Effects of caffeine and/or nasal CPAP treatment on laryngeal chemoreflexes in preterm lambs

Current knowledge suggests that laryngeal chemoreflexes (LCR) are involved in the occurrence of certain neonatal apneas/bradycardias, especially in the preterm newborn. While caffeine and/or nasal continuous positive airway pressure (nCPAP) are the most frequent options used for treating apneas in preterm newborns, their effects on LCR-related apneas/bradycardias are virtually unknown. The aim of the present study was to test the hypothesis that caffeine and/or nCPAP decreases LCR-related cardiorespiratory inhibition in a preterm ovine model. Seven preterm lambs were born vaginally on gestational day 133 (normal gestation: 147 days) after intramuscular injections of betamethasone and mifepristone. Five days after birth, a chronic surgical instrumentation was performed to record states of alertness, electrocardiogram, systemic arterial pressure, and electromyographic activity of a laryngeal constrictor muscle, as well as to insert a transcutaneous supraglottal catheter. LCR were induced in quiet sleep under four conditions: 1) control (without caffeine or nCPAP); 2) nCPAP (5 cmH2O, without caffeine); 3) caffeine (10 mg/kg infused intravenously for 30 min, without nCPAP); and 4) nCPAP + caffeine. Our results showed that nCPAP consistently blunted LCR-related cardiorespiratory inhibition vs. control condition, contrary to caffeine whose overall effect was nonsignificant. In addition, nCPAP condition was characterized by a more consistent and rapid arousal after HCl injection. No significant differences were observed between all tested conditions with regard to swallowing and cough. It is concluded that nCPAP should be further assessed for its usefulness in treating neonatal apneas linked to LCR

Cliophysics: Socio-political Reliability Theory, Polity Duration and African Political (In)stabilities

Quantification of historical sociological processes have recently gained attention among theoreticians in the effort of providing a solid theoretical understanding of the behaviors and regularities present in sociopolitical dynamics. Here we present a reliability theory of polity processes with emphases on individual political dynamics of African countries. We found that the structural properties of polity failure rates successfully capture the risk of political vulnerability and instabilities in which 87.50%, 75%, 71.43%, and 0% of the countries with monotonically increasing, unimodal, U-shaped and monotonically decreasing polity failure rates, respectively, have high level of state fragility indices. The quasi-U-shape relationship between average polity duration and regime types corroborates historical precedents and explains the stability of the autocracies and democracies.Comment: 4 pages, 3 figures, 1 tabl

Nuclear Targeting of IGF-1 Receptor in Orbital Fibroblasts from Graves' Disease: Apparent Role of ADAM17

Insulin-like growth factor-1 receptor (IGF-1R) comprises two subunits, including a ligand binding domain on extra- cellular IGF-1Rα and a tyrosine phosphorylation site located on IGF-1Rβ. IGF-1R is over-expressed by orbital fibroblasts in the autoimmune syndrome, Graves' disease (GD). When activated by IGF-1 or GD-derived IgG (GD-IgG), these fibroblasts produce RANTES and IL-16, while those from healthy donors do not. We now report that IGF-1 and GD-IgG provoke IGF-1R accumulation in the cell nucleus of GD fibroblasts where it co-localizes with chromatin. Nuclear IGF-1R is detected with anti-IGF-1Rα-specific mAb and migrates to approximately 110 kDa, consistent with its identity as an IGF-1R fragment. Nuclear IGF-1R migrating as a 200 kDa protein and consistent with an intact receptor was undetectable when probed with either anti-IGF-1Rα or anti-IGF-1Rβ mAbs. Nuclear redistribution of IGF-1R is absent in control orbital fibroblasts. In GD fibroblasts, it can be abolished by an IGF-1R-blocking mAb, 1H7 and by physiological concentrations of glucocorticoids. When cell-surface IGF-1R is cross-linked with 125I IGF-1, 125I-IGF-1/IGF-1R complexes accumulate in the nuclei of GD fibroblasts. This requires active ADAM17, a membrane associated metalloproteinase, and the phosphorylation of IGF-1R. In contrast, virally encoded IGF-1Rα/GFP fusion protein localizes equivalently in nuclei in both control and GD fibroblasts. This result suggests that generation of IGF-1R fragments may limit the accumulation of nuclear IGF-1R. We thus identify a heretofore-unrecognized behavior of IGF-1R that appears limited to GD-derived fibroblasts. Nuclear IGF-1R may play a role in disease pathogenesis

Epidemiological Characteristics of Classical Scrapie Outbreaks in 30 Sheep Flocks in the United Kingdom

Most previous analyses of scrapie outbreaks have focused on flocks run by research institutes, which may not reflect the field situation. Within this study, we attempt to rectify this deficit by describing the epidemiological characteristics of 30 sheep flocks naturally-infected with classical scrapie, and by exploring possible underlying causes of variation in the characteristics between flocks, including flock-level prion protein (PrP) genotype profile. In total, the study involved PrP genotype data for nearly 8600 animals and over 400 scrapie cases.We found that most scrapie cases were restricted to just two PrP genotypes (ARQ/VRQ and VRQ/VRQ), though two flocks had markedly different affected genotypes, despite having similar underlying genotype profiles to other flocks of the same breed; we identified differences amongst flocks in the age of cases of certain PrP genotypes; we found that the age-at-onset of clinical signs depended on peak incidence and flock type; we found evidence that purchasing infected animals is an important means of introducing scrapie to a flock; we found some evidence that flock-level PrP genotype profile and flock size account for variation in outbreak characteristics; identified seasonality in cases associated with lambing time in certain flocks; and we identified one case that was homozygous for phenylalanine at codon 141, a polymorphism associated with a very high risk of atypical scrapie, and 28 cases that were heterozygous at this codon.This paper presents the largest study to date on commercially-run sheep flocks naturally-infected with classical scrapie, involving 30 study flocks, more than 400 scrapie cases and over 8500 PrP genotypes. We show that some of the observed variation in epidemiological characteristics between farms is related to differences in their PrP genotype profile; although much remains unexplained and may instead be attributed to the stochastic nature of scrapie dynamics

