Probing Magnetic Exchange Interactions with Helium.

Controlling and sensing spin polarization of electrons forms the basis of spintronics. Here, we report a study of the effect of helium on the spin polarization of the tunneling current and magnetic contrast in spin-polarized scanning tunneling microscopy (SP STM). We show that the magnetic contrast in SP STM images recorded in the presence of helium depends sensitively on the tunneling conditions. From tunneling spectra and their variation across the atomic lattice we establish that the helium can be reversibly ejected from the tunneling junction by the tunneling electrons. The energy of the tunneling electrons required to eject the helium depends on the relative spin polarization of the tip and sample, making the microscope sensitive to the magnetic exchange interactions. We show that the time-averaged spin polarization of the tunneling current is suppressed in the presence of helium and thereby demonstrate voltage control of the spin polarization of the tunneling current across the tip-sample junction.

Tomographic mapping of the hidden dimension in quasi-particle interference.

Quasiparticle interference (QPI) imaging is well established to study the low-energy electronic structure in strongly correlated electron materials with unrivalled energy resolution. Yet, being a surface-sensitive technique, the interpretation of QPI only works well for anisotropic materials, where the dispersion in the direction perpendicular to the surface can be neglected and the quasiparticle interference is dominated by a quasi-2D electronic structure. Here, we explore QPI imaging of galena, a material with an electronic structure that does not exhibit pronounced anisotropy. We find that the quasiparticle interference signal is dominated by scattering vectors which are parallel to the surface plane however originate from bias-dependent cuts of the 3D electronic structure. We develop a formalism for the theoretical description of the QPI signal and demonstrate how this quasiparticle tomography can be used to obtain information about the 3D electronic structure and orbital character of the bands.

[Cold atmospheric pressure plasma for the treatment of acute and chronic wounds]. / Kaltes Atmosphärendruckplasma zur Behandlung akuter und chronischer Wunden.

BACKGROUND: Besides acute wounds (through trauma or surgical interventions), chronic wounds comprise a relatively large and heterogeneous group of diseases. These include leg ulcers with venous disease greatly prevailing arterial disease, diabetic foot syndrome, and pressure ulcers. Due to a considerable treatment resistance against such therapies, new and effective, additive treatment options especially for chronic wounds are needed. Wound treatment with cold atmospheric plasma (CAP) constitutes such an innovative option. OBJECTIVES: Current research regarding the efficacy of cold plasma for healing of acute and chronic wounds is summarized. MATERIALS AND METHODS: The literature on CAP applications in wound healing has been screened and reviewed. RESULTS: With CAP, several effects that promote wound healing can be simultaneously applied in one application. On the one hand, CAP exerts a strong and broad antimicrobial activity against biofilm. On the other hand, the plasma cocktail, which consists of reactive nitrogen and oxygen species, UV, and charged particles (electrical current), mediates tissue-stimulating, blood flow-promoting, and anti-inflammatory effects. Marked germ reduction on wounds and accelerated wound healing have already been convincingly demonstrated in controlled clinical studies. CONCLUSIONS: The comprehensive CAP study landscape with structured case report summaries and randomized case-control studies allows the conclusion that CAP is safe, effective, and easy to handle for wound treatment. The utilization of CAP in addition to standard wound treatments is starting to enter routine clinical practice.

How to measure coating thickness of tablets: Method comparison of optical coherence tomography, near-infrared spectroscopy and weight-, height- and diameter gain.

Film coating of pharmaceutical dosage forms, such as tablets and pellets, can be used to tailor the drug release profile. With that regard, a uniform coating thickness of a single tablet (intra-tablet), all tablets (inter-tablet) and subsequent batches (inter-batch) is crucial. We present a method comparison between in-line (optical coherence tomography and near-infrared spectroscopy) and well-established off-line (height-, weight- and diameter-gain) approaches to determining the coating thickness of tablets. We used single tablets drawn during a commercial coating process. Comparing the low intra- and high inter-tablet coating variability indicated that the tablets had a broad distribution of spray zone passes but at a random tablet orientation. Even at the end of the coating process at a mean coating thickness of about 70 µm, the inter-tablet standard deviation was about 9 µm or 13% relative standard deviation. Determining correlations between the methods identified the factors that contribute to the measurement uncertainty and bias for each method. Ultimately, we aimed to establish that in-line methods match or even surpass the conventional off-line reference methods in terms of accuracy and precision of coating thickness measurement.

