Analysis of the positional relationship of the long thoracic nerve considering clinical treatment.

INTRODUCTION: The long thoracic nerve (LTN) has a risk of being damaged during chest surgery and should be considered when performing anesthesia such as a serratus anterior plane block (SAPB). We analyzed the relationship between landmarks-the fourth to ninth intercostal space (ICS) at the midaxillary line (MAL), through which the distal part of the LTN passes-and the LTN. MATERIALS AND METHODS: We used 25 specimens from 17 embalmed Korean cadavers. The MAL, level of rib and ICS, and regions 5 cm anteroposterior to the MAL (aMAL/pMAL) were established to measure the position of the LTN crossing the MAL, pathway of the LTN, and entering points of the LTN to the SA. RESULTS: The LTN crossed the MAL in 76% of the specimens. The LTN crossed the MAL within the fifth to sixth rib level in 70.8%. Seventy-six percent of the branches entered the SA within the fourth to sixth ICS. The fifth rib and ICS were the most frequent regions aMAL; however, several branches were found pMAL. The LTN entered the SA in 92.6% of the specimens within 3 cm anterior and 1 cm posterior to the MAL. CONCLUSIONS: We set the danger zone as 4 cm near the MAL at the fourth to sixth ICS for thoracotomy. In addition, we proposed the fifth ICS in aMAL at the superficial plane as the alternative injection point for SAPB when blocking the LTN, and the fifth ICS in pMAL at the deep plane to prevent blocking the LTN.

Longitudinal muscular column in the prostatic urethral wall: Its form, shape, and possible function based on mathematical simulation in ejaculation.

BACKGROUND: The shape and function of the longitudinal muscular column (LMC) of the prostate have not been established in detail. The present study was undertaken to elucidate the roles of the LMC of the posterior wall of the prostatic urethra (PSU) in the emission phase of ejaculation by investigating the form and muscular arrangement of the LMC. METHODS: Prostates and urinary bladders were obtained from 14 Korean adult cadavers. Nine specimens were histologically analyzed using hematoxylin and eosin, Masson's trichrome, and Verhoeff-van Gieson staining. Two specimens were scanned using microcomputed tomography (micro-CT), and all scanned images were reconstructed into a three-dimensional model. RESULTS: At the proximal level of the prostate, the ejaculatory ducts (EDs) and prostatic utricle (PU) together were surrounded by circular smooth-muscle fibers. However, at the seminal colliculus (SC) where the EDs and PU opened, they were mainly surrounded by an abundance of longitudinal fibers. The longitudinal fibers posterior to the EDs and PU formed a distinctive LMC in the posterior urethral wall. In histologic sections and micro-CT images, the LMC extended distally from the level of the SC to the level of the membranous urethra (MBU). We simulated a potential mechanism of LMC using a mathematical model of its movements. CONCLUSIONS: Comprehensive analyses based on in-depth assessment of histologic characteristics and micro-CT images demonstrated extension of the LMC from the level of the SC to the level of the MBU, enabling a better understanding of ejaculation physiology involving the LMC. These results suggest that the LMC in the posterior wall of the PSU is a critical component of ejaculation by facilitating the ejection of seminal vesicle fluid into the PSU via well-coordinated contractions.

Deep-Asymmetry: Asymmetry Matrix Image for Deep Learning Method in Pre-Screening Depression.

To have an objective depression diagnosis, numerous studies based on machine learning and deep learning using electroencephalogram (EEG) have been conducted. Most studies depend on one-dimensional raw data and required fine feature extraction. To solve this problem, in the EEG visualization research field, short-time Fourier transform (STFT), wavelet, and coherence commonly used as method s for transferring EEG data to 2D images. However, we devised a new way from the concept that EEG's asymmetry was considered one of the major biomarkers of depression. This study proposes a deep-asymmetry methodology that converts the EEG's asymmetry feature into a matrix image and uses it as input to a convolutional neural network. The asymmetry matrix image in the alpha band achieved 98.85% accuracy and outperformed most of the methods presented in previous studies. This study indicates that the proposed method can be an effective tool for pre-screening major depressive disorder patients.

Intramuscular innervation patterns of the splenius capitis and splenius cervicis and their clinical implications for botulinum toxin injections.