Epidemiological Characteristics of Classical Scrapie Outbreaks in 30 Sheep Flocks in the United Kingdom

Most previous analyses of scrapie outbreaks have focused on flocks run by research institutes, which may not reflect the field situation. Within this study, we attempt to rectify this deficit by describing the epidemiological characteristics of 30 sheep flocks naturally-infected with classical scrapie, and by exploring possible underlying causes of variation in the characteristics between flocks, including flock-level prion protein (PrP) genotype profile. In total, the study involved PrP genotype data for nearly 8600 animals and over 400 scrapie cases.We found that most scrapie cases were restricted to just two PrP genotypes (ARQ/VRQ and VRQ/VRQ), though two flocks had markedly different affected genotypes, despite having similar underlying genotype profiles to other flocks of the same breed; we identified differences amongst flocks in the age of cases of certain PrP genotypes; we found that the age-at-onset of clinical signs depended on peak incidence and flock type; we found evidence that purchasing infected animals is an important means of introducing scrapie to a flock; we found some evidence that flock-level PrP genotype profile and flock size account for variation in outbreak characteristics; identified seasonality in cases associated with lambing time in certain flocks; and we identified one case that was homozygous for phenylalanine at codon 141, a polymorphism associated with a very high risk of atypical scrapie, and 28 cases that were heterozygous at this codon.This paper presents the largest study to date on commercially-run sheep flocks naturally-infected with classical scrapie, involving 30 study flocks, more than 400 scrapie cases and over 8500 PrP genotypes. We show that some of the observed variation in epidemiological characteristics between farms is related to differences in their PrP genotype profile; although much remains unexplained and may instead be attributed to the stochastic nature of scrapie dynamics

Effectiveness of Biosecurity Measures in Preventing Badger Visits to Farm Buildings

This is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Bovine tuberculosis caused by Mycobacterium bovis is a serious and economically important disease of cattle. Badgers have been implicated in the transmission and maintenance of the disease in the UK since the 1970s. Recent studies have provided substantial evidence of widespread and frequent visits by badgers to farm buildings during which there is the potential for close direct contact with cattle and contamination of cattle feed. METHODOLOGY: Here we evaluated the effectiveness of simple exclusion measures in improving farm biosecurity and preventing badger visits to farm buildings. In the first phase of the study, 32 farms were surveyed using motion-triggered infrared cameras on potential entrances to farm buildings to determine the background level of badger visits experienced by each farm. In the second phase, they were divided into four treatment groups; "Control", "Feed Storage", "Cattle Housing" and "Both", whereby no exclusion measures were installed, exclusion measures were installed on feed storage areas only, cattle housing only or both feed storage and cattle housing, respectively. Badger exclusion measures included sheet metal gates, adjustable metal panels for gates, sheet metal fencing, feed bins and electric fencing. Cameras were deployed for at least 365 nights in each phase on each farm. RESULTS: Badger visits to farm buildings occurred on 19 of the 32 farms in phase one. In phase two, the simple exclusion measures were 100% effective in preventing badger entry into farm buildings, as long as they were appropriately deployed. Furthermore, the installation of exclusion measures also reduced the level of badger visits to the rest of the farmyard. The findings of the present study clearly demonstrate how relatively simple practical measures can substantially reduce the likelihood of badger visits to buildings and reduce some of the potential for contact and disease transmission between badgers and cattle.This work was funded by Defra project number SE3119, http://www.defra.gov.uk/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Macroscopic quantum resonators (MAQRO)

Quantum physics challenges our understanding of the nature of physical reality and of space-time and suggests the necessity of radical revisions of their underlying concepts. Experimental tests of quantum phenomena involving massive macroscopic objects would provide novel insights into these fundamental questions. Making use of the unique environment provided by space, MAQRO aims at investigating this largely unexplored realm of macroscopic quantum physics. MAQRO has originally been proposed as a medium-sized fundamental-science space mission for the 2010 call of Cosmic Vision. MAQRO unites two experiments: DECIDE (DECoherence In Double-Slit Experiments) and CASE (Comparative Acceleration Sensing Experiment). The main scientific objective of MAQRO, which is addressed by the experiment DECIDE, is to test the predictions of quantum theory for quantum superpositions of macroscopic objects containing more than 10e8 atoms. Under these conditions, deviations due to various suggested alternative models to quantum theory would become visible. These models have been suggested to harmonize the paradoxical quantum phenomena both with the classical macroscopic world and with our notion of Minkowski space-time. The second scientific objective of MAQRO, which is addressed by the experiment CASE, is to demonstrate the performance of a novel type of inertial sensor based on optically trapped microspheres. CASE is a technology demonstrator that shows how the modular design of DECIDE allows to easily incorporate it with other missions that have compatible requirements in terms of spacecraft and orbit. CASE can, at the same time, serve as a test bench for the weak equivalence principle, i.e., the universality of free fall with test-masses differing in their mass by 7 orders of magnitude.Comment: Proposal for a medium-sized space mission, 28 pages, 9 figures - in v2, we corrected some minor mistakes and replaced fig. 9 with a higher-resolution version; Experimental Astronomy, March 2012, Online, Open Acces