Schnidejoch und Lötschenpass. Archäologische Forschungen in den Berner Alpen. Schnidejoch et Lötschenpass. Investigations archéologiques dans les Alpes bernoises.

Archäologie in den Hochalpen: Vom Rückgang der Gletscher sind auch archäologische Objekte betroffen. Über Jahrtausende hinweg haben sie im Eis überdauert, nun kommen sie zum Vorschein. Im Hitzesommer 2003 fand eine Wanderin am Schnidejoch ein fremdartiges Objekt aus Birkenrinde. Es erwies sich als Teil eines 4800 Jahre alten Bogenfutterals. In den Jahren 2004 bis 2011 unternahm der Archäologische Dienst des Kantons Bern über 30 Begehungen der Nordseite und – zusammen mit der Walliser Kantonsarchäologie – auch der Südseite des Schnidejochs. Zahlreiche weitere Funde aus Holz, Leder und Metall konnten geborgen und wissenschaftlich untersucht werden. Einzigartige Funde Zu den spektakulärsten Funden vom Schnidejoch zählt das Bogenfutteral aus Birkenrinde. Weiter stechen aus den rund 900 Funden ein Pfeilbogen, mehrere vollständige Pfeile und Fragmente einer Schale aus Ulmenholz hervor. Es handelt sich dabei um das älteste Holzgefäss der Schweiz. Weitere herausragende Funde sind ein bronzezeitliches Holzgefäss aus Birkenrinde, eine bronzezeitliche Gewandnadel sowie Bekleidung und Schuhe aus Leder. Archéologie dans les Alpes bernoises Le recul des glaciers a aussi un impact sur les découvertes archéologiques. Il fait réapparaître des objets préservés dans les glaces depuis des millénaires. Pendant l’été caniculaire de 2003, une randonneuse a découvert un objet singulier en écorce de bouleau, qui s’est avéré être un morceau de carquois vieux de 4800 ans. De 2004 à 2011, le Service archéologique du canton de Berne s’est rendu plus de trente fois sur le versant nord du Schnidejoch et, en collaboration avec le Service d’archéologie du canton du Valais, sur le versant sud de ce col. De nombreux autres objets en bois, cuir et métal ont pu être mis au jour et étudiés scientifiquement. Des découvertes uniques Le carquois en écorce de bouleau constitue l’une des découvertes les plus sensationnelles du Schnidejoch. Parmi les quelque 900 objets mis au jour figurent un arc, plusieurs flèches complètes et les fragments d’un bol en bois d’orme. Ce bol est le plus ancien récipient en bois de Suisse. D’autres trouvailles spectaculaires ont été faites, notamment un récipient en écorce de bouleau et une épingle à vêtements datant de l’Âge du Bronze ainsi que des vêtements et des chaussures en cuir.

Dihydropyrimidinase and β-ureidopropionase gene variation and severe fluoropyrimidine-related toxicity

AIMS To assess the association of DPYS and UPB1 genetic variation, encoding the catabolic enzymes downstream of dihydropyrimidine dehydrogenase, with early-onset toxicity from fluoropyrimidine-based chemotherapy. PATIENTS & METHODS The coding and exon-flanking regions of both genes were sequenced in a discovery subset (164 patients). Candidate variants were genotyped in the full cohort of 514 patients. RESULTS & CONCLUSIONS Novel rare deleterious variants in DPYS (c.253C > T and c.1217G > A) were detected once each in toxicity cases and may explain the occurrence of severe toxicity in individual patients, and associations of common variants in DPYS (c.1-1T > C: padjusted = 0.003; OR = 2.53; 95% CI: 1.39-4.62, and c.265-58T > C: padjusted = 0.039; OR = 0.61; 95% CI: 0.38-0.97) with 5-fluorouracil toxicity were replicated.

Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children

AIM To identify novel variants associated with anthracycline-induced cardiotoxicity and to assess these in a genotype-guided risk prediction model. PATIENTS & METHODS Two cohorts treated for childhood cancer (n = 344 and 218, respectively) were genotyped for 4578 SNPs in drug ADME and toxicity genes. RESULTS Significant associations were identified in SLC22A17 (rs4982753; p = 0.0078) and SLC22A7 (rs4149178; p = 0.0034), with replication in the second cohort (p = 0.0071 and 0.047, respectively). Additional evidence was found for SULT2B1 and several genes related to oxidative stress. Adding the SLC22 variants to the prediction model improved its discriminative ability (AUC 0.78 vs 0.75 [p = 0.029]). CONCLUSION Two novel variants in SLC22A17 and SLC22A7 were significantly associated with anthracycline-induced cardiotoxicity and improved a genotype-guided risk prediction model, which could improve patient risk stratification.

VIRTOPSY--scientific documentation, reconstruction and animation in forensic: individual and real 3D data based geo-metric approach including optical body/object surface and radiological CT/MRI scanning.

Until today, most of the documentation of forensic relevant medical findings is limited to traditional 2D photography, 2D conventional radiographs, sketches and verbal description. There are still some limitations of the classic documentation in forensic science especially if a 3D documentation is necessary. The goal of this paper is to demonstrate new 3D real data based geo-metric technology approaches. This paper present approaches to a 3D geo-metric documentation of injuries on the body surface and internal injuries in the living and deceased cases. Using modern imaging methods such as photogrammetry, optical surface and radiological CT/MRI scanning in combination it could be demonstrated that a real, full 3D data based individual documentation of the body surface and internal structures is possible in a non-invasive and non-destructive manner. Using the data merging/fusing and animation possibilities, it is possible to answer reconstructive questions of the dynamic development of patterned injuries (morphologic imprints) and to evaluate the possibility, that they are matchable or linkable to suspected injury-causing instruments. For the first time, to our knowledge, the method of optical and radiological 3D scanning was used to document the forensic relevant injuries of human body in combination with vehicle damages. By this complementary documentation approach, individual forensic real data based analysis and animation were possible linking body injuries to vehicle deformations or damages. These data allow conclusions to be drawn for automobile accident research, optimization of vehicle safety (pedestrian and passenger) and for further development of crash dummies. Real 3D data based documentation opens a new horizon for scientific reconstruction and animation by bringing added value and a real quality improvement in forensic science.

3D documentation and visualization of external injury findings by integration of simple photography in CT/MRI data sets (IprojeCT).

This study evaluated the feasibility of documenting patterned injury using three dimensions and true colour photography without complex 3D surface documentation methods. This method is based on a generated 3D surface model using radiologic slice images (CT) while the colour information is derived from photographs taken with commercially available cameras. The external patterned injuries were documented in 16 cases using digital photography as well as highly precise photogrammetry-supported 3D structured light scanning. The internal findings of these deceased were recorded using CT and MRI. For registration of the internal with the external data, two different types of radiographic markers were used and compared. The 3D surface model generated from CT slice images was linked with the photographs, and thereby digital true-colour 3D models of the patterned injuries could be created (Image projection onto CT/IprojeCT). In addition, these external models were merged with the models of the somatic interior. We demonstrated that 3D documentation and visualization of external injury findings by integration of digital photography in CT/MRI data sets is suitable for the 3D documentation of individual patterned injuries to a body. Nevertheless, this documentation method is not a substitution for photogrammetry and surface scanning, especially when the entire bodily surface is to be recorded in three dimensions including all external findings, and when precise data is required for comparing highly detailed injury features with the injury-inflicting tool.

