The reality of myoelectric prostheses : understanding what makes these devices difficult for some users to control

Users of myoelectric prostheses can often find them difficult to control. This can lead to passive-use of the device or total rejection, which can have detrimental effects on the contralateral limb due to overuse. Current clinically available prostheses are ‘open loop’ systems, and although considerable effort has been focused on developing biofeedback to “close the loop”, there is evidence from laboratory-based studies that other factors, notably improving predictability of response, may be as, if not more, important. Interestingly, despite a large volume of research aimed at improving myoelectric prostheses, it is not currently known which aspect of clinically available systems has the greatest impact on overall functionality and everyday usage. A protocol has therefore been designed to assess EMG skill of the user and predictability of the prosthesis response as significant parts of the control chain, and to relate these to functionality and everyday usage. Here we present the protocol and results from early pilot work. A set of experiments has been developed. Firstly to characterize user skill in generating the required level of EMG signal, as well as the speed with which users are able to make the decision to activate the appropriate muscles. Secondly, to measure unpredictability introduced at the skin-electrode interface, in order to understand the effects of the socket mounted electrode fit under different loads on the variability of time taken for the prosthetic hand to respond. To evaluate prosthesis user functionality, four different outcome measures are assessed. Using a simple upper limb functional task prosthesis users are assessed for (1) success of task completion, (2)task duration, (3) quality of movement, and (4) gaze behavior. To evaluate everyday usage away from the clinic, the symmetricity of their real-world arm use is assessed using activity monitoring. These methods will later be used to assess a prosthesis user cohort, to establish the relative contribution of each control factor to the individual measures of functionality and everyday usage (using multiple regression models). The results will support future researchers, designers and clinicians in concentrating their efforts on the area which will have the greatest impact on improving prosthesis use

Upper limb activity of twenty myoelectric prosthesis users and twenty healthy anatomically intact adults

The upper limb activity of twenty unilateral upper limb myoelectric prosthesis users and twenty anatomically intact adults were recorded over a 7-day period using two wrist worn accelerometers (Actigraph, LLC). This dataset reflects the real-world activities of the participants during their normal day-to-day routines. Participants included students, working adults, and retirees recruited from across the United Kingdom. This is the first published dataset of its kind and offers a potential wealth of knowledge into a poorly understood cohort. The raw unprocessed data files and the activity count data exported from the Actilife software are provided. We also provide a non-wear algorithm developed for the removal of prosthesis non-wear periods and resulting activity count data corresponding to prothesis wear periods. Finally, we have included the transposed activity diaries provided by the participants. Analysis to date has primarily involved assessment of the symmetry of upper limb activity, however, there is potential to undertake additional analysis such as understanding the differences in the way a prosthesis is used compared to an anatomical arm

Upper- and lower-limb amputees show reduced levels of eeriness for images of prosthetic hands

The uncanny phenomenon describes the feeling of unease associated with seeing an image which is close to appearing human. Prosthetic hands in particular are well-known to induce this effect. Little is known, however, about this phenomenon from the viewpoint of prosthesis users. We studied perceptions of eeriness and human-likeness for images of different types of mechanical, cosmetic, and anatomical hands in upper-limb prosthesis users (n=9), lower-limb prosthesis users (n=10), prosthetists (n=16), control participants with no prosthetic training (n=20), and control participants who were trained to use a myoelectric prosthetic hand simulator (n=23). Both the upper- and lowerlimb prosthesis user groups showed a reduced uncanny phenomenon (i.e., significantly lower levels of eeriness) for cosmetic prosthetic hands compared to the other groups, with no concomitant reduction in how these stimuli were rated in terms of human-likeness. However, a similar effect was found neither for prosthetists with prolonged visual experience of prosthetic hands, nor for the group with short-term training with the simulator. These findings in the prosthesis users therefore seem likely to be related to limb absence or prolonged experience with prostheses

Evaluating reachable workspace and user control over prehensor aperture for a body-powered prosthesis

Using a shoulder harness and control cable, a person can control the opening and closing of a bodypowered prosthesis prehensor. In many setups the cable does not pass adjacent to the shoulder joint center allowing shoulder flexion on the prosthetic side to be used for prehensor control. However, this makes cable setup a difficult compromise as prosthesis control is dependent on arm posture; too short and the space within which a person can reach may be unduly restricted, too long and the user may not be able to move their shoulder sufficiently to take up the inevitable slack at some postures and hence have no control over prehensor movement. Despite the fundamental importance of reachable workspace to users, to date there have been no studies in prosthetics on this aspect. Here, a methodology is presented to quantify the reduction in the reachable volume due to the harness, and to record the range-of-motion of the prehensor at a series of locations within the reachable workspace. Ten anatomically intact participants were assessed using a body-powered prosthesis simulator. Data was collected using a 3D motion capture system and an electronic goniometer. The harnessed reachable workspace was 38-85% the size of the unharnessed volume with participants struggling to reach across the body and above the head. Across all arm postures assessed, participants were only able to achieve full prehensor range-of-motion in 9%. The methodologies presented could be used to evaluate future designs of both body-powered and myoelectric prostheses

Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.

The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease

A qualitative reading of the ecological (dis)organisation of criminal associations. The case of the ?Famiglia Basilischi? in Italy

This paper combines the theoretical foundations of organisational ecology - one of the most important approaches in economic sociology - with classic criminological theories to interpret the birth, evolution and death of criminal associations. This mixed approach will support the interpretation of organised crime groups as phenomena strictly linked to the environment as well as to other competitors in criminal markets. This paper analyses the birth, evolution and death of a criminal association in Basilicata, Southern Italy, known as the ?Famiglia Basilischi?. The case is exemplary of how ecological conditions affect the success or failure of a newly formed criminal association. These conditions can therefore be indicators to interpret organised criminal activities in similar environments

Pressure-induced suppression of ferromagnetism in the itinerant ferromagnet LaCrSb3

We have performed an extensive pressure-dependent structural, spectroscopic, and electrical transport study of LaCrSb3. The ferromagnetic phase (TC=120 K at p = 0 GPa) is fully suppressed by p = 26.5 GPa and the Cr moment decreases steadily with increasing pressure. The unit-cell volume decreases smoothly up to p = 55 GPa. We find that the bulk modulus and suppression of the magnetism are in good agreement with theoretical predictions, but the Cr moment decreases smoothly with pressure, in contrast to steplike drops predicted by theory. The ferromagnetic ordering temperature appears to be driven by the Cr moment

Molecular Mechanisms Associated with Nicotine Pharmacology and Dependence.

Tobacco dependence is a leading cause of preventable disease and death worldwide. Nicotine, the main psychoactive component in tobacco cigarettes, has also been garnering increased popularity in its vaporized form, as derived from e-cigarette devices. Thus, an understanding of the molecular mechanisms underlying nicotine pharmacology and dependence is required to ascertain novel approaches to treat drug dependence. In this chapter, we review the field's current understanding of nicotine's actions in the brain, the neurocircuitry underlying drug dependence, factors that modulate the function of nicotinic acetylcholine receptors, and the role of specific genes in mitigating the vulnerability to develop nicotine dependence. In addition to nicotine's direct actions in the brain, other constituents in nicotine and tobacco products have also been found to alter drug use, and thus, evidence is provided to highlight this issue. Finally, currently available pharmacotherapeutic strategies are discussed, along with an outlook for future therapeutic directions to achieve to the goal of long-term nicotine cessation

The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

BACKGROUND: In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. METHODOLOGY/ PRINCIPAL FINDINGS: Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. CONCLUSIONS/SIGNIFICANCE: The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans