Minimum and early high-energy sonication protocol of MR-guided focused ultrasound thalamotomy for low-skull density ratio patients with essential tremor and Parkinson's disease.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless neurosurgical treatment for patients with medically refractory essential tremor and tremor-dominant Parkinson's disease. A low skull density ratio (SDR) < 0.40 is a known risk factor for treatment failure. The aim of this study was to identify useful sonication strategies for patients with a low SDR < 0.40 by modifying the standard sonication protocol using maximum high-energy sonication while minimizing the number of sonications. METHODS: The authors retrospectively analyzed the effects of modified MRgFUS sonication on low-SDR tremor patients. All patients underwent head CT scans to calculate their SDR. The SDR threshold for MRgFUS thalamotomy was 0.35. The patients in the early series underwent the standard sonication protocol targeting the ventral intermediate nucleus contralateral to the treated hand side. The patients with a low SDR < 0.40 in the late series underwent a modified sonication protocol, in which the number of alignment sonications was minimized and high-energy treatment sonication (> 36,000 J) was used. The authors evaluated the lesion volume the following day and tremor improvement and adverse events 3 and 12 months after the procedure. The sonication patterns between low-SDR patients treated using different sonication protocols were examined using Fisher's exact test. ANOVA was used to examine the lesion volume and tremor improvement in high- and low-SDR patients treated using different sonication protocols. RESULTS: Among 41 patients with an SDR < 0.40, 14 underwent standard sonication and 27 underwent modified sonication. Fewer alignment sonications and high-energy treatment sonications were used in the modified sonication group compared with the standard group (p < 0.001). The duration of modified sonication was significantly shorter than that of standard sonication (p < 0.001). The lesion volume and tremor improvement significantly differed among the high- and low-SDR groups with different sonication protocols (p < 0.001). Low-SDR patients treated using modified sonication protocols had comparable lesion volume and tremor improvement to the high-SDR group. The modified sonication protocol did not significantly increase adverse intraprocedural and postprocedural events. CONCLUSIONS: Minimizing alignment sonications and applying high-energy sonication in early treatment help to create an optimal lesion volume and control tremor in low-SDR patients.

Assessment of head-mounted display for exoscopic neurosurgery.

Background: Head-mounted display (HMD) arises as an alternative display system for surgery. This study aimed to assess the utility of a stereoscopic HMD for exoscopic neurosurgery. Methods: The leading operator and assistants were asked to assess the various aspects of the HMD characteristics compared to the monitor display using a visual analog scale (VAS)-based questionnaire. The VAS score ranged from 0 to 10 (0, HMD was significantly inferior to the monitor; 5, HMD and monitor display were equal; and 10, HMD was significantly superior to the monitor). Results: The surgeons and assistants used and evaluated HMD in seven exoscopic surgeries: three tumor removal, one aneurysm clipping, one anterior cervical discectomy and fusion, and two cervical laminectomy surgeries. The leading operators' assessment of HMD-based surgery was not different from monitor-based surgery; however, the assistants evaluated the field of view, overall image quality, and the assisting procedure as better in MHD-based surgery than monitor-based surgery (P = 0.039, 0.045, and 0.013, respectively). Conclusion: HMD-based exoscopic neurosurgery can be performed at a similar quality as monitor-based surgery. Surgical assistants may benefit from using HMD-based surgery.

Safety and Effects of a Four-Week Preoperative Low-Load Resistance Training With Blood Flow Restriction on Pre- and Postoperative Quadriceps Strength in Patients Undergoing Total Knee Arthroplasty: A Single-Blind Randomized Controlled Trial.

