This paper examines the link between the assassination of Michael Collins, the leader of the Irish Republican Army and then the National Army, and the rise in Gaelic Nationalism across Ireland after his death. Ireland struggled to gain independence from England throughout history because England controlled all aspects of Irish life. It was not until 1916, during the Easter Rising, that Collins started to play a key role in Ireland's mission to gain independence. As a result, Collins became a symbol of hope for Ireland's nationalism. On August 22, 1922, Michael Collins was assassinated and became a martyr for Ireland. For many years to come, Irish nationalists celebrated Collins with the highest honors for the important role he played in achieving Ireland's nationalism and independence. He was celebrated in art, politics, music, poetry, film, and national monuments.


A peer helping program was implemented at Central Middle School in Dawson Creek in the school year 1989-1990 following a school evaluation. This article describes the implementation of the program and its evaluation. The evaluation of the program included pre and post-training surveys of the trainees and an untrained comparison group on the acquisition of helping skills, personal development, and changes in self-concept, as well as surveys of parents, of the teaching staff, and the student body. Program evaluation methods and results are presented, and recommendations are made based on the evaluation.


The extent of biodegradation of polyurethane foams produced using the sugar bagasse from native sugar cane plant as a source for natural cellulose fibers for the production of cellulose based biodegradable polyurethane foams was explored in this study. Cellulose microfibers from sugar bagasse were isolated. The chemical and surface morphological structures of the isolated cellulose were characterized with FTIR, SEM, and Lignin content determination. Polyurethane foams were made from polyols containing as much as 25 ml liquid cellulose. The extent of biodegradability of the foams were evaluated using short-term accelerated laboratory experiments including microbial analysis, and soil burial experiments, to determine the integrity of the foams in the soil. The experimental results have shown that the foams studied biodegraded under anaerobic conditions. Weight loss and change in the tensile strength of the foams after biological exposure were observed. The composition of the foams and the liquid cellulose used in this study could have played a significant role in its yield to microbial attack during the biodegradation experiments.


Nerve Cyanide is very dangerous especially for human body and for this reason, perfect extent identification of cyanide is very worthy. In this research, PCF based cyanide sensor is illustrated where, sodium cyanide (NaCN) and potassium cyanide (KCN) are taken as analyte. COMSOL Multiphysics is conducted for the simulation of recommended model. The recommended model exhibits 88.5% sensitivity while NaCN is chosen as analyte at frequency 1.3 THz. This model has very insignificant effective material loss (EML) and only 0.0050 cm−1EML is noticed while KCN is chosen as analyte. Moreover, this recommended model has very negligible confinement loss $(1.2\times 10^{-13}\mathbf{dB}/\mathbf{cm})$.


In practice management, general practice falls into the category of small business with all its attendant generic problems. Disciplined planning and good financial management are not often seen in small business. These are required if general practitioners are to continue (or return to) the provision of high quality medical services. An effective budget process, especially cash-flow budgeting, is the key to successful planning and financial management. Budgeting will bring Control, Co-ordination, and Credibility to your practice. It will enable you to set goals and to achieve them.


The present invention pertains to a system, method, and device for treating sleep disorders. The present invention is particularly useful in the delivery of carbon dioxide (CO2) to a subject and in the treatment of sleep apnea. Furthermore, integration of components with various sensors and apparatuses associated therewith and attached thereto preferably complete a rebreathing circuit in the present invention. In various embodiments of the present invention where the above components are integrated as a rebreathing circuit, a subject is both the source and recipient of a controlled concentration of carbon dioxide. In such embodiments, treatment of sleep disorders becomes much more efficient and effective.


Learning goal-directed behavior in environments with sparse feedback is a major challenge for reinforcement learning algorithms. The primary difficulty arises due to insufficient exploration, resulting in an agent being unable to learn robust value functions. Intrinsically motivated agents can explore new behavior for its own sake rather than to directly solve problems. Such intrinsic behaviors could eventually help the agent solve tasks posed by the environment. We present hierarchical-DQN (h-DQN), a framework to integrate hierarchical value functions, operating at different temporal scales, with intrinsically motivated deep reinforcement learning. A top-level value function learns a policy over intrinsic goals, and a lower-level function learns a policy over atomic actions to satisfy the given goals. h-DQN allows for flexible goal specifications, such as functions over entities and relations. This provides an efficient space for exploration in complicated environments. We demonstrate the strength of our approach on two problems with very sparse, delayed feedback: (1) a complex discrete stochastic decision process, and (2) the classic ATARI game `Montezuma's Revenge'.


Network monitoring and diagnostics systems depict the running system's state and generate enormous amounts of unstructured data through log files, print statements, and other reports. It is not feasible to manually analyze all these files due to limited resources and the need to develop custom parsers to convert unstructured data into desirable file formats. Prior research focuses on rule-based and relationship-based parsing methods to parse unstructured data into structured file formats; these methods are labor-intensive and need large annotated datasets. This paper presents an unsupervised text processing pipeline that analyses such text files, removes extraneous information, identifies tabular components, and parses them into a structured file format. The proposed approach is resilient to changes in the data structure, does not require training data, and is domain-independent. We experiment and compare topic modeling and clustering approaches to verify the accuracy of the proposed technique. Our findings indicate that combining similarity and clustering algorithms to identify data components had better accuracy than topic modeling.


Importance An increased risk of lymphoma has been reported among patients receiving thiopurines for inflammatory bowel disease (IBD). The risk of lymphoma associated with anti–tumor necrosis factor (TNF) agents either alone or in combination with thiopurines is uncertain. Objective To assess the risk of lymphoma associated with thiopurines and anti-TNF agents, used alone or in combination, for the management of IBD. Design, Setting, and Participants Nationwide cohort study based on French National Health Insurance databases. Patients aged 18 years or older identified with IBD were included from January 1, 2009, through December 31, 2013, and followed up until December 31, 2015. Exposures At each time of the follow-up, patients were categorized as being exposed to thiopurine monotherapy, anti-TNF monotherapy, or combination therapy, or being unexposed. Main Outcomes and Measures The primary outcome was incident lymphoma. Results Among the 189 289 patients included (54% women; median age, 43 years [interquartile range, 32-56 years]) and followed up for a median of 6.7 years, 123 069 were never exposed during follow-up, 50 405 were exposed to thiopurine monotherapy, 30 294 to anti-TNF monotherapy, and 14 229 to combination therapy. Overall, 336 lymphoma cases occurred: 220 in unexposed patients (incidence rate [IR] per 1000 person-years, 0.26; 95% CI, 0.23-0.29), 70 in patients exposed to thiopurine monotherapy (IR, 0.54; 95% CI, 0.41-0.67), 32 in patients exposed to anti-TNF monotherapy (IR, 0.41; 95% CI, 0.27-0.55), and 14 in patients exposed to combination therapy (IR, 0.95; 95% CI, 0.45-1.45). In a multivariable Cox model, compared with unexposed patients, the risk of lymphoma was higher among those exposed to thiopurine monotherapy (adjusted hazard ratio [aHR], 2.60; 95% CI, 1.96-3.44; P < .001), anti-TNF monotherapy (aHR, 2.41; 95% CI, 1.60-3.64; P < .001), or combination therapy (aHR, 6.11; 95% CI, 3.46-10.8; P < .001). The risk was higher in patients exposed to combination therapy vs those exposed to thiopurine monotherapy (aHR, 2.35; 95% CI, 1.31-4.22; P < .001) or anti-TNF monotherapy (aHR, 2.53; 95% CI, 1.35-4.77; P < .001). Conclusions and Relevance Among adults with IBD, the use of thiopurine monotherapy or anti-TNF monotherapy was associated with a small but statistically significant increased risk of lymphoma compared with exposure to neither medication, and this risk was higher with combination therapy than with each of these treatments used alone. These findings may inform decisions regarding the benefits and risks of treatment.


This paper presents an efficient procedure based on 2-D convolutions to obtain delay-Doppler maps (DDMs) of Global Navigation Satellite Signals reflected (GNSS-R) over the sea surface and collected by a spaceborne receiver. Two DDM-derived observables (area and volume) are proposed to link the sea-state-induced brightness temperature to the measured normalized DDM. Finally, the requirements to use Global Positioning System reflectometry to accurately correct for the sea state impact on the L-band brightness temperature (quantization levels, decimation, truncation, and noise impact) are analyzed in view of its implementation in the Passive Advanced Unit instrument of the Spanish Earth Observation Satellite (SeoSAT/INGENIO) project.


In this paper we revisit the results in Caner and Hansen (2001), where the authors obtained novel limiting distributions of Wald type test statistics for testing for the presence of threshold nonlinearities in autoregressive models containing unit roots. Using the same framework, we obtain a new formulation of the limiting distribution of the Wald statistic for testing for threshold effects, correcting an expression that appeared in the main theorem presented by Caner and Hansen. Subsequently, we show that under a particular scenario that excludes stationary regressors such as lagged dependent variables and despite the presence of a unit root, this same limiting random variable takes a familiar form that is free of nuisance parameters and already tabulated in the literature, thus removing the need to use bootstrap based inferences. This is a novel and unusual occurrence in this literature on testing for the presence of nonlinear dynamics.


Understanding reusable software and assets within and among multiple organizations' system infrastructures can be challenging. IT systems might be widely distributed, and interconnections can be complicated. Ever-evolving computing technologies reduce an organization's in-house expertise for reusing software, even when leveraging software systems within its own firewalls. As such, the on-demand integration of software and capabilities might benefit from an outsourcing paradigm - described here as composition as a service.


The spleens from two patients with Felty's syndrome and the bone marrow from one patient with Felty's syndrome were examined for the presence of intracytoplasmic inclusions in neutrophils when stained with antibodies to IgG, IgM, IgA, and betalc. Four normal spleens from trauma patients were similarly examined. In both spleens and the bone marrow from the Felty patients, large inclusions were noted. In none of the four normal spleens were large inclusions present. These studies suggest that phagocytosis of immune complexes by neutrophils in Felty patients may induce sequestration of these cells in the spleen and bone marrow.


