The thyroglossal duct cysts (TGDCs) are the most common congenital anomaly of the thyroid, usually manifested as painless midline neck mass. Malignancy is very rare and is reported in around 1% of cases as an incidental finding after histopathological evaluation of resected cyst. Papillary carcinoma is the most common carcinoma reported in TGDC. Here, we report a case of 17-year-old-female, who presented with a gradually increasing midline neck mass which moves with swallowing. On imaging a diagnosis of infected TGDC was made. The Sistrunk operation was done and a diagnosis of primary papillary carcinoma arising in a TGDC was rendered histopathologically. The contemporary appearance of papillary carcinoma thyroid was reported in about 20% cases of TGDC carcinoma, thus it is essential to differentiate primary papillary carcinoma arising in a TGDC from those of metastatic papillary carcinoma thyroid by strict diagnostic criteria.


Introduction/Objectives Identification of groups of patients following similar trajectories of time-varying patient characteristics are often of considerable clinical value. This study provides an example of how the identification of trajectory groups of patients can be useful. Methods Using clinical and administrative data of a prospective cohort study aiming to improve the secondary prevention of osteoporosis-related fractures with a Fracture Liaison Service (FLS), trajectory groups for visit compliance over time (2-year follow-up) were predicted using group-based trajectory modeling. Predictors of trajectory groups were identified using multinomial logistic regressions. Results Among 532 participants (86% women, mean age 63 years), three trajectories were identified and interpreted as high followers, intermediate followers, and low followers. The predicted probability for group-membership was: 48.4% high followers, 28.1% intermediate followers, 23.5% low followers. A lower femoral bone mineral density and polypharmacy were predictors of being in the high followers compared to the low followers group; predictors for being in the intermediate followers group were polypharmacy and referral to a bone specialist at baseline. Conclusions Results provided information on visit compliance patterns and predictors for the patients undergoing the intervention. This information has important implications when implementing such health services and determining their effectiveness.


A large number of N-cyano amidine derivatives were prepared as potential histamine H2 receptor antagonists and evaluated for their inhibitory action on histamine-stimulated chronotropic response of isolated right atria from guinea pigs. Several selected compounds were assessed as inhibitors of gastric acid secretion induced by histamine in anesthetized dogs. Of these compounds, furan (8c) and [(diaminomethylene)amino]thiazole derivatives (16c) were found to be more potent than cimetidine in both assays. In contrast to the guanidine series, methyl substitution at the terminal nitrogen of the cyano amidines was detrimental to the activities. Furthermore, acid hydrolysis of the cyano amidines gave carbamoyl amidines, which proved to be more active than the cyano amidines, the converse of the case for guanidines. 3-[[[2-[(Diaminomethylene)amino]-4- thiazolyl]methyl]thio]-N'-carbamoylpropionamidine (16d) was the most potent of all the compounds tested and was approximately 30 times more active in vitro and 50 times more active in vivo than cimetidine.


Automatic text categorization is an effective method to increase the efficiency and quality of information utilizing. The combination of a set of different classifiers can often achieve higher classification accuracy. The concept of full information matrix is first given, and then an integration method of multiple classifiers based on adaptive weight adjusting is presented in this paper. The classifiers and their weights are determined automatically and adaptively with this method. The effective integration of each classifier抯 result can be realized by analyzing the statistical information of the classifier on the training set. The classification performance is promoted by the improvement of the precision and the recall. The effectiveness of the method is shown by the text classification experiments on the Reuters-21578 text sets.


Study Design. Cross-sectional survey. Objective. The aim of this study was to investigate the association between self-reported low back symptoms and symptoms in the hip, knee, and ankle in a high-risk occupational group. Summary of Background Data. Low back pain, with or without lower extremity referral, poses a major challenge to occupational productivity, especially in farming. Although low back symptoms can occur independent of lower extremity symptoms, anatomical positioning of nerves supplying the lower limbs means structural and physiological changes in the spine can lead to referred pain in the lower limbs, but the magnitude of the association between low back and lower extremity symptoms is unclear. Methods. Baseline postal questionnaire data from the Saskatchewan Farm Injury Cohort Study yielded surveys from 2653 adults from 1020 farms, who responded to Standardized Nordic Questionnaire (SNQ) items on "ache, pain, discomfort" in nine body parts during the last 12 months. Bivariate and multivariate regression modeling was performed with low back symptoms as the outcome and lower extremity symptoms as the independent variable. Results. After adjustment for age, sex, depression, and heavy lifting, low back symptom was significantly related with hip pain (odds ratio [OR] = 3.84, 95% confidence interval [CI] 3.04–4.84), knee pain (OR = 1.84, 95% CI 1.49–2.28), and ankle pain (OR = 1.79, 95% CI 1.40–2.29). Results showed a significant but decreasing relationship to low back symptoms as sites became more distal. Conclusion. Hip and low back symptoms are highly associated, suggesting a common mechanism may be at work. Although there appears be increased risk of knee and ankle region symptoms among those with back pain, the SNQ is not designed to differentiate types of referred symptoms (i.e., numbness, tingling, shooting pain) and/or clinical diagnoses. Other tools, possibly corroborated with clinical examination findings, are likely necessary for a more thorough investigation of referred pain patterns in this high-risk occupational group. Level of Evidence: 3


New generation electronic devices have become more and more sensitive to the effects of the natural radiation coming from the surrounding environment. These radiation sources are cosmic rays and radioactive impurities, able to corrupt the content of memory cells or to induce transient pulses in combinational logic. The growing sensitivity seems to be related to two main factors: the lower and lower charge needed to define the logic levels in advanced devices and the increasing number of basic components inside the modern integrated circuits. In this paper, are described state-of-art techniques to mitigate these effects as well as typical tests to verify the radiation-tolerance of the devices and/or systems.


Over an 18-month period nine infants in a neonatal intensive care unit developed hypertension (blood pressure, 115/88 to 280/140 mm Hg) at 2 to 45 days of age. Eight of the nine infants had indwelling umbilical artery catheters prior to onset of hypertension; six of the nine infants had evidence of a patent ductus arteriosus. Peripheral plasma renin activity was greater than 300 ng/ml/3 hr in six of eight infants. Angiograms were abnormal in six of seven infants and computerized renal scans were abnormal in all nine infants. One infant had congenital renal artery stenosis. Eight of nine infants had evidence of unilateral or bilateral renal artery thrombi which were felt to have emanated from an umbilical artery catheter or a ductus arteriosus. Hypertension in all infants was successfully controlled medically (follow-up of 3 to 27 months; mean, 14.4 months). Blood pressures remained normal when medication was discontinued. In our experience, neonatal renovascular hypertension is no longer uncommon, responds to aggressive medical management, and rarely requires early nephrectomy. Neonatal renovascular hypertension was usually associated with umbilical artery catheters positioned above the level of the renal arteries.


With the recent uptake on the linked open data on the Web, there are many interlinked data sets on the Web today. Interesting results that might not be obvious from this raw data itself, can be derived by computing answers to rules using the data and essentially connecting the dots to see the big picture. We describe a novel method to crawl the Web of data and make inferences that satisfy rules of a particular domain and to reinject the derived conclusions, along with the traces of computation, back into the read-write Web. We have developed a "Computation Agent" to do this using rules written in a formal Semantic Web rule language, and a user interface for viewing the data which includes the derived conclusions along with the justification.


The analysis of gas and vapors in the field is an important part of the environmental characterization and remediation process. The purpose of this article is to familiarize the reader with some of the analytical instrumentation currently used to determine the composition of gaseous samples. Although this section deals with portable instruments, on-site measurements warrant a brief mention. These measurements are often conducted with conventional analytical instruments operating from recreational vehicles. The samples have to be collected and transported to the instrument, and the first part of this article gives an overview of some of the techniques, such as canister and solid adsorbents, used for this purpose. Identification of compounds collected on-site or directly in the field can be done by gas chromatography (GC) and mass spectrometry (MS). A more comprehensive description of these laboratory-based techniques is found in a previous version of this article. An important part of the portable section covers direct-reading instruments such as gas sensors, electrochemical devices, ionization detectors, and colorimetric detectors. These instruments provide a limited amount of information and, most of the time, require prior knowledge of the content of the sample. However, they are small, portable, and cheaper than laboratory analytical instruments and therefore they have found a market. Portable instruments include miniaturized gas chromatographs and mass spectrometers. These instruments do not offer the high performance of their laboratory counterparts, but they give more information about the sample than direct-reading instruments. The next step in process measurement sophistication is to combine these techniques. The most popular hyphenated technique is coupling of a gas chromatograph with a mass spectrometer, but there are also powerful and lesser-known techniques such as GC combined with ion mobility spectrometry (IMS). IMS has found a market in military applications for the detection of chemical warfare agents. It offers less resolution than MS but operates at atmospheric pressure and is therefore truly portable. When combined with GC, it offers some interesting features which are described later.


Peanut or groundnut is one of the major oilseed crops in the world. It is rich in oil and proteins. Developing countries account for about 95% of the world peanut production. Asia alone accounts for 70% of this amount where the major producers India and China together represent over two-third of global output. Traditionally, groundnuts are dried in open sun to its safe moisture level for storage. Natural and artificial (hot air drying) drying methods of groundnuts are being used throughout the world. Artificial peanuts drying devices consume very large amount of energy. In this paper, present status of peanut and a comprehensive review of its drying methods are discussed. Recent developments in preservation and storage of groundnuts are also highlighted.


A.c.-susceptibility data of the re-entrant system (Fe65Ni35)1-xMnx, x = 0.084, reveal two peaks within the re-entrant region, if additional small d.c.-magnetic fields are applied. The peak at lower temperatures can be suppressed by field cooling. This is in qualitative agreement with the predictions of the GT and AT theories. Compared to the a.c.-technique, additional Mössbauer and d.c.-magnetization measurements show the onset of the spin freezing process at higher temperature. The field dependence of the peak temperatures is evaluated.


