslinking of small molecules to isolate chromatin (COSMIC), that identifies polyamide binding sites across the genome. COSMIC is similar to chromatin immunoprecipitation (ChIP), but differs in two important ways: (1) a photocrosslinker is employed to enable selective, temporally-controlled capture of polyamide binding events, and (2) the biotin affinity handle is used to purify polyamide-DNA conjugates under semi-denaturing conditions to decrease DNA that is non-covalently bound. COSMIC is a general strategy that can be used to reveal the genome-wide binding events of polyamides and other genome-targeting chemotherapeutic agents.

An adverse event capture and management system for cancer studies.

BackgroundComprehensive capture of Adverse Events (AEs) is crucial for monitoring for side effects of a therapy while assessing efficacy. For cancer studies, the National Cancer Institute has developed the Common Terminology Criteria for Adverse Events (CTCAE) as a required standard for recording attributes and grading AEs. The AE assessments should be part of the Electronic Health Record (EHR) system; yet, due to patient-centric EHR design and implementation, many EHR's don't provide straightforward functions to assess ongoing AEs to indicate a resolution or a grade change for clinical trials.MethodsAt UAMS, we have implemented a standards-based Adverse Event Reporting System (AERS) that is integrated with the Epic EHR and other research systems to track new and existing AEs, including automated lab result grading in a regulatory compliant manner. Within a patient's chart, providers can launch AERS, which opens the patient's ongoing AEs as default and allows providers to assess (resolution/ongoing) existing AEs. In another tab, it allows providers to create a new AE. Also, we have separated symptoms from diagnoses in the CTCAE to minimize inaccurate designation of the clinical observations. Upon completion of assessments, a physician would submit the AEs to the EHR via a Health Level 7 (HL7) message and then to other systems utilizing a Representational State Transfer Web Service.ConclusionsAERS currently supports CTCAE version 3 and 4 with more than 65 cancer studies and 350 patients on those studies. This type of standard integrated into the EHR aids in research and data sharing in a compliant, efficient, and safe manner.

A Hybrid Scenario Planning Methodology for Interactive Digital Media

In this article, we present a scenario planning approach that is a hybrid of three main schools of thought. We propose such an approach in order to develop scenarios for a contemporary, technology-driven and fast-moving industry such as Interactive Digital Media. Our approach, while essentially qualitative in nature, nevertheless draws from the rigors of quantitative methods in identifying and then tracking the significant Dimensions of Analysis that impact the industry. The capture and analysis of real-time events was automated by an off-the-shelf web crawler with analytic functions, thus making our approach scalable over a larger scope and for longer periods of time. A morphological technique using Multidimensional Scaling isolated strands within the events leading to the identification of trends. This was followed by the mapping of strands to three emergent themes — ownership, distribution and innovation — which were used in an expert construction exercise to formulate plausible scenarios. We suggest that the approach we describe is particularly applicable for dynamic scenario planning that requires revisiting key assumptions and market conditions on a regular basis. We conclude that the ability to develop strategic narratives is the overriding benefit of scenario planning rather than the purported ability to predict the future.

The hydrologic outcome of a Low Impact Development (LID) site including superposition with streamflow peaks

Hydrology plays a key role in mitigating environmental impacts with Stormwater Management (SWM). Site-level Low Impact Development (LID) is a promising approach but impeded by a lack of experience, performance metrics and comprehensive analysis. This study investigated the hydrologic performance of a small LID site (0.15 km2) including superposition with high flows of the receiving stream by monitoring precipitation, discharge and streamflow for 30 months. The results (73% event capture, 66–87% volume reduction, 39 L/ha/s peak discharge, 4.5% streamflow amplification) implied that site-level LID provides an alternative to conventional SWM even for unfavourable conditions. Weak performance related to underground storage, antecedent conditions, storm characteristics and freezing periods occurred seasonally; and a minimum storm capture volume could not be observed, but a maximum retention capacity. Future LID site designs should consider these characteristics and limitations, together with a differentiated analysis of a set of metrics for deducing environmental implications.

A pilot randomized trial of conventional versus advanced pelvic floor exercises to treat urinary incontinence after radical prostatectomy: a study protocol.

