Nasal Unit Transplantation: A Cadaveric Anatomical Feasibility Study.

Background The science and technical acumen in the field of vascularized composite allotransplantation has progressed rapidly over the past 15 years, and transplantation of specialized units of the face, such as the nose, appears possible. No study to date has evaluated the technical feasibility of isolated nasal unit transplantation (NUT). In this study, we explore the anatomy and technical specifics of NUT. Methods In this study, four fresh cadaver heads were studied. Bilateral vascular pedicle dissections were performed in each cadaver. The facial artery was cannulated and injected with food dye under physiologic pressure in two cadavers, and with lead oxide mixture in two cadavers to evaluate perfusion territories supplied by each vascular pedicle. Results The facial artery and vein were found to be adequate pedicles for NUT. Divergent courses of the vein and artery were consistently identified, which made for a bulky pedicle with necessary inclusion of large amounts of subcutaneous tissue. In all cases, the artery remained superficial, while the vein coursed in a deeper plane, and demonstrated consistent anastomoses with the superior transverse orbital arcade. While zinc oxide injection of the facial artery demonstrated filling of the nasal vasculature across the midline, dye perfusion studies suggested that unilateral arterial inflow may be insufficient to perfuse contralateral NUT components. Discrepancies in these two studies underscore the limitations of nondynamic assessment of nutritive perfusion. Conclusion NUT based on the facial artery and facial vein is technically feasible. Angiosome evaluation suggests that bilateral pedicle anastomoses may be required to ensure optimal perfusion.

Correction of tissue-motion effects on common-midpoint signals using reciprocal signals.

The near field signal redundancy algorithm for phase-aberration correction is sensitive to tissue motion because several separated transmissions are usually needed to acquire a set of common-midpoint signals. If tissues are moving significantly due to, for example, heart beats, the effects of tissue motion on common-midpoint signals need to be corrected before the phase-aberration profile can be successfully measured. Theoretical analyses in this paper show that the arrival-time difference between a pair of common-midpoint signals due to tissue motion is usually very similar to that between the pair of reciprocal signals acquired using the same two transmissions. Based on this conclusion, an algorithm for correcting tissue-motion effects on the peak position of cross-correlation functions between common-midpoint signals is proposed and initial experimental results are also presented.

Analysis of inpatient and high-risk medicine pharmacist interventions associated with insulin prescribing for hospital inpatients with diabetes.

Background Insulin is a high-risk medicine, associated with hospital medication errors. Pharmacists play an important role in the monitoring of patients on insulin.Objective To analyse interventions made by hospital pharmacists that were associated with insulin prescribing for inpatients with diabetes.Method Retrospective audit of pharmacist interventions for adult inpatients for an 8-month period, 1 June 2019-31 January 2020. Pharmacist interventions recorded in the electronic medication management system by inpatient unit and dedicated high-risk medicine pharmacists were extracted, screened, and analysed.Results Of 3975 pharmacist interventions 3356 (84.43%) were recorded by high-risk medicine pharmacists and 619 (15.57%) by inpatient unit pharmacists. July and August 2019 had the highest numbers of interventions with 628 and 643 (15.80 and 16.18%) respectively. Most of the interventions, namely 3410 (85.79%) were classified as medicine optimisation interventions and 565 (14.21%) as prescribing errors. In the medicine optimisation intervention category, 2985 (75.09%) were due to insulin not charted for ongoing administration.Conclusion This study provides insights into pharmacist interventions for inpatients on insulin, showing that high-risk medicine pharmacists recorded most interventions. The classification of the insulin interventions into medicine optimisation and prescribing errors provides useful information for the training of prescribers in insulin management.

Free viewing perceptual asymmetry for distance judgments: objects in right hemispace are closer than they appear.

Neurologically normal individuals demonstrate leftward biases in tasks of line bisection and judgments of brightness, numerosity, and size. Normals also report and demonstrate a right-sided bias when bumping into objects. Collectively, these results suggest that normals relatively neglect the right hemispace. The present experiment investigated the possibility that normals will also demonstrate leftward biases for judgments of distance. Participants viewed two equivalent but mirror-reversed three-dimensional shapes ("boxes" and "pyramids") of various orientations, sizes, and angles, making judgments about the perceived closeness of the stimuli. Significant leftward biases were exhibited for judgments of the closeness of boxes, but not for pyramids. The findings of the current study support the hypothesis that the normal tendency to bump into objects with the right side of one's body might be due to a perceptual asymmetry for distance judgments.

Subtotal Nasal Reconstruction Using a Custom 3-Dimensional Porous Polyethylene Construct.

Subtotal loss of the nose is a devastating occurrence. Traditional approaches to reconstruction have employed techniques that sequentially restore the nasal lining, support and external cover using autologous tissues. The results can be quite variable and are heavily weighted on surgical experience and expertise. We report a case of subtotal nasal reconstruction using a computer generated, 3-D printed porous polyethylene (PPE) scaffold. The patient is a 64-year-old man who presented with a sub-total nasal defect following excision of recurrent basal cell carcinoma. The missing parts comprised the distal half of the composite nose including the nasal floor and lining. The replacement nose was constructed on the patient's right radial forearm. A computer generated PPE nasal scaffold was prelaminated with a forearm flap for lining and a free temporal fascial flap and skin graft for external cover. Following healing, nostrils were created and the nasal construct was then microsurgically transferred to the face. At 18 months post-op, the reconstructed nose has remained stable and functional with excellent aesthetic appearance. The implications for use of 3-D scaffolds for composite nasal reconstruction are enormous.

The cross algorithm for phase-aberration correction in medical ultrasound images formed with two-dimensional arrays.

Common-midpoint signals in the near-field signal-redundancy (NFSR) algorithm for one-dimensional arrays are acquired using three consecutive transducer elements. An all-row-plus-two-column algorithm has been proposed to implement the one-dimensional NFSR algorithm on two dimensional arrays. The disadvantage of this method is that its ambiguity profile is not linear and a timeconsuming iterative method has to be used to linearize the ambiguity profile. An all-row-plus-two-column-and-a-diagonal algorithm has also been proposed. Its ambiguity profile is linear, but it is very sensitive to noise and cannot be used. In this paper, a novel cross algorithm is proposed to implement the NFSR algorithm on two-dimensional arrays. In this algorithm, common-midpoint signals are acquired using four adjacent transducer elements, which is not available in one-dimensional arrays. Its advantage includes a linear ambiguity profile and a higher measurement signal-to-noise ratio. The performance of the cross algorithm is evaluated theoretically. The region of redundancy is analyzed. The procedure for deriving the phaseaberration profile from peak positions of cross-correlation functions between common-midpoint signals is discussed. This algorithm is tested with a simulated data set acquired with a two-dimensional array, and the result shows that the cross algorithm performs better than the all-row plus-twocolumn NFSR algorithm.

Implementation of the near-field signal redundancy phase-aberration correction algorithm on two-dimensional arrays.

Near-field signal-redundancy (NFSR) algorithms for phase-aberration correction have been proposed and experimentally tested for linear and phased one-dimensional arrays. In this paper the performance of an all-row-plus-two-column, two-dimensional algorithm has been analyzed and tested with simulated data sets. This algorithm applies the NFSR algorithm for one-dimensional arrays to all the rows as well as the first and last columns of the array. The results from the two column measurements are used to derive a linear term for each row measurement result. These linear terms then are incorporated into the row results to obtain a two-dimensional phase aberration profile. The ambiguity phase aberration profile, which is the difference between the true and the derived phase aberration profiles, of this algorithm is not linear. Two methods, a trial-and-error method and a diagonal-measurement method, are proposed to linearize the ambiguity profile. The performance of these algorithms is analyzed and tested with simulated data sets.

Impact of propagation through an aberrating medium on the linear effective apodization of a nonlinearly generated second harmonic field.

