Mutual Validation of GNSS Height Measurements and High-precision Geometric-astronomical Leveling

The method of geometric-astronomical leveling is presented as a suited technique for the validation of GNSS (Global Navigation Satellite System) heights. In geometric-astronomical leveling, the ellipsoidal height differences are obtained by combining conventional spirit leveling and astronomical leveling. Astronomical leveling with recently developed digital zenith camera systems is capable of providing the geometry of equipotential surfaces of the gravity field accurate to a few 0.1 mm per km. This is comparable to the accuracy of spirit leveling. Consequently, geometric-astronomical leveling yields accurate ellipsoidal height differences that may serve as an independent check on GNSS height measurements at local scales. A test was performed in a local geodetic network near Hanover. GPS observations were simultaneously carried out at five stations over a time span of 48 h and processed considering state-of-the-art techniques and sophisticated new approaches to reduce station-dependent errors. The comparison of GPS height differences with those from geometric-astronomical leveling shows a promising agreement of some millimeters. The experiment indicates the currently achievable accuracy level of GPS height measurements and demonstrates the practical applicability of the proposed approach for the validation of GNSS height measurements as well as the evaluation of GNSS height processing strategies

A comparison of echocardiography to invasive measurement in the evaluation of pulmonary arterial hypertension in a rat model

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by progressive elevation in pulmonary artery pressure (PAP) and total pulmonary vascular resistance (TPVR). Recent advances in imaging techniques have allowed the development of new echocardiographic parameters to evaluate disease progression. However, there are no reports comparing the diagnostic performance of these non-invasive parameters to each other and to invasive measurements. Therefore, we investigated the diagnostic yield of echocardiographically derived TPVR and Doppler parameters of PAP in screening and measuring the severity of PAH in a rat model. Serial echocardiographic and invasive measurements were performed at baseline, 21 and 35 days after monocrotaline-induction of PAH. The most challenging echocardiographic derived TPVR measurement had good correlation with the invasive measurement (r = 0.92, P < 0.001) but also more simple and novel parameters of TPVR were found to be useful although the non-invasive TPVR measurement was feasible in only 29% of the studies due to lack of sufficient tricuspid valve regurgitation. However, echocardiographic measures of PAP, pulmonary artery flow acceleration time (PAAT) and deceleration (PAD), were measurable in all animals, and correlated with invasive PAP (r = −0.74 and r = 0.75, P < 0.001 for both). Right ventricular thickness and area correlated with invasive PAP (r = 0.59 and r = 0.64, P < 0.001 for both). Observer variability of the invasive and non-invasive parameters was low except in tissue-Doppler derived isovolumetric relaxation time. These non-invasive parameters may be used to replace invasive measurements in detecting successful disease induction and to complement invasive data in the evaluation of PAH severity in a rat model

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Sensitivity of Local Dynamic Stability of Over-Ground Walking to Balance Impairment Due to Galvanic Vestibular Stimulation

Impaired balance control during gait can be detected by local dynamic stability measures. For clinical applications, the use of a treadmill may be limiting. Therefore, the aim of this study was to test sensitivity of these stability measures collected during short episodes of over-ground walking by comparing normal to impaired balance control. Galvanic vestibular stimulation (GVS) was used to impair balance control in 12 healthy adults, while walking up and down a 10 m hallway. Trunk kinematics, collected by an inertial sensor, were divided into episodes of one stroll along the hallway. Local dynamic stability was quantified using short-term Lyapunov exponents (λs), and subjected to a bootstrap analysis to determine the effects of number of episodes analysed on precision and sensitivity of the measure. λs increased from 0.50 ± 0.06 to 0.56 ± 0.08 (p = 0.0045) when walking with GVS. With increasing number of episodes, coefficients of variation decreased from 10 ± 1.3% to 5 ± 0.7% and the number of p values >0.05 from 42 to 3.5%, indicating that both precision of estimates of λs and sensitivity to the effect of GVS increased. λs calculated over multiple episodes of over-ground walking appears to be a suitable measure to calculate local dynamic stability on group level

