Inhibition of Notch signaling induces extensive intussusceptive neo-angiogenesis by recruitment of mononuclear cells

Notch is an intercellular signaling pathway related mainly to sprouting neo-angiogenesis. The objective of our study was to evaluate the angiogenic mechanisms involved in the vascular augmentation (sprouting/intussusception) after Notch inhibition within perfused vascular beds using the chick area vasculosa and MxCreNotch1(lox/lox) mice. In vivo monitoring combined with morphological investigations demonstrated that inhibition of Notch signaling within perfused vascular beds remarkably induced intussusceptive angiogenesis (IA) with resultant dense immature capillary plexuses. The latter were characterized by 40 % increase in vascular density, pericyte detachment, enhanced vessel permeability, as well as recruitment and extravasation of mononuclear cells into the incipient transluminal pillars (quintessence of IA). Combination of Notch inhibition with injection of bone marrow-derived mononuclear cells dramatically enhanced IA with 80 % increase in vascular density and pillar number augmentation by 420 %. Additionally, there was down-regulation of ephrinB2 mRNA levels consequent to Notch inhibition. Inhibition of ephrinB2 or EphB4 signaling induced some pericyte detachment and resulted in up-regulation of VEGFRs but with neither an angiogenic response nor recruitment of mononuclear cells. Notably, Tie-2 receptor was down-regulated, and the chemotactic factors SDF-1/CXCR4 were up-regulated only due to the Notch inhibition. Disruption of Notch signaling at the fronts of developing vessels generally results in massive sprouting. On the contrary, in the already existing vascular beds, down-regulation of Notch signaling triggered rapid augmentation of the vasculature predominantly by IA. Notch inhibition disturbed vessel stability and led to pericyte detachment followed by extravasation of mononuclear cells. The mononuclear cells contributed to formation of transluminal pillars with sustained IA resulting in a dense vascular plexus without concomitant vascular remodeling and maturation.

Double arterial perfusion strategy for extensive thoracic aortic surgery to avoid lower body hypothermic circulatory arrest

OBJECTIVE To analyse our results of using a double arterial perfusion strategy to avoid lower body hypothermic circulatory arrest after extensive thoracic aortic surgery. METHODS We analysed the intra- and perioperative courses of 10 patients (median age 58 years, median logistic EuroSCORE 14.6) who underwent extensive thoracic aortic surgery with a double arterial perfusion strategy. The main goal of double arterial perfusion is to separate myocardial and supra-aortic from systemic perfusion. Aortic repair starts at the most distal level of the descending aorta, followed by reinsertion of the supra-aortic vessels, and ends with completion of the proximal anastomosis or by any kind of root repair as needed. RESULTS Seven of 10 patients had prior surgery of the thoracic aorta. Indications for surgery were post-dissection aneurysm in 4 patients, true aneurysm in 3, anastomotic aneurysms in 2 and Type B aortic dissection with pseudo-coarctation in 1. Surgical access was performed through median sternotomy with left hemi-clamshell extension in all cases. There was no in-hospital mortality, but perioperative neurological symptoms occurred in 2 patients. These 2 patients developed delayed stroke (after awaking) after an initial uneventful clinical course, and in 1 of them, neurological symptoms resolved completely during follow-up. The median follow-up was 7 (±13) months. There was no death and no need for additional redo surgery during this observational period. CONCLUSIONS Extensive surgery of the thoracic aorta using a double arterial perfusion technique in order to avoid lower body hypothermic circulatory arrest is an attractive option. Further refinements of this technique may enable the safe and effective simultaneous multisegmental treatment of thoracic aortic pathology in patients who would otherwise have to undergo a two-step surgical approach.

Use of a hand-assisted laparoscopic surgical technique for closure of an extensive mesojejunal rent in a horse

CASE DESCRIPTION A 7-year-old 573-kg (1,261 -lb) Swiss Warmblood gelding was evaluated because of signs of acute abdominal pain. CLINICAL FINDINGS Physical examination revealed a markedly distended abdomen with subjectively reduced borborygmi in all abdominal quadrants. A large, gas-distended viscus was present at the pelvic brim preventing complete palpation of the abdomen per rectum. Ultrasonographic evaluation could not be safely performed in the initial evaluation because of severe signs of abdominal pain. TREATMENT AND OUTCOME Ventral midline celiotomy was performed, and right dorsal displacement of the ascending colon was corrected. Progressive signs of abdominal pain after surgery prompted repeat ventral midline celiotomy, and small intestinal incarceration in a large, radial mesojejunal rent was detected. The incarceration was reduced, but the defect was not fully accessible for repair via the celiotomy. Repair of the mesenteric defect was not attempted, and conservative management was planned after surgery; however, signs of colic returned. A standard laparoscopic approach was attempted from both flanks in the standing patient, but the small intestine could not be adequately mobilized for full evaluation of the rent. Hand-assisted laparoscopic surgery (HALS) allowed identification and reduction of jejunal incarceration and repair of the mesenteric rent. Although minor ventral midline incisional complications were encountered, the horse recovered fully. CLINICAL RELEVANCE HALS techniques should be considered for repair of mesenteric rents in horses. In the horse of this report, HALS facilitated identification, evaluation, and repair of a large radial mesenteric rent that was not accessible from a ventral median celiotomy.

