Feasibility of Using EMG for Early Detection of the Facial Nerve During Robotic Direct Cochlear Access

HYPOTHESIS Facial nerve monitoring can be used synchronous with a high-precision robotic tool as a functional warning to prevent of a collision of the drill bit with the facial nerve during direct cochlear access (DCA). BACKGROUND Minimally invasive direct cochlear access (DCA) aims to eliminate the need for a mastoidectomy by drilling a small tunnel through the facial recess to the cochlea with the aid of stereotactic tool guidance. Because the procedure is performed in a blind manner, structures such as the facial nerve are at risk. Neuromonitoring is a commonly used tool to help surgeons identify the facial nerve (FN) during routine surgical procedures in the mastoid. Recently, neuromonitoring technology was integrated into a commercially available drill system enabling real-time monitoring of the FN. The objective of this study was to determine if this drilling system could be used to warn of an impending collision with the FN during robot-assisted DCA. MATERIALS AND METHODS The sheep was chosen as a suitable model for this study because of its similarity to the human ear anatomy. The same surgical workflow applicable to human patients was performed in the animal model. Bone screws, serving as reference fiducials, were placed in the skull near the ear canal. The sheep head was imaged using a computed tomographic scanner and segmentation of FN, mastoid, and other relevant structures as well as planning of drilling trajectories was carried out using a dedicated software tool. During the actual procedure, a surgical drill system was connected to a nerve monitor and guided by a custom built robot system. As the planned trajectories were drilled, stimulation and EMG response signals were recorded. A postoperative analysis was achieved after each surgery to determine the actual drilled positions. RESULTS Using the calibrated pose synchronized with the EMG signals, the precise relationship between distance to FN and EMG with 3 different stimulation intensities could be determined for 11 different tunnels drilled in 3 different subjects. CONCLUSION From the results, it was determined that the current implementation of the neuromonitoring system lacks sensitivity and repeatability necessary to be used as a warning device in robotic DCA. We hypothesize that this is primarily because of the stimulation pattern achieved using a noninsulated drill as a stimulating probe. Further work is necessary to determine whether specific changes to the design can improve the sensitivity and specificity.

MiR-205 is progressively down-regulated in lymph node metastasis but fails as a prognostic biomarker in high-risk prostate cancer

The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.

Are great Cascadia earthquakes recorded in the sedimentary records from small forearc lakes?

Here we investigate sedimentary records from four small inland lakes located in the southern Cascadia forearc region for evidence of earthquakes. Three of these lakes are in the Klamath Mountains near the Oregon–California border, and one is in the central Oregon Coast range. The sedimentary sequences recovered from these lakes are composed of normal lake sediment interbedded with disturbance event layers. The thickest of these layers are graded, and appear to be turbidites or linked debrites (turbidites with a basal debris-flow deposit), suggesting rapid deposition. Variations in particle size and organic content of these layers are reflected in the density and magnetic susceptibility data. The frequency and timing of these events, based on radiocarbon ages from detrital organics, is similar to the offshore seismogenic turbidite record from trench and slope basin cores along the Cascadia margin. Stratigraphic correlation of these anomalous deposits based on radiocarbon ages, down-core density, and magnetic susceptibility data between lake and offshore records suggest synchronous triggering. The areal extent and multiple depositional environments over which these events appear to correlate suggest that these deposits were most likely caused by shaking during great Cascadia earthquakes.

