Megathrust earthquake drives drastic organic carbon supply to the hadal trench.

The giant 2011 Tohoku-oki earthquake has been inferred to remobilise fine-grained, young surface sediment enriched in organic matter from the slope into the >7 km deep Japan Trench. Yet, this hypothesis and assessment of its significance for the carbon cycle has been hindered by limited data density and resolution in the hadal zone. Here we combine new high-resolution bathymetry data with sub-bottom profiler images and sediment cores taken during 2012-2016 in order to map for the first time the spatial extent of the earthquake-triggered event deposit along the hadal Japan Trench. We quantify a sediment volume of ~0.2 km3 deposited from spatially-widespread remobilisation of young surficial seafloor slope sediments triggered by the 2011 earthquake and its aftershock sequence. The mapped volume and organic carbon content in sediment cores encompassing the 2011 event reveals that this single tectonic event delivered >1 Tg of organic carbon to the hadal trench. This carbon supply is comparable to high carbon fluxes described for other Earth system processes, shedding new light on the impact of large earthquakes on long-term carbon cycling in the deep-sea.

Emergent biomarker derived from next-generation sequencing to identify pain patients requiring uncommonly high opioid doses.

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.

Combinatorial refinement of thin-film microstructure, properties and process conditions: iterative nanoscale search for self-assembled TiAlN nanolamellae.

Because of the tremendous variability of crystallite sizes and shapes in nano-materials, it is challenging to assess the corresponding size-property relationships and to identify microstructures with particular physical properties or even optimized functions. This task is especially difficult for nanomaterials formed by self-organization, where the spontaneous evolution of microstructure and properties is coupled. In this work, two compositionally graded TiAlN films were (i) grown using chemical vapour deposition by applying a varying ratio of reacting gases and (ii) subsequently analysed using cross-sectional synchrotron X-ray nanodiffraction, electron microscopy and nanoindentation in order to evaluate the microstructure and hardness depth gradients. The results indicate the formation of self-organized hexagonal-cubic and cubic-cubic nanolamellae with varying compositions and thicknesses in the range of ∼3-15 nm across the film thicknesses, depending on the actual composition of the reactive gas mixtures. On the basis of the occurrence of the nanolamellae and their correlation with the local film hardness, progressively narrower ranges of the composition and hardness were refined in three steps. The third film was produced using an AlCl3/TiCl4 precursor ratio of ∼1.9, resulting in the formation of an optimized lamellar microstructure with ∼1.3 nm thick cubic Ti(Al)N and ∼12 nm thick cubic Al(Ti)N nanolamellae which exhibits a maximal hardness of ∼36 GPa and an indentation modulus of ∼522 GPa. The presented approach of an iterative nanoscale search based on the application of cross-sectional synchrotron X-ray nanodiffraction and cross-sectional nanoindentation allows one to refine the relationship between (i) varying deposition conditions, (ii) gradients of microstructure and (iii) gradients of mechanical properties in nanostructured materials prepared as thin films. This is done in a combinatorial way in order to screen a wide range of deposition conditions, while identifying those that result in the formation of a particular microstructure with optimized functional attributes.

[Cross-sectional subject 14--training in pain]. / Querschnittsfach 14--Lehre zum Thema Schmerz.

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.

[Multimodal therapy programs for chronic pain]. / Multimodale Therapieprogramme für chronische Schmerzen.

Chronic pain is a common and disabling disorder with major consequences for patient quality of life and it is also a major economic burden to society. The management of chronic pain comprises a large range of different intervention strategies including pharmacological therapy, non-medicinal and invasive therapeutic options. While non-pharmacological and multimodal options are underused, monomodal options, especially pharmacotherapy and invasive therapies are overused. The effectiveness of multidisciplinary and multimodal treatment programs including physical and rehabilitation interventions and psychological treatment has been extensively studied in the last two decades. Evidence from randomized controlled trials demonstrates that there is low quality evidence for the effectiveness of exercise therapy alone, there is some evidence for the effectiveness of behavioral therapy and there is at least moderate evidence for the effectiveness of multidisciplinary and multimodal treatment and other active treatment reducing pain and increasing functional capacity at short and intermediate term. Therefore, blanket coverage with provision of adequate treatment programs for chronic pain as well as studies evaluating the best composition of treatment elements are needed. The characteristics of chronic pain, the necessary assessment procedures and treatment types are described.

