Improved Space Object Orbit Determination Using CMOS Detectors

CMOS-sensors, or in general Active Pixel Sensors (APS), are rapidly replacing CCDs in the consumer camera market. Due to significant technological advances during the past years these devices start to compete with CCDs also for demanding scientific imaging applications, in particular in the astronomy community. CMOS detectors offer a series of inherent advantages compared to CCDs, due to the structure of their basic pixel cells, which each contains their own amplifier and readout electronics. The most prominent advantages for space object observations are the extremely fast and flexible readout capabilities, feasibility for electronic shuttering and precise epoch registration,and the potential to perform image processing operations on-chip and in real-time. Here, the major challenges and design drivers for ground-based and space-based optical observation strategies for objects in Earth orbit have been analyzed. CMOS detector characteristics were critically evaluated and compared with the established CCD technology, especially with respect to the above mentioned observations. Finally, we simulated several observation scenarios for ground- and space-based sensor by assuming different observation and sensor properties. We will introduce the analyzed end-to-end simulations of the ground- and spacebased strategies in order to investigate the orbit determination accuracy and its sensitivity which may result from different values for the frame-rate, pixel scale, astrometric and epoch registration accuracies. Two cases were simulated, a survey assuming a ground-based sensor to observe objects in LEO for surveillance applications, and a statistical survey with a space-based sensor orbiting in LEO observing small-size debris in LEO. The ground-based LEO survey uses a dynamical fence close to the Earth shadow a few hours after sunset. For the space-based scenario a sensor in a sun-synchronous LEO orbit, always pointing in the anti-sun direction to achieve optimum illumination conditions for small LEO debris was simulated.

Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma

BACKGROUND Renal cell carcinoma (RCC) is marked by high mortality rate. To date, no robust risk stratification by clinical or molecular prognosticators of cancer-specific survival (CSS) has been established for early stages. Transcriptional profiling of small non-coding RNA gene products (miRNAs) seems promising for prognostic stratification. The expression of miR-21 and miR-126 was analysed in a large cohort of RCC patients; a combined risk score (CRS)-model was constructed based on expression levels of both miRNAs. METHODS Expression of miR-21 and miR-126 was evaluated by qRT-PCR in tumour and adjacent non-neoplastic tissue in n = 139 clear cell RCC patients. Relation of miR-21 and miR-126 expression with various clinical parameters was assessed. Parameters were analysed by uni- and multivariate COX regression. A factor derived from the z-score resulting from the COX model was determined for both miRs separately and a combined risk score (CRS) was calculated multiplying the relative expression of miR-21 and miR-126 by this factor. The best fitting COX model was selected by relative goodness-of-fit with the Akaike information criterion (AIC). RESULTS RCC with and without miR-21 up- and miR-126 downregulation differed significantly in synchronous metastatic status and CSS. Upregulation of miR-21 and downregulation of miR-126 were independently prognostic. A combined risk score (CRS) based on the expression of both miRs showed high sensitivity and specificity in predicting CSS and prediction was independent from any other clinico-pathological parameter. Association of CRS with CSS was successfully validated in a testing cohort containing patients with high and low risk for progressive disease. CONCLUSIONS A combined expression level of miR-21 and miR-126 accurately predicted CSS in two independent RCC cohorts and seems feasible for clinical application in assessing prognosis.

Computer planned, image-guided combined resection and ablation for bilobar colorectal liver metastases

For patients with extensive bilobar colorectal liver metastases (CRLM), initial surgery may not be feasible and a multimodal approach including microwave ablation (MWA) provides the only chance for prolonged survival. Intraoperative navigation systems may improve the accuracy of ablation and surgical resection of so-called "vanishing lesions", ultimately improving patient outcome. Clinical application of intraoperative navigated liver surgery is illustrated in a patient undergoing combined resection/MWA for multiple, synchronous, bilobar CRLM. Regular follow-up with computed tomography (CT) allowed for temporal development of the ablation zones. Of the ten lesions detected in a preoperative CT scan, the largest lesion was resected and the others were ablated using an intraoperative navigation system. Twelve months post-surgery a new lesion (Seg IVa) was detected and treated by trans-arterial embolization. Nineteen months post-surgery new liver and lung metastases were detected and a palliative chemotherapy started. The patient passed away four years after initial diagnosis. For patients with extensive CRLM not treatable by standard surgery, navigated MWA/resection may provide excellent tumor control, improving longer-term survival. Intraoperative navigation systems provide precise, real-time information to the surgeon, aiding the decision-making process and substantially improving the accuracy of both ablation and resection. Regular follow-ups including 3D modeling allow for early discrimination between ablation zones and recurrent tumor lesions.