BACKGROUND
New CKD-EPI and EKFC estimated GFR (eGFR) equations using creatinine (eGFRcr), cystatin C (eGFRcys) and both (eGFRcr-cys) have sufficient accuracy for use in clinical practice. A better understanding of the equations, including their performance in race, sex and age subgroups, is important for selection of eGFR equations for global implementation.

METHODS
We evaluated performance (bias and P30) of equations and methods used for equation development in an independent study population comprising 4050 adults pooled from 12 studies. The mean (SD) mGFR was 76.4 (29.6) ml/min/1.73 m2, age 57.0 (17.4) years, with 1557 (38%) women and 579 (14%) Black participants.

RESULTS
Coefficients for creatinine, cystatin C, age and sex in the CKD-EPI and EKFC equations are similar. Performance of the eGFRcr-cys equations in the overall population (bias <+ 5 ml/min/1.73 m2 and P30 >90%) was better than the eGFRcr or eGFRcys equations, with fewer differences among race, sex and age subgroups. Differences in performance across subgroups reflected differences in diversity of source populations and use of variables for race and sex for equation development. Larger differences among eGFRcr equations reflected regional population differences in non-GFR determinants of creatinine.

CONCLUSION
CKD-EPI and EKFC equations are approaching convergence. It is not possible to maximize both accuracy and uniformity in selecting one of the currently available eGFRcr equations for implementation across regions. Decisions should consider methods for equation development in addition to performance. Wider use of cystatin C with creatinine could maximize both accuracy and uniformity of GFR estimation using currently available equations.


Summary Many hypotheses have been proposed to account for the increased reproductive success with age documented in most birds. One, the mate familiarity hypothesis, suggests that older individuals are likely to have partners with whom they have bred before, which may enhance reproductive success. We found that pairs of house sparrows that bred together previously fledged more young than pairs that were newly formed. This was primarily due to newlyformed pairs with at least one yearling having fewer nesting attempts than continuing pairs. We also examined the possibility that continuing pairs were better coordinated in parental duties, but found no evidence for this in terms of amount of overlap at the nestbox or amount of time nestlings were unattended. Our results suggest the higher success of continuing pairs may be a matter of female age and quality and not due to benefits accrued by coordination with their mate.


Seeds of African marigold cv. 'Pusa Narangi Gainda' were irradiated with 0, 100, 200, 300 and 400 Grays of gamma rays to induce mutation. Seeds were sown just after irradiation and 30-day old seedlings were transplanted into beds. Reduction in survival percentage, plant height, number of branches, leaf number, leaf size, plant-spread, stem diameter, increased foliage and floral abnormalities were observed upon irradiation and with increase in dose of gamma rays. LD50 was determined on survival basis. Leaf abnormality manifested itself as leathery texture of leaf, enhanced and irregular leaf thickness, asymmetric development of pinnate leaflets, reduction in pinnae number, chlorophyll variegation, pale and deep green leaves, narrow leaves and small leaves. Percentage of abnormal leaves and plants increased with increase in dose of gamma rays. Fasciation of stem was a common abnormality observed in all the treatments. Days to bud initiation, earliness in colour-appearance and days to full bloom were all significantly delayed upon exposure to gamma rays. Flower-head size, height and weight were highest at the lowest dose. Number of ray florets and size (length and width) decreased with increasing radiation dose. Floral abnormalities and % of plants with abnormal flower-heads increased with increasing dose of gamma irradiation. Floral abnormality included fasciation of flower-head and asymmetric development of ray florets. Stimulating effect of gamma irradiation was observed at 100 Grays where almost all the characters studied showed positive correlation, including growth and yield attributes. It is concluded that exposure to 100 Grays of gamma rays in African marigold cv. Pusa Narangi Gainda results in higher yield and marketable bloom.


The rapid turnover rate of plasma proteins involved in coagulation has been offered as evidence for a process of continuous subclinical in vivo coagulation. By administration of a continuous intravenous drip of heparin to four normal subjects, no significant change was demonstrated in the rate of disappearance of proconvertin and prothrombin from the circulation after blocking the production of these factors by the administration of a large dose of Warfarin sodium. This evidence does not disprove the existence of continuous coagulation, but the rapid turnover rate of coagulation factors would not appear to be sound evidence for such a process.

Submitted on March 11, 1960


The problem of reconstitution of alimentary tract continuity within the thorax remains dynamic. Procedures in common usage pose the problems of peptic regurgitation, multiplicity and complexity of operations, nutritional defects, and recurrent stricture formation. As many of these difficulties appear to have been overcome by the use of esophagojejunostomy and esophagocologastrostomy via an anterior mediastinal tunnel, an experience with these operations is thought worthy of presentation. This exhibit demonstrates in some detail the operative techniques and their application to selected benign and malignant esophageal lesions. O. O. Age 18 months. Lye burn June 28, 1953. Gastrostomy July, 1953. Esophagocologastrostomy completed October, 1953, in two stages. R. R. Age 53 years. Carcinoma of the esophagus, middle third. Palliative reconstructive procedure attempted. Death on second postoperative day, of adrenal insufficiency (?). B. J. Age 2 years. Lye burn September, 1953. Gastrostomy October, 1953. Esophagocologastrostomy in one stage, May, 1954. H. P. Age 16


The goal of this paper is to construct some families of generalized Apostol-type special numbers and polynomials attached to the Dirichlet character. Using the p-adic q-Volkenborn integrals including the bosonic and the fermionic p-adic integrals on p-adic integers, we give generating functions for these numbers and polynomials. These numbers and polynomials are associated with some well-known special numbers and polynomials such as the Peters polynomials, the Boole polynomials, the generalized Apostol–Bernoulli numbers and polynomials, the generalized Apostol-Euler numbers and polynomials, the generalized Apostol–Daehee numbers and polynomials, the Stirling numbers and the Bernoulli numbers of the first kind. We investigate some properties of these numbers and polynomials with their generating functions. Using these generating functions and their functional equation, we derive some identities and relations including some special numbers and polynomials. Finally, we give p-adic q-Volkenborn integral representations for these numbers and polynomials with combinatorial sums.


Here it is shown that the Vlasov equation is an adequate model in case of high-intensity charged-particle beams. Several instances are analyzed when it is possible to construct an integral basis of the operator, associated with the dynamic system under study. This is the case, in particular, for the two-dimensional dynamic systems, just such systems describing the longitudinal motion of a perturbed system. For systems of more general structure we advance a method of reduction of the quasilinear Vlasov equation to an integral Fredholm equation. The main cases are examined when it is possible to construct kernels of corresponding integral operators. In particular, a feasibility to employ Feier - Chesaro kernels is demonstrated. Using the universality (according to V. I. Zubov) of Maxwell equations the problem of a search for stabilizing and focusing fields is reduced to the construction of Toeplitz matrix. Also conditions are analyzed, ensuring initiating of a continuous spectrum points within the spectrum of a dynamic system. Physically, this phenomenon is related to the chaotic motion of the particles. Also, the dispersion equation, expressed in terms of solutions to the Fredholm equation, is deduced.


Summary Under the forearc region off the Japanese Islands a conspicuous basal acoustic reflection plane can be traced at the surface of the acoustic basement from the oceanic plate into the bottom of the accretionary prism. Recent studies indicate this plane cannot be the upper boundary plane of the subducting oceanic plate, but must be the upper layer of the oceanic basaltic basement (or chert layer). The tectonic activity of the Wadati-Benioff zone appears to be a thrust movement which cuts the boundary between the oceanic basement and the overlying sediments. Thrusts cut the basal reflector and extend into the accretionary prism. Large earthquakes which occur at intermediate and shallow depths under the continental shelf and slope are a direct manifestation of these thrust movements. Thrust faulting also occurred in past geological time. Acidic and basic magma, possibly generated along the earthquake zone at intermediate depths, ascended along the thrust faults or associated normal faults. Intrusions occurred 15–16 Ma ago in the forearc region of Southwest Japan and 22 Ma ago in that of Northeast Japan; subsequently basins subsided landward of the intrusions. In some cases the forearc igneous rocks carried continental and oceanic crustal xenoliths. Good examples of such forearc igneous rocks, including xenoliths, occur in the Permian and Triassic structural belts of the Japanese Islands. The model described here is specific to the forearc regions of the Japanese Islands. We envisage that different tectonic parameters such as convergence rate and sediment supply may engender different structural processes in other forearcs.


The May 8, 2018, featured interview highlighted a study on treatment delays in pediatric refractory convulsive status epilepticus. For our What's Trending feature of the week, you will hear a discussion on focused ultrasound for the treatment of tremor.


Though survival is important to firms, especially to the Japanese big businesses, there are few empirical studies on their longevity. This paper conducts the statistical analysis on the longevity of the Japanese big businesses using data on 1,273 listed firms in the first section of Tokyo Stock Exchange. The result indicates that the longevity of the Japanese big businesses may go beyond a century on average, and the longevity had increased gradually in the post-WWII period. These findings suggest that the Japanese big businesses are stable. This paper also explores the relationship between this stability and the Japanese corporate systems.


Nucleotide binding leucine-rich repeat proteins (NLRs) are the major class of intracellular immune receptors in plants. NLRs typically function to specifically recognize pathogen effectors and to initiate and control defense responses that severely limit pathogen growth in plants (termed effector-triggered immunity, or ETI). Despite numerous reports supporting a central role in innate immunity, the molecular mechanisms driving NLR activation and downstream signaling remain largely elusive. Recent reports shed light on the pre- and post-activation dynamics of a few NLR-containing protein complexes. Recent technological advances in the use of proteomics may enable high-resolution definition of immune protein complexes and possible activation-relevant post-translational modifications of the components in these complexes. In this review, we focus on research aimed at characterizing pre- and post-activation NLR protein complexes and the molecular events that follow activation. We discuss the use of new or improved technologies as tools to unveil the molecular mechanisms that define NLR-mediated pathogen recognition.


