Molecular cloning, expression analysis and assignment of the porcine tumor necrosis factor superfamily member 10 gene (TNFSF10) to SSC13q34-->q36 by fluorescence in situ hybridization and radiation hybrid mapping

We have cloned the complete coding region of the porcine TNFSF10 gene. The porcine TNFSF10 cDNA has an ORF of 870 nucleotides and shares 85% identity with human TNFSF10, and 75% and 72% identity with rat and mouse Tnfsf10 coding sequences, respectively. The deduced porcine TNFSF10 protein consists of 289 amino acids with the calculated molecular mass of 33.5 kDa and a predicted pI of 8.15. The amino acid sequence similarities correspond to 86, 72 and 70% when compared with human, rat and mouse sequences, respectively. Northern blot analysis detected TNFSF10-specific transcripts (approximately 1.7 kb) in various organs of a 10-week-old pig, suggesting ubiquitous expression. Real-time RT-PCR studies of various organs from fetal (days 73 and 98) and postnatal stages (two weeks, eight months) demonstrated developmental and tissue-specific regulation of TNFSF10 mRNA abundance. The chromosomal location of the porcine TNFSF10 gene was determined by FISH of a specific BAC clone to metaphase chromosomes. This TNFSF10 BAC clone has been assigned to SSC13q34-->q36. Additionally, the localization of the TNFSF10 gene was verified by RH mapping on the porcine IMpRH panel.

Chronology of Lateglacial ice flow reorganization and deglaciation in the Gotthard Pass area, Central Swiss Alps, based on cosmogenic 10Be and in situ 14C

We reconstruct the timing of ice flow reconfiguration and deglaciation of the Central Alpine Gotthard Pass, Switzerland, using cosmogenic 10Be and in situ14C surface exposure dating. Combined with mapping of glacial erosional markers, exposure ages of bedrock surfaces reveal progressive glacier downwasting from the maximum LGM ice volume and a gradual reorganization of the paleoflow pattern with a southward migration of the ice divide. Exposure ages of ∼16–14 ka (snow corrected) give evidence for continuous early Lateglacial ice cover and indicate that the first deglaciation was contemporaneous with the decay of the large Gschnitz glacier system. In agreement with published ages from other Alpine passes, these data support the concept of large transection glaciers that persisted in the high Alps after the breakdown of the LGM ice masses in the foreland and possibly decayed as late as the onset of the Bølling warming. A younger group of ages around ∼12–13 ka records the timing of deglaciation following local glacier readvance during the Egesen stadial. Glacial erosional features and the distribution of exposure ages consistently imply that Egesen glaciers were of comparatively small volume and were following a topographically controlled paleoflow pattern. Dating of a boulder close to the pass elevation gives a minimum age of 11.1 ± 0.4 ka for final deglaciation by the end of the Younger Dryas. In situ14C data are overall in good agreement with the 10Be ages and confirm continuous exposure throughout the Holocene. However, in situ14C demonstrates that partial surface shielding, e.g. by snow, has to be incorporated in the exposure age calculations and the model of deglaciation.

In-situ, satellite measurement and model evidence on the dominant regional contribution to fine particulate matter levels in the Paris Megacity

A detailed characterization of air quality in the megacity of Paris (France) during two 1-month intensive campaigns and from additional 1-year observations revealed that about 70% of the urban background fine particulate matter (PM) is transported on average into the megacity from upwind regions. This dominant influence of regional sources was confirmed by in situ measurements during short intensive and longer-term campaigns, aerosol optical depth (AOD) measurements from ENVISAT, and modeling results from PMCAMx and CHIMERE chemistry transport models. While advection of sulfate is well documented for other megacities, there was surprisingly high contribution from long-range transport for both nitrate and organic aerosol. The origin of organic PM was investigated by comprehensive analysis of aerosol mass spectrometer (AMS), radiocarbon and tracer measurements during two intensive campaigns. Primary fossil fuel combustion emissions constituted less than 20%in winter and 40%in summer of carbonaceous fine PM, unexpectedly small for a megacity. Cooking activities and, during winter, residential wood burning are the major primary organic PM sources. This analysis suggests that the major part of secondary organic aerosol is of modern origin, i.e., from biogenic precursors and from wood burning. Black carbon concentrations are on the lower end of values encountered in megacities worldwide, but still represent an issue for air quality. These comparatively low air pollution levels are due to a combination of low emissions per inhabitant, flat terrain, and a meteorology that is in general not conducive to local pollution build-up. This revised picture of a megacity only being partially responsible for its own average and peak PM levels has important implications for air pollution regulation policies.

Virtopsy: postmortem imaging of the human heart in situ using MSCT and MRI.

