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1.
Electrophoresis ; 40(5): 817-823, 2019 03.
Article in English | MEDLINE | ID: mdl-30556148

ABSTRACT

With the growth of the biopharmaceutical industry, there is a need for rapid size-analysis of proteins on the megaDalton scale. The large pore sizes needed for such separations cannot be easily reached by pushing the current limits of size-exclusion chromatography or gel electrophoresis. The concept detailed here is the formation of arbitrarily wide pores by packing nonporous colloidal silica in capillaries. This method can be called packed-capillary electrophoresis, or "pCE". Electrophoresis of protein standards (11-155 kDa) by pCE, using 345 nm diameter particles in 100 µm diameter capillaries, gives 2x higher resolution than a typical PAGE gel in 1/6 of the time. The electropherograms show that pCE is highly efficient, with half-micrometer plate heights for all seven standards, giving 105 plates for a 50 mm length. The large pore radius of 65 nm enables baseline resolution of proteins of 0.72, 1.048 and 1.236 MDa in less than 15 min. The short separation time of pCE is attributed to the absence of small pores that restrict protein migration in gels. The pCE separation is applied to the analysis of a stressed pharmaceutical-grade IgG4 sample, giving unprecedented baseline resolution of monomer, dimer, trimer and tetramer in less than 10 min.


Subject(s)
Colloids/chemistry , Electrophoresis, Capillary/methods , Recombinant Proteins , Silicon Dioxide/chemistry , Particle Size , Porosity , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification
2.
Opt Express ; 26(12): 15045-15058, 2018 Jun 11.
Article in English | MEDLINE | ID: mdl-30114757

ABSTRACT

Residual IQ skew in a coherent transmitter severely degrades the performance of long-haul coherent optical communication systems. The impairment is particularly detrimental for a high baud-rate system using quadrature amplitude modulation (QAM). Furthermore, Nyquist pulse shaping increases the spectral efficiency for WDM systems. However, sharp roll-off of Nyquist pulse shaping further reduces the tolerance to residual IQ skew. Thus, certain trade-offs between spectral efficiency and roll-off factor should be made to improve the tolerance of residual IQ skew. We experimentally studied this trade-off and determined the optimal roll-off factor, channel spacing, receiver bandwidth, and equalizer length. The results serve as a guideline for high baud-rate coherent WDM systems.

3.
Opt Express ; 26(18): 23069-23083, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30184963

ABSTRACT

A novel method to simultaneously detect power imbalance, modulation strength, and bias drift of coherent IQ transmitter during the initial power-up is presented. This is achieved by sweeping gain scaling factor of finite impulse filter in a digital domain and monitoring the combined output power. Furthermore, by dithering gain scaling factor of finite impulse filter, the power imbalance is measured with live traffic. Those impairments can be compensated accordingly. For example, the power imbalance is compensated through adjustment of gain setting of a radio frequency amplifier. This novel method works for multiple channels over C band, and the built-in photodiode of coherent transmitter provides sufficient accuracy.

4.
Opt Express ; 26(10): 12970-12984, 2018 May 14.
Article in English | MEDLINE | ID: mdl-29801331

ABSTRACT

Bit error rate (BER) versus optical signal to noise ratio (OSNR) characteristics determines the transmission performance for coherent optical transponder. We have developed a model to predict BER versus OSNR at various receiver optical power (ROP). The model has three parameters, which are related to BER noise floor, filter mismatching, and OSNR value without noise loading. The model is applied to high baud rate and quadrature amplitude modulation (QAM) transponders. By considering the influence of baud rate on the fitting parameters, accurate prediction of performance for coherent transponder can be achieved over various baud rates. Novel applications enabled by this model include in-field measurement of BER versus OSNR, simple abstraction of coherent transponder, accurate OSNR monitor and coherent optical channel monitor.

