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While the dissociative recombination (DR) of ground-state molecular ions with low-energy free electrons is generally known to be exothermic, it has been predicted to be endothermic for a class of transition-metal oxide ions. To understand this unusual case, the electron recombination of titanium oxide ions (TiO+) with electrons has been experimentally investigated using the Cryogenic Storage Ring. In its low radiation field, the TiO+ ions relax internally to low rotational excitation (â²100 K). Under controlled collision energies down to â¼2 meV within the merged electron and ion beam configuration, fragment imaging has been applied to determine the kinetic energy released to Ti and O neutral reaction products. Detailed analysis of the fragment imaging data considering the reactant and product excitation channels reveals an endothermicity for the TiO+ dissociative electron recombination of (+4 ± 10) meV. This result improves the accuracy of the energy balance by a factor of 7 compared to that found indirectly from hitherto known molecular properties. Conversely, the present endothermicity yields improved dissociation energy values for D0(TiO) = (6.824 ± 0.010) eV and D0(TiO+) = (6.832 ± 0.010) eV. All thermochemistry values were compared to new coupled-cluster calculations and found to be in good agreement. Moreover, absolute rate coefficients for the electron recombination of rotationally relaxed ions have been measured, yielding an upper limit of 1 × 10-7 cm3 s-1 for typical conditions of cold astrophysical media. Strong variation of the DR rate with the TiO+ internal excitation is predicted. Furthermore, potential energy curves for TiO+ and TiO have been calculated using a multi-reference configuration interaction method to constrain quantum-dynamical paths driving the observed TiO+ electron recombination.
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BACKGROUND: Current guidelines recommend a personalized, multimodal, and interdisciplinary approach for the treatment of chronic pain. Already in the acute treatment of postoperative pain, it can be useful to minimize risk factors for chronification. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy for the treatment of chronic and acute pain. AIM OF THE WORK: The aim of this systematic review is to evaluate the clinical efficacy of aVNS in chronic and acute pain as well as its effect on medication intake. MATERIALS AND METHODS: A systematic literature search was carried out on the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence and evaluated via the Jadad scale as well as their scientific validity, and then analyzed in terms of indication, method, stimulation parameters, duration of treatment, efficacy, and safety. RESULTS: Twenty studies on chronic pain indications, ten studies on acute postoperative pain, as well as seven studies on experimental acute pain were identified and analyzed. The search revealed a total of nâ¯= 1105 aVNS-treated patients. The best evidence on the efficacy of aVNS is available for the indications chronic low back pain, chronic cervical syndrome, chronic abdominal pain, and chronic migraine as well as acute postoperative pain in oocyte aspiration, laparoscopic nephrectomy, and open colorectal surgery. Additionally a significant reduction in analgesic or opiate intake was evident in most studies. In three randomized controlled trials in chronic pain patients, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated. CONCLUSION: This review indicates that aVNS can be a complementary and effective non-drug treatment for patients with chronic and acute postoperative pain. Future studies in these indications should focus on standardizing and optimizing treatment parameters, inclusion of quality-of-life outcome parameters, and longer follow-up periods to better understand the sustainable therapeutic effect of aVNS.
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The advent of hard X-ray free-electron lasers enables nanoscopic X-ray imaging with sub-picosecond temporal resolution. X-ray grating interferometry offers a phase-sensitive full-field imaging technique where the phase retrieval can be carried out from a single exposure alone. Thus, the method is attractive for imaging applications at X-ray free-electron lasers where intrinsic pulse-to-pulse fluctuations pose a major challenge. In this work, the single-exposure phase imaging capabilities of grating interferometry are characterized by an implementation at the I13-1 beamline of Diamond Light Source (Oxfordshire, UK). For comparison purposes, propagation-based phase contrast imaging was also performed at the same instrument. The characterization is carried out in terms of the quantitativeness and the contrast-to-noise ratio of the phase reconstructions as well as via the achievable spatial resolution. By using a statistical image reconstruction scheme, previous limitations of grating interferometry regarding the spatial resolution can be mitigated as well as the experimental applicability of the technique.
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We present state-selected measurements of rotational cooling and excitation rates of CH^{+} molecular ions by inelastic electron collisions. The experiments are carried out at a cryogenic storage ring, making use of a monoenergetic electron beam at matched velocity in combination with state-sensitive laser dissociation of the CH^{+} ions for simultaneous monitoring of the rotational level populations. Employing storage times of up to 600 s, we create conditions where electron-induced cooling to the J=0 ground state dominates over radiative relaxation, allowing for the experimental determination of inelastic electron collision rates to benchmark state-of-the-art theoretical calculations. On a broader scale, our experiments pave the way to probe inelastic electron collisions for a variety of molecular ions relevant in various plasma environments.
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Radiofrequency denervation has been established for many years as an important minimally invasive procedure for the treatment of chronic pain conditions. Positive experiences of many users for various indications are contrasted by a nonuniform evidence. With meticulous patient selection and correct assessment of the indications a longer term reduction of pain, a reduced need for analgesics and an improvement in the quality of life can be achieved. The aim of this interdisciplinary position paper is to present the value of radiofrequency denervation in the treatment of chronic pain. The summarized recommendations of the expert group are based on the available evidence and on the clinical experiences of Austrian centers that frequently implement the procedure. The position paper contains recommendations on patient selection and proven indications. We discribe safety aspects, complications, side effects and contraindications.
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Dor Crônica , Dor Lombar , Articulação Zigapofisária , Áustria , Dor Crônica/terapia , Denervação , Humanos , Dor Lombar/cirurgia , Vértebras Lombares , Qualidade de Vida , Resultado do TratamentoRESUMO
The combination of grating-based phase-contrast imaging with X-ray microscopy can result in a complicated image formation. Generally, transverse shifts of the interference fringes are nonlinearly dependent on phase differences of the measured wave front. We present an iterative reconstruction scheme based on a regularized maximum likelihood cost function that fully takes this dependency into account. The scheme is validated by numerical simulations. It is particularly advantageous at low photon numbers and when the premises for deconvolution-based reconstructions are not met. Our reconstruction scheme hence enables a broader applicability of X-ray grating interferometry in imaging and wave front sensing.
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A method is presented to monitor the internal energy distribution of cluster anions via delayed electron detachment by pulsed photoexcitation and demonstrated on Co_{4}^{-} in an electrostatic ion beam trap. In a cryogenic operation, we calibrate the detachment delay to internal energy. By laser frequency scans, at room temperature, we reconstruct the time-dependent internal energy distribution of the clusters. The mean energies of ensembles from a cold and a hot ion source both approach thermal equilibrium. Our data yield a radiative emission law and the absorptivity of the cluster for thermal radiation.
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The purpose of the study was to validate the ambulatory blood pressure monitoring (ABPM) device custo screen pediatric in children aged 3 to 12 years according to the International Protocol of the European Society of Hypertension (ESH-IP revision 2010). Thirty-three children were included and systolic and diastolic blood pressure measurements were performed according to the ESH-IP. The protocol was modified for children considering data from the German Health Interview and Examination Survey for Children and Adolescents (KIGGS). The custo screen pediatric met all the requirements of the ESH-IP. The mean difference between the test device and the reference was -1.4 ± 3.0 mmHg for systolic blood pressure (SBP) and -0.7 ± 3.2 mmHg for diastolic blood pressure (DBP). For SBP and DBP, all 99 measurements were within the absolute difference of 10 mmHg between the test device and the reference. As to part 2 of the protocol, for DBP in all subjects, two out of three measurements were within 5 mmHg between the device and the standard, whereas for SBP in 32 of 33 subjects, two out of three measurements were within this range. CONCLUSION: The custo screen pediatric met all criteria of the ESH-IP review 2010, modified for children from 3 to about 12 years, and can be recommended for ABPM in children. What is Known: ⢠Validation of blood pressure measuring devices is essential to provide patients with an accurate blood pressure measuring device. ⢠The majority of devices has not been validated in children. What is New: ⢠Prior to the present validation, study protocol adjustments of ESH-IP review 2010 for children were defined according to German Health Interview and Examination Survey for Children and Adolescents 2013 (KIGGS). ⢠The custo screen pediatric test device met all criteria of ESH-IP revision 2010, modified for children, and can be recommended for ABPM in children aged 3 to about 12 years.