OSL and TL dating of the Middle Stone Age sequence at Diepkloof Rock Shelter (South Africa): a clarification

Diepkloof Rock Shelter offers an exceptional opportunity to study the onset and evolution of both Still Bay (SB) and Howiesons Poort (HP) techno-complexes. However, previous age estimates based on luminescence dating of burnt quartzites (Tribolo et al., 2009) and of sediments (Jacobs et al., 2008) were not in agreement. Here, we present new luminescence ages for 17 rock samples (equivalent dose estimated with a SAR-ITL protocol instead of classical MAAD-TL) as well as for 5 sediment samples (equivalent dose estimated with SAR-single grain OSL protocol) and an update of the 22 previous age estimates for burnt lithics (modified calibration and beta dose estimates). While a good agreement between the rock and sediment ages is obtained, these estimates are still significantly older than those reported by Jacobs et al. (2008). After our own analyses of the sediment from Diepkloof, it is suspected that these authors did not correctly chose the parameters for the equivalent dose determination, leading to an underestimate of the equivalent doses, and thus of the ages. From bottom to top, the mean ages are 100 ± 10 ka for stratigraphic unit (SU) Noël and 107 ± 11 ka for SU Mark (uncharacterized Lower MSA), 100 ± 10 ka for SU Lynn-Leo (Pre-SB type Lynn), 109 ± 10 ka for SUs Kim-Larry (SB), 105 ± 10 ka for SUs Kerry-Kate and 109 ± 10 ka for SU Jess (Early HP), 89 ± 8 ka for SU Jude (MSA type Jack), 77 ± 8 ka for SU John, 85 ± 9 ka for SU Fox, 83 ± 8 ka for SU Fred and 65 ± 8 ka for SU OB5 (Intermediate HP), 52 ± 5 ka for SUs OB2-4 (Late HP). This chronology, together with the technological analyses, greatly modifies the current chrono-cultural model regarding the SB and the HP and has important archaeological implications. Indeed, SB and HP no longer appear as short-lived techno-complexes with synchronous appearances for each and restricted to Oxygen Isotopic Stage (OIS) 4 across South Africa, as suggested by Jacobs et al. (2008, 2012). Rather, the sequence of Diepkloof supports a long chronology model with an early appearance of both SB and HP in the first half of OIS 5 and a long duration of the HP into OIS 3. These new dates imply that different technological traditions coexisted during OIS 5 and 4 in southern Africa and that SB and HP can no longer be considered as horizon markers.

Mass-movement and flood-induced deposits in Lake Ledro, southern Alps, Italy: implications for Holocene palaeohydrology and natural hazards

High-resolution seismic profiles and sediment cores from Lake Ledro combined with soil and riverbed samples from the lake's catchment area are used to assess the recurrence of natural hazards (earthquakes and flood events) in the southern Italian Alps during the Holocene. Two well-developed deltas and a flat central basin are identified on seismic profiles in Lake Ledro. Lake sediments have been finely laminated in the basin since 9000 cal. yr BP and frequently interrupted by two types of sedimentary events (SEs): light-coloured massive layers and dark-coloured graded beds. Optical analysis (quantitative organic petrography) of the organic matter present in soil, riverbed and lacustrine samples together with lake sediment bulk density and grain-size analysis illustrate that light-coloured layers consist of a mixture of lacustrine sediments and mainly contain algal particles similar to the ones observed in background sediments. Light-coloured layers thicker than 1.5 cm in the main basin of Lake Ledro are synchronous to numerous coeval mass-wasting deposits remoulding the slopes of the basin. They are interpreted as subaquatic mass-movements triggered by historical and pre-historical regional earthquakes dated to AD2005, AD1891, AD1045 and 1260, 2545, 2595, 3350, 3815, 4740, 7190, 9185 and 11 495 cal. yr BP. Darkcoloured SEs develop high-amplitude reflections in front of the deltas and in the deep central basin. These beds are mainly made of terrestrial organic matter (soils and lignocellulosic debris) and are interpreted as resulting from intense hyperpycnal flood event. Mapping and quantifying the amount of soil material accumulated in the Holocene hyperpycnal flood deposits of the sequence allow estimating that the equivalent soil thickness eroded over the catchment area reached up to 5mm during the largest Holocene flood events. Such significant soil erosion is interpreted as resulting from the combination of heavy rainfall and snowmelt. The recurrence of flash flood events during the Holocene was, however, not high enough to affect pedogenesis processes and highlight several wet regional periods during the Holocene. The Holocene period is divided into four phases of environmental evolution. Over the first half of the Holocene, a progressive stabilization of the soils present through the catchment of Lake Ledro was associated with a progressive reforestation of the area and only interrupted during the wet 8.2 event when the soil destabilization was particularly important. Lower soil erosion was recorded during the mid-Holocene climatic optimum (8000-4200 cal. yr BP) and associated with higher algal production. Between 4200 and 3100 cal. yr BP, both wetter climate and human activities within the drainage basin drastically increased soil erosion rates. Finally, from 3100 cal. yr BP to the present-day, data suggest increasing and changing human land use.