The rapid further development of computed tomography (CT) and magnetic resonance imaging (MRI) induced the idea to use these techniques for postmortem documentation of forensic findings. Until now, only a few institutes of forensic medicine have acquired experience in postmortem cross-sectional imaging. Protocols, image interpretation and visualization have to be adapted to the postmortem conditions. Especially, postmortem alterations, such as putrefaction and livores, different temperature of the corpse and the loss of the circulation are a challenge for the imaging process and interpretation. Advantages of postmortem imaging are the higher exposure and resolution available in CT when there is no concern for biologic effects of ionizing radiation, and the lack of cardiac motion artifacts during scanning. CT and MRI may become useful tools for postmortem documentation in forensic medicine. In Bern, 80 human corpses underwent postmortem imaging by CT and MRI prior to traditional autopsy until the month of August 2003. Here, we describe the imaging appearance of postmortem alterations--internal livores, putrefaction, postmortem clotting--and distinguish them from the forensic findings of the heart, such as calcification, endocarditis, myocardial infarction, myocardial scarring, injury and other morphological alterations.

In situ plasma measurements of fragmented comet 73P Schwassmann–Wachmann 3

The interiors of comets contain some of the most pristine material in the solar system. Comet 73P/Schwassmann–Wachmann 3, discovered in 1930, is a Jupiter-family comet with a 5.34-year period. This comet split into 5 fragments in 1995 and disintegrated into nearly 70 major pieces in 2006. In 2006 May and June, recently ionized cometary particles originating from fragments including and surrounding some of these major objects were collected with the ACE/SWICS and Wind/STICS sensors. Due to a combination of the instrument characteristics and the close proximity of the fragments passing between those spacecraft and the Sun, unique measurements regarding the charge state composition and the elemental abundances of both cometary and heliospheric plasma were made during that time. The cometary material released from some of these fragments can be identified by the concentrations of water-group pickup ions having a mass-per-charge ratio of 16–18 amu e−1, indicating that while these fragments are small, they are still actively sublimating. We present an analysis of cometary composition, spatial distribution, and heliospheric interactions, with a focus on helium, C+/O+, and water-group ions.

5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non-inferiority trial.

BACKGROUND In a phase 3, randomised, non-inferiority trial, accelerated partial breast irradiation (APBI) for patients with stage 0, I, and IIA breast cancer who underwent breast-conserving treatment was compared with whole-breast irradiation. Here, we present 5-year follow-up results. METHODS We did a phase 3, randomised, non-inferiority trial at 16 hospitals and medical centres in seven European countries. 1184 patients with low-risk invasive and ductal carcinoma in situ treated with breast-conserving surgery were centrally randomised to either whole-breast irradiation or APBI using multicatheter brachytherapy. The primary endpoint was local recurrence. Analysis was done according to treatment received. This trial is registered with ClinicalTrials.gov, number NCT00402519. FINDINGS Between April 20, 2004, and July 30, 2009, 551 patients had whole-breast irradiation with tumour-bed boost and 633 patients received APBI using interstitial multicatheter brachytherapy. At 5-year follow-up, nine patients treated with APBI and five patients receiving whole-breast irradiation had a local recurrence; the cumulative incidence of local recurrence was 1·44% (95% CI 0·51-2·38) with APBI and 0·92% (0·12-1·73) with whole-breast irradiation (difference 0·52%, 95% CI -0·72 to 1·75; p=0·42). No grade 4 late side-effects were reported. The 5-year risk of grade 2-3 late side-effects to the skin was 3·2% with APBI versus 5·7% with whole-breast irradiation (p=0·08), and 5-year risk of grade 2-3 subcutaneous tissue late side-effects was 7·6% versus 6·3% (p=0·53). The risk of severe (grade 3) fibrosis at 5 years was 0·2% with whole-breast irradiation and 0% with APBI (p=0·46). INTERPRETATION The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival. FUNDING German Cancer Aid.

Nail melanoma in situ: clinical, dermoscopic, pathologic clues, and steps for minimally invasive treatment

BACKGROUND Nail unit melanoma (NUM) is a variant of acral lentiginous melanoma. The differential diagnosis is wide but an acquired brown streak in the nail of a fair-skinned adult person must be considered a potential melanoma. Dermoscopy helps clinicians to more accurately decide if a nail apparatus biopsy is necessary. OBJECTIVE Detailed evaluation of clinical and dermoscopy features and description of conservative surgery of in situ NUM. METHODS Retrospective study of in situ NUM diagnosed and treated with conservative surgical management in the authors' center from 2008 to 2013. RESULTS Six cases of NUM were identified: 2 male and 4 female patients, age range at diagnosis of 44 to 76 years. All patients underwent complete nail unit removal with at least 6-mm security margins around the anatomic boundaries of the nail. The follow-up varies from 4 to 62 months. CONCLUSION Nail unit melanomas pose a difficult diagnostic and therapeutic challenge. Wide excision is sufficient, whereas phalanx amputation is unnecessary and associated with significant morbidity for patients with in situ or early invasive melanoma. Full-thickness skin grafting or second-intention healing after total nail unit excision is a simple procedure providing a good functional and cosmetic outcome.

