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Aim To evaluate whether both bolus insulin injection frequency and smart pen engagement were associated with changes in glycaemic control, using real-world data from adults with type 1 diabetes (T1D). Materials and Methods Adults using a smart pen (NovoPen 6) to administer bolus insulin (fast-acting insulin aspart or insulin aspart) alongside continuous glucose monitoring were eligible for inclusion. Smart pen engagement was characterized by number of days with pen data uploads over the previous 14 days. Glycaemic control was evaluated by analysing glucose metrics. Results Overall, data from 1194 individuals were analysed. The number of daily bolus injections was significantly associated with time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]; P < 0.0001). Individuals administering, on average, three daily bolus insulin injections had an estimated 11% chance of achieving >70% TIR. The probability of achieving >70% TIR increased with the mean number of daily bolus injections. However, the percentage of TIR was lower on days when individuals administered higher-than-average numbers of injections. The observed mean number of daily bolus injections administered across the study population was lower than the optimal number required to reach glycaemic targets (4.8 injections vs. 6-8 injections). Smart pen engagement was significantly associated with improved TIR. Conclusions Glycaemic control was associated with daily bolus insulin injection frequency and smart pen engagement. A treatment regimen combining an optimal bolus injection strategy, and effective smart pen engagement, may improve glycaemic control among adults with T1D.

We study electrohydrodynamic (EHD) linear (in)stability of microfluidic channel flows, i.e., the stability of interface between two shearing viscous (perfect) dielectrics exposed to an electric field in large aspect ratio microchannels. We then apply our results to particular microfluidic systems known as two-liquid electroosmotic (EO) pumps. Our novel results are detailed analytical expressions for the growth rate of two-dimensional EHD modes in Couette–Poiseuille flows in the limit of small Reynolds number (R); the expansions to both zeroth and first order in R are considered. The growth rates are complicated functions of viscosity-, height-, density-, and dielectric-constant ratio, as well as of wavenumbers and voltages. To make the results useful to experimentalists, e.g., for voltage-control EO pump operations, we also derive equations for the impending voltages of the neutral stability curves that divide stable from unstable regions in voltage–wavenumber stability diagrams. The voltage equations and the stability diagrams are given for all wavenumbers. We finally outline the flow regimes in which our first-order-R voltage corrections could potentially be experimentally measured. Our work gives insight into the coupling mechanism between electric field and shear flow in parallel-planes channel flows, correcting an analogous EHD expansion to small R from the literature. We also revisit the case of pure shear instability, when the first-order-R voltage correction equals zero, and replace the renowned instability mechanism due to viscosity stratification at small R with the mechanism due to discontinuity in the slope of the unperturbed velocity profile.

We design a linear chain trick algorithm for dynamical systems for which we have oscillatory time histories in the distributed time delay. We make use of this algorithmic framework to analyse memory effects in disease evolution in a population. The modelling is based on a susceptible-infected-recovered SIR-model and on a susceptible-exposed-infected-recovered SEIR-model through a kernel that dampens the activity based on the recent history of infectious individuals. This corresponds to adaptive behavior in the population or through governmental non-pharmaceutical interventions. We use the linear chain trick to show that such a model may be written in a Markovian way, and we analyze the stability of the system. We find that the adaptive behavior gives rise to either a stable equilibrium point or a stable limit cycle for a close to constant number of susceptibles, i.e. locally in time. We also show that the attack rate for this model is lower than it would be without the dampening, although the adaptive behavior disappears as time goes to infinity and the number of infected goes to zero.

This paper introduces a two-step procedure for stabilising a chaotic system around an arbitrary periodic orbit in a Poincaré map. The periodic orbit may be a period-n orbit traversing the Poincaré plane an integer n times before completing the periodic cycle. The order of traversing can also be chosen arbitrarily. Chaotic systems lack predictability due to positive Lyapunov exponents. For this reason, predictive control methods tend to perform poorly because the predictable horizon may be short. Current methods for stabilising chaotic systems work by controlling existing unstable periodic orbits. This paper proposes a method for stabilising the system on an arbitrary point in the Poincaré section. The method in this paper consists of two steps. In the first step, we pose an optimisation problem that computes an input signal that introduces a desired unstable or stable periodic orbit. In the second step, we use existing methods, such as the method using delay coordinate embedding developed by Ott, Grebogi and Yorke in 1990, to stabilise the system around the newly introduced periodic orbit. As an example, we demonstrate the method on the resistively and capacitively shunted driven Josephson junction.

