Implications of EMG channel count: enhancing pattern recognition online prosthetic testing.

Introduction: Myoelectric pattern recognition systems have shown promising control of upper limb powered prostheses and are now commercially available. These pattern recognition systems typically record from up to 8 muscle sites, whereas other control systems use two-site control. While previous offline studies have shown 8 or fewer sites to be optimal, real-time control was not evaluated. Methods: Six individuals with no limb absence and four individuals with a transradial amputation controlled a virtual upper limb prosthesis using pattern recognition control with 8 and 16 channels of EMG. Additionally, two of the individuals with a transradial amputation performed the Assessment for Capacity of Myoelectric Control (ACMC) with a multi-articulating hand and wrist prosthesis with the same channel count conditions. Results: Users had significant improvements in control when using 16 compared to 8 EMG channels including decreased classification error (p = 0.006), decreased completion time (p = 0.019), and increased path efficiency (p = 0.013) when controlling a virtual prosthesis. ACMC scores increased by more than three times the minimal detectable change from the 8 to the 16-channel condition. Discussion: The results of this study indicate that increasing EMG channel count beyond the clinical standard of 8 channels can benefit myoelectric pattern recognition users.

Myoelectric prosthesis hand grasp control following targeted muscle reinnervation in individuals with transradial amputation.

BACKGROUND: Despite the growing availability of multifunctional prosthetic hands, users' control and overall functional abilities with these hands remain limited. The combination of pattern recognition control and targeted muscle reinnervation (TMR) surgery, an innovative technique where amputated nerves are transferred to reinnervate new muscle targets in the residual limb, has been used to improve prosthesis control of individuals with more proximal upper limb amputations (i.e., shoulder disarticulation and transhumeral amputation). OBJECTIVE: The goal of this study was to determine if prosthesis hand grasp control improves following transradial TMR surgery. METHODS: Eight participants were trained to use a multi-articulating hand prosthesis under myoelectric pattern recognition control. All participated in home usage trials pre- and post-TMR surgery. Upper limb outcome measures were collected following each home trial. RESULTS: Three outcome measures (Southampton Hand Assessment Procedure, Jebsen-Taylor Hand Function Test, and Box and Blocks Test) improved 9-12 months post-TMR surgery compared with pre-surgery measures. The Assessment of Capacity for Myoelectric Control and Activities Measure for Upper Limb Amputees outcome measures had no difference pre- and post-surgery. An offline electromyography analysis showed a decrease in grip classification error post-TMR surgery compared to pre-TMR surgery. Additionally, a majority of subjects noted qualitative improvements in their residual limb and phantom limb sensations post-TMR. CONCLUSIONS: The potential for TMR surgery to result in more repeatable muscle contractions, possibly due to the reduction in pain levels and/or changes to phantom limb sensations, may increase functional use of many of the clinically available dexterous prosthetic hands.

User Performance With a Transradial Multi-Articulating Hand Prosthesis During Pattern Recognition and Direct Control Home Use.

With the increasing availability of more advanced prostheses individuals with a transradial amputation can now be fit with single to multi-degree of freedom hands. Reliable and accurate control of these multi-grip hands still remains challenging. This is the first multi-user study to investigate at-home control and use of a multi-grip hand prosthesis under pattern recognition and direct control. Individuals with a transradial amputation were fitted with and trained to use an OSSUR i-Limb Ultra Revolution with Coapt COMPLETE CONTROL system. They participated in two 8-week home trials using the hand under myoelectric direct and pattern recognition control in a randomized order. While at home, participants demonstrated broader usage of grips in pattern recognition compared to direct control. After the home trial, they showed significant improvements in the Assessment of Capacity for Myoelectric Control (ACMC) outcome measure while using pattern recognition control compared to direct control; other outcome measures showed no differences between control styles. Additionally, this study provided a unique opportunity to evaluate EMG signals during home use. Offline analysis of calibration data showed that users were 81.5% [7.1] accurate across a range of three to five grips. Although EMG signal noise was identified during some calibrations, overall EMG quality was sufficient to provide users with control performance at or better than direct control.

Usability, functionality, and efficacy of a custom myoelectric elbow-wrist-hand orthosis to assist elbow function in individuals with stroke.