When this book was published in 1984, it reframed the debate on the French Revolution, shifting the discussion from the Revolution's role in wider, extrinsic processes (such as modernization, capitalist development, and the rise of twentieth-century totalitarian regimes) to its central political significance: the discovery of the potential of political action to consciously transform society by molding character, culture, and social relations. In a new preface to this twentieth-anniversary edition, Hunt reconsiders her work in the light of the past twenty years' scholarship.


This paper combines Feasible Sequential Quadratic Programming (FSQP) and elasto-plastic finite element method to perform the inverse estimation of the material constitutive constants and friction coefficient in the nosing process. The aim is to improve the accuracy of constitutive constants and working parameters in the classical analysis based on the material flow homogeneity or trial and error. In the prediction of the friction coefficient at the interface between metal and tool surface, the simulated load, calculated from the optimal material constants, shows good coincidence with the experimental load when the optimal friction coefficient is reached. The investigation of these inverse models identify that the combination of FSQP and elasto-plastic finite element method can supply a useful optimal approach in the industrial application.


Background Repeated transarterial chemoembolization (TACE) can be associated with loss of its efficacy and subsequent tumor progression. Purpose To identify features of gadoxetic acid-enhanced magnetic resonance imaging (MRI) associated with TACE refractoriness and to develop a prediction model for estimating the risk of TACE refractoriness. Material and Methods Among 1025 patients with intermediate-stage hepatocellular carcinoma (HCC) who underwent TACE as a first-line treatment during 2010–2017, 427 patients who underwent preoperative gadoxetic acid-enhanced MRI were analyzed. According to the date of initial TACE, patients were divided into the development cohort (n = 211) and the test cohort (n = 216). TACE refractoriness was determined according to the Japan Society of Hepatology guidelines. Univariable and multivariable analyses were performed to investigate the association between clinical/MRI features and TACE refractoriness. The performance of the prediction model was internally and externally assessed using the C-index of discrimination and a Hosmer-Lemeshow goodness-of-fit test for calibration. Results By analyzing 427 patients, we constructed a prediction model with the following independent features associated with TACE refractoriness: maximum tumor size; tumor number; peritumoral hypointensity on hepatobiliary phase (HBP); and the presence of non-hypervascular hypointense nodule on HBP. This system enabled the prediction of TACE refractoriness in the development cohort (C-index, 0.796) and the test cohort (C-index, 0.738) with good discrimination and calibration abilities. Conclusion The prediction model based on gadoxetic acid-enhanced MRI features in addition to the known predictors including tumor size and number can be used to estimate the risk of TACE refractoriness in patients with intermediate-stage HCC.


Background: Rhinitis is one of the commonest occupational related respiratory disorders that is only restricted to the upper airway but can involve the lower respiratory tract with considerable airflow limitation, this study was conducted assess the ventilator function of persons exposed to saw dust with rhinitis symptoms Methods:  This is a cross sectional study carried out among 200 randomly selected saw mill workers and 200 healthy staff of Jos University Teaching Hospital staff in Jos metropolis from September to November 2008. Data on sociodemographic variables, symptoms of rhinitis, etc was obtained using a modified semi structured British medical research council questionnaire while respiratory function data was measured using a spirometry Result:  A total of 400 responds comprising of 200 saw mill workers and 200 controls participated in this study. Based on diagnostic criteria. 43% of the subjects fit into diagnosis of rhinitis, 33% had asthma symptoms and 24 % did not fit into any category compared to none of < 5% of the control group. The ventilatory function based on FEV1, FVC, FEV1/FVC ratio and PEFR showed a significant decline when matched with controls and predicted value, suggesting an airflow limitation among the rhinitis group. Conclusion:  Rhinitis associated with wood dust exposure is not restricted to airway but involves the entire respiratory tract with airflow limitation as one of its consequences. Keywords: Ventilatory function, Rhinitis, wood dust exposure


"Summer is on its way and my partner and I managed to grow this rose which has a wonderful scent." A picture of a beautiful orange flower accompanied the note—part of a weekly email sharing good news with the members of our research center. One year ago, an announcement like this could have seemed insignificant and irrelevant to the important work of science. But amid the difficulties of 2020, it was anything but. It put a smile on my face, and hopefully it did the same for my colleagues. It helped build human connection. And it reminded us that, even this year, good things happened.

> "Highlighting the positive moments … helped keep our spirits up."

Last year, the director of the research center in Australia where I serve as the business strategy manager asked me to help maintain a positive, productive culture. Back then, I didn't anticipate that the task was going to be so difficult. Then, of course, came 2020.

During the first half of the year, Australia experienced an extreme drought followed by devastating bushfires and heavy rainfall that brought massive flooding. Next came the pandemic. With people not coming in to the lab or staying only long enough to conduct their experiments, we lost our sense of interpersonal connection. Then, in July, our director shared that she had been diagnosed with a rare and aggressive cancer.

In the wake of that devastating announcement, one of the center's group leaders suggested we send our director weekly good news to keep her informed and to try to lift her spirits. One week later, we sent the first email. The rule was that no good news was too small to share. We reported the arrival of much-needed new computers for one lab, one of our group leaders being contacted by a journalist for their expert opinion on viruses in the context of the pandemic, a student submitting their thesis, a paper being published, and a group leader securing child care spots for their children.

The effect of this simple newsletter—which went to all the group leaders as well as our director—was profound. Many people responded, saying they enjoyed this informal venue for learning about their colleagues' successes. The flood of negative news had kept us from noticing the good things that were happening. Highlighting the positive moments didn't mean we were ignoring the larger catastrophes, but it helped keep our spirits up. I also realized that, prior to the newsletter, some group members didn't know about others' successes. Sharing these updates more publicly gave everyone a boost. After a few weeks, we decided to broaden the recipient list to include everyone at the center.

These days, we solicit good news every Wednesday and send out an email every Friday. The process and format are simple and no-frills, making the newsletter sustainable. At first I worried that people might be hesitant to share updates that seemed too insignificant, but the opposite has been true; they have been eager to highlight their endeavors and successes, big and small, professional and personal. Good news we've shared includes securing grants and fellowships, publishing papers, becoming parents, turning 40, and—of course—growing roses on one's balcony. "I love good news time," a colleague wrote after a recent email. "It really is uplifting."

Last month, one group leader's good news was that, after breaking his arm, he finally had his cast removed. The next week, he reported that his daughter broke her arm and offered the tongue-in-cheek hypothesis that the number of broken bones in his family is a conserved quantity. It wasn't exactly good news, but the joke made me chuckle. Equally important, it's personal news, and sharing it helps us stay connected in these difficult times.

With 2020 drawing to a close, we can hope for better things in 2021. But regardless of what the future holds, we plan to continue to share our good news.


This thesis aims to compare the potential in handling and performance between a brake based Electronic Stability Control system (ESC) with a system that integrates an active differential with ESC. Two control strategies that integrate an active differential and ESC are presented for two types of active differentials. The differentials are the Electronic Limited Slip Differential (eLSD) and the Direction Sensitive Locking Differential (DSLD).
The control strategies are developed and the results are evaluated using a simulation model that is implemented in Simulink. They tested for one driving case, the open loop sine with dwell maneuver. The different solutions are evaluated mainly with regard to three criteria that are specified in the American National Highway Traffic Safety Administration FMVSS 126 law requirement (NTHSA, 2007). They are also evaluated with respect to the yaw rate vs. steering wheel angle response, vehicle speed during the maneuver and vehicle trajectory.
All tests were performed without any time delays simulated for any actuator. The results show only a small difference between a normal ESC and the integrated solutions. The integrated system with an eLSD however does perform better than ESC overall but by a small margin.
Because of the small difference in results from the first simulations time delays are implemented for a second round of simulations that only compare the best integrated solution (ESC + eLSD) to only ESC. This is done to evaluate how much of an effect the time delays have on the end results. After the second round of simulations the results do indeed differ more in favor of the integrated system with the eLSD compared to only ESC. The yaw rate respond better to steering wheel inputs with smaller overshoots and more speed is conserved through the maneuver. This shows that the simulation model might not be complete enough to evaluate the performance difference between those systems and implementing time delays more extensively for all actuators is a recommendation for future work.


Planning HVDC facilities presents special physical and commercial challenges, especially in systems with deregulated markets. This paper describes some of the issues that must be addressed to successfully plan and operate an HVDC facility. Three case studies are discussed. It is beneficial to implement procedures that are as simple as possible yet maximize the secure and economical operation of the facility and the overall network


This paper presents a filtered-X Lyapunov algorithm for nonlinear active noise control (ANC) using second-order Volterra filter-based the filter-blank structure. Unlike many adaptive filtering schemes using gradient algorithm, a Lyapunov function of the tracking error is first defined, and second-order Volterra filter coefficients are adjusted using Lyapunov stability theory so that the error converges to zero asymptotically. Moreover, it has fast error convergence property and its stability is guaranteed by Lyapunov stability theory.


The exploration of atomic nuclei across the nuclear landscape poses a great challenge in nuclear theory. In this thesis, we investigate nuclei on the nuclear chart for which the effective number of degrees of freedom is significantly smaller than the number of nucleons. This phenomenon is called clustering and becomes extreme for so-called halo nuclei. These exotic nuclei occur along the neutron and proton driplines far from the valley of stability. They exhibit a scale separation apparent through the small separation energy of the loosely bound valence nucleons in contrast to the high binding and excitation energies of the core. By exploiting this scale separation, we construct an effective field theory (EFT) called Halo EFT which allows to describe these systems in a controlled and systematically improvable manner.