Aim To evaluate whether both bolus insulin injection frequency and smart pen engagement were associated with changes in glycaemic control, using real-world data from adults with type 1 diabetes (T1D). Materials and Methods Adults using a smart pen (NovoPen 6) to administer bolus insulin (fast-acting insulin aspart or insulin aspart) alongside continuous glucose monitoring were eligible for inclusion. Smart pen engagement was characterized by number of days with pen data uploads over the previous 14 days. Glycaemic control was evaluated by analysing glucose metrics. Results Overall, data from 1194 individuals were analysed. The number of daily bolus injections was significantly associated with time in range (TIR; 3.9-10.0 mmol/L [70-180 mg/dL]; P < 0.0001). Individuals administering, on average, three daily bolus insulin injections had an estimated 11% chance of achieving >70% TIR. The probability of achieving >70% TIR increased with the mean number of daily bolus injections. However, the percentage of TIR was lower on days when individuals administered higher-than-average numbers of injections. The observed mean number of daily bolus injections administered across the study population was lower than the optimal number required to reach glycaemic targets (4.8 injections vs. 6-8 injections). Smart pen engagement was significantly associated with improved TIR. Conclusions Glycaemic control was associated with daily bolus insulin injection frequency and smart pen engagement. A treatment regimen combining an optimal bolus injection strategy, and effective smart pen engagement, may improve glycaemic control among adults with T1D.

Background Chronic kidney disease (CKD) leads to an accumulation of waste products and causes adverse cardiometabolic effects. Objectives We investigated the health effects of the New Nordic Renal Diet (NNRD), a novel meal pattern reduced in phosphorus, protein, and sodium. Methods A 26-wk randomized trial compared the NNRD with a habitual diet. The NNRD group received weekly home deliveries of food and recipes. Monthly study visits included fasting blood samples, 24-h urine samples, blood pressure, and anthropometric measurements. Intention-to-treat analysis used linear mixed-effects models. Results Sixty patients, mean estimated glomerular filtration rate (eGFR) 34 mL/min/1.73 m2 and body mass index of 25–27 kg/m2, were included and 58 completed. Metabolic syndrome was present in 53% (NNRD group) and 57% (control group). The NNRD group (n = 30) reduced their 24-h urine phosphorus excretion by 19% (−153 mg; 95% confidence interval [CI]: −210, −95), control group (n = 30) (no change), between-group difference −171 mg (95% CI: −233, −109; P < 0.001). Proteinuria was reduced by 39% in the NNRD group (−0.33 g/d; 95% CI: −0.47, −0.18), control group (no change), between-group difference −0.34 g/d (95% CI: −0.52, −0.17; P < 0.001). Plasma urea was reduced by −1.5 mmol/L in the NNRD group (95% CI: −2.1, −0.9), control group (no change), between-group difference −1.4 mmol/L (95% CI: −2.0, −0.7; P < 0.001). Systolic blood pressure fell by −5.2 mmHg in the NNRD group (95% CI: −8.4, −2.1), control group (no change), between-group difference −3.9 mmHg (95% CI; −7.6, −0.2; P = 0.04). The NNRD group lost −1.7 kg (95% CI: −2.6, −0.8), control group (no change), between-group difference −2.0 kg (95% CI: −3.0, −1.0; P < 0.001). There were no effects on eGFR during the 26-wk intervention. Conclusion NNRD in moderate CKD reduces phosphorus excretion, proteinuria, systolic blood pressure, and weight, mainly by reducin, Background: Chronic kidney disease (CKD) leads to an accumulation of waste products and causes adverse cardiometabolic effects. Objectives: We investigated the health effects of the New Nordic Renal Diet (NNRD), a novel meal pattern reduced in phosphorus, protein, and sodium. Methods: A 26-wk randomized trial compared the NNRD with a habitual diet. The NNRD group received weekly home deliveries of food and recipes. Monthly study visits included fasting blood samples, 24-h urine samples, blood pressure, and anthropometric measurements. Intention-to-treat analysis used linear mixed-effects models. Results: Sixty patients, mean estimated glomerular filtration rate (eGFR) 34 mL/min/1.73 m2 and body mass index of 25–27 kg/m2, were included and 58 completed. Metabolic syndrome was present in 53% (NNRD group) and 57% (control group). The NNRD group (n = 30) reduced their 24-h urine phosphorus excretion by 19% (−153 mg; 95% confidence interval [CI]: −210, −95), control group (n = 30) (no change), between-group difference −171 mg (95% CI: −233, −109; P < 0.001). Proteinuria was reduced by 39% in the NNRD group (−0.33 g/d; 95% CI: −0.47, −0.18), control group (no change), between-group difference −0.34 g/d (95% CI: −0.52, −0.17; P < 0.001). Plasma urea was reduced by −1.5 mmol/L in the NNRD group (95% CI: −2.1, −0.9), control group (no change), between-group difference −1.4 mmol/L (95% CI: −2.0, −0.7; P < 0.001). Systolic blood pressure fell by −5.2 mmHg in the NNRD group (95% CI: −8.4, −2.1), control group (no change), between-group difference −3.9 mmHg (95% CI; −7.6, −0.2; P = 0.04). The NNRD group lost −1.7 kg (95% CI: −2.6, −0.8), control group (no change), between-group difference −2.0 kg (95% CI: −3.0, −1.0; P < 0.001). There were no effects on eGFR during the 26-wk intervention. Conclusion: NNRD in moderate CKD reduces phosphorus excretion, proteinuria, systolic blood pressure, and weight, mainly by reducing abdominal fat. This tria