GOCE: assessment of GPS-only gravity field determination

The GOCE satellite was orbiting the Earth in a Sun-synchronous orbit at a very low altitude for more than 4 years. This low orbit and the availability of high-quality data make it worthwhile to assess the contribution of GOCE GPS data to the recovery of both the static and time-variable gravity fields. We use the kinematic positions of the official GOCE precise science orbit (PSO) product to perform gravity field determination using the Celestial Mechanics Approach. The generated gravity field solutions reveal severe systematic errors centered along the geomagnetic equator. Their size is significantly coupled with the ionospheric density and thus generally increasing over the mission period. The systematic errors may be traced back to the kinematic positions of the PSO product and eventually to the ionosphere-free GPS carrier phase observations used for orbit determination. As they cannot be explained by the current higher order ionospheric correction model recommended by the IERS Conventions 2010, an empirical approach is presented by discarding GPS data affected by large ionospheric changes. Such a measure yields a strong reduction of the systematic errors along the geomagnetic equator in the gravity field recovery, and only marginally reduces the set of useable kinematic positions by at maximum 6 % for severe ionosphere conditions. Eventually it is shown that GOCE gravity field solutions based on kinematic positions have a limited sensitivity to the largest annual signal related to land hydrology.

GOCE: precise orbit determination for the entire mission

The Gravity field and steady-state Ocean Circulation Explorer (GOCE) was the first Earth explorer core mission of the European Space Agency. It was launched on March 17, 2009 into a Sun-synchronous dusk-dawn orbit and re-entered into the Earth’s atmosphere on November 11, 2013. The satellite altitude was between 255 and 225 km for the measurement phases. The European GOCE Gravity consortium is responsible for the Level 1b to Level 2 data processing in the frame of the GOCE High-level processing facility (HPF). The Precise Science Orbit (PSO) is one Level 2 product, which was produced under the responsibility of the Astronomical Institute of the University of Bern within the HPF. This PSO product has been continuously delivered during the entire mission. Regular checks guaranteed a high consistency and quality of the orbits. A correlation between solar activity, GPS data availability and quality of the orbits was found. The accuracy of the kinematic orbit primarily suffers from this. Improvements in modeling the range corrections at the retro-reflector array for the SLR measurements were made and implemented in the independent SLR validation for the GOCE PSO products. The satellite laser ranging (SLR) validation finally states an orbit accuracy of 2.42 cm for the kinematic and 1.84 cm for the reduced-dynamic orbits over the entire mission. The common-mode accelerations from the GOCE gradiometer were not used for the official PSO product, but in addition to the operational HPF work a study was performed to investigate to which extent common-mode accelerations improve the reduced-dynamic orbit determination results. The accelerometer data may be used to derive realistic constraints for the empirical accelerations estimated for the reduced-dynamic orbit determination, which already improves the orbit quality. On top of that the accelerometer data may further improve the orbit quality if realistic constraints and state-of-the-art background models such as gravity field and ocean tide models are used for the reduced-dynamic orbit determination.

A tephra lattice for Greenland and a reconstruction of volcanic events spanning 25–45 ka b2k

Tephra layers preserved within the Greenland ice-cores are crucial for the independent synchronisation of these high-resolution records to other palaeoclimatic archives. Here we present a new and detailed tephrochronological framework for the time period 25,000 e 45,000 a b2k that brings together results from 4 deep Greenland ice-cores. In total, 99 tephra deposits, the majority of which are preserved as cryptotephra, are described from the NGRIP, NEEM, GRIP and DYE-3 records. The major element signatures of single glass shards within these deposits indicate that 93 are basaltic in composition all originating from Iceland. Specifically, 43 originate from Grimsv € otn, 20 are thought to be sourced from the Katla volcanic system and 17 show affinity to the Kverkfj € oll system. Robust geochemical characterisations, independent ages derived from the GICC05 ice-core chronology, and the stratigraphic positions of these deposits relative to the Dansgaard-Oeschger climate events represent a key framework that provides new information on the frequency and nature of volcanic events in the North Atlantic region between GS-3 and GI-12. Of particular importance are 19 tephra deposits that lie on the rapid climatic transitions that punctuate the last glacial period. This framework of well-constrained, time-synchronous tie-lines represents an important step towards the independent synchronisation of marine, terrestrial and ice-core records from the North Atlantic region, in order to assess the phasing of rapid climatic changes during the last glacial period.