Techniques based on the nonlinearly generated second harmonic signal (tissue harmonic imaging) have rapidly supplanted linear (fundamental) imaging methods as the standard in two-dimensional echocardiography. Enhancements to the compactness of the nonlinearly generated second harmonic (2f) field component with respect to the fundamental (1f) field component are widely considered to be among the factors contributing to the observed image quality improvements. The objective of this study was to measure the impact of phase and amplitude aberrations resulting from propagation through an inhomogeneous tissue, on the beamwidths associated with: the fundamental (1f); the nonlinearly generated second harmonic (2f); and the linearly propagated, effective apodization signal at the same (21) frequency. Modifications to the transmit characteristics of a phased-array imaging system were validated with hydrophone measurements. Results demonstrate that the characteristics of the diffraction pattern associated with the linear-propagation effective apodization transmit case were found to be in good agreement with the detailed spatial characteristics of the nonlinearly generated second harmonic field. The effects of the abdominal wall tissue aberrators are apparent for all three of the beam profiles studied. Consistent with the improved image quality associated with harmonic imaging, the aberrated nonlinearly generated second harmonic beam was shown to remain more compact than the corresponding aberrated fundamental beam patterns in the presence of the interposed aberrator.

Novel stimuli are negative stimuli: evidence that negative affect is reduced in the mere exposure effect.

Repeated exposure of a nonreinforced stimulus results in an increased preference for that stimulus, the mere exposure effect. The present study repeatedly presented positive, negative, and neutrally affective faces to 48 participants while they made judgments about the emotional expression. Participants then rated the likeability of novel neutrally expressive faces and some of these previously presented faces, this time in their neutral expression. Faces originally presented as happy were rated as the most likeable, followed by faces originally presented as neutral. Negative and novel faces were not rated significantly differently from each other. These findings support the notion that the increase in preference towards repeatedly presented stimuli is the result of the reduction in negative affect, consistent with the modified two-factor uncertainty-reduction model and classical conditioning model of the mere exposure effect.

Spatial coherence of backscatter for the nonlinearly produced second harmonic for specific transmit apodizations.

To be successful, correlation-based, phase-aberration correction requires a high correlation among backscattered signals. For harmonic imaging, the spatial coherence of backscatter for the second harmonic component is different than the spatial coherence of backscatter for the fundamental component. The purpose of this work was to determine the effect of changing the transmit apodization on the spatial coherence of backscatter for the nonlinearly generated second harmonic. Our approach was to determine the effective apodizations for the fundamental and second harmonic using both experimental measurements and simulations. Two-dimensional measurements of the transverse cross sections of the finite-amplitude ultrasonic fields generated by rectangular and circular apertures were acquired with a hydrophone. Three different one-dimensional transmit apodization functions were investigated: uniform, Riesz, and trapezoidal. An effective apodization was obtained for each transmit apodization by backpropagating the values measured from within the transmit focal zone using a linear angular spectrum approach. Predictions of the spatial coherence of backscatter were obtained using the pulse-echo Van Cittert-Zernike theorem. In all cases the effective apodization at 2f was narrower than the transmit apodization. We demonstrate that certain transmit apodizations result in a greater spatial coherence of backscatter at the second harmonic than at the fundamental.

Spatial coherence of the nonlinearly generated second harmonic portion of backscatter for a clinical imaging system.

Correlation-based approaches to phase aberration correction rely on the spatial coherence of backscattered signals. The spatial coherence of backscatter from speckle-producing targets is predicted by the auto correlation of the transmit apodization (Van Cittert-Zernike theorem). Work by others indicates that the second harmonic beam has a wider mainlobe with lower sidelobes than a beam transmitted at 2f. The purpose of this paper is to demonstrate that the spatial coherence of backscatter for the second harmonic is different from that of the fundamental, as would be anticipated from applying the Van Cittert-Zernike theorem to the reported measurements of the second harmonic field. Another objective of this work is to introduce the concept of the effective apodization and to verify that the effective apodization of the second harmonic is narrower than the transmit apodization. The spatial coherence of backscatter was measured using three clinical arrays with a modified clinical imaging system. The spatial coherence results were verified using a pseudo-array scan in a transverse plane of the transmitted field with a hydrophone. An effective apodization was determined by backpropagating these values using a linear angular spectrum approach. The spatial coherence for the harmonic portion of backscatter differed systematically and significantly from the auto correlation of the transmit apodization.