Student modeling, the task of inferring a student's learning characteristics through their interactions with coursework, is a fundamental issue in intelligent education. Although the recent attempts from knowledge tracing and cognitive diagnosis propose several promising directions for improving the usability and effectiveness of current models, the existing public datasets are still insufficient to meet the need for these potential solutions due to their ignorance of complete exercising contexts, fine-grained concepts, and cognitive labels. In this paper, we present MoocRadar, a fine-grained, multi-aspect knowledge repository consisting of 2,513 exercise questions, 5,600 knowledge concepts, and over 12 million behavioral records. Specifically, we propose a framework to guarantee a high-quality and comprehensive annotation of fine-grained concepts and cognitive labels. The statistical and experimental results indicate that our dataset provides the basis for the future improvements of existing methods. Moreover, to support the convenient usage for researchers, we release a set of tools for data querying, model adaption, and even the extension of our repository, which are now available at https://github.com/THU-KEG/MOOC-Radar.


Summary Several novel derivatives bearing the 7-trifluoromethyl-4-(4-substituted anilino)-quinoline skeleton were synthesized and evaluated for their in vitro activity against the blood streaming form of the parasites Trypanosoma brucei rhodesiense, the trypomastigotes of Trypanosoma cruzi cultured in rat skeletal myoblasts, the amastigotes form of Leishmania donovani, Plasmodium falciparum (K1 strain) infected erythrocyte suspension, as well as their toxicity towards rat skeletal L-6 cells. In addition, three of the synthesized compounds were tested for their in vitro antitumor activity towards 60 human tumor cell lines by the National Cancer Institute (NCI). Compound 1-(4-{[7-(trifluoromethyl)quino-lin-4-yl]amino}phenyl)ethan-1-one thiosemicarbazone 23 exhibited potential activity against T. b. rhodesiense, T. cruzi and P. falciparum with IC50's of 0.278, 0.85 and 0.417 µg/ml, respectively. These values are even more valuable since this compound was clearly non-toxic (cytotoxicity IC50 > 90 µg/ml), leading to in vitro therapeutic indices of > 323, > 106 and > 216, respectively. Meanwhile, compound N-{4-[5-(4-chlorophenyl)-4,5-dihydroisoxazol-3-yl]phenyl}-7-(trifluoromethyl) quinolin-4-amine 21 showed broad spectrum antitumor activity with full panel median growth inhibition GI50 (MG-MID) of 1.95 µmol and total growth inhibition TGI (MG-MID) of 6.87 µmol, respectively. Compound 23 represents a very good prospective as a lead compound able to combat three tropical diseases at a time. However, the pattern for the antitumor activity did not parallel any of the antiparasitic ones, indicating that non-common mechanisms of action may exist among these activities.


The article is devoted to the problem of studying verbal conflict through the prism of judicial discourse. Consideration of this problem becomes especially important in the framework of verbal conflict studies. It examines the consolidation of the studied terminology in historical retrospect, singles out and describes the main approaches used by researchers to define the content of the notion «judicial discourse». Special attention is paid to the establishment of differences in the interpretation of the term «discourse», its functioning in linguistic and legal literature by domestic and foreign researchers. The prerequisites for the emergence of the notion in question are revealed, and the author's definition of the terms «judicial discourse» and «verbal conflict» is proposed. The spheres of usage of the notion in question (linguistic, publicist and social action theory), the basic interpretations of the notion of discourse taking into account its nature of interdisciplinary from the perspective of various sciences particularly philosophy, jurisprudence, legal linguistics, sociolinguistics, pragmalinguistics and linguophylosophy are established. Emphasis is placed on the need to address a verbal conflict, bearing in mind its pragmatic nature within the social-role characteristics of judicial discourse. Given that the clarification of contradictions between the parties is carried out in the course of verbal judicial interaction, it is particularly important to take into account the verbal behavior in the communication phase of the verbal conflict. Representing a state of confrontation between two sides, verbal conflict is considered by the authors as a kind of bilateral process of exchange of verbal acts, within the framework of which illocution of communicators is realized. Judicial discourse is defined by the authors as a linguistic professional activity, which has characteristics: sphere of functioning — a branch of law (legal discourse can be observed, where legal issues are dealt with and regulated); the subject matter and main motive of the judicial discourse — the notion of the law, as well as compliance with the law of the precedent under consideration; communication focus of judicial discourse — adjustment of social relations; the general cognitive identity of judicial discourse is the prevalence of facts over values.


Objectives: Self-administered vaginal rings are a promising method for delivery of topical anti-HIV microbicides and might offer an adherence advantage over daily or coitally-dependent dosage forms such as gels. This trial assessed the safety and pharmacokinetic aspects of the Dapivirine Vaginal Ring-004 when worn as multiple rings over sequential periods of ring use by healthy, sexually-active, HIV-negative women. Methods: This double-blind trial was conducted among 48 women (18-40 years). Participants were randomly assigned to two groups (A or B) and received (3:1) either the dapivirine or a placebo vaginal ring. Group A used two rings over a 56-day period and Group B used three rings over a 57-day period. Safety evaluations were conducted throughout the trial. Dapivirine concentrations were measured in plasma, vaginal fluid and cervical tissue samples collected during and after the 56 days (Group A) or 57 days (Group B) of vaginal ring use. Results: Ring-004 was safe and well tolerated in all participants. The pharmacokinetic profile demonstrated a rapid increase in plasma and vaginal fluid concentrations and achieved concentrations in vaginal fluids and cervical tissue well above the in vitro IC99 in cervical tissue (3.3 ng/mL) that were sustained for a 28 to 35-day ring use period (approximately 3000 times higher in vaginal fluids and 14 -1000 times higher in cervical tissue). Drug levels were associated with significant inhibitory activity of genital secretions against HIV ex vivo, a biomarker of pharmacodynamics. Individual plasma dapivirine concentrations did not exceed 553 pg/mL and were well below plasma concentrations at the maximum tolerated dose for oral treatment (mean Cmax 2286 ng/mL). Conclusions: The consecutive use of several rings over a period of up to 57 days was safe and well tolerated, and PK data indicate that a single Ring-004 is likely to be protective for at least 35 days.


Many infectious diseases have emerged or re-emerged during the past 50 years in South Korea. There were three outbreaks of foot and mouth disease (FMD) in South Korea between January 2010 and March 2011. Over 3.45 million animals were slaughtered (33.3% of the existing pigs, 8.4% of dairy cows and 3.4% of cattle). To select optimal degradation agents of animal cadavers, degradation rates and fertilizer components of pig cadavers were investigated using hydrogen chloride (HCl), potassium hydroxide (KOH) and sodium hydroxide (NaOH) hydrolysis methods. Degradation rates of pig cadavers using HCl, KOH and NaOH were 81.1, 82.8 and 91.6%, respectively. Total nitrogen (T-N) concentration in degradation solution of pig cadavers using KOH hydrolysis method was higher than that in NaOH and HCl hydrolysis methods. Total phosphorus (P₂O 5 ) concentrations in degradation solution of pig cadavers in all hydrolysis methods ranged 0.14 ~ 0.28%. Total potassium (K₂O) concentration for KOH hydrolysis method was higher than that for other hydrolysis methods. The concentration of T-N and K₂O in degradation solution of pig cadavers by KOH hydrolysis method were higher than that in NaOH and HCl hydrolysis methods. Thus, to recycle animal cadavers in agriculture, the optimal degradation agent for hydrolysis was KOH.


The artificial creation of human skin, tissue, and internal organs may sound like a futuristic dream but, incredibly, much of it is happening right now. In research facilities and hospitals around the world, scientists and medical researchers are using scanners and printers, traditionally reserved for auto design, model building, and product prototyping, to develop completely personalized treatments.


Soil samples collected near municipal schools (public/EMEI and private/EPEI schools), clubs (CLB), public squares (PS) and residential condominiums (CND) and samples of animal faeces from the Zoonosis Control Centre (CCZ) of the municipality of Votuporanga/SP were analysed using the Baermann method for the detection of zoonotic helminth larvae. The prevalence rates of the nematode genera identified were determined, and the results were compared using Fisher's exact and chi-square frequency tests. Information about cases of larvae migrans in the population were collected from the Family Health Units and the private health plans. All sites were positive for Ancylostoma spp. and, with the exception of EPEIs and dog faeces, for Strongyloides spp. The prevalence of Ancylostoma spp. was 87.5% for CND samples, 74.29% for EMIEs, 63.64% for CLB, 61.76% for PS and 64.29% for dog's and 42.86% for cats at CCZ. The prevalence of Strongyloides spp. ranged from 14.29% (cats/CCZ) to 41.18% (PS). Cases of cutaneous larva migrans were reported during interviews. Thus, from the public health perspective, the risk of individuals that frequent recreational areas in the municipality, especially children, to be infected by helminth larvae is noteworthy, indicating the need to develop policies aimed at controlling this important zoonosis.


Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL

In this study, we purpose the analysis of the DNA methylation profile of four different human breast cell lines, two non transformed and two tumoral, taking into account the influence of the environment in cell culturing.

The extracellular matrix was initially thought to serve as nothing more than a physical support for the cells. However, nowadays is very well known that the extracellular matrix is a key component in cell biology, regulating cell biology and tissue homeostasis. This suggests that there is a bidirectional crosstalk between the cells and the surrounding extracellular matrix.

Cell culturing is a commonly used technique in all areas of biology research. Usually, adherent cells are spreading in two-dimensional plates where they growth attached to the plastic surface in two directions. Mammary epithelial cells that are cultured on this conventional way fail to form acinar-like structures and loss tissue specific protein expression. Many of the microenvironment influences can be restored in cell culturing models by using three-dimensional cultures in extracellular matrix gels. 3D culturing of epithelial cells can help to reconstruct the acinar morphology seen in vivo and restore some mammary-specific function, like milk proteins production.