INTRODUCTION: After stroke, upper limb impairment affects independent performance of activities of daily living. We evaluated the usability, functionality, and efficacy of a myoelectric elbow-wrist-hand orthosis to provide support, limit unsafe motion, and enhance the functional motion of paralyzed or weak upper limbs. METHODS: Individuals with stroke participated in a single-session study to evaluate the device. Ability to activate the device was tested in supported and unsupported shoulder position, as well as the elbow range of motion, ability to maintain elbow position, and ability to lift and hold a range of weights while using the device. RESULTS: No adverse events were reported. 71% of users were able to operate the device in all three active myoelectric activation modes (Biceps, Triceps, Dual) during testing. Users were able to hold a range of wrist weights (0.5-2 lbs) for 10-120 seconds, with the largest percentage of participants able to hold weights with the device in Biceps Mode. CONCLUSIONS: The myoelectric elbow-wrist-hand orthosis improved range of motion during use and was efficacious at remediating upper extremity impairment after stroke. All users could operate the device in at least one mode, and most could lift and hold weights representative of some everyday objects using the device.

Trisomy 21-associated increases in chromosomal instability are unmasked by comparing isogenic trisomic/disomic leukocytes from people with mosaic Down syndrome.

Down syndrome, which results from a trisomic imbalance for chromosome 21, has been associated with 80+ phenotypic traits. However, the cellular changes that arise in somatic cells due to this aneuploid condition are not fully understood. The primary aim of this study was to determine if germline trisomy 21 is associated with an increase in spontaneous somatic cell chromosomal instability frequencies (SCINF). To achieve this aim, we quantified SCINF in people with mosaic Down syndrome using a cytokinesis-blocked micronucleus assay. By comparing values in their isogenic trisomic/disomic cells, we obtained a measure of differences in SCINF that are directly attributable to a trisomy 21 imbalance, since differential effects attributable to "background" genetic factors and environmental exposures could be eliminated. A cross-sectional assessment of 69 people with mosaic Down syndrome (ages 1 to 44; mean age of 12.84 years) showed a significantly higher frequency of micronuclei in their trisomic (0.37 ± 0.35 [mean ± standard deviation]) compared to disomic cells (0.18 ± 0.11)(P <0.0001). The daughter binucleates also showed significantly higher levels of abnormal patterns in the trisomic (1.68 ± 1.21) compared to disomic (0.35 ± 0.45) cells (P <0.0001). Moreover, a significant Age x Cell Type interaction was noted (P = 0.0113), indicating the relationship between age and SCINF differed between the trisomic and disomic cells. Similarly, a longitudinal assessment (mean time interval of 3.9 years; range of 2 to 6 years) of 18 participants showed a mean 1.63-fold increase in SCINF within individuals over time for their trisomic cells (P = 0.0186), compared to a 1.13-fold change in their disomic cells (P = 0.0464). In summary, these results showed a trisomy 21-associated, age-related increase in SCINF. They also underscore the strength of the isogenic mosaic Down syndrome model system for "unmasking" cellular changes arising from a trisomy 21 imbalance.

PLK1 Induces Chromosomal Instability and Overrides Cell-Cycle Checkpoints to Drive Tumorigenesis.

Polo-like kinase 1 (PLK1) is an essential cell-cycle regulator that is frequently overexpressed in various human cancers. To determine whether Plk1 overexpression drives tumorigenesis, we established transgenic mouse lines that ubiquitously express increased levels of Plk1. High Plk1 levels were a driving force for different types of spontaneous tumors. Increased Plk1 levels resulted in multiple defects in mitosis and cytokinesis, supernumerary centrosomes, and compromised cell-cycle checkpoints, allowing accumulation of chromosomal instability (CIN), which resulted in aneuploidy and tumor formation. Clinically, higher expression of PLK1 positively associated with an increase in genome-wide copy-number alterations in multiple human cancers. This study provides in vivo evidence that aberrant expression of PLK1 triggers CIN and tumorigenesis and highlights potential therapeutic opportunities for CIN-positive cancers. SIGNIFICANCE: These findings establish roles for PLK1 as a potent proto-oncogene and a CIN gene and provide insights for the development of effective treatment regimens across PLK1-overexpressing and CIN-positive cancers.

Exploring augmented grasping capabilities in a multi-synergistic soft bionic hand.

BACKGROUND: State-of-the-art bionic hands incorporate hi-tech devices which try to overcome limitations of conventional single grip systems. Unfortunately, their complexity often limits mechanical robustness and intuitive prosthesis control. Recently, the translation of neuroscientific theories (i.e. postural synergies) in software and hardware architecture of artificial devices is opening new approaches for the design and control of upper-limb prostheses. METHODS: Following these emerging principles, previous research on the SoftHand Pro, which embeds one physical synergy, showed promising results in terms of intuitiveness, robustness, and grasping performance. To explore these principles also in hands with augmented capabilities, this paper describes the SoftHand 2 Pro, a second generation of the device with 19 degrees-of-freedom and a second synergistic layer. After a description of the proposed device, the work explores a continuous switching control method based on a myoelectric pattern recognition classifier. RESULTS: The combined system was validated using standardized assessments with able-bodied and, for the first time, amputee subjects. Results show an average improvement of more than 30% of fine grasp capabilities and about 10% of hand function compared with the first generation SoftHand Pro. CONCLUSIONS: Encouraging results suggest how this approach could be a viable way towards the design of more natural, reliable, and intuitive dexterous hands.

Pattern recognition and direct control home use of a multi-articulating hand prosthesis.

Although more multi-articulating hand prostheses have become commercially available, replacing a missing hand remains challenging from a control perspective. This study investigated myoelectric direct control and pattern recognition home use of a multi-articulating hand prosthesis for individuals with a transradial amputation. Four participants were fitted with an i-limb Ultra Revolution hand and a Coapt COMPLETE CONTROL system. An occupational therapist provided training for each control style and how to use the various grips. The number of grips available to each individual was determined by clinician and user feedback to optimize both the number of grips available and the reliability of grip selection. Home trial data corresponding to individual usage were recorded. No significant differences were found between direct and pattern recognition control home trials in regards to trial length (p=0.96), days powered on (p=0.21), or total time powered on (p=0.91). There was a higher average number of configured grips for direct control at 4.8 [0.5] compared to 3.8 [0.5] for pattern recognition control, but this difference did not reach significance (p=0.092). Across all hand close movements, users spent a majority of time $(\gt80$%) in one grip when using direct control. For pattern recognition usage was spread across more grips $(\gt45$% time in one grip, 25% time in a 2nd grip, and 20% time in a 3rd grip). Pattern recognition control may provide users with a more intuitive way to select and use the various grips available to them.

Control within a virtual environment is correlated to functional outcomes when using a physical prosthesis.

BACKGROUND: Advances such as targeted muscle reinnervation and pattern recognition control may provide improved control of upper limb myoelectric prostheses, but evaluating user function remains challenging. Virtual environments are cost-effective and immersive tools that are increasingly used to provide practice and evaluate prosthesis control, but the relationship between virtual and physical outcomes-i.e., whether practice in a virtual environment translates to improved physical performance-is not understood. METHODS: Nine people with transhumeral amputations who previously had targeted muscle reinnervation surgery were fitted with a myoelectric prosthesis comprising a commercially available elbow, wrist, terminal device, and pattern recognition control system. Virtual and physical outcome measures were obtained before and after a 6-week home trial of the prosthesis. RESULTS: After the home trial, subjects showed statistically significant improvements (p < 0.05) in offline classification error, the virtual Target Achievement Control test, and the physical Southampton Hand Assessment Procedure and Box and Blocks Test. A trend toward improvement was also observed in the physical Clothespin Relocation task and Jebsen-Taylor test; however, these changes were not statistically significant. The median completion time in the virtual test correlated strongly and significantly with the Southampton Hand Assessment Procedure (p = 0.05, R = - 0.86), Box and Blocks Test (p = 0.007, R = - 0.82), Jebsen-Taylor Test (p = 0.003, R = 0.87), and the Assessment of Capacity for Myoelectric Control (p = 0.005,R = - 0.85). The classification error performance only had a significant correlation with the Clothespin Relocation Test (p = 0.018, R = .76). CONCLUSIONS: In-home practice with a pattern recognition-controlled prosthesis improves functional control, as measured by both virtual and physical outcome measures. However, virtual measures need to be validated and standardized to ensure reliability in a clinical or research setting. TRIAL REGISTRATION: This is a registered clinical trial: NCT03097978 .