5.
J Vasc Surg ; 68(5): 1281-1286, 2018 11.
Article in English | MEDLINE | ID: mdl-30369410

ABSTRACT

INTRODUCTION: Fenestrated endovascular aneurysm repair (FEVAR) is the highest radiation dose procedure performed by vascular surgeons. We sought to characterize the radiation dose to patients and staff during FEVAR procedures with different premanufactured devices. METHODS: A single-center prospective study of FEVARs was performed over 24 months. Three FEVAR devices were included: off-the-shelf (OTS; t-Branch, p-Branch), Zenith Fenestrated (ZFen), and investigational custom-made devices (CMDs). Radiation doses to the surgeon, trainee, anesthesiologist, and scrub/circulating nurses were measured using a personal dosimetry system (DoseAware, Philips Healthcare, Amsterdam, The Netherlands). Procedure type, patient body mass index (BMI), reference air kerma (RAK), and kerma area product (KAP) were recorded. RAK and KAP were corrected for BMI based on an exponential fit of fluoroscopy dose rate and the dose per radiographic frame. Operator dose was corrected for BMI by the ratio of corrected to actual KAP. A one-sided Wilcox rank-sum test was used to compare personnel radiation doses, RAKs, and KAPs between procedure types. Statistical significance was set at P ≤ .05. RESULTS: There were 80 FEVARs performed by a single surgeon on a Philips Allura XperFD20 fluoroscopy system equipped with Clarity technology. Average BMI was 27 kg/m2. Sixty CMDs (36 four-, 21 three-, and 3 two-vessel fenestrations), 11 ZFens (8 three- and 3 two-vessel fenestrations), and 9 OTS devices (4 p-Branch, 5 t-Branch) were included. ZFens had significantly lower patient (1800 mGy vs 2950 mGy; P = .004), operator (120 µSv vs 370 µSv; P = .004), assistant (60 µSv vs 210 µSv; P = .003), circulator (10 µSv vs 30 µSv; P = .049), and scrub nurse dose (10 µSv vs 40 µSv; P = .02) compared with CMDs. OTS devices had significantly lower operator (220 µSv vs 370 µSv; P = .04), assistant (110 µSv vs 210 µSv; P = .02), and circulator doses (4 µSv vs 30 µSv; P = .001) compared with CMDs. Four-vessel fenestrated devices had significantly higher patient dose (3020 mGy) compared with three-vessel FEVARs (2670 mGy; P = .03) and two-vessel FEVARs (1600 mGy; P = .0007), and significantly higher operator dose (440 µSv) compared with three-vessel FEVARs (170 µSv; P = .0005). Patient dose was lowest with ZFens. Operating room personnel dose was lower with ZFens and OTS devices compared with CMDs. Four-vessel fenestrations required significantly more radiation compared with those involving three-vessel fenestrations; however, the dose increase was only 12% and should not preclude operators from extending coverage, if anatomically required. CONCLUSIONS: Overall, patient and personnel radiation doses during FEVAR with all devices were within acceptable limits and lower in our series than previously reported.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Endovascular Procedures/instrumentation , Occupational Exposure , Radiation Dosage , Radiation Exposure , Radiography, Interventional , Aortic Aneurysm, Abdominal/diagnostic imaging , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Humans , Occupational Exposure/adverse effects , Occupational Health , Operative Time , Patient Safety , Prospective Studies , Prosthesis Design , Radiation Exposure/adverse effects , Radiation Monitoring , Radiography, Interventional/adverse effects , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
6.
J Vasc Surg ; 68(2): 567-571, 2018 08.
Article in English | MEDLINE | ID: mdl-29544995

ABSTRACT

OBJECTIVE: Radiation to the interventionalist's brain during fluoroscopically guided interventions (FGIs) may increase the incidence of cerebral neoplasms. Lead equivalent surgical caps claim to reduce radiation brain doses by 50% to 95%. We sought to determine the efficacy of the RADPAD (Worldwide Innovations & Technologies, Lenexa, Kan) No Brainer surgical cap (0.06 mm lead equivalent at 90 kVp) in reducing radiation dose to the surgeon's and trainee's head during FGIs and to a phantom to determine relative brain dose reductions. METHODS: Optically stimulated, luminescent nanoDot detectors (Landauer, Glenwood, Ill) inside and outside of the cap at the left temporal position were used to measure cap attenuation during FGIs. To check relative brain doses, nanoDot detectors were placed in 15 positions within an anthropomorphic head phantom (ATOM model 701; CIRS, Norfolk, Va). The phantom was positioned to represent a primary operator performing femoral access. Fluorography was performed on a plastic scatter phantom at 80 kVp for an exposure of 5 Gy reference air kerma with or without the hat. For each brain location, the percentage dose reduction with the hat was calculated. Means and standard errors were calculated using a pooled linear mixed model with repeated measurements. Anatomically similar locations were combined into five groups: upper brain, upper skull, midbrain, eyes, and left temporal position. RESULTS: This was a prospective, single-center study that included 29 endovascular aortic aneurysm procedures. The average procedure reference air kerma was 2.6 Gy. The hat attenuation at the temporal position for the attending physician and fellow was 60% ± 20% and 33% ± 36%, respectively. The equivalent phantom measurements demonstrated an attenuation of 71% ± 2.0% (P < .0001). In the interior phantom locations, attenuation was statistically significant for the skull (6% ± 1.4%) and upper brain (7.2% ± 1.0%; P < .0001) but not for the middle brain (1.4% ± 1.0%; P = .15) or the eyes (-1.5% ± 1.4%; P = .28). CONCLUSIONS: The No Brainer surgical cap attenuates direct X rays at the superficial temporal location; however, the majority of radiation to an interventionalist's brain originates from scatter radiation from angles not shadowed by the cap as demonstrated by the trivial percentage brain dose reductions measured in the phantom. Radiation protective caps have minimal clinical relevance.


Subject(s)
Head/radiation effects , Lead , Occupational Exposure/prevention & control , Occupational Health , Protective Clothing , Radiation Dosage , Radiation Exposure/prevention & control , Radiography, Interventional , Surgeons , Surgical Attire , Vascular Surgical Procedures , Equipment Design , Fluoroscopy , Humans , Occupational Exposure/adverse effects , Optically Stimulated Luminescence Dosimetry , Prospective Studies , Protective Factors , Radiation Exposure/adverse effects , Radiography, Interventional/adverse effects , Risk Factors , Scattering, Radiation , Texas , Vascular Surgical Procedures/adverse effects
7.
Nicotine Tob Res ; 20(4): 425-433, 2018 03 06.
Article in English | MEDLINE | ID: mdl-28460123