INTRODUCTION: The purpose of this study was to clearly characterize the intramuscular nerve distributions of the splenius capitis and splenius cervicis muscles that are both responsible for the onset of a chronic tension type headache and to use this information to identify the effective botulinum toxin (BoNT) injection sites. MATERIALS AND METHODS: Ten splenius capitis and splenius cervicis specimens were subjected to Sihler's staining to reveal intramuscular nerve arborization patterns and determined the optimal location for BoNT injection. RESULTS: Nerve distribution patterns in the splenius capitis were identified as nerve pathways that travel down toward the origin point and others that travel up toward the insertion point. This neuromuscular innervation from the central (50%) point was distributed evenly in these two directions. The neural pathways of splenius cervicis traveled vertically from the insertion point to the origin point. If the length from the muscle origin point to the insertion point is normalized to 100%, motor neurons innervate the muscle from around the 30% to the 70% point. CONCLUSIONS: The safest and most-effective BoNT injection sites for the splenius capitis and splenius cervicis were found at around the 50% point and the 30% to the 70% point, respectively.

A Detailed Analysis of the Blood Supply to the Subscapularis Muscle.

This study aimed to provide a comprehensive description of the arterial supply to the subscapularis (SSC) muscle. This will provide critical information for various surgical procedures. Ten specimens of embalmed Korean cadavers were dissected and subjected to modified Sihler's method to reveal the branching pattern of the arteries surrounding the subscapularis, and its intramuscular blood supply. The SSC muscle was generally supplied by branches from the subclavian artery (suprascapular artery, supraSA; circumflex scapular artery, CxSA; and dorsal scapular artery, dSA) and the axillary artery (subscapular artery, subSA; lateral thoracic artery, LTA; posterior circumflex humeral artery, PCxHA; and a branch of the axillary artery, AAbr). The anterior aspect of the muscle was supplied by the subSA, LTA, CxSA, supraSA, and AAbr. The posterior aspect of the muscle was supplied by the supraSA, PCxHA, and subSA. The dSA was more scarcely distributed than the other arteries. In two cases, the dSA supplied the portion of the muscle near the medial border of the scapular. The anterior side of the muscle tendon was supplied by the CxSA, and its posterior side was supplied by the PCxHA. The subSA can be considered to be the main branch supplying the SSA based on its distribution area of arteries. It was mostly situated within the lower region of the SSC. After distributing to the anterior surface of the SSC, some branches of the subSA reached the posterior surface as perforating branches. Clin. Anat. 32:642-647, 2019. © 2019 Wiley Periodicals, Inc.

Interfascicular septum of the calcaneal tunnel and its relationship with the plantar nerves: A cadaveric study.

The relationship between the plantar nerves and internal fascial structure of the calcaneal tunnel is clinically important to alleviate pain of the sole. The study aimed to investigate the three-dimensional (3D) anatomy of the calcaneal tunnel and its internal fascial septal structure by using microcomputed tomography (mCT) with a phosphotungstic acid preparation, histologic examination, and ultrasound-guided simulation. Twenty-one fixed cadavers and three fresh-frozen cadavers (13 men and 11 women, mean age 82.1 years at death) were used in this study. The 3D images of the calcaneal tunnel harvested by mCT were analyzed in detail. Modified Masson trichrome staining and serial sectional dissection after ultrasound-guided injection were conducted to verify the 3D anatomy. Within the calcaneal tunnel, the interfascicular septum (IFS) commenced proximal to the malleolar-calcaneal line and distal to the bifurcation of the tibial nerve into the plantar nerves. The medial and lateral plantar nerves were separated by the IFS, which divided the calcaneal tunnel into two compartments. The plantar nerves were ramified into two or three branches within each compartment. The IFS terminated around the talocalcaneonavicular joint, and the plantar nerves traveled into the sole. Clinical manipulation of the plantar nerves should be performed in consideration of the fact that they are clearly separated by the IFS. Clin. Anat. 32:877-882, 2019. © 2019 Wiley Periodicals, Inc.

Intramuscular innervation of the subscapularis muscle and its clinical implication for the BoNT injection: An anatomical study using the modified Sihler's staining.

