Dynamic Covalent Amphiphilic Polymer Conetworks Based on End-Linked Pluronic F108: Preparation, Characterization, and Evaluation as Matrices for Gel Polymer Electrolytes.

We present the development of a platform of well-defined, dynamic covalent amphiphilic polymer conetworks (APCN) based on an α,ω-dibenzaldehyde end-functionalized linear amphiphilic poly(ethylene glycol)-b-poly(propylene glycol)-b-poly(ethylene glycol) (PEG-b-PPG-b-PEG, Pluronic) copolymer end-linked with a triacylhydrazide oligo(ethylene glycol) triarmed star cross-linker. The developed APCNs were characterized in terms of their rheological (increase in the storage modulus by a factor of 2 with increase in temperature from 10 to 50 °C), self-healing, self-assembling, and mechanical properties and evaluated as a matrix for gel polymer electrolytes (GPEs) in both the stretched and unstretched states. Our results show that water-loaded APCNs almost completely self-mend, self-organize at room temperature into a body-centered cubic structure with long-range order exhibiting an aggregation number of around 80, and display an exceptional room temperature stretchability of ∼2400%. Furthermore, ionic liquid-loaded APCNs could serve as gel polymer electrolytes (GPEs), displaying a substantial ion conductivity in the unstretched state, which was gradually reduced upon elongation up to a strain of 4, above which it gradually increased. Finally, it was found that recycled (dissolved and re-formed) ionic liquid-loaded APCNs could be reused as GPEs preserving 50-70% of their original ion conductivity.

Size-dependent bistability of magnetic states in soft magnetic cap arrays.

We have investigated the size dependent energy barrier regarding the transition between magnetic vortex and collinear states in dense arrays of magnetic cap structures hosting magnetic vortices. The cap structures were formed by the deposition of soft magnetic thin films on top of large arrays of densely packed polystyrene spheres. The energy barrier associated with the magnetic field assisted switching from a collinear magnetic state to a non-uniform vortex state (or vice versa) was tuned by tailoring the diameter and thickness of the soft magnetic caps. At a sufficient temperature, known as the bifurcation temperature, the thermal energy overcomes this energy barrier and magnetic bistability with a hysteresis-free switching occurs between the two magnetic states. In magnetic caps with a fixed thickness, the bifurcation temperature decreases with increasing cap diameter. On the other hand, for a fixed diameter, the bifurcation temperature increases with an increase in film thickness of the cap structure. This study demonstrates that the bifurcation temperature can be easily tailored by changing the magnetostatic energy contribution which in turn affects the energy barrier and thus the magnetic bistability.

Strategy to simulate and fit 2D grazing-incidence small-angle X-ray scattering patterns of nanostructured thin films.

Grazing-incidence small-angle X-ray scattering (GISAXS) is a widely used method for the characterization of the nanostructure of supported thin films and enables time-resolved in situ measurements. The 2D scattering patterns contain detailed information about the nanostructures within the film and at its surface. However, this information is distorted not only by the reflection of the X-ray beam at the substrate-film interface and its refraction at the film surface but also by scattering of the substrate, the sample holder and other types of parasitic background scattering. In this work, a new, efficient strategy to simulate and fit 2D GISAXS patterns that explicitly includes these effects is introduced and demonstrated for (i) a model case nanostructured thin film on a substrate and (ii) experimental data from a microphase-separated block copolymer thin film. To make the protocol efficient, characteristic linecuts through the 2D GISAXS patterns, where the different contributions dominate, are analysed. The contributions of the substrate and the parasitic background scattering - which ideally are measured separately - are determined first and are used in the analysis of the 2D GISAXS patterns of the nanostructured, supported film. The nanostructures at the film surface and within the film are added step by step to the real-space model of the simulation, and their structural parameters are determined by minimizing the difference between simulated and experimental scattering patterns in the selected linecuts. Although in the present work the strategy is adapted for and tested with BornAgain, it can be easily used with other types of simulation software. The strategy is also applicable to grazing-incidence small-angle neutron scattering.

Nanoscale disintegration kinetics of mesoglobules in aqueous poly(N-isopropylacrylamide) solutions revealed by small-angle neutron scattering and pressure jumps.