ABSTRACT

Background: Electronic cigarettes (ECs) can influence nicotine addiction by delivering aerosolized nicotine. We investigated if nicotine from ECs is delivered to the brain ß2*-nicotinic acetylcholine receptors (ß2*-nAChR) and how this relates to the behavioral effects and nicotine delivery from cigarettes. Methods: Seven nicotine users participated in positron emission tomography (PET) studies with (-)-[18F]Flubatine before and after nicotine challenge with 0, 8, and 36 mg/ml nicotine in a 3.3 Volt, 1.5 Ohm EC or a standard tobacco cigarette. Craving was evaluated before and after product use. Results: Average ß2*-nAChR occupancy was higher after 36 mg/ml EC challenge compared to 8 mg/ml EC at trend level. Average ß2*-nAChR occupancy after tobacco cigarette smoking was 68 ± 18% and was not different compared with 8 mg/ml (64 ± 17%,) or 36 mg/ml (84 ± 3%) nicotine in EC users. Area under the curve (AUC) of blood nicotine level was higher in the cigarette smoking group compared with the 8mg/ml group (p = 0.03), but similar compared with the 36 mg/ml EC (p = 0.29). Drug craving was reduced after use of the tobacco cigarette, 8 mg/ml EC, and 36 mg/ml EC. Conclusions: In this novel investigation of EC effects at ß2*-nAChRs, we show that average ß2*-nAChR occupancy was higher after 36 mg/ml EC challenge compared with 8 mg/ml EC. Receptor occupancy and arterial blood nicotine levels after cigarette smoking were similar to 36 mg/ml EC use under controlled conditions. These findings suggest that the ECs studied here have abuse liability and may provide an adequate alternative nicotine delivery system for cigarette smokers. Implications: This is the first study to directly determine the neurologic effects of electronic cigarettes on human brain beta-2 nicotinic acetylcholine receptors using PET neuroimaging with (-)-[18F]Flubatine, a novel radiotracer. Our findings suggest that the e-cigarettes studied here have abuse liability and may provide an adequate alternative nicotine delivery system for cigarette smokers.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Electronic Nicotine Delivery Systems , Positron-Emission Tomography/methods , Receptors, Nicotinic/metabolism , Smoking/metabolism , Adult , Brain/drug effects , Female , Humans , Male , Nicotine/administration & dosage , Nicotine/metabolism , Nicotiana/metabolism , Tobacco Use Disorder/diagnostic imaging , Tobacco Use Disorder/metabolism
8.
Opt Express ; 24(6): 6719-34, 2016 Mar 21.
Article in English | MEDLINE | ID: mdl-27136859

ABSTRACT

Dual-polarization quadrature amplitude modulation (DP-QAM) is one of the feasible paths towards 100-Gb/s, 400-Gb/s and 1-Tb/s optical fiber communications systems. For DP-QAM transmitter, the time mismatch between the in-phase and quadrature (IQ) or x-polarized and y-polarized (XY) tributary channels is known as the IQ or XY skew. Large uncompensated IQ or XY skew can significantly degrade the optical fiber communications system performance. Sometimes, time-interleaved return-to-zero (RZ) DP signal is preferred with lower nonlinear polarization scattering induced penalty. In this work, detection and alignment of DP-QAM transmitter IQ and XY skews using reconfigurable interference is experimentally demonstrated. For IQ skew detection, a total dynamic range of 26.4 dB is achieved with ~1-dB power change for 0.5-ps skew from well alignment. For XY skew detection, it shows 23.2-dB dynamic range, and ~1.5-dB power change is achieved for 1-ps XY skew. Fast detection algorithm for arbitrary skew is also proposed and experimentally verified. The scheme is compatible with different modulation formats, flexible data sequences, and variable waveforms.

9.
J Vasc Surg ; 64(5): 1357-1365, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27471175

ABSTRACT

BACKGROUND: A new proprietary image-processing system known as AlluraClarity, developed by Philips Healthcare (Best, The Netherlands) for radiation-based interventional procedures, claims to lower radiation dose while preserving image quality using noise-reduction algorithms. This study determined whether the surgeon and patient radiation dose during complex endovascular procedures (CEPs) is decreased after the implementation of this new operating system. METHODS: Radiation dose to operators, procedure type, reference air kerma, kerma area product, and patient body mass index were recorded during CEPs on two Philips Allura FD 20 fluoroscopy systems with and without Clarity. Operator dose during CEPs was measured using optically stimulable, luminescent nanoDot (Landauer Inc, Glenwood, Ill) detectors placed outside the lead apron at the left upper chest position. nanoDots were read using a microStar ii (Landauer Inc) medical dosimetry system. For the CEPs in the Clarity group, the radiation dose to surgeons was also measured by the DoseAware (Philips Healthcare) personal dosimetry system. Side-by-side measurements of DoseAware and nanoDots allowed for cross-calibration between systems. Operator effective dose was determined using a modified Niklason algorithm. To control for patient size and case complexity, the average fluoroscopy dose rate and the dose per radiographic frame were adjusted for body mass index differences and then compared between the groups with and without Clarity by procedure. Additional factors, for example, physician practice patterns, that may have affected operator dose were inferred by comparing the ratio of the operator dose to procedural kerma area product with and without Clarity. A one-sided Wilcoxon rank sum test was used to compare groups for radiation doses, reference air kermas, and operating practices for each procedure type. RESULTS: The analysis included 234 CEPs; 95 performed without Clarity and 139 with Clarity. Practice patterns of operators during procedures with and without Clarity were not significantly different. For all cases, procedure radiation dose to the patient and the primary and assistant operators were significantly decreased in the Clarity group by 60% compared with the non-Clarity group. By procedure type, fluorography dose rates decreased from 44% for fenestrated endovascular repair and up to 70% with lower extremity interventions. Fluoroscopy dose rates also significantly decreased, from about 37% to 47%, depending on procedure type. CONCLUSIONS: The AlluraClarity system reduces the patient and primary operator's radiation dose by more than half during CEPs. This feature appears to be an effective tool in lowering the radiation dose while maintaining image quality.


