Absence of Arrhythmogenicity with Biphasic Pulsed Electric Fields Delivered to Porcine Airways.

Pulsed electric field (PEF) technologies treat many types of tissue. Many systems mandate synchronization to the cardiac cycle to avoid the induction of cardiac arrhythmias. Significant differences between PEF systems make the assessment of cardiac safety from one technology to another challenging. A growing body of evidence suggests that shorter duration biphasic pulses obviate the need for cardiac synchronization, even when delivered in a monopolar fashion. This study theoretically evaluates the risk profile of different PEF parameters. It then tests a monopolar, biphasic, microsecond-scale PEF technology for arrhythmogenic potential. PEF applications of increasing likelihood to induce an arrhythmia were delivered. The energy was delivered throughout the cardiac cycle, including both single and multiple packets, and then with concentrated delivery on the t-wave. There were no sustained changes to the electrocardiogram waveform or to the cardiac rhythm, despite delivering energy during the most vulnerable phase of the cardiac cycle, and delivery of multiple packets of PEF energy across the cardiac cycle. Only isolated premature-atrial contractions (PAC) were observed. This study provides evidence that certain varieties of biphasic, monopolar PEF delivery do not require synchronized energy delivery to prevent harmful arrhythmias.

Luminance contrast provides metric depth information.

The perception of depth from retinal images depends on information from multiple visual cues. One potential depth cue is the statistical relationship between luminance and distance; darker points in a local region of an image tend to be farther away than brighter points. We establish that this statistical relationship acts as a quantitative cue to depth. We show that luminance variations affect depth in naturalistic scenes containing multiple cues to depth. This occurred when the correlation between variations of luminance and depth was manipulated within an object, but not between objects. This is consistent with the local nature of the statistical relationship in natural scenes. We also showed that perceived depth increases as contrast is increased, but only when the depth signalled by luminance and binocular disparity are consistent. Our results show that the negative correlation between luminance and distance, as found under diffuse lighting, provides a depth cue that is combined with depth from binocular disparity, in a way that is consistent with the simultaneous estimation of surface depth and reflectance variations. Adopting more complex lighting models such as ambient occlusion in computer rendering will thus contribute to the accuracy as well as the aesthetic appearance of three-dimensional graphics.

Reduced motion external defibrillation: Reduced subject motion with equivalent defibrillation efficiency validated in swine.

BACKGROUND: External defibrillators are used for arrhythmia cardioversion and for defibrillating during cardiac arrest. During defibrillation, short-duration biphasic pulses cause intense motion due to rapid chest-wall muscle contraction. A reduced motion external defibrillator (RMD) was constructed by integrating a commercial defibrillator with a Tetanizing-waveform generator. A long-duration, low-amplitude, tetanizing waveform slowly stimulated the chest musculature before the biphasic pulse, reducing muscle contraction during the shock. OBJECTIVE: The purpose of this study was to evaluate RMD defibrillation in swine for subject motion during defibrillation pulses and for defibrillation effectiveness. RMD defibrillation can reduce the duration of arrhythmia ablation therapy or simplify cardioversion procedures. METHODS: The tetanizing unit delivered a triangular 1-kHz pulse of 0.25- to 2.0-second duration and 10- to 100-V peak amplitude, subsequently triggering the conventional defibrillator to output standard 1- to 200-J energy biphasic pulses at the next R wave. Forward limb motion was evaluated by measuring peak acceleration and limb work during RMD (tetanizing + biphasic) or biphasic pulse-only waveforms at 10-3-second sampling rate. Seven swine were arrested electrically and subsequently defibrillated. Biphasic pulse-only and RMD defibrillations were repeated 25-35 times per swine, varying tetanizing parameters and biphasic pulse energy. Defibrillation thresholds (DFTs) were established by measuring the minimum energy required to restore sinus rhythm with biphasic pulse-only or RMD defibrillations. RESULTS: Two forward-limb acceleration peaks occurred during both the tetanizing waveform and biphasic pulse, indicating rapid and slower nociceptic (pain sensation) nerve fiber activation. Optimal RMD tetanizing parameters (25-35 V, 0.25- to 0.75-second duration), relative to biphasic pulse-only defibrillations, resulted in 74% ± 10% smaller peak accelerations and 85% ± 10% reduced limb work. DFT energies were identical when comparing RMD to biphasic pulse-only defibrillations. CONCLUSION: Relative to conventional defibrillations, RMD defibrillations maintain rhythm restoration efficiency with drastically reduced subject motion.

Public Health Emergency Response Leadership Training: A Qualitative Assessment of Existing Educational Opportunities and Perceived Facilitators, Barriers, and Priorities in Professional Development.