Usage of Complementary Medicine in Switzerland: Results of the Swiss Health Survey 2012 and Development Since 2007

Background Complementary medicine (CM) is popular in Switzerland. Several CM methods (traditional Chinese medicine/acupuncture, homeopathy, anthroposophic medicine, neural therapy, and herbal medicine) are currently covered by the mandatory basic health insurance when performed by a certified physician. Treatments by non-medical therapists are partially covered by a supplemental and optional health insurance. In this study, we investigated the frequency of CM use including the evolvement over time, the most popular methods, and the user profile. Methods Data of the Swiss Health Surveys 2007 and 2012 were used. In 2007 and 2012, a population of 14,432 and 18,357, respectively, aged 15 years or older answered the written questionnaire. A set of questions queried about the frequency of use of various CM methods within the last 12 months before the survey. Proportions of usage and 95% confidence intervals were calculated for these methods and CM in general. Users and non-users of CM were compared using logistic regression models. Results The most popular methods in 2012 were homeopathy, naturopathy, osteopathy, herbal medicine, and acupuncture. The average number of treatments within the 12 months preceding the survey ranged from 3 for homeopathy to 6 for acupuncture. 25.0% of the population at the age of 15 and older had used at least one CM method in the previous 12 months. People with a chronic illness or a poor self-perceived health status were more likely to use CM. Similar to other countries, women, people of middle age, and those with higher education were more likely to use CM. 59.9% of the adult population had a supplemental health insurance that partly covered CM treatments. Conclusions Usage of CM in Switzerland remained unchanged between 2007 and 2012. The user profile in Switzerland was similar to other countries, such as Germany, United Kingdom, United States or Australia.

Non-Contact Documentation of Physical Characteristics of Ecstasy Tablets, Hemp Coins, and Imprint Punches by using 3D Optical Surface Scanning

The description of seized illicit ecstasy tablets and other pressed drug products is an important step in casework. The physical and visual analysis and the description of the characteristics can be employed for intelligence purposes. Besides photography and manual measurements of dimensions, some optical instruments are employed for detailed measurements of physical characteristics. In this work, the method of 3D surface digitizing is introduced as a suitable tool for highly accurate documentation of small objects, especially for pressed drug products. The resulting detailed information about the geometry, and the results of an automatic comparison of apparently uniform tablets and coins with punches, can support drug intelligence.

Virtopsy in der Unfallrekonstruktion

Mit der Virtopsy hat das Institut für Rechtmedizin der Universität Bern unter Prof. Dr. med. R. Dirnhofer und Prof. Dr. med. M. Thali die Rechtsmedizin über die ganze Welt revolutioniert. Obwohl einzelne Techniken, aus dem klinischen Medizinalltag stammend, bereits zu früherer Zeit im einen oder andere Autopsie-Saal bereits zur Anwendung kamen, waren es die Berner Rechtsmediziner, Radiologen und Ingenieure, welche diese kombinierten. Unter dem Begriff Virtopsy vereint sich die Nutzung von medizinischen bildgebenden Verfahren mit dem Erfassen der Körperoberfläche mittels 3D-Oberflächenscanning. Dadurch hat Virtopsy, nebst den rekonstruktiven Möglichkeiten, ein immenses Potential für die Dokumentation sowohl vom Verstorbenen als auch von Verletzungen von Lebenden. Gerade mittels der räumlichen Darstellung von inneren Verletzungen und Frakturen können diese für den medizinischen Laien optimal dargestellt und verständlich gemacht werden. Bei der Klärung von Verkehrsunfällen, insbesondere bei Kollisionen von Motorfahrzeugen mit Fussgängern oder Zweiradfahrern - gegenüber welchen der Mensch besonders exponiert und verletzlich ist - aber auch zur Klärung von Verletzungen an Fahrzeuginsassen, zeigen sich die rekonstruktiven Möglichkeiten von Virtopsy. Dabei gilt zu beachten, dass die 3D-Dokumentation mittels den erwähnten Verfahren eine Akquisition von digitalen Daten, nicht automatisch eine vollständige Auswertung zur Folge haben muss. Trotzdem zeigt sich, dass viele offene Fragen erst im Nachhinein auftreten, wenn die Befunde und Spuren nicht mehr zugänglich sind. Die mittels Virtopsy erhobenen digitalen Daten lassen sich jedoch zu jedem Zeitpunkt neu befunden oder weiter bearbeiten und können auch in Zukunft zur Klärung eines Unfallereignisses beitragen.