Subject(s)
Endovascular Procedures , Occupational Exposure/prevention & control , Occupational Health , Radiation Dosage , Radiation Exposure/prevention & control , Radiographic Image Interpretation, Computer-Assisted/methods , Radiography, Interventional , Software , Surgeons , Algorithms , Endovascular Procedures/adverse effects , Fluoroscopy , Humans , Occupational Exposure/adverse effects , Practice Patterns, Physicians' , Predictive Value of Tests , Radiation Dosimeters , Radiation Exposure/adverse effects , Radiation Monitoring/instrumentation , Radiography, Interventional/adverse effects , Risk Factors , Texas
10.
Alcohol Clin Exp Res ; 40(4): 698-705, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26971694

ABSTRACT

BACKGROUND: Alcohol dependence and tobacco smoking are highly comorbid, and treating both conditions simultaneously is controversial. Previously, we showed that tobacco smoking interferes with GABAA receptor neuroadaptations during alcohol withdrawal in humans, while this effect did not occur with continued nicotine use during alcohol abstinence in nonhuman primates. Here, we extend our previous work by measuring GABAA receptor availability with positron emission tomography (PET) during drug abstinence in nonhuman primates exposed to alcohol alone, nicotine and alcohol together, and alcohol abstinence with continued nicotine exposure. METHODS: Twenty-four adolescent male rhesus macaques orally self-administered alcohol and nicotine, available separately in water and saccharin, over 20 weeks. The groups included alcohol alone (n = 8); nicotine and alcohol with simultaneous abstinence (n = 8); nicotine and alcohol with alcohol abstinence while nicotine was still available (n = 8); and a pilot group of animals consuming nicotine alone (n = 6). Animals were imaged with [(11)C]flumazenil PET to measure binding potential (BPND), an index of GABAA receptor availability. Imaging occurred at baseline (drug-naíve), and following alcohol and/or nicotine cessation at 1 day, 8 days, and 12 weeks of abstinence. Generalized linear mixed models were used to examine the time course of [(11)C]flumazenil BPND during alcohol abstinence across groups. RESULTS: Animals consumed 3.95 ± 1.22 g/kg/d alcohol and 55.4 ± 35.1 mg/kg/d nicotine. No significant group effects were observed in [(11)C]flumazenil BPND during alcohol abstinence; however, a main effect of time was detected. Post hoc analyses indicated that all groups abstaining from alcohol exhibited significantly increased GABAA receptor availability at 1 day and 8 days (but not 12 weeks) of abstinence relative to baseline, while no changes in [(11)C]flumazenil BPND during nicotine abstinence alone were observed. CONCLUSIONS: These data indicate that neither nicotine nor nicotine abstinence interferes with GABAA receptor neuroadaptations during alcohol withdrawal. This conclusion is consistent with our previous study and does not contradict the use of nicotine replacement therapies or non-nicotinic-acting pharmaceuticals to quit smoking during alcohol withdrawal from a GABAergic perspective.


Subject(s)
Alcohol Abstinence , Alcoholism/metabolism , Ethanol/metabolism , Nicotine/metabolism , Receptors, GABA-A/metabolism , Substance Withdrawal Syndrome/metabolism , Adaptation, Physiological/physiology , Alcoholism/diagnostic imaging , Animals , Ethanol/administration & dosage , Macaca mulatta , Male , Nicotine/administration & dosage , Positron-Emission Tomography , Self Administration , Substance Withdrawal Syndrome/diagnostic imaging
11.
Oecologia ; 181(2): 381-90, 2016 06.
Article in English | MEDLINE | ID: mdl-26886130

ABSTRACT

Although plant growth is generally recognized to be influenced by allocation to defense, genetic background (e.g., inbreeding), and gender, rarely have those factors been addressed collectively. In quaking aspen (Populus tremuloides Michx.), phenolic glycosides (PGs) and condensed tannins (CTs) constitute up to 30 % of leaf dry weight. To quantify the allocation cost of this chemical defense, we measured growth, defense chemistry, and individual heterozygosity (H obs at 16 microsatellite loci) for male and female trees in both controlled and natural environments. The controlled environment consisted of 12 juvenile genets grown for 3 years in a common garden, with replication. The natural environment consisted of 51 mature genets in wild populations, from which we sampled multiple ramets (trees) per genet. Concentrations of PGs and CTs were negatively correlated. PGs were uncorrelated with growth, but CT production represented a major cost. Across the range of CT levels found in wild-grown trees, growth rates varied by 2.6-fold, such that a 10 % increase in CT concentration occurred with a 38.5 % decrease in growth. H obs had a marked effect on aspen growth: for wild trees, a 10 % increase in H obs corresponded to a 12.5 % increase in growth. In wild trees, this CT effect was significant only in females, in which reproduction seems to exacerbate the cost of defense, while the H obs effect was significant only in males. Despite the lower growth rate of low-H obs trees, their higher CT levels may improve survival, which could account for the deficit of heterozygotes repeatedly found in natural aspen populations.