Shoulder pain is commonly associated with spasticity of the rotator cuff muscles including the subscapularis (SSC). The aim of this study was to elucidate the intramuscular innervation pattern of the SSC using the modified Sihler's staining technique to facilitate the targeting of botulinum neurotoxin (BoNT) injections to alleviate shoulder spasticity. Ten SSC specimens (mean age, 81.5 years) were used in this study. Modified Sihler's staining was used to clarify the muscle and to stain the intramuscular nerves. Their extramuscular and intramuscular innervation patterns were examined. The upper subscapular, lower subscapular, thoracodorsal, and axillary nerves (USN, LSN, TDN, and AXN) innervated the SSC in 100%, 80%, 20%, and 40% of specimens, respectively. There was an anastomosis between the USN and LSN in the central portion of the SSC in more than half of the cases. The USN innervated the overall portion of the muscle. In contrast, the additional branches from the TDN and AXN innervated the inferior SSC portion. The superficial branches of the USN were mostly distributed in the superior SSC portion while the deep branches were distributed in the inferior portion. As a major intramuscular nerve within the SSC, the USN should be targeted by a BoNT injection. Regarding the USN distribution, the aim should be to spread the BoNT injectate within the central SSC portion. For supplementary injection to the AXN, the lateral approach would be more appropriate than alternatives. A physician performing a BoNT injection should consider the intramuscular innervation of the SSC portion. Clin. Anat. 32:110-116, 2019. © 2018 Wiley Periodicals, Inc.

Anatomical consideration of the occipital cutaneous nerves and artery for the safe treatment of occipital neuralgia.

There is no standardized approach to the greater occipital nerve (GON) block technique for treating occipital neuralgia. The aim of the present study was to validate the previously-suggested guidelines for conventional injection techniques and to provide navigational guidelines for safe GON block. The GON, lesser occipital nerve (LON) and occipital artery (OA) were carefully dissected in the occipital region of embalmed cadavers. Using a 3 D digitizer, the GON, LON, and OA were observed on the two reference lines. The distances between the landmarks were recorded and statistically analyzed. On the superior nuchal line, the mean distances between the external occipital protuberance (EOP) and the most medial branch of the GON was 33.5 mm. The mean distance between the EOP and the most medial branch of the OA was 37.4 mm. On the EOP-mastoid process (MP) line, the GON was on the medial third and the LON the lateral third of the EOP-MP line. The safe injection points on the EOP-MP line are about 3 cm from the EOP, 1 cm inferior parallel to the EOP-MP line, and about 3 cm away from the MP. Clin. Anat. 31:1058-1064, 2018. © 2018 Wiley Periodicals, Inc.

Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus.

Mycobacterium abscessus is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the in vitro, intracellular, and in vivo activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of M. abscessus infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several M. abscessus strains in vitro and in a macrophage model of infection. In the murine model, a similar efficacy to linezolid was achieved, especially in the lungs. We induced laboratory-generated resistance to LCB01-0371; sequencing analysis revealed mutations in rplC of T424C and G419A and a nucleotide insertion at the 503 position. Furthermore, LCB01-0371 inhibited the growth of amikacin-, cefoxitin-, and clarithromycin-resistant strains. Collectively, our data indicate that LCB01-0371 might represent a promising new class of oxazolidinones with improved safety, which may replace linezolid for the treatment of M. abscessus.

Physical Activity Patterns in Infants With and Without Down Syndrome.

PURPOSE: Individuals with Down syndrome (DS) are at greater risk for obesity than their peers who are developing typically. One factor contributing to an early onset of obesity is low levels of physical activity (PA). However, there is little known regarding PA patterns during infancy. METHODS: The purpose of this study was to examine the daily PA patterns in 22 infants developing typically and 11 infants with Down syndrome (aged 1-12 months) using Actigraph GT3X+ (wrist and ankle). RESULTS: No significant differences between groups were identified in PA counts at the ankle. Both groups produced significantly more PA at the wrist than at the ankle and PA counts increased across months in age. CONCLUSION: This study represents an important first step in establishing baseline PA patterns during infancy.

Measuring the prediction difficulty of individual cases in a dataset using machine learning.