Identification and control of the disintegration mechanism of polymer nanoparticles are essential for applications in transport and release including polymer delivery systems. Structural changes during the disintegration of poly(N-isopropylacrylamide) (PNIPAM) mesoglobules in aqueous solution are studied in situ and in real time using kinetic small-angle neutron scattering with a time resolution of 50 ms. Simultaneously length scales between 1 and 100 nm are resolved. By initiating phase separation through fast pressure jumps across the coexistence line, 3 wt% PNIPAM solutions are rapidly brought into the one-phase state. Starting at the same temperature (35.1 °C) and pressure (17 MPa) the target pressure is varied over the range 25-48 MPa, allowing to systematically alter the osmotic pressure of the solvent within the mesoglobules. Initially, the mesoglobules have a radius of gyration of about 80 nm and contain a small amount of water. Two disintegration mechanisms are identified: (i) for target pressures close to the coexistence line, single polymers are released from the surface of the mesoglobules, and the mesoglobules decrease in size, which takes ∼30 s. (ii) For target pressures more distant from the coexistence line, the mesoglobules are swollen by water, and subsequently the chains become more and more loosely associated. In this case, disintegration proceeds within less than 10 s, controlled by the osmotic pressure of the solvent.

Solvent Vapor Annealing of a Diblock Copolymer Thin Film with a Nonselective and a Selective Solvent: Importance of Pathway for the Morphological Changes.

Diblock copolymer thin films of polystyrene-block-poly(dimethyl siloxane) (PS-b-PDMS) featuring PDMS cylinders in a PS matrix are investigated during solvent vapor annealing with mixtures of n-heptane (which is strongly selective for PDMS) and toluene (which is close to nonselective for both blocks). Swelling in the vapor of one of the pure solvents and exchanging it stepwise by the vapor of the other solvent is compared to swelling in a given binary solvent vapor mixture for a prolonged time. The resulting structural changes, such as ordering of the cylinders on a hexagonal lattice and their transition into lamellae, are followed using in situ, real-time grazing-incidence small-angle X-ray scattering (GISAXS). In three runs, the sequence of solvent vapor swelling and vapor exchange is varied. Compiling the resulting morphologies in a diagram of states in dependence on the solvent content in the film and in the minority nanodomains allows insight into the role of the glass transition of the PS matrix for the ordering processes and their time scales. Based on these findings, a protocol is suggested to efficiently obtain an order-to-order transition from the cylindrical morphology with random domain orientation to the oriented lamellar state.

Formation and Growth of Mesoglobules in Aqueous Poly(N-isopropylacrylamide) Solutions Revealed with Kinetic Small-Angle Neutron Scattering and Fast Pressure Jumps.

The phase transition from swollen chains to polymer mesoglobules of an aqueous solution of poly(N-isopropylacrylamide) is investigated with kinetic small-angle neutron scattering with 50 ms time resolution in conjunction with millisecond pressure jumps across the coexistence line. The time-resolved study evidenced three distinct regimes: fractal clusters form during the first second and transform into compact mesoglobules. During the following ∼20 s, these grow by diffusion-limited coalescence. The final step consists of a slow growth characterized by an energy barrier of several kBT. The method opens opportunities for kinetic structural studies of multicomponent systems over wide length and time scales and gives a structural picture spanning from the chain collapse to mesoscopic phase separation.

Evaluation of segmentation methods on head and neck CT: Auto-segmentation challenge 2015.

PURPOSE: Automated delineation of structures and organs is a key step in medical imaging. However, due to the large number and diversity of structures and the large variety of segmentation algorithms, a consensus is lacking as to which automated segmentation method works best for certain applications. Segmentation challenges are a good approach for unbiased evaluation and comparison of segmentation algorithms. METHODS: In this work, we describe and present the results of the Head and Neck Auto-Segmentation Challenge 2015, a satellite event at the Medical Image Computing and Computer Assisted Interventions (MICCAI) 2015 conference. Six teams participated in a challenge to segment nine structures in the head and neck region of CT images: brainstem, mandible, chiasm, bilateral optic nerves, bilateral parotid glands, and bilateral submandibular glands. RESULTS: This paper presents the quantitative results of this challenge using multiple established error metrics and a well-defined ranking system. The strengths and weaknesses of the different auto-segmentation approaches are analyzed and discussed. CONCLUSIONS: The Head and Neck Auto-Segmentation Challenge 2015 was a good opportunity to assess the current state-of-the-art in segmentation of organs at risk for radiotherapy treatment. Participating teams had the possibility to compare their approaches to other methods under unbiased and standardized circumstances. The results demonstrate a clear tendency toward more general purpose and fewer structure-specific segmentation algorithms.

Vertical vs Lateral Macrophase Separation in Thin Films of Block Copolymer Mixtures: Computer Simulations and GISAXS Experiments.