BackgroundRadical prostatectomy is the most common and effective treatment for localized prostate cancer. Unfortunately, radical prostatectomy is associated with urinary incontinence and has a significant negative impact on quality of life. Pelvic floor exercises are the most common non-invasive management strategy for urinary incontinence following radical prostatectomy; however, studies provide inconsistent findings regarding their efficacy. One potential reason for sub-optimal efficacy of these interventions is the under-utilization of regional muscles that normally co-activate with the pelvic floor, such as the transverse abdominis, rectus abdominis, and the diaphragm. Two novel approaches to improve urinary continence recovery are ‘Pfilates’ and ‘Hypopressives’ that combine traditional pelvic floor exercises with the activation of additional supportive muscles. Our study will compare an advanced pelvic floor exercise training program that includes Pfilates and Hypopressives, to a conventional pelvic floor exercises regimen for the treatment of post-radical prostatectomy urinary incontinence.Methods/DesignThis is a pilot, randomized controlled trial of advanced pelvic floor muscle training versus conventional pelvic floor exercises for men with localized prostate cancer undergoing radical prostatectomy. Eighty-eight men who will be undergoing radical prostatectomy at hospitals in Toronto, Canada will be recruited. Eligible participants must not have undergone androgen deprivation therapy and/or radiation therapy. Participants will be randomized 1:1 to receive 26 weeks of the advanced or conventional pelvic floor exercise programs. Each program will be progressive and have comparable exercise volume. The primary outcomes are related to feasibility for a large, adequately powered randomized controlled trial to determine efficacy for the treatment of urinary incontinence. Feasibility will be assessed via recruitment success, participant retention, outcome capture, intervention adherence, and prevalence of adverse events. Secondary outcomes of intervention efficacy include measures of pelvic floor strength, urinary incontinence, erectile function, and quality of life. Secondary outcome measures will be collected prior to surgery (baseline), and at 2, 6, 12, 26-weeks post-operatively.DiscussionPfilates and Hypopressives are novel approaches to optimizing urinary function after radical prostatectomy. This trial will provide the foundation of data for future, large-scale trials to definitively describe the effect of these advanced pelvic floor exercise modalities compared to conventional pelvic floor exercise regimes for men with prostate cancer undergoing radical prostatectomy Trial registrationClinicalstrials.gov Identifier: NCT02233608.

Improved capture of adverse events after spinal surgery procedures with a longitudinal administrative database.

The significant medical and economic tolls of spinal disorders, increasing volume of spine surgeries, and focus on quality metrics have made it imperative to understand postoperative complications. This study demonstrates the utility of a longitudinal administrative database for capturing overall and procedure-specific complication rates after various spine surgery procedures. The Thomson Reuters MarketScan Commercial Claims and Encounters and the Medicare Supplemental and Coordination of Benefits database was used to conduct a retrospective analysis of longitudinal administrative data from a sample of approximately 189,000 patients. Overall and procedure-specific complication rates at 5 time points ranging from immediately postoperatively (index) to 30 days postoperatively were computed. The results indicated that the frequency of individual complication types increased at different rates. The overall complication rate including all spine surgeries was 13.6% at the index time point and increased to 22.8% at 30 days postoperatively. The frequencies of wound dehiscence, infection, and other wound complications exhibited large increases between 10 and 20 days postoperatively, while complication rates for new chronic pain, delirium, and dysrhythmia increased more gradually over the 30-day period studied. When specific surgical procedures were considered, 30-day complication rates ranged from 8.6% in single-level anterior cervical fusions to 27.3% in multilevel combined anterior and posterior lumbar spine fusions. This study demonstrates the usefulness of a longitudinal administrative database in assessing postoperative complication rates after spine surgery. Use of this database gave results that were comparable to those in prospective studies and superior to those obtained with nonlongitudinal administrative databases. Longitudinal administrative data may improve the understanding of overall and procedure-specific complication rates after spine surgery.

