MIDOT: A novel probe for monitoring high-current flat transmission lines

A novel inductive probe, termed MIDOT, was developed for monitoring high-current flat transmission lines. While being inexpensive the probe does not require calibration, is resistant to both shock waves and temperature variations, and it is easy to manufacture and mount. It generates strong output signals that are relatively easy to interpret and has a detection region limited to a pre-defined part of the transmission line. The theoretical background related to the MIDOT probes, together with their practical implementation in both preliminary experimentation and high-current tests, is also presented in the paper. The novel probe can be used to benchmark existing 2D numerical codes used in calculating the current distribution inside the conductors of a transmission line but can easily detect an early movement of a transmission line component. The probe can also find other applications, such as locating the position of a pulsed current flowing through a thin wire

Beta cell death by cell-free DNA and outcome after clinical islet transplantation

Background: Optimizing engraftment and early survival after clinical islet transplantation is critical to long-term function, but there are no reliable, quantifiable measures to assess beta cell death. Circulating cell free DNA (cfDNA) derived from beta cells has been identified as a novel biomarker to detect cell loss, and was recently validated in new-onset type 1 diabetes and in islet transplant patients. Methods: Herein we report beta cell cfDNA measurements after allotransplantation in 37 subjects and the correlation with clinical outcomes. Results: A distinctive peak of cfDNA was observed 1hr after transplantation in 31/37 (83.8%) of subjects. The presence and magnitude of this signal did not correlate with transplant outcome. The 1hr signal represents dead beta cells carried over into the recipient after islet isolation and culture, combined with acute cell death post infusion. Beta cell cfDNA was also detected 24hrs post-transplant (8/37 subjects, 21.6%). This signal was associated with higher 1-month insulin requirements (p=0.04), lower 1-month stimulated C-peptide levels (p=0.01) and overall worse 3-month engraftment, by insulin independence (ROC:AUC=0.70, p=0.03) and Beta 2 score (ROC:AUC=0.77, p=0.006). Conclusions: cfDNA-based estimation of beta cell death 24hrs after islet allotransplantation correlates with clinical outcome and could predict early engraftment.B.G.-L. is supported through the Alberta Innovates :Health Solutions (AIHS) Clinician Fellowship and through the CNTRP. A.P. is supported through AIHS Postgraduate Fellowship and CNTRP. A.M.J.S. is supported through AIHS, and holds a Canada Research Chair in Transplantation Surgery and Regenerative Medicine funded through the Government of Canada. A.M.J.S. is also funded by AIHS Collaborative Research and Innovation Opportunity Team Award and the Diabetes Research Institute Foundation of Canada (DRIFCan). Supported by grants from the Juvenile Diabetes Research Foundation (JDRF) (3-SRA-2014-38-Q-R, to Y.D. and A.M.J.S.), National Institute of Health (NIH) (HIRN grant UC4 DK104216, to Y.D.), DON foundation (Stichting Diabetes Onderzoek Nederland) (to Y.D), the European Union (ELASTISLET project, to Y.D.) and the Kahn foundation (to Y.D., R.S., and B.G.). Supported in part by a grant from The United States Agency for International Development (USAID) American Schools and Hospitals Abroad Program for the upgrading of the Hebrew University sequencing core facilit

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy: A Review for the Otolaryngologist

Background: Cystic fibrosis (CF) is a genetic disease that may result in multiple systemic disorders and potentially fatal severe respiratory compromise. However, the advent of CF transmembrane conductance regulator (CFTR) modulators has changed the management of CF for patients with select mutations. Although clinical trials have highlighted increased pulmonary function and decreased exacerbations as a result of these novel therapies, their effect on the sinuses has not been well-described. Objective: Our objective is to review the CFTR modulators to provide otolaryngologists, physicians who frequently care for patients with CF, a basic understanding of these drugs and their effects on chronic rhinosinusitis (CRS) in patients with CF. Methods: The clinically approved and available CFTR modulators and specific indications for their use are reviewed. Additionally, a systematic review of these therapies and effects on CRS in CF was performed. Results: Four Food and Drug Administration approved CFTR modulators are available for patients with CF. Current drugs are approved for gating, residual function, or F508del mutations. Multiple reports describe CFTR modulators’ increase in transepithelial ion transport in nasal epithelial cultures; however, clinical studies regarding effects of these modulators on sinonasal health are limited to 5 studies that present new data of the effects of CFTR modulators in CRS. Conclusions: CFTR modulators have changed management of CF. Initial studies of these medications demonstrate promising results in CF; however, there is a paucity of literature describing the effect of CFTR modulators on CF-associated CRS, although initial results are encouraging

Comparative study of simulated nebulized and spray particle deposition in chronic rhinosinusitis patients

Background: Topical intranasal drugs are widely prescribed for chronic rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). Methods: Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of 3 subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-µm to 120-µm sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-µm to 30-µm droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. Results: Among nebulized droplet sizes, 11-µm to 14-µm droplets achieved at least 50% of MSDF in all 6 sinonasal cavities. Four of 6 sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. Conclusion: Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement

Sinus Development and Pneumatization in a Primary Ciliary Dyskinesia Cohort

Background: Primary ciliary dyskinesia (PCD) is a genetically diverse disease which causes impaired mucociliary clearance, and results in pulmonary, otologic, and rhinologic disease in affected patients. Genetic mutations in multiple genes impair the ability of patients to clear mucous from the lungs, middle ear, and sinonasal cavity and lead to chronic pulmonary and sinonasal symptoms. Methods: We identified 17 PCD patients who had available CT scans. Volumes for bilateral maxillary, sphenoid, and frontal sinuses were calculated. A control population of patients who had preoperative CT scans for endoscopic endonasal resection of skull base pathology without sinonasal cavity involvement was also identified. Results: The mean age of PCD was 33 and ranged from 13 to 54 years. Patients were age- and gender-matched to a control group that underwent resection of anterior skull-base tumors and had a mean age of 35 that ranged between 17–53 years old. The volumes for all thee sinus cavities were significantly smaller (p < 0.007) compared to the control population. The average Lund-Mackay score was 10.6 in the PCD cohort (range 6–16) in comparison to an average of 0.7 in the control cohort (range 0–2). Conclusions: Overall sinus volumes were smaller in patients with PCD compared to our control population. Future studies will be aimed at understanding defects in sinus development as a function of specific genetic mutations in PCD patients. Ultimately, a better understanding of the underlying pathophysiology of PCD will allow us to identify the optimal treatment practices for this unique patient group

Well, I wouldn\u27t be any worse off, would I, than I am now? A qualitative study of decision-making, hopes, and realities of adults with type 1 diabetes undergoing islet cell transplantation

BACKGROUND: For selected individuals with type 1 diabetes, pancreatic islet transplantation (IT) prevents recurrent severe hypoglycemia and optimizes glycemia, although ongoing systemic immunosuppression is needed. Our aim was to explore candidates and recipients\u27 expectations of transplantation, their experience of being on the waiting list, and (for recipients) the procedure and life posttransplant. METHODS: Cross-sectional qualitative research design using semistructured interviews with 16 adults (8 pretransplant, 8 posttransplant; from 4 UK centers (n = 13) and 1 Canadian center (n = 3)). Interviews were audio-recorded, transcribed, and underwent inductive thematic analysis. RESULTS: Interviewees were aged (mean &plusmn; SD) 52 &plusmn; 10 years (range, 30-64); duration of diabetes, 36 &plusmn; 9 years (range, 21-56); 12 (75%) were women. Narrative accounts centered on expectations, hopes, and realities; decision-making; waiting and uncertainty; the procedure, hospital stay, and follow-up. Expected benefits included fewer severe hypoglycemic episodes, reduced need for insulin, preventing onset/progression of complications and improved psychological well-being. These were realized for most, at least in the short term. Most interviewees described well-informed, shared decision-making with clinicians and family, and managing their expectations. Although life &quot;on the list&quot; could be stressful, and immunosuppressant side effects were severe, interviewees reported &quot;no regrets.&quot; Posttransplant, interviewees experienced increased confidence, through freedom from hypoglycemia and regained glycemic control, which tempered any disappointment about continued reliance on insulin. Most viewed their transplant as a success, though several reflected upon setbacks and hidden hopes for becoming &quot;insulin-free.&quot; CONCLUSIONS: Independently undertaken interviews demonstrated realistic and balanced expectations of IT and indicate how to optimize the process and support for future IT candidates

Mometasone absorption in cultured airway epithelium

Background: Topical mometasone is frequently used as an intranasal spray, on drug-eluting stents, and compounded by specialty pharmacies as a sinus rinse. A typical sinus rinse contains 1.2 mg of mometasone dissolved in 240 mL of buffered saline and is flushed through the sinonasal cavity. The mometasone irrigation rapidly flows to the contralateral sinonasal cavity or the nasopharynx with a contact time on the order of 5 to 10 seconds. However, no information is available on the absorption rate of topical mometasone on the sinonasal surface. Methods: To determine the absorption characteristics of mometasone, we harvested nasal epithelium from 2 healthy donors and differentiated them into a mature ciliated epithelium on Millicell membranes. We applied mometasone to the apical surface for various time intervals and then rinsed off non-absorbed mometasone with phosphate-buffered saline. Millicell membranes with the adherent epithelial cells were then harvested and stored in guanidine hydrochloride for quantification using high-performance liquid chromatography–mass spectrometry. Results: Fifty percent of the maximal absorption occurred after an average of 38 minutes after application, and maximal absorption occurred after an average of 114 minutes. Conclusion: Our data provide an estimate for rates of absorption of mometasone applied to the sinonasal cavity and suggest that the absorption rates poorly match contact time during saline lavage

Defining the impact of dietary macronutrient balance on PCOS traits

Lifestyle, mainly dietary, interventions are first-line treatment for women with polycystic ovary syndrome (PCOS), but the optimal diet remains undefined. We combined a hyperandrogenized PCOS mouse model with a systematic macronutrient approach, to elucidate the impact of dietary macronutrients on the development of PCOS. We identify that an optimum dietary macronutrient balance of a low protein, medium carbohydrate and fat diet can ameliorate key PCOS reproductive traits. However, PCOS mice display a hindered ability for their metabolic system to respond to diet variations, and varying macronutrient balance did not have a beneficial effect on the development of metabolic PCOS traits. We reveal that PCOS traits in a hyperandrogenic PCOS mouse model are ameliorated selectively by diet, with reproductive traits displaying greater sensitivity than metabolic traits to dietary mac ronutrient balance. Hence, providing evidence to support the development of evidence-based dietary interventions as a promising strategy for the treatment of PCOS, especially repro ductive traits.Valentina Rodriguez Paris, Samantha M. Solon-Biet, Alistair M. Senior, Melissa C. Edwards Reena Desai, Nicodemus Tedl

Numerical evaluation of spray position for improved nasal drug delivery

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare. Finally, with respiratory mucosa as the initial coronavirus infection site, our findings are relevant to intra-nasal vaccines that are in-development, to mitigate the COVID-19 pandemic