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The goal of this study was to perform in situ electrochemical polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) in peripheral nerves to create a soft, precisely located injectable conductive polymer electrode for bi-directional communication. Intraneural PEDOT polymerization was performed to target both outer and inner fascicles via custom fabricated 3D printed cuff electrodes and monomer injection strategies using a combination electrode-cannula system. Electrochemistry, histology, and laser light sheet microscopy revealed the presence of PEDOT at specified locations inside of peripheral nerve. This work demonstrates the potential for using in situ PEDOT electrodeposition as an injectable electrode for recording and stimulation of peripheral nerves.
Recent proposals suggest early adversity sets in motion particularly chronic and neurobiologically distinct trajectories of internalizing symptoms. However, few prospective studies in high-risk samples delineate distinct trajectories of internalizing symptoms from preschool age onward. We examined trajectories in a high-risk cohort, oversampled for internalizing symptoms, several preschool risk/maintenance factors, and school-age outcomes. Parents of 325 children completed the Strengths and Difficulties Questionnaire on up to four waves of data collection from preschool (3–5 years) to school age (8–9 years) and Preschool Age Psychiatric Assessment interviews at both ages. Multi-informant data were collected on risk factors and symptoms. Growth mixture modelling identified four trajectory classes of internalizing symptoms with stable low, rising low-to-moderate, stable moderate, and stable high symptoms. Children in the stable high symptom trajectory manifested clinically relevant internalizing symptoms, mainly diagnosed with anxiety disorders/depression at preschool and school age. Trajectories differed regarding loss/separation experience, maltreatment, maternal psychopathology, temperament, and stress-hormone regulation with loss/separation, temperament, maternal psychopathology, and stress-hormone regulation (trend) significantly contributing to explained variance. At school age, trajectories continued to differ on symptoms, disorders, and impairment. Our study is among the first to show that severe early adversity may trigger a chronic and neurobiologically distinct internalizing trajectory from preschool age onward.
The ability to interface electronic materials with the peripheral nervous system is required for stimulation and monitoring of neural signals. Thus, the design and engineering of robust neural interfaces that maintain material-tissue contact in the presence of material or tissue micromotion offer the potential to conduct novel measurements and develop future therapies that require chronic interface with the peripheral nervous system. However, such remains an open challenge given the constraints of existing materials sets and manufacturing approaches for design and fabrication of neural interfaces. Here, we investigated the potential to leverage a rapid prototyping approach for the design and fabrication of nerve cuffs that contain supporting features to mechanically stabilize the interaction between cuff electrodes and peripheral nerve. A hybrid 3D printing and robotic-embedding (i.e., pick-and-place) system was used to design and fabricate silicone nerve cuffs (800 µm diameter) containing conforming platinum (Pt) electrodes. We demonstrate that the electrical impedance of the cuff electrodes can be reduced by deposition of the conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) on cuff electrodes via a post-processing electropolymerization technique. The computer-aided design and manufacturing approach was also used to design and integrate supporting features to the cuff that mechanically stabilize the interface between the cuff electrodes and the peripheral nerve. Both ‘self-locking’ and suture-assisted locking mechanisms are demonstrated based on the principle of making geometric alterations to the cuff opening via 3D printing. Ultimately, this work shows 3D printing offers considerable opportunity to integrate supporting features, and potentially even novel electronic materials, into nerve cuffs that can support the design and engineering of next generation neural interfaces.
