The First Successful Combined Full Face and Bilateral Hand Transplant.

BACKGROUND: Vascularized composite allotransplantation has redefined the frontiers of plastic and reconstructive surgery. At the cutting edge of this evolving paradigm, the authors present the first successful combined full face and bilateral hand transplant. METHODS: A 21-year-old man presented for evaluation with sequelae of an 80 percent total body surface area burn injury sustained after a motor vehicle accident. The injury included full face and bilateral upper extremity composite tissue defects, resulting in reduced quality of life and loss of independence. Multidisciplinary evaluation confirmed eligibility for combined face and bilateral hand transplantation. The operative approach was validated through 11 cadaveric rehearsals utilizing computerized surgical planning. Institutional review board and organ procurement organization approvals were obtained. The recipient, his caregiver, and the donor family consented to the procedure. RESULTS: Combined full face (i.e., eyelids, ears, nose, lips, and skeletal subunits) and bilateral hand transplantation (i.e., forearm level) was performed over 23 hours on August 12 to 13, 2020. Triple induction and maintenance immunosuppressive therapy and infection prophylaxis were administered. Plasmapheresis was necessary postoperatively. Minor revisions were performed over seven subsequent operations, including five left upper extremity, seven right upper extremity, and seven facial secondary procedures. At 8 months, the patient was approaching functional independence and remained free of acute rejection. He had significantly improved range of motion, motor power, and sensation of the face and hand allografts. CONCLUSIONS: Combined face and bilateral hand transplantation is feasible. This was the most comprehensive vascularized composite allotransplantation procedure successfully performed to date, marking a new milestone in plastic and reconstructive surgery for patients with otherwise irremediable injuries.

Plastic Surgery amidst the Pandemic: The New York University Experience at the Epicenter of the COVID-19 Crisis.

SUMMARY: The coronavirus disease of 2019 pandemic became a global threat in a matter of weeks, with its future implications yet to be defined. New York City was swiftly declared the epicenter of the pandemic in the United States as case numbers grew exponentially in a matter of days, quickly threatening to overwhelm the capacity of the health care system. This burgeoning crisis led practitioners across specialties to adapt and mobilize rapidly. Plastic surgeons and trainees within the New York University Langone Health system faced uncertainty in terms of future practice, in addition to immediate and long-term effects on undergraduate and graduate medical education. The administration remained vigilant and adaptive, enacting departmental policies prioritizing safety and productivity, with early deployment of faculty for clinical support at the front lines. The authors anticipate that this pandemic will have far-reaching effects on the future of plastic surgery education, trends in the pursuit of elective surgical procedures, and considerable consequences for certain research endeavors. Undoubtedly, there will be substantial impact on the physical and mental well-being of health care practitioners across specialties. Coordinated efforts and clear lines of communication between the Department of Plastic Surgery and its faculty and trainees allowed a concerted effort toward the immediate challenge of tempering the spread of coronavirus disease of 2019 and preserving structure and throughput for education and research. Adaptation and creativity have ultimately allowed for early rebooting of in-person clinical and surgical practice. The authors present their coordinated efforts and lessons gleaned from their experience to inform their community's preparedness as this formidable challenge evolves.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Facial Transplantation for an Irreparable Central and Lower Face Injury: A Modernized Approach to a Classic Challenge.

BACKGROUND: Facial transplantation introduced a paradigm shift in the reconstruction of extensive facial defects. Although the feasibility of the procedure is well established, new challenges face the field in its second decade. METHODS: The authors' team has successfully treated patients with extensive thermal and ballistic facial injuries with allotransplantation. The authors further validate facial transplantation as a reconstructive solution for irreparable facial injuries. Following informed consent and institutional review board approval, a partial face and double jaw transplantation was performed in a 25-year-old man who sustained ballistic facial trauma. Extensive team preparations, thorough patient evaluation, preoperative diagnostic imaging, three-dimensional printing technology, intraoperative surgical navigation, and the use of dual induction immunosuppression contributed to the success of the procedure. RESULTS: The procedure was performed on January 5 and 6, 2018, and lasted nearly 25 hours. The patient underwent hyoid and genioglossus advancement for floor-of-mouth dehiscence, and palate wound dehiscence repair on postoperative day 11. Open reduction and internal fixation of left mandibular nonunion were performed on postoperative day 108. Nearly 1 year postoperatively, the patient demonstrates excellent aesthetic outcomes, intelligible speech, and is tolerating an oral diet. He remains free from acute rejection. CONCLUSIONS: The authors validate facial transplantation as the modern answer to the classic reconstructive challenge imposed by extensive facial defects resulting from ballistic injury. Relying on a multidisciplinary collaborative approach, coupled with innovative emerging technologies and immunosuppression protocols, can overcome significant challenges in facial transplantation and reinforce its position as the highest rung on the reconstructive ladder. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Cosmological Constraints from Multiple Probes in the Dark Energy Survey.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