Wer lenkte den PW?

Die Rekonstruktion von Verkehrsunfällen ist ein interdisziplinäres Arbeitsgebiet. Verschiedene Institutionen wie z.B. die Polizei, die Rechtsmedizin oder die Unfallanalyse befassen sich mit der Beantwortung von juristischen Fragestellungen bei Verkehrsunfällen. Die modernen 3D-Dokumentations- und Analysemethoden und der Einsatz der bildgebenden Verfahren in der Rechtsmedizin ermöglichen eine disziplinübergreifende Auswertung der vorhandenen Spuren und Befunde und eröffnen damit ganz neue Horizonte und Dimensionen. Zudem ermöglichen sie es auch dem technischen Laien, eine bildliche Vorstellung der komplexen unfalldynamischen Abläufe zu geben. Im vorliegenden Beitrag wird anhand eines Falles die interdisziplinäre Fallanalyse und morphometrische 3D-Rekonstruktion vorgestellt und erläutert. Dieser Fall wurde Jahre nach dem Ereignis in Auftrag gegeben zur Klärung der Frage, wer den PW zum Unfallzeitpunkt gelenkt hatte. Die morphometrische 3D-Rekonstruktion umfasst die Ermittlung des Unfallhergangs, des biomechanischen Verhaltens der Fahrzeuginsassen und der Entstehung ihrer Verletzungen sowie der Entstehung der Blutspuren und weiterer Spuren und Beschädigungen im Fahrzeuginneren. Die Fahrzeuginsassen werden mittels Photogrammetrie und optischem 3D-Oberflächenscanning dreidimensional dokumentiert. Von verletzten Insassen werden zusätzlich die Daten klinischer radiologischer Untersuchungen von verstorbenen die vor der Obduktion durchgeführte Computertomographie (CT) und Magnetresonanztomographie (MRT) in die 3D-Analyse integriert. Das Fahrzeug und alle unfallrelevanten Objekte werden ebenfalls mittels Photogrammetrie und 3D-Oberflächenscanning erfasst. Ein 3D- Situationsplan der Örtlichkeit mit allen Spuren wird von der Polizei mittels Photogrammetrie und Laserscanning erstellt und in die Auswertung integriert. Anhand dieser 3D-Daten, insbesondere der Spuren am Unfallort und der Beschädigungen des Fahrzeuges, wird der Unfallablauf und daraus resultierend das biomechanische Verhalten der Fahrzeuginsassen rekonstruiert und in der Animationssoftware 3DS Max Design nachgestellt. Basierend auf den gewonnenen Erkenntnissen können morphometrische Vergleiche der Verletzungen mit den relevanten Strukturen im Fahrzeuginneren durchgeführt und so ermittelt werden, wie diese Verletzungen entstanden sind und auf welchen Sitzen die Insassen während des Unfalles sassen. Neben den Verletzungen können auch die Körpergrössen der Insassen Hinweise zur Ermittlung des Lenkers geben. Die Möglichkeiten der morphometrischen Rekonstruktion mittels der 3D-Techniken sind weitreichend und können oft entscheidende Erkenntnisse für das Ermittlungsverfahren liefern.

Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis of individual patient data