Subject(s)
Plant Leaves , Populus/genetics , Environment , Heterozygote , Trees
12.
J Vasc Surg ; 62(2): 457-63, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25937608

ABSTRACT

BACKGROUND: Surgeon radiation dose during complex fluoroscopically guided interventions (FGIs) has not been well studied. We sought to characterize radiation exposure to surgeons during FGIs based on procedure type, operator position, level of operator training, upper vs lower body exposure, and addition of protective shielding. METHODS: Optically stimulable, luminescent nanoDot (Landauer, Inc, Glenwood, Ill) detectors were used to measure radiation dose prospectively to surgeons during FGIs. The nanoDot dosimeters were placed outside the lead apron of the primary and assistant operators at the left upper chest and left lower pelvis positions. For each case, the procedure type, the reference air kerma, the kerma-area product, the relative position of the operator, the level of training of the fellow, and the presence or absence of external additional shielding devices were recorded. Three positions were assigned on the right-hand side of the patient in decreasing relative proximity to the flat panel detector (A, B, and C, respectively). Position A (main operator) was closest to the flat panel detector. Position D was on the left side of the patient at the brachial access site. The nanoDots were read using a microSTARii medical dosimetry system (Landauer, Inc) after every procedure. The nanoDot dosimetry system was calibrated for scattered radiation in an endovascular suite with a National Institute of Standards and Technology traceable solid-state radiation detector (Piranha T20; RTI Electronics, Fairfield, NJ). Comparative statistical analysis of nanoDot dose levels between categories was performed by analysis of variance with Tukey pairwise comparisons. Bonferroni correction was used for multiple comparisons. RESULTS: There were 415 nanoDot measurements with the following case distribution: 16 thoracic endovascular aortic repairs/endovascular aneurysm repairs, 18 fenestrated endovascular aneurysm repairs (FEVARs), 13 embolizations, 41 lower extremity interventions, 10 fistulograms, 13 visceral interventions, and 3 cerebrovascular procedures. The mean operator effective dose for FEVARs was higher than for other case types (P < .03), 20 µSv at position A and 9 µSv at position B. For all case types, position A (9.0 µSv) and position D (20 µSv) received statistically higher effective doses than position B (4 µSv) or position C (0.4 µSv) (P < .001). However, the mean operator effective dose for position D was not statistically different from that for position A. The addition of the lead skirt significantly decreased the lower body dose (33 ± 3.4 µSv to 6.3 ± 3.3 µSv) but not the upper body dose (6.5 ± 3.3 µSv to 5.7 ± 2.2 µSv). Neither ceiling-mounted shielding nor level of fellow training affected operator dose. CONCLUSIONS: Surgeon radiation dose during FGIs depends on case type, operator position, and table skirt use but not on the level of fellow training. On the basis of these data, the primary operator could perform approximately 12 FEVARs/wk and have an annual dose <10 mSv, which would not exceed lifetime occupational dose limits during a 35-year career. With practical case loads, operator doses are relatively low and unlikely to exceed occupational limits.


Subject(s)
Endovascular Procedures , Fluoroscopy , Occupational Exposure , Radiation Dosage , Vascular Surgical Procedures , Humans , Radiation Monitoring
13.
J Vasc Surg ; 61(4): 902-6, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25601500

ABSTRACT

BACKGROUND: Endovascular aortic aneurysm repairs (EVARs) with fenestrated (FEVAR) stent grafts are high radiation dose cases, yet no skin injuries were found retrospectively in our 61 cases with a mean peak skin dose (PSD) of 6.8 Gy. We hypothesize that skin injury is under-reported. This study examined deterministic effects in FEVARs after procedural changes implemented to detect skin injury. METHODS: All FEVARs during a 6-month period with a radiation dose of 5 Gy reference air kerma (RAK; National Council on Radiation Protection and Measurements threshold for substantial radiation dose level [SRDL]) were included. Patients were questioned about skin erythema, epilation, and necrosis, with a physical examination of the back completed daily until discharge and then at 2 and 4 weeks and at 3 and 6 months. PSD distributions were calculated with custom software using input data from fluoroscopic machine logs. These calculations have been validated against Gafchromic (Ashland Inc, Covington, Ky) film measurements. Dose was summed for the subset of patients with multiple procedures ≤6 months of the SRDL event, consistent with the joint commission recommendations. RESULTS: Twenty-two patients, 21 FEVARs and one embolization, reached an RAK of 5 Gy. The embolization procedure was excluded from review. The average RAK was 7.6 ± 2.0 Gy (range, 5.1-11.4 Gy), with a mean PSD of 4.8 ± 2.0 Gy (range, 2.3-10.4 Gy). Fifty-two percent of patients had multiple endovascular procedures ≤6 months of the SRDL event. The mean RAK for this subset was 10.0 ± 2.9 Gy (range, 5.5-15.1 Gy), with a mean PSD of 6.6 ± 1.9 Gy (range, 3.4-9.4 Gy). One patient died before the first postoperative visit. No radiation skin injuries were found. Putative risk factors for skin injury were evaluated and included smoking (32%), diabetes (14%), cytotoxic drugs (9%), and fair skin type (91%). No other risk factors were present (hyperthyroidism, collagen vascular disorders). CONCLUSIONS: Deterministic skin injuries are uncommon after FEVAR, even at high RAK levels, regardless of cumulative dose effects. This study addresses the concern of missed injuries based on the retrospective clinical examination findings that were published in our previous work. Even with more comprehensive postoperative skin examinations and patient questioning, the fact that no skin injuries were found suggests that radiation-induced skin injuries are multifactorial and not solely dose dependent.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortography/adverse effects , Blood Vessel Prosthesis Implantation/methods , Endovascular Procedures/methods , Radiation Dosage , Radiodermatitis/etiology , Skin/radiation effects , Aortic Aneurysm, Abdominal/diagnosis , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Erythema/etiology , Female , Humans , Male , Necrosis , Predictive Value of Tests , Prosthesis Design , Radiodermatitis/diagnosis , Retrospective Studies , Risk Assessment , Risk Factors , Skin/pathology , Stents , Time Factors , Treatment Outcome
14.
Ann Vasc Surg ; 29(4): 841.e1-3, 2015.
Article in English | MEDLINE | ID: mdl-25744231

ABSTRACT

We report a case of leiomyosarcoma of the thoracic aorta in a 49-year-old male patient with history of hypertrophic cardiomyopathy. The only presenting symptom was back pain localized under the left scapula with the frequency and severity of the pain increasing with time. Imaging studies detected the presence of an aortic tumor. The tumor was excised en bloc, and an interposition graft was implanted. The histology showed a fully excised grade 3 leiomyosarcoma. This article discusses features of this rare condition.


Subject(s)
Aorta, Thoracic/pathology , Cardiomyopathy, Hypertrophic/complications , Leiomyosarcoma/pathology , Vascular Neoplasms/pathology , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/surgery , Aortography/methods , Back Pain/etiology , Blood Vessel Prosthesis Implantation , Cardiomyopathy, Hypertrophic/diagnosis , Humans , Leiomyosarcoma/complications , Leiomyosarcoma/surgery , Male , Middle Aged , Neoplasm Grading , Tomography, X-Ray Computed , Treatment Outcome , Vascular Neoplasms/complications , Vascular Neoplasms/surgery
15.
J Vasc Surg ; 60(3): 742-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24768364

ABSTRACT

BACKGROUND: Radiation-induced skin injury is a serious potential complication of fluoroscopically guided interventions. Transient erythema occurs at doses of 2 to 5 Gy, whereas permanent epilation, ulceration, and desquamation are expected at doses above this level. Complex endovascular procedures (CEPs), such as fenestrated endovascular aortic aneurysm repair (FEVAR), are associated with high radiation doses, yet the prevalence of radiation-induced skin injury is unknown. We hypothesized that skin injury after these exposures is likely to be underrecognized and underreported. This study examined the frequency and severity of deterministic effects and evaluated patient characteristics that might predispose to radiation injury in CEP. METHODS: CEP was defined as a procedure with a radiation dose ≥5 Gy (National Council on Radiation Protection and Measurements threshold for substantial radiation dose level [SRDL]). Radiation dose and operating factors were recorded for all CEPs performed in a hybrid room during a 30-month period. Patient medical records were retrospectively reviewed for evidence of skin injury. Patients were seen in follow-up daily until discharge and then at weeks 2 and 6, months 3 and 6, and 1 year. Phone interviews were conducted to determine the presence of any skin-related complaints. Peak skin dose (PSD) distributions were calculated for FEVARs with custom software employing input data from fluoroscopic machine logs. These calculations were validated against Gafchromic film (Ashland Inc, Covington, Ky) measurements. Dose was summed for the subset of patients with multiple procedures within 6 months of the SRDL event, consistent with Joint Commission recommendations. RESULTS: Sixty-one CEPs reached a reference air kerma (RAK) of 5 Gy (50 FEVARs, six embolizations, one thoracic endovascular aortic repair, one endovascular aneurysm repair, one carotid intervention, and two visceral interventions). The patient cohort was 79% male and had a mean body mass index of 31. The average RAK was 8 ± 2 Gy (5.0-15.9 Gy). Sixteen patients had multiple CEPs within 6 months of the SRDL event, with a mean cumulative RAK of 12 ± 3 Gy (7.0-18.4 Gy). The mean FEVAR PSD was 6.6 ± 3.6 Gy (3.7-17.8 Gy), with a mean PSD/RAK ratio of 0.78. Gafchromic film dose measurements were not statistically different from PSD estimations, with a constant of proportionality of 0.99. Three patients were lost to follow-up before their first postoperative visit. No radiation skin injuries were found. CONCLUSIONS: This study represents the largest analysis of deterministic skin injury after CEPs, and our results suggest that it is less frequent than expected and not increased in CEPs.


Subject(s)
Endovascular Procedures/adverse effects , Erythema/etiology , Radiodermatitis/etiology , Radiography, Interventional/adverse effects , Skin Ulcer/etiology , Erythema/diagnosis , Female , Fluoroscopy , Humans , Male , Radiation Dosage , Radiodermatitis/diagnosis , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Skin Ulcer/diagnosis , Time Factors , Treatment Outcome
16.
J Osteopath Med ; 124(1): 5-11, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-37580988