RTD-based material tracking in a fully-continuous dry granulation tableting line.

Continuous manufacturing (CM) offers quality and cost-effectiveness benefits over currently dominating batch processing. One challenge that needs to be addressed when implementing CM is traceability of materials through the process, which is needed for the batch/lot definition and control strategy. In this work the residence time distributions (RTD) of single unit operations (blender, roller compactor and tablet press) of a continuous dry granulation tableting line were captured with NIR based methods at selected mass flow rates to create training data. RTD models for continuous operated unit operations and the entire line were developed based on transfer functions. For semi-continuously operated bucket conveyor and pneumatic transport an assumption based the operation frequency was used. For validation of the parametrized process model, a pre-defined API step change and its propagation through the manufacturing line was computed and compared to multi-scale experimental runs conducted with the fully assembled continuous operated manufacturing line. This novel approach showed a very good prediction power at the selected mass flow rates for a complete continuous dry granulation line. Furthermore, it shows and proves the capabilities of process simulation as a tool to support development and control of pharmaceutical manufacturing processes.

Fermiology and Superconductivity of Topological Surface States in PdTe_{2}.

We study the low-energy surface electronic structure of the transition-metal dichalcogenide superconductor PdTe_{2} by spin- and angle-resolved photoemission, scanning tunneling microscopy, and density-functional theory-based supercell calculations. Comparing PdTe_{2} with its sister compound PtSe_{2}, we demonstrate how enhanced interlayer hopping in the Te-based material drives a band inversion within the antibonding p-orbital manifold well above the Fermi level. We show how this mediates spin-polarized topological surface states which form rich multivalley Fermi surfaces with complex spin textures. Scanning tunneling spectroscopy reveals type-II superconductivity at the surface, and moreover shows no evidence for an unconventional component of its superconducting order parameter, despite the presence of topological surface states.

The levels of vancomycin in the blood and the wound after the local treatment of bone and soft-tissue infection with antibiotic-loaded calcium sulphate as carrier material.

AIMS: Calcium sulphate (CaSO4) is a resorbable material that can be used simultaneously as filler of a dead space and as a carrier for the local application of antibiotics. Our aim was to describe the systemic exposure and the wound fluid concentrations of vancomycin in patients treated with vancomycin-loaded CaSO4 as an adjunct to the routine therapy of bone and joint infections. PATIENTS AND METHODS: A total of 680 post-operative blood and 233 wound fluid samples were available for analysis from 94 implantations performed in 87 patients for various infective indications. Up to 6 g of vancomycin were used. Non-compartmental pharmacokinetic analysis was performed on the data from 37 patients treated for an infection of the hip. RESULTS: The overall systemic exposure remained within a safe range, even in patients with post-operative renal failure, none requiring removal of the pellets. Local concentrations were approximately ten times higher than with polymethylmethacrylate (PMMA) as a carrier, but remained below reported cell toxicity thresholds. Decreasing concentrations in wound fluid were observed over several weeks, but remained above the common minimum inhibitory concentrations for Staphylococcus up to three months post-operatively. CONCLUSION: This study provides the first pharmacokinetic description of the local application of vancomycin with CaSO4 as a carrier, documenting slow release, systemic safety and a release profile far more interesting than from PMMA. In particular, considering in vitro data, concentrations of vancomycin active against staphylococcal biofilm were seen for several weeks. Cite this article: Bone Joint J 2017;99-B:1537-44.

Cryogenic STM in 3D vector magnetic fields realized through a rotatable insert.

Spin-polarized scanning tunneling microscopy (SP-STM) performed in vector magnetic fields promises atomic scale imaging of magnetic structure, providing complete information on the local spin texture of a sample in three dimensions. Here, we have designed and constructed a turntable system for a low temperature STM which in combination with a 2D vector magnet provides magnetic fields of up to 5 T in any direction relative to the tip-sample geometry. This enables STM imaging and spectroscopy to be performed at the same atomic-scale location and field-of-view on the sample, and most importantly, without experiencing any change on the tip apex before and after field switching. Combined with a ferromagnetic tip, this enables us to study the magnetization of complex magnetic orders in all three spatial directions.

Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement.

OBJECTIVES: Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature. METHODS: In this study, a total of 38 frequently used antibiotic agents were maintained at 37°C in saline solution, and degradation and antibacterial activity assessed over six weeks. The impact of an initial supplementary heat exposure mimicking exothermically curing bone cement was also tested as this material is commonly used as a local delivery vehicle. Antibiotic degradation was assessed by liquid chromatography coupled to mass spectrometry, or by immunoassays, as appropriate. Antibacterial activity over time was determined by the Kirby-Bauer disk diffusion assay. RESULTS: The heat exposure mimicking curing bone cement had minimal effect on stability for most antibiotics, except for gentamicin which experienced approximately 25% degradation as measured by immunoassay. Beta-lactam antibiotics were found to degrade quite rapidly at 37°C regardless of whether there was an initial heat exposure. Excellent long-term stability was observed for aminoglycosides, glycopeptides, tetracyclines and quinolones under both conditions. CONCLUSIONS: This study provides a valuable dataset for orthopaedic surgeons considering local application of antibiotics, and for material scientists looking to develop next-generation controlled or extended-release antibiotic carriers.Cite this article: E. Samara, T. F. Moriarty, L. A. Decosterd, R. G. Richards, E. Gautier, P. Wahl. Antibiotic stability over six weeks in aqueous solution at body temperature with and without heat treatment that mimics the curing of bone cement. Bone Joint J 2017;6:296-306. DOI: 10.1302/2046-3758.65.BJR-2017-0276.R1.

Continuous monitoring of API content, API distribution and crushing strength after tableting via near-infrared chemical imaging.

Near-infrared chemical imaging (NIR-CI) with high-speed cameras based on the push-broom acquisition principle is a rapidly-evolving and can be used for a variety of purposes, from classification (and sorting) of products to mapping spatial distribution of materials. The present study examined if NIR-CI is suitable for tablet manufacturing. To that end, the tablets were introduced into the CI system via a flat belt conveyor. A formulation, which consisted of 4wt.%-6wt.% caffeine, 5wt.% crospovidone as a disintegrant, 88wt.%-90wt.% lactose as a filler and 1wt.% magnesium stearate as a lubricator, was tableted at compression forces ranging from 5kN to 30kN. The intra- and inter-tablet homogeneity of caffeine and the tablet's hardness were analyzed via NIR-CI. For the homogeneity evaluation, two methods were applied: standard deviation (SD) and distributional homogeneity index (DHI). The results showed that the SD of caffeine in a single tablet increased with an increase in the caffeine content. This was attributed to natural variations in a binary mixture of caffeine and excipients. Overall, the chosen NIR-CI setup has strong potential to be transferred to the production scale to monitor all tablets in a production stream.

Development of a design space and predictive statistical model for capsule filling of low-fill-weight inhalation products.

The objectives of this study were to develop a predictive statistical model for low-fill-weight capsule filling of inhalation products with dosator nozzles via the quality by design (QbD) approach and based on that to create refined models that include quadratic terms for significant parameters. Various controllable process parameters and uncontrolled material attributes of 12 powders were initially screened using a linear model with partial least square (PLS) regression to determine their effect on the critical quality attributes (CQA; fill weight and weight variability). After identifying critical material attributes (CMAs) and critical process parameters (CPPs) that influenced the CQA, model refinement was performed to study if interactions or quadratic terms influence the model. Based on the assessment of the effects of the CPPs and CMAs on fill weight and weight variability for low-fill-weight inhalation products, we developed an excellent linear predictive model for fill weight (R(2 )= 0.96, Q(2 )= 0.96 for powders with good flow properties and R(2 )= 0.94, Q(2 )= 0.93 for cohesive powders) and a model that provides a good approximation of the fill weight variability for each powder group. We validated the model, established a design space for the performance of different types of inhalation grade lactose on low-fill weight capsule filling and successfully used the CMAs and CPPs to predict fill weight of powders that were not included in the development set.

Acute metabolic, hormonal, and psychological responses to strength training with superimposed EMS at the beginning and the end of a 6 week training period.