In the first part, we investigate the one-neutron halo structures within ¹⁵C. They appear in the ground 1/2⁺ and in the first excited 5/2⁺ state. The ground state is predominantly bound in an S-wave while the 5/2⁺ excited state is predominantly bound in a D-wave. Within Halo EFT, using standard Cartesian coordinates, we discuss static electromagnetic properties as well as electromagnetic transitions in halo nuclei and apply our results to ¹⁵C. Since our results are universal, we are able to compare them to ab initio results. This possibility enables us to determine unknown low-energy constants, in turn increasing the predictive power of our Halo EFT.

The second system is the one-neutron halo nucleus ³¹Ne which is bound in a P-wave. In this case, we construct a Halo EFT using a spherical basis, an approach ideally suited for the inclusion of halo states beyond the S-wave. Thereby, we investigate the electromagnetic E1 breakup reaction into the continuum consisting of the neutron and ³⁰Ne core. Additionally, we provide results for static properties and discuss the deformation of ³¹Ne due to the non-vanishing quadrupole moment.

The third part is a pilot study of the weak decay of the valence neutron of the halo nucleus ¹¹Be into the continuum within Halo EFT. This process, denoted ¹¹Be → ¹⁰Be + p + e⁻ + νₑ, is called beta-delayed proton emission. The experimental determination of the branching ratio for this decay remains an unsolved problem due to inconsistent measurements in different experiments. We calculate the rate of this rare decay with a robust uncertainty estimate. We also discuss the impact of a recently discovered resonance in ¹¹B on the branching ratio and compare it to different experimental results.

In the fourth and final part of this thesis, we investigate the universal behavior of weakly bound charged systems in three- and one-dimensional space. The focus lies on the study of one-proton halo nuclei bound in an S-wave. In particular, the impact of the repulsive long-ranged Coulomb force is analyzed. It introduces an additional length scale D (or momentum scale kᴄ). We classify universal regimes characterized by the different hierarchies of the Coulomb-modified scattering length aᴄ and D.


In the mid 1980's it will be possible to put a million devices (transistors or active MOS gate electrodes) onto a single silicon chip. General trends in the evolution of silicon integrated circuits are reviewed and design constraints for emerging VLSI circuits are analyzed. Desirable architectural features in modern computers are then discussed and consequences for an implementation with large-scale integrated circuits are investigated. The resulting recommended processor design includes features such as an on-chip memory hierarchy, multiple homogeneous caches for enhanced execution parallelism, support for complex data structures and high-level languages, a flexible instruction set, and communication hardware. It is concluded that a viable modular building block for the next generation of computing systems will be a self-contained computer on a single chip. A tentative allocation of the one milion transistors to the various functional blocks is given, and the result is a memory intensive design.


This study reports the impact of infection by the mermithid nematode Gasteromermis sp. on the secondary sexual morphology and behaviour of its adult mayfly host Baetis bicaudatus. By applying the technique of flow cytometry I show that both male and female mayflies are infected by the parasite. The external secondary sexual characters of infected male hosts are feminized resulting in the formation of intersexes and it is possible that some infected males undergo complete sex reversal. The external morphology of infected female hosts is not altered. The behaviour of infected hosts is also affected. Infected mayflies join unparasitized females in upstream dispersal and ovipositing behaviour. I suggest that these alterations are induced by the parasite as an adaptive strategy that ensures: (i) upstream dispersal; (ii) return to water for completion of parasite life cycle; and (iii) maximum use of host nutrients.


We apply inviscid rapid distortion theory to the limiting hyperbolic case of turbulent plain strain flow in a rotating frame and investigate the dependence of the evolution of the turbulent kinetic energy on the frame rotation rate. We derive an analytical two-dimensional solution that, unlike previous oversimplified pressureless analyses, allows for an accurate approximation of the three-dimensional initially isotropic problem. From the analytical solutions, we determine the correct stability criterion for the evolution of the turbulent kinetic energy in this flow. Also, we calculate the asymptotic states of the turbulence, in terms of the normalized Reynolds stresses and structure dimensionality tensor components, which coincide with the exact three-dimensional numerical results.


Using of a safe life approach is necessitated by the small critical crack sizes and rapid crack growth rates resulting from the severe vibratory environment of rotorcraft. However Based on the success of damage tolerance initiative for airframe structure, a crack growth based on damage tolerance approach is being examined for implementation into the design and management of dynamic components. In this paper the crack growth behavior in low cycle fatigue (LCF) and high cycle fatigue (HCF) are compared and the accuracy of several damage tolerance analysis methods in determining the crack growth life from an initial detectable crack size 1.25 mm to 12 mm for a rotorcraft main rotor yoke are investigated. The real rotorcraft materials measured by experiment and the fatigue load mean frequency spectrum based on statistical usage spectrum are adopted. The crack growth equations used in the programs are discussed to provide a basis for understanding the results. The results show that the load less than the safe fatigue limit has an important effect on crack growth life and it is reasonable for the material that the cut-off stress ratio for the threshold stress intensity factor range is set 0.7.


In case-control studies of complex disease genes, allele frequencies or allele positivities at candidate loci or markers are compared between cases and controls. Although 2 x 2 contingency tables based on allele frequency and allele positivity are generally used to perform simple statistical tests (e.g. a comparison of two proportions and a chi2 test), little is known about the difference in power between the two tables. In this study, we investigated the number of subjects required to obtain a power of 1-beta with a significance level of alpha for the allele frequency and allele positivity tables. A large difference in the required number of subjects was found between the two tables. Allele positivity tables were suitable for the detection of susceptibility alleles showing a dominant mode of inheritance (MOI). On the other hand, allele frequency tables were suitable for the identification of susceptibility alleles showing a recessive MOI or a multiplicative MOI. In the case of an additive MOI, a suitable table was determined by combining the frequency of the susceptibility allele and the penetrance. These results imply that there are cases in which true association is detected based on one contingency table and is not detected based on another. A simulation analysis revealed that the type I error rate was not much inflated under the null hypothesis of no association, even when a statistical test was performed twice using both allele frequency and allele positivity tables. In contrast, under the alternative hypothesis, the loss of power was marked when a test was performed once using an unsuitable table. In conclusion, statistical tests should be performed using both tables, without adjustment of multiplicity, in case-control studies of complex disease genes when the study objective is exploratory.


RATIONALE
When comparing patients' pain ratings with the health care professional's conception of pain assessed by Visual Analogue Scales (VAS) ratings, statistical problems arise.

METHOD AND RESULT
In this data simulation study we have shown that the tendency for health care professionals to underestimate severe pain compared with mild pain is probably not attributed to difficulties in judging severe pain more often than mild but the result of professionals having a different and often narrower distribution of their ratings compared with patients.


Analysis of permafrost dynamics with a three-phase, two-component flow system coupled to heat transport is used to evaluate transient changes in groundwater seepage. Both seasonal and annual analysis of flow is conducted, assuming three warming temperature trends over a ten year period, representing three climate change scenarios. Previous results have indicated that a reduction in temporal variability of groundwater flow is expected to occur for a moderate temperature trend over long warming time periods. Here, new results indicate this is also expected for larger rates-of-change of temperature increase and over shorter time periods. Additionally it is shown that short-term annual flow variability may serve as early indicators for permafrost degradation also for greater warming trends, rather than solely relying on long-term changes in mean flows.


To analyze stress during the intermediate stage of gestation, 43 multiparous, crossbred Santa Ines, pregnant ewes, with a average age of 5 and average body weight (BW) of 60kg, were challenged with a intravenous administration of 0.8µg.kg-1 of LPS (lipopolysaccharide E. coli - outer membrane cell of gram-negative bacteria), diluted in physiological saline solution - simulating an immune stressor. The females were placed in individual cages at feedlot, with adaptation period of 5 days before the begin of sampling, with free access to good water quality, shade and food in the trough (corn silage and mineral supplementation). The ewes were divided into three groups, with a completely randomized design (CRD): CG - control group, with 15 animals that were not subjected to stress; IG - intermediate group stage, with 14 animals undergoing stress at 70 days of gestation; FG – final group, made up of 14 animals undergoing stress at 120 days of gestation. The variables used to investigate stress were measured during the intermediate stages of pregnancy in a 24 hour sampling, with this was possible to observe the change in rectal temperature (RT) and blood levels of cortisol by its circadian rhythm. Shortly after the baseline sampling, the treatment corresponding to the intermediate stage of gestation was submitted to stress, with the sampling interval of one hour each, from the first to the third samplings and after it the samplings was taken from two to two hours till the end of 24h sampling. At the same time, a dose of placebo was administered in the animals that didn't receive LPS, equalizing the effect of the invasive needle. The study was approved by Ethics Committee of FZEA/USP (13.1.2109.74.8). Variance analysis was performed with multiple comparisons of means by Tukey test with 5%. Significant difference in RT between IG and the other treatments at 07:00 h, 09:00 h, 11:00 h, 23:00 h, 01:00 h, 03:00 h and 05:00 h were observed, with no difference (P>0.05) between CG and FG in those times. As cortisol levels during the circadian rhythm, the figures for IG were higher than the CG and FG to 06:00 h, 07:00 h, 09:00 h, 11:00 h, 13:00 h, 15:00 h, 01:00 h and 03:00 h. No significant differences (P>0.05) were observed between CG and FG in any of the crops of cortisol. The highest RT for IG was observed at 21:00 h, with a range of 1.26°C basal RT, but there was no significant difference within treatments at 9:00, a time that had the highest the amount of cortisol. As the values of RT the three treatments differed at 9:00 h, where it was found the highest value of serum cortisol in time for IG, with a difference of basal crop of 12.4225 µg d/L (P<0.05). The use of LPS to induce stress in sheep at the intermediate stage of pregnancy promotes interference in the values of rectal temperature and blood cortisol levels when measured during the circadian rhythm.