OBJECTIVE: We aimed to understand the current training environment for developing public health emergency response leaders and highlight facilitators and barriers in accessing targeted training. DESIGN: We designed 4 focus groups to gather organizational perspectives on public health emergency response leadership development. Discussions were recorded, transcribed, coded, and analyzed to synthesize key themes. SETTING: Focus groups were convened at the 2019 Preparedness Summit (March 27-28) in St Louis, Missouri. PARTICIPANTS: Twenty-three public health professionals from 9 Public Health Emergency Preparedness (PHEP) Cooperative Agreement award recipient jurisdictions and 12 local health departments participated. MAIN OUTCOME MEASURES: We examined the current availability, relevance, specificity, and utility of educational content and delivery modalities. Facilitators and barriers were identified as opportunities to improve training access. RESULTS: Generic emergency management training is considered important and widely available but with limited application in public health practice. Existing leadership training opportunities in public health emergency response are limited and not widely known. While organizational support and accessible training facilitate participation, resource constraints (ie, funding, time, and staff) exist as key barriers. In addition, frequent staff turnover and attrition that result in loss of institutional knowledge likely hinder effective public health emergency responses. CONCLUSION: Effective public health emergency response depends on capable leaders not only well versed in specialized technical disciplines and practices but also familiar with-or preferably fluent in-emergency management principles and functions. This study demonstrated that well-aimed training strategies and organizational planning are essential in developing public health emergency response leaders. Specifically, leadership development may accrue considerable benefit from a standardized training curriculum. In addition, scalable training programs developed through public, private, and academic partnerships may lessen resource demands on individual organizations to facilitate training access. Finally, training practicums (eg, mentoring, shadowing) may provide opportunities to facilitate active learning and preserve institutional knowledge through leadership transitions.

State of public health emergency response leadership training: A multitiered organizational perspective.

OBJECTIVE: To capture organizational level information on the current state of public health emergency response leadership training. DESIGN: A web-based questionnaire. PARTICIPANTS: This multitiered assessment of health departments included two distinct respondent groups: (1) Public Health Emergency Preparedness (PHEP) Cooperative Agreement recipients (n = 34) and (2) local health departments (LHDs) (n = 169) representative of different agency sizes and populations served. RESULTS: Overall, PHEP and LHD respondents expressed a clear preference for participatory learning with practical drills/exercises and participatory workshops as the preferred training delivery modes. Compared with technical and role-specific training, leadership training was less available. For both PHEP and LHD respondents, staff availability for training is most notably limited due to lack of time. For PHEP respondents, a common factor limiting agency ability to offer training is lack of mentors/instructors, whereas for LHD respondents, it is limited funding. CONCLUSIONS: Efforts should focus on increasing accessibility and the continued development of rigorous and effective training based on practical experience in all aspects of multitiered public health emergency response leadership.

In Vitro Cell Selectivity of Reversible and Irreversible: Electroporation in Cardiac Tissue.

[Figure: see text].

Comparison of tandem ureteral stents, cryoplasty, and cutting balloon ureteroplasty in treatment of refractory transplant ureteral strictures.

The objective of study was to compare clinical outcome of cryoplasty, tandem stents, and cutting balloon ureteroplasty as "bailout procedures" to prevent surgical intervention or stent dependency in renal transplant patients with refractory ureteral stricture. All patients who underwent a bailout procedure from June 11, 2003, to August 8, 2015, at a single institution were reviewed retrospectively. Refractory ureteral stricture was defined as ureteral stenosis not responding to at least two prior percutaneous plain balloon ureteroplasties. Primary patency was defined as stable allograft function following the procedure with unobstructed urine outflow, not requiring indwelling ureteral stent, repeat ureteroplasty, or surgical revision. Sixty-one procedures were performed on 51 patients. Patients were followed up for a median of 286 days. Overall primary patency rate was 26.1%. Primary patency rate by method was 38.1%, 23.1%, and 14.3% after cryoplasty, tandem stent placement, and cutting balloon dilatation, respectively (P = .260). Primary patency rate was higher in early (<3 months post-transplant) ureteral strictures (35.7% vs 13.3%; P = .047). More complications identified in patients who had tandem ureteral stents (P = .00754). As some renal transplant patients may not be good operative candidates for ureteral revision, it would be reasonable to attempt one of these "bailout" interventions as long as the clinical team and patient are aware of overall low potential for achieving primary patency.

The Association of Biomarkers of Inflammation and Extracellular Matrix Degradation With the Risk of Abdominal Aortic Aneurysm: The ARIC Study.