A pulsating auroral X-ray hot spot on Jupiter

Jupiter's X-ray aurora has been thought to be excited by energetic sulphur and oxygen ions precipitating from the inner magnetosphere into the planet's polar regions(1-3). Here we report high-spatial-resolution observations that demonstrate that most of Jupiter's northern auroral X-rays come from a 'hot spot' located significantly poleward of the latitudes connected to the inner magnetosphere. The hot spot seems to be fixed in magnetic latitude and longitude and occurs in a region where anomalous infrared(4-7) and ultraviolet(8) emissions have also been observed. We infer from the data that the particles that excite the aurora originate in the outer magnetosphere. The hot spot X-rays pulsate with an approximately 45-min period, a period similar to that reported for high-latitude radio and energetic electron bursts observed by near-Jupiter spacecraft(9,10). These results invalidate the idea that jovian auroral X-ray emissions are mainly excited by steady precipitation of energetic heavy ions from the inner magnetosphere. Instead, the X-rays seem to result from currently unexplained processes in the outer magnetosphere that produce highly localized and highly variable emissions over an extremely wide range of wavelengths.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62624/1/4151000a.pd

Pattern and determinants of BCG immunisation delays in a sub-Saharan African community

<p>Abstract</p> <p>Background</p> <p>Childhood immunisation is recognised worldwide as an essential component of health systems and an indispensable indicator of quality of care for vaccine-preventable diseases. While performance of immunisation programmes is more commonly measured by coverage, ensuring that every child is immunised at the earliest/appropriate age is an important public health goal. This study therefore set out to determine the pattern and predictors of Bacille de Calmette-Guérin (BCG) immunisation delays in the first three months of life in a Sub-Saharan African community where BCG is scheduled at birth in order to facilitate necessary changes in current policy and practices for improved services.</p> <p>Methods</p> <p>A cross-sectional study in which immunisation delays among infants aged 0-3 months attending community-based BCG clinics in Lagos, Nigeria over a 2-year period from July 2005 to June 2007 were assessed by survival analysis and associated factors determined by multivariable logistic regression. Population attributable risk (PAR) was computed for the predictors of delays.</p> <p>Results</p> <p>BCG was delayed beyond three months in 31.6% of all eligible infants. Of 5171 infants enrolled, 3380 (65.4%) were immunised within two weeks and a further 1265 (24.5%) by six weeks. A significantly higher proportion of infants born in hospitals were vaccinated in the first six weeks compared to those born outside hospitals. Undernourishment was predictive of delays beyond 2 and 6 weeks while treated hyperbilirubinaemia was associated with decreased odds for any delays. Lack of antenatal care and multiple gestations were also predictive of delays beyond 6 weeks. Undernourishment was associated with the highest PAR for delays beyond 2 weeks (18.7%) and 6 weeks (20.8%).</p> <p>Conclusions</p> <p>BCG immunisation is associated with significant delays in this setting and infants at increased risk of delays can be identified and supported early possibly through improved maternal uptake of antenatal care. Combining BCG with subsequent immunisation(s) at 6 weeks for infants who missed the BCG may be considered.</p

Amyloid Oligomer Conformation in a Group of Natively Folded Proteins

Recent in vitro and in vivo studies suggest that destabilized proteins with defective folding induce aggregation and toxicity in protein-misfolding diseases. One such unstable protein state is called amyloid oligomer, a precursor of fully aggregated forms of amyloid. Detection of various amyloid oligomers with A11, an anti-amyloid oligomer conformation-specific antibody, revealed that the amyloid oligomer represents a generic conformation and suggested that toxic β-aggregation processes possess a common mechanism. By using A11 antibody as a probe in combination with mass spectrometric analysis, we identified GroEL in bacterial lysates as a protein that may potentially have an amyloid oligomer conformation. Surprisingly, A11 reacted not only with purified GroEL but also with several purified heat shock proteins, including human Hsp27, 40, 70, 90; yeast Hsp104; and bovine Hsc70. The native folds of A11-reactive proteins in purified samples were characterized by their anti-β-aggregation activity in terms of both functionality and in contrast to the β-aggregation promoting activity of misfolded pathogenic amyloid oligomers. The conformation-dependent binding of A11 with natively folded Hsp27 was supported by the concurrent loss of A11 reactivity and anti-β-aggregation activity of heat-treated Hsp27 samples. Moreover, we observed consistent anti-β-aggregation activity not only by chaperones containing an amyloid oligomer conformation but also by several A11-immunoreactive non-chaperone proteins. From these results, we suggest that the amyloid oligomer conformation is present in a group of natively folded proteins. The inhibitory effects of A11 antibody on both GroEL/ES-assisted luciferase refolding and Hsp70-mediated decelerated nucleation of Aβ aggregation suggested that the A11-binding sites on these chaperones might be functionally important. Finally, we employed a computational approach to uncover possible A11-binding sites on these targets. Since the β-sheet edge was a common structural motif having the most similar physicochemical properties in the A11-reactive proteins we analyzed, we propose that the β-sheet edge in some natively folded amyloid oligomers is designed positively to prevent β aggregation

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy