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Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumour that occurs in the pons of the brainstem and accounts for over 80% of all brainstem gliomas. The median age at diagnosis is 6–7 years old, with less than 10% overall survival 2 years after diagnosis and less than 1% after 5 years. DIPGs are surgically inaccessible, and radiation therapy provides only transient benefit, with death ensuing from relentless local tumour infiltration. DIPGs are now the leading cause of brain tumour deaths in children, with a societal cancer burden in years of life lost (YLL) of more than 67 per individual, versus approximately 14 and 16 YLL for lung and breast cancer respectively. More than 95 clinical drug trials have been conducted on children with DIPGs, and all have failed to improve survival. No single or combination chemotherapeutic strategy has been successful to date because of our inability to identify targeted drugs for this disease and to deliver these drugs across an intact blood-brain barrier (BBB). Accordingly, there has been an increased focus on immunotherapy research in DIPG, with explorations into treatments such as chimeric antigen receptor T (CAR-T) cells, immune checkpoint blockades, cancer vaccines, and autologous cell transfer therapy. Here, we review the most recent advances in identifying genetic factors influencing the development of immunotherapy for DIPG. Additionally, we explore emerging technologies such as Magnetic Resonance-guided Focused Ultrasound (MRgFUS) in potential combinatorial approaches to treat DIPG.

Background: Ketamine has demonstrated efficacy in treating depression unresponsive to traditional interventions and is increasingly utilized in psychiatric practice. However, limited information is available regarding effectiveness in patients with psychiatric comorbidity. The aim of this study is to compare the response of ketamine treatment for depression in patients in a community sample with and without one or more coexisting psychiatric diagnoses. Methods: A retrospective review of medical records from a community ketamine clinic was done. Statistical analyses compared response to intravenous ketamine treatment, as defined by a 50% reduction in Patient Health Questionnaire (PHQ-9) score or final score of

Lower extremity powered exoskeletons help people with movement disorders to perform daily activities and are used increasingly in gait retraining and rehabilitation. Studies of powered exoskeletons often focus on technological aspects such as actuators, control methods, energy and effects on gait. Limited research has been conducted on how different mechanical design parameters can affect the user. In this paper, we study the effects of weight distributions of knee exoskeleton components on simulated muscle activities during three functional movements. Four knee exoskeleton CAD models were developed based on actual motor and gear reducer products. Different placements of the motor and gearbox resulted in different weight distributions. One unilateral knee exoskeleton prototype was fabricated and tested on 5 healthy subjects. Simulation results were compared to observed electromyography signals. Muscle activities varied among weight distributions and movements, wherein no one physical design was optimal for all movements. We describe how a powered exoskeleton’s core components can be expected to affect a user’s ability and performance. Exoskeleton physical design should ideally take the user’s activity goals and ability into consideration.

BACKGROUND: Amputation at the transfemoral (TF) level reduces the rate of successful prosthetic fitting, functional outcome, and quality of life (QoL) compared with transtibial amputation. The TF socket interface is considered the most critical part of the prosthesis, but socket discomfort is still the most common user complaint. Direct Socket for transfemoral prosthesis users is a novel interface fabrication process where the socket is shaped and laminated directly on the residual limb and delivered in a single visit. OBJECTIVE(S): The aim of this study was to investigate if prosthetic users' quality of life (QoL), comfort, and mobility with a Direct Socket TF interface were comparable to their experience with their previous prostheses. METHODOLOGY: The pre/post design prospective cohort study included 47 subjects. From this cohort, 36 subjects completed the 6-months follow-up (mean age 58 years, 27 males). Outcomes at baseline included EQ-5D-5L®, PLUS-M™, CLASS, ABC, AMPPRO, and TUG. At 6-weeks and 6-months, subjects repeated all measures. Seven Certified Prosthetist (CP) investigators performed observations and data collection at six different sites (from July 2018 to April 2020). FINDINGS: Results showed significant improvement in all outcome measures for the 36 subjects that completed both 6-weeks and 6-months follow-ups. CLASS sub-scales showed significantly improved stability, suspension, comfort, and socket appearance. Improvement in K-Level and less use of assistive devices were observed with the AMPPRO instrument, indicating improved user mobility and performance. QoL was also increased, as measured in Quality-Adjusted-Life-Years (QALY) from the EQ-5D-5L. CONCLUSION: Evidence from the findings demonstrate that the Direct Socket TF system and procedure can be a good alternative to the traditional method of prosthetic interface delivery. Layman's Abstract After lower limb amputation, the goal for most people is to regain mobility and independence and return to normal daily activities. Typically, people with transfemoral amputation are less likely to receive a prosthesis or fully use a prosthesis as compared to people with transtibial amputation. Moreover, their quality of life is also lower. The Direct Socket TF method is a new way of fabricating a prosthetic socket for users with above-knee amputation, enabling fabrication directly onto the residual limb and delivery of the socket in a single visit. In this study, we wanted to understand how the effect of Direct Socket TF on prosthetic 'user's quality of life, health, mobility level, and balance would compare to their previous prosthesis. This new Direct Socket TF procedure was implemented in six different prosthetic clinics across the United States and used by 36 prosthetic users for six months. Our first article on this study describes increased user satisfaction with their new interface and the single visit service model. This second article on the same clinical investigation documents the significant improvement in outcomes compared to their original interface in terms of quality of life, confidence, mobility, comfort, stability, and activity level. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/36065/27923 Direct Socket TF – Summary (YouTube): https://www.youtube.com/watch?v=-fvVFqjgxjo How To Cite: Walker J, Marable W.R, Smith C, Sigurjónsson B.Þ, Atlason I.F, Johannesson G.A. Clinical outcome of transfemoral direct socket interface (part 2). Canadian Prosthetics & Orthotics Journal. 2021;Volume 4, Issue 1, No.6. https://doi.org/10.33137/cpoj.v4i1.36065 Corresponding Author: Anton Johannesson, PhD TeamOlmed, Kistagången 12, 164 40 Kista, Stockholm, Sweden. E-mail: ajohannesson@teamolmed.se ORCID: https://orcid.org/0000-0001-8729-458X

