Detection of back-to-back proton pairs in charged-current neutrino interactions with the ArgoNeuT detector in the NuMI low energy beam line

Short range nucleon-nucleon correlations in nuclei (NN SRC) carry important information on nuclear structure and dynamics. NN SRC have been extensively probed through two-nucleon knock- out reactions in both pion and electron scattering experiments. We report here on the detection of two-nucleon knock-out events from neutrino interactions and discuss their topological features as possibly involving NN SRC content in the target argon nuclei. The ArgoNeuT detector in the Main Injector neutrino beam at Fermilab has recorded a sample of 30 fully reconstructed charged current events where the leading muon is accompanied by a pair of protons at the interaction vertex, 19 of which have both protons above the Fermi momentum of the Ar nucleus. Out of these 19 events, four are found with the two protons in a strictly back-to-back high momenta configuration directly observed in the final state and can be associated to nucleon Resonance pionless mechanisms involving a pre-existing short range correlated np pair in the nucleus. Another fraction (four events) of the remaining 15 events have a reconstructed back-to-back configuration of a np pair in the initial state, a signature compatible with one-body Quasi Elastic interaction on a neutron in a SRC pair. The detection of these two subsamples of the collected (mu- + 2p) events suggests that mechanisms directly involving nucleon-nucleon SRC pairs in the nucleus are active and can be efficiently explored in neutrino-argon interactions with the LAr TPC technology.

Manual Electrode Array Insertion Through a Robot-assisted Minimal Invasive Cochleostomy: Feasibility and Comparison of Two Different Electrode Array Subtypes.

HYPOTHESIS To evaluate the feasibility and the results of insertion of two types of electrode arrays in a robotically assisted surgical approach. BACKGROUND Recent publications demonstrated that robot-assisted surgery allows the implantation of free-fitting electrode arrays through a cochleostomy drilled via a narrow bony tunnel (DCA). We investigated if electrode arrays from different manufacturers could be used with this approach. METHODS Cone-beam CT imaging was performed on fivecadaveric heads after placement of fiducial screws. Relevant anatomical structures were segmented and the DCA trajectory, including the position of the cochleostomy, was defined to target the center of the scala tympani while reducing the risk of lesions to the facial nerve. Med-El Flex 28 and Cochlear CI422 electrodes were implanted on both sides, and their position was verified by cone-beam CT. Finally, temporal bones were dissected to assess the occurrence of damage to anatomical structures during DCA drilling. RESULTS The cochleostomy site was directed in the scala tympani in 9 of 10 cases. The insertion of electrode arrays was successful in 19 of 20 attempts. No facial nerve damage was observed. The average difference between the planned and the postoperative trajectory was 0.17 ± 0.19 mm at the level of the facial nerve. The average depth of insertion was 305.5 ± 55.2 and 243 ± 32.1 degrees with Med-El and Cochlear arrays, respectively. CONCLUSIONS Robot-assisted surgery is a reliable tool to allow cochlear implantation through a cochleostomy. Technical solutions must be developed to improve the electrode array insertion using this approach.

Quick divergence but slow convergence during ecotype formation in lake and stream stickleback pairs of variable age

When genetic constraints restrict phenotypic evolution, diversification can be predicted to evolve along so-called lines of least resistance. To address the importance of such constraints and their resolution, studies of parallel phenotypic divergence that differ in their age are valuable. Here, we investigate the parapatric evolution of six lake and stream threespine stickleback systems from Iceland and Switzerland, ranging in age from a few decades to several millennia. Using phenotypic data, we test for parallelism in ecotypic divergence between parapatric lake and stream populations and compare the observed patterns to an ancestral-like marine population. We find strong and consistent phenotypic divergence, both among lake and stream populations and between our freshwater populations and the marine population. Interestingly, ecotypic divergence in low-dimensional phenotype space (i.e. single traits) is rapid and seems to be often completed within 100 years. Yet, the dimensionality of ecotypic divergence was highest in our oldest systems and only there parallel evolution of unrelated ecotypes was strong enough to overwrite phylogenetic contingency. Moreover, the dimensionality of divergence in different systems varies between trait complexes, suggesting different constraints and evolutionary pathways to their resolution among freshwater systems.