Three-Dimensional Analysis of Donor Masks for Facial Transplantation.

BACKGROUND: Face transplant teams have an ethical responsibility to restore the donor's likeness after allograft procurement. This has been achieved with masks constructed from facial impressions and three-dimensional printing. The authors compare the accuracy of conventional impression and three-dimensional printing technology. METHODS: For three subjects, a three-dimensionally-printed mask was created using advanced three-dimensional imaging and PolyJet technology. Three silicone masks were made using an impression technique; a mold requiring direct contact with each subject's face was reinforced by plaster bands and filled with silicone. Digital models of the face and both masks of each subject were acquired with Vectra H1 Imaging or Artec scanners. Each digital mask model was overlaid onto its corresponding digital face model using a seven-landmark coregistration; part comparison was performed. The absolute deviation between each digital mask and digital face model was compared with the Mann-Whitney U test. RESULTS: The absolute deviation (in millimeters) of each digitally printed mask model relative to the digital face model was significantly smaller than that of the digital silicone mask model (subject 1, 0.61 versus 1.29, p < 0.001; subject 2, 2.59 versus 2.87, p < 0.001; subject 3, 1.77 versus 4.20, p < 0.001). Mean cost and production times were $720 and 40.2 hours for three-dimensionally printed masks, and $735 and 11 hours for silicone masks. CONCLUSIONS: Surface analysis shows that three-dimensionally-printed masks offer greater surface accuracy than silicone masks. Greater donor resemblance without additional risk to the allograft may make three-dimensionally-printed masks the superior choice for face transplant teams. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Long-distance care of face transplant recipients in the United States.

Promising aesthetic and functional outcomes in facial transplantation have fueled the interest of patients and providers alike. However, there are currently only 11 active face transplant centers in the United States, and only five have accumulated operative experience to date, resulting in an extremely unbalanced geographical distribution of providers. Since face transplant recipients must receive life-long follow-up, this presents unique challenges for face transplant candidates and provider teams, as long-distance travel may add considerable difficulty to pre- and post-transplant care. Furthermore, by compromising follow-up, this burden of travel may impact the ability of experienced face transplant centers to collect data, share knowledge as these patients are followed, and continue to advance the field. This article highlights the unique logistical and ethical implications of the highly probable long-distance nature of face transplant care in the United States, a challenging aspect of management that has not been previously discussed in the literature. Furthermore, we review current strategies in the long-distance management of solid organ transplantation (SOT) recipients, and propose several possibilities to help address these challenges in facial transplantation based on SOT experience.

Exchange coupling between laterally adjacent nanomagnets.

We experimentally demonstrate exchange-coupling between laterally adjacent nanomagnets. Our results show that two neighboring nanomagnets that are each antiferromagnetically exchange-coupled to a common ferromagnetic bottom layer can be brought into strong ferromagnetic interaction. Simulations show that interlayer exchange coupling effectively promotes ferromagnetic alignment between the two nanomagnets, as opposed to antiferromagnetic alignment due to dipole-coupling. In order to experimentally demonstrate the proposed scheme, we fabricated arrays of pairs of elongated, single-domain nanomagnets. Magnetic force microscopy measurements show that most of the pairs are ferromagnetically ordered. The results are in agreement with micromagnetic simulations. The presented scheme can achieve coupling strengths that are significantly stronger than dipole coupling, potentially enabling far-reaching applications in Nanomagnet Logic, spin-wave devices and three-dimensional storage and computing.

Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant: A Reconstructive Solution for the Full Face and Total Scalp Burn.

BACKGROUND: Reconstruction of extensive facial and scalp burns can be increasingly challenging, especially in patients that have undergone multiple procedures with less than ideal outcomes resulting in restricting neck and oral contractures, eyelid dysfunction, and suboptimal aesthetic appearance. METHODS: To establish a reconstructive solution for this challenging deformity, a multidisciplinary team was assembled to develop the foundation to a facial vascularized composite allotransplantation program. The strategy of developing and executing a clinical transplant was derived on the basis of fostering a cohesive and supportive institutional clinical environment, implementing computer software and advanced technology, establishing a cadaveric transplant model, performing a research facial procurement, and selecting an optimal candidate with the aforementioned burn defect who was well informed and had the desire to undergo face transplantation. RESULTS: Approval from the institutional review board and organ procurement organization enabled our face transplant team to successfully perform a total face, eyelids, ears, scalp, and skeletal subunit transplant in a 41-year-old man with a full face and total scalp burn. CONCLUSIONS: The culmination of knowledge attained from previous experiences continues to influence the progression of facial vascularized composite allotransplantation. This surgical endeavor methodically and effectively synchronized the fundamental principles of aesthetic, craniofacial, and microvascular surgery to restore appearance and function to a patient suffering from failed conventional surgery for full face and total scalp burns. This procedure represents the most extensive soft-tissue clinical face transplant performed to date. CLINICAL QUESTION/LEVEL OF EVIDEMCE: Therapeutic, V.

Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant Cadaver Simulation: The Culmination of Aesthetic, Craniofacial, and Microsurgery Principles.

BACKGROUND: The application of aesthetic, craniofacial, and microsurgical principles in the execution of face transplantation may improve outcomes. Optimal soft-tissue face transplantation can be achieved by incorporating subunit facial skeletal replacement and subsequent tissue resuspension. The purpose of this study was to establish a reconstructive solution for a full face and scalp burn and to evaluate outcome precision and consistency. METHODS: Seven mock face transplants (14 cadavers) were completed in the span of 1 year. Components of the vascularized composite allograft included the eyelids, nose, lips, facial muscles, oral mucosa, total scalp, and ears; and skeletal subunits of the zygoma, nasal bone, and genial segment. Virtual surgical planning was used for osteotomy selection, and to evaluate postoperative precision of hard- and soft-tissue elements. RESULTS: Each transplant experience decreased each subsequent transplant surgical time. Prefabricated cutting guides facilitated a faster dissection of both donor and recipient tissue, requiring minimal alteration to the allograft for proper fixation of bony segments during inset. Regardless of donor-to-recipient size discrepancy, ample soft tissue was available to achieve tension-free allograft inset. Differences between virtual transplant simulation and posttransplant measurements were minimal or insignificant, supporting replicable and precise outcomes. CONCLUSIONS: This facial transplant model was designed to optimize reconstruction of extensive soft-tissue defects of the craniofacial region representative of electrical, thermal, and chemical burns, by incorporating skeletal subunits within the allograft. The implementation of aesthetic, craniofacial, and microsurgical principles and computer-assisted technology improves surgical precision, decreases operative time, and may optimize function.

Total Face, Eyelids, Ears, Scalp, and Skeletal Subunit Transplant Research Procurement: A Translational Simulation Model.

BACKGROUND: Cadaveric face transplant models are routinely used for technical allograft design, perfusion assessment, and transplant simulation but are associated with substantial limitations. The purpose of this study was to describe the experience of implementing a translational donor research facial procurement and solid organ allograft recovery model. METHODS: Institutional review board approval was obtained, and a 49-year-old, brain-dead donor was identified for facial vascularized composite allograft research procurement. The family generously consented to donation of solid organs and the total face, eyelids, ears, scalp, and skeletal subunit allograft. RESULTS: The successful sequence of computed tomographic scanning, fabrication and postprocessing of patient-specific cutting guides, tracheostomy placement, preoperative fluorescent angiography, silicone mask facial impression, donor facial allograft recovery, postprocurement fluorescent angiography, and successful recovery of kidneys and liver occurred without any donor instability. Preservation of the bilateral external carotid arteries, facial arteries, occipital arteries, and bilateral thyrolinguofacial and internal jugular veins provided reliable and robust perfusion to the entirety of the allograft. Total time of facial procurement was 10 hours 57 minutes. CONCLUSIONS: Essential to clinical face transplant outcomes is the preparedness of the institution, multidisciplinary face transplant team, organ procurement organization, and solid organ transplant colleagues. A translational facial research procurement and solid organ recovery model serves as an educational experience to modify processes and address procedural, anatomical, and logistical concerns for institutions developing a clinical face transplantation program. This methodical approach best simulates the stressors and challenges that can be expected during clinical face transplantation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Wide-Field Lensing Mass Maps from Dark Energy Survey Science Verification Data.