Mixtures of two diblock copolymers of very different lengths may feature both macro- and microphase separation; however, not much is known about the mechanisms of separation in diblock copolymer thin films. In the present work, we study thin films of mixtures of two compositionally symmetric block copolymers, both in the one-phase and in the two-phase state, combining coarse-grained molecular simulations (dissipative particle dynamics, DPD) with scattering experiments (grazing-incidence small-angle X-ray scattering, GISAXS). We reveal that the film thickness and selective adsorption of different blocks to the substrate control the distribution of macrophases within the film as well as the orientation of the lamellae therein. In thick films, the mixtures separate in the vertical direction into three layers: Two layers being rich in short copolymers are formed near the film interfaces, whereas a layer being rich in long copolymers is located in the film core. The lamellar orientation in the layers rich in short copolymers is dictated by the surface selectivity, and this orientation only weakly affects the vertical orientation of lamellae in the film core. This provides the opportunity to control the domain orientation in the copolymer films by mixing block copolymers with low-molecular additives instead of relying on a more complicated chemical modification of the substrate. In thinner films, a lateral phase separation appears.

Evaluation of prostate segmentation algorithms for MRI: the PROMISE12 challenge.

Prostate MRI image segmentation has been an area of intense research due to the increased use of MRI as a modality for the clinical workup of prostate cancer. Segmentation is useful for various tasks, e.g. to accurately localize prostate boundaries for radiotherapy or to initialize multi-modal registration algorithms. In the past, it has been difficult for research groups to evaluate prostate segmentation algorithms on multi-center, multi-vendor and multi-protocol data. Especially because we are dealing with MR images, image appearance, resolution and the presence of artifacts are affected by differences in scanners and/or protocols, which in turn can have a large influence on algorithm accuracy. The Prostate MR Image Segmentation (PROMISE12) challenge was setup to allow a fair and meaningful comparison of segmentation methods on the basis of performance and robustness. In this work we will discuss the initial results of the online PROMISE12 challenge, and the results obtained in the live challenge workshop hosted by the MICCAI2012 conference. In the challenge, 100 prostate MR cases from 4 different centers were included, with differences in scanner manufacturer, field strength and protocol. A total of 11 teams from academic research groups and industry participated. Algorithms showed a wide variety in methods and implementation, including active appearance models, atlas registration and level sets. Evaluation was performed using boundary and volume based metrics which were combined into a single score relating the metrics to human expert performance. The winners of the challenge where the algorithms by teams Imorphics and ScrAutoProstate, with scores of 85.72 and 84.29 overall. Both algorithms where significantly better than all other algorithms in the challenge (p<0.05) and had an efficient implementation with a run time of 8min and 3s per case respectively. Overall, active appearance model based approaches seemed to outperform other approaches like multi-atlas registration, both on accuracy and computation time. Although average algorithm performance was good to excellent and the Imorphics algorithm outperformed the second observer on average, we showed that algorithm combination might lead to further improvement, indicating that optimal performance for prostate segmentation is not yet obtained. All results are available online at http://promise12.grand-challenge.org/.

Functional-conservative treatment of extra-articular physeal fractures of the proximal phalanges in children and adolescents.

BACKGROUND: Fractures of the proximal phalanges of the fingers are common injuries in children and adolescents. The majority can be treated by closed reduction and splinting, and complications are rare. The purpose of the prospective study was to document the results of functional-conservative treatment of extra-articular physeal fractures using either a functional forearm cast or the Lucerne Cast (LuCa). METHODS: Clinical and radiographic results of 13 pediatric patients having 13 extra-articular physeal fractures (e.g., juxta-epiphyseal fractures, Salter-Harris type I or II physeal fractures) of the proximal phalanges were recorded through a minimum follow-up of 6 months. Intra-articular physeal fractures (Salter-Harris type III or IV), fractures involving the proximal interphalangeal joint (PIPJ), pathological fractures, open fractures, and concomitant injuries of the tendons were excluded. RESULTS: Fracture consolidation was achieved in all cases within 4 weeks. No palmar apex angulations, no rotational deformities, and no PIPJ extension lags could be observed. All patients achieved full total active range of motion within 3 months. CONCLUSIONS: Well-reduced extra-articular physeal fractures of the proximal phalanges can be effectively treated using functional-conservative casts. Although children may need a functional forearm cast, a LuCa is adequate in compliant adolescents.Level of Evidence The level of evidence for the study is Level II (therapeutic studies).

Immune response deviation and enhanced expression of chemokine receptor CCR4 in TBI patients due to unknown serum factors.