Adaptive coherent averaging for real-time electrocardiogram enhancement.

This paper presents an adaptive coherent averaging structure capable of removing broad-band interference from the electrocardiogram (ECG) while preserving the morphological features of the signal. The proposed structure improves the signal-to-noise ratio (SNR) of the adaptive line enhancer (ALE) while maintaining robustness to quasi-periodic signals. The least mean-square (LMS) and recursive least-square (RLS) adaptive algorithms are implemented. Analysis and comparison of the results is provided, leading to an optimized hybrid implementation. The cascade nature of the proposed structure is both scalable and suitable for implementation in real-time hardware.

Timing-error-difference calibration of a two-dimensional array imaging system using the overlapping-subaperture algorithm.

Timing errors in the transmitting and receiving electronic channels of an imaging system can generate different transmission and reception phase-aberration profiles. To decide if these two profiles need to be measured separately, an overlapping-subaperture algorithm has been proposed in a previous paper to measure the difference between timing errors in transmitting and receiving channels connected to each element in a two-dimensional array. This algorithm has been used to calibrate a custom built imaging system with a curved linear two-dimensional array, and the results are presented in this paper. The experimental results have demonstrated that the overlapping-subaperture algorithm is capable of calibrating the timing-error-difference profile of this imaging system with a standard deviation of only a few nanoseconds. Experimental results have also shown that the time-error-difference profile of this imaging system is smaller than one tenth of a wavelength and there is no need to measure the transmission and reception phase-aberration profiles separately. The derived average phase-aberration profile using the near-field signal-redundancy algorithm can be used to correct phase aberrations for both transmission and reception.

Comparative efficacy of a secretory phospholipase A2 inhibitor with conventional anti-inflammatory agents in a rat model of antigen-induced arthritis.

INTRODUCTION: Previously, secretory phospholipase A2 (sPLA2) inhibition has been used as an adjunct to conventional rheumatoid arthritis therapy in human clinical trials without significant improvement of arthritic pathology. In this study, we compared the efficacy of a potent and orally active group IIa secretory phospholipase A2 inhibitor (sPLA2I) to conventional anti-arthritic agents; infliximab, leflunomide and prednisolone, in a rat model of antigen-induced arthritis. METHODS: Initially, to establish efficacy and dose-response, rats were orally dosed with the sPLA2I (1 and 5 mg/kg) two days prior to arthritis induction, and then daily throughout the 14-day study period. In the second trial, rats were orally dosed with the sPLA2I (5 and 10 mg/kg/day) beginning two days after the induction of arthritis, at the peak of joint swelling. Separate groups of rats were also dosed with the tumour necrosis factor-alpha (TNF-α) inhibitor infliximab (single 3 mg/kg i.v. injection), leflunomide (10 mg/kg/day, oral) or prednisolone (1 mg/kg/day, oral) at this same time point and used as comparative treatments. RESULTS: In the pathology prevention trial, both 1 and 5 mg/kg dose groups of sPLA2I demonstrated a significant reduction in joint swelling and gait disturbances; however, only the higher 5 mg/kg dose resulted in significantly reduced histopathology scores. In the post-induction trial, rats dosed with sPLA2I showed a significant improvement in joint swelling and gait scoring, whereas none of the conventional therapeutics achieved a significant decrease in both of these two disease markers. Histopathological scoring at the end-point of the study demonstrated significantly reduced median scores in rats treated with 10 mg/kg sPLA2I and leflunomide. CONCLUSIONS: The results from this study suggest a pathogenic role for sPLA2 enzymes in this model of arthritis in rats, and the potential clinical utility of sPLA2 inhibition as a safer, and more effective, alternative to conventional anti-arthritic therapeutics.

Safety and complications reporting update on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique.