BACKGROUND: Mastoidectomy is a complex procedure which can be trained on human cadaveric temporal bones or simulation models. The number of repetitions offered in most training curricula is considerably less than what is normally required for motor skills acquisition in crafts or sports. Directed, self-regulated virtual reality simulation training may provide unlimited repetitions but the effect on learning of extended but unsupervised training is unknown. This study recorded extended learning curves of novices in virtual reality simulation mastoidectomy training. METHODS: Six medical students used the visible ear temporal bone simulator at home for 100 repetitions. Virtual temporal bones were later assessed by 2 blinded experts on a 26-point modified Welling Scale. RESULTS: Four participants completed 100 procedures each and 2 participants completed 50 procedures. Learning curves and plots of time demonstrated great variation: one participant improved gradually during the first 50 procedures and sustained a high performance; another participant achieved only 16 points after 50 procedures; a third participant demonstrated mediocre performances between 10 and 15 points but only used about 5 minutes per procedure. The remaining 3 participants achieved high but fluctuating scores with very limited time use per procedure. Their score per time exceeds the performance of experienced otosurgeons and suggests the use of save/restore gaming strategies to inflate their performance. CONCLUSION: Deliberate learners may reach proficiency in virtual reality simulation of mastoidectomy after 50 repetitions. However, even 100 repetitions cannot guarantee proficiency if motivation fails. Creative “gaming” behavior must be considered and opposed by motivation, supervision, testing, and certification.

A computational investigation has beenconducted for a weakly nonlinear model of acoustical plane wave propagation in a cylindrical tube. Atthe left end a harmonic driving actuator excites standing waves in the tube with a solid wall at the righthand end. For driving frequencies a little higher thanthe frst resonance frequency of the simple waveequation, neglecting nonlinearities and dissipation,we observe formation of oscillating shock waves inthe weakly nonlinear model. A little above the second harmonic frequency of the simple linear waveequation we observe two counter propagating shockwaves in the tube. Increasing the driving frequencyfurther the oscillation mode turns into two parallelpropagating shocks. A Hamiltonian energy analysisis included, which demonstrates balance between theenergy input from the driver and the dissipation of thewave dynamics.

Purpose: Temporal bone surgery requires excellent surgical skills and simulation-based training can aid novices’ skills acquisition. However, simulation-based training is challenged by early stagnation of performance after few performances. Structured self-assessment during practice might enhance learning by inducing reflection and engagement in the learning task. In this study, structured self-assessment was introduced during virtual reality (VR) simulation of mastoidectomy to investigate the effects on subsequent performance during cadaveric dissection. Methods: A prospective educational study with comparison with historical controls (reference cohort). At a temporal bone dissection course, eighteen participants performed structured self-assessment during 3 h of VR simulation mastoidectomy training before proceeding to cadaver dissection (intervention cohort). At a previous course, eighteen participants received identical VR simulation training but without the structured self-assessment (reference cohort). Final products from VR simulation and cadaveric dissection were recorded and assessed by two blinded raters using a 19-point modified Welling Scale. Results: The intervention cohort completed fewer procedures (average 4.2) during VR simulation training than the reference cohort (average 5.7). Nevertheless, the intervention cohort achieved a significantly higher average performance score both in VR simulation (11.1 points, 95% CI [10.6–11.5]) and subsequent cadaveric dissection (11.8 points, 95% CI [10.7–12.8]) compared with the reference cohort, who scored 9.1 points (95% CI [8.7–9.5]) during VR simulation and 5.8 points (95% CI [4.8–6.8]) during cadaveric dissection. Conclusions: Structured self-assessment is a valuable learning support during self-directed VR simulation training of mastoidectomy and the positive effect on performance transfers to subsequent cadaveric dissection performance.

Irritant contact dermatitis (ICD) occurs frequently with the use of diabetes devices, but no guidelines for treatment exist. Since subsequent devices need intact skin for intended use, quick healing is crucial. Normal wound healing is expected to be 7-10 days. This was a single-center cross-over study that investigated the effectiveness of an occlusive hydrocolloid-based patch versus nonocclusive treatment of ICD. Participants were aged 6-20 years with active ICD caused by using diabetes device. First study period was patch treatment for 3 days. A control arm was initiated if a new ICD occurred within 30 days. ICD healed completely in 21% of the patch group but none in the controls. Itching was reported as an adverse event (AE) in both arms, but only one additional AE was noted in the patch arm: an infection at a different site from investigated. The hydrocolloid-based patch showed signs of faster healing of ICD with no additional AEs, but larger studies are needed.