A reliable risk score for stage IV esophagogastric cancer

BACKGROUND The role of surgery for patients with metastatic esophagogastric adenocarcinoma (EGC) is not defined. The purpose of this study was to define selection criteria for patients who may benefit from resection following systemic chemotherapy. METHODS From 1987 to 2007, 160 patients presenting with synchronous metastatic EGC (cT3/4 cNany cM0/1 finally pM1) were treated with chemotherapy followed by resection of the primary tumor and metastases. Clinical and histopathological data, site and number of metastases were analyzed. A prognostic score was established and validated in a second cohort from another academic center (n = 32). RESULTS The median survival (MS) in cohort 1 was 13.6 months. Significant prognostic factors were grading (p = 0.046), ypT- (p = 0.001), ypN- (p = 0.011) and R-category (p = 0.015), lymphangiosis (p = 0.021), clinical (p = 0.004) and histopathological response (p = 0.006), but not localization or number of metastases. The addition of grading (G1/2:0 points; G3/4:1 points), clinical response (responder: 0; nonresponder: 1) and R-category (complete:0; R1:1; R2:2) defines two groups of patients with significantly different survival (p = 0.001) [low risk group (Score 0/1), n = 22: MS 35.3 months, 3-year-survival 47.6%); high risk group (Score 2/3/4) n = 126: MS 12.0 months, 3-year-survival 14.2%]. The score showed a strong trend in the validation cohort (p = 0.063) [low risk group (MS not reached, 3-year-survival 57.1%); high risk group (MS 19.9 months, 3-year-survival 6.7%)]. CONCLUSION We observed long-term survival after resection of metastatic EGC. A simple clinical score may help to identify a subgroup of patients with a high chance of benefit from resection. However, the accurate estimation of achieving a complete resection, which is an integral element of the score, remains challenging.

Restoring tactile awareness through the rubber hand illusion in cervical spinal cord injury

BACKGROUND Bodily sensations are an important component of corporeal awareness. Spinal cord injury can leave affected body parts insentient and unmoving, leading to specific disturbances in the mental representation of one's own body and the sense of self. OBJECTIVE Here, we explored how illusions induced by multisensory stimulation influence immediate sensory signals and tactile awareness in patients with spinal cord injuries. METHODS The rubber hand illusion paradigm was applied to 2 patients with chronic and complete spinal cord injury of the sixth cervical spine, with severe somatosensory impairments in 2 of 5 fingers. RESULTS Both patients experienced a strong illusion of ownership of the rubber hand during synchronous, but not asynchronous, stroking. They also, spontaneously reported basic tactile sensations in their previously numb fingers. Tactile awareness from seeing the rubber hand was enhanced by progressively increasing the stimulation duration. CONCLUSIONS Multisensory illusions directly and specifically modulate the reemergence of sensory memories and enhance tactile sensation, despite (or as a result of) prior deafferentation. When sensory inputs are lost, and are later illusorily regained, the brain updates a coherent body image even several years after the body has become permanently unable to feel. This particular example of neural plasticity represents a significant opportunity to strengthen the sense of the self and the feelings of embodiment in patients with spinal cord injury.