The deglaciation history of the Simplon region (southern Swiss Alps) constrained by 10Be exposure dating of ice-molded bedrock surfaces

The deglaciation history of the Swiss Alps after the Last Glacial Maximum involved the decay of several ice domes and the subsequent disintegration of valley glaciers at high altitude. Here we use bedrock exposure dating to reconstruct the temporal and spatial pattern of ice retreat at the Simplon Pass (altitude: ∼2000 m) located 40 km southwest of the ‘Rhône ice dome’. Eleven 10Be exposure ages from glacially polished quartz veins and ice-molded bedrock surfaces cluster tightly between 13.5 ± 0.6 ka and 15.4 ± 0.6 ka (internal errors) indicating that the Simplon Pass depression became ice-free at 14.1 ± 0.4 ka (external error of mean age). This age constraint is interpreted to record the melting of the high valley glaciers in the Simplon Pass region during the warm Bølling–Allerød interstadial shortly after the Oldest Dryas stadial. Two bedrock samples collected a few hundred meters above the pass depression yield older 10Be ages of 17.8 ± 0.6 ka and 18.0 ± 0.6 ka. These ages likely reflect the initial downwasting of the Rhône ice dome and the termination of the ice transfluence from the ice dome across the Simplon Pass toward the southern foreland. There, the retreat of the piedmont glacier in Val d’Ossola was roughly synchronous with the decay of the Rhône ice dome in the interior of the mountain belt, as shown by 10Be ages of 17.7 ± 0.9 ka and 16.1 ± 0.6 ka for a whaleback at ∼500 m elevation near Montecrestese in northern Italy. In combination with well-dated paleoclimate records derived from lake sediments, our new age data suggest that during the deglaciation of the European Alps the decay of ice domes was approximately synchronous with the retreat of piedmont glaciers in the foreland and was followed by the melting of high-altitude valley glaciers after the transition from the Oldest Dryas to the Bølling–Allerød, when mean annual temperatures rose rapidly by ∼3 °C.

The first major incision of the Swiss Deckenschotter landscape

The Swiss Deckenschotter (“cover gravels”) is the oldest Quaternary units in the northern Swiss Alpine Foreland. They are a succession of glaciofluvial gravel layers intercalated with glacial and/or overbank deposits. This lithostratigraphic sequence is called Deckenschotter because it “covers” Molasse or Mesozoic bedrock and forms mesa-type hill-tops. Deckenschotter occurs both within and beyond the extent of the Last Glacial Maximum glaciers. The Swiss Deckenschotter consist of two sub-units: Höhere (Higher) and Tiefere (Lower) Deckenschotter. Although the Höhere Deckenschotter sub-unit (HDS) is topographically higher than the Tiefere Deckenschotter, it is older. The only available age for the Swiss Deckenschotter is 2.5–1.8 Ma based on mammal remains found in HDS at the Irchel site. In this study, we present an exposure age for the topographically lowest HDS, calculated from a cosmogenic 10Be depth-profile. Our results show that the first phase of the Deckenschotter glaciations in the Swiss Alps terminated at least 1,020+80−120 ka ago, which is indicated by a significant fluvial incision. This line of evidence seems to be close to synchronous with the beginning of the Mid-Pleistocene Revolution, when the frequency of the glacial-interglacial cyclicity changed from 41 to 100 ka and the amplitude from low to high, between marine isotope stages 23 and 22.

Fire ecology north and south of the Alps since the last ice age

Wildfires are very rare in central Europe, which is probably why fire effects on vegetation have been neglected by most central European ecologists and palaeoecologists. Presently, reconstructions of fire history and fire ecology are almost absent. We analysed sediment cores from lakes on the Swiss Plateau (Lobsigensee and Soppensee) for pollen and charcoal to investigate the relationship between vegetation and fire. Microscopic charcoal evidence suggests increasing regional fire frequencies during the Neolithic (7350-4150 cal. BP, 5400-2200 BC) and the subsequent prehistoric epochs at Lobsigensee, whereas at Soppensee burnings remained rather rare until modern times. Neolithic peaks of charcoal at 6200 and 5500 cal. BP (4250 and 3550 BC) coincided with declines of pollen of fire-sensitive taxa at both sites (e.g., Ulmus, Tilia, Hedera, Fagus), suggesting synchronous vegetational responses to fire at regional scales. However, correlation analysis between charcoal and pollen for the period 6600-4400 cal. BP (4650-2650 BC) revealed no significant link between fire and vegetation at Soppensee, whereas at Lobsigensee increases of Corylus and decreases of Fagus were related to fire events. Fire impact on vegetation increased during the subsequent epochs at both sites. Correlation analyses of charcoal and pollen data for the period 4250-1150 cal. BP (2300 BC -AD 800) suggest that fires were intentionally set to disrupt forests and to provide open areas for arable and pastoral farming (e.g., significant positive correlations between charcoal and Cerealia, Plantago lanceolata, Asteroideae). These results are compared with southern European records (Lago di Origlio, Lago di Muzzano), which are situated in particularly fire-prone environments. After the Mesolithic period (I1 200-7350 cal. BP, 9250-5400 BC), charcoal influx was higher by an order of magnitude in the south, suggesting more frequent fires. Neolithic fires caused similar though more pronounced responses of vegetation in the south (e.g., expansions of Corylus). Post-Neolithic land-use practices involving (controlled) burning culminated in both regions at about 2550 cal. BP (c. 600 BC). However, fire-caused disappearances of entire forest communities were confined to the southern sites. Such differences in fire effects among the sites are explained by the dissimilar importance of fire as a result of different climatic conditions and cultural activities. Our results imply that the remaining (fire-sensitive) fragments of central European vegetation north of the Alps are especially endangered by increasing fire frequencies resulting from predicted climatic change.

Activation of metabotropic glutamate 5 and NMDA receptors underlies the induction of persistent bursting and associated long-lasting changes in CA3 recurrent connections.

The aim of this study was to describe the induction and expression mechanisms of a persistent bursting activity in a horizontal slice preparation of the rat limbic system that includes the ventral part of the hippocampus and the entorhinal cortex. Disinhibition of this preparation by bicuculline led to interictal-like bursts in the CA3 region that triggered synchronous activity in the entorhinal cortex. Washout of bicuculline after a 1 hr application resulted in a maintained production of hippocampal bursts that continued to spread to the entorhinal cortex. Separation of CA3 from the entorhinal cortex caused the activity in the latter to become asynchronous with CA3 activity in the presence of bicuculline and disappear after washout; however, in CA3, neither the induction of bursting nor its persistence were affected. Associated with the CA3 persistent bursting, a strengthening of recurrent collateral excitatory input to CA3 pyramidal cells and a decreased input to CA3 interneurons was found. Both the induction of the persistent bursting and the changes in synaptic strength were prevented by antagonists of metabotropic glutamate 5 (mGlu5) or NMDA receptors or protein synthesis inhibitors and did not occur in slices from mGlu5 receptor knock-out mice. The above findings suggest potential synaptic mechanisms by which the hippocampus switches to a persistent interictal bursting mode that may support a spread of interictal-like bursting to surrounding temporal lobe regions.

Small Cell Carcinoma of the Urinary Bladder: A Retrospective, Multicenter Rare Cancer Network Study of 107 Patients

PURPOSE Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB. METHODS AND MATERIALS Fifteen academic Rare Cancer Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors. RESULTS The study included 107 patients (mean [±standard deviation, SD] age, 69.6 [±10.6] years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7). CONCLUSIONS The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.

Younger Dryas and Allerød summer temperatures at Gerzensee (Switzerland) inferred from fossil pollen and cladoceran assemblages

Linear- and unimodal-based inference models for mean summer temperatures (partial least squares, weighted averaging, and weighted averaging partial least squares models) were applied to a high-resolution pollen and cladoceran stratigraphy from Gerzensee, Switzerland. The time-window of investigation included the Allerød, the Younger Dryas, and the Preboreal. Characteristic major and minor oscillations in the oxygen-isotope stratigraphy, such as the Gerzensee oscillation, the onset and end of the Younger Dryas stadial, and the Preboreal oscillation, were identified by isotope analysis of bulk-sediment carbonates of the same core and were used as independent indicators for hemispheric or global scale climatic change. In general, the pollen-inferred mean summer temperature reconstruction using all three inference models follows the oxygen-isotope curve more closely than the cladoceran curve. The cladoceran-inferred reconstruction suggests generally warmer summers than the pollen-based reconstructions, which may be an effect of terrestrial vegetation not being in equilibrium with climate due to migrational lags during the Late Glacial and early Holocene. Allerød summer temperatures range between 11 and 12°C based on pollen, whereas the cladoceran-inferred temperatures lie between 11 and 13°C. Pollen and cladocera-inferred reconstructions both suggest a drop to 9–10°C at the beginning of the Younger Dryas. Although the Allerød–Younger Dryas transition lasted 150–160 years in the oxygen-isotope stratigraphy, the pollen-inferred cooling took 180–190 years and the cladoceran-inferred cooling lasted 250–260 years. The pollen-inferred summer temperature rise to 11.5–12°C at the transition from the Younger Dryas to the Preboreal preceded the oxygen-isotope signal by several decades, whereas the cladoceran-inferred warming lagged. Major discrepancies between the pollen- and cladoceran-inference models are observed for the Preboreal, where the cladoceran-inference model suggests mean summer temperatures of up to 14–15°C. Both pollen- and cladoceran-inferred reconstructions suggest a cooling that may be related to the Gerzensee oscillation, but there is no evidence for a cooling synchronous with the Preboreal oscillation as recorded in the oxygen-isotope record. For the Gerzensee oscillation the inferred cooling was ca. 1 and 0.5°C based on pollen and cladocera, respectively, which lies well within the inherent prediction errors of the inference models.