Carboplatin and paclitaxel plus ASA404 as first-line chemotherapy for extensive-stage small-cell lung cancer: a multicenter single arm phase II trial (SAKK 15/08)

INTRODUCTION Small-cell lung cancer (SCLC) is a highly vascularized tumor. ASA404 is a tumor vascular disrupting agent. This is the first trial to report the effects of combining chemotherapy with ASA404 in SCLC. METHODS Patients with untreated metastatic SCLC were treated with carboplatin (area under curve, 6) plus paclitaxel (175 mg/m(2)) plus ASA404 (1800 mg/m(2)) on day 1 every 21 days for up to 6 cycles. The primary endpoint was the progression-free survival (PFS) rate at 24 weeks. RESULTS Median age was 61 years; 53% were women, 41% had weight loss; and 96% had a performance status of 0-1. Twelve patients completed all 6 cycles, and most adverse events were related to chemotherapy. Median PFS and time to progression were 7.0 months (95% CI, 5.7-9.4 months) and 7.5 months (95% CI, 5.7-9.4 months), respectively. The progression-free survival (PFS) rate at 24 weeks was 41% (95% CI, 18%-65%). The overall response rate was 94%. The median overall survival time was 14.2 months (95% CI, 8.2-16.0 months) and 1-year survival was 57%. The median follow-up time was 17.7 months. Due to negative results with ASA404 in non-small-cell lung cancer trials, the trial was stopped prematurely after 17 of 56 planned patients were being accrued. CONCLUSIONS This is the first report of a clinical trial with a vascular disrupting agent in SCLC. No unexpected toxicity was observed. PFS was not prolonged with carboplatin and paclitaxel plus ASA404.

Heart rate variability in response to pain stimulus in VLBW infants followed longitudinally during NICU stay.

The objective of this longitudinal study, conducted in a neonatal intensive care unit, was to characterize the response to pain of high-risk very low birth weight infants (<1,500 g) from 23 to 38 weeks post-menstrual age (PMA) by measuring heart rate variability (HRV). Heart period data were recorded before, during, and after a heel lanced or wrist venipunctured blood draw for routine clinical evaluation. Pain response to the blood draw procedure and age-related changes of HRV in low-frequency and high-frequency bands were modeled with linear mixed-effects models. HRV in both bands decreased during pain, followed by a recovery to near-baseline levels. Venipuncture and mechanical ventilation were factors that attenuated the HRV response to pain. HRV at the baseline increased with post-menstrual age but the growth rate of high-frequency power was reduced in mechanically ventilated infants. There was some evidence that low-frequency HRV response to pain improved with advancing PMA.

The Most Extensive Holocene Advance in the Stauning Alper, East Greenland, Occurred in the Little Ice Age

We present glacial geologic and chronologic data concerning the Holocene ice extent in the Stauning Alper of East Greenland. The retreat of ice from the late-glacial position back into the mountains was accomplished by at least 11 000 cal years B.P. The only recorded advance after this time occurred during the past few centuries (the Little Ice Age). Therefore, we postulate that the Little Ice Age event represents the maximum Holocene ice extent in this part of East Greenland.

Prospective Memory, Retrospective Memory, Executive Functions, and Metacognition: How they are linked longitudinally in young elementary school children