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Monitorização Ambulatorial da Pressão Arterial/instrumentação , Monitores de Pressão Arterial/normas , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial/normas , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Humanos , Masculino , Guias de Prática Clínica como Assunto , Valores de Referência , Reprodutibilidade dos Testes , Sociedades MédicasRESUMO
We report the synthesis of plasmonic Cu2-x Se@ZnS core@shell nanoparticles (NPs). We used a shell growth approach, starting from Cu2-x Se NPs that have been shown before to exhibit a localized surface plasmon resonance (LSPR). By careful synthesis planning we avoided cation exchange reactions and received core@shell nanoparticles that, after oxidation under air, exhibit a strong LSPR in the NIR. Interestingly, the crystalline, closed ZnS shell that we grew with variable thickness still allowed a slow oxidation of the core under ambient conditions, while the core was effectively protected from reduction, even in the presence of reducing agents such as borane tert-butyamine complex and diisobutylaluminum hydride, giving rise to a stable particle LSPR, also under strongly reducing conditions.
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T cell-engaging CD19/CD3-bispecific BiTE Ab blinatumomab has shown an 80% complete molecular response rate and prolonged leukemia-free survival in patients with minimal residual B-lineage acute lymphoblastic leukemia (MRD(+) B-ALL). Here, we report that lymphocytes in all patients of a phase 2 study responded to continuous infusion of blinatumomab in a strikingly similar fashion. After start of infusion, B-cell counts dropped to < 1 B cell/µL within an average of 2 days and remained essentially undetectable for the entire treatment period. By contrast, T-cell counts in all patients declined to a nadir within < 1 day and recovered to baseline within a few days. T cells then expanded and on average more than doubled over baseline within 2-3 weeks under continued infusion of blinatumomab. A significant percentage of reappearing CD8(+) and CD4(+) T cells newly expressed activation marker CD69. Shortly after start of infusion, a transient release of cytokines dominated by IL-10, IL-6, and IFN-γ was observed, which no longer occurred on start of a second treatment cycle. The response of lymphocytes in leukemic patients to continuous infusion of blinatumomab helps to better understand the mode of action of this and other globally T cell-engaging Abs. The trial is registered with www.clinicaltrials.gov identifier NCT00560794.
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Anticorpos Biespecíficos/administração & dosagem , Antígenos CD19/imunologia , Complexo CD3/imunologia , Sistema Imunitário/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adulto , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/farmacocinética , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Soro Antilinfocitário/metabolismo , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/farmacocinética , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Bombas de Infusão , Ativação Linfocitária/efeitos dos fármacos , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Resultado do TratamentoRESUMO
We present the concluding result from an Ives-Stilwell-type time dilation experiment using 7Li+ ions confined at a velocity of ß=v/c=0.338 in the storage ring ESR at Darmstadt. A Λ-type three-level system within the hyperfine structure of the 7Li+3S1 â3P2 line is driven by two laser beams aligned parallel and antiparallel relative to the ion beam. The lasers' Doppler shifted frequencies required for resonance are measured with an accuracy of <4×10(-9) using optical-optical double resonance spectroscopy. This allows us to verify the special relativity relation between the time dilation factor γ and the velocity ß, γâ1-ß2=1 to within ±2.3×10(-9) at this velocity. The result, which is singled out by a high boost velocity ß, is also interpreted within Lorentz invariance violating test theories.
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The absolute configuration of (R,R)-2,3-dideuterooxirane, which has been independently determined using Coulomb explosion imaging, has been unambiguously chemically correlated with the stereochemical key reference (+)-glyceraldehyde. This puts the absolute configuration of D(+)-glyceraldehyde on firm experimental grounds.
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The visible spectrum of H3(+) is studied using high-sensitivity action spectroscopy in a cryogenic radiofrequency multipole trap. Advances are made to measure the weak ro-vibrational transitions from the lowest rotational states of H3(+) up to high excitation energies providing visible line intensities and, after normalisation to an infrared calibration line, the corresponding Einstein B coefficients. Ab initio predictions for the Einstein B coefficients are obtained from a highly precise dipole moment surface of H3(+) and found to be in excellent agreement, even in the region where states have been classified as chaotic.
