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Two-dimensional thermographic particle image velocimetry (T-PIV) is presented for the in situ measurement in optically accessible internal combustion (IC) engines. Temperature and velocity measurements are combined using thermographic phosphor particles as tracers for PIV. For three commercially available phosphors (BAM:Eu2+, ZnO, and ZnO:Zn), temperature sensitivity, luminescence intensity at high temperatures and laser-fluence dependence were evaluated for phosphor-coated surfaces in a high-temperature cell. ZnO:Zn was identified as the best-suited candidate for engine in-cylinder measurements and further analyzed in the aerosolized state at temperatures up to 775 K to generate calibration data required for signal quantification in engine experiments. T-PIV was successfully applied in the IC engine to simultaneously obtain instantaneous two-dimensional velocity and temperature fields using the intensity-ratio method. Despite a measurement uncertainty (±1σ basis) of only 3.7 K at 317 K (1.2%) to 24.4 K (4.2%) at 575 K, this technique suffers from low signal intensities due to thermal quenching at increasing temperatures, which leads to reduced accuracy as the piston approaches top dead center. Thermographic measurements were successful to visualize local temperature changes due to evaporative cooling after fuel injection. The measured mean gas temperatures agreed well with zero-dimensional simulations that use additional wall-temperature measurements from thermographic phosphor measurements based on the lifetime method as input for heat transfer calculations.

Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS). Despite its wide clinical use, the mechanisms underlying clinical response are not understood. This study aimed to reveal immune markers of therapeutic response to DMF treatment in MS. For this purpose, we prospectively collected peripheral blood mononuclear cells (PBMCs) from a highly characterized cohort of 44 individuals with MS before and at 12 and 48 wk of DMF treatment. Single cells were profiled using high-dimensional mass cytometry. To capture the heterogeneity of different immune subsets, we adopted a bioinformatic multipanel approach that allowed cell population–cluster assignment of more than 50 different parameters, including lineage and activation markers as well as chemokine receptors and cytokines. Data were further analyzed in a semiunbiased fashion implementing a supervised representation learning approach to capture subtle longitudinal immune changes characteristic for therapy response. With this approach, we identified a population of memory T helper cells expressing high levels of neuroinflammatory cytokines (granulocyte–macrophage colony-stimulating factor [GM-CSF], interferon γ [IFNγ]) as well as CXCR3, whose abundance correlated with treatment response. Using spectral flow cytometry, we confirmed these findings in a second cohort of patients. Serum neurofilament light-chain levels confirmed the correlation of this immune cell signature with axonal damage. The identified cell population is expanded in peripheral blood under natalizumab treatment, substantiating a specific role in treatment response. We propose that depletion of GM-CSF–, IFNγ-, and CXCR3-expressing T helper cells is the main mechanism of action of DMF and allows monitoring of treatment response., Proceedings of the National Academy of Sciences of the United States of America, 119 (31), ISSN:0027-8424, ISSN:1091-6490

Treatment with dimethyl fumarate (DMF) leads to lymphopenia and infectious complications in a subset of patients with multiple sclerosis (MS). Here, we aimed to reveal immune markers of DMF-associated lymphopenia. This prospective observational study longitudinally assessed 31 individuals with MS by single-cell mass cytometry before and after 12 and 48 weeks of DMF therapy. Employing a neural network-based representation learning approach, we identified a CCR4-expressing T helper cell population negatively associated with relevant lymphopenia. CCR4-expressing T helper cells represent a candidate prognostic biomarker for the development of relevant lymphopenia in patients undergoing DMF treatment. ANN NEUROL 2022;91:676-681.

By the middle of February 2021, the COVID-19 pandemics are still ongoing. Globally, 110 million cases have been recorded. More than 2.4 million people have died from the disease caused by the novel SARS-CoV-2 virus. Figures presented in this chapter are taken from the WHO database (WHO 2021), except those from Hawai’i (New York Times database 2021) and Easter Island (France24 2021). All currencies have been converted into USD using Oanda database (Oanda 2020) as of February 9, 2021. In many Pacific Island Countries and Territories (PICT), however, morbidity and mortality have been low. Most PICs have no cases. Where cases exist, mortality has been low with a few exceptions. That being said, social and economic consequences are severe in all places. The chapter gives a brief reflection on historical experience with epidemics in the Pacific Island region. The remainder of the chapter looks at the epidemiology of the COVID-19 pandemics, the “who, when, and where” of COVID-19 in the Pacific Islands, its associated risk factors, and possible ways to control the pandemics. Medical preparedness of PICT health systems in PICTs, and their material and organizational constitution are covered as well as the support PICT received from outside to deal with the situation. The chapter also provides an account of social and economic impacts of COVID-19, including challenges to care for Pacific Islanders away from home. Some PICs (Fiji, Solomon Islands, Tonga, and Vanuatu) had to deal with severe tropical cyclones just at the time when governments tried to implement measures against COVID-19. To conclude, the chapter provides recommendations of how to strengthen PICT capabilities and capacities to improve preparedness against similar medical treats in the future. In the chapter, Fiji and Papua New Guinea (PNG) stand in the center of analysis. Some other Pacific Islands and Territories were included, where reported cases emerged and/or where important situations arose. In a few instances, the chapter also looks at the situation Pacific Islanders faced outside their countries.