Succeeding in everyday activities often requires executive functioning (EF), metacognitive abilities (MC) and memory skills such as prospective memory (PM) and retrospective memory (RM). These cognitive abilities seem to gradually develop in childhood, possibly influencing each other during development. From a theoretical point of view, it is likely that they are closely interrelated, especially in children. Their empirical relation, however, is less clear. A model that links these cognitive abilities can help to better understand the relation between PM and RM and other cognitive processes. In this project we studied the longitudinal development of PM, RM, EF, and MC in 7-8 year old elementary school children across half a year. 119 second graders (MT1 = 95 months, SDT1, = 4.8 months) completed the same PM, RM, EF and MC tasks twice with a time-lag of 7 months. The developmental progression was analysed using paired t-tests, the longitudinal relationships were analysed using confirmatory factor analysis and all fit indices are in accordance with Hu and Bentler (1998). In general, performance improved significantly (ps < .001) and effect sizes ranged from .45 to .62 (Cohen’s d). CFA revealed a good model fit, c2(227, 119) = 242.56, p = .23, TLI = .973, CFI = .979, RMSEA = .024. At T1, significant cross-sectional links were found between PM T1 and RM T1, between PM T1 and EF T1, and between EF T1 and MC T1. Moreover, significant longitudinal links were found between EFT1 and PMT2 and between EFT1 and MCT2; EF T1 and RM T2 were marginally linked. Results underline previous findings showing that PM, RM, EF, and MC develop significantly during childhood, even within this short time period. Results also indicate that these cognitive abilities are linked not only cross-sectionally, but longitudinally. Most relevant, however, is the predictive role of EF for both metacognition and memory.

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

Duplicate genes emerge as copy-number variations (CNVs) at the population level, and remain copy-number polymorphic until they are fixed or lost. The successful establishment of such structural polymorphisms in the genome plays an important role in evolution by promoting genetic diversity, complexity and innovation. To characterize the early evolutionary stages of duplicate genes and their potential adaptive benefits, we combine comparative genomics with population genomics analyses to evaluate the distribution and impact of CNVs across natural populations of an eco-genomic model, the three-spined stickleback. With whole genome sequences of 66 individuals from populations inhabiting three distinct habitats, we find that CNVs generally occur at low frequencies and are often only found in one of the 11 populations surveyed. A subset of CNVs, however, displays copy-number differentiation between populations, showing elevated within-population frequencies consistent with local adaptation. By comparing teleost genomes to identify lineage-specific genes and duplications in sticklebacks, we highlight rampant gene content differences among individuals in which over 30% of young duplicate genes are CNVs. These CNV genes are evolving rapidly at the molecular level and are enriched with functional categories associated with environmental interactions, depicting the dynamic early copy-number polymorphic stage of genes during population differentiation.

Der Togovertrag, extensive und wirthschaftliche Kolonialpolitik

Aus: Koloniales Jahrbuch. 1897

Contribution of woody habitat islands to the conservation of birds and their potential ecosystem services in an extensive Colombian rangeland

The conservation of birds and their habitats is essential to maintain well-functioning ecosystems including human-dominated habitats. In simplified or homogenized landscapes, patches of natural and semi-natural habitat are essential for the survival of plant and animal populations. We compared species composition and diversity of trees and birds between gallery forests, tree islands and hedges in a Colombian savanna landscape to assess how fragmented woody plant communities affect forest bird communities and how differences in habitat characteristics influenced bird species traits and their potential ecosystem function. Bird and tree diversity was higher in forests than in tree islands and hedges. Soil depth influenced woody species distribution, and canopy cover and tree height determined bird species distribution, resulting in plant and bird communities that mainly differed between forest and non-forest habitat. Bird and tree species and traits widely co-varied. Bird species in tree islands and hedges were on average smaller, less specialized to habitat and more tolerant to disturbance than in forest, but dietary differences did not emerge. Despite being less complex and diverse than forests, hedges and tree islands significantly contribute to the conservation of forest biodiversity in the savanna matrix. Forest fragments remain essential for the conservation of forest specialists, but hedges and tree islands facilitate spillover of more tolerant forest birds and their ecological functions such as seed dispersal from forest to the savanna matrix.

Extensive management of field margins enhances their potential to mitigate soil erosion

Soil erosion is a widespread problem in agricultural landscapes, particularly in regions with strong rainfall events. Vegetated field margins can mitigate negative impacts of soil erosion by trapping eroded material. In this data set, we present data of sediment trapped by 12 field margins during the monsoon season of 2013 in an agricultural landscape in the Haean-myun catchment in South Korea. Prior to the beginning of monsoon season, we equipped a total of 12 sites representing three replicates for each of four different types of field margins ("managed flat", "managed steep", "natural flat" and "natural steep") with Astroturf mats with a size of 34 cm x 25 cm (850 cm**2). The mats (n = 15 / site) were installed at three levels: upslope, immediately before the field margin to quantify the sediments that reach it, in the middle of the field margin to quantify the locally trapped sediments, and after the field margin at the downslope edge to quantify the sediments that leave the field margin to the next field or to the stream. Sediment was collected after each rain event until the end of the monsoon season.