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OBJECTIVES: The goal of this study was to evaluate the long-term efficacy and safety of peripheral nerve field stimulation (PNFS) for chronic low back pain (cLBP). MATERIALS AND METHODS: In this prospective, multicenter observational study, 118 patients were admitted to 11 centers throughout Austria and Switzerland. After a screening visit, all patients underwent a trial stimulation period of at least seven days before implantation of the permanent system. Leads were placed in the subcutaneous tissues of the lower back directly in the region of greatest pain. One hundred five patients were implanted with a permanent stimulating system. Patients' evaluation of pain and functional levels were completed before implantation and one, three, and six months after implantation. Adverse events, medication usage, and coverage of the painful area and predictive value of transcutaneous electrical nerve stimulation (TENS) were monitored. RESULTS: All pain and quality-of-life measures showed statistically significant improvement during the treatment period. These included the average pain visual analog scale, the Oswestry Disability Questionnaire, the Becks Depression Inventory, and the Short Form-12 item Health survey. Additionally, medication usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants showed a highly significant reduction. Complications requiring surgical intervention were reported in 9.6% of the patients. The degree of coverage of painful areas seems to be an important criterion for efficacy of PNFS, whereas TENS is presumably no predictor. CONCLUSIONS: This prospective, multicenter study confirms that PNFS is an effective therapy for the management of cLBP. Significant improvements in many aspects of the pain condition were measured, and complications were minimal.
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Dor Lombar/diagnóstico , Dor Lombar/terapia , Medição da Dor/métodos , Estimulação Elétrica Nervosa Transcutânea/métodos , Seguimentos , Humanos , Dor Lombar/fisiopatologia , Estudos Prospectivos , Resultado do TratamentoRESUMO
Municipal solid waste management systems of many developing countries are commonly constrained by factors such as limited financial resources and poor governance, making it a difficult proposition to break with complex, entrenched and unsustainable technologies and systems. This article highlights strategic partnerships as a way to affect a distributed agency among several sets of stakeholders to break so-called path dependencies, which occur when such unsustainable pathways arise, stabilize and become self-reinforcing over time. Experiences from a North-South collaborative effort provide some lessons in such partnership building: In Uganda and Denmark, respectively, the World Wildlife Fund and the network organization access2innovation have mobilized stakeholders around improving the municipal solid waste management system in Kasese District. Through a municipal solid waste management system characterization and mapping exercise, some emergent lessons and guiding principles in partnership building point to both pitfalls and opportunities for designing sustainable pathways. First, socio-technical lock-in effects in the municipal solid waste management system can stand in the way of partnerships based on introducing biogas or incineration technologies. However, opportunities in the municipal solid waste management system can exist within other areas, and synergies can be sought with interlinking systems, such as those represented with sanitation.
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Cidades , Conservação dos Recursos Naturais/métodos , Eliminação de Resíduos/economia , Eliminação de Resíduos/métodos , Dinamarca , Cooperação Internacional , Técnicas de Planejamento , UgandaRESUMO
As the demand for silicone polymers continues to grow across various industries, the need for effective recycling methods has become increasingly important, because recycling silicone products reduces landfill waste, conserves resources, and uses less energy. Chemical recycling involves the depolymerization of silicone waste into oligomers, which can then be used to produce virgin-grade silicone. While this sector of the recycling industry is still in its infancy-we estimate that 35,000 to 45,000 metric tons of silicone waste will be chemically recycled worldwide in 2024-an increasing number of companies are beginning to explore the implementation of closed-loop systems to recycle silicones. This article examines the technical options and challenges for recycling silicone polymers, the major degradation chemistries available for depolymerizing silicones, and the current industrial reality of chemical recycling of silicones.
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In Germany, physicians qualify for emergency medicine by combining a specialty medical training-e.g. internal medicine-with advanced training in emergency medicine according to the statutes of the State Chambers of Physicians largely based upon the Guideline Regulations on Specialty Training of the German Medical Association. Internal medicine and their associated subspecialities represent an important column of emergency medicine. For the internal medicine aspects of emergency medicine, this curriculum presents an overview of knowledge, skills (competence levels I-III) as well as behaviours and attitudes allowing for the best treatment of patients. These include general aspects (structure and process quality, primary diagnostics and therapy as well as indication for subsequent treatment; resuscitation room management; diagnostics and monitoring; general therapeutic measures; hygiene measures; and pharmacotherapy) and also specific aspects concerning angiology, endocrinology, diabetology and metabolism, gastroenterology, geriatric medicine, hematology and oncology, infectiology, cardiology, nephrology, palliative care, pneumology, rheumatology and toxicology. Publications focussing on contents of advanced training are quoted in order to support this concept. The curriculum has primarily been written for internists for their advanced emergency training, but it may generally show practising emergency physicians the broad spectrum of internal medicine diseases or comorbidities presented by patients attending the emergency department.