High-resolution mineral dust and sea ice proxy records from the Talos Dome ice core

In this study we report on new non-sea salt calcium (nssCa2+, mineral dust proxy) and sea salt sodium (ssNa+, sea ice proxy) records along the East Antarctic Talos Dome deep ice core in centennial resolution reaching back 150 thousand years (ka) before present. During glacial conditions nssCa2+ fluxes in Talos Dome are strongly related to temperature as has been observed before in other deep Antarctic ice core records, and has been associated with synchronous changes in the main source region (southern South America) during climate variations in the last glacial. However, during warmer climate conditions Talos Dome mineral dust input is clearly elevated compared to other records mainly due to the contribution of additional local dust sources in the Ross Sea area. Based on a simple transport model, we compare nssCa2+ fluxes of different East Antarctic ice cores. From this multi-site comparison we conclude that changes in transport efficiency or atmospheric lifetime of dust particles do have a minor effect compared to source strength changes on the large-scale concentration changes observed in Antarctic ice cores during climate variations of the past 150 ka. Our transport model applied on ice core data is further validated by climate model data. The availability of multiple East Antarctic nssCa2+ records also allows for a revision of a former estimate on the atmospheric CO2 sensitivity to reduced dust induced iron fertilisation in the Southern Ocean during the transition from the Last Glacial Maximum to the Holocene (T1). While a former estimate based on the EPICA Dome C (EDC) record only suggested 20 ppm, we find that reduced dust induced iron fertilisation in the Southern Ocean may be responsible for up to 40 ppm of the total atmospheric CO2 increase during T1. During the last interglacial, ssNa+ levels of EDC and EPICA Dronning Maud Land (EDML) are only half of the Holocene levels, in line with higher temperatures during that period, indicating much reduced sea ice extent in the Atlantic as well as the Indian Ocean sector of the Southern Ocean. In contrast, Holocene ssNa+ flux in Talos Dome is about the same as during the last interglacial, indicating that there was similar ice cover present in the Ross Sea area during MIS 5.5 as during the Holocene.

A meta-analysis of cambium phenology and growth: linear and non-linear patterns in conifers of the northern hemisphere

Background and Aims Ongoing global warming has been implicated in shifting phenological patterns such as the timing and duration of the growing season across a wide variety of ecosystems. Linear models are routinely used to extrapolate these observed shifts in phenology into the future and to estimate changes in associated ecosystem properties such as net primary productivity. Yet, in nature, linear relationships may be special cases. Biological processes frequently follow more complex, non-linear patterns according to limiting factors that generate shifts and discontinuities, or contain thresholds beyond which responses change abruptly. This study investigates to what extent cambium phenology is associated with xylem growth and differentiation across conifer species of the northern hemisphere. Methods Xylem cell production is compared with the periods of cambial activity and cell differentiation assessed on a weekly time scale on histological sections of cambium and wood tissue collected from the stems of nine species in Canada and Europe over 1–9 years per site from 1998 to 2011. Key Results The dynamics of xylogenesis were surprisingly homogeneous among conifer species, although dispersions from the average were obviously observed. Within the range analysed, the relationships between the phenological timings were linear, with several slopes showing values close to or not statistically different from 1. The relationships between the phenological timings and cell production were distinctly non-linear, and involved an exponential pattern. Conclusions The trees adjust their phenological timings according to linear patterns. Thus, shifts of one phenological phase are associated with synchronous and comparable shifts of the successive phases. However, small increases in the duration of xylogenesis could correspond to a substantial increase in cell production. The findings suggest that the length of the growing season and the resulting amount of growth could respond differently to changes in environmental conditions.