Summary Current data generation capabilities in the life sciences render scientists in an apparently contradicting situation. While it is possible to simultaneously measure an ever-increasing number of systems parameters, the resulting data are becoming increasingly difficult to interpret. Latent variable modeling allows for such interpretation by learning non-measurable hidden variables from observations. This review gives an overview over the different formal approaches to latent variable modeling, as well as applications at different scales of biological systems, such as molecular structures, intra- and intercellular regulatory up to physiological networks. The focus is on demonstrating how these approaches have enabled interpretable representations and ultimately insights in each of these domains. We anticipate that a wider dissemination of latent variable modeling in the life sciences will enable a more effective and productive interpretation of studies based on heterogeneous and high-dimensional data modalities., The bigger picture Current data generation capabilities in the life sciences render scientists in an apparently contradicting situation. While it is possible to simultaneously measure an ever-increasing number of systems parameters, the resulting data are becoming increasingly difficult to interpret. Latent variable modeling has proved to be a formal machine learning paradigm to achieve such interpretation by learning non-measurable hidden variables from observations. This review summarizes concepts and applications of this paradigm in the life sciences., Current data generation capabilities in the life sciences render scientists in an apparently contradicting situation. While it is possible to simultaneously measure an ever-increasing number of systems parameters, the resulting data are becoming increasingly difficult to interpret. Latent variable modeling has proved to be a formal machine learning paradigm to achieve such interpretation by learning non-measurable hidden variables from observations. This review summarizes concepts and applications of this paradigm in the life sciences.

Clustering high-dimensional data, such as images or biological measurements, is a long-standing problem and has been studied extensively. Recently, Deep Clustering has gained popularity due to its flexibility in fitting the specific peculiarities of complex data. Here we introduce the Mixture-of-Experts Similarity Variational Autoencoder (MoE-Sim-VAE), a novel generative clustering model. The model can learn multi-modal distributions of high-dimensional data and use these to generate realistic data with high efficacy and efficiency. MoE-Sim-VAE is based on a Variational Autoencoder (VAE), where the decoder consists of a Mixture-of-Experts (MoE) architecture. This specific architecture allows for various modes of the data to be automatically learned by means of the experts. Additionally, we encourage the lower dimensional latent representation of our model to follow a Gaussian mixture distribution and to accurately represent the similarities between the data points. We assess the performance of our model on the MNIST benchmark data set and challenging real-world tasks of clustering mouse organs from single-cell RNA-sequencing measurements and defining cell subpopulations from mass cytometry (CyTOF) measurements on hundreds of different datasets. MoE-Sim-VAE exhibits superior clustering performance on all these tasks in comparison to the baselines as well as competitor methods., PLoS Computational Biology, 17 (6), ISSN:1553-734X, ISSN:1553-7358

IntroductionEndometriosis is associated with both cyclic and non-cyclic pelvic pain. Many patients do not remain symptom free, even after guideline-oriented treatment. This study aimed to identify differences in endometriosis-associated pain and test for possible associations with hormone therapy.MethodsThe results presented here are based on a cross-sectional study conducted at the Charité Endometriosis Center in Berlin in which pain profile data were collected via a questionnaire from women with a confirmed diagnosis of endometriosis. The questionnaire contained items concerning cyclic and non-cyclic pain, pain intensity, and pain duration. SPSS software was used to perform the statistical analysis, including descriptive and analytical statistics.ResultsOf 239 women surveyed, 121 (50.6%) reported current hormone therapy, and 185 (77.4%) reported previous hormone therapy. Moreover, 84% had current (cyclic and non-cyclic) pain symptoms, which were severe enough to warrant treatment in nearly 70% of all cases. Hormone therapy was only found to be associated with a slight, non-significant advantage in patients with “cyclic pain”. The reverse was true of non-cyclic pain: women on hormone therapy reported a greater incidence of pain, greater pain intensity, more frequent need for treatment, and more pain days.ConclusionsWith a very broad interpretation of our findings, it can be concluded that hormone therapy achieves some degree of pain reduction via down-regulation of the ovarian cycle, at least in the case of cyclic pain, whereas non-cyclic pain does not respond or no longer responds to hormones.