Background/Objectives Enhancing preoperative quadriceps strength and mitigating quadriceps strength loss due to total knee arthroplasty (TKA) is crucial for post-TKA recovery. This study compared the safety and effect of a four-week preoperative regimen of low-load resistance training with blood flow restriction (LLRT-BFR) with those of low-intensity resistance training with slow movement and tonic force generation (LST) on the pre- and postoperative quadriceps strength in patients undergoing TKA. Methods In this randomized controlled trial, 22 patients were assigned to either the LLRT-BFR (n=11) or LST (n=11) group. Primary outcomes included changes in quadriceps strength before and after the intervention and surgery. To assess safety, we monitored D-dimer and high-sensitivity C-reactive protein levels pre- and post-intervention. Statistical analysis involved independent samples t-tests and Mann-Whitney U tests for group comparisons of quadriceps strength changes. Additionally, a two-way repeated-measures analysis of variance was used to assess safety parameters. Results No significant differences were observed between the BFR and LST groups in terms of the rate of increase in quadriceps strength pre- and post-intervention (BFR: median 12.1%, interquartile range -0.8% to 19.5%; LST: median 6.2%, interquartile range 2.7% to 14.7%; p>0.99) or in the rate of reduction in quadriceps strength pre- and post-surgery (BFR: mean -72.4%, standard deviation ±11.2%; LST: mean -75.3%, standard deviation ±12.2%; p=0.57). Safety assessments showed no significant main effects of time, group, or interaction on the safety parameters (all p>0.05). Conclusions LLRT-BFR and LST demonstrated comparable effects on quadriceps strength before and after intervention and surgery in patients undergoing TKA. The lack of significant changes in the safety parameters supports the safety profile of both interventions, indicating their suitability for preoperative conditioning in patients scheduled for TKA.

Quantitative susceptibility mapping and a nonlinearly transformed atlas for targeting the ventral intermediate nucleus of the thalamus in a patient with tremor and thalamic hypertrophy: illustrative case.

BACKGROUND: The ventral intermediate nucleus (Vim) of the thalamus is a surgical target for treating various types of tremor. Because it is difficult to visualize the Vim using standard magnetic resonance imaging, the structure is usually targeted based on the anterior and posterior commissures. This standard targeting method is practical in most patients but not in those with thalamic asymmetry. The authors examined the usefulness of quantitative susceptibility mapping (QSM) and transformed Vim atlas images to estimate the Vim localization in a patient with tremor and significant thalamic hypertrophy. OBSERVATIONS: A 51-year-old right-handed female had experienced a predominant left-hand action tremor for 6 years. Magnetic resonance imaging showed significant hypertrophy of the right thalamus and caudal shift of the thalamic ventral border. The authors referred to the QSM images to localize the decreased susceptibility area within the lateral ventral thalamic nuclei to target the Vim. In addition, the nonlinearly transformed Vim atlas images complemented the imaging-based targeting. The radiofrequency thalamotomy at the modified Vim target relieved the tremor completely. LESSONS: A combination of QSM and nonlinear transformation of the thalamic atlas can be helpful in the targeting method of the Vim for tremor patients with thalamic asymmetry.

Temporally organized representations of reward and risk in the human brain.

The value and uncertainty associated with choice alternatives constitute critical features relevant for decisions. However, the manner in which reward and risk representations are temporally organized in the brain remains elusive. Here we leverage the spatiotemporal precision of intracranial electroencephalography, along with a simple card game designed to elicit the unfolding computation of a set of reward and risk variables, to uncover this temporal organization. Reward outcome representations across wide-spread regions follow a sequential order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We further highlight the role of the anterior insula in generalizing between reward prediction error and risk prediction error codes. Together our results emphasize the importance of neural dynamics for understanding value-based decisions under uncertainty.

Low back pain improvement after cervical laminoplasty in patients without tandem lumbar stenosis.