Increased intraoperative epidural pressure in lumbar spinal stenosis patients with a positive nerve root sedimentation sign

Purpose The sedimentation sign (SedSign) has been shown to discriminate well between selected patients with and without lumbar spinal stenosis (LSS). The purpose of this study was to compare the pressure values associated with LSS versus non-LSS and discuss whether a positive SedSign may be related to increased epidural pressure at the level of the stenosis. Methods We measured the intraoperative epidural pressure in five patients without LSS and a negative SedSign, and in five patients with LSS and a positive SedSign using a Codman TM catheter in prone position under radioscopy. Results Patients with a negative SedSign had a median epidural pressure of 9 mmHg independent of the measurement location. Breath and pulse-synchronous waves accounted for 1–3 mmHg. In patients with monosegmental LSS and a positive SedSign, the epidural pressure above and below the stenosis was similar (median 8–9 mmHg). At the level of the stenosis the median epidural pressure was 22 mmHg. A breath and pulse-synchronous wave was present cranial to the stenosis, but absent below. These findings were independent of the cross-sectional area of the spinal canal at the level of the stenosis. Conclusions Patients with LSS have an increased epidural pressure at the level of the stenosis and altered pressure wave characteristics below. We argue that the absence of sedimentation of lumbar nerve roots to the dorsal part of the dural sac in supine position may be due to tethering of affected nerve roots at the level of the stenosis.

Simultaneous registration of ECG and cardiac motion by a single esophageal probe

Long-term surface ECG is routinely used to diagnose paroxysmal arrhythmias. However, this method only provides information about the heart's electrical activity. To this end, we investigated a novel esophageal catheter that features synchronous esophageal ECG and acceleration measurements, the latter being a record of the heart's mechanical activity. The acceleration data were quantified in a small study and successfully linked to the activity sequences of the heart in all subjects. The acceleration signals were additionally transformed into motion. The extracted cardiac motion was proved to be a valid reference input for an adaptive filter capable of removing relevant baseline wandering in the recorded esophageal ECGs. Taking both capabilities into account, the proposed recorder might be a promising tool for future long-term heart monitoring.

High-resolution late-glacial chronology for the Gerzensee lake record (Switzerland): δ18O correlation between a Gerzensee-stack and NGRIP

Oxygen-isotope variations were analyzed on bulk samples of shallow-water lake marl from Gerzensee, Switzerland, in order to evaluate major and minor climatic oscillations during the late-glacial. To highlight the overall signature of the Gerzensee δ18O record, δ18O records of four parallel sediment cores were first correlated by synchronizing major isotope shifts and pollen abundances. Then the records were stacked with a weighting depending on the differing sampling resolution. To develop a precise chronology, the δ18O-stack was then correlated with the NGRIP δ18O record applying a Monte Carlo simulation, relying on the assumption that the shifts in δ18O were climate-driven and synchronous in both archives. The established chronology on the GICC05 time scale is the basis for (1) comparing the δ18O changes recorded in Gerzensee with observed climatic and environmental fluctuations over the whole North Atlantic region, and (2) comparing sedimentological and biological changes during the rapid warming with smaller climatic variations during the Bølling/Allerød period. The δ18O record of Gerzensee is characterized by two major isotope shifts at the onset and at the termination of the Bølling/Allerød warm period, as well as four intervening negative shifts labeled GI-1e2, d, c2, and b, which show a shift of one third to one fourth of the major δ18O shifts at the beginning and end of the Bølling/Allerød. Despite some inconsistency in terminology, these oscillations can be observed in various climatic proxies over wide regions in the North Atlantic region, especially in reconstructed colder temperatures, and they seem to be caused by hemispheric climatic variations.