Friend or faculty: Social networking sites, dual relationships, and context collapse in higher education

Students and faculty have always interacted informally, on campus and off. Social networking sites (SNSs), like Facebook, introduce another space in which they interact, contributing to a blurring of boundaries between professional and personal personas. Communications on SNSs may be seen as simply an extension of on- and off-campus lives, and hence fall under the same policies governing institutional codes of conduct. The medium however, allowing for the capture and broadcast of events in academic and everyday lives, merits special considerations for contemporary faculty and administrators. The objective of this critical review is synthesize literature discussing dual relationships, context collapse, and digital persistence to contextualize and inform policy development regarding the use of SNSs in higher education. The review will contribute to discussions and decision-making on what should be done in response to these ubiquitous and novel channels for communication, connection and disclosure, and promote awareness of the implications for the connections fostered and the digital traces left behind in networked social spaces.

"Are You Sure?": Lapses in Self-Reported Activities Among Healthy Older Adults Reporting Online.

Accurate retrospective reporting of activities and symptoms has been shown to be problematic for older adults, yet standard clinical care relies on self-reports to aid in assessment and management. Our aim was to examine the relationship between self-report and sensor-based measures of activity. We administered an online activity survey to participants in our ongoing longitudinal study of in-home ubiquitous monitoring. We found a wide range of accuracies when comparing self-report with time-stamped sensor-based data. Of the 95 participants who completed the 2-hr activity log, nearly one quarter did not complete the task in a way that could potentially be compared with sensor data. Where comparisons were possible, agreement between self-reported and sensor-based activity was achieved by a minority of participants. The findings suggest that capture of real-time events with unobtrusive activity monitoring may be a more reliable approach to describing behavioral patterns and meaningful changes in older adults.

Practical scheduling for stochastic event capture in energy harvesting sensor networks

Existing scheduling schemes for stochastic event capture with rechargeable sensors either adopt simplified assumptions on event's properties or provide no performance guarantee. Considering the stochasticity of event staying time and event capture utility, we investigate the sensor scheduling problem aiming to maximise the overall quality of monitoring (QoM) in event capture application of energy harvesting sensor networks. We first provide a paradigm to calculate the QoM of a point of interests (PoI) and formulate the scheduling problem as an optimisation problem. Although we find that this problem is NP-complete, we prove that the problem can be cast as maximisation of a submodular function subject to matroid constraints. Accordingly, we can design centralised and distributed algorithms, each of which achieves a factor of 1=2 of the optimum. We evaluate the performance of our solution through simulations, and simulation results show that our scheme outperforms former works.

Probing the Trafficking Routes of KCNQ1 and KCNE1 After Their ER Exit

Background: KCNQ1 (Q1, pore-forming channel subunit) and KCNE1 (E1, regulatory subunit) associate to form the slow delayed rectifier (IKs) channel, important for cardiac action potential repolarization. Although Q1/E1 are obligatory partners in cardiomyocytes, in adult ventricular myocytes the two are not well colocalized: E1 is on the lateral cell surface while Q1 is mainly in the intracellular junctional SR. This appears to contradict data from heterologous expression or non-cardiac cell types, which suggest that Q1/E1 assemble into IKs when they are still in ER or soon thereafter. The current study is designed to distinguish between 2 scenarios. First, Q1 and E1 traffic from ER to the plasma membrane together, followed by Q1 internalization to the ER/SR compartment. Alternatively, Q1 and E1 traffic on different routes from ER to their separate destinations.Methods: COS-7 cells transfected with Q-GFP/E1-dsR are cultured in presence of brefeldin A (BFA) for 12 – 16 hr, to allow protein translation without ER exit. Cells are imaged in absence of BFA but presence of cycloheximide+dynasore (blocking protein translation and endocytosis). Time-lapse images (Zeiss 710, 37oC) of 4-um optic slice (to maximize capture of trafficking events in thin cytosol of COS-7 cells) are recorded till the Q1-GFP and E1-dsR distribution reaches quasi steady-state (> 2 hr).Results: BFA removal allows ER exit and Golgi reconstruction. E1-dsR exits ER in distinct vesicles, more frequently at the cell periphery. These vesicles gradually cluster to the peri-nuclear region, entering the post-BFA Golgi. Q1-QFP stays in the ER compartment for > 2 hr. Its ER location is confirmed by FRAP experiments.Conclusion: Our data support the second scenario. Experiments are in progress to test whether E1-dsR and Q1-GFP behave the same when expressed in a cardiac myocyte environment.