[Medical educational evaluation of the German Pain Congress 2012. In the context of the CanMEDS physician competency framework]. / Deutscher Schmerzkongress 2012 aus medizindidaktischer Sicht. Bewertung unter Berücksichtigung der im Rahmenmodell CanMEDS definierten Arztrollen.

BACKGROUND: Professionals in the medical field are expected to participate in continuing medical education in the sense of lifelong learning. The authors took this occasion to evaluate the most important national convention in pain medicine concerning its role in medical education. MATERIAL AND METHODS: The participants of the 37th German Pain Congress (17-20 October 2012 in Mannheim) were asked to complete a questionnaire concerning content and design of the convention. The aim of this study was to analyze the distribution of different physician competencies in the program. For this purpose the congress program was analyzed with respect to the various medical role models as defined in the Canadian medical education directions for specialists (CanMEDS) framework. RESULTS: The participants considered the quality of the different sessions of the German Pain Congress to be good. The poster sessions were considered to be the second most important educational format in the congress following the live sessions. Concerning the content of the congress the participants wished more emphasis on the role of interprofessional partners, such as nursing and psychotherapy. The CanMEDS physician roles of manager, communicator, health advisor and professional paragon were underrepresented in the congress program in this study. CONCLUSION: Regarding content and educational value, the congress design could benefit from additional Praktikerseminaren (practical seminars). The role of interprofessional partners should be more emphasized. In addition the program could become more attractive through a more balanced distribution of the CanMEDS roles.

[Pain medicine as a cross-sectional subject in German medical schools. An opportunity for general pain management]. / Das Querschnittsfach "Schmerzmedizin". Chance für die Allgemeine Schmerzmedizin.

BACKGROUND: Unrelieved pain is a substantial public health concern owing in part to deficits in clinical expertise among physicians. In most medical faculties worldwide, teaching on pain and pain management is either nonexistent or limited to a small number of students attending voluntary courses. In light of the fact that pain is the most frequent reason to seek medical advice, the lack of formal training of pain medicine is considered the leading reason for inadequate pain management. Therefore, the patients' unmet needs for adequate diagnosis and therapy call for action. SITUATION: Pain assessment and effective pain management should be a priority in the health care system. The limited number of pain specialists available in hospitals and primary care and CME (continuous medical education) activities focusing on pain are not sufficient to solve the problem. Every practicing physician should, therefore, have basic knowledge of the most prominent painful conditions and management strategies. To achieve this goal, pain medicine should become an integral part of the undergraduate curriculum for medical students. In Germany, pain medicine became a mandatory subject in undergraduate medical studies in 2012. PERSPECTIVE: The introduction of pain medicine into the undergraduate curriculum in Germany is a major challenge regarding the development and implementation processes. This article describes current instruments and implementation strategies for pain medicine as a new cross-sectional subject in Germany.

Dermoscopy of acral melanoma: a multicenter study on behalf of the international dermoscopy society.

BACKGROUND: Most studies on dermoscopy of acral lesions were conducted in Asian populations. In this study, we analyzed these features in a predominantly Caucasian population. OBJECTIVE: Estimate the prevalence of dermoscopic features in acral lesions, and assess their level of agreement between observers. METHODS: In this retrospective multicenter study, 167 acral lesions (66 melanomas) were evaluated for 13 dermoscopic patterns by 26 physicians, via a secured Internet platform. RESULTS: Parallel furrow pattern, bizarre pattern, and diffuse pigmentation with variable shades of brown had the highest prevalence. The agreement for lesion patterns between physicians was variable. Agreement was dependent on the level of diagnostic difficulty. CONCLUSION: Lesions with a diameter >1 cm were more likely to be melanoma. We found as well that a benign pattern can be seen in parts of melanomas. For this reason one should evaluate an acral lesion for the presence of malignant patterns first.