In this chapter, we use the lens of Statecraft to analyse the philosophical foundations of the European integration enterprise. We advance a theory of Statecraft that posits that the state evolves through successive eras that are characterized by distinctive hallmarks. The 'state-nation' of the Industrial Revolution drew on the resources of its subjects and garnered for itself as much international resources as possible to strengthen and solidify the economic base of the polity. More laissez-faire policies internally, mercantilism and gunboat diplomacy on the trade front, as well as competition for colonial resources, accorded with the ethos of the state-nation. In time, the state-nation evolved into a 'nation-state' dedicated internally to providing 'welfare' (which we define to encompass both entitlements and welfare-enhancing regulation) to its nation. Collaboration with other states in an international trade framework dedicated to liberalizing trade while theoretically allowing each participant to set its chosen welfare level accorded with this model. Decolonization of nations artificially established by the colonial powers, the establishment of a United Nations based on territorial integrity and sovereign equals, and a general system of international law providing few encroachments on national sovereignty were twentieth-century phenomena consistent with the age of the nation-state.


This paper describes the implementation and forecasting results of a hybrid fuzzy neural technique, which combines neural network modeling, and techniques from fuzzy logic and fuzzy set theory for electric load forecasting. The strengths of this powerful technique lie in its ability to forecast accurately on weekdays, as well as, on weekends, public holidays, and days before and after public holidays. Furthermore, use of fuzzy logic effectively handles the load variations due to special events. The fuzzy-neural network (FNN) has been extensively tested on actual data obtained from a power system for 24-hour ahead prediction based on forecast weather information. Very impressive results, with an average error of 0.62% on weekdays, 0.83% on Saturdays and 1.17% on Sundays and public holidays have been obtained. This approach avoids complex mathematical calculations and training on many years of data, and is simple to implement on a personal computer.


Spontaneous hemorrhage from hepatic tumors is an uncommon but serious complication. Recently, interventional radiologic (IR) techniques are being used increasingly in the management of these patients. We report our 16-year experience in managing spontaneous hemorrhage from liver tumors. Twenty-six consecutive patients were diagnosed with spontaneous liver hemorrhage between 1995 and 2011. Initial management was operative in eight, IR in six, and supportive in 12 patients. Of those managed operatively, five were segmentectomies; one hemihepatectomy; one wedge resection; and one packing who later died from coagulopathy. In the IR patients, seven had an angiographic embolization; two required reembolization; one underwent resection of a hepatic adenoma 21 days after angiographic embolization. The malignant lesions included hepatocellular carcinoma (n = 6), angiosarcoma (n = 1), metastatic squamous cell carcinoma (n = 1), metastatic leiomyosarcoma (n = 1), nonsquamous cell carcinoma (n = 1), or metastatic angiosarcoma (n = 1). Benign diseases included hepatic adenoma (n = 5), end-stage liver disease (n = 1), and polycystic liver (n = 1). Spontaneous hemorrhage from the liver occurs evenly from benign or malignant causes, one-third of which are primary liver disease. If the patients presents emergently, angiographic embolization may control the bleeding and allow for elective resection once the sequelae of bleeding have resolved.


This paper is concerned with the present status and future projections for emerging technologies that can be utilized in light-duty vehicles in the next five to ten years to significantly reduce their CO2 emissions. The emerging technologies considered are modern clean diesel engines and hybrid-electric powertrains using batteries and/or ultracapacitors for energy storage. Throughout the study, six classes of vehicles –compact passenger cars to large SUVs -were considered. For each vehicle class, computer simulations (Advisor 2002) and cost analyses were performed for conventional ICE and mild and full parallel hybrids using port- fuel injected and lean burn gasoline engines and direct- injection turbo-charged diesel engines to determine the fuel economy and differential costs for the various vehicle designs using the conventional gasoline PFI engine vehicle as the baseline. CO2 emissions (gmCO2/mi) for each driveline and vehicle case were calculated from the fuel economy values. On a percentage or ratio basis, the analyses indicated that the fuel economy gains, CO2 emissions reductions, and cost/price increases due to the use of the advanced engines and hybrid-electric drivelines were essentially independent of vehicle class. This means that a regulation specifying the same fractional reductions in CO2 emissions for all the vehicle classes would not favor one class over the others. The results of the study were then used to calculate the increase in the CAFE standard (miles per gallon gasoline for the new car fleet) that was feasible using each of the emerging technologies and the associated vehicle price increase that would be incurred. It was determined that the CAFE standard could be increased to 38 mpg and 48 mpg using the PFI and lean-burn gasoline engines, respectively, in mild hybrids with an associated percentage price increase of 7-9%. The CAFE standard could be increased to 42 mpg and 52 mpg using the PFI and lean-burn gasoline engines, respectively, in full hybrids with an associated cost increase of 16-18%. The CAFE increases using the diesel engines in mild hybrids were close to those of gasoline engines in full hybrids. The vehicle price increases using diesel engines in hybrids were 17-23% compared to the baseline ICE vehicles using the PFI engine. The fleet CO2 emissions corresponding to the cited CAFE standards were 185-234 gmCO2/mi for the mild hybrids using gasoline engines and 170-208 gmCO2/mi for full hybrids. The corresponding values using diesel engines are189-216 gmCO2/mi. The CO2 emissions of the new car fleet for a CAFE standard of 27.5 mpg are 322 gmCO2/mi indicating that implementing the hybrid powertrain technologies in the new car fleet could reduce CO2 emissions of the fleet by 25-50%.


Combining data content with visual embellishments, infographics can effectively deliver messages in an engaging and memorable manner. Various authoring tools have been proposed to facilitate the creation of infographics. However, creating a professional infographic with these authoring tools is still not an easy task, requiring much time and design expertise. Therefore, these tools are generally not attractive to casual users, who are either unwilling to take time to learn the tools or lacking in proper design expertise to create a professional infographic. In this paper, we explore an alternative approach: to automatically generate infographics from natural language statements. We first conducted a preliminary study to explore the design space of infographics. Based on the preliminary study, we built a proof-of-concept system that automatically converts statements about simple proportion-related statistics to a set of infographics with pre-designed styles. Finally, we demonstrated the usability and usefulness of the system through sample results, exhibits, and expert reviews.


The E1 protein of human papillomavirus (HPV) type 16 is the only known papillomavirus E1 which does not contain any proline residues in the phosphate-loop (P-loop) of its ATP-binding site. To ascertain whether this feature influences the activities of HPV-16 E1, we generated a mutant HPV-16 E1 (E1Pro) in which prolines are inserted in place of alanines in this site, making the P-loop identical to its bovine papillomavirus type 1 counterpart. Glutathione S-transferase (GST) fusion proteins (GSTE1wt and GSTE1Pro) were produced, purified and used to assay for ATP-binding ability, ATPase activity and ability to complex with the HPV-16 E2 protein. The results show that the lack of prolines in the P-loop, which is unique to HPV-16 E1, significantly weakens its ATP-binding and ATPase activities without affecting its ability to complex with the HPV-16 E2 protein.


Abstract We present the case of an 18-year-old girl who was sexually assaulted with transanal forearm penetration resulting in a fourth-degree perineal laceration. Fisting is an uncommon sexual practice consisting in the penetration of the vagina, anus, or both of them with fingers, hand (fist) or forearm. Perineal lacerations are a relatively common finding in both consensual and nonconsensual fisting victims. Even though cases of fisting with first-, second-, and third-degree lacerations have been reported in literature, only one previous case of fourth-degree perineal laceration has been described in a woman, who died after anal fisting. The clinical and morphological findings related to this sexual practice have been presented. No previous reports concerning nonfatal cases of fourth-degree perineal laceration, due to anal fisting, exists in literature. We report a case in which the forensic evaluation and the identification of the sexual assault were delayed because of both the atypical and uncommon pattern of injury and the unconsciousness of the patient. The information gathered thanks to this article would support forensic pathologists and sexual assault forensic examiners in recognizing doubtful cases, and this is particularly important when the suspect of sexual assault arise.


Reflecting on peace is intimately connected to how one conceptualizes violence. Moreover, thinking about violence is closely tied to how one conceives of socio-political life and the fundamental problems or threats that it faces. Political disagreement then, translates into disparate notions of violence and of peace. In light of this, some theorists, including Johan Galtung, advocate adoption of a singular, extended definition of violence that can accommodate this divide, paired with a corresponding two-part understanding of peace. In this paper, I argue there are reasons to be wary of this strategy, and to doubt the success of Galtung's efforts. Specifically, I problematize the methods that obscure substantive disagreement concerning violence and that ultimately limit our ability to conceptualize forms of peace. I then demonstrate the depths such disagreement can reach and thus illustrate both the limitations of existing extended notions of violence (such as Galtung's) as well as the correspondingly divergent ideals of peace. I end by sketching an alternative account of violence that aims to avoid these flaws and thus offer grounds for a novel understanding of peace.


Against the background of current reforms in higher education, we analyze the traditional education of Japanese doctoral students in philosophy of education from Western and Japanese perspectives by focusing on learning as self-education, on being and learning with others, on the socialization into the profession, and on the study of the foreign subject. Imai's explication of the Japanese construction of the adult self as instrumental is compared to Gadamer's ideas on self-education and education with others. A significant element of doctoral education in Japan involves the learning of certain forms (kata) of professional conduct: belonging to a group, occupying a clear position in the social hierarchy, and developing a close mentoring relationship that fosters strong feelings of loyalty, harmony and respect. Furthermore, reciprocal dependence (amae) is analyzed and contrasted with the Western ideal of autonomy and maturity. Finally, the study of the foreign subject is considered in light of Gadamer's and Hegel's notion of making a home in the alien. Saito affirms a cross-cultural reading of foreign philosophical texts, claiming that they destabilize the native culture and turn a teacher in philosophy of education into a translator and prophet of her own as well as the foreign culture.


