Virtually optimized insoles for offloading the diabetic foot: a randomized crossover study

Integration of objective biomechanical measures of foot function into the design process for insoles has been shown to provide enhanced plantar tissue protection for individuals at-risk of plantar ulceration. The use of virtual simulations utilizing numerical modeling techniques offers a potential approach to further optimize these devices. In a patient population at-risk of foot ulceration, we aimed to compare the pressure offloading performance of insoles that were optimized via numerical simulation techniques against shape-based devices. Twenty participants with diabetes and at-risk feet were enrolled in this study. Three pairs of personalized insoles: one based on shape data and subsequently manufactured via direct milling; and two were based on a design derived from shape, pressure, and ultrasound data which underwent a finite element analysis-based virtual optimization procedure. For the latter set of insole designs, one pair was manufactured via direct milling, and a second pair was manufactured through 3D printing. The offloading performance of the insoles was analyzed for forefoot regions identified as having elevated plantar pressures. In 88% of the regions of interest, the use of virtually optimized insoles resulted in lower peak plantar pressures compared to the shape-based devices. Overall, the virtually optimized insoles significantly reduced peak pressures by a mean of 41.3 kPa (p < 0.001, 95% CI [31.1, 51.5]) for milled and 40.5 kPa (p < 0.001, 95% CI [26.4, 54.5]) for printed devices compared to shape-based insoles. The integration of virtual optimization into the insole design process resulted in improved offloading performance compared to standard, shape-based devices.Full Tex

Automated reduction of submillimetre single-dish heterodyne data from the James Clerk Maxwell Telescope using ORAC-DR

With the advent of modern multi-detector heterodyne instruments that can result in observations generating thousands of spectra per minute it is no longer feasible to reduce these data as individual spectra. We describe the automated data reduction procedure used to generate baselined data cubes from heterodyne data obtained at the James Clerk Maxwell Telescope. The system can automatically detect baseline regions in spectra and automatically determine regridding parameters, all without input from a user. Additionally it can detect and remove spectra suffering from transient interference effects or anomalous baselines. The pipeline is written as a set of recipes using the ORAC-DR pipeline environment with the algorithmic code using Starlink software packages and infrastructure. The algorithms presented here can be applied to other heterodyne array instruments and have been applied to data from historical JCMT heterodyne instrumentation.Comment: 18 pages, 13 figures, submitted to Monthly Notices of the Royal Astronomical Societ

Selective suppression of local interneuron circuits in human motor cortex contributes to movement preparation.

Changes in neural activity occur in the motor cortex prior to movement, but the nature and purpose of this preparatory activity is unclear. To investigate this in the human (male and female) brain non-invasively, we used transcranial magnetic stimulation (TMS) to probe the excitability of distinct sets of excitatory inputs to corticospinal neurones during the warning period of various reaction time tasks. Using two separate methods (H-reflex conditioning and directional effects of TMS), we show that a specific set of excitatory inputs to corticospinal neurones are suppressed during motor preparation, whilst another set of inputs remain unaffected. To probe the behavioural relevance of this suppression, we examined whether the strength of the selective preparatory inhibition in each trial was related to reaction time. Surprisingly, the greater the amount of selective preparatory inhibition, the faster the reaction time was. This suggests that the inhibition of inputs to corticospinal neurones is not involved in preventing release of movement but may in fact facilitate rapid reactions. Thus, selective suppression of a specific set of motor cortical neurones may be a key aspect of successful movement preparation.Significance statementMovement preparation evokes substantial activity in the motor cortex despite no apparent movement. One explanation for the lack of movement is that motor cortical output in this period is gated by an inhibitory mechanism. This notion was supported by previous non-invasive TMS studies of human motor cortex indicating a reduction of corticospinal excitability. On the contrary, our data supports the idea that there is a coordinated balance of activity upstream of the corticospinal output neurones. This includes a suppression of specific local circuits that supports, rather than inhibits, the rapid generation of prepared movements. Thus, the selective suppression of local circuits appears to be an essential part of successful movement preparation, instead of an external control mechanism

Relationship between blood pressure values, depressive symptoms and cardiovascular outcomes in patients with cardiometabolic disease

We studied joint effect of blood pressure-BP and depression on risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35537 patients with coronary heart disease, diabetes or stroke underwent depression screening and BP was recorded concurrently. We used Cox’s proportional hazards to calculate risk of major adverse cardiovascular event-MACE (myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with baseline BP and depression. 11% (3939) had experienced MACE within 4 years. Patients with very high systolic BP-SBP (160-240) hazard ratio-HR 1.28 and with depression (HR 1.22) at baseline had significantly higher adjusted risk. Depression had significant interaction with SBP in risk prediction (p=0.03). Patients with combination of SBP and depression at baseline had 83% higher adjusted risk of MACE, as compared to patients with reference SBP and without depression. Patients with cardiometabolic disease and comorbid depression may benefit from closer monitoring of SBP