Different levels of prediction difficulty are one of the key factors that researchers encounter when applying machine learning to data. Although previous studies have introduced various metrics for assessing the prediction difficulty of individual cases, these metrics require specific dataset preconditions. In this paper, we propose three novel metrics for measuring the prediction difficulty of individual cases using fully-connected feedforward neural networks. The first metric is based on the complexity of the neural network needed to make a correct prediction. The second metric employs a pair of neural networks: one makes a prediction for a given case, and the other predicts whether the prediction made by the first model is likely to be correct. The third metric assesses the variability of the neural network's predictions. We investigated these metrics using a variety of datasets, visualized their values, and compared them to fifteen existing metrics from the literature. The results demonstrate that the proposed case difficulty metrics were better able to differentiate various levels of difficulty than most of the existing metrics and show constant effectiveness across diverse datasets. We expect our metrics will provide researchers with a new perspective on understanding their datasets and applying machine learning in various fields.

Retrodural space of Okada in the posterior ligamentous complex region: clinical and anatomical findings relevant to lumbar interlaminar epidural injection.

BACKGROUND: The retrodural space of Okada is a potential space posterior to the ligamentum flavum that allows communication with the bilateral facet joints. However, the actual anatomy of this space has not been clearly visualized to date. We sought to investigate the characteristics of patients showing contrast spreading to the facet joint space during epidural injection and to clarify the anatomical structures of the retrodural space and adjacent ligamentous tissues in cadaveric specimens. METHODS: Fluoroscopic images of patients who underwent fluoroscopy-guided lumbar interlaminar epidural injection were assessed for contrast flow to the facet joints. Patient demographics, preprocedural imaging study findings, and epidural approaches were analyzed. The anatomical study included the sectional dissection, micro-CT imaging, and histological evaluation of lumbar spine specimens from 16 embalmed cadavers. RESULTS: Fluoroscopic images of 605 epidural injections were analyzed. Among them, 36 with inadvertent spread into the facet joints (5.9%) were identified. Multivariate analysis revealed that facet joint pathologies were significantly associated with inadvertent spread into the facet joints (OR 4.382; 95% CI 1.160 to 16.558; p=0.029). Micro-CT and histological findings consistently showed a retrodural space between the ligamentum flavum and interspinous ligament. Various anatomical communication routes in the posterior ligamentous complex leading to this space were observed in specimens with degenerative and pathological changes. CONCLUSION: Degenerative and pathological facet joint changes were associated with a higher incidence of spread into the retrodural space during epidural injection. Our findings confirm anatomical evidence for a false loss of resistance before the needle enters the epidural space.

Anatomical study of the adductor canal: three-dimensional micro-computed tomography, histological, and immunofluorescence findings relevant to neural blockade.

BACKGROUND: A precise anatomical understanding of the adductor canal (AC) and its neural components is essential for discerning the action mechanism of the AC block. We therefore aimed to clarify the detailed anatomy of the AC using micro-computed tomography (micro-CT), histological evaluation, and immunofluorescence (IF) assays. METHODS: Gross dissections of 39 thighs provided morphometric data relevant to injection landmarks. Serial sectional images of the AC were defined using micro-CT and ultrasonography. The fascial and neural structures of the AC proper were histologically evaluated using Masson's trichrome and Verhoeff-Van Gieson staining, and double IF staining using choline acetyltransferase (ChAT) and neurofilament 200 antibodies. RESULTS: The posteromedial branch insertion of the nerve to vastus medialis (NVM) into the lateral border of the AC proper was lower (14.5 ± 2.4 cm [mean ± SD] above the base of the patella) than the origin of the proximal AC. The AC consists of a thin subsartorial fascia in the proximal region and a thick aponeurosis-like vastoadductor membrane in the distal region. In the proximal AC, the posteromedial branch of the NVM (pmNVM) consistently contained both sensory and motor fibers, and more ChAT-positive fibers were observed than in the saphenous nerve (27.5 ± 11.2 / 104 vs. 4.2 ± 2.6 / 104 [counts/µm2], P < 0.001). CONCLUSIONS: Anatomical differences in fascial structures between the proximal and distal AC and a mixed neural component of the neighboring pmNVM have been visualized using micro-CT images, histological evaluation, and IF assays.

The Impact of a Rater Training Program on the TGMD-3 Scoring Accuracy of Pre-Service Adapted Physical Education Teachers.