Custom, rapid prototype thumb prosthesis for partial-hand amputation: A case report.

BACKGROUND: Due to advancements in three-dimensional printing, custom-made prostheses are becoming more viable options for persons with difficult cases of prosthetic management. The purpose of this article was to develop a custom voluntary-closing, body-powered thumb mechanism for a partial-hand amputee who had amputations of the index finger and thumb on the left, non-dominant hand. Case description and methods: The prosthesis model was manufactured using rapid prototype technology and was developed to provide greater force and functionality, and to decrease overall size compared to traditional hand prostheses. Findings and outcomes: Following device iterations and occupational therapy sessions, the patient achieved higher functionality in performing daily tasks such as cooking and cleaning, and in completing the Box and Blocks test, though some limitations still precluded full acceptance of the device. CONCLUSION: This case study represents a unique approach in the development of custom-made devices that may increase prostheses acceptance rates among partial-hand amputees. Clinical relevance Many partial-hand amputees report experiencing trouble in finding a device that fits their needs. This study highlights the potential of using rapid prototyping technology to design a prosthesis that meets a user's specific desires.

Myoelectric Pattern Recognition Outperforms Direct Control for Transhumeral Amputees with Targeted Muscle Reinnervation: A Randomized Clinical Trial.

Recently commercialized powered prosthetic arm systems hold great potential in restoring function for people with upper-limb loss. However, effective use of such devices remains limited by conventional (direct) control methods, which rely on electromyographic signals produced from a limited set of muscles. Targeted Muscle Reinnervation (TMR) is a nerve transfer procedure that creates additional recording sites for myoelectric prosthesis control. The effects of TMR may be enhanced when paired with pattern recognition technology. We sought to compare pattern recognition and direct control in eight transhumeral amputees who had TMR in a balanced randomized cross-over study. Subjects performed a 6-8 week home trial using direct and pattern recognition control with a custom prostheses made from commercially available parts. Subjects showed statistically better performance in the Southampton Hand Assessment Procedure (p = 0.04) and the Clothespin relocation task (p = 0.02). Notably, these tests required movements along 3 degrees of freedom. Seven of 8 subjects preferred pattern recognition control over direct control. This study was the first home trial large enough to establish clinical and statistical significance in comparing pattern recognition with direct control. Results demonstrate that pattern recognition is a viable option and has functional advantages over direct control.

A Comparison of Pattern Recognition Control and Direct Control of a Multiple Degree-of-Freedom Transradial Prosthesis.

With existing conventional prosthesis control (direct control), individuals with a transradial amputation use two opposing muscle groups to control each prosthesis motor. As component complexity increases, subjects must switch the prosthesis into different modes to control each component in sequence. Pattern recognition control offers the ability to control multiple movements in a seamless manner without switching. In this paper, three individuals with a transradial amputation completed a home trial to compare direct control and pattern recognition control of a multiple degree-of-freedom prosthesis. Outcome measures before and after the home trial, together with subject questionnaires, were used to evaluate functional control. Although small, this trial has implications for the implementation of pattern recognition in commercial control systems and for future research studies.

Design and evaluation of voluntary opening and voluntary closing prosthetic terminal device.

Body-powered prostheses use a cable-operated system to generate forces and move prosthetic joints. However, this control system can only generate forces in one direction, so current body-powered prehensor designs allow the user either to voluntarily open or voluntarily close the tongs. Both voluntary opening (VO) and voluntary closing (VC) modes of operation have advantages for certain tasks, and many end-users desire a terminal device that can switch between the two modes. However, such a terminal device must maintain the same thumb position (i.e., point of Bowden cable attachment) and movement direction in both modes in order to avoid the need to readjust the harness after every mode switch. In this study, we demonstrate a simple design that fulfills these requirements while allowing the user to switch easily between modes. We describe the design concept, describe a rugged split-hook prototype, provide specifications (size, weight, efficiency, etc.), and present a pilot study in which five subjects with intact arms and two subjects with amputation used the VO and VC split-hook prehensor to perform the Southampton Hand Assessment Procedure. Subjects performed an average of 4 to 7 (+/- 0.2) points better when they could choose to switch between modes on a task-by-task basis than when they were constrained to using only VO or VC modes.