OBJECTIVES: The aim was to determine metabolic and hormonal responses to strength training with or without superimposed electromyostimulation (EMS) at the beginning and the end of a 6 week training period. METHODS: 20 strength trained subjects were randomly assigned to two groups. The first group (S) performed 4 sets of back squats with a constantly adjusted additional load of their individual 10 repetition maximum (10 RM) twice a week over 6 weeks. The second group (S+E) did the same training program with superimposed EMS on leg and trunk muscles. Physiological responses were determined before and after the first (TS 1) and the last training session (TS 12). RESULTS: No significant differences of hormonal responses could be observed between groups and TSs. However, small to large effects on metabolism occurred between groups and TSs. Delayed onset muscle soreness (DOMS) was significantly higher 48h after TS 1 for S+E. CONCLUSIONS: Despite a higher DOMS after S+E, there is no acute effect of superimposed EMS on hormonal response to exhaustive resistance exercise. We suggest that, because of the high resistance during 10 RM bouts, most of the muscle fibers are already activated and superimposed EMS only activates few additional muscle fibers.

Acute effects of superimposed electromyostimulation during cycling on myokines and markers of muscle damage.

OBJECTIVES: The purpose of the present study was to evaluate the effects of superimposed electromyostimulation (E) during cycling on myokines and markers of muscle damage, as E might be a useful tool to induce a high local stimulus to skeletal muscle during endurance training without performing high external workloads. METHODS: 13 subjects participated in three experimental trials each lasting 60 min in a randomized order. 1) Cycling (C), 2) Cycling with superimposed E (C+E) and 3) E. Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), creatine kinase (CK) and myoglobin were determined before (pre) and 0', 30', 60', 240' and 24h after each intervention. RESULTS: Only C+E caused significant increases in levels of CK and myoglobin. BDNF and IL-6 significantly increased after C and C+E, however increases for IL-6 were significantly higher after C+E compared to C. CONCLUSION: The present study showed that superimposed E during cycling might be a useful tool to induce a high local stimulus to skeletal muscle even when performing low to moderate external workloads. This effect might be due the activation of additional muscle fibers and mild eccentric work due to the concomitant activation of agonist and antagonist. However the higher load to skeletal muscle has to be taken into account.

Low in vitro third-body wear on total hip prostheses induced by calcium sulphate used for local antibiotic therapy.

In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied - preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE) and cross-linked polyethylene (XLPE) against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear.

Active vs. passive recovery during high-intensity training influences hormonal response.

The aim of the present study was to compare the effects of active (A) vs. passive (P) recovery during high-intensity interval training on the acute hormonal and metabolic response. Twelve triathletes/cyclists performed four 4 min intervals on a cycle ergometer, either with A- or P-recovery between each bout. Testosterone, hGH, cortisol, VEGF, HGF and MIF were determined pre, 0', 30', 60' and 180' after both interventions. Metabolic perturbations were characterized by lactate, blood gas and spirometric analysis. A-recovery caused significant increases in circulating levels of cortisol, testosterone, T/C ratio, hGH, VEGF and HGF. Transient higher levels were found for cortisol, testosterone, hGH, VEGF, HGF and MIF after A-recovery compared to P-recovery, despite no differences in metabolic perturbations. A-recovery was more demanding from an athlete's point of view. Based on the data of testosterone, hGH and the T/C-ratio, as well as on the data of VEGF and HGF it appears that this kind of exercise protocol with A-recovery phases between the intervals may promote anabolic processes and may lead to pro-angiogenic conditions more than with P-recovery. These data support the findings that also the long term effects of both recovery modes seem to differ, and that both can induce specific adaptations.

Acute hormonal responses before and after 2 weeks of HIT in well trained junior triathletes.

The aim was to compare the acute hormonal response to a single HIT session at the beginning and end of a HIT shock microcycle. 13 male junior triathletes (15.8±1.8 yrs.) performed 16 HIT sessions within a 2 week period. Venous blood samples were collected before and after the first and last HIT session. Significant increases in cortisol (first session +89.7%; last session +70.3%) and hGH (first session +435.1%; last session +314.6%) concentrations were observed after both training sessions (P<0.05). The acute responses of cortisol, hGH, T3, and fT3 were not different between the first and last HIT sessions (P=1.00). Although no acute changes in testosterone were detected after the training sessions, testosterone concentrations were significantly higher at all time points (62.6-80.1%) during the last compared to first training session (P≤0.001). Findings from the present study reveal that 16 sessions of HIT led to significant increases in baseline concentrations of serum testosterone. This might indicate a heightened anabolic state even in junior triathletes. Based on the hormonal data, we conclude that at the end of this 2 week microcycle no familiarization effect was evident and that the training stimulus produced by HIT was still great enough to "stress" the athletes and induce positive training adaptations.