Animal and human laboratory studies suggest that the pathogenesis of abdominal aortic aneurysms (AAAs) involves inflammation and degradation and remodeling of the extracellular matrix. This study prospectively assessed the association between biomarkers for these mechanisms and the presence of AAA during 24 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) study. The ARIC prospectively identified clinically diagnosed AAAs in 15 792 men and women from baseline in 1987 to 1989 to 2011 using hospital discharge codes and death records. Additional asymptomatic AAAs were detected by an abdominal ultrasound scan in 2011 to 2013. Matrix metalloproteinase (MMP)-3, MMP-9, interleukin 6 (IL-6), N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin were measured in blood samples collected between 1987 and 1992 in participants with AAA (544 clinically diagnosed AAAs and 72 ultrasound-detected AAAs) and a random sample of 723 participants selected from baseline and matched with AAAs by age, race and sex. Higher concentrations of MMP-9 and IL-6 were associated with future risk of clinically diagnosed AAA (hazard ratios [95% confidence intervals]: 1.55 [1.22-1.97] and 1.87 [1.48-2.35], respectively, comparing highest versus lowest tertiles) after multivariable adjustment ( P for trend < .001). Matrix metalloproteinase-9 was also associated with ultrasound-detected AAA. In conclusion, blood concentrations of MMP-9 and IL-6 measured in middle age predicted the risk of AAA during 24 years of follow-up.

The effect of image position on the Independent Components of natural binocular images.

Human visual performance degrades substantially as the angular distance from the fovea increases. This decrease in performance is found for both binocular and monocular vision. Although analysis of the statistics of natural images has provided significant insights into human visual processing, little research has focused on the statistical content of binocular images at eccentric angles. We applied Independent Component Analysis to rectangular image patches cut from locations within binocular images corresponding to different degrees of eccentricity. The distribution of components learned from the varying locations was examined to determine how these distributions varied across eccentricity. We found a general trend towards a broader spread of horizontal and vertical position disparity tunings in eccentric regions compared to the fovea, with the horizontal spread more pronounced than the vertical spread. Eccentric locations above the centroid show a strong bias towards far-tuned components, eccentric locations below the centroid show a strong bias towards near-tuned components. These distributions exhibit substantial similarities with physiological measurements in V1, however in common with previous research we also observe important differences, in particular distributions of binocular phase disparity which do not match physiology.

Function, Shoulder Motion, Pain, and Lymphedema in Breast Cancer With and Without Axillary Web Syndrome: An 18-Month Follow-Up.

Background: Axillary web syndrome (AWS) can develop following breast cancer surgery and presents as a tight band of tissue in the axilla with shoulder abduction. Objective: The objectives were to determine the prevalence and natural history of AWS and the association between AWS and function, range of motion, pain, lymphedema, and body mass index (BMI). Design: This study was a longitudinal prospective cohort study utilizing a repeated measures design. Methods: Axillary web syndrome, function, shoulder range of motion, pain, and lymphedema (using circumference, bioimpedance spectroscopy, tissue dielectric constant) were assessed in women at 2, 4, and 12 weeks and 18 months following breast cancer surgery. Prevalence of AWS and the association with the measured outcomes were analyzed. Results: Thirty-six women agreed to participate in the study. The cumulative prevalence of AWS was 50% (18/36) at 18 months following breast cancer surgery. AWS was identified as a risk factor for reduced function. Women with AWS had statistically reduced range of motion, lower BMI, and higher number of lymph nodes removed compared to the non-AWS group. Forty-one percent (13/32) of women had AWS at 18 months. AWS reoccurred in 6 women following resolution, and a new case developed beyond the early postoperative period. The overall prevalence of physical impairments ranged from 66% to 97% within the first 18 months following surgery regardless of AWS. Limitations: Limitations include a small sample size and potential treatment effect. Conclusion: AWS occurs in approximately 50% of women following breast cancer surgery. It can persist for 18 months and potentially longer, develop beyond the early postoperative time period, and reoccur after resolution. Clinicians need to be aware of the chronicity of AWS and its association with reduced range of motion and function.

Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery of Sleeping Beauty Transposons: Implications for Non-Viral Gene Therapy of Systemic Disease.

