Carn Goedog medieval house and settlement, Pembrokeshire

This report describes the investigation in 2011 and 2015 of two groups of relict houses on an upland common on the north flank of the Preseli hills in North Pembrokeshire. Their locations, along with medieval records, provide strong indications that these were seasonal settlements. Excavation of one subrectangular building (House C) produced finds that included medieval pottery and a spindle whorl with Romanesque decoration. A radiocarbon date of cal. AD 1030–1200 at 95.4% confidence from charcoal in the hearth of this building provides the earliest firm date identified as yet for hafodydd (‘seasonal settlements’) in Wale

Evidence of re-osseointegration after electrolytic cleaning and regenerative therapy of peri-implantitis in humans: a case report with four implants.

OBJECTIVE To evaluate re-osseointegration after electrolytic cleaning and regenerative therapy of dental implants with peri-implantitis in humans. MATERIAL AND METHODS Four dental implants that developed peri-implantitis underwent electrolytic cleaning followed by regenerative therapy with guided bone regeneration. All four implants developed recurrent peri-implantitis and were therefore explanted 6 to 13 months later. Radiographic bone level, probing depth, and bleeding on probing were determined at the time of surgery, 6 months later, and before implant retrieval. The peri-implant tissues were histologically and histomorphometrically analyzed. RESULTS All four implants demonstrated radiographic and histological bone gain, reduced probing depth, and bleeding on probing. Radiographic bone gain was 5.8 mm mesially and 4.8 mm distally for implant #1, 3.3 mm and 2.3 mm for implant #2, 3.1 mm and 0.5 mm for implant #3, and 3.5 mm and 2.8 mm for implant #4. The histometric mean and maximum vertical bone gain for implant #1 to #4 was 1.65 mm and 2.54 mm, 3.04 mm and 3.47 mm, 0.43 mm and 1.27 mm, and 4.16 mm and 5.22 mm, respectively. The percentage of re-osseointegration for implant #1 to #4 was 21.0%, 36.9%, 5.7%, and 39.0%, respectively. In one implant, the newly formed bone was deposited directly onto calculus on the implant surface. CONCLUSIONS We found that (1) re-osseointegration is possible on a formerly contaminated implant surface and (2) the electrolytic cleaning process seems to be effective enough at sites with calculus residues. CLINICAL RELEVANCE Since re-osseointegration can be achieved by electrolytic cleaning, this decontamination technique may be considered as a future treatment concept

Inhibition of IGF1-R overcomes IGFBP7-induced chemotherapy resistance in T-ALL

Background T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease with the need for treatment optimization. Previously, high expression of Insulin-like growth factor binding protein 7 (IGFBP7), a member of the IGF system, was identified as negative prognostic factor in adult T-ALL patients. Since aberrant IGFBP7 expression was observed in a variety of neoplasia and was relevant for prognosis in T-ALL, we investigated the functional role of IGFBP7 in Jurkat and Molt-4 cells as in vitro models for T-ALL. Methods Jurkat and Molt-4 cells were stably transfected with an IGFBP7 over-expression vector or the empty vector as control. Proliferation of the cells was assessed by WST-1 assays and cell cycle status was measured by flow-cytometry after BrDU/7-AAD staining. The effect of IGFBP7 over-expression on sensitivity to cytostatic drugs was determined in AnnexinV/7-AAD assays. IGF1-R protein expression was measured by Western Blot and flow-cytometric analysis. IGF1-R associated gene expression profiles were generated from microarray gene expression data of 86 T-ALL patients from the Microarrays Innovations in Leukemia (MILE) multicenter study. Results IGFBP7-transfected Jurkat cells proliferated less, leading to a longer survival in a nutrient–limited environment. Both IGFBP7-transfected Jurkat and Molt-4 cells showed an arrest in the G0/G1 cell cycle phase. Furthermore, Jurkat IGFBP7-transfected cells were resistant to vincristine and asparaginase treatment. Surface expression and whole protein measurement of IGF1-R protein expression showed a reduced abundance of the receptor after IGFBP7 transfection in Jurkat cells. Interestingly, combination of the IGF1-R inhibitor NPV-AEW541 restored sensitivity to vincristine in IGFBP7-transfected cells. Additionally, IGF1-R associated GEP revealed an up-regulation of important drivers of T-ALL pathogenesis and regulators of chemo-resistance and apoptosis such as NOTCH1, BCL-2, PRKCI, and TP53. Conclusion This study revealed a proliferation inhibiting effect of IGFBP7 by G0/G1 arrest and a drug resistance-inducing effect of IGFBP7 against vincristine and asparaginase in T-ALL. These results provide a model for the previously observed association between high IGFBP7 expression and chemotherapy failure in T-ALL patients. Since the resistance against vincristine was abolished by IGF1-R inhibition, IGFBP7 could serve as biomarker for patients who may benefit from therapies including IGF1-R inhibitors in combination with chemotherapy