An internationally approved and globally used classification scheme for the diagnosis of CHD has long been sought. The International Paediatric and Congenital Cardiac Code (IPCCC), which was produced and has been maintained by the International Society for Nomenclature of Paediatric and Congenital Heart Disease (the International Nomenclature Society), is used widely, but has spawned many “short list” versions that differ in content depending on the user. Thus, efforts to have a uniform identification of patients with CHD using a single up-to-date and coordinated nomenclature system continue to be thwarted, even if a common nomenclature has been used as a basis for composing various “short lists”. In an attempt to solve this problem, the International Nomenclature Society has linked its efforts with those of the World Health Organization to obtain a globally accepted nomenclature tree for CHD within the 11th iteration of the International Classification of Diseases (ICD-11). The International Nomenclature Society has submitted a hierarchical nomenclature tree for CHD to the World Health Organization that is expected to serve increasingly as the “short list” for all communities interested in coding for congenital cardiology. This article reviews the history of the International Classification of Diseases and of the IPCCC, and outlines the process used in developing the ICD-11 congenital cardiac disease diagnostic list and the definitions for each term on the list. An overview of the content of the congenital heart anomaly section of the Foundation Component of ICD-11, published herein in its entirety, is also included. Future plans for the International Nomenclature Society include linking again with the World Health Organization to tackle procedural nomenclature as it relates to cardiac malformations. By doing so, the Society will continue its role in standardising nomenclature for CHD across the globe, thereby promoting research and better outcomes for fetuses, children, and adults with congenital heart anomalies.
Children with hypoplastic left heart syndrome are at a risk for neurodevelopmental delays. Current guidelines recommend systematic evaluation and management of neurodevelopmental outcomes with referral for early intervention services. The Single Ventricle Reconstruction Trial represents the largest cohort of children with hypoplastic left heart syndrome ever assembled. Data on life events and resource utilisation have been collected annually. We sought to determine the type and prevalence of early intervention services used from age 1 to 4 years and factors associated with utilisation of services.
Data from 14-month neurodevelopmental assessment and annual medical history forms were used. We assessed the impact of social risk and geographic differences. Fisher exact tests and logistic regression were used to evaluate associations.
Annual medical history forms were available for 302 of 314 children. Greater than half of the children (52–69%) were not receiving services at any age assessed, whereas 20–32% were receiving two or more therapies each year. Utilisation was significantly lower in year 4 (31%) compared with years 1–3 (with a range from 40 to 48%) (p<0.001). Social risk factors were not associated with the use of services at any age but there were significant geographic differences. Significant delay was reported by parents in 18–43% of children at ages 3 and 4.
Despite significant neurodevelopmental delays, early intervention service utilisation was low in this cohort. As survival has improved for children with hypoplastic left heart syndrome, attention must shift to strategies to optimise developmental outcomes, including enrolment in early intervention when merited.
Reconstruction with a vascularised flap provides the most reliable outcome, with post-operative cerebrospinal fluid leak rates of less than 5 per cent. This article aims to review and summarise the critical technical aspects of the vascularised flaps most commonly used for skull base reconstruction.
Vascularised flaps are classified as intranasal or extranasal. The intranasal group includes the Hadad–Bassagaisteguy nasoseptal flap, the Caicedo reverse nasoseptal flap, the nasoseptal rescue flap, the posteriorly or anteriorly based lateral wall flaps, and the middle turbinate flap. Extranasal flaps include the transfrontal pericranial and transpterygoid temporoparietal flaps.
The Hadad–Bassagaisteguy nasoseptal flap is overwhelmingly favoured for reconstructing extensive defects of anterior, middle and posterior cranial base. Its pertinent technical features are described. However, it is essential to master the skills required for the various extranasal or regional vascularised flaps because each can offer a reconstructive alternative for specific patients, especially when open approaches are needed and/or intranasal vascularised flaps are not feasible.
We study the stability of small amplitude harmonic perturbation at the interface of a gel material surrounded by air. The equations describing the system's dynamics are solved using classical perturbation methods. Assuming that the amplitude decays over time, we establish conditions for the system to return to its equilibrium state. The proposed model includes the effect of the boundary conditions and can be extended to more general situation in which the material is surrounded by an arbitrary fluid.