UNLABELLED: Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the safety of culture expanded MSC's for human use has only just begun to be reported. METHODS: Between 2006 and 2010, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=50; group 2: n=290-one patient in both groups). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints or into intervertebral discs with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites. RESULTS: The mean age of patients treated was 53 +/- 13.85 years; 214 were males and 125 females with mean follow-up time from any procedure being 435 days +/- 261 days. Number of contacts initiated based on time from first procedure was 482 at 3 months, 433 at 6 months, 316 contacts at 12 months, 110 contacts at 24 months, and 22 contacts at 36 months. For Group 1, 50 patients underwent 210 MRI surveillance procedures at 3 months, 6 months, 1, 2, and 3 years which failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented significantly less morbidity than is commonly reported for more invasive surgical procedures, all of which were either self-limited or were remedied with therapeutic measures. Two patients were diagnosed with cancer out of 339 patients treated since study inception; however, this was almost certainly unrelated to the MSC therapy and the neoplasm rate in similar to that seen in the U.S. Caucasian population. Knee outcome data was collected on a subset of patients. Here, > 75% improvement was reported in 41.4% while decreasing the improvement threshold to > 50% improvement, 63.2% reported an improvement. At an average reporting time of 11.3 months from first procedure average reported relief in the knee sample equaled 53.1% (n=133 reporting). CONCLUSIONS: Using both intensive high field MRI tracking and complications surveillance in 339 patients, no neoplastic complications were detected at any stem cell re-implantation site. These findings are consistent with our prior publication and other published reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs for orthopedic use.

Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique.

UNLABELLED: ABSTRUCT: Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the complication rate for autologous MSC therapy is only now beginning to be reported. METHODS: Between 2005 and 2009, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=45; group 2: n=182). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints (n=213) or into intervertebral discs (n=13) with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites. RESULTS: Mean follow-up from the time of the re-implant procedure was 10.6 +/- 7.3 months. Serial MRI's at 3 months, 6 months, 1 year and 2 years failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented 7 cases of probable procedure-related complications (thought to be associated with the re-implant procedure itself) and three cases of possible stem cell complications, all of which were either self-limited or were remedied with simple therapeutic measures. One patient was diagnosed with cancer; however, this was almost certainly unrelated to the MSC therapy. CONCLUSIONS: Using both high field MRI tracking and general surveillance in 227 patients, no neoplastic complications were detected at any stem cell re-implantation site. These findings are consistent with other reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs that were expanded in vitro for limited periods.

Lateral biases in assumptions of lighting position.

People presume that the light source in pictures comes from above, and there is some evidence that this phenomenon also demonstrates lateral biases. When investigators present multiple ambiguous stimuli or visually complex objects, people assume that the source of light is from above, and to the left. However, when single relatively simple stimuli are presented, this lateral bias is not readily observed. To investigate whether lateral bias is dependent on the number of stimuli presented, the present experiment employs a within-subjects design to present single spheres or pairs of spheres. Contrary to our expectations, leftward biases were exhibited in both the single-sphere condition and the paired-spheres condition. Single spheres that were lit from the left were more likely to be judged as convex than comparable spheres lit from the right. Similarly, when pairs of laterally lit spheres were presented and participants were asked to judge which sphere appeared to be more convex, participants chose spheres lit from the left regardless of the angle of illumination. Collectively, these results suggest that there are lateral biases in assumptions of illumination position and that these biases do not depend on the number of stimuli being perceived at any given time.

Rightward biases in free-viewing visual bisection tasks: implications for leftward responses biases on similar tasks.

Neurologically normal individuals exhibit strong leftward response biases during free-viewing perceptual judgments of brightness, quantity, and size. When participants view two mirror-reversed objects and they are forced to choose which object appears darker, more numerous, or larger, the stimulus with the relevant feature on the left side is chosen 60-75% of the time. This effect could be influenced by inaccurate judgments of the true centre-point of the objects being compared. In order to test this possibility, 10 participants completed three visual bisection tasks on stimuli known to elicit strong leftward response biases. Participants were monitored using a remote eye-tracking device and instructed to stare at the subjective midpoint of objects presented on a computer screen. Although it was predicted that bisection errors would deviate to the left of centre (as is the case in the line bisection literature), the opposite effect was found. Significant rightward bisection errors were evident on two of the three tasks, and the leftward biases seen during forced-choice tasks could be the result of misjudgments to the right of centre on these same tasks.