The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice, including hemophilia A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis types I and VII caused by α-L-iduronidase (IDUA) and ß-glucuronidase (GUSB) deficiency, respectively. Modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs were recently reported. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), transgenic protein in the plasma was demonstrated for up to 6 weeks post infusion. This study reports that immunosuppression of dogs with gadolinium chloride (GdCl3) prolonged the presence of cSEAP in the circulation up to 5.5 months after a single vector infusion. Transgene expression declined gradually but appeared to stabilize after about 2 months at approximately fourfold baseline level. Durability of transgenic protein expression in the plasma was inversely associated with transient increase of liver enzymes alanine transaminase and aspartate transaminase in response to the plasmid delivery procedure, which suggests a deleterious effect of hepatocellular toxicity on transgene expression. GdCl3 treatment was ineffective for repeat vector infusions. In parallel studies, dogs were infused with potentially therapeutic transposons. Activities of transgenic IDUA and GUSB in plasma peaked at 50-350% of wildtype, but in the absence of immunosuppression lasted only a few days. Transposition was detectable by excision assay only when the most efficient transposase, SB100X, was used. Dogs infused with transposons encoding canine clotting factor IX (cFIX) were treated with GdCl3 and showed expression profiles similar to those in cSEAP-infused dogs, with expression peaking at 40% wt (2 µg/mL). It is concluded that GdCl3 can support extended transgene expression after hydrodynamic introduction of SB transposons in dogs, but that alternative regimens will be required to achieve therapeutic levels of transgene products.

Transgene Expression in Dogs After Liver-Directed Hydrodynamic Delivery of Sleeping Beauty Transposons Using Balloon Catheters.

The Sleeping Beauty transposon system has been extensively tested for integration of reporter and therapeutic genes in vitro and in vivo in mice. Dogs were used as a large animal model for human therapy and minimally invasive infusion of DNA solutions. DNA solutions were delivered into the entire liver or the left side of the liver using balloon catheters for temporary occlusion of venous outflow. A peak intravascular pressure between 80 and 140 mmHg supported sufficient DNA delivery in dog liver for detection of secretable reporter proteins. Secretable reporters allowed monitoring of the time course of gene products detectable in the circulation postinfusion. Canine secreted alkaline phosphatase reporter protein levels were measured in plasma, with expression detectable for up to 6 weeks, while expression of canine erythropoietin was detectable for 7-10 days. All animals exhibited a transient increase in blood transaminases that normalized within 10 days; otherwise the treated animals were clinically normal. These results demonstrate the utility of a secreted reporter protein for real-time monitoring of gene expression in the liver in a large animal model but highlight the need for improved delivery in target tissues to support integration and long-term expression of Sleeping Beauty transposons.

Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities).

OBJECTIVE: Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs. APPROACH AND RESULTS: In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident AAAs. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic AAAs were identified. We estimated the lifetime risk of AAA from the index age 45 years through 85 years of age. At age 45, the lifetime risk for AAA was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower AAA lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical AAA and asymptomatic AAA. CONCLUSIONS: At least 1 in 9 middle-aged current smokers developed AAA in their lifetime. Smoking cessation reduced the lifetime risk of AAA.

Ideal Binocular Disparity Detectors Learned Using Independent Subspace Analysis on Binocular Natural Image Pairs.

An influential theory of mammalian vision, known as the efficient coding hypothesis, holds that early stages in the visual cortex attempts to form an efficient coding of ecologically valid stimuli. Although numerous authors have successfully modelled some aspects of early vision mathematically, closer inspection has found substantial discrepancies between the predictions of some of these models and observations of neurons in the visual cortex. In particular analysis of linear-non-linear models of simple-cells using Independent Component Analysis has found a strong bias towards features on the horoptor. In order to investigate the link between the information content of binocular images, mathematical models of complex cells and physiological recordings, we applied Independent Subspace Analysis to binocular image patches in order to learn a set of complex-cell-like models. We found that these complex-cell-like models exhibited a wide range of binocular disparity-discriminability, although only a minority exhibited high binocular discrimination scores. However, in common with the linear-non-linear model case we found that feature detection was limited to the horoptor suggesting that current mathematical models are limited in their ability to explain the functionality of the visual cortex.

Tetanizing prepulse: A novel strategy to mitigate implantable cardioverter-defibrillator shock-related pain.