DNA methylation plays a significant role in the epigenetic regulation of chromatin structure and gene expression. In this work, we tried to analyze the DNA methylation profile of four different human breast cell lines growth in 2 and 3 dimensions to assess the influence of DNA methylation in the two models. HMEC (finite lifespan human mammary epithelial cell line), MCF10A (spontaneously immortalized, but not transform, human breast epithelial cell line), MCF7 (human breast adenocarcinoma cell line, metastasic) and MDA-MB-231 (human breast adenocarcinoma cell line, metastasic) were growth in plates with and without MatrigelTM basement Membrane Matrix Growth Factor Reduced (BD). 3D culturing was done by spreading the cells in the matrix surface and allowing them to form the characteristic acini of the mammary gland. Morphological differences are evident between the 2 and 3D culture models, being much more accurate the 3D model from a phenotypic point of view. DNA mehtylation status was done by illumina's Infinium Microarrays, comparing the methylation profile of each cell line growth in 2 and 3D. We determined in this way which genes are differentially methylated in 2 and 3 dimensions.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3013. doi:10.1158/1538-7445.AM2011-3013


A landmark study of architectural photography and its key themes, illustrated with arresting images from collections across the globe. From the earliest examples of the genre in the nineteenth century to today's digital revolution, renowned expert Robert Elwall skillfully focuses on the changing aesthetic of the medium worldwide.


This thesis presents a subset of the author's published works, and describes the impact his work has
had on ocean forecasting systems. This impact can be broadly divided into two themes, the
underpinning development of ocean forecasting models and the implementation, tuning and
evaluation of those models to ensure they provide skilful products, with value to users. The systems
described in this dissertation are recognised as amongst the best available, and are being used by
commercial operators, military decisions makers and governmental organisations, as well as
research users. They also form the basis on which future systems will be developed, meeting the
challenges and addressing the priorities discussed in the thesis. The author expects to have a
substantive impact on driving the research agenda in these areas over the coming years.


Two structural design studies were made, based on current tec.hnology and on an estimate of technology to be available in the mid 1980's, to assess the relative merits of structural concepts and materials for an advanced arrow wing configuration cruising at Mach 2.7. Preliminary studies were made to insure compliance of the configuration with general design criteria, integrate the propulsion system with the airframe, and define an efficient structural arrangement. Material and concept selection, detailed structural analysis, structural design and airplane mass analysis were completed for the first study based on current technology. In the second study, based on estimated future technology, structural sizing for strength and a preliminary assessment of the flutter of a strength designed composite structure were completed. In both studies, an advanced computerized structural design system was used, in conjunction with a relatively complex finite element model, for detailed analysis and sizing of structural members.


The pattern design of brassieres is the core technology for the design and manufacture of brassieres, while the female breast shape and part dimensions are the foundations for pattern design of brassieres. Based upon 3D body scanning, this paper studied the relationship between the breast root shape and the steel ring by considering the features of the pattern design of the brassiere. It concludes that the breast root girth is a complicated three-dimensional curve; it's inappropriate for the neighboring size's brassieres to adopt the steel ring with the same specification; the material design of the steel ring should be moderate. The purpose is to provide human body basis for pattern design of brassieres and achieve more standard and scientific pattern design of the brassiere by the underwear enterprises.


It is shown that, when two coherent waves are obliquely incident to a one-dimensional nonlinear optical superlattice containing Kerr-form dielectric nonlinearity, an incident-dependent two-dimensional nonlinear optical superlattice can be constructed. This structure can be bistable. There exist two types of optical bistable mechanism, i.e., the index-modulation mechanism and distributed feedback mechanism. Owing to the index-modulation mechanism, the threshold for the bistability is lower than that of a more traditional one-dimensional distributed feedback structure.


"A Conspiracy of Optimism" explains the controversy now raging over the U.S. Forest Service's management of America's national forests. Confronted with the dual mandate of production and preservation, the U.S. Forest Service decided it could achieve both goals through more intensive management. For a few decades after World War Two, this "conspiracy of optimism" masked the fact that high levels of resource extraction were destroying forest ecosystems. The effects of intensive management--massive clear-cuts, polluted streams, declining wildlife populations, and marred scenery--initiated several decades of environmental conflict that continues to the present. Hirt documents the roots of this conflict and illuminates recent changes in administration and policy that suggest a hopeful future for federal lands.


Data visualization environments help users understand and analyze their data by permitting interactive browsing of graphical representations of the data. To further facilitate understanding and analysis, many visualization environments have special features known as portals, which are sub-windows of a data canvas. Portals provide a way to display multiple graphical representations simultaneously, in a nested fashion. This makes portals an extremely powerful and flexible paradigm for data visualization. Unfortunately, with this flexibility comes complexity. There are over a hundred possible ways each portal can be configured to exhibit different behaviors. Many of these behaviors are confusing and certain behaviors can be inappropriate for a particular setting. It is desirable to eliminate confusing and inappropriate behaviors. The authors construct a taxonomy of portal behaviors and give recommendations to help designers of visualization systems decide which behaviors are intuitive and appropriate for a particular setting. They apply these recommendations to an example setting that is fully visually programmable and analyze the resulting reduced set of behaviors. Finally, the authors consider a real visualization environment and demonstrate some problems associated with behaviors that do not follow their recommendations.


Various stimuli-responsive composite particles with a high control of their internal structure and their corresponding hollow capsules are synthesized and characterized by photon correlation spectroscopy, TEM, and AFM. Core-shell particles with a silica core and a thermoresponsive shell are obtained by polymerization of N-isopropylacrylamide (NIPAM) in the presence of silica seeds grafted with a high density of gamma-methacryloxypropyltrimethoxysilane (MPS). The influence of the synthesis conditions is studied. The shell thickness increases when the monomer concentration increases in a limited range where uniform composite particles with a single core are obtained. At constant monomer concentration, the shell thickness does not depend on the size of the silica seeds, but the presence of free unbound microgels is observed when the silica surface area decreases. A range of particle diameters and shell thicknesses is thus obtained, which can lead to the corresponding hollow capsules by exposure to hydrofluoric acid solution. The volume phase transition temperature of these materials can be easily tuned by replacing the NIPAM monomer by another N-alkylacrylamide derivative. However, the incorporation of comonomers such as acrylic acid (AA) and a phenylboronic acid (PBA) derivative inhibits the formation of core-shell structures. In order to get pH or glucose responsiveness, these functional groups can be incorporated in the outer shell of a core-double shell structure, with pNIPAM as intermediate shell. pH-responsive and glucose-responsive composite particles are obtained by this method with a high control of their internal structure.


This paper proposes a MIMO 2×2 solution to increase the capacity of HF radio links through the ionospheric channel. A diversity in the transmitted polarizations replaces the classical space diversity and authorizes a compact set up in a context of decametric wavelengths. After a theoretical step of capacity estimation, an HF 2×2 MIMO system has been designed and tested on a 280 km long radio link. The data transfer rate reaches up to 24.09 kbps (in a 4.2 kHz bandwidth) with a good quality of service. (5 pages)


Received Signal Strength Indicator (RSSI) was deemed that it is not applicable for WLAN localization directly, as it is highly influenced by environment and limited by the measurement device. This distortion must be avoided to improve RSSI based distance measurement accuracy. Some method has been introduced to achieve this purpose such as Statistical Mean Value Model (SMVM) and Gauss Model (GM). This paper studies a new method namely Ensemble Empirical Mode Decomposition (EEMD) to process RSSI. A WLAN infrastructure includes one transmitter and one receiver was setup in outdoor and indoor environment to evaluate the performance of this method. The experiment consists of two aspects of transmitter movement reproduction and error analysis followed by a performance comparison with other well-known existing methods. Based on the experiment result, EEMD can efficiently normalize the RSSI reading related to distance and reproduce the movement of transmitter. In addition, EEMD presented more valid accuracy in outdoor environment than indoor environment.


Objective: We report the case of a 14-year-old girl that presented chronic osteomyelitis with extrusion of the proximal phalanx, after a traumatic event three months before, in the rural setting of Djoum, Cameroon. Massive defects of the proximal phalanx of the thumb are uncommon, mostly associated with traumatic amputations or tumors. The aim of this study is to describe our experience in the management of this injury in a low resource center and its mid-term clinical results.
Methods: The presence of an active infection and the lack of technological support determined our treatment choice. Extensive debridement, metacarpophalangeal arthrodesis with 2 Kirschner wires and first web space deepening were performed. Rifampicin and trimethoprim-sulfamethoxazole were prescribed empirically for four months.
Results: At 6-month-following-up the patient was pain-free. Complete arthrodesis of the distal phalanx and first metacarpal was confirmed in clinical assessment. The thumb was slightly pronated, and it permitted good opposability against second, third and fourth fingers. The sensitivity of the thumb tip kept intact. The overall function was rather good, with a QuickDASH score of 18 at the two-year follow-up visit. She was satisfied with final pinch ability and had returned to her normal activities.
Conclusions: We suggest that in a disadvantaged rural environment, metacarpophalangeal arthrodesis associated to first web space deepening may be a reliable treatment for a massive defect of the proximal phalanx of the thumb due to chronic osteomyelitis achieving a satisfactory hand function.


Monoclonal antibodies raised to the high-sulfur fraction of solubilized wool protein were used to study the location of these proteins in sections of Merino sheep skin, using indirect immunofluorescence. Poor antibody binding was observed to untreated wool follicles, but mild trypsin digestion of the sections allowed penetration of the antibodies and specific antibody localization was observed. The high-sulfur protein monoclonal antibodies bound to the cells of the wool cortex in the keratogenous zone, and to the cells of the inner root sheath and fibre cuticle regions. The specificities of the antibodies were determined by their binding to high-sulfur proteins separated using high-performance liquid chromatography.