: Strength measurement of the hand grip is at the core of most protocols of functional assessment of the upper limb and in rehabilitation plays a major role in the analysis of treatment efficacy and patients' occupational ability. The aims of this study were to: a) verify the repeatability of strength measurements made during performance of the hand grip and three types of pinch, carried out under isometric and isokinetic conditions; b) compare maximal isometric strength with the corresponding isokinetic value for each of the manoeuvres studied; c) investigate the correlations between the strength expressed in the different manoeuvres, under both isometric and isokinetic conditions. We studied 14 voluntary subjects over three sessions conducted at 48-hr intervals, employing a computerized isokinetic dynamometer Lido WorkSet equipped with device N(o) 21 for the study of pinch (lateral pinch, pulp pinch, chuck pinch) and device N(o) 52 for the grip study. Isometric contractions resulted stronger than isokinetic ones, and the hand grip was found to be the manoeuvre able to produce most strength. The repeatability of each strength measurement test over the three days was high (Intraclass Correlation Coefficients: 0.89-0.93). Correlations between the isometric and isokinetic performance for each of the manoeuvres examined were always high (Pearson's r coefficients: 0.89-0.95) as were those between the different manoeuvres, whether performed in isometric or isokinetic modality (r: 0.60-0.94).


High latitude ecosystems are prone to phenological mismatches due to climate change- driven advances in the growing season and changing arrival times of migratory herbivores. These changes have the potential to alter biogeochemical cycling and contribute to feedbacks on climate change by altering greenhouse gas (GHG) emissions of carbon dioxide (CO2), methane (CH4) and nitrous oxide (N2O) through large regions of the Arctic. Yet the effects of phenological mismatches on gas fluxes are currently unexplored. We used a three-year field experiment that altered the start of the growing season and timing of grazing to investigate how phenological mismatch affects GHG exchange. We found early grazing increased mean GHG emission to the atmosphere despite lower CH4 emissions due to grazing-induced changes in vegetation structure that increased uptake of CO2. In contrast, late grazing reduced GHG emissions because greater plant productivity led to an increase in CO2 uptake that overcame the increase in CH4 emission. Timing of grazing was an important control on both CO2 and CH4 emissions, and net GHG exchange was the result of opposing fluxes of CO2 and CH4. N2O played a negligible role in GHG flux. Advancing the growing season had a smaller effect on GHG emissions than changes to timing of grazing in this study. Our results suggest that a phenological mismatch that delays timing of grazing relative to the growing season, a change which is already developing along in western coastal Alaska, will reduce GHG emissions to the atmosphere through increased CO2 uptake despite greater CH4 emissions.


1. A diet of whole wheat and whole dried milk has been shown to promote a higher survival rate, among W-Swiss mice subjected to S. enteritidis infection, than that promoted by a "synthetic" diet. 2. The demonstration of this ability of diet to condition natural resistance has been found to depend upon the genetic constitution of the mice employed. The demonstration has been possible in W-Swiss mice, a strain only moderately inbred and retaining a degree of genetic variability. The demonstration has not been possible in three highly inbred strains of mice selected so that they differed predictably from one another in natural resistance. 3. The nutritional factors involved are present in whole wheat and are absent or negligible in dried whole milk. Their nature has not yet been determined.


The present study investigated the effects of the apolipoprotein E (ApoE) epsilon4 allele, a risk factor for Alzheimer's disease (AD), on olfactory function in Down syndrome (DS). Brain areas critical to olfactory processing, particularly the entorhinal cortex, show the earliest neuropathological changes in AD. Functionally, odor identification has been shown to be impaired in AD and in persons with the epsilon4 allele. DS is also a risk factor for AD. Thus, we hypothesized greater impairment in epsilon4 positive DS participants. Olfactory function was assessed with the San Diego Odor Identification Test in 34 participants with DS and 34 normal controls. Genomic DNA was prepared from blood samples to obtain ApoE status for the DS participants. Results indicate (1) that participants with DS had significant deficits in olfactory functioning; and (2) that among DS participants, those with an epsilon4 allele had poorer odor identification than those without an epsilon4 allele. The results support the hypothesis that individuals with DS who have an additional genetic risk factor for AD, the ApoE epsilon4 allele, exhibit greater deficits in odor identification. Areas of the brain involved in odor identification may be particularly affected in individuals with DS who carry the epsilon4 allele.


Given a graph G where each node is associated with a set of attributes, attributed network embedding (ANE) maps each node v 2 G to a compact vector Xv, which can be used in downstream machine learning tasks in a variety of applications. Existing ANE solutions do not scale to massive graphs due to prohibitive computation costs or generation of low-quality embeddings. This paper proposes PANE, an effective and scalable approach to ANE computation for massive graphs in a single server that achieves state-of-the-art result quality on multiple benchmark datasets for two common prediction tasks: link prediction and node classification. Under the hood, PANE takes inspiration from well-established data management techniques to scale up ANE in a single server. Specifically, it exploits a carefully formulated problem based on a novel random walk model, a highly efficient solver, and non-trivial parallelization by utilizing modern multi-core CPUs. Extensive experiments demonstrate that PANE consistently outperforms all existing methods in terms of result quality, while being orders of magnitude faster.


The development of an adequate animal model for peritoneal research remains an object of concern. In vivo peritoneal dialysis (PD) research is hampered by the large variety of available models that make interpretation of results and comparison of studies very difficult. Species and strain of experimental animals, method of peritoneal access, study duration, measures of solute transport and ultrafiltration, and sampling for histology differ substantially among the various research groups. A collective effort to discuss the shortcomings and merits of the different experimental models may lead to a consensus on a standardized animal model of PD.


Background: Flemingia strobilifera (FS) R.Br. (Fabaceae) is an important medicinal plant. In wealth of India it has been reported that roots of FS are used by santals in epilepsy, hysteria, insomnia, and to relieve pain. In Burma also the roots of F. strobilifera are used to treat epilepsy. Objective: To investigate anticonvulsant potential of 95% ethanol extract and four subsequent fractions (petroleum ether, chloroform, ethyl acetate, and aqueous fractions of the roots of FS against pentylenetetrazole (PTZ) and maximal electroshock (MES) induced convulsions. Material and Methods: All the fractions and crude ethanol extract were administered (i.e., 200, 400, 600 mg/kg, p.o.) for 7 days and at the end of the treatment convulsions were induced experimentally using pentylenetetrazole and Maximal electroshock Test. Diazepam and phenytoin (4 mg/kg, i.p. and 20 mg/kg, i.p., respectively) were used as reference anticonvulsant drugs against experimentally induced convulsions. The latency of tonic convulsions and the numbers of animals protected from tonic convulsions were noted. Results: High doses (200 and 300 mg/kg, p.o.) of ethyl acetate fraction and 95% ethanol crude extract (400 and 600 mg/kg, p.o.) significantly reduced the duration of seizure induced by maximal electroshock (MES). The same dose also protected from pentylenetetrzole-induced tonic seizures and significantly delayed the onset of tonic seizures. However, pet, ether, chloroform, and aqueous fraction at any of the doses used (i.e., 100, 200, 300 mg/kg, p.o.) did not show any significant effect on PTZ and MES induced convulsions. The treatment with crude ethanolic extract and ethyl acetate fraction caused signs of central nervous system depressant action in the locomotor activity test, confirmed by the potentiation of sodium pentobarbital sleeping time. Both did not cause disturbance in motor coordination assessed by rotarod test. Conclusion: The data suggest that crude ethanol extract and ethyl acetate fraction of roots of Flemingia strobilifera have a central nervous system depressant action and behave as a potential anticonvulsant. It may produce its anticonvulsant effect via non-specific mechanism since it reduced the duration of seizures produced by maximal electroshock as well as delayed the latency of seizures produced by pentylenetetrazole.


We present StyleTune, a mobile app for interactive style transfer enhancement that enables global and spatial control over stroke elements and can generate high fidelity outputs. The app uses adjustable neural style transfer (NST) networks to enable art-direction of stroke size and orientation in the output image. The implemented approach enables continuous and seamless edits through a unified stroke-size representation in the feature space of the style transfer network. StyleTune introduces a three-stage user interface, that enables users to first explore global stroke parametrizations for a chosen NST. They can then interactively locally retouch the stroke size and orientation using brush metaphors. Finally, high resolution outputs of 20 Megapixels and more can be obtained using a patch-based upsampling and local detail transfer approach, that transfers small-scale details such as paint-bristles and canvas structure. The app uses Apple's CoreML and Metal APIs for efficient on-device processing.


Policy for the protection of water resources requires a more holistic and integrated approach to transcend disciplinary boundaries, to overcome fragmented governance, and to create ownership of solutions through collaborative planning. In this Australian case study I summarise critical water quality characteristics (salinity, acidity, nitrogen, phosphorus, carbon, turbidity, micropollutants and pathogenic organisms) and management options in the context of the needs of stakeholders. Stakeholders are: dryland and irrigation farmers; urban and industrial users; and the aquatic environment. Management options are: changes in land use; interception methods (such as filtration by riparian vegetation, use of artificial wetlands and evaporation ponds); reliance on technological water treatment methods; reuse; and trading. Clearly, the protection of water resources is a 'wicked' problem. Critical decision-making requires greater emphasis on inclusive agricultural, ecocentric and technological thinking that includes: an understanding of the water cycle; consideration of interaction between stressors and use of systems approaches; better methods to value the aquatic environment; assessment of land use impacts on water resources; use of incentives to change behaviour; and community involvement to create sustainable futures through transformation and resilience practice. To their credit, Australians are working together to explore solutions and support is available. Some examples are provided.