Extensive boiling as a precipitation mechanism for precious and base metal ores, Bienaventurada Mine, Huancavelica, Perú

The Bienaventurada mine operates a polymetallic Ag-Pb-Zn (Cu, Au) vein system of the low sulphidation epithermal type. Fluid inclusions, FI, are abundant in quartz, sphalerite and adularia. FI petrography demonstrates typical primary growth zoning which occurs frequently in crystalline quartz, and defines the most common primary FI. These are usually very small, but several types of primary, P, and secondary, S, FI Assemblages (FIAs) comprising FI of measurable size (3 to > 100 μm) can also be identified through careful petrographic work. The fluids are aqueous and undersaturated, and no evidence of CO2 was found; the degree of fill is usually high (~70-80 %) in the L-rich inclusions, but extremely low in V-rich inclusions. The measured microthermometric values are very consistent in the FIAs selected; they are for the most part roughly similar in the P and S assemblages: the median is typically ~258ºC for total homogenization temperatures, Th, and -1.5 ºC for ice melting temperatures, Tm (corresponding to 2.57 wt% NaCl eq). The widespread occurrence of L-rich and V-rich FI in the same FIA and the consistent Th values point to an extensive boiling system along the vein. In these conditions, Th equals T of trapping, and the ores are assumed to have been precipitated from an aqueous low salinity boiling fluid, of likely meteoric origin, at some 250-280º C, under ~500 m hydrostatic head.

Cálculo de pilas con aparatos de apoyo tipo POT y tablero con punto fijo

In recent years a great number of high speed railway bridges have been constructed within the Spanish borders. Due to the demanding high speed trains route's geometrical requirements, bridges frequently show remarkable lengths. This fact is the main reason why railway bridges are overall longer than roadway bridges. In the same line, it is also worth highlighting the importance of high speed trains braking forces compared to vehicles. While vehicles braking forces can be tackled easily, the railway braking forces demand the existence of a fixed-point. It is generally located at abutments where the no-displacements requirement can be more easily achieved. In some other cases the fixed-point is placed in one of the interior columns. As a consequence of these bridges' length and the need of a fixed-point, temperature, creep and shrinkage strains lead to fairly significant deck displacements, which become greater with the distance to the fixed-point. These displacements need to be accommodated by the piers and bearings deformation. Regular elastomeric bearings are not able to allow such displacements and therefore are not suitable for this task. For this reason, the use of sliding PTFE POT bearings has been an extensive practice mainly because they permit sliding with low friction. This is not the only reason of the extensive use of these bearings to high-speed railways bridges. The value of the vertical loads at each bent is significantly higher than in roadway bridges. This is so mainly because the live loads due to trains traffic are much greater than vehicles. Thus, gravel rails foundation represents a non-negligible permanent load at all. All this together increases the value of vertical loads to be withstood. This high vertical load demand discards the use of conventional bearings for excessive compressions. The PTFE POT bearings' higher technology allows to accommodate this level of compression thanks to their design. The previously explained high-speed railway bridge configuration leads to a key fact regarding longitudinal horizontal loads (such as breaking forces) which is the transmission of these loads entirely to the fixed-point alone. Piers do not receive these longitudinal horizontal loads since PTFE POT bearings displayed are longitudinally free-sliding. This means that longitudinal horizontal actions on top of piers will not be forces but imposed displacements. This feature leads to the need to approach these piers design in a different manner that when piers are elastically linked to superstructure, which is the case of elastomeric bearings. In response to the previous, the main goal of this Thesis is to present a Design Method for columns displaying either longitudinally fixed POT bearings or longitudinally free PTFE POT bearings within bridges with fixed-point deck configuration, applicable to railway and road vehicles bridges. The method was developed with the intention to account for all major parameters that play a role in these columns behavior. The long process that has finally led to the method's formulation is rooted in the understanding of these column's behavior. All the assumptions made to elaborate the formulations contained in this method have been made in benefit of conservatives results. The singularity of the analysis of columns with this configuration is due to a combination of different aspects. One of the first steps of this work was to study they of these design aspects and understand the role each plays in the column's response. Among these aspects, special attention was dedicated to the column's own creep due to permanent actions such us rheological deck displacements, and also to the longitudinally guided PTFE POT bearings implications in the design of the column. The result of this study is the Design Method presented in this Thesis, that allows to work out a compliant vertical reinforcement distribution along the column. The design of horizontal reinforcement due to shear forces is not addressed in this Thesis. The method's formulations are meant to be applicable to the greatest number of cases, leaving to the engineer judgement many of the different parameters values. In this regard, this method is a helpful tool for a wide range of cases. The widespread use of European standards in the more recent years, in particular the so-called Eurocodes, has been one of the reasons why this Thesis has been developed in accordance with Eurocodes. Same trend has been followed for the bearings design implications, which are covered by the rather recent European code EN-1337. One of the most relevant aspects that this work has taken from the Eurocodes is the non-linear calculations security format. The biaxial bending simplified approach that shows the Design Method presented in this work also lies on Eurocodes recommendations. The columns under analysis are governed by a set of dimensionless parameters that are presented in this work. The identification of these parameters is a helpful for design purposes for two columns with identical dimensionless parameters may be designed together. The first group of these parameters have to do with the cross-sectional behavior, represented in the bending-curvature diagrams. A second group of parameters define the columns response. Thanks to this identification of the governing dimensionless parameters, it has been possible what has been named as Dimensionless Design Curves, which basically allows to obtain in a reduced time a preliminary vertical reinforcement column distribution. These curves are of little use nowadays, firstly because each family of curves refer to specific values of many different parameters and secondly because the use of computers allows for extremely quick and accurate calculations.

