Hypnotic and opioid anesthetic drug interactions on the CNS, focus on response surface modeling

This chapter will present the conceptual and applied approaches to capture the interaction of anesthetic hypnotic drugs with opioid drugs, as used in the clinical anesthetic state. The graphic and mathematical approaches used to capture hypnotic/opiate anesthetic drug interactions will be presented. This chapter is not a review article about interaction modeling, but focuses on specific drug interactions within a quite narrow field, anesthesia.

Ecology of larval fishes and large zooplankton in the Keweenaw Current region of Lake Superior, with special focus on lake herring, Coregonus artedi

I assessed the influence of the Keweenaw Current and spring thermal bar on the distribution of larval fishes and large zooplankton in Lake Superior. In 1998 and 1999, samples were collected from inshore (0.2 – 3.0 km from shore) and offshore (5.0 – 9.0 km from shore) locations on three transects off the western coast of the Keweenaw Peninsula, Michigan. For larval fishes, density and size distribution patterns of lake herring (Coregonus artedi), rainbow smelt (Osmerus mordax), burbot (Lota lota), deepwater sculpin (Myoxocephalus thompsoni), and spoonhead sculpin (Cottus ricei) suggest a seasonal inshore to offshore movement. For zooplankton, seasonal warming appeared to be the major factor that limited planktonic catches of the primarily benthic Mysisrelicta and Diporeia spp., while simultaneously stimulated growth and reproduction of the cladocerans Daphnia spp., Holopedium gibberum, and Bythotrephes cederstroemi. In contrast, calanoid copepods as a group were abundant throughout the entire sampling season. The greatest abundances of zooplankton were generally encountered offshore, even for the cladocerans, which apparently expanded from inshore to offshore locations with seasonal warming. In 2000, sampling efforts focused on lake herring. Samples were collected from surface waters at 0.1 – 17.0 km from shore on two transects. Lake herring larvae were also reared in the laboratory from eggs in order to validate the use of otolith microstructure for aging. Increment deposition was not statistically different from a daily rate starting from 28 days after hatching, near the time of yolk-sac absorption, but larvae with lower growth rates could not be aged as accurately. In Lake Superior, lake herring tended to be slightly more abundant, larger, and older at inshore locations, but a dense patch of younger larvae was also encountered 7 – 13 km from shore. The distribution iiipatterns suggest that larvae were transported by prevailing currents into the study region, possibly from the more productive spawning regions in western Lake Superior. Growth rates were suppressed at offshore locations where temperatures were less than 8°C. These results indicate that lake herring larvae may be transported far distances from spawning concentrations by longshore currents, and water temperatures may largely control their growth.

Evolution of the Southern Kenya Rift from Miocene to present with a focus on the Magadi area

The Kenya (a.k.a., Gregory) Rift is a geologically active area located within the eastern branch of the larger East African Rift System (EARS). The study area is located in the southern Kenya Rift between 1° South and the Kenya-Tanzania border (covering approximately 1.5 square degrees, semi-centered on Lake Magadi) and is predominantly filled with extrusive igneous rocks (mostly basalts, phonolites and trachytes) of Miocene age or younger. Sediments are thin, less than 1.5Ma, and are confined to small grabens. The EARS can serve both as an analogue for ancient continental rifting and as a modern laboratory to observe the geologic processes responsible for rifting. This study demonstrates that vintage (as in older, quality maps published by the Kenya Geological Survey, that may be outdated based on newer findings) quarter-degree maps can be successfully combined with recently published data, and used to interpret satellite (mainly Landsat 7) images to produce versatile, updated digital maps. The study area has been remapped using this procedure and although it covers a large area, the mapping retains a quadrangle level of detail. Additionally, all geologic mapping elements (formations, faults, etc.) have been correlated across older map boundaries so that geologic units don't end artificially at degree boundaries within the study area. These elements have also been saved as individual digital files to facilitate future analysis. A series of maps showing the evolution of the southern Kenya rift from the Miocene to the present was created by combining the updated geologic map with age dates for geologic formations and fault displacements. Over 200 age dates covering the entire length of the Kenya Rift have been compiled for this study, and 6 paleo-maps were constructed to demonstrate the evolution of the area, starting with the eruption of the Kishalduga and Lisudwa melanephelinites onto the metamorphic basement around 15Ma. These eruptions occurred before the initial rift faulting and were followed by a massive eruption of phonolites between 13-10 Ma that covered most of the Kenya dome. This was followed by a period of relative quiescence, until the initial faulting defined the western boundary of the rift around 7Ma. The resulting graben was asymmetrical until corresponding faults to the east developed around 3Ma. The rift valley was flooded by basalts and trachytes between 3Ma and 700ka, after which the volcanic activity slowed to a near halt. Since 700ka most of the deposition has been comprised of sediments, mainly from lakes occupying the various basins in the area. The main results of this study are, in addition to a detailed interpretation of the rift development, a new geologic map that correlates dozens of formations across old map boundaries and a compilation of over 300 age dates. Specific products include paleomaps, tables of fault timing and displacement, and volume estimates of volcanic formations. The study concludes with a generalization of the present environment at Magadi including discussions of lagoon chemistry, mantle gases in relation to the trona deposit, and biology of the hot springs. Several biologic samples were collected during the 2006 field season in an attempt to characterize the organisms that are commonly seen in the present Lake Magadi environment. Samples were selected to represent the different, distinctive forms that are found in the hotsprings. Each sample had it own distinctive growth habit, and analysis showed that each was formed by a different cyanobacterial. Actual algae was rare in the collected samples, and represented by a few scattered diatoms.