ABSTRACT

CONTEXT: The COVID-19 pandemic disrupted clinical research in many medical and surgical fields, resulting in research waste and loss of treatment for patients. Although other areas have been explored, the extent of the pandemic's influence on osteoarthritis (OA) trials is currently unknown. OBJECTIVES: This study aims to explore the reasons for termination of clinical trials investigating OA during the COVID-19 pandemic. METHODS: We searched ClinicalTrials.gov for OA trials and characterized their reason for discontinuation, noting where trialists directly cited the COVID-19 pandemic as the reason for trial discontinuation. We also coded other common reasons for trial discontinuation. Descriptive and inferential statistics were performed to determine the difference in enrollment, funding source, trial phase, allocation, and intervention type between the trials terminated early due to pandemic and nonpandemic reasons. RESULTS: Out of 135 clinical trials, 119 were included and 27 (22.7 %) of them reported the COVID-19 pandemic as a primary reason for discontinuation, which was the overall most common reason for OA trial discontinuation during the study period. We found statistically significant differences for trials discontinued due to pandemic vs. non-pandemic-related reasons, with trials having sites outside the United States, randomized allocation, and drug or device intervention type being most affected. However, there was no statistically significant difference between groups regarding trial phase, funding source, or enrollment. CONCLUSIONS: This study highlights the impact of the COVID-19 pandemic on the clinical trials related to OA. We found that many trials reported discontinuation directly due to the pandemic, which may lead to the loss or delay of novel treatments for OA. To avoid such discontinuation in the future, alternative methods for conducting OA-related clinical trials should be explored and implemented.


Subject(s)
COVID-19 , Osteoarthritis , Humans , United States/epidemiology , COVID-19/epidemiology , Pandemics , Osteoarthritis/epidemiology , Osteoarthritis/therapy
17.
Anal Chem ; 85(15): 7102-8, 2013 Aug 06.
Article in English | MEDLINE | ID: mdl-23796076

ABSTRACT

The enzyme-linked immunosorbent assay is commonly used for research and clinical applications but typically suffers from a limited linear range and is difficult to multiplex. The fluorophore-linked immunosorbent assay is a closely related technique with good linear range and the ability to detect multiple antigens simultaneously but is typically less sensitive. Here, we demonstrate a near-infrared, surface-enhanced fluorophore-linked immunosorbent assay with sensitivity comparable to its enzyme-linked counterpart. A 59-fold enhancement to sensitivity (slope of linear fit) and an 8-fold improvement in LOD are demonstrated on a direct assay with rabbit immunoglobulin-G as a model system. The technique is also tested on a clinically relevant assay to detect alpha-fetoprotein, in which a 42-fold enhancement to sensitivity is demonstrated along with a 16-fold improvement in LOD. The technique enables these accomplishments while maintaining the entire traditional assay protocol and simply adding two steps at the end. This technique may prove superior to current protocols for biomarker research and clinical diagnoses, which require high sensitivity along with quantitation over an extended range.


Subject(s)
Fluorescent Dyes/chemistry , Immunosorbent Techniques , Infrared Rays , Animals , Benzenesulfonates/chemistry , Immunoglobulin G/immunology , Indoles/chemistry , Spectrometry, Fluorescence , Surface Properties , alpha-Fetoproteins/analysis
18.
J Vasc Surg ; 58(3): 715-21, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23688628

ABSTRACT

OBJECTIVE: Complex endovascular procedures such as fenestrated endovascular aneurysm repair (FEVAR) are associated with higher radiation doses compared with other fluoroscopically guided interventions (FGIs). The purpose of this study was to determine whether surgeon education on radiation dose control can lead to lower reference air kerma (RAK) and peak skin dose (PSD) levels in high-dose procedures. METHODS: Radiation dose and operating factors were recorded for FGI performed in a hybrid room over a 16-month period. Cases exceeding 6 Gy RAK were investigated according to institutional policy. Information obtained from these investigations led to surgeon education focused on reducing patient dose. Points addressed included increasing table height, utilizing collimation and angulation, decreasing magnification modes, and maintaining minimal patient-to-detector distance. Procedural RAK doses and operating factors were compared 8 months pre- (group A) and 8 months post- (group B) educational intervention using analysis of variance with Tukey pairwise comparisons and t-tests. PSD distributions were calculated using custom software employing input data from fluoroscopic machine logs. RESULTS: Of 447 procedures performed, 300 FGIs had sufficient data to be included in the analysis (54% lower extremity, 11% thoracic endovascular aneurysm repair, 10% cerebral, 8% FEVAR, 7% endovascular aneurysm repair, 5% visceral, and 5% embolization). Twenty-one cases were investigated for exceeding 6 Gy RAK. FEVAR comprised 70% of the investigated cases and had a significantly higher median RAK dose compared with all other FGIs (P < .0001). There was no difference in body mass index between groups A and B; however, increasing body mass index was an indicator for increased RAK. PSD calculations were performed for the 122 procedures that focused on the thorax and abdomen (group A, 80 patients; group B, 42 patients). Surgeon education most strongly affected table height, with an average table height elevation of 10 cm per case after education (P < .0001). The dose index (PSD/RAK ratio) was used to track changes in operating practices, and it decreased from 1.14 to 0.79 after education (P < .0001). These changes resulted in an estimated 16% reduction in PSD. There was a trend toward a decrease in patient to detector distance, and the use of collimation increased from 25% to 40% (P < .001) for all cases; however, these did not result in a decrease in PSD. The number of cases that exceeded 6 Gy RAK did not change after education; however, the proportion of non-FEVAR cases that exceeded 6 Gy decreased from 40% to 20%. CONCLUSIONS: Surgeon education on the appropriate use of technical factors during FGIs improved operating practice, reduced patient radiation dose, and decreased the number of non-FEVAR cases that exceeded 6 Gy. It is essential that vascular surgeons be educated in best operating practices to lower PSD; nonetheless, FEVAR remains a high-dose procedure.