Introduction: Given that some plant-based foods, such as potatoes, adversely affect cardiovascular disease (CVD) risk factors, this study was performed to assess the association between plant dietary patterns and these risk factors. Methods: This cross-sectional study was conducted among 371 healthy 18 to 50 year-old Iranian women. Participant dietary intake was assessed using a validated food frequency questionnaire. Nineteen food groups were ranked in deciles and received scores from 1 to 10. An overall plant-based dietary index (PDI), a healthy plant-based dietary index (hPDI), and an unhealthy plant-based dietary index (uPDI) were calculated. Results: Participants who scored in the top tertile of the PDI or uPDI consumed less fat and protein and more carbohydrates, compared to women in the lowest tertile (P < 0.05). There was no significant variation in macronutrient consumption between the highest and lowest tertiles of hPDI. Participants who scored in the highest tertile of PDI had lower low density cholesterol level (LDL) (79.61 ± 14.36 mg dL−1 vs. 83.01 ± 14.96 mg/dL−1, P = 0.021). In addition, higher adherence to uPDI was associated with higher triglyceride (TG) levels compared to participants with lower adherence (101.5 ± 56.55 mg/dL−1 vs. 97.70 ± 56.46 mg dL−1, P < 0.0001). Here was no significant association between PDI, hPDI and uPDI and CVD risk factors in regression model. Conclusion: We found no significant association between plant-based dietary indices and CVD risk factors in women, except for LDL-C and TG. Future cohort studies are needed to confirm these findings.


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Background and objectives Complete remission (CR) after induction therapy is the first treatment goal in acute myeloid leukemia (AML) patients. The aim of this study is to determine the ability of the Vivia's novel ex vivo drug sensitivity platform Exvitech analyzing leukemic cell death to predict the CR rates after induction chemotherapy with cytarabine (Ara-C) and idarubicin (Ida) in 1st line AML.

Patients and Methods This non-interventional and prospective study included samples from adult patients over 18 years of age diagnosed with de novo AML in Spanish centers from the PETHEMA group. Marrow samples were collected at diagnosis, sent to the Vivia laboratories, and incubated for 48 hours in whole samples in well plates containing Ara-C, Ida, or the combination Ara-C+Ida, each at 8 different concentrations to calculate dose responses. Annexin V-FITC was used to quantify the drug-induced apoptosis. Pharmacological responses are calculated using pharmacokinetic population models. Induction response was assessed according to the Cheson criteria (2003). Patients attaining a CR/CRi were classified as responders. The remaining patients were considered as resistant. Patients dying during induction response assessment were non-evaluable. The correlation was modeled using a generalized additive model with a logit link and a binomial distribution for residuals. Kernel density estimates were then used to plot empirical probability density functions for both groups. Their separation was quantified as the area under the ROC curve and a cut point was selected using the Youden's criteria to optimize the classification probabilities (sensitivity, specificity). 95% confidence intervals for sampling errors were calculated for all these quantifiers.

Results 125 patient samples were used to calculate the dose response curves for Ara-C alone, Ida alone, and the synergism of the Ara-C plus Ida combination. For clinical correlation we used 64 patients with a median age of 55 years (range 31 to 72). Dose responses for Ara-C alone are shown in [Figure 1.A][2]; note that for many samples there is a significant number (>20%) of resistant cells to Ara-C (bracket). This is a strong clinical predictor of resistance because in the patient the drug will never be present at these high doses for 48 h. The second variable that is a good predictor of response is the synergism between these 2 drugs. The generalized additive model identified an algebraic combination of these 2 variables that yielded the best marker to separate both groups of patients. The probability density functions had minimal overlap. The area under the corresponding ROC curve was 0.965 (0.928, 1.000), and the classification probabilities for the optimal cut point (set at 0.414 for the marker), expressed as percentages, were 85% (62.1% to 96.8%) and 86.4% (72.6% to 94.8%) for sensitivity and specificity, respectively. Results are shown in [Figure 1.B][2]; Forty-four patients (68.8%) achieved CR after Ida+Ara-C, and the remaining 20 (31.3%) were resistant. Correlations of the PM test are shown in [Figure 1.B][2]. Seventeen of the 20 (85%) patients who fail to achieve CR were predicted as resistance in the ex vivo test. Thirty-eight of the 44 patients (86.4%) who achieved CR showed good ex vivo sensitivity to Ida+Ara-C predicting for CR. When the ex vivo test predicted a patient as sensitive it was correct in 38/39 cases (93%), and when it predicted resistant it was correct 17/23 cases (74%). Overall, 45 patients (86%) had an accurate prediction of their response to treatment.

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Conclusions This study shows that this novel ex vivo pharmacological profile test is able to predict the clinical response to Ida+Ara-C induction. We are increasing the number of patients in this ongoing study, and we are planning a PM Test-adapted Clinical Trial.

Disclosures: Martinez: Vivia Biotech: Employment. Ortega: Vivia Biotech: Employment. Primo: Vivia Biotech: Employment. Hernandez-Campo: Vivia Biotech: Employment. Rojas: Vivia Biotech: Employment. Bennett: Vivia Biotech: Employment. Liebana: Vivia Biotech: Employment. Lopez: Vivia Biotech: Employment. Ballesteros: Vivia Biotech: Equity Ownership.

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The Mesozoic basement at Kawerau Geothermal Field comprises well indurated, inter-bedded sandstones and argillites with a complex structural history. These rocks have very low matrix porosity but nonetheless host both geothermal production and injection. Fluid flow therefore is localized in fault and fracture networks. The geometry of, and potential controls on, these fluid pathways is revealed by an integrated study of borehole acoustic image logs, geologic, drilling and reservoir data from two deep geothermal injection wells. Well permeability, as interpreted from pressure, temperature, and fluid velocity logs acquired during well completion testing, correlates with large aperture fractures and zones where cross-cutting fractures are densely distributed. The occurrence of large aperture fractures also correlates with the occurrence of high sandstone proportions in the drill cuttings. A similar spatial relationship between fracture aperture and rock type occurs in exposed basement greywacke hosted Kuaotunu epithermal deposit, Coromandel Peninsula, New Zealand. These observations demonstrate the importance of understanding material properties when exploiting and stimulating fracture permeability. Despite the complex structural history of the basement greywacke, nearly all large aperture fractures identified from image logs were found to be optimally orientated for reactivation within the modern stress field. Comparison between the orientations of fractures observed down-hole and the orientation of field-scale faults interpreted from vertical displacement between wells reveals a structural relationship across scales. An understanding of the relationship between the modern stress field, field-scale structures and fractures that contribute to wellbore flow can be applied to the mapping of reservoir fracture permeability.


Purpose: The bony skeleton serves as the scaffolding for the soft tissues of the face; however, age-related changes of bony morphology are not well defined. This study sought to compare the anatomic relationships of the facial skeleton and soft tissue structures between young and old men and women. Methods: A retrospective review of CT scans of 100 consecutive patients imaged at Duke University Medical Center between 2004 and 2007 was performed using the Vitrea software package. The study population included 25 younger women (aged 18–30 years), 25 younger men, 25 older women (aged 55–65 years), and 25 older men. Using a standardized reference line, the distances from the anterior corneal plane to the superior orbital rim, lateral orbital rim, lower eyelid fat pad, inferior orbital rim, anterior cheek mass, and pyriform aperture were measured. Three-dimensional bony reconstructions were used to record the angular measurements of 4 bony regions: glabellar, orbital, maxillary, and pyriform aperture. Results: The glabellar (p = 0.02), orbital (p = 0.0007), maxillary (p = 0.0001), and pyriform (p = 0.008) angles all decreased with age. The maxillary pyriform (p = 0.003) and infraorbital rim (p = 0.02) regressed with age. Anterior cheek mass became less prominent with age (p = 0.001), but the lower eyelid fat pad migrated anteriorly over time (p = 0.007). Conclusions: The facial skeleton appears to remodel throughout adulthood. Relative to the globe, the facial skeleton appears to rotate such that the frontal bone moves anteriorly and inferiorly while the maxilla moves posteriorly and superiorly. This rotation causes bony angles to become more acute and likely has an effect on the position of overlying soft tissues. These changes appear to be more dramatic in women.


In past investigation, most of studies on seismic analysis for soil structure interaction effect are small and generally design building were considered to be fixed at their support. In actual condition, flexibility of the bases soil medium were generate some deformation in foundation element and will be shows detrimental effects on the system behavior. This can make a beneficial result on the overall structure response if flexible bases were considered during seismic analysis. The present study attempts to compare the behavior of reinforced concrete medium rise building with soil structure interaction effect and fixed bases under vertical earthquake. The eight-storey irregular 2D frame models were subjected to ground motion from 4 stations with peak ground acceleration ratios vertical to horizontal (V/H) between ranges 0.95 to 1.16. During simulation of simplified model, Impedance Function has been applied to calculate the stiffness of such spring. The structural response quantities were considered displacement histories and axial load variation. The result shows that the consideration of soil structure interaction effect may increase such response behavior.


It is essential to develop a safety culture with the participation of university teachers and students in actions and studies that can contribute to safer and more sustainable practices in academic laboratories. The present work analyzes the potential of a training program to raise awareness and establish environmental education and green chemistry concepts concerning procedures for the management and treatment of chemical waste generated in experimental classes. This is a qualitative case study providing a critical perspective of environmental education. The training activity, lasting 45 minutes, was conducted with 66 students entering Chemistry courses at a Brazilian public university. Data collection was carried out using an initial questionnaire to identify the students' prior knowledge, and a final one applied after the training period. The questionnaires contained open questions and closed questions with a Likert-type scale. The results showed that the training activity contributed to the students' understanding of the concepts, procedures, and attitudes related to the management and treatment of chemical waste, including the interrelations among the environmental, social, and economic impacts of waste management, the importance of correct separation and storage of residues for disposal using different types of treatment, the civil liability of the academic community for the residues generated, and how the 3Rs principles can favor sustainable practices in the academic context.