Climate change has become one of the most crucial global challenges of the 21st century. It was in the 1960s when discussions about global warming found their way to – at first – small groups of physical scientists. The question then was if global warming could scientifically be proven, and if so, what exactly were its causes, and how could it be prevented from reaching dangerous levels. Once human-made global warming became an accepted paradigm, scientific efforts concentrated on mitigation, on necessary steps to check climate change by reducing emissions of greenhouse gases, and to slow down deforestation destroying sinks of carbon dioxide (CO2). The Kyoto Protocol (1997) became the major instrument of the mitigation paradigm. Today’s paradigm acknowledges that mitigation, even if complete and immediate, can no longer prevent climate change. In its latest reports, the Intergovernmental Panel on Climate Change (IPCC) highlights that climate change is already happening (IPCC 2014). Emphasis has to be given to effective global climate protection, in order to minimise changes to the Earth’s climate and to find ways to adapt to the impacts of climate change.

Next-generation sequencing (NGS) provides unrestricted access to the genome, but it produces ‘big data’ exceeding in amount and complexity the classical analytical approaches. We introduce a bioinformatics-based classifying biomarker that uses emergent properties in genetics to separate pain patients requiring extremely high opioid doses from controls. Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) classifier that provided a diagnostic accuracy of 80.6±4%. This outperformed alternative classifiers such as reportedly functional opioid receptor gene variants or complex biomarkers obtained via multiple regression or decision tree analysis. The accumulation of several genetic variants with only minor functional influences may result in a qualitative consequence affecting complex phenotypes, pointing at emergent properties in genetics.

Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. As compared with reference data from healthy controls, patients with CPSP showed alterations of thermal and mechanical thresholds on the body area contralateral to their stroke (P < 0.01). Patients with sensory stroke but without CPSP (non-pain sensory stroke [NPSS] patients) exhibited similar albeit less pronounced contralesional changes. Paradoxical heat sensation (PHS) and dynamic mechanical allodynia (DMA) showed higher values in CPSP, and an elevated cold detection threshold (CDT) was seen more often in CPSP than in patients with NPSS (P < 0.05). In patients with CPSP, changes in CDT, PHS, dynamic mechanical allodynia, and temporal pain summation (wind-up ratio) each correlated with the presence of pain (P < 0.05). On the homologous ipsilesional body area, both patient groups showed additional significant abnormalities as compared with the reference data, which strongly resembled the contralesional changes. In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.

Supplemental Digital Content is Available in the Text., Introduction: The burden of untreated postoperative pain is high. Objective: This study assessed feasibility of using quality improvement (QI) tools to improve management of perioperative pain in hospitals in multiple developing countries. Methods: The International Pain Registry and Developing Countries working groups, from the International Association for the Study of Pain (IASP), sponsored the project and PAIN OUT, a QI and research network, coordinated it, and provided the research tools. The IASP published a call about the project on its website. Principal investigators (PIs) were responsible for implementing a preintervention and postintervention study in 1 to 2 surgical wards in their hospitals, and they were free to choose the QI intervention. Trained surveyors used standardized and validated web-based tools for collecting findings about perioperative pain management and patient reported outcomes (PROs). Four processes and PROs, independent of surgery type, assessed effectiveness of the interventions. Results: Forty-three providers responded to the call; 13 applications were selected; and PIs from 8 hospitals, in 14 wards, in 7 countries, completed the study. Interventions focused on teaching providers about pain management. Processes improved in 35% and PROs in 37.5% of wards. Conclusions: The project proved useful on multiple levels. It offered PIs a framework and tools to perform QI work and findings to present to colleagues and administration. Management practices and PROs improved on some wards. Interpretation of change proved complex, site-dependent, and related to multiple factors. PAIN OUT gained experience coordinating a multicentre, international QI project. The IASP promoted research, education, and QI work.

The root cap protects the stem cell niche of angiosperm roots from damage. In Arabidopsis, lateral root cap (LRC) cells covering the meristematic zone are regularly lost through programmed cell death, while the outermost layer of the root cap covering the tip is repeatedly sloughed. Efficient coordination with stem cells producing new layers is needed to maintain a constant size of the cap. We present a signalling pair, the peptide IDA-LIKE1 (IDL1) and its receptor HAESA-LIKE2 (HSL2), mediating such communication. Live imaging over several days characterized this process from initial fractures in LRC cell files to full separation of a layer. Enhanced expression of IDL1 in the separating root cap layers resulted in increased frequency of sloughing, balanced with generation of new layers in a HSL2-dependent manner. Transcriptome analyses linked IDL1-HSL2 signalling to the transcription factors BEARSKIN1/2 and genes associated with programmed cell death. Mutations in either IDL1 or HSL2 slowed down cell division, maturation and separation. Thus, IDL1-HSL2 signalling potentiates dynamic regulation of the homeostatic balance between stem cell division and sloughing activity.