We present a mass map reconstructed from weak gravitational lensing shear measurements over 139 deg2 from the Dark Energy Survey science verification data. The mass map probes both luminous and dark matter, thus providing a tool for studying cosmology. We find good agreement between the mass map and the distribution of massive galaxy clusters identified using a red-sequence cluster finder. Potential candidates for superclusters and voids are identified using these maps. We measure the cross-correlation between the mass map and a magnitude-limited foreground galaxy sample and find a detection at the 6.8σ level with 20 arc min smoothing. These measurements are consistent with simulated galaxy catalogs based on N-body simulations from a cold dark matter model with a cosmological constant. This suggests low systematics uncertainties in the map. We summarize our key findings in this Letter; the detailed methodology and tests for systematics are presented in a companion paper.

Bone and cartilage demonstrate changes localized to bone marrow edema-like lesions within osteoarthritic knees.

OBJECTIVE: Our objective is to understand the biological and mechanical pathways linking cartilage, bone, and marrow changes in the progression of osteoarthritis (OA). The aim of the present study was to evaluate bone structure and composition within bone marrow edema-like lesion (BMEL) regions associated with knee OA. METHODS: Tibial plateau specimens (n = 18) were collected from 10 subjects with knee OA during total knee arthroplasty (TKA). Magnetic resonance (MR) imaging was used to identify BMEL and quantify metrics of cartilage composition. Micro-computed tomography (µCT) and high-resolution peripheral quantitative computed tomography (HR-pQCT) were used to quantify density and microstructure of the subchondral trabecular bone. Fourier transform infrared (FTIR) spectroscopy was used to quantify tissue composition. RESULTS: Trabecular bone within BMEL was higher in volume fraction, with more and thicker trabeculae that were more plate-like in structure compared to unaffected regions. BMEL trabecular tissue composition had decreased phosphate and carbonate content. Marrow infiltration by a fibrous collagen network and evidence of increased bone remodeling were present. Structural and compositional changes were specifically localized to regions underlying cartilage degradation. CONCLUSION: These results support the paradigm of focal interactions among bone, marrow, and cartilage in the progression of knee OA. Quantitative evaluation of tissue changes and interactions may aid in the understanding of disease pathophysiology and provide imaging markers for disease progression.

Nanomagnet logic: progress toward system-level integration.

Quoting the International Technology Roadmap for Semiconductors (ITRS) 2009 Emerging Research Devices section, 'Nanomagnetic logic (NML) has potential advantages relative to CMOS of being non-volatile, dense, low-power, and radiation-hard. Such magnetic elements are compatible with MRAM technology, which can provide input­output interfaces. Compatibility with MRAM also promises a natural integration of memory and logic. Nanomagnetic logic also appears to be scalable to the ultimate limit of using individual atomic spins.' This article reviews progress toward complete and reliable NML systems. More specifically, we (i) review experimental progress toward fundamental characteristics a device must possess if it is to be used in a digital system, (ii) consider how the NML design space may impact the system-level energy (especially when considering the clock needed to drive a computation), (iii) explain--using both the NML design space and a discussion of clocking as context­how reliable circuit operation may be achieved, (iv) highlight experimental efforts regarding CMOS friendly clock structures for NML systems, (v) explain how electrical I/O could be achieved, and (vi) conclude with a brief discussion of suitable architectures for this technology. Throughout the article, we attempt to identify important areas for future work.

Non-majority magnetic logic gates: a review of experiments and future prospects for 'shape-based' logic.