Palliative Care teaching in Germany - concepts and future developments.

BACKGROUND: Following recent modifications of the Medical Licensure Act (ÄApprO) in the year 2009, palliative care was introduced as a compulsory 13(th) cross-disciplinary subject (Q13) in the undergraduate curriculum. Its implementation must have taken place before the beginning of the final year ('practical year') in August 2013 and has to be substantiated for the medical exams taking place in October 2014. Very diverse structures pertaining to palliative care teaching were described in previous surveys at various medical faculties in Germany. As a result, the current and future plans and concepts related to content and exams of a mandatory Q13 course at the respective faculty sites should be ascertained. METHODS: Since 2006, the German Medical Students' Association (bvmd) has been carrying out a bi-annual survey at all medical faculties in Germany regarding the current situation of teaching in the field of palliative care. After designing and piloting an online survey in May 2010, a one-month online survey took place. The data was assessed using a descriptive approach. RESULTS: 31 of 36 medical faculties took part in the survey. At the time of questioning, 15 faculties already taught courses according to the requirements of the new ÄApprO; at three sites the Q13 is yet to be introduced commencing in 2012. A teaching curriculum for Q13 already existed at 15 faculty sites, partly based on the curricular requirements of the German Association for Palliative Medicine (DGP). Six sites described an implementation process as yet without an independent curriculum. Most of the faculties aim for 21-40 course hours, which will for the most part be provided as lectures, seminars or less often in more assisted and intense formats. The majority of the participating faculties intend an examination containing multiple choice questions. At 8 universities there is an independent Chair for palliative medicine (5 more are planned); this was linked with a higher degree of mandatory teaching in alignment with the requirements of the ÄApprO. A broad spectrum of educationally-involved occupational groups, specialist disciplines and external co-operating partners, were mentioned. CONCLUSION: The infrastructural prerequisites of the present curricular concepts and the degree of implementation of the Q13 according to the requirements of the new ÄApprO diverge significantly among the various medical faculties. The efforts made to produce a qualitatively high standard of teaching with regard to the multifaceted questions concerning the support for severely and terminally ill patients is as much reflected in the survey, as the special implications of an independent Chair for palliative medicine for the implementation of the requirements by law. The participation of various occupational groups in this survey as well as the broad spectrum of those involved highlights the interdisciplinary and multi-professional dimension of teaching in palliative care.

Feasibility of international data collection and feedback on post-operative pain data: proof of concept.

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.

Correlation of in vitro and in vivo models for the oral absorption of peptide drugs.

The aim of this study was to evaluate two in vitro models, Caco-2 monolayer and rat intestinal mucosa, regarding their linear correlation with in vivo bioavailability data of therapeutic peptide drugs after oral administration in rat and human. Furthermore the impact of molecular mass (Mm) of the according peptides on their permeability was evaluated. Transport experiments with commercially available water soluble peptide drugs were conducted using Caco-2 cell monolayer grown on transwell filter membranes and with freshly excised rat intestinal mucosa mounted in Using type chambers. Apparent permeability coefficients (P (app)) were calculated and compared with in vivo data derived from the literature. It was shown that, besides a few exceptions, the Mm of peptides linearly correlates with permeability across rat intestinal mucosa (R (2) = 0.86; y = -196.22x + 1354.24), with rat oral bioavailability (R (2) = 0.64; y = -401.90x + 1268.86) as well as with human oral bioavailability (R (2) = 0.91; y = -359.43x + 1103.83). Furthermore it was shown that P (app) values of investigated hydrophilic peptides across Caco-2 monolayer displayed lower permeability than across rat intestinal mucosa. A correlation between P (app) values across rat intestinal mucosa and in vivo oral bioavailability in human (R (2) = 0.98; y = 2.11x + 0.34) attests the rat in vitro model to be a very useful prediction model for human oral bioavailability of hydrophilic peptide drugs. Presented correlations encourage the use of the rat in vitro model for the prediction of human oral bioavailabilities of hydrophilic peptide drugs.