Divergent Macroparasite Infections in Parapatric Swiss Lake-Stream Pairs of Threespine Stickleback (Gasterosteus aculeatus)

Spatial heterogeneity in diversity and intensity of parasitism is a typical feature of most host-parasite interactions, but understanding of the evolutionary implications of such variation is limited. One possible outcome of infection heterogeneities is parasite-mediated divergent selection between host populations, ecotypes or species which may facilitate the process of ecological speciation. However, very few studies have described infections in population-pairs along the speciation continuum from low to moderate or high degree of genetic differentiation that would address the possibility of parasite-mediated divergent selection in the early stages of the speciation process. Here we provide an example of divergent parasitism in freshwater fish ecotypes by examining macroparasite infections in threespine stickleback (Gasterosteus aculeatus) of four Swiss lake systems each harbouring parapatric lake-stream ecotype pairs. We demonstrate significant differences in infections within and between the pairs that are driven particularly by the parasite taxa transmitted to fish from benthic invertebrates. The magnitude of the differences tended to correlate positively with the extent of neutral genetic differentiation between the parapatric lake and stream populations of stickleback, whereas no such correlation was found among allopatric populations from similar or contrasting habitats. This suggests that genetic differentiation is unrelated to the magnitude of parasite infection contrasts when gene flow is constrained by geographical barriers while in the absence of physical barriers, genetic differentiation and the magnitude of differences in infections tend to be positively correlated.

Blackfolds, plane waves and minimal surfaces

Minimal surfaces in Euclidean space provide examples of possible non-compact horizon geometries and topologies in asymptotically flat space-time. On the other hand, the existence of limiting surfaces in the space-time provides a simple mechanism for making these configurations compact. Limiting surfaces appear naturally in a given space-time by making minimal surfaces rotate but they are also inherent to plane wave or de Sitter space-times in which case minimal surfaces can be static and compact. We use the blackfold approach in order to scan for possible black hole horizon geometries and topologies in asymptotically flat, plane wave and de Sitter space-times. In the process we uncover several new configurations, such as black helicoids and catenoids, some of which have an asymptotically flat counterpart. In particular, we find that the ultraspinning regime of singly-spinning Myers-Perry black holes, described in terms of the simplest minimal surface (the plane), can be obtained as a limit of a black helicoid, suggesting that these two families of black holes are connected. We also show that minimal surfaces embedded in spheres rather than Euclidean space can be used to construct static compact horizons in asymptotically de Sitter space-times.

Minimal residual disease in cancer therapy - Small things make all the difference

Minimal residual disease (MRD) is a major hurdle in the eradication of malignant tumors. Despite the high sensitivity of various cancers to treatment, some residual cancer cells persist and lead to tumor recurrence and treatment failure. Obvious reasons for residual disease include mechanisms of secondary therapy resistance, such as the presence of mutant cells that are insensitive to the drugs, or the presence of cells that become drug resistant due to activation of survival pathways. In addition to such unambiguous resistance modalities, several patients with relapsing tumors do not show refractory disease and respond again when the initial therapy is repeated. These cases cannot be explained by the selection of mutant tumor cells, and the precise mechanisms underlying this clinical drug resistance are ill-defined. In the current review, we put special emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms of MRD that are independent of secondary therapy resistance. In particular, we show that studying genetically engineered mouse models (GEMMs), which highly resemble the disease in humans, provides a complementary approach to understand MRD. In these animal models, specific mechanisms of secondary resistance can be excluded by targeted genetic modifications. This allows a clear distinction between the selection of cells with stable secondary resistance and mechanisms that result in the survival of residual cells but do not provoke secondary drug resistance. Mechanisms that may explain the latter feature include special biochemical defense properties of cancer stem cells, metabolic peculiarities such as the dependence on autophagy, drug-tolerant persisting cells, intratumoral heterogeneity, secreted factors from the microenvironment, tumor vascularization patterns and immunosurveillance-related factors. We propose in the current review that a common feature of these various mechanisms is cancer cell dormancy. Therefore, dormant cancer cells appear to be an important target in the attempt to eradicate residual cancer cells, and eventually cure patients who repeatedly respond to anticancer therapy but lack complete tumor eradication.