This study aimed to examine the impact of a TGMD-3 rater training program on pre-service adapted physical education (APE) teachers' ability to score fundamental motor skills for children with developmental disabilities (DD). The training program consisted of a description of the TGMD-3 instrument and DD, as well as content focused on skill performance and correct scoring through systematic analysis of 13 FMS via the instrument. Three experts established the standard score through the TGMD-3 performance evaluation of a child with DD. Thirty-nine pre-service APE teachers in the experimental group and 30 pre-service teachers in the control group completed the pre- and post-test process in this study. There were significant impacts on the pre-service teachers' ability to score the locomotor, ball skill subtests, and total skill scores (p < 0.05) compared to the control group. Specifically, the results of the three locomotor skills (running, horizontal jump, & slide) and three ball skills (two-hand strike, dribble, & kick) significantly improved in scoring accuracy. The results of this study can evidence that a TGMD-3 rater training program for pre-service APE teachers enhances the scoring accuracy of FMS among children with DD.

Development of an ICT-Based Exergame Program for Children with Developmental Disabilities.

The purpose of this study was to develop an information and communications technology (ICT)-based exergame for children with developmental disabilities (DD) and to examine its impacts on physical fitness and fundamental motor skills (FMS). The ICT-based exergame consisted of visual and auditory demonstrations of diverse locomotor movement and object manipulation activities by the virtual characters. A total of 52 children with DD participated in the present study. The participants were divided into twenty-seven children in the experimental group and 25 children with DD in the control group. The experimental group participants engaged in the exergame program for 12 weeks. All participants' muscle strength (i.e., standing long jump) and four fundamental motor skills, such as the horizontal jump, hop, overhand throw, and dribble, were assessed during the pre- and post-test process. There were significant impacts on physical fitness and FMS (p < 0.001) between the groups. Specifically, the results of three FMS (hop, overhand throw, and dribble) and standing long jump significantly improved in children with DD except for the horizontal jump skill. The results of this study is evidence that the ICT-based exergame program for children with DD may be utilized to improve physical fitness and FMS in children with DD.

Effect of a Cognitive Function and Social Skills-Based Digital Exercise Therapy Using IoT on Motor Coordination in Children with Intellectual and Developmental Disability.

This study aimed to determine the effects of a virtual reality exercise program based on cognitive function and social skills on motor coordination in children with intellectual and developmental disabilities (IDD). Thirty-five children with IDD were randomly assigned to either the cognitive function and social skills-based virtual reality exercise system (CS-VR) group or the conventional virtual reality exercise system (C-VR) group. Before and after the intervention, each participant was tested for motor coordination (extended horizontal jump, hop, stationary dribble, overarm throw) and exercise performance (standing long jump, YMCA step test). Compared with the C-VR group, the CS-VR group showed significant improvements in motor coordination in terms of extended horizontal jump, hop, and overarm throw (p < 0.01, p < 0.05, and p < 0.01, respectively). In addition, compared with the C-VR group, the CS-VR group showed a significant increase in standing long jump (p < 0.01), although no significant between-group variation was found in stationary dribble and recovery heart rate (RHR) as part of the YMCA step test (p > 0.05, and p > 0.05, respectively). These results suggest that for the development of motor skills in children with IDD, it is essential to develop an exercise program that reflects the levels of cognitive functions and social skills of these children.

The pathway of injectate spread during thoracic intertransverse process (ITP) block: Micro-computed tomography findings and anatomical evaluations.

STUDY OBJECTIVE: To investigate the mechanism of action of the thoracic intertransverse process (ITP) block. DESIGN: Three-dimensional micro-computed tomography (3D micro-CT) study and cadaveric evaluation. SETTING: A translational research unit for anatomy and analgesia in a university hospital. PATIENTS: Twelve embalmed and three non-embalmed human cadavers were used in this study. MEASUREMENTS: Micro-CT images of the mid-thoracic paravertebral space and its adjacent ligamentous tissues were acquired and 3D images were reconstructed. Manual dissection and histologic examination of these structures complemented the images. To confirm our findings, the dye-spreading pattern after ultrasound-guided ITP injection of 20 mL dye solution at T4-T5 was evaluated. MAIN RESULTS: Micro-CT and histologic findings showed that the costotransverse foramen (the medial slit of the superior costotransverse ligament) and the costotransverse space (between the rib and the transverse process) were potential pathways to the thoracic paravertebral space during ITP block. Single-level ITP injection with a dye solution resulted in a multilevel segmental paravertebral spread in cadaveric evaluation. CONCLUSIONS: The space posterior to the superior costotransverse ligament, the target area for ITP blocks, has potential anatomical pathways to the thoracic paravertebral space. The costotransverse foramen and the costotransverse space provided the anatomical conduit for the anterior and intersegmental paravertebral spread of the ITP block.