Content congruency and its interplay with temporal synchrony modulate integration between rhythmic audiovisual streams.

Both lower-level stimulus factors (e.g., temporal proximity) and higher-level cognitive factors (e.g., content congruency) are known to influence multisensory integration. The former can direct attention in a converging manner, and the latter can indicate whether information from the two modalities belongs together. The present research investigated whether and how these two factors interacted in the perception of rhythmic, audiovisual (AV) streams derived from a human movement scenario. Congruency here was based on sensorimotor correspondence pertaining to rhythm perception. Participants attended to bimodal stimuli consisting of a humanlike figure moving regularly to a sequence of auditory beat, and detected a possible auditory temporal deviant. The figure moved either downwards (congruently) or upwards (incongruently) to the downbeat, while in both situations the movement was either synchronous with the beat, or lagging behind it. Greater cross-modal binding was expected to hinder deviant detection. Results revealed poorer detection for congruent than for incongruent streams, suggesting stronger integration in the former. False alarms increased in asynchronous stimuli only for congruent streams, indicating greater tendency for deviant report due to visual capture of asynchronous auditory events. In addition, a greater increase in perceived synchrony was associated with a greater reduction in false alarms for congruent streams, while the pattern was reversed for incongruent ones. These results demonstrate that content congruency as a top-down factor not only promotes integration, but also modulates bottom-up effects of synchrony. Results are also discussed regarding how theories of integration and attentional entrainment may be combined in the context of rhythmic multisensory stimuli.

Validation of Health Event Capture in the Marshfield Epidemiologic Study Area.

In this study, health event capture is broadly defined as the degree to which a group of people use a particular provider network as their primary source of health care services. The Marshfield Epidemiologic Study Area (MESA) is a valuable resource for population-based health research, but the completeness of health event capture has not been validated in recent years. Our objective was to determine the current level of outpatient and inpatient health event capture by Marshfield Clinic (MC) facilities and affiliated hospitals for people living within MESA. A stratified sample survey with strata defined by MESA region (Central or North) and age group (<18 years or ≥18 years). 24 ZIP codes in central and northern Wisconsin, USA. 2,485 individuals participated of the 4,313 sampled cohort members residing in MESA Central (N=61,041) and MESA North (N=25,906) on February 22, 2011. A health care utilization survey was mailed to a random sample stratified by age group and MESA region. Telephone interviews were attempted for nonrespondents. The survey requested information on sources of outpatient care and overnight hospital admissions. Population proportions representing health event capture metrics and corresponding 95% confidence intervals (CI) were estimated with analytic weights applied to account for the survey design. Among those with an outpatient visit during the past 24 months, the most recent visit of an estimated 93% (95% CI, 91% - 94%) was at a MC facility. The most recent admission of an estimated 93% (95% CI, 90% - 96%) of those hospitalized in the past 24 months was at a hospital affiliated with MC. The proportion admitted to MC affiliated hospitals was higher for residents of MESA Central (97%) compared to MESA North (83%). A high proportion of outpatient visits and inpatient admissions in MESA Central and MESA North are accessible in the MC electronic health record. This pattern of high health event capture has been demonstrated since the inception of MESA in 1991. The results from this study validate and support the continued use of MESA for population-based epidemiologic and clinical research.

Do Changes in Transplant Practice Influence Risk of Therapy-Related Myelodysplasia/ Acute Myeloid Leukemia after Autologous Hematopoietic Cell Transplantation (aHCT) for Non-Hodgkin Lymphoma (NHL)?