The significance of multiple blue-grey dots (granularity) for the dermoscopic diagnosis of melanoma.

BACKGROUND: The presence of multiple blue-grey dots (MBGD) is widely used by clinicians to decide if a pigmented lesion should be removed, but only little is known about their significance. OBJECTIVES: To evaluate the significance of MBGD for the dermoscopic diagnosis of melanoma. METHODS: In part 1 we retrospectively evaluated 340 pigmented lesions for the presence and morphological appearance of granularity. One hundred and seventy melanomas were included and matched with 170 benign and dysplastic naevi which were randomly chosen from our collection. In part 2, 3773 lesions were examined prospectively in at-risk patients: all lesions with granularity were recorded, surgically removed and subjected to histopathological examination. RESULTS: In part 1, granularity was found in 26.5% of the benign lesions and 93.5% of melanomas. The presence of granularity, granularity at the periphery, irregularly distributed granularity and granularity in association with red and white colour were statistically highly significant for the diagnosis of melanoma (P < 0.001). In part 2, granularity was found in 1.08% of the 3773 lesions and more frequently in sun-damaged skin. Sensitivity for the diagnosis of melanoma was 85% and specificity 99%. CONCLUSIONS: After the revision of many lesions with MBGD, we concluded that the term 'granularity' better describes this entity. Lesions with irregular granularity (periphery, irregularly distributed) should be removed especially if they are associated with red, blue or white colour. Lesions with a benign dermoscopy pattern which have granularity with a regular appearance and involving only a small portion of the lesion do not require surgical excision.

Three-point checklist of dermoscopy: an open internet study.

BACKGROUND: In a pilot study, the three-point checklist of dermoscopy has been shown to represent a valid and reproducible tool with high sensitivity for the diagnosis of skin cancer in the hands of a small group of nonexperts. OBJECTIVES: To re-evaluate these preliminary results in a large number of observers independently from their profession and expertise in dermoscopy. METHODS: The study was conducted via the internet to provide worldwide access for participants. After a short web-based tutorial, the participants evaluated dermoscopic images of 165 (116 benign and 49 malignant) skin lesions (15 training and 150 test lesions). For each lesion participants scored the presence of the three-point checklist criteria (asymmetry, atypical network and blue-white structures). Kappa values, odds ratios, sensitivity, specificity and likelihood ratios were estimated. RESULTS: Overall, 150 participants joined the study. The three-point checklist showed good interobserver reproducibility (kappa value: 0.53). Sensitivity for skin cancer (melanoma and basal cell carcinoma) was 91.0% and this value remained basically uninfluenced by the observers' professional profile. Only 20 participants lacking any experience in dermoscopy performed significantly more poorly, but the sensitivity was still remarkably high (86.7%) when considering that they were untrained novices in dermoscopy. The specificity was 71.9% and was significantly influenced by the profession, with dermatologists performing best. CONCLUSIONS: Our study confirms that the three-point checklist is a feasible, simple, accurate and reproducible skin cancer screening tool.

[Pain management in gastrointestinal oncology]. / Schmerztherapie in der gastroenterologischen Onkologie.

Abdominal cancer is commonly associated with pain needing medical attention. Effective pain management is available to control pain. Oral opioids are the foundation of analgesic therapy. With adequate implementation of therapeutic guidelines into clinical practice including the use of co-analgesics, adjuvants and non-pharmacological treatment options the quality of life of abdominal cancer patients can be considerably improved. Only in a minority of patients with refractory pain more sophisticated options of pain management will be necessary, e. g., epidural, intrathecal or neurolytic techniques. In this situation the consultation of a pain therapist is recommended.