BACKGROUND: Severe brain trauma leads to an activation of the immune system. To this date, neither the exact perturbation of the specific immune reaction induced by the traumatic brain injury (TBI), nor the interactions leading to the infiltration of peripheral immune cells into the brain are fully understood. PATIENTS AND METHODS: Serum was collected from 17 patients with TBI and a long bone fracture, 24 patients with an isolated long bone fracture and from healthy individuals. The effect of the serum on normal human monocytes and T-lymphocytes was tested in vitro by assessing proliferation and expression of surface markers, chemokine receptors and cytokines. RESULTS: Serum collected from patients with a TBI and a long bone fracture increased the expression of the chemokine receptor CCR4 in monocytes when compared to patients with an isolated long bone fracture. Extending this comparison to T-lymphocytes, the serum from TBI patients induced lower proliferation rates and decreased expression of the pro-inflammatory cytokine TNF-alpha, while simultaneously increasing the secretion of immune-modulatory cytokines (IL-4, IL-10 and TGF-beta) (p<0.05). CONCLUSION: Patients with a TBI release currently unknown soluble factors into the circulating blood that up regulate expression of chemokine receptor CCR4 in peripheral blood monocytes whilst concurrently inducing expression of immunosuppressive cytokines by activated T-lymphocytes.

A case-matched controlled study on high-voltage electrical injuries vs thermal burns.

The aim of this study was to provide an increased level of evidence on surgical management of high-tension electrical injuries compared with thermal burns using a case-controlled study design. Sixty-eight patients (64 males, 4 females, aged 33.7 +/- 13 years) with high-tension electrical burns were matched for age, gender, and burnt extent with a cohort of patients sustaining thermal burns. Data were analyzed for cause of accident (occupational vs nonoccupational), concomitant injuries, extent of burn and burn depth, surgical management, complications, and hospital stay. High-tension electrical burn patients required an average of 5.2 +/- 4 operations (range, 1-23 operations) compared with 3.3 +/- 1.9 (range, 1-10 operations) after thermal burns (P = .0019). Amputation rates (19.7% vs 1.5%), escharotomy/fasciotomy rates (47% vs 21%), and total hospitalization days (44 d vs 32 d) were significantly higher in high-tension electrical injuries (P < .05). Creatinine kinase levels were significantly elevated during the first 2 days in patients with subsequent amputations. Free flap failure was observed during the first 4 weeks after the trauma, whereas no flap failure occurred at later stages. Local, pedicled, and distant flaps were used in 15% of the patients. The mortality in both groups was 13.2% vs 11%, respectively (nonsignificant). High-voltage electrical injury remains a complex surgical challenge. When performing free flap coverage, caution must be taken for a vulnerable phase lasting up to 4 weeks after the trauma. This phase is likely the result of a progressive intima lesion, potentially hazardous to microvascular reconstruction. The use of pedicle flaps may resemble an alternative to free flaps during this period.

Morbidity and recurrence after completion lymph node dissection following sentinel lymph node biopsy in cutaneous malignant melanoma.

OBJECTIVE: To assess the nature and rates of complications and recurrences after completion lymph node dissection (CLND) following positive sentinel lymph node biopsy (SLNB) in melanoma patients. SUMMARY BACKGROUND DATA: In contrast to SLNB, CLND is associated with considerable morbidity. CLND delays nodal recurrence, thereby prolonging disease-free survival (DFS), but not overall melanoma-specific survival. Elaborate studies on morbidity and recurrence rates after CLND are scarce. Therefore, many controversies concerning extent and nature of CLND exist. METHODS: We conducted a retrospective study on 100 melanoma patients, on whom we performed CLND between October 1999 and December 2005. The median observation period was 38.8 months. RESULTS: We performed a total of 102 CLNDs, [46.1% axillary (47/102), 42.2% groin (43/102), 11.8% neck (12/102)]. Groin dissection (GD) and axillary dissection (AD) led to comparable morbidity (47.6% and 46.8%), but complications were more severe in GD, mandating additional surgery in 25.6% (11/43), versus 8.5% (4/47) in AD. Of the GD patients, 18.5% (8/43) were readmitted for complications compared with 10.4% (5/47) of AD patients. Only 8.3% (1/12) of ND patients suffered complications, mandating neither readmittance nor further surgery. During the median observation period, 65 (65%) of these patients showed DFS, and 35 (35%) exhibited recurrences after a median DFS of 12.5 months. Of the recurrences, 31.4% were nodal, 42.9% distant, and 25.7% local/in-transit. Of our AD patients, 28.3% suffered recurrences (13/46), as did 33.3% of the GD (14/42) and 66.7% of the ND patients (8/12). CONCLUSIONS: CLND is fraught with considerable morbidity. Local control of the dissected nodal basins was achieved with a modified radical approach in ADs (levels I + II only) and, to a lesser extent, GDs, but not in NDs. Clinical trials are necessary to establish guidelines on the extent of lymphatic dissection.