Background: t-MDS/AML is the leading cause of non-relapse mortality after aHCT for NHL. Older age at aHCT, exposure to total body irradiation (TBI), and low number of CD34+ cells infused are associated with an increased risk of developing t-MDS/AML. However, over the past decade, aHCT has been increasingly used for older patient populations (potential for increase in t-MDS/AML risk). On the other hand, use of TBI has declined and number of CD34+ cells infused has increased (potential for decrease in t-MDS/AML risk). The impact of these changes in aHCT clinical practice on t-MDS/AML risk has not been assessed, and is addressed here.Methods: Information regarding t-MDS/AML diagnosis was procured from medical records and California Cancer Registry to ensure near-complete capture of events. Competing risk analysis was used to describe the cumulative incidence of t-MDS/AML, and to evaluate the role of host and aHCT-related factors in the development of t-MDS/AML. In order to understand the impact of changing clinical practices, patients were classified into those transplanted in the early era (1986-2002) vs. recent era (2003-2009).Results: A total of 1,261 consecutive patients received aHCT for NHL between 1986 and 2009 at City of Hope, and were followed for development of t-MDS/AML until 12/31/2011. Median age at aHCT was 50y (range, 5-78). Compared with patients transplanted in early era, those transplanted in recent era were more likely to be ≥50y at aHCT (recent era: 65% vs early era: 44%, p<0.001); less likely to be conditioned with TBI (recent era: 17% vs. early era: 67%, p<0.001); but more likely to receive a larger CD34+ cell dose (>3x10(6)/Kg: recent era 18% vs. early era: 12%, p<0.0001). After a median follow-up of 4.8y (range, 0.02-24.6),78 patients developed t-MDS/AML, yielding a 15y cumulative incidence of 7.5%. The cumulative incidence of t-MDS/AML was higher among those ≥50y (10.0% vs. 5.3%, p=0.002), and among those exposed to TBI (8.8% vs. 5.2%, p=0.07). Taken together, older patients exposed to TBI had a significantly higher cumulative incidence of t-MDS/AML (10.9%), as compared with younger patients not exposed to TBI (2.3%, p<0.001, Figure). Furthermore, the cumulative incidence of t-MDS/AML was higher among those with a low CD34+ cell dose (<3x10(6)/Kg) (14.2%) vs. those with a high CD34+ cell dose (≥3x10(6)/Kg) infusion (4.3%, p<0.0001). Multivariable competing risk analysis (adjusted for era) demonstrated the independent and significant impact of older age (≥50y: HR=2.4, 95%CI, 1.5-3.9, p=0.0004 [ref grp: <50y]), exposure to TBI (HR=1.8, 95%CI, 1.1-3.1, p=0.02 [ref grp: no TBI]), and low CD34+ cell count (<3x10(6)/Kg, HR=3.3, 95%CI, 1.9-5.8, p<0.0001 [ref grp: ≥3x10(6)/Kg]) in increasing the risk of t-MDS/AML. The impact these findings in light of changing practices with time is detailed in Table and summarized here. Multivariable analysis (taking age at aHCT into account) demonstrated that the risk of t-MDS/AML was reduced by 50% among those transplanted in the recent era (HR=0.5, 95%CI, 0.3-0.9, p=0.03 [ref grp: early era]) (Model 1). However, inclusion of TBI and CD34+ cell count in the model abrogated the reduction in the risk of t-MDS/AML during the recent era (HR=0.97, 95%CI, 0.5-1.9, p=0.9, referent grp: early era) (Model 2).Conclusions: This large study spanning over 25y confirms the independent role of age at aHCT, TBI, and CD34+ cell count in t-MDS/AML risk. More importantly, the study delineates the risk of t-MDS/AML in the context of changes in clinical practice of aHCT for NHL, demonstrating a reduction in the incidence of t-MDS/AML (despite an increase in age limit for aHCT) that is likely due to the declining practice of using TBI and the ability to use a higher number of CD34+ cells for aHCT.TableModel 1Model 2Model 3HR (95% CI), p-valueHR (95% CI), p-valueHR (95% CI), p-valueEra of aHCT1986-20021.01.01.02003-20090.54 (0.3-0.9), p=0.030.71 (0.4-1.3), p=0.30.97 (0.5-1.9) p=0.9Age at aHCT<50y1.01.01.0≥50y2.09 (1.3-3.4), p=0.0022.25 (1.4-3.6), p=0.00072.41 (1.5-3.9) p=0.0004Conditioning with TBINo TBI1.01.0Yes TBI1.80 (1.1-3.0), p=0.021.8 (1.1-3.1) p=0.02CD 34 counts>31.0≤33.32 (1.9-5.8) p<0.001missing2.36 (1.2-4.5) p=0.01 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.