OBJECTIVE
The study evaluates salt taste sensibility, urinary sodium excretion and blood pressure (BP) in normotensive persons. The hypothesis was that a higher salt taste threshold (STT) can be associated to a higher 24 hour natriuresis and increased BP levels.

METHODS
Twenty four not hypertensive volunteers were selected. To evaluate STT, different concentrations of sodium chloride were used. Individuals were submitted to 24 hour ambulatory blood pressure monitoring (ABPM) and the 24 hour urine was collected for sodium dosage. Patients were divided in two groups related to higher or normal STT.

RESULTS
Both groups did not differ regarding age or body mass index (BMI). There was no difference between the groups regarding demographic variables, alcohol or tobacco use, and ABPM. Twenty-four hour natriuresis was significantly higher in the group with increased STT. Using Pearson's correlation coefficient, with the significance determined by Student-t test, there was a strong correlation between 24 hour Systolic BP and BMI, Diastolic BP and BMI, and a regular correlation between STT with 24 hour natriuresis and Systolic BP with 24 hour natriuresis.

CONCLUSION
Twenty four hour natriuresis was significantly higher in individuals with higher STT, suggesting that this avidity for salt is followed by higher ingestion of sodium. There was strong association between BP and BMI. The association between STT and BP levels was not confirmed. Increasing the number of persons, the age bracket, and of hypertensive patients may lead to a better understanding of the relations between STT, natriuresis and BP variation.


The higher education sector has seen a shift in teaching approaches over the past decade with an increase in the use of video for delivering lecture content as part of a flipped classroom or blended learning model. Advances in video technologies have provided opportunities for students to now annotate videos as a strategy to support their achievement of the intended learning outcomes. However, there are few studies exploring the relationship between video annotations, student approaches to learning, and academic performance. This study seeks to narrow this gap by investigating the impact of students' use of video annotation software coupled with their approaches to learning and academic performance in the context of a flipped learning environment. Preliminary findings reveal a significant positive relationship between annotating videos and exam results. However, negative effects of surface approaches to learning, cognitive strategy use and test anxiety on midterm grades were also noted. This indicates a need to better promote and scaffold higher order cognitive strategies and deeper learning with the use of video annotation software.


Objective: To determine serum thiol/disulfide homeostasis in panic disorder (PD). Methods: Serum native thiol, total thiol, and disulfide levels were measured in the patients with 40 PD patients and 40 healthy subjects. Serum native thiol, total thiol, and disulfide levels were measured with a novel colorimetric, automated method. The thiol-disulfide ratio was also calculated. Results: The native thiol (p < 0.001) and total thiol (p < 0.001) levels, and the native thiol/total thiol (p < 0.001) ratio were significantly lower, whereas disulfide/native thiol (p < 0.001) and disulfide/total thiol (p < 0.001) ratio significantly increased in the PD patient group compared to the control group. The cut-off value was 92.26, 3.83 and 3.56 for native thiol/total thiol, disulfide/native thiol and disulfide/total thiol respectively. Conclusion: This is the first study in the literature to evaluate thiol-disulfide homeostasis in patients with PD. Our results suggest that the disulfide/thiol ratio is significantly greater in panic disorder patients.


In semiconducting carbon nanotube quantum dots that contain a few interacting electrons the electron-electron correlation is always important. The states of up to six interacting electrons in such a dot are calculated by exact diagonalisation of a 2-band, effective mass Hamiltonian. The addition energy and the few-electron density are investigated for a wide range of dots with different physical properties and, in a large proportion of these dots, the electrons are found to form Wigner molecules.


We study heterotic Calabi-Yau models with hypercharge flux breaking, where the visible E-8 gauge group is directly broken to the standard model group by a nonflat gauge bundle, rather than by a two-step process involving an intermediate grand unified theory and a Wilson line. It is shown that the required alternative E-8 embeddings of hypercharge, normalized as required for gauge unification, can be found and we classify these possibilities. However, for all but one of these embeddings we prove a general no-go theorem which asserts that no suitable geometry and vector bundle leading to a standard model spectrum can be found. Intuitively, this happens due to the large number of index conditions which have to be imposed in order to obtain a correct physical spectrum in the absence of an underlying grand unified theory.


We believe this is the first collection of papers to be devoted entirely to reservoir geochemistry, which is an area of growing scientific and economic importance. The main aim of reservoir geochemistry is to understand the distributions and origin(s) of the petroleums, waters and minerals in the reservoir and account for their possible spatial and compositional variation. This is ideally related to basin history and location of source-rock kitchens and migration pathways. As well as being of interest in its own right, reservoir geochemistry has many important practical applications during petroleum exploration, appraisal and development. The most important uses are related to proving or disproving connectivity between different regions of a particular well or horizon. During exploration, reservoir geochemistry can indicate the direction from which a field filled, pointing the way for future wells. During production, studies of variations in composition with time may also be made, although this is a little studied area at present. Published accounts of the origins and applications of reservoir fluid differences appear to be relatively recent. England et al. (1987) noted the phenomenon and were probably the first to relate it to migration and subsequent time-scales of inreservoir mixing. Workers, particularly in the USA, have developed the use of 'gas chromatography (GC) fingerprinting' to distinguish different oil families, often in reservoirs with numerous thin hydrocarbon-bearing intervals (Kaufman et al. 1990). Effects due to the Earth's gravitational field were first considered by Sage & Lacey (1939). An extensive bibliography is presented by Larter & Aplin


The increasing number and diversity of available mouse models of human cancer and their growing importance in scientific research have resulted in an enormous increase in the amount and types of data generated from these models. These models represent powerful tools for studying biological and genetic mechanisms of cancer and for translation into potential clinical therapeutics. However, the amount of available data makes it challenging to identify and evaluate specific models and data important for an individual laboratory9s research. Placing these data in their proper genetic context is crucial to understanding the biochemical and molecular mechanisms of initiation, progression, and metastasis of different cancers. In addition, the ability of the immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mouse strain to host patient derived xenograft (PDX) models only increases the number of available models and the data produced from them. The Mouse Tumor Biology (MTB) Database provides access to data from mouse and PDX models of human tumors and the tools to analyze these data, facilitating the discovery and evaluation of novel mouse and PDX models of human cancers (http://tumor.informatics.jax.org). MTB includes data on endogenously arising tumors (both spontaneous and induced) in genetically defined mice (inbred, hybrid, mutant, and genetically engineered mice) and information from PDX models of human tumors and provides freely available web access to these data. MTB integrates data from peer-reviewed literature, laboratories studying mouse models of human cancer, production mouse colonies at The Jackson Laboratory (JAX), colonies of aging mice from the Jackson Aging Center, and PDX data from the Jackson Laboratory Patient-derived xenograft resource. MTB also incorporates data from PathBase, and mouse gene expression data sets from NCBI9s Gene Expression Omnibus (GEO) and the Array Express Database. Data include tumor classification, incidence and latency, tumor associated quantitative trait loci (QTL), pathology reports, images and genetic changes in tumors (somatic) and background strain (germline). Data type specific query forms (tumor, genetic etc.) allow detailed searches. MTB also can be searched using human gene symbols for orthologous mouse genes and associated data. Pathology images are submitted by the scientific community, from primary literature (with publisher permission), and from JAX colonies. MTB also includes immunohistochemistry data on over 500 antibodies with accompanying images of positive control samples and links to the respective vendors. MTB encourages direct submission of mouse tumor data and images from the cancer research community and has developed a web-based system to facilitate submission of data. Standard nomenclature, controlled vocabularies and literature citations facilitate data integration and robust searches. MTB is integrated with the Mouse Genome Informatics resource (MGI, http://www.informatics.jax.org) and provides links to other related online resources such as the Mouse Phenome Database (MPD), the Biology of the Mammary Gland Web Site, and the NCI Mouse Repository. MTB is supported by NCI grant CA089713. Citation Format: Dale A. Begley, Debra M. Krupke, Steven B. Neuhauser, Joel E. Richardson, John P. Sundberg, Carol J. Bult, Janan T. Eppig. The Mouse Tumor Biology (MTB) Database: An electronic tool for identifying and evaluating mouse and PDX models of human cancer. [abstract]. In: Proceedings of the AACR Special Conference: The Translational Impact of Model Organisms in Cancer; Nov 5-8, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(11 Suppl):Abstract nr A05.


Cables made to IEC and US standards, while having the same purpose, are of widely different designs. Cables made to one standard cannot be made to match the requirements of the other. The cable made to the US standards have been used in the US and throughout most of the world. The IEC standards have not been widely used in Europe where national and private industrial and utility standards have prevailed. IEC standards have been mainly used in countries where there have not been strong electrical codes. The European Union's adaptation of the IEC standards under the harmonized EN standards of CENELEC adds the force of law to the standards. This will promote a wider use of the IEC (CENELEC) standards on the European continent, although each country could still apply its national rules to the CENELEC standard. This is scheduled to change because all CENELEC European harmonized documents have already been withdrawn and replaced by European Norms. These are the same, word for word, in all European countries. CENELEC members are also members of the IEC and, therefore, do not operate a competitive policy with respect to the IEC. International harmonization of standards must be done at the IEC level. The addition of the CE mark to products meeting CENELEC is similar to the application of the UL mark to products meeting UL standards in the US Worldwide harmonization of standards looks to be a long process. North American and European electrical systems are based on different voltages or frequencies, different conductor sizes, and a different concept of what an electrical system should do.