Cellular networks are ubiquitous in nature. Most engineered materials are polycrystalline microstructures composed of a myriad of small grains separated by grain boundaries, thus comprising cellular networks. The recently discovered grain boundary character distribution (GBCD) is an empirical distribution of the relative length (in 2D) or area (in 3D) of interface with a given lattice misorientation and normal. During the coarsening, or growth, process, an initially random grain boundary arrangement reaches a steady state that is strongly correlated to the interfacial energy density. In simulation, if the given energy density depends only on lattice misorientation, then the steady state GBCD and the energy are related by a Boltzmann distribution. This is among the simplest non-random distributions, corresponding to independent trials with respect to the energy. Why does such simplicity emerge from such complexity? Here we describe an entropy based theory which suggests that the evolution of the GBCD satisfies a Fokker-Planck Equation, an equation whose stationary state is a Boltzmann distribution.
This article discusses novel algorithms for molecular-dynamics (MD) simulations with short-ranged forces on modern multi- and many-core processors like the Intel Xeon Phi. A task-based approach to the parallelization of MD on shared-memory computers and a tiling scheme to facilitate the SIMD vectorization of the force calculations is described. The algorithms have been tested with three different potentials and the resulting speed-ups on Intel Xeon Phi coprocessors are shown.
We present a theoretical approach for modeling electrolyte solutions at interfaces that reaches into the mesoscale while retaining molecular detail. The total Hamiltonian of the system includes interactions arising from density and charge density (ion correlation) fluctuations, direct Coulomb interactions between ions, and at interfaces the image interactions, ion-solid and ion-water dispersion interactions. The model was validated against its ability to reproduce ion activity in 1:1 and 2:1 electrolyte solutions in the 0-2 M concentration range, its ability to capture the ion-specific effect in 1:1 electrolytes at the air-water interface, and solvent structure in a confined environment between hydrophobic surfaces, revealing the central role of ion hydration interactions in specific ion thermodynamic properties in the bulk solutions and at interfaces. The model is readily extensible to treat electrolyte interactions and forces across charged solid-water interfaces.
A sensor which detects mechanical stresses and stores the position and the strength of these loads by color change of embedded quantum dots (QDs) is presented. The top and bottom electrodes of the sensor are inkjet-printed which leads to a fast and accurate deposition of thin (approx. 50 - 300 nm) and conductive layers. The used silver and poly(3,4-ethylenedioxythio-phene) polystyrene sulfonate (PEDOT:PSS) inks are optimized in terms of printability and opportunities of functionality forming without influencing the active layer of the sensor. The active layer of the sensor is spin-coated and consists of the QDs embedded in semi-conducting poly(9-vinylcarba-zole) (PVK). The hole transport characteristic of PVK and the band level alignment of the used materials ensures the preferred injection of only one type of charge carrier into the QDs. As a result the mechanical stress is visualized by a decreasing in photoluminescence (PL) of the QDs.
The class of almost completely decomposable groups with a critical typeset of type
and a homocyclic regulator quotient of exponent
is shown to be of bounded representation type. There are only
types of indecomposables, all of rank
New welfare has been prominent in recent European social policy debates. It involves mobilising more people into paid work, improving human capital and ensuring fairer access to opportunities. This programme is attractive to business (more workers, better human capital and reduced social conflict to enhance productivity and profitability) and to citizens (more widely accessible job-opportunities with better rewards): a relatively low-cost approach to the difficulties governments face in maintaining support and meeting social goals as inequalities widen.
The general move towards ‘new welfare’ gathered momentum during the past two decades, given extra impetus by the 2007–09 recession and subsequent stagnation. While employment rates rose during the prosperous years before the crisis, there was no commensurate reduction in poverty. Over the same period the share of economic growth returned to labour fell, labour markets were increasingly de-regulated and inequality increased. This raises the question of whether new welfare's economic goals (higher employment, improved human capital) and social goals (better job quality and incomes) may come into conflict.
This paper examines data for seventeen European countries over the period 2001 to 2007. It shows that new welfare is much more successful at achieving higher employment than at reducing poverty, even during prosperity, and that the approach pays insufficient attention to structural factors, such as the falling wage share, and to institutional issues, such as labour market deregulation.
The course of bipolar disorder progressively worsens in some patients. Although responses to pharmacotherapy appear to diminish with greater chronicity, less is known about whether patients' prior courses of illness are related to responses to psychotherapy.
Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy with collaborative care (a three-session psycho-educational intervention). We assessed whether the number of previous mood episodes, age of illness onset, and illness duration predicted or moderated the likelihood of recovery and time until recovery from a depressive episode in patients in the two treatments.
Independently of treatment condition, participants with one to nine prior depressive episodes were more likely to recover and had faster time to recovery than those with 20 or more prior depressive episodes. Participants with fewer than 20 prior manic episodes had faster time to recovery than those with 20 or more episodes. Longer illness duration predicted a longer time to recovery. Participants were more likely to recover in intensive psychotherapy than collaborative care if they had 10–20 prior episodes of depression [number needed to treat (NNT) = 2.0], but equally likely to respond to psychotherapy and collaborative care if they had one to nine (NNT = 32.0) or >20 (NNT = 9.0) depressive episodes.
Number of previous mood episodes and illness duration are associated with the likelihood and speed of recovery among bipolar patients receiving psychosocial treatments for depression.
The silicon carbide (SiC) market is gaining momentum hence productivity in device manufacturing has to be improved. The current transition from 100 mm SiC-wafers to 150 mm SiC-wafers requires novel processes in the front-end as well as the back-end of SiC-chip production. Dicing of fully processed SiC-wafers is becoming a bottleneck process since current state-of-the-art mechanical blade dicing faces heavy tool wear and achieves low throughput due to low feed rates in the range of only a few mm/s. This paper presents latest results of the novel dicing technology Thermal Laser Separation (TLS) applied for separating SiC-JFETs. We demonstrate for the first time that TLS is capable of dicing fully processed 4H-SiC wafers, including back side metal layer stacks, process control monitoring (PCM), and metal structures inside the dicing streets with feed rates up to 200 mm/s. TLS thus paves the way to efficient dicing of 150 mm SiC-wafers.
Feed intake behavior was studied between 9 weeks of age and slaughter in a total of 36 gilts, 32 immunocastrates, 33 surgically castrated barrows and 33 boars from 36 litters. Consequences for the concentration of substances contributing to off odor of pork (skatole, indole) were evaluated. Animals were kept in groups of 12 pigs of the same sex and treatment and fed ad libitum (13.4 MJ ME, 17% CP, 1.1% lysine). Individual feed intake behavior was recorded continuously by an electronic feeder. Immunocastration was carried out with two injections of Improvac with at least 4 weeks between both injections (1st: 12 to 17 weeks of age, 2nd: 19 to 21 weeks of age). Feed intake/day increased from an average of 0.91 ± 0.02 kg/day up to 3.15 ± 0.04 kg/day before slaughter. This increase was associated with a 50% reduction in the number of meals/day (from 15.8 ± 0.44 to 7.2 ± 0.29 meals/day). The larger meal sizes resulted from an increase in both, the duration of feed intake/meal and the feed intake rate (g/min). In addition, sex and treatment differences were observed: Feed intake in boars was lower than in all other groups due to a reduction in the number of meals/day and in the time spent feeding/day. In females, time spent feeding/day was quite similar to boars, but resulted from a higher number of meals of shorter duration. Barrows had a significantly higher feed intake because of a higher number of meals/day resulting in more time spent feeding/day. The feed intake rate was similar in boars, gilts and barrows and showed an increasing trend during the study, starting from about 15 g/min up to four times the amount. Immunocastration affected feed intake behavior severely, especially the meal size increased dramatically because of higher feed intake rate, which exceeded that of all other groups by 25% at the end of the study. The number of meals/day was not influenced by immunocastration and was almost identical to that of boars. Highest skatole concentrations were measured in fat of boars, whereas indole concentrations were higher in immunocastrates than in all other groups. In gilts and barrows, skatole concentrations were related to growth rate. Additionally, the feeding rate was an important factor explaining the variability in skatole/indole concentrations in adipose tissue. The physiological mechanisms however need further clarification.