There has been persistent growth in the professional pain management specialists, principally in paediatrics, neurology, rehabilitation medicine, as well as anaesthesia. The same growth has been seen in other healthcare professions. In this chapter of European Pain Management we focus on the rise of specialty pain medicine and its implications for education, governance, and professional identity. In many European countries, pain medicine is not an independent specialism, despite the growth in need and the technical and scientific knowledge required. Advances in education and training are also reviewed, and this chapter concludes with a discussion of how to advance the role of pain medicine, and the leadership needed within European countries and across Europe.

The introduction of pain medicine (cross-sectional subject 14, QF 14) into the Human Medicine study program is a great opportunity. A knowledge gap concerning the treatment of pain patients outside of specialized pain centers has been recognized for many years. This gap might be closed or at least reduced by a compulsory curriculum in pain medicine. If implementation of new lessons for QF 14 is not possible, pain medicine could be represented by labelled elements in the existing curriculum, in order to highlight the field. The core curriculum must now be converted into appropriate teaching and test formats. Due to the autonomy and heterogeneity of German medical faculties, no uniform solution will be achieved. In contrast, this diversity and the entirely new implementation of the cross-sectional subject will allow structured evaluation of different teaching and examination formats with respect to teaching outcome in benchmarking investigations in the coming semesters. Practically experienced lecturers and theory-driven medical educationalists are called upon to get involved with the development, implementation, and evaluation of pain medicine in undergraduate education in Germany. Teaching enthusiasts are encouraged to dedicate themselves to the strenuous, but stimulating task of implementing QF 14. The Deutsche Schmerzgesellschaft (German Pain Society) will offer support for this.

Im Sinne des lebenslangen Lernens wird von allen in der Medizin tatigen Berufsgruppen eine kontinuierliche Weiterbildung erwartet. Dies nahmen die Autoren zum Anlass, den wichtigsten nationalen Kongress im Bereich der Schmerzmedizin aus medizindidaktischer Perspektive zu untersuchen. Die Teilnehmer des 37. Deutschen Schmerzkongresses der Deutschen Schmerzgesellschaft (17.–20. Oktober 2012 in Mannheim) wurden mit einem 5-seitigen Fragebogen zu Kongressinhalten und Veranstaltungsformaten befragt. Um die Gewichtung der angebotenen Veranstaltungen bezuglich der unterschiedlichen arztlichen Kompetenzen zu erfassen, wurde das Programm des Kongresses auf die im Rahmenmodell CanMEDS definierten Arztrollen hin untersucht. Die Qualitat der bisherigen Fortbildungsangebote des Deutschen Schmerzkongresses schatzten die Teilnehmer als gut ein. Die Posterausstellung wurde nach den Symposien als zweitwichtigste Lehrveranstaltung angesehen. Die Teilnehmer auserten die meisten inhaltlichen Wunsche fur zukunftige Kongresse mit Bezug auf die interprofessionellen Partner der Pflege sowie der Psychotherapie. Die Arztrollen des Managers, Kommunikators, Gesundheitsberaters und professionellen Vorbilds sind im untersuchten Kongressprogramm unterreprasentiert. Das Kongressdesign konnte durch ein erweitertes Angebot an Praktikerseminaren didaktisch, inhaltlich und in Bezug auf die Zielgruppen aufgewertet werden. Inhaltlich wird von den Teilnehmern eine noch umfanglichere Berucksichtigung der interprofessionellen Partner gewunscht. Dies konnte zusammen mit einer ausgewogeneren Verteilung der einzelnen Arztrollen im Programm die Attraktivitat der Veranstaltung zusatzlich steigern.

Rationale, aims and objectives: Management of post‐operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence‐based medicine (EBM)‐derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient‐reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making. Methods: PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self‐sustaining, not‐for‐profit project, targeting health care professionals caring for patients undergoing surgery. Results: The growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet‐based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in‐depth analysis; and (2) the case‐based clinical decision support system offers practice‐based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM. Conclusion: PAIN OUT, a large, growing international registry, allows use of ‘real‐life’ data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care.