Megalith quarries for Stonehenge’s bluestones. Review

Geologists and archaeologists have long known that the bluestones of Stonehenge came from the Preseli Hills of west Wales, 230km away, but only recently have some of their exact geological sources been identified. Two of these quarries - Carn Goedog and Craig Rhos-y-felin - have now been excavated to reveal evidence of megalith quarrying around 3000 BC - the same period as the first stage of the construction of Stonehenge. The authors present evidence for the extraction of the stone pillars and consider how they were transported, including the possibility that they were erected in a temporary monument close to the quarries, before completing their journey to Stonehenge

FLT3 mutations in Early T-Cell Precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup

Methods for calibrating the gain and offset of the DSSC detector for the European XFEL

The DEPFET Sensor with Signal Compression (DSSC) will be a 2d 1Mpx imaging detector for the European X-­ray Free Electron Laser Facility (XFEL.EU). The DSSC is foreseen as an imaging detector for soft X-­radiation from 0.5 keV up to 6 keV. Driven by its scientific requirements, the design goals of the detector system are single photon detection, a high dynamic range and a high frame rate of up to 4.5 MHz. Signal compression, amplification and digitization will be performed in the focal plane. Utilizing an in-­pixel active filtering stage and an 8/9-­bit ADC, the detector will provide parallel readout of all pixels. Here the results of studies on the stability and performance of a parameterized model for determining gain and offset in DSSC prototype calibration line spectra will be presented

Craig Rhos-y-felin: A Welsh bluestone megalith quarry for Stonehenge

The long-distance transport of the bluestones from south Wales to Stonehenge is one of the most remarkable achievements of Neolithic societies in north-west Europe. Where precisely these stones were quarried, when they were extracted and how they were transported has long been a subject of speculation, experiment and controversy. The discovery of a megalithic bluestone quarry at Craig Rhos-y-felin in 2011 marked a turning point in this research. Subsequent excavations have provided details of the quarrying process along with direct dating evidence for the extraction of bluestone monoliths at this location, demonstrating both Neolithic and Early Bronze Age activity

Effect of yoghurt containing Bifidobacterium lactis Bb12® on faecal excretion of secretory immunoglobulin A and human beta-defensin 2 in healthy adult volunteers

<p>Abstract</p> <p>Background</p> <p>Probiotics are used to provide health benefits. The present study tested the effect of a probiotic yoghurt on faecal output of beta-defensin and immunoglobulin A in a group of young healthy women eating a defined diet.</p> <p>Findings</p> <p>26 women aged 18-21 (median 19) years residing in a hostel were given 200 ml normal yoghurt every day for a week, followed by probiotic yoghurt containing <it>Bifidobacterium lactis </it>Bb12^®(10⁹in 200 ml) for three weeks, followed again by normal yoghurt for four weeks. Stool samples were collected at 0, 4 and 8 weeks and assayed for immunoglobulin A and human beta-defensin-2 by ELISA. All participants tolerated both normal and probiotic yoghurt well. Human beta-defensin-2 levels in faeces were not altered during the course of the study. On the other hand, compared to the basal sample, faecal IgA increased during probiotic feeding (P = 0.0184) and returned to normal after cessation of probiotic yoghurt intake.</p> <p>Conclusions</p> <p><it>Bifidobacterium lactis </it>Bb12^®increased secretory IgA output in faeces. This property may explain the ability of probiotics to prevent gastrointestinal and lower respiratory tract infections.</p

Utilizing Co-Creative Principles to Develop an E-Learning Platform for Interprofessional Training on Tinnitus: The Erasmus+ Project Tin-TRAC

Tinnitus treatment, diagnosis and management across Europe varies significantly. The lack of national clinical guidelines for tinnitus management in most European countries and the absence of a common language across all disciplines involved is reflected in the diversification of healthcare practices. Interprofessional Training for Tinnitus Researchers and Clinicians (Tin-TRAC) is an Erasmus+ project that aims to develop common educational ground in the form of an e-Learning platform, co-created by patients, researchers and clinicians, which is able to unify tinnitus diagnosis and treatment strategies across Europe. A pan-European thematic educational platform integrating the best practices and latest research achievements with regard to tinnitus diagnosis and management has the potential to act as a facilitator of the reduction of interdisciplinary and interregional practice diversification. A detailed analysis of the educational needs of clinicians and researchers across disciplines will be followed by the co-creative development of the curriculum. Reusable learning objects will incorporate the training contents and will be integrated in an open e-Learning platform. Tin-TRAC envisions that its output will answer the need to create a common language across the clinicians and researchers of different disciplines that are involved in tinnitus management, and reduce patients’ prolonged suffering, non-adherence and endless referral trajectories