Background The Liver Imaging Reporting and Data System Treatment Response (LR-TR) algorithm is used to assess the response of hepatocellular carcinoma (HCC) to local-regional therapy (LRT) based on enhancement patterns. The potential value of adding MRI ancillary features (AFs) needs to be investigated. Purpose To evaluate the potential application of MRI AFs in category adjustment to detect pathologic tumor viability in comparison with the LR-TR algorithm in CT and gadoxetic acid-enhanced MRI. Materials and Methods This retrospective study included patients with HCCs treated with LRT followed by surgical resection or liver transplantation between January 2014 and December 2017 who underwent both post-LRT CT and gadoxetic acid-enhanced MRI. For each treated observation, treatment response (TR) categories were assigned based on a consensus reading of three radiologists according to the LR-TR algorithm in CT and MRI and according to the MRI-modified TR algorithm in which MRI AFs were allowed for category adjustment. The diagnostic performances of CT LR-TR viable, MRI LR-TR viable, and MRI-modified TR viable categories were compared intraindividually with the McNemar test, with pathologic tumor viability used as a reference standard. Results A total of 138 patients (119 men; mean age, 58 years ± 9 [standard deviation]) with 138 treated observations (108 pathologically viable) were evaluated. The sensitivity and specificity of CT LR-TR viable and MRI LR-TR viable categories for predicting tumor viability were 73% (79 of 108 lesions; 95% confidence interval [CI]: 64%, 81%) versus 76% (82 of 108 lesions; 95% CI: 67%, 84%) and 90% (27 of 30 lesions; 95% CI: 74%, 98%) versus 83% (25 of 30 lesions; 95% CI: 65%, 94%), respectively, without differences between CT and MRI (P = .65 and P = .63, respectively). MRI-modified TR viable category had higher sensitivity (84% [91 of 108 lesions; 95% CI: 76%, 91%]) than CT or MRI LR-TR viable category (P = .002 and P = .01, respectively), without difference in specificity (80% [24 of 30 lesions]; 95% CI: 61%, 92%) (P = .38 and P > .99, respectively). Conclusion The application of MRI ancillary features to the Liver Imaging Reporting and Data System Treatment Response algorithm resulted in higher sensitivity and no change in specificity compared with CT or MRI enhancement patterns alone in the prediction of pathologic tumor viability in patients with hepatocellular carcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Do and Mendiratta-Lala in this issue.


Oral administration of thyrotropin-releasing hormone (TRH) caused deterioration in the clinical status of seven out of nine schizophrenic men. This change was particularly apparent in the four patients diagnosed as paranoid schizophrenics. Such changes might be expected from a drug with properties similar to amphetamine.


In especially the context of a writing centre, learning takes place during, and as part of, the conversations between the writing centre consultant and the student. This interaction is an integral part of writing centre research and is the focus of this largely qualitative study, employing a politeness lens. While there is some research on the politeness strategies employed by writing center consultants, there is very little research on the use of humour and its accompanying laughter to enhance rapport and interaction. The use of humour in the context of a writing centre is particularly relevant especially in light of the power dynamics and 'distance' inherent in the student-consultant relationship. This study therefore analysed a corpus of 10 video-recorded and transcribed writing centre consultations through a politeness lens in an effort to fill this gap. Our findings indicate that humour used positively can have positive effects, bridge the gap and create rapport and solidarity in complex relationships. The analysis also demonstrates how humour and laughter as used in the context of a writing centre consultation enhances interaction, creates a more positive learning environment and lessens the stress and anxiety students generally associate with academic writing. Keywords: positive politeness, negative politeness, humour, writing centre, academic writing


Canine hypoadrenocorticism is believed to be an immune-related condition. It is rare in the overall dog population but shows a breed-related predisposition with Standard poodles and Portuguese water dogs having a greater prevalence of the condition. It shares many similarities with human primary adrenal insufficiency and is believed to be a naturally occurring, spontaneous model for the human condition. Short haplotype blocks and low levels of linkage disequilibrium in the human genome mean that the identification of genetic contributors to the condition requires large sample numbers. Pedigree dogs have high linkage disequilibrium and long haplotypes within a breed, increasing the potential of identifying novel genes that contribute to canine genetic disease. We investigated 222 SNPs from 42 genes that have been associated or may be implicated in human Addison's disease. We conducted case-control analyses in 3 pedigree dog breeds (Labrador retriever: affected n = 30, unaffected = 76; Cocker Spaniel: affected n = 19, unaffected = 53; Springer spaniel: affected n = 26, unaffected = 46) and identified 8 associated alleles in genes COL4A4, OSBPL9, CTLA4, PTPN22, and STXBP5 in 3 pedigree breeds. Association with immune response genes PTPN22 and CTLA4 in certain breeds suggests an underlying immunopathogenesis of the disease. These results suggest that canine hypoadrenocorticism could be a useful model for studying comparative genetics relevant to human Addison's disease.


Background Prions, infectious agents associated with prion diseases such as Creutzfeldt-Jakob disease in humans, bovine spongiform encephalopathy (BSE) in cattle, and scrapie in sheep and goats, are primarily comprised of PrPSc, a protease-resistant misfolded isoform of the cellular prion protein PrPC. Protein misfolding cyclic amplification (PMCA) is a highly sensitive technique used to detect minute amounts of scrapie PrPSc. However, the current PMCA technique has been unsuccessful in achieving good amplification in cattle. The detailed distribution of PrPSc in BSE-affected cattle therefore remains unknown. Methodology/Principal Findings We report here that PrPSc derived from BSE-affected cattle can be amplified ultra-efficiently by PMCA in the presence of sulfated dextran compounds. This method is capable of amplifying very small amounts of PrPSc from the saliva, palatine tonsils, lymph nodes, ileocecal region, and muscular tissues of BSE-affected cattle. Individual differences in the distribution of PrPSc in spleen and cerebrospinal fluid samples were observed in terminal-stage animals. However, the presence of PrPSc in blood was not substantiated in the BSE-affected cattle examined. Conclusions/Significance The distribution of PrPSc is not restricted to the nervous system and can spread to peripheral tissues in the terminal disease stage. The finding that PrPSc could be amplified in the saliva of an asymptomatic animal suggests a potential usefulness of this technique for BSE diagnosis. This highly sensitive method also has other practical applications, including safety evaluation or safety assurance of products and byproducts manufactured from bovine source materials.


This article analyses the short and the long-term relations between higher education and unemployment in Turkey for the period 1960–2007. It chooses the recently developed ARDL cointegration and Granger causality of Dolado and Lutkepohl (1996) methods. While the proxy of unemployment is total unemployment rate, higher education graduates were chosen to represent higher education. The cointegration and error correction analysis show that higher education is one of the factors which increases the unemployment rate both in the short and the long-run in Turkey. In addition, findings of causality analysis reveal that there is a bi-directional causality between higher education and unemployment and support evidence in favour of Plumper and Schneider (2007)'s theory. Overall, the study concludes that, if governments wish to benefit optimally from the higher education graduates in Turkey, they should not invest more in higher education than the economy needs.


If you look back, basically the practice of education in Indonesia since the beginning is more likely to be holistic education, because education in Indonesia is more colored by Islamic education. It's just that in its journey there is a shift, especially when it comes in contact with education from the West which is influenced by positiveistic philosophy, and things like that continue to this day.
Scott H. Forbes and Robin Ann Martin in a paper - titled What Holistic Education Claims About Itself: An Analysis of Holistic Schools' Literature emphasizes that if one tries to trace the origins of holistic education it will be difficult because this concept has basically existed since ancient times and can be found in almost all concepts of education, one of the driving forces is humanitarian religious attitudes. In line with that opinion, it is important to trace the concept of hilistic education in Islam, especially those discussed in al-Zarnuji's Ta'lim al-Muta'allim.
Islamic education, including those listed in al-Zarnuji's Kitab Ta'limal-Muta'allim, illustrates a complete and holistic education that seeks to develop all the potential of both cognitive, affective and pro-motoric students, including physically and spiritually. The education is directed towards the attainment of the pleasure of Allah, and is not only for the sake of mere geography.
This kind of education is a necessity at this time, given the shift in values and enthusiasm in carrying out teaching and learning activities. This activity has lost its vital role in bringing students closer to God, so that those born are graduates who are secular and keep their knowledge and sources of knowledge away.


Films of pure and Sn-doped semiconducting Inz03 were prepared by reactive e-beam evaporation. The spectral absorption coefficient was evaluated by spectrophotometry in the (2—6)-eV range. The extracted band gap increases with electron density (n, ) approximately as n, for n, (10 ' cm This result is interpreted within an effective-mass model for n-doped semiconductors well above the Mott critical density. Because of the high degree of doping, the impurities are ionized and the associated electrons occupy the bottom of the conduction band in the form of an electron gas. The model accounts for a Burstein-Moss shift as well as electron-electron and electron-impurity scattering treated in the random-phase approximation. Experiments and theory were reconciled by assuming a parabolic valence band with an effective mass -0.6m. Earlier work on doped oxide semiconductors are assessed in the light of the present results.


In India, as is happening world wide, the use of coronary interventions is likely to maintain the pace of growth seen in the past decade. This will be facilitated by better access to experienced cardiologists and catheterisation laboratories across the country. Similar growth has occurred in cardiovascular surgery despite constraints of infrastructure and affordability. Cardiovascular research established four decades ago is being carried forward with provision of indigenous technology equal to the best in the world, but tailored to local need and affordability.