Relationship of depression screening in cardiometabolic disease with vascular events and mortality: findings from a large primary care cohort with 4 years follow-up

Aims: Benefits of routine depression screening for cardiometabolic disease patients remain unclear. We examined the association between depression screening and all-cause mortality and vascular events in cardiometabolic disease patients. Methods and results: 125 143 patients with cardiometabolic diseases (coronary heart disease, diabetes or previous stroke) in the UK participated in primary care chronic disease management in 2008/09, which included depression screening using the Hospital Anxiety and Depression Score. 10 670 receiving depression treatment exempted, 35 537 screened, while 78 936 not screened. We studied all-cause mortality and vascular events at 4 years, by electronic data linkage of 124 414 patients (99.4%) on primary care registers to hospital discharge and mortality records and used Cox proportional hazards on matched data using propensity score. Mean age for the screened and not screened population was 69 years (standard deviation—SD 11.9) and 67 years (SD 14.3), respectively; 58% (20 658) of the screened population were men and 65.3% (22 726) were socioeconomically deprived, compared with 54.2% (42 727) and 67.4% (51 686), respectively, in the not screened population. The screened population had lower all-cause mortality (Hazard Ratio—HR 0.89) and vascular events (HR 0.85) in the matched data of N = 21 893 patients each in the screened and the unscreened groups. Conclusion: Depression screening was associated with a reduction in all-cause mortality and vascular events in patients with cardiometabolic diseases. The uptake of screening was poor for unknown reasons. Reverse causality and confounding by disease severity and quality of care are important possible limitations. Further research to determine reproducibility and explore underlying mechanisms is merited

Geodesics for Efficient Creation and Propagation of Order along Ising Spin Chains

Experiments in coherent nuclear and electron magnetic resonance, and optical spectroscopy correspond to control of quantum mechanical ensembles, guiding them from initial to final target states by unitary transformations. The control inputs (pulse sequences) that accomplish these unitary transformations should take as little time as possible so as to minimize the effects of relaxation and decoherence and to optimize the sensitivity of the experiments. Here we give efficient syntheses of various unitary transformations on Ising spin chains of arbitrary length. The efficient realization of the unitary transformations presented here is obtained by computing geodesics on a sphere under a special metric. We show that contrary to the conventional belief, it is possible to propagate a spin order along an Ising spin chain with coupling strength J (in units of Hz), significantly faster than 1/(2J) per step. The methods presented here are expected to be useful for immediate and future applications involving control of spin dynamics in coherent spectroscopy and quantum information processing

Predicting cortical bone adaptation to axial loading in the mouse tibia

The development of predictive mathematical models can contribute to a deeper understanding of the specific stages of bone mechanobiology and the process by which bone adapts to mechanical forces. The objective of this work was to predict, with spatial accuracy, cortical bone adaptation to mechanical load, in order to better understand the mechanical cues that might be driving adaptation. The axial tibial loading model was used to trigger cortical bone adaptation in C57BL/6 mice and provide relevant biological and biomechanical information. A method for mapping cortical thickness in the mouse tibia diaphysis was developed, allowing for a thorough spatial description of where bone adaptation occurs. Poroelastic finite-element (FE) models were used to determine the structural response of the tibia upon axial loading and interstitial fluid velocity as the mechanical stimulus. FE models were coupled with mechanobiological governing equations, which accounted for non-static loads and assumed that bone responds instantly to local mechanical cues in an on–off manner. The presented formulation was able to simulate the areas of adaptation and accurately reproduce the distributions of cortical thickening observed in the experimental data with a statistically significant positive correlation (Kendall's τ rank coefficient τ = 0.51, p < 0.001). This work demonstrates that computational models can spatially predict cortical bone mechanoadaptation to a time variant stimulus. Such models could be used in the design of more efficient loading protocols and drug therapies that target the relevant physiological mechanisms

Ultrathin Oxide Films by Atomic Layer Deposition on Graphene

In this paper, a method is presented to create and characterize mechanically robust, free standing, ultrathin, oxide films with controlled, nanometer-scale thickness using Atomic Layer Deposition (ALD) on graphene. Aluminum oxide films were deposited onto suspended graphene membranes using ALD. Subsequent etching of the graphene left pure aluminum oxide films only a few atoms in thickness. A pressurized blister test was used to determine that these ultrathin films have a Young's modulus of 154 \pm 13 GPa. This Young's modulus is comparable to much thicker alumina ALD films. This behavior indicates that these ultrathin two-dimensional films have excellent mechanical integrity. The films are also impermeable to standard gases suggesting they are pinhole-free. These continuous ultrathin films are expected to enable new applications in fields such as thin film coatings, membranes and flexible electronics.Comment: Nano Letters (just accepted