Obwohl Schmerzen der bei Weitem haufigste Grund sind, einen Arzt aufzusuchen, konnten Arzte ihre Ausbildung abschliesen, ohne sich mit Schmerz und Schmerzmanagement auseinandergesetzt zu haben. Die resultierende Unsicherheit ist vermutlich einer der Hauptgrunde, weshalb eine angemessene Behandlung unterbleibt. Viele Patienten beklagen daher zu Recht eine Ignoranz seitens des medizinischen Personals gegenuber ihrem Leiden. Dem Anspruch auf Schmerzerfassung und der Sicherstellung der Therapie akuter und chronischer Schmerzen gebuhrt hochste Prioritat. Die Angebote zur Zusatzweiterbildung „Spezielle Schmerztherapie“ und schmerzmedizinische Fortbildungen fur entsprechend Interessierte konnten dies allein nicht erreichen. Jeder Arzt muss daher schmerzmedizinische Grundkenntnisse haben. Die Schmerzmedizin muss daher in den Curricula der medizinischen Fakultaten verankert werden. In Deutschland ist es 2012 gelungen, weltweit erstmals (mit Frankreich) die Schmerzmedizin durch Aufnahme in die arztliche Approbationsordnung als Pflichtfach in der studentischen Lehre zu etablieren. Die Anderung der Approbationsordnung ist eine Herausforderung fur die Fakultaten, die curricularen und formalen Strukturen der Schmerzmedizin in der Lehre kurzfristig zu definieren und anschliesend zu implementieren. Dieser Artikel berichtet uber das Kerncurriculum Schmerzmedizin der Deutschen Schmerzgesellschaft und uber erste praktische Erfahrungen mit der Umsetzung dieses Curriculums in Modell-, Reform- und Regelstudiengangen.

BACKGROUND: Human volunteer studies demonstrate ketamine-reversible opioid-induced hyperalgesia, consistent with reports of increased postoperative pain and analgesic consumption. However, recent clinical trials showed controversial results after intraoperative administration of high-dose remifentanil. OBJECTIVE: To investigate in lower abdominal surgery patients whether postoperative pain intensity and analgesic consumption are increased following intraoperative high-dose vs. low-dose remifentanil, and whether this could be prevented by preoperative administration of the NMDA antagonist amantadine. DESIGN: Randomised, placebo-controlled, clinical study. SETTING: University hospital. PATIENTS: Sixty patients scheduled for elective major lower abdominal surgery. INTERVENTIONS: Patients were randomly assigned to one of three anaesthetic regimens. First, in the group 'low-dose remifentanil and preoperative isotonic saline' (n=15), a remifentanil infusion was maintained at a rate of 0.1 μg kg min throughout anaesthesia, and the end-tidal concentration of sevoflurane started at 0.5 minimum alveolar concentration (MAC) and was increased by 0.2% increments according to clinical demand. Preoperatively, 500 ml NaCl 0.9% were infused as study solution. Second, in the group 'high-dose remifentanil and preoperative saline' (n=17), the end-tidal concentration of sevoflurane was maintained at 0.5 MAC throughout anaesthesia. A remifentanil infusion was started at a rate of 0.2 μg kg min and subsequently increased by 0.05 μg kg min increments to clinical demand. Preoperatively, these patients also received a solution of 500 ml NaCl 0.9% as study solution. Third, the group 'high-dose remifentanil and preoperative amantadine' (n=16) received the same anaesthetic protocol as the second group, but the preoperative study solution was substituted by amantadine (200 mg/500 ml). MAIN OUTCOME MEASURES: Pain intensity measured by the numerical rating scale and cumulative morphine consumption. RESULTS: The remifentanil dose in both high-dose groups was significantly higher compared with the low-dose remifentanil group (0.20±0.04 and 0.23±0.02 vs. 0.08±0.04 μg kg min; P

This article reviews the role of analgesic drugs with a particular emphasis on opioids. Opioids are the oldest and most potent drugs for the treatment of severe pain, but they are burdened by detrimental side effects such as respiratory depression, addiction, sedation, nausea, and constipation. Their clinical application is undisputed in acute (e.g., perioperative) and cancer pain, but their long-term use in chronic pain has met increasing scrutiny and has contributed to the current opioid crisis. We discuss epidemiological data, pharmacological principles, clinical applications, and research strategies aiming at novel opioids with reduced side effects.

Post-operative pain exacts a high toll from patients, families, healthcare professionals and healthcare systems worldwide. PAIN-OUT is a research project funded by the European Union's 7th Framework Program designed to develop effective, evidence-based approaches to improve pain management after surgery, including creating a registry for feedback, benchmarking and decision support. In preparation for PAIN-OUT, we conducted a pilot study to evaluate the feasibility of international data collection with feedback to participating sites. Adult orthopaedic or general surgery patients consented to participate between May and October 2008 at 14 collaborating hospitals in 13 countries. Project staff collected patient-reported outcomes and process data from 688 patients and entered the data into an online database. Project staff in 10 institutions met the enrolment criteria of collecting data from at least 50 patients. The completeness and quality of the data, as assessed by rate of missing data, were acceptable; only 2% of process data and 0.06% of patient-reported outcome data were missing. Participating institutions received access to select items as Web-based feedback comparing their outcomes to those of the other sites, presented anonymously. We achieved proof of concept because staff and patients in all 14 sites cooperated well despite marked differences in cultures, nationalities and languages, and a central database management team was able to provide valuable feedback to all.