Alternative splicing of pre-mRNA in cancer: focus on G protein-coupled peptide hormone receptors

Through alternative splicing, multiple different transcripts can be generated from a single gene. Alternative splicing represents an important molecular mechanism of gene regulation in physiological processes such as developmental programming as well as in disease. In cancer, splicing is significantly altered. Tumors express a different collection of alternative spliceoforms than normal tissues. Many tumor-associated splice variants arise from genes with an established role in carcinogenesis or tumor progression, and their functions can be oncogenic. This raises the possibility that products of alternative splicing play a pathogenic role in cancer. Moreover, cancer-associated spliceoforms represent potential diagnostic biomarkers and therapeutic targets. G protein-coupled peptide hormone receptors provide a good illustration of alternative splicing in cancer. The wild-type forms of these receptors have long been known to be expressed in cancer and to modulate tumor cell functions. They are also recognized as attractive clinical targets. Recently, splice variants of these receptors have been increasingly identified in various types of cancer. In particular, alternative cholecystokinin type 2, secretin, and growth hormone-releasing hormone receptor spliceoforms are expressed in tumors. Peptide hormone receptor splice variants can fundamentally differ from their wild-type receptor counterparts in pharmacological and functional characteristics, in their distribution in normal and malignant tissues, and in their potential use for clinical applications.

The chemokine CCL20 and its receptor CCR6 in human malignancy with focus on colorectal cancer

Chemokines are a superfamily of small chemotactic cytokines, which interact with their G-protein-coupled receptors. These interactions regulate multiple physiological functions, particularly tissue architecture and compartment-specific migration of white blood cells. It has been found that the chemokine/chemokine receptor system has been utilized by cancer cells for migration and metastasis. The chemokine receptor CCR6 is expressed in colorectal cancer and several other cancer types, and stimulation by its physiological chemokine ligand CCL20 has been reported to promote cancer cell proliferation and migration in vitro. Moreover, CCR6/CCL20 interactions apparently play a role in organ selective liver metastasis of colorectal cancer. Here, we review the literature on expression patterns of CCL20 and CCR6 and their physiological interactions as well as the currently presumed role of CCR6 and CCL20 in the formation of colorectal cancer liver metastasis, providing a potential basis for novel treatment strategies.

Apatani phonology and lexicon, with a special focus on tone

Despite being one of the most extensively researched of Eastern Himalayan languages, the basic morphological and phonological-prosodic properties of Apatani (Tibeto-Burman > Tani > Western) have not yet been adequately described. This article attempts such a description, focusing especially on interactions between segmental-syllabic phonology and tone in Apatani. We highlight three features in particular – vowel length, nasality and a glottal stop – which contribute to contrastively-weighted syllables in Apatani, which are consistently under-represented in previous descriptions of Apatani, and in absence of which tone in Apatani cannot be effectively analysed. We conclude that Apatani has two “underlying”, lexically-specified tone categories H and L, whose interaction with word structure and syllable weight produce a maximum of three “surface” pitch contours – level, falling and rising – on disyllabic phonological words. Two appendices provide a set of diagnostic procedures for the discovery and description of Apatani tone categories, as well as an Apatani lexicon of approximately one thousand entries.