We discuss the experimental demonstration of non-majority, two-input, nanomagnet logic (NML) AND and OR gates. While gate designs still can incorporate the symmetric, rounded-rectangle magnets used in the three-input majority gate experiments by Imre (2006 Science 311 205-8), our new designs also leverage magnets with an edge that has a well-defined 'slant'. In rectangular and ellipsoid nanomagnets, the easy axis of the device coincides with its longer edge. For a magnet with a slanted edge, the easy and hard axes are 'tilted', and magnetic fields applied along the (geometrical) hard axis alone can set the easy axis magnetization state. This switching phenomenon can be employed to realize NML Boolean logic gates with both reduced footprints and critical path delays. Experimental demonstrations of two-input AND and OR gates are supported by corresponding micromagnetic simulations with temperature effects associated with a 300 K environment. Simulations suggest that the time evolution of experimentally demonstrated structures is correct, and that designs can also tolerate clock field misalignment. Additionally, simulations suggest that a slanted-edge 'compute magnet' can (i) be driven by two anti-ferromagnetically ordered lines of NML devices (for input) and (ii) drive an anti-ferromagnetically ordered line (for output). Both are essential if slanted-edge devices are to be used in NML circuits. We conclude with a discussion of extensibility and scaling prospects for shape-based computation with nanomagnets.

Majority logic gate for magnetic quantum-dot cellular automata.

We describe the operation of, and demonstrate logic functionality in, networks of physically coupled, nanometer-scale magnets designed for digital computation in magnetic quantum-dot cellular automata (MQCA) systems. MQCA offer low power dissipation and high integration density of functional elements and operate at room temperature. The basic MQCA logic gate, that is, the three-input majority logic gate, is demonstrated.

Factors predictive of difficult colonoscopy.

BACKGROUND: Prediction of a technically difficult colonoscopy may influence patient selection and procedure scheduling. Identification of predictive factors may be difficult because a common endpoint used to evaluate the success of colonoscopy is intubation of the cecum, which is usually achieved. The goal of this study was to examine the feasibility of using an alternative measure, time required for cecal intubation, to identify factors that can impact performance of colonoscopy. METHODS: The time required for cecal intubation was prospectively recorded for 802 consecutive outpatient colonoscopies performed by 7 experienced gastroenterologists. Patient data collected included height, weight, age, bowel habits, surgical history, and findings at colonoscopy. Forty-seven examinations that were stopped because of disease or unacceptable bowel preparation were excluded. The impact of the patient characteristics of the remaining sample of 755 patients on the median time required for cecal intubation for men and women was examined. RESULTS: Older age and female gender, body mass index < or =25.0 (regardless of gender), diverticular disease in women, and a history of constipation or reported laxative use in men were predictors of difficult colonoscopy. CONCLUSIONS: By using median time required for cecal intubation, several patient characteristics were identified that may predict technical difficulty at colonoscopy. These findings have implications for practice and teaching.

Critical flicker frequency responses in visual cortex.

Critical flicker frequency (CFF) threshold is defined as the frequency at which a flickering light is indistinguishable from a steady, non-flickering light. CFF is useful for assessing the temporal characteristics of the visual system. While CFF responses are believed to reflect activity in the central visual system, little is known about how these temporal frequencies are processed in the visual cortex. The current paper estimated the CFF threshold for cells in the rat visual cortex by recording single unit responses to flickering stimuli. Results showed that: (1) there was a broad range of temporal tuning, (2) CFF threshold was lower in simple cells than in complex and hypercomplex cells, and (3) there was no significant difference in CFF threshold between areas 17 and 18.

Pharmacokinetic interactions between cyclosporine and bupropion or methylphenidate.

A 10-year-old boy with a history of heart transplantation had a potentially life-threatening decrease in his cyclosporine (CSA) blood levels during administration of bupropion. Subsequently he had an increase in CSA levels while receiving methylphenidate. These occurrences represent potential drug-drug interactions in children not previously documented in the literature. The CSA-bupropion and CSA-methylphenidate interactions merit further investigation, particularly because psychotropic agents are often prescribed in combination with immunosuppressants in transplantation patients of all ages.