Strontium isotope stratigraphy in the Late Cretaceous: Numerical calibration of the Sr isotope curve and intercontinental correlation for the campanian

The white Chalk exposed in quarries at Lagerdorf and Kronsmoor, northwestern Germany, provides a standard section for the European Upper Cretaceous. The Sr-87/Sr-86 values of nannofossil chalk and belemnite calcite increase upward through 330 m of section, from less than or equal to 0.70746 in the Upper Santonian to greater than or equal to 0.70777 in the Lower Maastrichtian. The data define three linear trends separated by major points of inflection at stratigraphic heights in the section of 162 m (75.5 Ma) in the Upper Campanian Galerites vulgaris zone and at -6 m (82.9 Ma), just above the base of the Campanian in the Inoceramus lingua/Goniateuthis quadrata zone. The temporal rate of change of Sr-87/Sr-86 was constant through each of the linear segments of our isotope ''curve'' when viewed at the resolution of our average sampling interval (0.15 m.y.). Fine structure, if rear, may record brief (<100 kyr) excursions of (SrSr)-Sr-87-Sr-86 from values expected from the overall trends. In Lagerdorf, the boundary between the Santonian and Campanian stages, taken here as the level of first occurrence of the belemnite Gonioteuthis granulataquadrata, has an Sr-87/Sr-86 Of 0.707473 +/- 5. This is within error of the values of 0.707457 +/- 16 for this boundary in the U.S. western interior (base of the Scaphites leei III zone) and 0.707479 +/- 9 for this boundary in the English Chalk (top of the Marsupites testudinarius zone). In Kronsmoor, the boundary between the Campanian and Maastrichtian stages, taken here as the level of first occurrence of the belemnite Belemnella lanceolata, has an Sr-87/Sr-86 of 0.707723 +/- 4. This is within error of the values of 0.707725 +/- 20 for this boundary in the U.S. western interior (base of the Baculites eliasi zone) and 0.707728 +/- 5 for this boundary in the English Chalk (defined as in Germany)

Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice

Peer reviewedPublisher PD

Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

Robust Estimation for Linear Panel Data Models

In different fields of applications including, but not limited to, behavioral, environmental, medical sciences and econometrics, the use of panel data regression models has become increasingly popular as a general framework for making meaningful statistical inferences. However, when the ordinary least squares (OLS) method is used to estimate the model parameters, presence of outliers may significantly alter the adequacy of such models by producing biased and inefficient estimates. In this work we propose a new, weighted likelihood based robust estimation procedure for linear panel data models with fixed and random effects. The finite sample performances of the proposed estimators have been illustrated through an extensive simulation study as well as with an application to blood pressure data set. Our thorough study demonstrates that the proposed estimators show significantly better performances over the traditional methods in the presence of outliers and produce competitive results to the OLS based estimates when no outliers are present in the data set

A multi-sensory interactive reading experience for visually impaired children; a user evaluation

© 2018 Springer-Verlag London Ltd., part of Springer Nature The children’s experience of reading is enhanced by visual displays, and through picture book experiences, young children expose themselves to develop socially, personally, intellectually, and culturally. While a sighted person’s mental imagining is constructed mostly through visual experiences, a visually impaired person’s mental images are a product of haptic, taste, smell, and sounds. In this paper, we are introducing a picture book with multi-sensory interactions for the visually impaired children. The key novelty in our concept is the integration of multi-sensory interactions (touch, sound, and smell) to create a new reading experience for visually impaired. Also, this concept is highlighting the lack of appropriately designed sensory reading experiences for visually impaired children. We have conducted a user study with 10 educators, and 25 children from a special school for visually impaired in Malaysia, and our evaluation revealed that this book is engaging and a novel experience of multi-sensory interactions to both children and educators

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Resource use data by patient report or hospital records: Do they agree?

Background: Economic evaluations alongside clinical trials are becoming increasingly common. Cost data are often collected through the use of postal questionnaires; however, the accuracy of this method is uncertain. We compared postal questionnaires with hospital records for collecting data on physiotherapy service use. Methods: As part of a randomised trial of orthopaedic medicine compared with orthopaedic surgery we collected physiotherapy use data on a group of patients from retrospective postal questionnaires and from hospital records. Results: 315 patients were referred for physiotherapy. Hospital data on attendances was available for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two methods produced significantly different estimates of resource use with patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records. Conclusions: Using questionnaires in this study produced data on a greater number of patients compared with examination of hospital records. However, the two data sources did differ in the quantity of physiotherapy used and this should be taken into account in any analysi

Methodological bias in cluster randomised trials

Background: Cluster randomised trials can be susceptible to a range of methodological problems. These problems are not commonly recognised by many researchers. In this paper we discuss the issues that can lead to bias in cluster trials. Methods: We used a sample of cluster randomised trials from a recent review and from a systematic review of hip protectors. We compared the mean age of participants between intervention groups in a sample of 'good' cluster trials with a sample of potentially biased trials. We also compared the effect sizes, in a funnel plot, between hip protector trials that used individual randomisation compared with those that used cluster randomisation. Results: There is a tendency for cluster trials, with evidence methodological biases, to also show an age imbalance between treatment groups. In a funnel plot we show that all cluster trials show a large positive effect of hip protectors whilst individually randomised trials show a range of positive and negative effects, suggesting that cluster trials may be producing a biased estimate of effect. Conclusion: Methodological biases in the design and execution of cluster randomised trials is frequent. Some of these biases associated with the use of cluster designs can be avoided through careful attention to the design of cluster trials. Firstly, if possible, individual allocation should be used. Secondly, if cluster allocation is required, then ideally participants should be identified before random allocation of the clusters. Third, if prior identification is not possible, then an independent recruiter should be used to recruit participants