State-of-the-art of imaging detecting endoleaks post-EVAR with special focus on low-flow endoleaks.

Endovascular aortic repair (EVAR) necessitates lifelong surveillance for the patient, in order to detect complications timely. Endoleaks (ELs) are among the most common complications of EVAR. Especially type II ELs can have a very unpredictable clinical course and this can range from spontaneous sealing to aortic rupture. Subgroups of this type of EL need to be identified in order to make a proper risk stratification. Aim of this review is to describe the existing imaging techniques, including their advantages and disadvantages in the context of post-EVAR surveillance with a particular emphasis on low-flow ELs. Low flow ELs cause pressurization of the aortic aneurysm sac with a low velocity filling, leading to difficulty of detection by routine imaging protocols for EVAR surveillance, e.g. bi- or triphasic multislice computed tomographic angiography, magnetic resonance imaging and contrast enhanced ultrasound. In this article, we review the imaging possibilities of ELs and discuss the different imaging strategies available for depicting low flow ELs.

Factors influencing the accuracy of fetal weight estimation with a focus on preterm birth at the limit of viability: a systematic literature review

BACKGROUND Fetal weight estimation (FWE) is an important factor for clinical management decisions, especially in imminent preterm birth at the limit of viability between 23(0/7) and 26(0/7) weeks of gestation. It is crucial to detect and eliminate factors that have a negative impact on the accuracy of FWE. DATA SOURCES In this systematic literature review, we investigated 14 factors that may influence the accuracy of FWE, in particular in preterm neonates born at the limit of viability. RESULTS We found that gestational age, maternal body mass index, amniotic fluid index and ruptured membranes, presentation of the fetus, location of the placenta and the presence of multiple fetuses do not seem to have an impact on FWE accuracy. The influence of the examiner's grade of experience and that of fetal gender were discussed controversially. Fetal weight, time interval between estimation and delivery and the use of different formulas seem to have an evident effect on FWE accuracy. No results were obtained on the impact of active labor. DISCUSSION This review reveals that only few studies investigated factors possibly influencing the accuracy of FWE in preterm neonates at the limit of viability. Further research in this specific age group on potential confounding factors is needed.

Focus on emotion as a catalyst of memory updating during reconsolidation

We share the idea of Lane et al. that successful psychotherapy exerts its effects through memory reconsolidation. To support it, we add further evidence that a behavioral interference may trigger memory update during reconsolidation. Furthermore, we propose that – in addition to replacing maladaptive emotions – new emotions experienced in the therapeutic process catalyze reconsolidation of the updated memory structure.

Pre-clinical in vivo models for the screening of bone biomaterials for oral/craniofacial indications: focus on small-animal models.

Preclinical in vivo experimental studies are performed for evaluating proof-of-principle concepts, safety and possible unwanted reactions of candidate bone biomaterials before proceeding to clinical testing. Specifically, models involving small animals have been developed for screening bone biomaterials for their potential to enhance bone formation. No single model can completely recreate the anatomic, physiologic, biomechanic and functional environment of the human mouth and jaws. Relevant aspects regarding physiology, anatomy, dimensions and handling are discussed in this paper to elucidate the advantages and disadvantages of small-animal models. Model selection should be based not on the 'expertise' or capacities of the team, but rather on a scientifically solid rationale, and the animal model selected should reflect the question for which an answer is sought. The rationale for using heterotopic or orthotopic testing sites, and intraosseous, periosseous or extraskeletal defect models, is discussed. The paper also discusses the relevance of critical size defect modeling, with focus on calvarial defects in rodents. In addition, the rabbit sinus model and the capsule model in the rat mandible are presented and discussed in detail. All animal experiments should be designed with care and include sample-size and study-power calculations, thus allowing generation of meaningful data. Moreover, animal experiments are subject to ethical approval by the relevant authority. All procedures and the postoperative handling and care, including postoperative analgesics, should follow best practice.

Large-scale land acquisitions: Focus on South-East Asia: International Development Policy

Large-scale land acquisition, or "land grabbing", has become a key research topic among scholars interested in agrarian change, development, and the environment. The term "land acquisitions" refers to a highly contested process in terms of governance and impacts on livelihoods and human rights. This book focuses on South-East Asia. A series of thematic and in-depth case studies put "land grabbing" into specific historical and institutional contexts. The volume also offers a human rights analysis of the phenomenon, examining the potential and limits of human rights mechanisms aimed at preventing and mitigating land grabs' negative consequences.