Viele Patienten mit chronischen Erkrankungen haben spirituelle und existenzielle Bedurfnisse, die im Gesundheitssystem zumeist ausgeblendet werden, obwohl sie fur viele essenziell sind und ihre Unterstutzung oft mit einer besseren Lebensqualitat assoziiert sind. Wenn diese identifiziert sind, konnen Arzte, Pflegende, Seelsorger, aber auch Angehorige auf diese reagieren und den Patienten in seiner Auseinandersetzung mit chronischer Krankheit unterstutzen. Diese Unterstutzung schafft letztendlich die Bedingungen, damit sich wesentliche Aspekte der Lebensqualitat der Patienten verbessern konnen.

Introduction Medical care of patients with chronic pain has not yet been thoroughly analysed in the German health care system. In particular, there are only sparse data on the use of complementary treatments in chronic pain patients. Materials and methods In this multi-centre, prospective observational study with a comprehensive retrospective section, we analysed the qualitative and quantitative aspects of health care pathways in patients with chronic pain. Over a period of 10 months, patients with the three most common chronic pain syndromes were recruited consecutively at pain clinics in Berlin, Germany. Patients provided information on their prior medical histories and various forms of therapies by means of standardised interviews, and completed specific questionnaires on pain and quality of life. This article reports on data from the retrospective part of the study. Results Out of 288 participants (mean age 51.8 years, 72% women) 136 suffered from headache, 99 from low back pain and 53 from neuropathic pain. Patients had a history of chronic pain ranging from 1 to 30 years. Chronicity according to Gerbershagen (grade I: 33%, grade II: 42%, grade III: 25%) was moderate. Complementary therapies were used by up to two-thirds of patients before admission. Up to 54% of the patients indicated an improvement in syndromes under complementary medicine. Conclusion Patients utilised various complementary treatment approaches and indicated substantial subjective responses. The utilisation patterns did not follow systematic treatment approaches or recommendations based on current guidelines. These data are only valid for the German health care system. Early integration of different treatment options that consider patients’ preferences might improve the outcome.

Ein Funftel bis ein Viertel der Allgemeinbevolkerung und mehr als drei Viertel der Tumorkranken mit Opioid-Dauermedikation leiden unter Obstipation. Somatische und funktionale Ursachen sind fur die Entstehung von Obstipation verantwortlich. Wenn moglich sollte die Therapie von Obstipation kausal sein, haufig ist aber eine symptomatische Therapie notwendig. Neben Allgemeinmasnahmen sind Laxanzien die wichtigste Therapieoption. Die Laxanzien werden nach ihren Wirkmechanismen klassifiziert und wurden aufgrund von Expertenmeinungen in ein Stufenschema eingruppiert, das sich in der klinischen Praxis bewahrt hat. Wahrend Lactulose das prophylaktisch wirksame Laxans der Wahl bei Nichttumorpatienten ist, ist Macrogol das Prophylaktikum der Wahl beim Tumorkranken mit Opioid-Dauermedikation. Beim Tumorkranken mit Opioid-Dauermedikation ist eine Laxanzientherapie zur Obstipationsprophylaxe obligat. Anwendungshinweise fur ausgesuchte Laxanzien sind in Tabelle 8 zusammengefasst.

No patient needs to have pain? Providing the best possible pain relief is as challenging for the anaesthesiologist as it is necessary for the patient's quality of life. The WHO algorithm allows sufficient and satisfactorty treatment of 90 % of all cancer patients. This case report describes alternatives to the WHO algorithm for the remaining 10 % of cases. The alternatives concern opioidrotation, intravenous administration, and neuroaxial application. Indications for these alternative strategies are either opiod-insensitive incidental pain or neuropathic pain. Procedure and complications are discussed with the reader.