An anatomical and radiological study of the tectorial membrane and its clinical implications.

The radiological image of an intact tectorial membrane (TM) became an important favorable prognostic factor for craniovertebral instability. This study visualized the fascial layers of the TM and adjacent connective tissues with clinical significance by micro-CT and histological analysis. The TM firmly attached to the bony surface of the clivus, traversed the atlantoaxial joint posteriorly, and was inserted to the body of the axis showing wide distribution on the craniovertebral junction. The supradental space between the clivus, dens of the axis, anterior atlantooccipital membrane, and the TM contained profound venous networks within the adipose tissues. At the body of the axis, the compact TM layer is gradually divided into multiple layers and the deeper TM layers reached the axis while the superficial layer continued to the posterior longitudinal ligament of the lower vertebrae. The consistent presence of the fat pad and venous plexus in the supradental space and firm stabilization of the TM on the craniovertebral junction was demonstrated by high-resolution radiologic images and histological analysis. The evaluation of the TM integrity is a promising diagnostic factor for traumatic craniovertebral dislocation.

Micro-computed tomography with contrast enhancement: An excellent technique for soft tissue examination in humans.

Manual dissection and histologic examination are commonly used to investigate human structures, but there are limitations in the damage caused to delicate structures or the provision of limited information. Micro-computed tomography (microCT) enables a three-dimensional volume-rendered observation of the sample without destruction and deformation, but it can only visualize hard tissues in general. Therefore, contrast-enhancing agents are needed to help in visualizing soft tissue. This study aimed to introduce microCT with phosphotungstic acid preparation (PTA-microCT) by applying the method to different types of human tissue. Specimens from human cadavers were used to examine the orbicularis retaining ligament (ORL), nasolabial fold (NLF), and the calcaneal tunnel of the sole. Using PTA-microCT, relevant information of human structures was identified. In the ORL study, tiny and delicate ligamentous fibers were visualized in detail with multidirectional continuity. In the NLF study, complex structural formation consisting of various types of soft tissue were investigated comprehensively. In the calcaneal tunnel study, the space surrounded by diverse features and its inner vulnerable structures were examined without damage. Consequently, we successfully applied the PTA-microCT technique to the analysis of specific human soft tissue structures that are challenging to analyze by conventional methods.

Anatomy of the thoracic paravertebral space: 3D micro-CT findings and their clinical implications for nerve blockade.

BACKGROUND: A precise anatomical understanding of the thoracic paravertebral space (TPVS) is essential to understanding how an injection outside this space can result in paravertebral spread. Therefore, we aimed to clarify the three-dimensional (3D) structures of the TPVS and adjacent tissues using micro-CT, and investigate the potential routes for nerve blockade in this area. METHODS: Eleven embalmed cadavers were used in this study. Micro-CT images of the TPVS were acquired after phosphotungstic acid preparation at the mid-thoracic region. The TPVS was examined meticulously based on its 3D topography. RESULTS: Micro-CT images clearly showed the serial topography of the TPVS and its adjacent spaces. First, the TPVS was a very narrow space with the posterior intercostal vessels very close to the pleura. Second, the superior costotransverse ligament (SCTL) incompletely formed the posterior wall of the TPVS between the internal intercostal membrane and vertebral body. Third, the retro-SCTL space broadly communicated with the TPVS via slits, costotransverse space, intervertebral foramen, and erector spinae compartment. Fourth, the costotransverse space was intersegmentally connected to the adjacent retro-SCTL space. CONCLUSIONS: A non-destructive, multi-sectional approach using 3D micro-CT more comprehensively demonstrated the real topography of the intricate TPVS than previous cadaver studies. The posterior boundary and connectivity of the TPVS provides an anatomical rationale for the notion that paravertebral spread can be achieved with an injection outside this space.