Temperature measurement and control system for transtibial prostheses: single subject clinical evaluation.

The snug fit of a prosthetic socket over the residual limb can disturb thermal balance and put skin integrity in jeopardy by providing an unpleasant and infectious environment. The prototype of a temperature measurement and control (TM&C) system was previously introduced to resolve thermal problems related to prostheses. This study evaluates its clinical application in a setting with reversal, single subject design. The TM&C system was installed on a fabricated prosthetic socket of a man with unilateral transtibial amputation. Skin temperature of the residual limb without prosthesis at baseline and with prosthesis during rest and walking was evaluated. The thermal sense and thermal comfort of the participant were also evaluated. The results showed different skin temperature around the residual limb with a temperature decrease tendency from proximal to distal. The TM&C system decreased skin temperature rise after prosthesis wearing. The same situation occurred during walking, but the thermal power of the TM&C system was insufficient to overcome heat build-up in some regions of the residual limb. The participant reported no significant change of thermal sense and thermal comfort. Further investigations are warranted to examine thermography pattern of the residual limb, thermal sense, and thermal comfort in people with amputation.N/

Temperature measurement and control system for transtibial prostheses: functional evaluation.

The accumulation of heat inside the prosthetic socket increases skin temperature and fosters perspiration, which consequently leads to high tissue stress, friction blister, discomfort, unpleasant odor, and decreased prosthesis suspension and use. In the present study, the prototype of a temperature measurement and control (TM&C) system was designed, fabricated, and functionally evaluated in a phantom model of the transtibial prosthetic socket. The TM&C system was comprised of 12 thermistors divided equally into two groups that arranged internal and external to a prosthetic silicone liner. Its control system was programmed to select the required heating or cooling function of a thermal pump to provide thermal equilibrium based on the amount of temperature difference from a defined set temperature, or the amount of difference between the mean temperature recorded by inside and outside thermistors. A thin layer of aluminum was used for thermal conduction between the thermal pump and different sites around the silicone liner. The results showed functionality of the TM&C system for thermoregulation inside the prosthetic socket. However, enhancing the structure of this TM&C system, increasing its thermal power, and decreasing its weight and cost are main priorities before further development.The Hong Kong Polytechnic University supported all expenses of functional evaluation. Moreover, The ST&G Corporation, South Korea, has donated silicone liners for functional evaluation. The authors received no more support for conduction of this stud

Total Synthesis of (±)-Phomoidride D

Described herein is a synthetic strategy for the total synthesis of (±)‐phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels–Alder cycloaddition. A subsequent SmI2‐mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion

A novel de novo BRCA1 mutation in a Chinese woman with early onset breast cancer

Germline mutations in the two breast cancer susceptibility genes, BRCA1 and BRCA2 account for a significant portion of hereditary breast/ovarian cancer. De novo mutations such as multiple exon deletion are rarely occurred in BRCA1 and BRCA2. During our mutation screening for BRCA1/2 genes to Chinese women with risk factors for hereditary breast/ovarian cancer, we identified a novel germline mutation, consisting of a deletion from exons 1 to 12 in BRCA1 gene, in a patient diagnosed with early onset triple negative breast cancer with no family history of cancer. None of her parents carried the mutation and molecular analysis showed that this novel de novo germline mutation resulted in down-regulation of BRCA1 gene expression

Localizing FRBs through VLBI with the Algonquin Radio Observatory 10 m Telescope

The Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB experiment has detected thousands of fast radio bursts (FRBs) due to its sensitivity and wide field of view; however, its low angular resolution prevents it from localizing events to their host galaxies. Very long baseline interferometry (VLBI), triggered by FRB detections from CHIME/FRB will solve the challenge of localization for non-repeating events. Using a refurbished 10 m radio dish at the Algonquin Radio Observatory located in Ontario Canada, we developed a testbed for a VLBI experiment with a theoretical λ/D ≲ 30 mas. We provide an overview of the 10 m system and describe its refurbishment, the data acquisition, and a procedure for fringe fitting that simultaneously estimates the geometric delay used for localization and the dispersive delay from the ionosphere. Using single pulses from the Crab pulsar, we validate the system and localization procedure, and analyze the clock stability between sites, which is critical for coherently delay referencing an FRB event. We find a localization of ∼200 mas is possible with the performance of the current system (single-baseline). Furthermore, for sources with insufficient signal or restricted wideband to simultaneously measure both geometric and ionospheric delays, we show that the differential ionospheric contribution between the two sites must be measured to a precision of 1 × 10-8 pc cm-3 to provide a reasonable localization from a detection in the 400-800 MHz band. Finally we show detection of an FRB observed simultaneously in the CHIME and the Algonquin 10 m telescope, the first non-repeating FRB in this long baseline. This project serves as a testbed for the forthcoming CHIME/FRB Outriggers project

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population. METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials. RESULTS: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner. CONCLUSION: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients

Histidine-Rich Glycoprotein Protects from Systemic Candida Infection

Fungi, such as Candida spp., are commonly found on the skin and at mucosal surfaces. Yet, they rarely cause invasive infections in immunocompetent individuals, an observation reflecting the ability of our innate immune system to control potentially invasive microbes found at biological boundaries. Antimicrobial proteins and peptides are becoming increasingly recognized as important effectors of innate immunity. This is illustrated further by the present investigation, demonstrating a novel antifungal role of histidine-rich glycoprotein (HRG), an abundant and multimodular plasma protein. HRG bound to Candida cells, and induced breaks in the cell walls of the organisms. Correspondingly, HRG preferentially lysed ergosterol-containing liposomes but not cholesterol-containing ones, indicating a specificity for fungal versus other types of eukaryotic membranes. Both antifungal and membrane-rupturing activities of HRG were enhanced at low pH, and mapped to the histidine-rich region of the protein. Ex vivo, HRG-containing plasma as well as fibrin clots exerted antifungal effects. In vivo, Hrg−/− mice were susceptible to infection by C. albicans, in contrast to wild-type mice, which were highly resistant to infection. The results demonstrate a key and previously unknown antifungal role of HRG in innate immunity