Synchronous carotid and coronary bypass surgery using minimal extracorporeal circulation does not increase the risk of in-hospital stroke compared to isolated carotid endarterectomy under general anaesthesia

Gebiet: Chirurgie Abstract: Introduction: Carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) could be approached in a combined or a staged fashion. Some crucial studies have shown no significant difference in peri-operative stroke and death rate in combined versus staged CEA/CABG. At present conventional extracorporeal circulation (CECC) is regarded as the gold standard for performing on-pump coronary artery bypass grafting. On contrary, the use of minimized extracorporeal circulation (MECC) for CABG diminishes hemodilution, blood-air contact, foreign surface contact and inflammatory response. At the same time, general anaesthesia (GA) is a potential risk factor for higher perioperative stroke rate after isolated CEA, not only for the ipsilateral but also for the contralateral side especially in case of contralateral high-grade stenosis or occlusion. The aim of the study was to analyze if synchronous CEA/CABG using MECC (CEA/CABG group) allows reducing the perioperative stroke risk to the level of isolated CEA performed under GA (CEA-GA group). – Methods: A retrospective analysis of all patients who underwent CEA at our institution between January 2005 and December 2012 was performed. We compared outcomes between all patients undergoing CEA/CABG to all isolated CEA-GA during the same time period. The CEA/CABG group was additionally compared to a reference group consisting of patients undergoing isolated CEA in local anaesthesia. Primary outcome was in-hospital stroke. – Results: A total of 367 CEAs were performed, from which 46 patients were excluded having either off-pump CABG or other cardiac surgery procedures than CABG combined with CEA. Out of 321 patients, 74 were in the CEA/CABG and 64 in the CEA-GA group. There was a significantly higher rate of symptomatic stenoses among patients in the CEA-GA group (p<0.002). Three (4.1%) strokes in the CEA/CABG group were registered, two ipsilateral (2.7%) and one contralateral (1.4%) to the operated side. In the CEA-GA group 2 ipsilateral strokes (3.1%) occurred. No difference was noticed between the groups (p=1.000). One patient with stroke in each group had a symptomatic stenosis preoperatively. – Conclusions: Outcome with regard to mortality and neurologic injury is very good in both -patients undergoing CEA alone as well as patients undergoing synchronous CEA and CABG using the MECC system. Although the CEA/CABG group showed slightly increased risk of stroke, it can be considered as combined treatment in particular clinical situations.

Use of minimal invasive extracorporeal circulation in cardiac surgery: principles, definitions and potential benefits. A position paper from the Minimal invasive Extra-Corporeal Technologies international Society (MiECTiS).

Minimal invasive extracorporeal circulation (MiECC) systems have initiated important efforts within science and technology to further improve the biocompatibility of cardiopulmonary bypass components to minimize the adverse effects and improve end-organ protection. The Minimal invasive Extra-Corporeal Technologies international Society was founded to create an international forum for the exchange of ideas on clinical application and research of minimal invasive extracorporeal circulation technology. The present work is a consensus document developed to standardize the terminology and the definition of minimal invasive extracorporeal circulation technology as well as to provide recommendations for the clinical practice. The goal of this manuscript is to promote the use of MiECC systems into clinical practice as a multidisciplinary strategy involving cardiac surgeons, anaesthesiologists and perfusionists.

Minimal invasive extracorporeal circulation should become the standard practice in coronary revascularization surgery†.