BACKGROUND: Skeletal muscle activation has been implicated as the source of pain associated with implantable cardioverter-defibrillator shocks. We hypothesized that the skeletal muscle response to defibrillatory shocks could be attenuated with a tetanizing prepulse immediately before biphasic shock delivery. OBJECTIVE: The purpose of this study was to test the ability of tetanizing prepulses to reduce the skeletal muscle activation associated with defibrillation. METHODS: Seven adult pigs were studied. A left ventricular coil and subcutaneous dummy can in the right thorax were used to deliver either pure biphasic waveforms or test waveforms consisting of a tetanizing pulse of high-frequency alternating current (HFAC) ramped to an amplitude of 5-100 V over 0.25-1 second, immediately followed by a biphasic shock of approximately 9 J (ramped HFAC and biphasic [rHFAC+B]). We used limb acceleration and rate of force development as surrogate measures of pain. Test and control waveforms were delivered in sinus rhythm and induced ventricular fibrillation to test defibrillation efficacy. RESULTS: Defibrillation threshold energy was indistinguishable between rHFAC+B and pure biphasic shocks. Peak acceleration and rate of force development were reduced by 72% ± 7% and 71% ± 22%, respectively, with a 25-V, 1-second rHFAC+B waveform compared with pure biphasic shocks. Notably, rHFAC+B with a 9-J biphasic shock produced significantly less skeletal muscle activation than a 0.1-J pure biphasic shock. CONCLUSION: A putative source of implantable cardioverter-defibrillator shock-related pain can be mitigated using a tetanizing prepulse followed by biphasic shock. Human studies will be required to assess true pain reduction with this approach.

Encoding and estimation of first- and second-order binocular disparity in natural images.

The first stage of processing of binocular information in the visual cortex is performed by mechanisms that are bandpass-tuned for spatial frequency and orientation. Psychophysical and physiological evidence have also demonstrated the existence of second-order mechanisms in binocular processing, which can encode disparities that are not directly accessible to first-order mechanisms. We compared the responses of first- and second-order binocular filters to natural images. We found that the responses of the second-order mechanisms are to some extent correlated with the responses of the first-order mechanisms, and that they can contribute to increasing both the accuracy, and depth range, of binocular stereopsis.

Fibromuscular Dysplasia in a Normotensive Patient Presented With Renal Infarct: Case Report and Endovascular Technique.

Fibromuscular dysplasia (FMD) is a well-known disease, but its diagnosis can be challenging. Typically, the symptomatic FMD are reported by young and middle aged people with high blood pressure refractory to medical treatment. We present a rare case of a young, healthy, and normotensive patient who presented with pain secondary to renal infarction, without any prior signs or symptoms or history of hypertension. This presentation of FMD has not been previously described. The typical but subtle angiographic findings of the macro-aneurysmal FMD as well as the successful endovascular treatment are discussed herein. The macro-aneurysmal form of FMD should be considered in the differential diagnosis of acute renal infarction in young and middle aged patients even if they do not have a history of hypertension.

Movement, Function, Pain, and Postoperative Edema in Axillary Web Syndrome.

BACKGROUND: Axillary web syndrome (AWS) is a condition that may develop following breast cancer surgery and that presents as a palpable axillary cord of tissue. OBJECTIVE: The purposes of this study were: (1) to determine the clinical characteristics of AWS related to movement, function, pain, and postoperative edema and (2) to define the incidence of and risk factors for AWS within the first 3 months following breast cancer surgery. DESIGN: This was a prospective cohort study with a repeated-measures design. METHODS: Women who underwent breast cancer surgery with sentinel node biopsy or axillary lymph node dissection (N=36) were assessed for AWS, shoulder range of motion, function, pain, and postoperative edema (using girth measurements, bioimpedance, and tissue dielectric constant) at 2, 4, and 12 weeks. Demographic characteristics were used for risk analysis. RESULTS: Seventeen women (47.2%) developed AWS, and AWS persisted in 10 participants (27.8%) at 12 weeks. Abduction range of motion was significantly lower in the AWS group compared with the non-AWS group at 2 and 4 weeks. There were no differences between groups in measurements of function, pain, or edema at any time point. Trunk edema measured by dielectric constant was present in both groups, with an incidence of 55%. Multivariate analysis determined lower body mass index as being significantly associated with AWS (odds ratio=0.86; 95% confidence interval=0.74, 1.00). LIMITATIONS: Limitations included a short follow-up time and a small sample size. CONCLUSION: Axillary web syndrome is prevalent following breast/axilla surgery for early-stage breast cancer and may persist beyond 12 weeks. The early consequences include movement restriction, but the long-term effects of persistent AWS cords are yet unknown. Low body mass index is considered a risk factor for AWS.

Imaging venous disease: pearls and pitfalls.

In this day of rapidly advancing quantitative and molecular imaging techniques, imaging of veins and venous pathology still primarily relies on qualitative interpretation of ultrasound and venographic images. This article is primarily dedicated to understanding the nuances of the qualitative use of these two, by now, "old-fashioned" modalities. As such, the article is an attempt to help the imaging practitioner, in their daily practice, to avoid some of the interpretive mishaps that can befall the unwary. There are special strengths of the 3-dimensional imaging techniques of magnetic resonance imaging and computed tomography venography that will be briefly mentioned and discussed as to when and where they should be added to the venous imaging armamentarium.