OBJECTIVES: Unrelieved pain is a substantial public health concern necessitating improvements in medical education. The Advancing the Provision of Pain Education and Learning (APPEAL) study aimed to determine current levels and methods of undergraduate pain medicine education in Europe. DESIGN AND METHODS: Using a cross-sectional design, publicly available curriculum information was sought from all medical schools in 15 representative European countries in 2012-2013. Descriptive analyses were performed on: the provision of pain teaching in dedicated pain modules, other modules or within the broader curriculum; whether pain teaching was compulsory or elective; the number of hours/credits spent teaching pain; pain topics; and teaching and assessment methods. RESULTS: Curriculum elements were publicly available from 242 of 249 identified schools (97%). In 55% (133/242) of schools, pain was taught only within compulsory non-pain-specific modules. The next most common approaches were for pain teaching to be provided wholly or in part via a dedicated pain module (74/242; 31%) or via a vertical or integrated approach to teaching through the broader curriculum, rather than within any specific module (17/242; 7%). The curricula of 17/242 schools (7%) showed no evidence of any pain teaching. Dedicated pain modules were most common in France (27/31 schools; 87%). Excluding France, only 22% (47/211 schools) provided a dedicated pain module and in only 9% (18/211) was this compulsory. Overall, the median number of hours spent teaching pain was 12.0 (range 4-56.0 h; IQR: 12.0) for compulsory dedicated pain modules and 9.0 (range 1.0-60.0 h; IQR: 10.5) for other compulsory (non-pain specific) modules. Pain medicine was principally taught in classrooms and assessed by conventional examinations. There was substantial international variation throughout. CONCLUSIONS: Documented pain teaching in many European medical schools falls far short of what might be expected given the prevalence and public health burden of pain. The project was funded by Mundipharma International Ltd.

Neuropathic pain is a priority health issue [5], which currently is the topic of the 2014–2015 Global Year Against Neuropathic Pain campaign of the International Association for the Study of Pain (http://www.iasp-pain.org/GlobalYear/NeuropathicPain). Between 6% and 10% of adults are affected by chronic pain with neuropathic features [6,14,25], and this prevalence is significantly greater among individuals with specific conditions. For example, neuropathic pain is a common comorbidity in infectious diseases such as HIV, leprosy, and herpes zoster, and in non-infectious conditions such as diabetes mellitus, stroke, multiple sclerosis, and traumatic limb and spinal cord injury [7,13,16,19,21]. The pain is associated with significant decreases in quality of life and socioeconomic well-being, even more so than non-neuropathic chronic pain [9,20,22]. Developing and emerging countries share the greatest burden of conditions that predispose to development of neuropathic pain [5,10], and can ill afford the negative consequences of this pain. There are medicines with proven efficacy in the treatment of neuropathic pain [11,12]. Nevertheless, the pain can be difficult to treat, with significant inter-individual variation in efficacy within and between drug classes, independent of the presumed aetiology of the neuropathy [2,4]. Effective management of neuropathic pain within a population therefore requires access to a small, but crucial group of drug classes with proven efficacy. The World Health Organization’s (WHO) model list of essential medicines (http://www.who.int/selection_medicines/list/en/) presents those medicines deemed necessary to meet priority health needs, and local implementation of essential medicines policies is associated with improved quality use of medicines [15,18]. But, none of the analgesic medicines included in the WHO model list are recommended as first-line treatments for neuropathic pain [11]. Thus the WHO model list is not a good framework from which national policies on managing neuropathic pain can be structured and countries routinely adapt the model list according to local needs and resources [18]. To estimate the nominal availability of medicines recommended for the treatment of neuropathic pain in developing and emerging countries, we assessed national essential medicines lists (NEMLs) for the inclusion of recommended treatments. We also assessed whether the coverage of recommended drugs classes on these NEMLs was dependent on countries’ economic status.

In this Letter, we present a method for calculating transport properties of molecular conductors using a time-independent scattering approach based on Green’s functions with absorbing boundaries. The method, which has been used before for chemical reaction dynamics in a grid basis [Seideman, Miller, J. Chem. Phys. 96 (1992) 4412], is formulated here in an LCAO-MO form within simple Huckel theory and extended Huckel theory (EHT), respectively. Test calculations are for a quasi-one-dimensional atom chain. As a more realistic application, the organic molecules benzene-1,4-dithiolate and biphenyl-4,4′-dithiolate between gold electrodes are studied.

Short term hyperglycemia has previously been shown to induce a blood flow increase in the retina. The mechanism behind this effect is poorly understood. We set out to investigate whether exercise-induced hyperlactatemia may alter the response of retinal blood flow to hyperglycemia.We performed a randomized, controlled two-way cross over study comprising 12 healthy subjects, performed a 6-minutes period of dynamic exercise during an euglcaemic or hyperglycaemic insulin clamp. Retinal blood flow was assessed by combined vessel size measurement with the Zeiss retinal vessel analyzer and measurement of red blood cell velocities using bi-directional laser Doppler velocimetry. Retinal and systemic hemodynamic parameters were measured before, immediately after and 10 and 20 minutes after isometric exercise.On the euglycemic study day retinal blood flow increased after dynamic exercise. The maximum increase in retinal blood flow was observed 10 minutes after the end of exercise when lactate plasma concentration peaked. Hyperglycemia increased retinal blood flow under basal conditions, but had no incremental effect during exercise induced hyperlactatemia.Our results indicate that both lactate and glucose induce an increase in retinal blood flow in healthy humans. This may indicate a common pathway between glucose and lactate induced blood flow changes in the human retina.