PURPOSE: This study aimed to demonstrate the impact of lumbar spinal stenosis (LSS) on LBP after cervical laminoplasty for cervical spinal stenosis by analyzing the clinical characteristics and surgical outcomes. METHODS: This retrospective cohort study analyzed 56 consecutive patients with cervical spinal stenosis who underwent cervical laminoplasty. Data on age, sex, Japanese Orthopaedic Association (JOA) scores, JOA Back Pain Evaluation Questionnaire (BPEQ), and visual analog scale (VAS) were collected. The patients with VAS for LBP ≥ 30 or more were included and divided into two groups: without LSS [LSS (-)]or with LSS [LSS (+)]. Preoperative clinical characteristics and postoperative changes were compared between the groups. RESULTS: Preoperative VAS for LBP were 50.7 ± 16.2 mm and 59.8 ± 19.5 mm in the LSS (+) and LSS (-), respectively (p = 0.09). Patients in the LSS (-) were younger (57.6 ± 11.2 vs. 70.7 ± 8.6, p < 0.001) and showed significantly milder preoperative lumbar symptoms in terms of JOA and BPEQ. Patients in the LSS (-) group showed more postoperative changes in low back pain (18.3 ± 26.4 vs. - 8.3 ± 37.6, p = 0.005) and lumbar function (10.8 ± 25.7 vs. - 2.0 ± 22.5, p = 0.04) at BPEQ, and higher recovery in terms of VAS of LBP (23.0 ± 23.8 mm vs. 5.3 ± 25.9 mm, p = 0.008) and buttocks and low limbs (12.5 ± 35.0 mm vs. - 4.3 ± 24.4 mm, p = 0.029). Nine patients in the LSS (+) group underwent lumbar surgery at 12.8 ± 8.5 months after cervical laminoplasty. CONCLUSION: LBP improved after cervical laminoplasty in patients without lumbar stenosis.

Reorganization of Corticospinal Projections after Prominent Recovery of Finger Dexterity from Partial Spinal Cord Injury in Macaque Monkeys.

We investigated morphologic changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in seven macaque monkeys. All monkeys exhibited prominent recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional (n = 4) and ipsilesional (n = 3) hand area of primary motor cortex (M1) were investigated at 5-29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and bouton-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gray matter around the lesion, and terminating in ipsilesional Laminae VI/VII and IX were observed. In addition, axons and terminals from the ipsilesional M1 increased in the ipsilesional Lamina IX after recrossing the midline, which were not observed in intact monkeys. Conversely, axons originating from the ipsilesional M1 and directed toward the contralesional Lamina VII decreased. These results suggest that multiple reorganizations of the corticospinal projections to spinal segments both rostral and caudal to the lesion originating from bilateral M1 underlie a prominent recovery in long-term after spinal cord injury.

Temporally organized representations of reward and risk in the human brain.

The value and uncertainty associated with choice alternatives constitute critical features along which decisions are made. While the neural substrates supporting reward and risk processing have been investigated, the temporal organization by which these computations are encoded remains elusive. Here we leverage the high spatiotemporal precision of intracranial electroencephalography (iEEG) to uncover how representations of decision-related computations unfold in time. We present evidence of locally distributed representations of reward and risk variables that are temporally organized across multiple regions of interest. Reward outcome representations across wide-spread regions follow a temporally cascading order along the anteroposterior axis of the brain. In contrast, expected value can be decoded from multiple regions at the same time, and error signals in both reward and risk domains reflect a mixture of sequential and parallel encoding. We highlight the role of the anterior insula in generalizing between reward prediction error (RePE) and risk prediction error (RiPE), within which the encoding of RePE in the distributed iEEG signal predicts RiPE. Together our results emphasize the utility of uncovering temporal dynamics in the human brain for understanding how computational processes critical for value-based decisions under uncertainty unfold.

Mapping effective connectivity of human amygdala subdivisions with intracranial stimulation.

The primate amygdala is a complex consisting of over a dozen nuclei that have been implicated in a host of cognitive functions, individual differences, and psychiatric illnesses. These functions are implemented through distinct connectivity profiles, which have been documented in animals but remain largely unknown in humans. Here we present results from 25 neurosurgical patients who had concurrent electrical stimulation of the amygdala with intracranial electroencephalography (electrical stimulation tract-tracing; es-TT), or fMRI (electrical stimulation fMRI; es-fMRI), methods providing strong inferences about effective connectivity of amygdala subdivisions with the rest of the brain. We quantified functional connectivity with medial and lateral amygdala, the temporal order of these connections on the timescale of milliseconds, and also detail second-order effective connectivity among the key nodes. These findings provide a uniquely detailed characterization of human amygdala functional connectivity that will inform functional neuroimaging studies in healthy and clinical populations.

Effects of Long-term Hybrid Assistive Limb Use on Gait in Patients with Amyotrophic Lateral Sclerosis.