Objective 3-D printing offers convenient and low-cost mastoidectomy training; nonetheless, training benefits using 3-D-printed temporal bones remain largely unexplored. In this study, we have collected validity evidence for a low-cost, 3-D-printed temporal bone for mastoidectomy training and established a credible pass/fail score for performance on the model. Study design A prospective educational study gathering validity evidence using Messick's validity framework. Setting Seven Danish otorhinolaryngology training institutions. Participants Eighteen otorhinolaryngology residents (novices) and 11 experienced otosurgeons (experts). Intervention Residents and experienced otosurgeons each performed two to three anatomical mastoidectomies on a low-cost, 3-D-printed temporal bone model produced in-house. After drilling, mastoidectomy performances were rated by three blinded experts using a 25-item modified Welling scale (WS). Main outcome measure Validity evidence using Messick's framework including reliability assessment applying both classical test theory and Generalizability theory. Results Novices achieved a mean score of 13.9 points; experienced otosurgeons achieved 23.2 points. Using the contrasting groups method, we established a 21/25-point pass/fail level. The Generalizability coefficient was 0.91, and 75% of the score variance was attributable to participant performance, indicating a high level of assessment reliability. Subsequent D studies revealed that two raters rating one performance or one rater rating two performances were sufficiently reliable for high-stakes assessment. Conclusion Validity evidence supports using a low-cost, 3-D-printed model for mastoidectomy training. The model can be printed in-house using consumer-grade 3-D printers and serves as an additional training tool in the temporal bone curriculum. For competency-based training, we established a cut-off score of 21 of 25 WS points using the contrasting groups method.

Background: Otosclerosis is a common ear disease that causes fixation of the stapes and conductive hearing impairment. However, the pathogenesis of otosclerosis is still unknown. Otosclerosis could be associated with the unique bony environment found in the otic capsule. Normal bone remodelling is almost completely absent around the inner ear after birth allowing degenerative changes and dead osteocytes to accumulate. High levels of inner ear anti resorptive osteoprotegerin (OPG) is most likely responsible for this capsular configuration. Studies have demonstrated how osteocyte lifespan variation creates occasional clusters of dead osteocytes, so-called cellular voids, at otosclerotic predilection sites in the human otic capsule. These cellular voids have been suggested as possible starting points of otosclerosis. Aim: To describe the cellular viability in otosclerotic lesions and compare it to that of cellular voids. Materials and Methods: The study was based on unbiased stereological quantifications in undecalcified human temporal bones with otosclerosis. Results: Osteocyte viability was found to vary within the otosclerotic lesions. Furthermore, the results presented here illustrate that inactive otosclerotic lesions consist of mainly dead interstitial bone, much like cellular voids. Conclusions and significance: Focal degeneration in the otic capsule may play an important role in the pathogenesis of otosclerosis.

Objective: Metabolic acidosis and the uremic toxins, indoxyl sulphate (IS) and p-cresyl sulphate (PCS), are associated with increased risks of kidney disease progression, muscle catabolism, cardiovascular disease, and mortality in patients with chronic kidney disease (CKD). The New Nordic Renal Diet (NNRD) is a plant focused meal pattern, with reduced phosphorus and protein content compared to an average Danish diet. Due to a higher amount of plant-based products, we hypothesized that NNRD would reduce renal excretion of acids and uremic toxins. Thus, we evaluated the effects of NNRD on metabolic acidosis and uremic toxins in patients with moderate CKD, stages 3-4.Design and methods: This post hoc analysis is based on a randomized controlled crossover trial comparing 1-week of the NNRD to a control period of an average Danish diet with a 1-week period, in patients with CKD stages 3 and 4. Urine pH and urine excretion of bicarbonate, ammonium, titratable acids, IS and PCS alongside plasma total CO2 (tCO2) were measured at days 1, 4, and 7 in 18 patients.Results: After 7 days on NNRD 24-h urine net acid excretion (NAE) was decreased by 80% (P<.001), 24-h urine excretion of ammonium and bicarbonate decreased by 34% (P<.001) and increased by 678% (P<.001), respectively, compared with the control period. Plasma tCO2 was increased by 8% (P=.005). Moreover, 24-hour urine excretion of PCS and IS were reduced by 31% (P=.018) and 29% (P<.001), respectively.Conclusion: One week of NNRD in patients suffering from moderate CKD effectively improved metabolic acidosis with a marked reduction in urine NAE that included a large increase in urine bicarbonate excretion. In addition, NNRD reduced urinary excretion of the uremic toxins PCS and IS. These results encourage further investigations of the long-term effects of NNRD on renal protection in p