BACKGROUND The best-known cause of intolerance to fluoropyrimidines is dihydropyrimidine dehydrogenase (DPD) deficiency, which can result from deleterious polymorphisms in the gene encoding DPD (DPYD), including DPYD*2A and c.2846A>T. Three other variants-DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A-have been associated with DPD deficiency, but no definitive evidence for the clinical validity of these variants is available. The primary objective of this systematic review and meta-analysis was to assess the clinical validity of c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity. METHODS We did a systematic review of the literature published before Dec 17, 2014, to identify cohort studies investigating associations between DPYD c.1679T>G, c.1236G>A/HapB3, and c.1601G>A and severe (grade ≥3) fluoropyrimidine-associated toxicity in patients treated with fluoropyrimidines (fluorouracil, capecitabine, or tegafur-uracil as single agents, in combination with other anticancer drugs, or with radiotherapy). Individual patient data were retrieved and analysed in a multivariable analysis to obtain an adjusted relative risk (RR). Effect estimates were pooled by use of a random-effects meta-analysis. The threshold for significance was set at a p value of less than 0·0167 (Bonferroni correction). FINDINGS 7365 patients from eight studies were included in the meta-analysis. DPYD c.1679T>G was significantly associated with fluoropyrimidine-associated toxicity (adjusted RR 4·40, 95% CI 2·08-9·30, p<0·0001), as was c.1236G>A/HapB3 (1·59, 1·29-1·97, p<0·0001). The association between c.1601G>A and fluoropyrimidine-associated toxicity was not significant (adjusted RR 1·52, 95% CI 0·86-2·70, p=0·15). Analysis of individual types of toxicity showed consistent associations of c.1679T>G and c.1236G>A/HapB3 with gastrointestinal toxicity (adjusted RR 5·72, 95% CI 1·40-23·33, p=0·015; and 2·04, 1·49-2·78, p<0·0001, respectively) and haematological toxicity (adjusted RR 9·76, 95% CI 3·03-31·48, p=0·00014; and 2·07, 1·17-3·68, p=0·013, respectively), but not with hand-foot syndrome. DPYD*2A and c.2846A>T were also significantly associated with severe fluoropyrimidine-associated toxicity (adjusted RR 2·85, 95% CI 1·75-4·62, p<0·0001; and 3·02, 2·22-4·10, p<0·0001, respectively). INTERPRETATION DPYD variants c.1679T>G and c.1236G>A/HapB3 are clinically relevant predictors of fluoropyrimidine-associated toxicity. Upfront screening for these variants, in addition to the established variants DPYD*2A and c.2846A>T, is recommended to improve the safety of patients with cancer treated with fluoropyrimidines. FUNDING None.

Cisplatin Nephrotoxicity and Longitudinal Growth in Children With Solid Tumors: A Retrospective Cohort Study

Cisplatin, a major antineoplastic drug used in the treatment of solid tumors, is a known nephrotoxin. This retrospective cohort study evaluated the prevalence and severity of cisplatin nephrotoxicity in 54 children and its impact on height and weight.We recorded the weight, height, serum creatinine, and electrolytes in each cisplatin cycle and after 12 months of treatment. Nephrotoxicity was graded as follows: normal renal function (Grade 0); asymptomatic electrolyte disorders, including an increase in serum creatinine, up to 1.5 times baseline value (Grade 1); need for electrolyte supplementation <3 months and/or increase in serum creatinine 1.5 to 1.9 times from baseline (Grade 2); increase in serum creatinine 2 to 2.9 times from baseline or need for electrolyte supplementation for more than 3 months after treatment completion (Grade 3); and increase in serum creatinine ≥3 times from baseline or renal replacement therapy (Grade 4).Nephrotoxicity was observed in 41 subjects (75.9%). Grade 1 nephrotoxicity was observed in 18 patients (33.3%), Grade 2 in 5 patients (9.2%), and Grade 3 in 18 patients (33.3%). None had Grade 4 nephrotoxicity. Nephrotoxicity patients were younger and received higher cisplatin dose, they also had impairment in longitudinal growth manifested as statistically significant worsening on the height Z Score at 12 months after treatment. We used a multiple logistic regression model using the delta of height Z Score (baseline-12 months) as dependent variable in order to adjust for the main confounder variables such as: germ cell tumor, cisplatin total dose, serum magnesium levels at 12 months, gender, and nephrotoxicity grade. Patients with nephrotoxicity Grade 1 where at higher risk of not growing (OR 5.1, 95% CI 1.07-24.3, P=0.04). The cisplatin total dose had a significant negative relationship with magnesium levels at 12 months (Spearman r=-0.527, P=<0.001).