Subject(s)
Education, Medical, Continuing , Endovascular Procedures/education , Radiation Dosage , Radiography, Interventional , Radiology, Interventional/education , Clinical Competence , Endovascular Procedures/adverse effects , Fluoroscopy , Health Knowledge, Attitudes, Practice , Humans , Operating Rooms , Patient Safety , Radiation Injuries/prevention & control , Radiography, Interventional/adverse effects , Retrospective Studies , Treatment Outcome
19.
Foodborne Pathog Dis ; 10(6): 559-65, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23638850

ABSTRACT

Escherichia coli O157 is a foodborne pathogen that can be transmitted by contaminated ground beef and is shed naturally in cattle feces. Recent reports indicated that feeding distillers' grains (DG) to cattle increased fecal shedding and prevalence of E. coli O157. In Minnesota, feeding DG with solubles (DGS) to livestock became widespread within the last 10 years, but there is no report about the prevalence of E. coli O157 in beef cattle in this state. This study was undertaken to survey the fecal prevalence of E. coli O157 in cattle fed diets containing DG and its association with environmental conditions and management practices. Fecal samples were collected from three feedlots during a 1-year period. All animals in those feedlots were fed different DGS levels. E. coli O157 presence was determined using a combination of enrichment, immunomagnetic separation, plating onto sorbitol MacConkey agar, and confirmation of isolates by immunoassay and multiplex virulence genes polymerase chain reaction analysis. Overall, E. coli O157 was confirmed in 9.7% of samples. Prevalence during summer was 30% and declined to less than 10% the rest of the year. In animals grouped by dietary DGS concentration, no significant difference in prevalence (12.0 and 5.5%) was detected between the low and the high average groups (less and more than 20%). Previous feeding of DGS before arriving to the feedlot also had no influence on fecal prevalence. The presence of several interacting variables, uncontrolled in a real-life feedlot environment, was the likely reason for our observation and suggested that at the levels studied, DGS had no effect on the STEC O157 prevalence in cattle populations.


Subject(s)
Animal Feed , Animal Husbandry/methods , Cattle/microbiology , Edible Grain , Escherichia coli O157/growth & development , Waste Products , Alcoholic Beverages/economics , Animal Feed/adverse effects , Animal Feed/economics , Animal Husbandry/economics , Animals , Bacterial Shedding , Biofuels/economics , Distillation , Edible Grain/adverse effects , Escherichia coli O157/classification , Escherichia coli O157/isolation & purification , Escherichia coli O157/metabolism , Ethanol/metabolism , Feces/microbiology , Female , Fermentation , Food-Processing Industry/economics , Male , Meat-Packing Industry/economics , Meat-Packing Industry/methods , Minnesota , Molecular Typing , Seasons , Virulence Factors/genetics , Virulence Factors/metabolism , Waste Products/adverse effects , Waste Products/economics
20.
Neuropsychopharmacology ; 48(4): 683-689, 2023 03.
Article in English | MEDLINE | ID: mdl-36681758

ABSTRACT

The cholinergic system is a critical mediator of cognition in animals. People who smoke cigarettes exhibit cognitive deficits, especially during quit attempts. Few studies jointly examine the cholinergic system and cognition in people while trying to quit smoking. We used positron emission tomography (PET) brain imaging with the ß2-subunit containing nicotinic acetylcholine receptor (ß2*-nAChR) partial agonist radioligand (-)-[18F]flubatine and the acetylcholinesterase inhibitor physostigmine to jointly examine the cholinergic system, smoking status, and cognition. (-)-[18F]Flubatine scans and cognitive data were acquired from twenty people who recently stopped smoking cigarettes (aged 38 ± 11 years; 6 female, 14 male; abstinent 7 ± 1 days) and 27 people who never smoked cigarettes (aged 29 ± 8 years; 11 female, 16 male). A subset of fifteen recently abstinent smokers and 21 never smokers received a mid-scan physostigmine challenge to increase acetylcholine levels. Regional volume of distribution (VT) was estimated with equilibrium analysis at "baseline" and post-physostigmine. Participants completed a cognitive battery prior to (-)-[18F]flubatine injection and physostigmine administration assessing executive function (Groton Maze Learning test), verbal learning (International Shopping List test), and working memory (One Back test). Physostigmine significantly decreased cortical (-)-[18F]flubatine VT, consistent with increased cortical acetylcholine levels reducing the number of ß2*-nAChR sites available for (-)-[18F]flubatine binding, at comparable magnitudes across groups (p values < 0.05). A larger magnitude of physostigmine-induced decrease in (-)-[18F]flubatine VT was significantly associated with worse executive function in people who recently stopped smoking (p values < 0.05). These findings underscore the role of the cholinergic system in early smoking cessation and highlight the importance of neuroscience-informed treatment strategies.


Subject(s)
Acetylcholine , Receptors, Nicotinic , Animals , Male , Female , Acetylcholine/metabolism , Acetylcholinesterase , Physostigmine , Positron-Emission Tomography/methods , Brain/diagnostic imaging , Brain/metabolism , Receptors, Nicotinic/metabolism , Cognition , Cholinergic Agents , Smoking/adverse effects
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