Abstract Context. The increasing intensity and extent of anthropogenically mediated salinisation in freshwater systems has the potential to affect freshwater species through physiological and ecological processes. Determining responses to salinisation is critical to predicting impacts on fauna. Aims. We aimed to quantify the response of wild-caught turtles from freshwater lakes that had become saline in the lower Murray River catchment. Methods. Plasma electrolytes of all three species of freshwater turtle from South Australia were compared among two freshwater sites (Horseshoe Lagoon and Swan Reach), a brackish lake (Lake Bonney) and a saline lake (Lake Alexandrina). Key results. Chelodina longicollis, C. expansa and Emydura macquarii from a brackish lake had higher concentrations of plasma sodium and chloride than those from freshwater habitats. However, osmolytes known to increase under severe osmotic stress (urea and uric acid) were not elevated in brackish sites. Turtles from the highly saline lake were colonised by an invasive marine worm which encased the carapace and inhibited limb movement. Conclusions. Freshwater turtles in brackish backwaters had little response to salinity, whereas the C. longicollis in a saline lake had a significant physiological response caused by salt and further impacts from colonisation of marine worms. Implications. Short periods of high salinity are unlikely to adversely affect freshwater turtles. However, secondary ecological processes, such as immobilisation from a marine worm may cause unexpected impacts on freshwater fauna.


Experience-dependent organization of neuronal connectivity is a critical component of brain development, but how experience shapes prefrontal cortex (PFC) development is unknown. Here, we assessed how social play behaviour, which is highly abundant during post-weaning development, shapes PFC function and connectivity. We subjected juvenile rats to social play deprivation (SPD), followed by resocialization until adulthood. In a PFC-dependent probabilistic reversal learning task, SPD rats earned a similar number of rewards, but achieved more reversals than control rats. Computational trial-by-trial analysis showed that SPD rats displayed a simplified cognitive strategy. In addition, inhibitory synaptic currents were significantly reduced in layer 5 PFC cells of SPD rats, with specific changes in parvalbumin- and cannabinoid receptor 1-positive perisomatic inhibitory synapses. Thus, SPD has a long-lasting impact on PFC inhibition via synapse-specific alterations, associated with simplified cognitive strategies. We conclude that proper PFC development depends on pertinent social experience during a restricted time period.


To examine gender differences in the long-term prognosis of patients with myocardial infarction, 1000 patients with myocardial infarction were studied after coronary arteriography. Over a follow-up period of 3.3 +/- 2.0 years, 65 patients died from cardiac causes and 301 experienced cardiac events (death, reinfarction and revascularization). Overall, the 5-year cardiac mortality was 8%: that in females (12.4%) was significantly higher than that in males (6.6%) (p = 0.0073). The overall 5-year cardiac event-rate was 35%, with no significant difference between females and males (41.1% vs 33.3%). Univariate analysis revealed that differences in age (57.8 +/- 9.8 years in males vs 64.8 +/- 8.9 years in females, p < 0.0001), presence of smoking habit, obesity, hypercholesterolemia, hypertension, heart failure, right coronary artery disease, nicorandil administration, hypolipidemic, diuretic and anti-hypertensive treatment, and warfarin administration were present between men and women. The mortality rate in elderly females tended to be higher than that in their male counterparts. Multivariate analysis demonstrated that number of diseased vessels, post-infarction angina and left main trunk disease were significant predictors for cardiac death in both sexes, while gender was not. Therefore, gender did not appear to affect the long-term prognosis after age-adjustment among patients with myocardial infarction in the Western part of Japan.


The purpose of this study was to examine the direct effect of emotion regulation (deep acting and surface acting) on service-oriented  organizational citizenship behavior (SO-OCB), an to test  for moderating effects  of gender on the relationship between emotion regulation and SO-OCB. The subjects of this study were the frontline service employee at the four star hotels in Padang, West Sumatera, including personnel at front desks, in service centers, in housekeeping, and in restaurants.  For data analyses, a series of hierarchical moderated regression analyses with a method of sub group were employed. The study finds that deep acting and surface acting significantly  affects SO-OCB.  Male and Female moderated the relationship between deep acting and SO-OCB.  Male moderated the relationship between surface acting and SO-OCB, but Female did not moderate the relationship between surface acting and SO-OCB.


The linearized fluid and Maxwell's equations are used to calculate the dispersion relation for the transverse magnetic modes of a partially filled, plasma-lined, cylindrical waveguide interacting with a relativistic electron beam. Both the plasma liner and the electron beam are assumed to be cold, and the system is immersed in an infinite axial magnetic guide field. The dispersion relation is then used to calculate the growth rate for the instability between the slow-wave modes (Trivelpiece-Gould modes) of the plasma guide and the slow-space charge mode of the electron beam. The calculation is done in the high-gain, strong coupling limit. >


Abstract In 1986 the U.S. Nuclear Regulatory Commission (USNRC) implemented a safety goal policy in response to the 1979 Three Mile Island accident. This policy addresses the question, "How safe is safe enough?" by specifying quantitative health objectives (QHOs) for comparison with average individual early fatality and latent cancer fatality risk results computed from nuclear power plant (NPP) probabilistic risk assessments (PRAs). Comparisons of PRA results to the QHOs or other subsidiary numerical objectives are used to determine whether proposed regulatory actions should be rejected based on potential safety benefit relative to the level of residual risk to the public, before performing detailed cost-benefit analyses to determine whether they could be justified on their net value basis. Lessons learned from recent operational experience—including the 2011 Fukushima accident—indicate that concurrent accidents involving multiple units at a shared site can occur with non-negligible frequency. Yet, risk contributions from such scenarios are excluded by policy from safety goal evaluations for the nearly 60% of the U.S. NPP sites that include multiple units. The objectives of this paper are to (1) present an approach for estimating multiple unit risk metrics for comparison with the safety goal QHOs using accident scenarios from the State-of-the-Art Reactor Consequence Analyses (SOARCA) Project; and (2) using this approach, evaluate the effects of including risk contributions from concurrent multiunit accidents in safety goal evaluations. The approach is demonstrated using a two-unit case study involving two representative NPP sites that are each comprised of two co-located operating reactor units. This paper (1) summarizes results and insights obtained from the two-unit case study; (2) describes additional considerations for applying methods to sites comprised of two or more units, including other major radiological sources; and (3) identifies potential areas for further research.


5-fluorouracil (5-FU) is one of the most commonly used agents in treatment of the cancer. The administered 5-FU is degraded mainly in the liver by dihydropyrimidine dehydrogenase (DPD), which is the initial rate-limiting enzyme in the catabolic pathway of pyrimidine. This enzyme activity in the tumors has been shown to correlate with the effectiveness of 5-FU against tumors. Therefore, to understand the regulation of DPD gene expression is critical in cancer chemotherapy. Since several studies suggested correlation of DPD activity with the cell proliferation rate we studied the DPD gene expression during liver regeneration. DPD enzyme activity decreased rapidly [24 h after partial hepatectomy (PH): 57% of the control] and remained low until 72 h after PH. Protein content also decreased after PH, however, the lowest level (43.2+/-6.3% of control) was reached only 48 h after PH. The DPD mRNA decreased rapidly to about 20% of control 24 h after PH and then recovered to the control level 72 h after PH. The present results indicate that the DPD gene expression is regulated first at the mRNA level when the hepatocytes enter the cell cycle. The protein content of DPD changed in proportion to the level of DPD mRNA with a 24-h lag, suggesting very little regulation at the translational level. There was a discrepancy between the DPD enzyme activity and the protein content, 24 and 72 h after PH, suggesting that the enzyme activity is modulated also by modification of the protein, and the cell proliferation rate is one of the factors that influences the modification.


Despite the wealth of micro–macro data on short-term demographic dynamics, the impact of metropolitan growth and economic downturns on local fertility is still under-investigated in advanced economies. Recent studies in low-fertility contexts have assumed suburban birth rates as being systematically higher than urban and rural rates. This assumption (hereafter, known as the 'suburban fertility hypothesis') was grounded on stylized facts and spatial regularities that imply a significant role of both macro (contextual) and micro (behavioral) factors positively influencing fertility in suburban locations. To verify such a hypothesis from a macro (contextual) perspective, the present study compares the general fertility rate of urban, suburban, and rural settlements of the Athens' metropolitan region (Greece) at various observation years between 1860 and 2020. Long-term Athens' growth represented a sort of 'quasi-experiment' for Mediterranean Europe, linking sequential urban stages and distinctive waves of economic expansion and recession. Using multivariate exploratory analysis and global/local econometric models, a dominant 'rural' fertility regime was recorded for 1860 and 1884. A characteristic 'urban' fertility regime was, instead, found over a relatively long, intermediate period between 1956 and 1990. Higher fertility in suburban settlements (10 km away from downtown Athens, on average) was, finally, observed since 2000. Considering a sufficiently long-time interval, the existence of multiple fertility regimes along the distance gradient has demonstrated how fertility dynamics are intrinsically bonded with metropolitan growth, economic downturns, and social transformations in Mediterranean Europe.


Genetic iron-overload disorders, mainly hereditary hemochromatosis and untransfused β-thalassemia, affect a large population worldwide. The primary etiology of iron overload in these diseases is insufficient production of hepcidin by the liver, leading to excessive intestinal iron absorption and iron efflux from macrophages. Hepcidin agonists would therefore be expected to ameliorate iron overload in hereditary hemochromatosis and β-thalassemia. In the current study, we screened our synthetic library of 210 thiazolidinone compounds and identified three thiazolidinone compounds, 93, 156 and 165, which stimulated hepatic hepcidin production. In a hemochromatosis mouse model with hemochromatosis deficiency, the three compounds prevented the development of iron overload and elicited iron redistribution from the liver to the spleen. Moreover, these compounds also greatly ameliorated iron overload and mitigated ineffective erythropoiesis in β-thalassemic mice. Compounds 93, 156 and 165 acted by promoting SMAD1/5/8 signaling through differentially repressing ERK1/2 phosphorylation and decreasing transmembrane protease serine 6 activity. Additionally, compounds 93, 156 and 165 targeted erythroid regulators to strengthen hepcidin expression. Therefore, our hepcidin agonists induced hepcidin expression synergistically through a direct action on hepatocytes via SMAD1/5/8 signaling and an indirect action via eythroid cells. By increasing hepcidin production, thiazolidinone compounds may provide a useful alternative for the treatment of iron-overload disorders.