Objective To assess the long-term effects of hybrid assistive limb (HAL) treatment on gait in patients with amyotrophic lateral sclerosis (ALS). Methods Three courses of treatment with HAL were administered to three women with ALS. Each course had a four- to five-week duration, during which the treatment was performed nine times, with a rest period of at least two months between each course. Gait ability (2-minutes-walk and 10-m-walk tests), ALS Functional Rating Scale-Revised, and respiratory function tests were performed before and after each treatment course. Patients Patients diagnosed with ALS, according to the updated Awaji criteria, by board-certified neurologists in the Department of Neurology and Department of Rehabilitation Medicine, Toho University Omori Faculty of Medicine between January and December 2019 were recruited. Results The average time from the start to the end of the 3 courses was 319.7±33.7 days. A multiple regression analysis was performed for the 2-minutes-walk and 10-m-walk tests, using the baseline value, each participant's ID, and time point as covariates. Changes after each course were considered outcomes. Following the 3 treatment courses, the 2-minutes walk distance improved by 16.61 m (95% confidence interval, -9.33-42.54) compared with the baseline value, but this improvement was not statistically significant (p=0.21). However, cadence significantly improved by 1.30 steps (95% confidence interval, 0.17-2.42; p=0.02). Conclusion Long-term, repetitive HAL treatments may help patients with ALS maintain their gait.

Robot-assisted training using hybrid assistive limb ameliorates gait ability in patients with amyotrophic lateral sclerosis.

OBJECTIVE: The Hybrid Assistive Limb (HAL; CYBERDYNE, Inc., Japan) is a wearable robot device that provides effective gait assistance according to voluntary intention by detecting weak bioelectrical signals of neuromuscular activity on the surface of the skin. We used HAL for patients with amyotrophic lateral sclerosis (ALS) to determine whether HAL training had an effect on their gait ability. METHODS: We conducted a single-center, single-arm, observational study. Patients with ALS underwent HAL training once per day (20-40 min per session) for 9-10 days for at least 4 weeks. Gait ability was evaluated using the 2-minute walk test, the 10-meter walk test without the assistance of HAL, and activities of daily living (ADL) using the Barthel Index and Functional Independence Measures before and after a full course of HAL training. RESULTS: There were no dropouts or adverse events during the observation period. Gait function improved after HAL training. The 2-minute walk test revealed a mean gait distance of 73.87 m (36.65) at baseline and 89.9m (36.70) after HAL training (p = 0.004). The 10-meter walk test showed significantly improved cadence, although gait speed, step length on the 10-m walk, or ADL measurements did not change significantly. CONCLUSIONS: Although HAL is not a curative treatment for ALS, our data suggest that HAL may be effective in ameliorating and preserving gait ability in patients with ALS.

Daptomycin for the Treatment of Gram-Positive Periprosthetic Hip Infections: Can Daptomycin Prevent the Implant Removal?

Introduction Management of periprosthetic hip infections (PHIs) generally consists of implant removal and thorough debridement, accompanied by appropriate antibiotic therapy. Daptomycin (DAP) is a novel antibiotic, which allowed for implant retention in several patients after treating their infected joints. However, there is no consensus about implant retention or removal during the treatment of PHIs. The aim of this study was to examine the effect of DAP and to determine a surgical treatment strategy. Methods This study retrospectively evaluated 20 patients between August 2014 and December 2018, divided into implant retention (n=9) and implant removal groups (n=11). Infection control and risk of recurrent infection were evaluated. Infection control was defined as not requiring implant removal after the final treatment. Results Infection control rates in implant retention and implant removal groups were 67% and 90%, respectively. All late chronic infections resulted in failure cases within the implant retention group. In the implant retention group, mean preoperative risk scores for successful cases were significantly higher than those for failure cases (p<0.05). Conclusions Patients with low risk did not require implant removal, suggesting that DAP may be a breakthrough alternative to traditional PHI management.

Emergence of metamagnetic transition, re-entrant cluster glass and spin phonon coupling in Tb2CoMnO6.

The double perovskite compound Tb2CoMnO6has been investigated using x-ray absorption spectroscopy (XAS), Raman spectroscopy, magnetic measurements andab initioband structure calculations. It is observed that both anti-ferromagnetic (AFM) and ferromagnetic (FM) phase coexist in this material. The presence of anti-site disorder (ASD) has been established from the analysis of neutron diffraction data. Moreover, a prominent metamagnetic transition is observed in theM(H) behavior that has been explained with the drastic reorientation of the pinned domain which are aligned antiparallel by the antiphase boundaries (APBs) at zero field. The ASD further gives rise to spin frustration at low temperature which leads to the re-entrant cluster glass ∼33 K. The coupling between phononic degree of freedom and spin in the system has also been demonstrated. It is observed that the theoretical calculation is consistent with that of the experimentally observed behavior.

Role of the nucleus accumbens in functional recovery from spinal cord injury.

Post brain damage depression impedes functional recovery. On the other hand, higher motivation facilitates functional recovery after damage to the central nervous system, but the neural mechanism of psychological effects on functional recovery is unclear. The nucleus accumbens (NAcc), a motivation center, has not been considered directly involved in motor function. Recently, it was demonstrated that the NAcc makes a direct contribution to motor performance after spinal cord injury by facilitating motor cortex activity. In this perspective, we first summarize our investigation of role of NAcc in motor control during the recovery course after spinal cord injury, followed by a discussion of the current knowledge regarding the relationship between the recovery and NAcc after neuronal damage.

Effects of preoperative low-intensity training with slow movement on early quadriceps weakness after total knee arthroplasty in patients with knee osteoarthritis: a retrospective propensity score-matched study.

BACKGROUND: Severe and early quadriceps weakness (QW) after total knee arthroplasty (TKA), which is caused by acute inflammation resulting from surgical trauma and tourniquet-induced ischemia-reperfusion (IR) injury, can be especially problematic. We focused on tourniquet-induced IR injury, because it has been shown to be preventable through ischemic and exercise preconditioning. Low-intensity resistance exercise with slow movement and tonic force generation (LST) share some similarities with ischemic and exercise preconditioning. The present study primarily aimed to clarify the efficacy of preoperative LST program as prehabilitation for early QW among patients with TKA using propensity score matching analysis. METHODS: This single-center retrospective observational study used data from patients with knee osteoarthritis (n = 277) who were scheduled to undergo unilateral TKA between August 2015 and January 2017. Those with missing outcome data due to their inability to perform tests were excluded. The LST group included participants who performed LST and aerobic exercise (LST session) more than seven times for three months prior to surgery. The control group included participants who performed less than eight LST sessions, a general and light exercise or had no exercise for three months prior to surgery. Knee circumference, thigh volume, knee pain during quadriceps strength test (QST) and timed up and go test (TUG), quadriceps strength, and TUG were measured before and 4 days after surgery. Knee swelling, thigh swelling, Δknee pain, QW, and ΔTUG were determined by comparing pre- and postoperative measurements. RESULTS: Propensity score matching generated 41 matched pairs who had nearly balanced characteristics. The LST group had a significantly lower knee and thigh swelling, QW, and ΔTUG compared to the control group (all, p < 0.05). No significant differences in Δknee pain during the QST and TUG were observed between both groups (both, p > 0.05). CONCLUSIONS: The present study demonstrated the beneficial effects of preoperative LST program on knee swelling, thigh swelling, QW, and walking disability immediately after TKA.

Coronary spastic angina after the administration of intravenous immunoglobulin in myasthenia gravis: a case report.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by antibodies that block or destroy nicotinic acetylcholine receptors at the neuromuscular junction. Most of MG patients need immunosuppression agents in addition to treatments that alleviate the symptoms. Intravenous immunoglobulin (IVIg) and plasma exchange are specific treatments given to patients with severe MG and myasthenia gravis crisis. IVIg therapy can cause an increase in serum viscosity; therefore, the risk for thromboembolic events, such as stroke, myocardial infarction, and pulmonary embolism, are reported after IVIg therapy. CASE PRESENTATION: An MG patient was treated with pyridostigmine bromide and prednisolone. The patient's symptoms worsened 26 days after the commencement of treatment and was presented with head drop and dyspnea. The patient was diagnosed with MG crisis and IVIg was initiated. However, the patient reported chest pain and dyspnea 3 days after IVIg had started. An electrocardiogram (ECG) revealed ST elevations in leads II, III, and aVF. A cardiac catheterization was performed and stenosis, obstruction, and sclerosis were ruled out. Glyceryl trinitrate relieved the patient's symptoms, suggesting coronary spastic angina (CSA). CONCLUSIONS: We report the first case of CSA after IVIg. Practitioners should be aware of the potential risks of CSA when administering IVIg for MG patients, in particular in old patients with vascular risk factors.