We read with great interest the large-scale network meta-analysis by Kowalewski et al. comparing clinical outcomes of patients undergoing coronary artery bypass grafting (CABG) operated on using minimal invasive extracorporeal circulation (MiECC) or off-pump (OPCAB) with those undergoing surgery on conventional cardiopulmonary bypass (CPB) [1]. The authors actually integrated into single study two recently published meta-analysis comparing MiECC and OPCAB with conventional CPB, respectively [2, 3] into a single study. According to the results of this study, MiECC and OPCAB are both strongly associated with improved perioperative outcomes following CABG when compared with CABG performed on conventional CPB. The authors conclude that MiECC may represent an attractive compromise between OPCAB and conventional CPB. After carefully reading the whole manuscript, it becomes evident that the role of MiECC is clearly undervalued. Detailed statistical analysis using the surface under the cumulative ranking probabilities indicated that MiECC represented the safer and more effective intervention regarding all-cause mortality and protection from myocardial infarction, cerebral stroke, postoperative atrial fibrillation and renal dysfunction when compared with OPCAB. Even though no significant statistical differences were demonstrated between MiECC and OPCAB, the superiority of MiECC is obvious by the hierarchy of treatments in the probability analysis, which ranked MiECC as the first treatment followed by OPCAB and conventional CPB. Thus, MiECC does not represent a compromise between OPCAB and conventional CPB, but an attractive dominant technique in CABG surgery. These results are consistent with the largest published meta-analysis by Anastasiadis et al. comparing MiECC versus conventional CPB including a total of 2770 patients. A significant decrease in mortality was observed when MiECC was used, which was also associated with reduced risk of postoperative myocardial infarction and neurological events [4]. Similarly, another recent meta-analysis by Benedetto et al. compared MiECC versus OPCAB and resulted in comparable outcomes between these two surgical techniques [5]. As stated in the text, superiority of MiECC observed in the current network meta-analysis, when compared with OPCAB, could be attributed to the fact that MiECC offers the potential for complete revascularization, whereas OPCAB poses a challenge for unexperienced surgeons; especially when distal marginal branches on the lateral and/or posterior wall of the heart need revascularization. This is reflected by a significantly lower number of distal anastomoses performed in OPCAB when compared with conventional CPB. Therefore, taking into consideration the literature published up to date, including the results of the current article, we advocate that MiECC should be integrated in the clinical practice guidelines as a state-of-the-art technique and become a standard practice for perfusion in coronary revascularization surgery.

Direct Mechanical Intervention Versus Combined Intravenous and Mechanical Intervention in Large Artery Anterior Circulation Stroke: A Matched-Pairs Analysis.

BACKGROUND AND PURPOSE Five randomized controlled trials have consistently shown that mechanical thrombectomy (MT) in addition to best medical treatment (±intravenous tissue-type plasminogen activator) improves outcome after acute ischemic stroke in patients with large artery anterior circulation stroke. Whether direct MT is equally effective as combined intravenous thrombolysis with MT (ie, bridging thrombolysis) remains unclear. METHODS We retrospectively compared clinical and radiological outcomes in 167 bridging patients with 255 patients receiving direct MT because of large artery anterior circulation stroke. We matched all patients from the direct MT group who would have qualified for intravenous tissue-type plasminogen activator with controls from the bridging group, using multivariate and propensity score analyses. Functional independence was defined as modified Rankin Scale score of 0 to 2. RESULTS From February 2009 to August 2014, 40 patients from the direct MT group would have qualified for bridging thrombolysis but were treated with MT only. Clinical and radiological characteristics did not differ from the bridging cohort, except for higher rates of hypercholesterolemia (P=0.019), coronary heart disease (P=0.039), and shorter intervals from symptom onset to endovascular intervention (P=0.01) in the direct MT group. Functional independence, mortality, and intracerebral hemorrhage rates did not differ (P>0.1). After multivariate matching analysis outcome in both groups did not differ, except for lower rates of asymptomatic intracerebral hemorrhage (P=0.023) and lower mortality (P=0.007) in the direct MT group. CONCLUSIONS In patients with large anterior circulation stroke, direct mechanical intervention seems to be equally effective as bridging thrombolysis. A randomized trial comparing direct MT with bridging therapy is warranted.

Fast Algorithms Using Minimal Data Structures for Common Topological Relationships in Large, Irregularly-spaced Topographic Data Sets

Digital terrain models (DTM) typically contain large numbers of postings, from hundreds of thousands to billions. Many algorithms that run on DTMs require topological knowledge of the postings, such as finding nearest neighbors, finding the posting closest to a chosen location, etc. If the postings are arranged irregu- larly, topological information is costly to compute and to store. This paper offers a practical approach to organizing and searching irregularly-space data sets by presenting a collection of efficient algorithms (O(N),O(lgN)) that compute important topological relationships with only a simple supporting data structure. These relationships include finding the postings within a window, locating the posting nearest a point of interest, finding the neighborhood of postings nearest a point of interest, and ordering the neighborhood counter-clockwise. These algorithms depend only on two sorted arrays of two-element tuples, holding a planimetric coordinate and an integer identification number indicating which posting the coordinate belongs to. There is one array for each planimetric coordinate (eastings and northings). These two arrays cost minimal overhead to create and store but permit the data to remain arranged irregularly.