Twenty consecutive patients suffering from myofascial pain dysfunction (MPD) were assigned to a waiting-list, serving as a no-treatment control period. Inclusion criteria were: (i) pain in the temporomandibular region for at least 3 months, (ii) no evidence of internal derangement or osteoarthritis and (iii) symptoms of postural dysfunction. Treatment consisted of active and passive jaw movement exercises, correction of body posture and relaxation techniques. The following main outcome measures were evaluated: (i) pain at rest, (ii) pain at stress, (iii) impairment, (iv) mouth opening at base-line, before and after treatment and at 6-month follow-up. All patients completed the study and no adverse effects occurred. During control period no significant changes occurred. After treatment six patients had no pain at all (chi-square: P

Management of post-operative pain is unsatisfactory worldwide. An estimated 240 million patients undergo surgery each year. Forty to 60% of these patients report clinically significant pain. Discrepancy exists between availability of evidence-based medicine (EBM)-derived knowledge about management of perioperative pain and increased implementation of related practices versus lack of improvement in patient-reported outcomes (PROs). We aimed to assist health care providers to optimize perioperative pain management by developing and validating a medical registry that measures variability in care, identifies best pain management practices and assists clinicians in decision making.PAIN OUT was established from 2009 to 2012 with funding from the European Commission. It now continues as a self-sustaining, not-for-profit project, targeting health care professionals caring for patients undergoing surgery.The growing registry includes data from 40 898 patients, 60 hospitals and 17 countries. Collaborators upload data (demographics, clinical, PROs) from patients undergoing surgery in their hospital/ward into an Internet-based portal. Two modules make use of the data: (1) online, immediate feedback and benchmarking compares PROs across sites while offline analysis permits in-depth analysis; and (2) the case-based clinical decision support system offers practice-based treatment recommendations for individual patients; it is available now as a prototype. The Electronic Knowledge Library provides succinct summaries on perioperative pain management, supporting knowledge transfer and application of EBM.PAIN OUT, a large, growing international registry, allows use of 'real-life' data related to management of perioperative pain. Ultimately, comparative analysis through audit, feedback and benchmarking will improve quality of care.

Der maligne Knochenschmerz wird vom Patienten als gut umschrieben und leicht lokalisierbar angegeben. Die am haufigsten verwendeten Schmerzbeschreibungen sind „stechend“, „bohrend“ und „dumpf“. Ein wichtiger Hinweis ist die Belastungsabhangigkeit der Schmerzen. Die WHO-Stufenleiter zur Kontrolle des malignen Knochenschmerzes ist oft unzureichend. Ursachlich ist die Belastungsabhangigkeit der Schmerzen. Ein Analgesieniveau, das ausreichend fur die Schmerzspitzen ware, fuhrt zu relativer Uberdosierung in Phasen der Ruhe. Deshalb gehort neben einer adaquaten Basistherapie in das Therapiekonzept eine schnell anflutende Bedarfsmedikation. Transmukosale Fentanylpraparationen sind eine gute Alternative zur oralen Bedarfsmedikation. Bei Versagen sind die intravenose Therapie via Portsystem, ggf. die Addition von Ketamin oder die ruckenmarksnahe Applikation via Kathetersystem wirksame Optionen.

The background and purpose of this investigation was to evaluate the use of a treatment protocol which included active and passive jaw movements, manual therapy techniques, correction of body posture, and relaxation techniques for the treatment of temporomandibular joint (TMJ) osteoarthrosis (OA). Twenty consecutive patients suffering from TMJ OA participated in this study.a. pain in the temporomandibular region; b. symptoms lasting at least three months; and c. radiologically proven OA. All patients were assigned to a waiting list, serving as a no treatment control period. Nineteen patients completed the study. No adverse effects occurred. During the control period (mean duration 35 days), the parameters did not change significantly. After treatment (mean duration 46 days) pain, impairment, and incisal edge clearance improved significantly (Wilcoxon test p0.001). At follow-up, pain and impairment were further reduced. The number of patients experiencing no pain at rest (80%), chi-square test p = 0.02) and stress (47%), chi-square test p = 0.03), and no impairment (37%), chi-square test p = 0.05) increased significantly. This therapeutic treatment protocol seems to be useful treatment for the symptoms of clinical dysfunction in OA of the TMJ.