Ferromagnetic metal conversion directly from two-dimensional nickel hydroxide.

We have demonstrated a direct metallic conversion from nickel hydroxide nanosheets to nickel metal nanostructures by thermal annealing in vacuum. The metal transition of the single-layer nanosheets deposited on a Si substrate was revealed by x-ray absorption near edge structure (XANES) measurements. The XANES signal significantly changed at annealing temperatures above 250 °C. The metal transition temperature coincides with the reported temperatures at which layered nickel hydroxide nanosheets are converted to nickel oxide nanosheets by calcination in air. Auger measurements confirmed that a dissociation of oxygen from the hydroxide nanosheet induces the metallic conversion. The converted nickel metallic structures exhibit ferromagnetic behavior revealed by x-ray magnetic circular dichroism (XMCD) measurement. Atomic force microscopy measurements indicate that diffusions of nickel atoms on the substrates leads to a structural change from a 2D-like structure to a particle-like structure.

Functional Connectivity Analysis and Prediction of Pain Relief in Association with Spinal Decompression Surgery.

BACKGROUND: Although spinal decompression surgery is an effective treatment for myelopathy-induced upper limb pain, some postoperative patients suffer from residual pain in spite of adequate decompression. However, the neural mechanism underlying the poor outcome of pain relief is still unclear. The goal of this study was to explore the brain mechanisms involved in the poor recovery of upper limb pain after the spinal decompression surgery by using functional connectivity (FC) analysis. METHODS: In this cross-sectional study, 17 patients who underwent cervical spinal decompression surgery were included. Functional MRI (fMRI) during a tactile stimulus for each hand was performed at 1 day before and 7 days after the surgery. In total, 34 fMRI scans (17 left and right upper limbs, respectively) were obtained before and after the surgery, respectively. The patients were divided into poor-recovery and good-recovery groups, and then we searched for the FC that was related to poor-recovery. RESULTS: The poor-recovery group (n = 15) showed significantly stronger connectivity between the postcentral gyrus (postCG) and dorsolateral prefrontal cortex (DLPFC) than the good-recovery group (n = 12) preoperatively. When the cutoff value of the preoperative FC between the left postCG and right middle frontal gyrus included in DLPFC was >0.17, the sensitivity and specificity for poor recovery were 73% and 75%, respectively. CONCLUSIONS: Our study showed that FC between the postCG and DLPFC may be a predictor of pain relief. This result suggested that assessing FC can lead to more informed surgical interventions for cervical spondylotic myelopathy.

The Ventral Striatum is a Key Node for Functional Recovery of Finger Dexterity After Spinal Cord Injury in Monkeys.

In a recent study, we demonstrated that the ventral striatum (VSt) controls finger movements directly during the early recovery stage after spinal cord injury (SCI), implying that the VSt may be a part of neural substrates responsible for the recovery of dexterous finger movements. The VSt is accepted widely as a key node for motivation, but is not thought to be involved in the direct control of limb movements. Therefore, whether a causal relationship exists between the VSt and motor recovery after SCI is unknown, and the role of the VSt in the recovery of dexterous finger movements orfinger movements in general after SCI remains unclear. In the present study, functional brain imaging in a macaque model of SCI revealed a strengthened functional connectivity between motor-related areas and the VSt during the recovery process for precision grip, but not whole finger grip after SCI. Furthermore, permanent lesion of the VSt impeded the recoveryof precision grip, but not coarse grip. Thus, the VSt was needed specifically for functional recovery of dexterous finger movements. These results suggest that the VSt is the key node of the cortical reorganization required for functional recovery of finger dexterity.