Responses to rapid warming at Termination 1a at Gerzensee (Central Europe): Primary succession, albedo, soils, lake development, and ecological interactions

The transition from the Oldest Dryas to the Bølling around 14,685 cal yr BP was a period of extremely rapid climatic warming. From a single core of lake marl taken at Gerzensee (Switzerland) we studied the transition in stable isotopes of oxygen and carbon on bulk sediment and charophyte remains, as well as on monospecific samples of ostracods, after Pisidium a; in addition pollen, chironomids, and Cladocera were analyzed. The δ18O record serves as an estimate of mean air temperature, and by correlation to the one from NGRIP in Greenland it provides a timescale. The timing of responses: The statistically significant zone boundaries of the biostratigraphies are telescoped at the rapid increase of about 3‰ in δ18O at the onset of Bølling. Biotic responses may have occurred within sampling resolution (8 to 16 years), although younger zone boundaries are less synchronous. Gradual and longer-lasting responses include complex processes such as primary or secular succession. During the late-glacial interstadial of Bølling and Allerød, two stronger and two weaker cool phases were found. Biological processes involved in the responses occurred on levels of individuals (e.g. pollen productivity), of populations (increases or decreases, immigration, or extinction), and on the ecosystem level (species interactions such as facilitation or competition). Abiotic and biotic interactions include pedogenesis, nitrogen-fixation, nutrient cycling, catchment hydrology, water chemistry of the lake and albedo (controlled by the transition from tundra to forest). For the Swiss Plateau this major change in vegetation induced a change in the mammal fauna, which in turn led to changes in the tool-making by Paleolithic people.

Multi-proxy summer and winter precipitation reconstruction for southern Africa over the last 200 years

This study presents the first consolidation of palaeoclimate proxy records from multiple archives to develop statistical rainfall reconstructions for southern Africa covering the last two centuries. State-of-the-art ensemble reconstructions reveal multi-decadal rainfall variability in the summer and winter rainfall zones. A decrease in precipitation amount over time is identified in the summer rainfall zone. No significant change in precipitation amount occurred in the winter rainfall zone, but rainfall variability has increased over time. Generally synchronous rainfall fluctuations between the two zones are identified on decadal scales, with common wet (dry) periods reconstructed around 1890 (1930). A strong relationship between seasonal rainfall and sea surface temperatures (SSTs) in the surrounding oceans is confirmed. Coherence among decadal-scale fluctuations of southern African rainfall, regional SST, SSTs in the Pacific Ocean and rainfall in south-eastern Australia suggest SST-rainfall teleconnections across the southern hemisphere. Temporal breakdowns of the SST-rainfall relationship in the southern African regions and the connection between the two rainfall zones are observed, for example during the 1950s. Our results confirm the complex interplay between large-scale teleconnections, regional SSTs and local effects in modulating multi-decadal southern African rainfall variability over long timescales.

Local changes in neocortical circuit dynamics coincide with the spread of seizures to thalamus in a model of epilepsy

During the generalization of epileptic seizures, pathological activity in one brain area recruits distant brain structures into joint synchronous discharges. However, it remains unknown whether specific changes in local circuit activity are related to the aberrant recruitment of anatomically distant structures into epileptiform discharges. Further, it is not known whether aberrant areas recruit or entrain healthy ones into pathological activity. Here we study the dynamics of local circuit activity during the spread of epileptiform discharges in the zero-magnesium in vitro model of epilepsy. We employ high-speed multi-photon imaging in combination with dual whole-cell recordings in acute thalamocortical (TC) slices of the juvenile mouse to characterize the generalization of epileptic activity between neocortex and thalamus. We find that, although both structures are exposed to zero-magnesium, the initial onset of focal epileptiform discharge occurs in cortex. This suggests that local recurrent connectivity that is particularly prevalent in cortex is important for the initiation of seizure activity. Subsequent recruitment of thalamus into joint, generalized discharges is coincident with an increase in the coherence of local cortical circuit activity that itself does not depend on thalamus. Finally, the intensity of population discharges is positively correlated between both brain areas. This suggests that during and after seizure generalization not only the timing but also the amplitude of epileptiform discharges in thalamus is entrained by cortex. Together these results suggest a central role of neocortical activity for the onset and the structure of pathological recruitment of thalamus into joint synchronous epileptiform discharges.