Some advances in extensive bridge monitoring using low cost dynamic characterization

Dynamic measurements will become a standard for bridge monitoring in the near future. This fact will produce an important cost reduction for maintenance. US Administration has a long term intensive research program in order to diminish the estimated current maintenance cost of US$7 billion per year over 20 years. An optimal intervention maintenance program demands a historical dynamical record, as well as an updated mathematical model of the structure to be monitored. In case that a model of the structure is not actually available it is possible to produce it, however this possibility does not exist for missing measurement records from the past. Current acquisition systems to monitor structures can be made more efficient by introducing the following improvements, under development in the Spanish research Project “Low cost bridge health monitoring by ambient vibration tests using wireless sensors”: (a) a complete wireless system to acquire sensor data, (b) a wireless system that permits the localization and the hardware identification of the whole sensor system. The applied localization system has been object of a recent patent, and (c) automatization of the modal identification process, aimed to diminish human intervention. This system is assembled with cheap components and allows the simultaneous use of a large number of sensors at a low placement cost. The engineer’s intervention is limited to the selection of sensor positions, probably based on a preliminary FE analysis. In case of multiple setups, also the position of a number of fixed reference sensors has to be decided. The wireless localization system will obtain the exact coordinates of all these sensors positions. When the selection of optimal positions is difficult, for example because of the lack of a proper FE model, this can be compensated by using a higher number of measuring (also reference) points. The described low cost acquisition system allows the responsible bridge administration to obtain historical dynamic identification records at reasonable costs that will be used in future maintenance programs. Therefore, due to the importance of the baseline monitoring record of a new bridge, a monitoring test just after its construction should be highly recommended, if not compulsory.

Effect of late weaning and use of alternative cages on performance of does, suckling and fattening rabbits under extensive reproductive management

The effects of the combined use of long lactation periods (46 days) with alternative cages on the reproductive and growth performance of 104 rabbit does and their litters during five consecutive reproductive cycles were studied. Half of does were housed in conventional polyvalent cages (39 cm×100 cm×30 cm) and the other half in alternative polyvalent cages (39 cm×100 cm×60 cm), with a raised platform. Half of the rabbit does in each type of cage were weaned at 32 and the other half at 46 days after parturition. Longer lactation negatively affected the body weight (P<0.001), fat and energy content (P<0.05) of rabbit does at the end of the lactation period, but this effect decreased with the number of parturitions. Fertility, prolificacy and doe mortality were not affected by lactation length. Late weaning led to higher litter size (by 8.9%) and litter weight (by 11.3%) at the end of growing period (P<0.001) and lower feed conversion ratio per cage during the experimental period (13.5%) than weaning at 32 day (P<0.001). These results were paralleled by lower mortality (12.6 vs. 17.6%; P<0.01) of young rabbits weaned later during the overall experimental period. Differences in performance as a result of different weaning ages were only observed during cycles with worst health status (third and fifth cycles) in which late weaning decreased mortality. Type of cage did not affect doe body weight and body condition, mortality, fertility, prolificacy and litter size during the five reproductive cycles. Nevertheless, at day 21 litter weight and feed conversion ratio between 3 and 21 day were 4.2% higher (P<0.01) and 5.0% lower (P<0.05), respectively, in animals housed in alternative rather than in conventional cages. Alternative cages also led to heavier litters at 59 days (P<0.01). It was concluded that the combined use of longer lactations and cages with higher available surface with a raised platform could be alternatives to improve animal welfare in farmed rabbit.