Purpose: Although the majority of patients with HPV+ oropharyngeal cancers have a favorable prognosis, there are some patients with tumors that are resistant to aggressive chemoradiotherapy with unusual patterns of locoregional and systemic recurrences. Therefore, more effective therapies are needed. In this study, we investigated the chemosensitizing efficacy of the selective Wee-1 kinase inhibitor, AZD-1775, in HPV+ head and neck squamous cell carcinoma (HNSCC). Experimental Design: Clonogenic survival assays and an orthotopic mouse model of HPV+ oral cancer were used to examine the in vitro and in vivo sensitivity of HPV+ HNSCC cell lines to AZD-1775 in combination with cisplatin, respectively. Cell-cycle analysis, DNA damage (γH2AX), homologous recombination (HR), and apoptosis were examined to dissect molecular mechanisms. Results: We found that AZD-1775 displays single-agent activity and enhances the response of HPV+ HNSCC cells to cisplatin both in vitro and in vivo. The sensitivity of the HPV+ HNSCC cells to AZD-1775 alone or in combination with cisplatin was associated with G2 checkpoint abrogation, persistent DNA damage, and apoptosis induction. This finding of AZD-1775 increasing the sensitivity of HPV+ HNSCC cells to cisplatin through apoptosis was not seen previously in the HPV− HNSCC cancer cells and is accompanied by a decreased expression of the antiapoptotic proteins, MCl-1and XIAP, which appear to be cleaved following AZD-1775 treatment. Conclusions: AZD-1775 selectively sensitizes HPV+ HNSCC cells and orthotopic oral xenografts to cisplatin through apoptosis and support the clinical investigation of AZD-1775 in combination with cisplatin particularly in patients with advanced and recurrent metastatic HPV+ HNSCC tumors. Clin Cancer Res; 21(21); 4831–44. ©2015 AACR.


Homologous chromosomes pair, and then migrate to opposite poles of the spindle at meiosis I. In most eukaryotic organisms, reciprocal recombinations (crossovers) between the homologs are critical to the success of this process. Individuals with defects in meiotic recombination typically produce high levels of aneuploid gametes and exhibit low fertility or are sterile. The experiments described here were designed to test whether different crossovers are equally able to contribute to the fidelity of meiotic chromosome segregation in yeast. These experiments were performed with model chromosomes with which it was possible to control and measure the distributions of meiotic crossovers in wild-type cells. Physical and genetic approaches were used to map crossover positions on model chromosomes and to correlate crossover position with meiotic segregation behavior. The results show that crossovers at different chromosomal positions have different abilities to enhance the fidelity of meiotic segregation.


We study the real-time evolution of large open quantum spin systems in two spatial dimensions, whose dynamics is entirely driven by a dissipative coupling to the environment. We consider different dissipative processes and investigate the real-time evolution from an ordered phase of the Heisenberg or XY model towards a disordered phase at late times, disregarding unitary Hamiltonian dynamics. The corresponding Kossakowski-Lindblad equation is solved via an efficient cluster algorithm. We find that the symmetry of the dissipative process determines the time scales, which govern the approach towards a new equilibrium phase at late times. Most notably, we find a slow equilibration if the dissipative process conserves any of the magnetization Fourier modes. In these cases, the dynamics can be interpreted as a diffusion process of the conserved quantity.


A land cover map that represents the land surface of the earth is based primarily on analysis of remotely sensed images. However, the rate of concordance of existing land cover maps is not high. This lack of concordance results from a difference in classification methods and observation conditions of remotely sensed images. Also, conducting field surveys around the world is unrealistic. Therefore, we use ground level photographs from photo-sharing sites instead of field surveys. We propose a method to classify areas into land cover types using image features, geo-tags, titles and tags. Additionally, we create the land cover map using classified photographs. We evaluate the method using ground truth created manually. Results show that the accuracy of the proposed method is about 70 percent in New York.


Abstract Ulota panchengiana Q.H.Wang & Y.Jia is described and illustrated as a new species from China. It is characterized by both stomata that are scattered throughout the urn and by naked calyptra, two remarkable characters that are rarely found in Ulota species from the northern Hemisphere. Ulota panchengiana is easily recognized by the combination of the following characters: lanceolate leaves with an ovate base, the presence of a few rows of hyaline cells at the basal leaf margin, and long seta. The ecology, geographical distribution, variation, and morphological comparison with related taxa are discussed. Ulota morrisonensis, endemic to Taiwan, is easily misidentified as U. crispa. However, based on a study of an isotype of the former species and in response to a recent reevaluation of the circumscription of U. crispa, we confirm its rank as a species and discuss obvious morphological differences between the two species. A revised key to Chinese Ulota species is provided.


Direct cell-to-cell transfer of ions and small signaling molecules via gap junctions plays a key role in vessel wall homeostasis. Vascular endothelial gap junctional channels are formed by the connexin (Cx) proteins Cx37, Cx40, and Cx43. The mechanisms regulating connexin expression and assembly into functional channels have not been fully identified. We investigated the dynamic regulation of endothelial gap junctional intercellular communication (GJIC) by fluid flow and the participation of each vascular connexin in functional human endothelial gap junctions in vitro. Human aortic endothelial cells (HAEC) were exposed for 5, 16, and 24 h to physiological flows in a parallel-plate flow chamber. Connexin protein expression and localization were evaluated by immunocytochemistry, and functional GJIC was evaluated by dye injection. Connexin-mimetic peptide inhibitors were used to assess the specific connexin composition of functional channels. HAEC monolayers in culture exhibited baseline functional communication at a striking low level despite abundant expression of Cx43 and Cx40 localized at cell-to-cell appositions. Upon exposure to flow, GJIC by dye spread demonstrated a significant time-dependent increase from baseline levels, reaching 7.5-fold in 24 h. Inhibition studies revealed that this response was mediated primarily by Cx40, with lesser contributions of the other two vascular connexins assembled into functional homotypic and/or heterotypic channels. This is the first study to demonstrate that flow simultaneously and differentially regulates expression of the Cx37, Cx40, and Cx43 proteins and their involvement in the augmentation of intercellular communication by dye transfer in human endothelial cells in vitro.


The diagnosis of early-stage atherosclerosis is important for preventing cardiovascular diseases such as a stroke or a heart attack. The main cause of such diseases is atherosclerosis. In early-stage atherosclerosis, the luminal surface of the arterial wall becomes rough because of the detachment of endothelial cells and the degeneration of the internal elastic layer. Therefore, it would be useful if the minute luminal surface roughness of the carotid arterial wall observed in the early stage of atherosclerosis can be measured noninvasively by ultrasonography. In conventional ultrasonography, the axial resolution of a B-mode image depends on the ultrasonic pulse length of 150 µm (at 10 MHz) because a B-mode image is constructed using the amplitude of the RF echo. However, the thickness of an endothelial cell covering the luminal surface is 10–20 µm. Therefore, a minute surface roughness cannot be measured from a conventional B-mode image. We have realized the transcutaneous measurement of such a minute surface roughness of about 10 µm using the phased-tracking method. However, the lateral spatial resolution degrades owing to the point spread function (PSF) because the diameter of an ultrasonic beam is finite. In the present study, we proposed a method of improving the lateral spatial resolution in the estimation of surface roughness using a Wiener filter to suppress the effect of the PSF of the ultrasound system employed. The proposed method was validated using a phantom and then applied to the in vivo measurement of carotid arteries.


The use of mobile agents based computing in this emerging world of electronic transaction is becoming increasingly prevalent due to the enormous benefits and services that can be derived from it. They are good for distributed applications and hence an excellent paradigm when group communications are involved. Secure group communication is a significant research area prompted by the growing popularity of many types group based cryptography and collaborative application. In this paper, we focus on secure group communication based on mobile agents. In doing so, we use elliptic curve cryptography (ECC) as key exchange protocol, XOR operation and hash function to achieve provable secure and efficient management for group communication.


ABSTRACT: Efficient use of water resources is the key to guarantee water suply for future human consumption and irrigation. in the irrigated areas of the Cerrado region pressurized irrigation systems allow high efficiency in water conduction. However, lack of knowledge in crop water requirement determine inadequated crop water management. Negative effect on crop due to excessive watering or irrigation in deficit are commonly seen in the irrigated agriculture. Using adequated crop coefficients determined in the Cerrado Biome, pan evaporation method can be used to help farmers in irrigation scheduling. By using a weighting lisimeter installed in a 8 ha area irrigated by center pivot, crop coeficients were determined for BRS 195 barley crop. These values are about 25% higher than the values found in the literature and explain why this method was not frequently used for irrigation scheduling in the Cerrado Biome.


Age-related decline in visual functions is a prevalent health problem among elderly people, and no effective therapies are available up-to-date. Axon degeneration and myelin loss in optic nerves (ONs) are age-dependent and become evident in middle-aged (13-18 months) and old (20-22 months) mice of either sex compared with adult mice (3-8 months), accompanied by functional deficits. Oligodendrocyte (OL) turnover is actively going on in adult ONs. However, the longitudinal change and functional significance of OL turnover in aging ONs remain largely unknown. Here, using cell-lineage labeling and tracing, we reported that oligodendrogenesis displayed an age-dependent decrease in aging ONs. To understand whether active OL turnover is required for maintaining axons and visual function, we conditionally deleted the transcription factor Olig2 in the oligodendrocyte precursor cells of young mice. Genetically dampening OL turnover by Olig2 ablation resulted in accelerated axon loss and retinal degeneration, and subsequently impaired ON signal transmission, suggesting that OL turnover is an important mechanism to sustain axon survival and visual function. To test whether enhancing oligodendrogenesis can prevent age-related visual deficits, 12-month-old mice were treated with clemastine, a pro-myelination drug, or induced deletion of the muscarinic receptor 1 in oligodendrocyte precursor cells. The clemastine treatment or muscarinic receptor 1 deletion significantly increased new OL generation in the aged ONs and consequently preserved visual function and retinal integrity. Together, our data indicate that dynamic OL turnover in ONs is required for axon survival and visual function, and enhancing new OL generation represents a potential approach to reversing age-related declines of visual function. SIGNIFICANCE STATEMENT Oligodendrocyte (OL) turnover has been reported in adult optic nerves (ONs), but the longitudinal change and functional significance of OL turnover during aging remain largely unknown. Using cell-lineage tracing and oligodendroglia-specific manipulation, this study reported that OL generation was active in adult ONs and the efficiency decreased in an age-dependent manner. Genetically dampening OL generation by Olig2 ablation resulted in significant axon loss and retinal degeneration, along with delayed visual signal transmission. Conversely, pro-myelination approaches significantly increased new myelin generation in aging ONs, and consequently preserved retinal integrity and visual function. Our findings indicate that promoting OL generation might be a promising strategy to preserve visual function from age-related decline.