Outcomes of Active Surveillance for Ductal Carcinoma in Situ: A Computational Risk Analysis.

BACKGROUND Ductal carcinoma in situ (DCIS) is a noninvasive breast lesion with uncertain risk for invasive progression. Usual care (UC) for DCIS consists of treatment upon diagnosis, thus potentially overtreating patients with low propensity for progression. One strategy to reduce overtreatment is active surveillance (AS), whereby DCIS is treated only upon detection of invasive disease. Our goal was to perform a quantitative evaluation of outcomes following an AS strategy for DCIS. METHODS Age-stratified, 10-year disease-specific cumulative mortality (DSCM) for AS was calculated using a computational risk projection model based upon published estimates for natural history parameters, and Surveillance, Epidemiology, and End Results data for outcomes. AS projections were compared with the DSCM for patients who received UC. To quantify the propagation of parameter uncertainty, a 95% projection range (PR) was computed, and sensitivity analyses were performed. RESULTS Under the assumption that AS cannot outperform UC, the projected median differences in 10-year DSCM between AS and UC when diagnosed at ages 40, 55, and 70 years were 2.6% (PR = 1.4%-5.1%), 1.5% (PR = 0.5%-3.5%), and 0.6% (PR = 0.0%-2.4), respectively. Corresponding median numbers of patients needed to treat to avert one breast cancer death were 38.3 (PR = 19.7-69.9), 67.3 (PR = 28.7-211.4), and 157.2 (PR = 41.1-3872.8), respectively. Sensitivity analyses showed that the parameter with greatest impact on DSCM was the probability of understaging invasive cancer at diagnosis. CONCLUSION AS could be a viable management strategy for carefully selected DCIS patients, particularly among older age groups and those with substantial competing mortality risks. The effectiveness of AS could be markedly improved by reducing the rate of understaging.

Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ

BACKGROUND Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. RESULTS One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). CONCLUSIONS We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.

Dissolution-Precipitation in Porous Media: Experiments and Modelling

The evolution of porosity due to dissolution/precipitation processes of minerals and the associated change of transport parameters are of major interest for natural geological environments and engineered underground structures. We designed a reproducible and fast to conduct 2D experiment, which is flexible enough to investigate several process couplings implemented in the numerical code OpenGeosys-GEM (OGS-GEM). We investigated advective-diffusive transport of solutes, effect of liquid phase density on advective transport, and kinetically controlled dissolution/precipitation reactions causing porosity changes. In addition, the system allowed to investigate the influence of microscopic (pore scale) processes on macroscopic (continuum scale) transport. A Plexiglas tank of dimension 10 × 10 cm was filled with a 1 cm thick reactive layer consisting of a bimodal grain size distribution of celestite (SrSO4) crystals, sandwiched between two layers of sand. A barium chloride solution was injected into the tank causing an asymmetric flow field to develop. As the barium chloride reached the celestite region, dissolution of celestite was initiated and barite precipitated. Due to the higher molar volume of barite, its precipitation caused a porosity decrease and thus also a decrease in the permeability of the porous medium. The change of flow in space and time was observed via injection of conservative tracers and analysis of effluents. In addition, an extensive post-mortem analysis of the reacted medium was conducted. We could successfully model the flow (with and without fluid density effects) and the transport of conservative tracers with a (continuum scale) reactive transport model. The prediction of the reactive experiments initially failed. Only the inclusion of information from post-mortem analysis gave a satisfactory match for the case where the flow field changed due to dissolution/precipitation reactions. We concentrated on the refinement of post-mortem analysis and the investigation of the dissolution/precipitation mechanisms at the pore scale. Our analytical techniques combined scanning electron microscopy (SEM) and synchrotron X-ray micro-diffraction/micro-fluorescence performed at the XAS beamline (Swiss Light Source). The newly formed phases include an epitaxial growth of barite micro-crystals on large celestite crystals (epitaxial growth) and a nano-crystalline barite phase (resulting from the dissolution of small celestite crystals) with residues of celestite crystals in the pore interstices. Classical nucleation theory, using well-established and estimated parameters describing barite precipitation, was applied to explain the mineralogical changes occurring in our system. Our pore scale investigation showed limits of the continuum scale reactive transport model. Although kinetic effects were implemented by fixing two distinct rates for the dissolution of large and small celestite crystals, instantaneous precipitation of barite was assumed as soon as oversaturation occurred. Precipitation kinetics, passivation of large celestite crystals and metastability of supersaturated solutions, i.e. the conditions under which nucleation cannot occur despite high supersaturation, were neglected. These results will be used to develop a pore scale model that describes precipitation and dissolution of crystals at the pore scale for various transport and chemical conditions. Pore scale modelling can be used to parameterize constitutive equations to introduce pore-scale corrections into macroscopic (continuum) reactive transport models. Microscopic understanding of the system is fundamental for modelling from the pore to the continuum scale.