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Currículo , Medicina de Emergência , Serviço Hospitalar de Emergência , Medicina Interna , Medicina Interna/educação , Humanos , Alemanha , Medicina de Emergência/educação , Competência Clínica , Educação de Pós-Graduação em MedicinaRESUMO
Epidermal growth factor receptor (EGFR)-specific monoclonal antibodies predominantly inhibit colorectal cancer (CRC) growth by interfering with receptor signaling. Recent analyses have shown that patients with CRC with mutated KRAS and BRAF oncogenes do not profit from treatment with such antibodies. Here we have used the binding domains of cetuximab and pantitumumab for constructing T cell-engaging BiTE antibodies. Both EGFR-specific BiTE antibodies mediated potent redirected lysis of KRAS- and BRAF-mutated CRC lines by human T cells at subpicomolar concentrations. The cetuximab-based BiTE antibody also prevented at very low doses growth of tumors from KRAS- and BRAF-mutated human CRC xenografts, whereas cetuximab was not effective. In nonhuman primates, no significant adverse events were observed during treatment for 3 wk at BiTE serum concentrations inducing, within 1 d, complete lysis of EGFR-overexpressing cancer cells. EGFR-specific BiTE antibodies may have potential to treat CRC that does not respond to conventional antibodies.
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Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Receptores ErbB/antagonistas & inibidores , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Cetuximab , Neoplasias Colorretais/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Genes ras/efeitos dos fármacos , Humanos , Mutação/efeitos dos fármacos , Neoplasias/genética , Proteínas Proto-Oncogênicas B-raf , Fatores de RiscoRESUMO
Additive manufacturing allows for the production of complex components using various types of materials such as plastics, metals and ceramics without the need for molding tools. In the field of high-performance polymers, semi-crystalline polymers such as polyetheretherketone (PEEK) or amorphous polymers such as polyetherimide (PEI) are already successfully applied. Contrary to semi-crystalline and amorphous polymers, thermotropic liquid crystalline polymers (LCPs) do not change into an isotropic liquid during melting. Instead, they possess anisotropic properties in their liquid phase. Within the scope of this work, this special group of polymers was investigated with regard to its suitability for processing by means of fused filament fabrication. Using an LCP with a low melting temperature of around 280 °C is compared to processing an LCP that exhibits a high melting temperature around 330 °C. In doing so, it was revealed that the achievable mechanical properties strongly depend on the process parameters such as the direction of deposition, printing temperature, printing speed and layer height. At a layer height of 0.10 mm, a Young's modulus of 27.3 GPa was achieved. Moreover, by employing an annealing step after the printing process, the tensile strength could be increased up to 406 MPa at a layer height of 0.15 mm. Regarding the general suitability for FFF as well as the achieved uniaxial mechanical properties, the LCP with a low melting temperature was advantageous compared to the LCP with a high melting temperature.
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Background and Hypothesis: Dysfunction of the dopamine system is the leading neurobiological hypothesis of schizophrenia. In this study, we tested this hypothesis in the context of aberrance salience theory of delusions using catecholamine depletion. We hypothesized that acute dopamine depletion improves both positive symptoms and salience attribution in individuals with schizophrenia. Study Design: Catecholamine depletion was achieved by oral administration of alpha-methyl-para-tyrosine (AMPT) in 15 individuals with schizophrenia and 15 healthy volunteers. The study design consisted of a randomized, double-blind, placebo-controlled crossover, single-site experimental trial. The main outcome measures were the Scale for the Assessment of Positive Symptoms and the Salience Attribution Test. Study Results: Catecholamine depletion transiently reduced specific psychotic symptoms in symptomatic individuals with schizophrenia, namely delusions and positive formal thought disorder (interaction treatment-by-timepoint, P = .013 and P = .010, respectively). We also found trends for catecholamine depletion to increase relevant bias and adaptive salience in participants with schizophrenia while decreasing them in healthy controls (interaction group-by-treatment, P = .060 and P = .089, respectively). Exploratory analyses revealed that in participants with schizophrenia, higher relevant bias at 3 hours after the end of AMPT treatment corresponded to lower delusional symptoms (Spearman's rho = -0.761, P = .001). Conclusions: This study suggests that the relationship between dopamine hyperactivity and delusional symptoms in schizophrenia is mediated by impaired attribution of salience to reward-predicting stimuli.