OBJECTIVE
To validate transient elastography (Fibroscan) in assessment of hepatic fibrosis in autoimmune hepatitis (AIH).

METHODS
Liver stiffness was assessed using Fibroscan in totally 30 patients with AIH. We compared the results of Fibroscan with the Scheuer fibrosis stage in liver biopsy in each patient.

RESULTS
4 patients were shown as liver fibrosis stage S0, 6 as S1, 5 as S2, 11 as S3 and 4 as S4. Failure of the Fibroscan measurement occurred in 1 case (3.3%) because of her increased body mass index (BMI). The stiffness of Fibroscan was significantly correlated with the liver biopsy fibrosis stage (r = 0.801, P less than 0.001). The liver stiffnesses between mild and moderate fibrosis (S0-2) and advanced fibrosis (S3-4) were significantly different (t = -3.937, P = 0.001).

CONCLUSION
Transient elastography (Fibroscan) is a promising non-invasive method for detection of fibrosis in patients with autoimmune hepatitis. Its use for the follow up and management of these patients and should be evaluated further.


The detn. of glycerol in aq. allergenic products is accomplished by gas chromatog. using a column packed with Chromosorb 101 and FID. Quantitation is performed using the internal std. technique. The method is accurate to within 1% and has proved to be superior to the gas chromatog. method currently recommended in terms of efficiency, selectivity, and reliability. [on SciFinder (R)]


SUMMARY: Capitella of Mycotypha africana and M. microspora regularly produce sterigmata of two lengths. Spores of M. africana are dimorphic and this is probably also the case in M. microspora. A membrane which separates from the spore, particularly on germination, is interpreted as evidence that the spore of M. africana is a sporangiole and it is suggested that the genus Mycotypha should probably be classified in Thamnidiaceae.


Riparian ecosystems are hotspots for ecological restoration globally because of the disproportionately high value and diversity of the ecological functions and services which they support and their high level of vulnerability to anthropogenic pressures, including climate change. Degraded riparian ecosystems are associated with many serious anthropogenic problems including increased river bank erosion, water quality decline, increased flood risk and biodiversity loss. Conventional approaches to riparian restoration, however, are frequently too narrow in focus – spatially, temporally, ecologically and socially – to adequately or equitably address the goals to which they aspire. Climate change, along with the intensification of other human pressures, means that static, historically oriented restoration objectives focused solely on prior ecological composition and structure are unlikely to be defensible, achievable or appropriate in the Anthropocene. Conversely, open‐ended restoration strategies lacking clear objectives and targets entail substantial risks such as significant biodiversity losses, especially of native species. A functional approach to planning and prioritising riparian restoration interventions offers an intermediate alternative that is still framed by measurable targets but allows for greater consideration of broader temporal, spatial and cultural influences. Here, we provide an overview of major riparian functions across multiple scales and identify key drivers of, and threats to, these. We also discuss practical approaches to restoring and promoting riparian functions and highlight some key concerns for the development of policy and management of robust riparian restoration in the Anthropocene.


Background The Japan Paediatric Society is currently surveying information management strategies at other societies in order to gain insight for the future development of their own information management strategy. To this end, we conducted a survey of personal information management strategies upon admission to subcommittees of the Japan Paediatric Society as a pilot study. Objective The present study aimed to clarify the state of personal information management upon admission to Japan Paediatric Society subcommittees in order to determine information management strategies in the future. Methods The contract terms for physicians upon admission to Japan Paediatric Society subcommittees were examined based on subcommittee websites. Results Of the 23 subcommittees, 21 had websites, and one did not have a working URL to the website (as of April 4, 2014). Moreover, one subcommittee did not have information pertaining to admission on its website. Accordingly, we surveyed the 19 subcommittees which had websites that could be analysed. Information provided by the subcommittee websites included the following: basic information regarding how personal information is handled, 3; recommendation required, 5; name, 19 ( furigana , 16; English 6), gender, 15; birthdate, 17; home address, 19; home phone (fax), 19; e-mail address, 18; workplace, 19; work address, 19; work phone number, 19; specialty, 10; and highest academic degree, 5. Conclusion From the perspective of information management, the Japan Paediatric Society must maintain close collaboration with the various subcommittees in the future.


This paper discusses the identification and measurement of intangible assets in the public sector. A discussion of intellectual capital theory identifies and classifies a number of intangible assets of relevance to the public sector. Multidimensional scaling and related multivariate techniques are proposed for their detection and quantification. The methodology is illustrated with a case study: the provision of council services through the Internet by Spanish municipalities. The technique identifies three intangible assets related to external structural capital: service, image and transparency. Five strategic groups reveal the different objectives, strategic use of the Internet, and actions taken by the various Spanish councils.


Sexuality is central to our individual lives, our society, and our evolution, but its etiology is not thoroughly understood. Using data from 4904 Australian twins who completed a questionnaire on sexual attitudes and behaviours, I investigated the genetic and environmental influences underlying variation in and covariation between psychological and behavioural aspects of sexuality. Moreover, I explored the role of sexuality traits in several different contexts: evolution, mental health, public health, personality, and problematic behaviour. Before presenting reports of the four main empirical studies in this thesis, I make the case for the importance of studying human sexuality, outline previous findings on the etiology of individual differences in sexuality, and describe the behavioural genetic principles and techniques that were used in the investigations. I also present an additional fifth paper reporting a behavioural genetic analysis of EEG power, which I undertook in order to learn twin data modelling and complex multivariate techniques. In the first empirical paper I investigated sexual orientation from an evolutionary perspective. As sexual orientation is genetically influenced, it is not known how homosexuality, which tends to lower reproductive success, is maintained in the population at a relatively high frequency. I tested the hypothesis that while genes predisposing to homosexuality reduce homosexuals' reproductive success, they may confer some advantage for heterosexuals who carry them. Results showed that psychologically masculine females and feminine men are 1) more likely to be nonheterosexual, but 2) when they are heterosexual have more opposite-sex sexual partners. Genetic modelling revealed that both these relationships are partly due to pleiotropic genetic influences common to each trait. Further, heterosexuals with a nonheterosexual twin had more opposite-sex partners than do heterosexual twin pairs. Taken together, these results suggest that genes predisposing to homosexuality may confer a mating advantage in heterosexuals, which could contribute to the evolution and maintenance of homosexuality in the population. In the second empirical paper I investigated sexual orientation from the perspective of mental health risk. Large epidemiological studies have shown that homosexuals are at much greater risk of psychiatric disorder than the general population. This has been assumed, with some supporting evidence, to be because of the prejudice and discrimination experienced by homosexuals in a heterosexist society. Here I tested the viability of alternative explanations, using Eysenck's Neuroticism and Psychoticism scales as markers for psychiatric vulnerability. Firstly, I tested whether apparent sexual orientation differences in psychiatric vulnerability simply mirror sex differences – for our traits, this would predict nonheterosexual males having elevated Neuroticism scores as females do, and nonheterosexual females having elevated Psychoticism scores as males do. The results contradicted this idea, with nonheterosexual men and women scoring significantly higher on both Neuroticism and Psychoticism than their heterosexual counterparts, suggesting an overall elevation of psychiatric risk in nonheterosexuals. Secondly, I used the genetically informative sample to assess the viability of explanations invoking a common cause of both nonheterosexuality and psychiatric vulnerability. We found significant genetic correlations between sexual orientation and both Neuroticism and Psychoticism, but no corresponding environmental correlations, suggesting that if there is a common cause of both nonheterosexuality and psychiatric vulnerability it is likely to have a genetic basis rather than an environmental basis. The third empirical paper investigated the etiology of risky sexual behaviour, which is relevant to public health and welfare through its role in STD transmission and unwanted pregnancies. Results showed that variation in risky sexual behaviour is due to genetic, shared environmental, and unshared environmental influences to approximately equal degrees. The genetic influences partly overlapped with genetic influences on dispositional factors, with significant genetic correlations between risky sexual behaviour and Eysenck's Impulsivity, Extraversion, Psychoticism, and Neuroticism. This suggests that the genetic influences that shape our personality may also predispose us to risky sexual behaviour. The fourth empirical paper investigated the etiology of a strong association (r = .50) between risky sexual behaviour and adolescent misconduct. Results indicated that the association is due to overlapping genetic and environmental influences, but that in males genes are the primary source of the association whereas in females shared environment plays the greater role. These findings suggest that a general predisposition to risky behaviour may manifest in different potentially harmful ways in adolescence (misconduct) and adulthood (risky sexual behaviour), and that different processes are involved in male and female etiology. Following the empirical reports, I provide a general discussion of my research findings and the study of human sexuality more generally. After summarising the findings and their implications, I then provide a detailed description of potential limitations of the research and to what extent they qualify the conclusions drawn. I also critically discuss the absence of sexuality traits from the major models of personality, and why this and other shortcomings make the personality models inadequate from an evolutionary perspective. Finally, I suggest directions for future research in light of the research and discussion presented in this thesis.


Executive summary Policy context Musculoskeletal conditions, including rheumatoid arthritis, osteoarthritis and osteoporosis, are prevalent in the Australian population, and they impose a substantial burden on the health care system and the community, reflected by their status as a national health priority area. They are the main cause of impaired physical functioning globally. These conditions have high chronicity rates and often have a long term impact, leading to reduced mobility and dexterity, chronic pain, reduced capacity for employment, and negative impact on family and social life. Much of the care for these conditions is provided in primary health care (PHC) settings.