Exoskeletons are increasingly used in rehabilitation and daily life in patients with motor disorders after neurological injuries. In this paper, a realistic human knee exoskeleton model based on a physical system was generated, a human–machine system was created in a musculoskeletal modeling software, and human–machine interactions based on different assistive strategies were simulated. The developed human–machine system makes it possible to compute torques, muscle impulse, contact forces, and interactive forces involved in simulated movements. Assistive strategies modeled as a rotational actuator, a simple pendulum model, and a damped pendulum model were applied to the knee exoskeleton during simulated normal and fast gait. We found that the rotational actuator–based assistive controller could reduce the user's required physiological knee extensor torque and muscle impulse by a small amount, which suggests that joint rotational direction should be considered when developing an assistive strategy. Compared to the simple pendulum model, the damped pendulum model based controller made little difference during swing, but further decreased the user's required knee flexor torque during late stance. The trade-off that we identified between interaction forces and physiological torque, of which muscle impulse is the main contributor, should be considered when designing controllers for a physical exoskeleton system. Detailed information at joint and muscle levels provided in this human–machine system can contribute to the controller design optimization of assistive exoskeletons for rehabilitation and movement assistance.

BACKGROUND: Direct Socket for transfemoral (DS-TF) prosthetic user is a novel method of fabricating a laminated interface on to the residual limb but requires different training, production method and service model than what most prosthetists are familiar with. This method and model may improve patient satisfaction by enabling interface fabrication and delivery in one visit. OBJECTIVES: Document patient satisfaction regarding DS-TF interface versus the prosthetic users’ previous socket in terms of interface function and the clinic service model. METHODOLOGY: In this longitudinal study (from July 2018 to April 2020), the DS-TF was implemented in six prosthetic clinics across the United States. Certified prosthetists (CP) and assistants were trained using a standard protocol. 47 prosthetic users participated, both those in need of a new socket and those without need. Two modules from the Orthotics and Prosthetics Users’ Survey (OPUS), involving questions related to satisfaction with the Device and Services, was used to evaluate each DS-TF user outcome vs. baseline. The only part of the prosthesis that was replaced was the interface, except in 2 cases. FINDINGS: Each DS-TF interface was fabricated, fit and delivered in a single clinic visit. At 6-months follow-up, 38 users reported an average of 29.8% increase in satisfaction with their new interface compared with original, and a 14.8% increase in satisfaction with the services they received from the clinic in providing of the new prosthesis vs. their original prosthesis. The main outcome increases were between baseline (initial fitting) and 6-week follow-up and remained consistent after 6 months. This improvement was consistent irrespective if the user needed a new socket for clinical reasons or not. CONCLUSION: This study shows that after a standardized training and implementation, the DS-TF fabrication process including a new interface, improves the user’s satisfaction with their prosthetic device and services. Layman's Abstract The connection between an amputee’s remaining limb and their prosthesis is called the interface and is the most critical part in a prosthetic system for the user satisfaction, comfort and mobility. Interfaces commonly consist of two parts; a flexible “liner” rolled onto the limb, which then goes into a hard socket custom-made by the prosthetist. The assembled interface then provides a secure connection between the users remaining limb and the prosthesis. Historically the prosthetist’s fabrication and fitting procedure required many hours of time and multiple visits to the prosthetic clinic before the interface was delivered to the user. Direct Socket for above knee prosthetic users is a new method of fabricating laminated sockets directly on the residual limb that enables fabrication and delivery in a single visit. However, Direct Socket require different training and methods than what most prosthetists are