Acute metabolic, hormonal, and psychological responses to different endurance training protocols.

In the last years, mainly 2 high-intensity-training (HIT) protocols became common: first, a Wingate-based "all-out" protocol and second, a 4×4 min protocol. However, no direct comparison between these protocols exists, and also a comparison with high-volume-training (HVT) is missing. Therefore, the aim of the present study was to compare these 3 endurance training protocols on metabolic, hormonal, and psychological responses. Twelve subjects performed: 1) HVT [130 min at 55% peak power output (PPO)]; 2) 4×4 min at 95% PPO; 3) 4×30 s all-out. Human growth hormone (hGH), testosterone, and cortisol were determined before (pre) and 0', 30', 60', 180' after each intervention. Metabolic stimuli and perturbations were characterized by lactate, blood gas (pH, BE, HCO3⁻, pO2, PCO2), and spirometric analysis. Furthermore, changes of the person's perceived physical state were determined. The 4×30 s training caused the highest increases in cortisol and hGH, followed by 4 × 4 min and HVT. Testosterone levels were significantly increased by all 3 exercise protocols. Metabolic stress was highest during and after 4×30 s, followed by 4×4 min and HVT. The 4×30 s training was also the most demanding intervention from an athlete's point of view. In conclusion, the results suggest that 4×30 s and 4×4 min promote anabolic processes more than HVT, due to higher increases of hGH, testosterone, and the T/C ratio. It can be speculated that the acute hormonal increase and the metabolic perturbations might play a positive role in optimizing training adaptation and in eliciting health benefits as it has been shown by previous long term training studies using similar exercise protocols.

Construction and performance of a dilution-refrigerator based spectroscopic-imaging scanning tunneling microscope.

We report on the set-up and performance of a dilution-refrigerator based spectroscopic imaging scanning tunneling microscope. It operates at temperatures below 10 mK and in magnetic fields up to 14T. The system allows for sample transfer and in situ cleavage. We present first-results demonstrating atomic resolution and the multi-gap structure of the superconducting gap of NbSe(2) at base temperature. To determine the energy resolution of our system we have measured a normal metal/vacuum/superconductor tunneling junction consisting of an aluminum tip on a gold sample. Our system allows for continuous measurements at base temperature on time scales of up to ≈170 h.

Responses of angiogenic growth factors to exercise, to hypoxia and to exercise under hypoxic conditions.

The purpose of the present study was to compare the acute hormonal response of angiogenic regulators to a short-term hypoxic exposure at different altitudes with and without exercise. 7 subjects participated in 5 experimental trials. 2 times subjects stayed in a sedentary position for 90 min at 2000 m or 4000 m, respectively. The same was carried out again in combination with exercise at the same relative intensity (2 mmol∙L(-1) of lactate). The fifth trial consisted of 90 min exercise at sea level. Venous blood samples were taken under resting conditions, 0 and 180 min after each condition to determine VEGF, EPO, IL-6, IL-8 and IGF-1 serum concentrations. EPO, VEGF, and IL-8 showed increases only, when hypoxia was combined with exercise. IL-6 was increased after exercise, independent of altitude. IGF-1 showed no changes in any intervention. The present study suggests that short term hypoxic exposure combined with low intensity exercise is able to up-regulate angiogenic regulators, which might be beneficial to induce angiogenesis and to improve endurance performance. However, in some cases high altitudes are needed, or it can be speculated that exercise intensity needs to be increased.

A stiff scanning tunneling microscopy head for measurement at low temperatures and in high magnetic fields.

We have developed a measurement head for scanning tunneling microscopy (STM) and specifically for spectroscopic imaging STM which is optimized for high mechanical stiffness and good thermal conductivity by choice of material. The main components of the microscope head are made of sapphire. Sapphire has been chosen from several competing possibilities based on finite element modeling of the fundamental vibrational modes of the body. We demonstrate operation of the STM head in topographic imaging and tunneling spectroscopy at temperatures down to below 2 K.