Acute allograft rejection and immunosuppression: influence on endogenous melatonin secretion.

Melatonin displays a dose-dependent immunoregulatory effect in vitro and in vivo. Exogenous high-dose melatonin therapy exerted an immunosuppressive effect, abrogating acute rejection (AR), significantly prolonging transplant survival. Endogenous melatonin secretion, in response to heterotopic rat cardiac allograft transplantation (Tx), was investigated during the AR response and under standardized immunosuppressive maintenance therapy with cyclosporin A (CsA) and rapamycin (RPM). Recipients of syngeneic transplants, and recipients of allogeneic grafts, either untreated or receiving immunosuppressive therapy constituted the experimental groups. Endogenous circadian melatonin levels were measured at 07:00, 19:00, and 24:00 hr, using a novel radioimmunoassay (RIA) procedure, under standardized 12-hr-light/dark-conditions (light off: 19:00 hr; light on: 07:00 hr), before and after Tx. Neither the operative trauma, nor the challenge with a perfused allograft or the AR response influenced endogenous melatonin peak secretion. Immunosuppressive therapy with CsA led to a significant increase in peak secretion, measured for days 7 (212 +/- 40.7 pg/mL; P < 0.05), 14 (255 +/- 13.9 pg/mL; P < 0.001), and 21 (219 +/- 34 pg/mL; P < 0.01) after Tx, as compared with naïve animals (155 +/- 25.8 pg/mL). In contrast, treatment with RPM significantly decreased the melatonin peak post-Tx up to day 7 (87 +/- 25.2 pg/mL; P < 0.001), compared with naïve animals (155 +/- 25.8 pg/mL). These findings imply a robust nature of the endogenous circadian melatonin secretion kinetics, even against the background of profound allogeneic stimuli. Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin secretion, indicating a specific secondary action of these drugs. Further studies are necessary to disclose the long-term effect of immunosuppressive therapy on circadian melatonin secretion in transplant recipients.

CD26/dipeptidylpeptidase IV-targeted therapy of acute lung rejection in rats.

BACKGROUND: CD26 is a T-cell co-stimulator, and interacts with adenosine deaminase, human immunodeficiency virus (HIV) Tat-1 protein and extracellular matrix. It possesses dipeptidylpeptidase IV (DPP IV) catalytic activity, which is linked to its co-stimulatory efficacy. We investigated the effect of specific DPP IV systemic activity inhibition on acute pulmonary rejection. METHODS: Rat single-lung transplantation (Tx) was performed (LBNF1/LEW donor/recipient) in two groups (n = 12). Group I (n = 6) received daily treatment with a Pro-Pro-diphenylphosphonate derivative (AB197), and Group II served as an untreated control. At Day 5 post-Tx, ventilatory parameters, cytotoxicity and mixed lymphocyte reaction were analyzed and staining for ISHLT rejection grade and proliferating cell nuclear antigen (PCNA) was performed. RESULTS: Treatment with AB192 abrogated acute rejection and preserved pulmonary function up to Day 5 post-Tx for PO2 (Group II: 24.9 +/- 6.9 mm Hg; Group I: 149.5 +/- 24.3 mm Hg; p < 0.001), PCO2 (Group II: 53.3 +/- 13.6 mm Hg; Group I: 39.0 +/- 9.8 mm Hg; p < 0.05) and peak airway pressure (Group II: 50.7 +/- 17.2 mm Hg; Group I: 20.2 +/- 10.0 mm Hg; p < 0.01). Controls showed moderate/severe rejection (ISHLT Grade A2 or 3), grafts from inhibited hosts revealed no/mild rejection (Grade A0 to 2: Group II: 2.8 +/- 0.3; Group I: 1.25 +/- 1.0; p < 0.005). Proliferating cell nuclear antigen (PCNA) staining of rejection-associated cellular infiltrates showed a significant reduction in positivity in perivascular infiltrates (34 +/- 11.5%; p < 0.05) and bronchial surface epithelium (31.7 +/- 10.6%; p < 0.05) in Group I vs Group II (55.9 +/- 8.4% and 57.2 +/- 4.5%). CONCLUSIONS: Irreversible enzymatic inhibition of DPP IV has been shown to abrogate acute pulmonary rejection, maintain pulmonary function, and preserve histomorphologic architecture. These results extend earlier findings and illustrate the role of CD26/DPP IV in alloantigen-mediated immune responses.