familiar with. This new procedure was implemented in six different prosthetic clinics across the United States. Seven CP’s were trained, each in their clinic and the method was tested on 38 users for a period of 6 months. The users filled in questionnaires about their experience and satisfaction using their existing socket, as well as their satisfaction of using their new socket. Overall, the Direct Socket prosthetic users reported after the 6-months follow-up significantly greater (29.8%) satisfaction with their new socket compared to their previous socket. They also reported 14.8% increase in satisfaction with the services they obtained from the clinic when receiving the new socket, compared to their satisfaction with receiving their original socket. Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/34672/26933 How To Cite: Marable W.R, Smith C, Sigurjónsson B.Þ, Atlason I.F, Johannesson G.A. Transfemoral socket fabrication method using direct casting: outcomes regarding patient satisfaction with device and services. Canadian Prosthetics & Orthotics Journal. 2020;Volume 3, Issue 2, No.6. https://doi.org/10.33137/cpoj.v3i2.34672 Corresponding Author: G. Anton Johannesson, PhD TeamOlmed, Kistagången 12, 164 40 Kista, Stockholm, Sweden. E-mail: ajohannesson@teamolmed.se ORCID: https://orcid.org/0000-0001-8729-458X

Gait phase recognition is of great importance in the development of assistance-as-needed robotic devices, such as exoskeletons. In order for a powered exoskeleton with phase-based control to determine and provide proper assistance to the wearer during gait, the user’s current gait phase must first be identified accurately. Gait phase recognition can potentially be achieved through input from wearable sensors. Deep convolutional neural networks (DCNN) is a machine learning approach that is widely used in image recognition. User kinematics, measured from inertial measurement unit (IMU) output, can be considered as an ‘image’ since it exhibits some local ‘spatial’ pattern when the sensor data is arranged in sequence. We propose a specialized DCNN to distinguish five phases in a gait cycle, based on IMU data and classified with foot switch information. The DCNN showed approximately 97% accuracy during an offline evaluation of gait phase recognition. Accuracy was highest in the swing phase and lowest in terminal stance.

Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and genomic real-time polymerase chain reaction (PCR). Furthermore, we show that there is loss of physiological KLF4 expression in more than 40% of primary medulloblastomas both at the RNA and protein levels. Medulloblastoma cell lines drastically increase the expression of KLF4 in response to the demethylating agent 5-azacytidine and demonstrate dense methylation of the promoter CpG island by bisulfite sequencing. Methylation-specific PCR targeting the KLF4 promoter demonstrates CpG methylation in approximately 16% of primary medulloblastomas. Reexpression of KLF4 in the D283 medulloblastoma cell line results in significant growth suppression both in vitro and in vivo. We conclude that KLF4 is inactivated by either genetic or epigenetic mechanisms in a large subset of medulloblastomas and that it likely functions as a tumor suppressor gene in the pathogenesis of medulloblastoma.

Agricultural water demands can conflict with habitat needs in many North Coast watersheds. Understanding different water use patterns can help reduce conflict over limited supplies. We measured on-farm crop water use and conducted grower interviews to estimate the agricultural water demand in the upper Russian River and Navarro River watersheds. Annual agricultural water demand was less than 11% in the Russian River, and 2% in Navarro River, of the total annual discharge in each watershed. However, because demands are concentrated in the dry season when instream flows are at a minimum, these relatively small amounts can represent a significant constraint to stream habitat conditions. We have shared our study results in broad basin and community water resource planning efforts, including flow management of the Russian and Navarro rivers and implementation of the Sustainable Groundwater Management Act in the Ukiah Basin. Findings and recommendations from this study have influenced on-the-ground solutions to meet water demand in these watersheds, including construction of off-stream wintertime storage capacity to replace summertime stream diversions, and use of a municipal recycled water conveyance system as a replacement for summer diversions.