Sedimentological and biostratigraphical analyses of short sediment cores from Hagelseewli (2339 m a.s.l.) in the Swiss Alps

Several short sediment cores of between 35 and 40 cm from Hagelseewli, a small, remote lake in the Swiss Alps at an elevation of 2339 m a.s.l. were correlated according to their organic matter content. The sediments are characterized by organic silts and show in their uppermost part a surprisingly high amount of organic matter (30-35%). Synchronous changes, occurring in pollen from snow-bed vegetation, the alga Pediastrum, chironomids, and grain-size composition, point to a climatic change interpreted as cooler or shorter summers that led to prolonged ice-cover on the lake. According to palynological results the sediments date back to at least the early 15th century A.D., with the cooling phase encompassing the period between late 16th and the mid-19th century thus coinciding with the Little Ice Age. Low concentrations of both chironomid head capsules and cladoceran remains in combination with results from fossil pigment analyses point to longer periods of bottom-water anoxia as a result of long-lasting ice-cover that prevented mixing of the water column. According to our results aquatic biota in Hagelseewli are mainly indirectly influenced by climate change. The duration of ice-cover on the lake controls the mixing of the water column as well as light-availability for phytoplankton blooms.

Rebound-associated vertebral fractures after discontinuation of denosumab-from clinic and biomechanics.

Rebound-associated vertebral fractures may follow treatment discontinuation of highly potent reversible bone antiresorptives, resulting from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone. INTRODUCTION The purposes of this study are to characterize rebound-associated vertebral fractures following the discontinuation of a highly potent reversible antiresorptive therapy based on clinical observation and propose a pathophysiological rationale. METHODS This study is a case report of multiple vertebral fractures early after discontinuation of denosumab therapy in a patient with hormone receptor-positive non-metastatic breast cancer treated with an aromatase inhibitor. RESULTS Discontinuation of highly potent reversible bone antiresorptives such as denosumab may expose patients to an increased fracture risk due to the joined effects of absent microdamage repair during therapy followed by synchronous excess activation of multiple bone remodelling units at the time of loss-of-effect. We suggest the term rebound-associated vertebral fractures (RVF) for this phenomenon characterized by the presence of multiple new clinical vertebral fractures, associated with either no or low trauma, in a context consistent with the presence of high bone turnover and rapid loss of lumbar spine bone mineral density (BMD) occurring within 3 to 12 months after discontinuation (loss-of-effect) of a reversible antiresorptive therapy in the absence of secondary causes of bone loss or fractures. Unlike atypical femoral fractures that emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, RVF originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of highly potent reversible antiresorptives. CONCLUSIONS Studies are urgently needed to i) prove the underlying pathophysiological processes suggested above, ii) establish the predictive criteria exposing patients to an increased risk of RVF, and iii) determine appropriate treatment regimens to be applied in such patients.

Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness.

During non-rapid eye movement (NREM) sleep, synchronous synaptic activity in the thalamocortical network generates predominantly low-frequency oscillations (<4 Hz) that are modulated by inhibitory inputs from the thalamic reticular nucleus (TRN). Whether TRN cells integrate sleep-wake signals from subcortical circuits remains unclear. We found that GABA neurons from the lateral hypothalamus (LHGABA) exert a strong inhibitory control over TRN GABA neurons (TRNGABA). We found that optogenetic activation of this circuit recapitulated state-dependent changes of TRN neuron activity in behaving mice and induced rapid arousal during NREM, but not REM, sleep. During deep anesthesia, activation of this circuit induced sustained cortical arousal. In contrast, optogenetic silencing of LHGABA-TRNGABA transmission increased the duration of NREM sleep and amplitude of delta (1-4 Hz) oscillations. Collectively, these results demonstrate that TRN cells integrate subcortical arousal inputs selectively during NREM sleep and may participate in sleep intensity.