Elevated TRF2 in advanced breast cancers with short telomeres.

Telomere repeat binding factor 2 (TRF2) binds directly to telomeres and preserves the structural integrity of chromosome ends. In vitro models suggest that expression of TRF2 protein increases during mammary cancer progression. However, a recent study has reported that TRF2 mRNA levels tend to be lower in clinical specimens of malignant breast tissue. Here, we conduct the first large-scale investigation to assess the levels and cellular localization of the TRF2 protein in normal, pre-malignant and malignant breast tissues. Breast tissue arrays, containing normal, ductal carcinoma in situ (DCIS) and invasive carcinoma specimens, were used to assess the expression and localization of TRF2 protein. Telomere lengths were semi-quantitatively measured using a pantelomeric peptide nucleic acid probe. A mixed effects modeling approach was used to assess the relationship between TRF2 expression and telomeric signal scores across disease states or clinical staging. We demonstrate that TRF2 is exclusively nuclear with a trend toward lower expression with increased malignancy. More case-to-case variability of TRF2 immunostaining intensity was noted amongst the invasive carcinomas than the other disease groups. Invasive carcinomas also displayed variable telomere lengths while telomeres in normal mammary epithelium were generally longer. Statistical analyses revealed that increased TRF2 immunostaining intensity in invasive carcinomas is associated with shorter telomeres and shorter telomeres correlate with a higher TNM stage. All immortalized and cancer cell lines within the array displayed strong, nuclear TRF2 expression. Our data indicate that elevated expression of TRF2 is not a frequent occurrence during the transformation of breast cancer cells in vivo, but higher levels of this telomere-binding protein may be important for protecting advanced cancer cells with critically short telomeres. Our findings also reinforce the concept that serially propagated cancer cells, although tumor-derived, may not model all types of authentic tumors especially those demonstrating genetic heterogeneity.

Translocations and amplifications of chromosome 12 in liposarcoma demonstrated by the LSI CHOP breakapart rearrangement probe.

CONTEXT: Liposarcomas display a number of molecular abnormalities involving chromosome 12. Myxoid and round cell liposarcomas are characterized by t(12;16)(q13; p11) or t(12;22)(q13;q12) translocations. Amplifications occur within the 12q13-15 region of atypical lipomatous tumors and well-differentiated liposarcomas but not lipomas. OBJECTIVE: To investigate the performance characteristics of the LSI CHOP Breakapart Rearrangement Probe for the diagnosis of myxoid/round cell liposarcomas and atypical lipomas/well-differentiated liposarcomas. DESIGN: We investigated a series of lipomatous neoplasms (5 lipomas, 5 well-differentiated liposarcomas, 22 myxoid/round cell liposarcomas, 2 liposarcomas not otherwise specified, and 2 dedifferentiated liposarcomas) and normal myometrium for abnormalities in the q13-15 region of chromosome 12. Cases were studied for the presence or absence of t(12;16)(q13;p11) or t(12;22)(q13;q12) translocations by the LSI CHOP Breakapart Rearrangement Probe. These probes contain a sequence encompassing the SAS and CDK4 genes. Four or more copies of this sequence were considered to represent amplification of these genes. RESULTS: Rearrangement of the CHOP gene was seen in all evaluable myxoid liposarcomas. Rearrangements were seen in 1 dedifferentiated liposarcoma but not in normal myometrium or lipomas. Probe signal amplification was seen in all 5 well-differentiated liposarcomas and 1 myxoid liposarcoma. No signal amplification was seen in lipomas or myometrium. CONCLUSIONS: Demonstration of translocations t(12; 16)(q13;p11) and t(12;22)(q13;q12) by the LSI CHOP Breakapart Rearrangement Probe appears to correlate with round cell/myxoid liposarcoma. The probe also demonstrated amplification of the 12q13-15 region in well-differentiated liposarcomas, making it useful for the diagnosis of these neoplasms. In a significant percentage of cases, high background fluorescence or poor probe staining made interpretation difficult.