ABSTRACT Human scavenger receptor class B, member 2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL1) have been identified to be the cellular receptors for enterovirus 71 (EV71). We compared the EV71 infection efficiencies of mouse L cells that expressed SCARB2 (L-SCARB2) and PSGL1 (L-PSGL1) and the abilities of SCARB2 and PSGL1 to bind to the virus. L-SCARB2 cells bound a reduced amount of EV71 compared to L-PSGL1 cells. However, EV71 could infect L-SCARB2 cells more efficiently than L-PSGL1 cells. The results suggested that the difference in the binding capacities of the two receptors was not the sole determinant of the infection efficiency and that SCARB2 plays an essential role after attaching to virions. Therefore, we examined the viral entry into L-SCARB2 cells and L-PSGL1 cells by immunofluorescence microscopy. In both cells, we detected internalized EV71 virions that colocalized with an early endosome marker. We then performed a sucrose density gradient centrifugation analysis to evaluate viral uncoating. After incubating the EV71 virion with L-SCARB2 cells or soluble SCARB2 under acidic conditions below pH 6.0, we observed that part of the native virion was converted into an empty capsid that lacked both genomic RNA and VP4 capsid proteins. The results suggested that the uncoating of EV71 requires both SCARB2 and an acidic environment and occurs after the internalization of the virus-receptor complex into endosomes. However, the empty capsid formation was not observed after incubation with L-PSGL1 cells or soluble PSGL1 under any of the tested pH conditions. These results indicated that SCARB2 is capable of viral binding, viral internalization, and viral uncoating and that the low infection efficiency of L-PSGL1 cells is due to the inability of PSGL1 to induce viral uncoating. The characterization of SCARB2 as an uncoating receptor greatly contributes to the understanding of the early steps of EV71 infection.


The effect of 1 mg hydrocortisone (HC) administered 3 h before the experiment was studied the bioelectric activity of ventral roots of spinal cord, the size and morphology of motoric neurons and also the size of synaptic endings being measured under different frequency of electric stimulation in frogs. It was found that the effect of HC on the electric activity of spinal cord and morphology of its neural elements was dependent on the stimulation used. Under the resting conditins the administration of HC resulted in a small decrease of the size of neurons. Under a low frequency stimulation HC did not affect the electric activity of spinal cord, but prevented the swelling of neurons and of synaptic endings resulting from the stimulation. Under a high frequency stimulation themorphology of neurons was remarkably changed, a shrinkage of these and an appearance of "dark" cells being found. Also these changes were prevented by the administration of HC. It was concluded that in all experiments HC prevented the changes resulting from electrostimulation, its effect, however, being dependent on the parameters of the stimulation used.


Some of the regions of the anomalously high sea-floor topography in today's oceans may be modern allochthonous terranes moving with their oceanic plates. Fated to collide with and be accreted to adjacent continents, they may create complex volcanism, cut off and trap oceanic crust, and cause orogenic deformaton. The accretion of plateaus during subduction of oceanic plates may be responsible for mountain building comparable to that produced by the collision of continents.


ABSTRACT Point-bar deposits in the Clear Fork Group (Lower Permian) of north-central Texas are exposed both in cross section and in plan as exhumed arcuate accretionary ridges. A thin basal lag of locally derived caliche and mudstone fragments is overlain by a 2 to 3 m thick epsilon cross-stratified unit which fines upward from very fine sandstone at the base to mudstone at the top. Sandstone beds in the epsilon units are almost entirely cross-laminated and were deposited by straight-crested ripples, most of which are oriented at 40° to 65° to the main channel direction. The Clear Fork point bars were deposited by small, variable-discharge, perennial streams with high sinuosity. The straight-crested ripples migrating on the point bar surfaces are oblique rather than perpendicular to the near-bed flow direction. The cause of such considerable obliquity was primarily a large transverse gradient in local downstream sediment transport rate and, to a lesser degree, components of transverse near-bed fluid velocity due to helicoidal flow.


The use of electronic health records (EHRs) is increasingly common in applied research, providing the opportunity to answer more relevant and detailed clinical questions. Among others, assessing the quality of routine care, enabling pragmatic clinical trials, investigating temporal trends and the natural evolution of diseases. The effective use of EHRs in medical research provides several opportunities, but challenges persist. The principal aim of this Thesis consists of investigating methodological challenges, with focus on the multilevel structure of EHRs. First, I studied shared frailty survival models for clustered survival data and the impact of model misspecification on estimates of risk and heterogeneity. Then, I investigated joint models for longitudinal and survival data and their use to account for the drop-out and observation processes in the analysis of longitudinal data. Drop-out and the timing between observations are likely not independent of the outcome of interest in the settings of EHRs, therefore violating common assumptions of traditional methods. Focussing on the observation process, I compared the joint modelling approach to other methods previously proposed in the literature via Monte Carlo simulation. Lastly, given the use of simulation methods throughout this Thesis, I introduced newly-developed software in R to aid, support, and supplement their analysis. The results of this Thesis highlight the importance of properly modelling the baseline hazard, frailty distribution, and assessing model fit in shared frailty survival models, as clinically-relevant biases may arise otherwise. Moreover, the joint modelling approach showed superior performance and flexibility when modelling the observation process, with a consistent pattern across all simulated scenarios. I illustrated the above-mentioned results in practice using real-world data on chronic kidney disease and intensive care medicine, emphasising once again the requirement for appropriate statistical methods that can accommodate the complexities commonly encountered in the settings of EHRs.


Dear Reader

Our Centre is three years old and so we find ourselves at the half-way point in our first funding-phase. This occasion, like our forthcoming Midterm Conference in July this year, offers an opportunity for both retrospective and prospective reflection. In the course of these first three years, we have managed, with and through our visiting academics, to bring into being an impressive research-community, which has embraced scholars from across all continents, representing twenty-three nationalities and nine academic disciplines. Reflecting their diverse academic and regional backgrounds, these scholars have adopted a variety of approaches to the Centre's core task: to explore the potential for global cooperation, and the limits to it, by studying the new orders and structures of governance currently emerging in society and the cultural premises and dynamics that underlie them. We aim to go beyond a general consideration of our core research-theme and include in our focus the new dynamics that have become apparent in recent years – Russia's new imperial stance, for example, and the emergence of 'transnational models' (such as the Islamic State) which are completely outpacing the nation-state. Besides this, however, we have explicitly set ourselves the task of enhancing our role as a platform for active, global cross-linkage with relevant research institutions and consultative bodies all over the world. By doing this, we aim to foster the development of a line of research that brings together challenging questions on cooperation from a variety of academic domains. We warmly invite you to let the following pages fire your imagination and motivate you to get involved in the quest to expand our platform.

We wish you an inspiring read!

Markus Bockenforde
Tobias Debiel
Claus Leggewie
Dirk Messner


In a previous study on neonatal tetanus (NNT), we provided information on clinico-epidemiological data and reported a case-fatality rate of 60.3%. The present report covers a 7-year period, January 1984 to December 1990, and amongst others, focuses on tetanus toxoid vaccine (TT) coverage of pregnant women. The subjects were those with a diagnosis of NNT and other neonatal admissions. Total neonatal admissions, NNT admissions, neonatal deaths, and NNT deaths were: 4,315, 471, 727, and 221 respectively. The overall NNT case-fatality rate was 46.9%. The highest NNT admission rate was in the third quarter of 1984, with a significant decline subsequently except for the increase in 1989. The neonatal tetanus rate began dropping appreciably from 1988 although less than 10% of the mothers in 1990 received two doses of TT. The improper immunization of the mothers during pregnancy with TT is worrying particularly several years into the Expanded Programme on Immunization (EPI), more so as the experience is not unique to Port Harcourt. We suggest intervention at the community level, operational research, and ethnographic studies to determine possible underlying factors to be carried out in all health zones of the country.


Somatic cells derived from human pluripotent stem cell (hPSC) sources hold significant potential as a means to improve current in vitro screening assays. However, their inconsistent ability to recapitulate the structural and functional characteristics of native cells has raised questions regarding their ability to accurately predict the functional behavior of human tissues when exposed to chemical or pathological insults. In addition, the lack of cytoskeletal organization within conventional culture platforms prevents analysis of how structural changes in human tissues affect functional performance. Using cation-permeable hydrogels, we describe the production of multiwell nanotopographically-patterned microelectrode arrays (nanoMEAs) for studying the effect of structural organization on hPSC-derived cardiomyocyte and neuronal function in vitro. We demonstrate that nanoscale topographic substrate cues promote the development of more ordered cardiac and neuronal monolayers while simultaneously enhancing cytoskeletal organization, protein expression patterns, and electrophysiological function in these cells. We then show that these phenotypic improvements act to alter the sensitivity of hPSC-derived cardiomyocytes to treatment with arrhythmogenic and conduction-blocking compounds that target structural features of the cardiomyocyte. Similarly, we demonstrate that neuron sensitivity to synaptic blockers is increased when cells are maintained on nanotopographically-patterned Nafion surfaces. The improved structural and functional capacity of hPSC-derived cardiomyocyte and neuronal populations maintained on nanoMEAs may have important implications for improving the predictive capabilities of cell-based electrophysiological assays used in preclinical screening applications.


The skin of severely scorbutic guinea pigs which were losing weight contained no detectible neutral salt-extractible collagen. Conditions of growth (weight gain) which actively induced the formation of neutral salt-extractible collagen in the skin of normal guinea pigs failed to do so in the animal with ascorbic acid deficiency. No excess of non-collagenous proline was found in neutral salt extracts of scorbutic skin as compared with normal. Fractionation of these extracts failed to reveal the presence of significant amounts of a soluble component containing unusual proportions of glycine and proline relative to hydroxyproline. It is concluded that deficiency of ascorbic acid either interferes with the synthesis of new collagen in intact skin or causes its destruction and removal as rapidly as it is produced.