Utility of EGFR and PTEN numerical aberrations in the evaluation of diffusely infiltrating astrocytomas. Laboratory investigation.

OBJECT: Diffusely infiltrating astrocytomas are the most common primary brain tumors. As a group, they demonstrate an inherent tendency toward malignant progression. Histological grading using the guidelines of the World Health Organization (WHO) remains the gold standard for predicting the biological behavior of these tumors. Although useful, this grading system is often limited due to small sample sizes and the subjectivity in interpretation. Given the important roles for EGFR and PTEN in the malignant progression of astrocytomas, the authors hypothesized that the fraction of tumor cells with aberrations in these genetic loci would correlate with the histological grade. METHODS: The authors evaluated 217 consecutive diffusely infiltrating astrocytomas that were graded using the WHO guidelines, including 16 diffuse astrocytomas (WHO Grade II), 72 anaplastic astrocytomas ([AAs] WHO Grade III), and 129 glioblastomas multiforme ([GBMs] WHO Grade IV). Cases were evaluated quantitatively using dual-color fluorescence in situ hybridization with probes for the EGFR and PTEN loci and the centromeres of chromosomes 7 and 10. RESULTS: The population of tumor cells with polysomy of chromosome 7 and the EGFR locus and monosomy of chromosome 10 and the PTEN locus correlated significantly with histological grade. In particular, high-grade astrocytomas (that is, AAs and GBMs) had elevated fractions of tumor cells with polysomy of chromosome 7 and the EGFR locus and monosomy of chromosome 10 and the PTEN locus. Using these findings, the authors generated a mathematical model capable of subcategorizing high-grade astrocytomas. The successful model incorporated only the percentage of tumor cells with polysomy of EGFR and monosomy of PTEN, as well as patient age. The predictions of this model correlated with survival in a manner similar to histopathological grading. CONCLUSIONS: The findings presented in this study emphasize the utility of combining histological interpretation and molecular testing in the evaluation of infiltrating astrocytomas. These results underscore the utility of building a grading framework that combines histopathological and molecular analysis.

Second messenger systems in human gliomas.

CONTEXT: Patients with glioblastoma (astrocytoma, World Health Organization grade IV) exhibit 2-year survival rates of less than 20% despite significant advances in therapeutic options available to patients. Epidermal growth factor receptor (EGFR) hyperexpression is one of the most commonly encountered abnormalities in this tumor. However, EGFR expression, amplification, and mutations are poorly predictive of patient survival. Investigators have taken to exploiting the sensitivities of activated downstream targets in the EGFR second messenger pathways to certain inhibitory drugs to downregulate their neoplastic messages promoting cell growth and inhibiting cell death. OBJECTIVE: It is important to both gain some understanding of the functional significance of these pathways and to understand the role the pathologist might play in characterizing the activation status of certain downstream messenger proteins that are targeted in these brain tumor therapies. We have reviewed the literature regarding histologic assays that have been incorporated into trials of these new drugs and report on the methods used to study these proteins and the conclusions of these studies. DATA SOURCES: Literature review and primary material from Duke University (Durham, NC) Department of Pathology archives. CONCLUSIONS: To date, drug trial reports indicate that identification of the presence of the EGFR variant, EGFRvIII, and measurement of the activated downstream targets, phospho-Akt, phospho-S6, and phospho-MAPK, may be useful in predicting sensitivity to some of the EGFR kinase inhibitors. No studies to date have identified prognostic significance related to immunoreactivity status among any of these markers that is independent of histologic grade.

Desmoplastic small round cell tumor: using FISH as an ancillary technique to support cytologic diagnosis in an unusual case.

Desmoplastic small round cell tumor is a rare and aggressive neoplasm that predominantly affects young males. In almost all cases, a reciprocal translocation is present resulting in the fusion of the Ewing sarcoma gene with the Wilms' tumor gene. Here we describe an unusual case occurring in a 59-year-old male, in which fluorescence in situ hybridization (FISH) was used in conjunction with immunohistochemical studies to confirm the diagnosis. To our knowledge, this is the first reported case of using FISH as an ancillary technique to confirm the cytologic diagnosis of this tumor.