bluuebunny/crossref_metadata_2025 huggingface dataset:
Tell-Me-A-Story (TEMAS) Assessment for Culturally Diverse Children and Adolescents
Authors: Costantino Giuseppe , Litman Leib , Waxman Richard , Dupertuis Daniel , Pais Ernesto , Rosenzweig Cheskie , Forti Guadalupe , Paronik Jessica , Canales Maria M. F.
Published: December 2014

The Tell-Me-A-Story (TEMAS) narrative test is a multicultural measure developed for both minority and nonminority children and adolescents. As the off-spring of the Thematic Apperception Test (TAT), it enhances several narrative features, including the use of chromatic cards, diminished ambiguity and structured pictorial stimuli of the cards, familiar and contemporary themes, problem-solving situations, and an objective scoring system. This article describes the standardization of the TEMAS in the US, the validation of the Orthodox Jewish version of the TEMAS, and the internal reliability of the Argentinian version of the TEMAS. In the US, the test was normed on a sample of 642 children (281 boys and 361 girls) from public schools in the New York City area, ages 5–13 years, with a mean age of 8.9 years (SD = 1.9). The total sample represented four ethnic/racial groups: Puerto Rican and other Hispanic, Black, and White children. The TEMAS measures 10 personality functions, 18 cognitive functions, and seven affective functions. This paper presents two studies. The first study describes the reliability of the TEMAS measurement, using the Argentinian version of the TEMAS. The second study provides the rationale as well as the procedures for developing culturally suitable pictures, and also presents novel data for the cultural validity of the Orthodox Jewish version of the TEMAS. Overall, these results provide support for TEMAS as a reliable and culturally valid tool for the measurement of cognitive, personality, and affective functioning.
The Music Apperception Test
Authors: van den Daele Leland
Published: December 2014

The Music Apperception Test (MAT) asks respondents to “tell a story to the music.” Brief compositions portray basic emotions followed by 30-s silent periods. The MAT relies on the emotional import of music, so narratives vary for content, settings, and outcomes. Stories are recorded and transcribed for coding. Thirty-seven MAT variables in ten categories of response are described: Fluency, Latency, Time to Termination, Pace, Content, Interaction, Off-Task Response, Voice, Narrative Style, and Affective Fit. Provisional norms for children, adolescents, and adults, are based on 2,016 responses of 168 individuals. Split-half and test–retest reliabilities for quantitative variables, latency and fluency, exceed .90. Current research is summarized, clinical application is discussed, and recommendations are made for future research.
The Dynamics of TAT Process
Authors: Verdon Benoît , Chabert Catherine , Azoulay Catherine , Emmanuelli Michèle , Neau Françoise , Vibert Sarah , Louët Estelle
Published: December 2014

After many years of clinical practice, research and the teaching of projective tests, Shentoub and her colleagues (Debray, Brelet, Chabert & al.) put forward an original and rigorous method of analysis and interpretation of the TAT protocols in terms of psychoanalysis and clinical psychopathology. They developed the TAT process theory in order to understand how the subject builds a narrative.

Our article will emphasize the source of the analytical approach developed by V. Shentoub in the 1950s to current research; the necessity of marking the boundary between the manifest and latent content in the cards; the procedure for analyzing the narrative, supported by an analysis sheet for understanding the stories' structure and identifying the defense mechanisms; and how developing hypotheses about how the mental functions are organized, as well as their potential psychopathological characteristics; and the formulation of a diagnosis in psychodynamic terms.

In conjunction with the analysis and interpretation of the Rorschach test, this approach allows us to develop an overview of the subject's mental functioning, taking into account both the psychopathological elements that may threaten the subject and the potential for a therapeutic process. We will illustrate this by comparing neurotic, borderline, and psychotic personalities.
Emergence of Primary Processes in the TAT of the Parisian School in Adults With Schizophrenia
Authors: Lelé Alvaro José , Flores-Mendoza Carmen Elvira , de La Plata Cury Tardivo Leila Salomão
Published: December 2014

This study aims to investigate the primary processes of thoughts and how these are expressed in the Thematic Apperception Test (TAT). The primary process, characteristic of schizophrenic individuals, is an essential concept in the psychoanalytic theories concerning the unconscious aspects of psychic functioning. It is characterized by the absence of coherence and logical relationships, unawareness of temporal relationships and the reality principle. In this study, the TAT was analyzed according to the Parisian School, focusing particularly the emergences of the primary processes. The participants were 32 individuals divided in two groups of 16 each: a clinical group medically diagnosed as schizophrenic patients and a nonclinical group with 50% men and 50% women between 24 and 60 years of age. The study considered the procedures of Series A, B, C, and E of the TAT discourse analysis sheet. The Mann–Whitney test showed statistically significant differences between the groups in the E Series. Also, nine subcriteria from the E Series correctly classified 93.8% of the sample. It has been concluded that the E Series of TAT adequately differentiates between the clinical group diagnosed with schizophrenia and the group of individuals without this pathology.
A Study on the Psychometric Properties of the Fairy Tale Test (FTT)
Authors: Coulacoglou Carina
Published: December 2014

The Fairy Tale Test (FTT) is a projective personality measure that provides a comprehensive evaluation of the child’s personality. The test consists of 21 cards that depict popular fairy tale characters that are administered in sets of three. Having three versions of the same character allows the child to project different aspects of self and activates the emergence of several defense mechanisms such as undoing, reaction formation, and splitting. The test is administered in the form of a semi-structured interview. Children’s responses are interpreted in a quantitative and qualitative way. Quantitative interpretation includes the rating of 30 personality variables on a 1–3 scale, while qualitative evaluation consists of the analysis of ego functions and the nature of anxiety. The FTT was standardized in Greece on a sample of 873 nonclinical children. The construct validity was examined through the application of factor analyses that led to the formation of 13 first-order and 5 second-order factors. Criterion validity included the comparison of the FTT factors with those derived from the AQ, the BYI, and the CBCL. The results confirmed the dichotomy of reactive and proactive aggression and disclosed their association with victims and bullies.
Bounded Sobolev norms for Klein-Gordon equations under non-resonant perturbation
Authors: Fang Daoyuan , Han Zheng , Wang W.-M.
Published: December 2014

In this paper, we prove Anderson localization for the Klein-Gordon operator on the circle 𝕋 under non-resonant perturbations. Furthermore, using the result, we show that the Sobolev norms of solutions to the corresponding Klein-Gordon equations remain bounded for all time.
Weyl’s theory in the generalized Lie algebroids framework
Authors: Arcuş Constantin M. , Peyghan Esmaeil , Sharahi Esa
Published: December 2014

The geometry of the Lie algebroid generalized tangent bundle of a generalized Lie algebroid is developed. Formulas of Ricci type and identities of Cartan and Bianchi type are presented. Introducing the notion of geodesic of a mechanical ρ,η-system with respect to a (ρ, η)-spray, the Berwald (ρ, η)-derivative operator, and its mixed curvature, we obtain main results to conceptualize the Weyl’s method in this general framework. Finally, we obtain two new results of Weyl type for the geometry of mechanical ρ,η-systems. In this way, it is proved that the projectively related sprays first have the same geodesics rather to an increasing parameter transformation and second their Berwald derivatives verify a respective relation.
Effects of Sr2+ substitution on photoluminescence characteristics of Ba1−x−ySryZrSi3O9:xEu2+ phosphors
Authors: Chiang Chung-Hao , Gong Syuan-Jhih , Lin Han-Yu , Zhan Ting-Shi , Chu Sheng-Yuan
Published: December 2014

In this work, single-phase Ba1−x−ySryZrSi3O9:xEu2+ phosphors were synthesized via the solid-state reaction method. The crystal structure and luminescence properties were investigated using X-ray diffraction and photoluminescence measurements, respectively. An increase of the dopant Sr2+ increased the emission intensity of the phosphors. The peak intensity of the samples was at y = 0.4 under near-ultraviolet light excitation (397 nm). The wavelength of the emission peaks red-shifts slightly from 477 to 483 nm due to the splitting of the 5d energy level. Sr2+ ions have a smaller ionic radius than that of Ba2+ ions, and thus the dopant changes the crystal structure, improving the energy transfer efficiency between luminescence centers. More Eu2+ solid solubility was found in Ba0.6−xSr0.4ZrSi3O9:xEu2+ phosphors (10 mol. %) than in the host BaZrSi3O9 (6 mol. %), which enhanced the emission intensity. In addition, the thermal reliability of the phosphors was studied.
Structural, magnetic, and transport properties of sputtered hexagonal MnNiGa thin films
Authors: Li Yueqing , Liu E. K. , Wu G. H. , Wang Wenhong , Liu Zhongyuan
Published: December 2014

We report on a systematical study of the structure, magnetism, and magnetotransport behavior of the hexagonal MnNiGa films deposited on thermally oxidized Si (001) substrates by magnetron sputtering. X-ray diffractions reveal that all the films deposited at different temperatures crystallized in hexagonal Ni2In-type structure (space group P63/mmc). Scanning electron microscopy observations show that the surface morphology of the films varies with deposition temperature, and energy dispersive spectroscopy analysis shows compositions of the films remain nearly unchanged, independent of the deposition temperature. Magnetic measurements indicate that all films are ferromagnetic and exhibit a magnetic anisotropy behavior. The magnetoresistance (MR) exhibits a negative temperature- and field-dependent behavior. The possible origin of the negative MR is discussed. Furthermore, we found that the Hall effect is dominated by an anomalous Hall effect (AHE) only due to skew scattering independent of the deposition temperature of films. Moreover, the anomalous Hall resistivity presents a non-monotonously temperature-dependent behavior.
Surface engineering of the quality factor of metal coated microcantilevers
Authors: Ergincan O. , Kooi B. J. , Palasantzas G.
Published: December 2014

We performed noise measurements to obtain the quality factor (Q) and frequency shift of gold coated microcantilevers before and after surface modification using focused ion beam. As a result of our studies, it is demonstrated that surface engineering offers a promising method to control and increase the Q factor up to 50% for operation in vacuum. Surface modification could also lead to deviations from the known Q ∼ P−1 behavior at low vacuum pressures P within the molecular regime. Finally, at higher pressures within the continuum regime, where Q is less sensitive to surface changes, a power scaling Q ∼ Pc with c ≈ 0.3 was found instead of c = 0.5. The latter is explained via a semi-empirical formulation to account for continuum dissipation mechanisms at significant Reynolds numbers Re ∼ 1.
Stopping potential and ion beamlet control for micro-resistive patterning through sub-Debye length plasma apertures
Authors: Chowdhury Abhishek , Chatterjee Sanghamitro , Dutta Apurba , Bhattacharjee Sudeep
Published: December 2014

Focused multiple ion beamlets from a microwave plasma source is investigated for localized micron-scale modification of substrates in a patterned manner. Plasma electrodes (PE) with an array of through apertures having aperture diameters of the order of plasma Debye length are investigated for generating the beamlets. Extraction through sub-Debye length apertures becomes possible when the PE is kept at floating potential. It is found that the current – voltage characteristics of the extracted beamlets exhibits interesting features such as a space-charge-limited region that has a different behaviour than the conventional Child-Langmuir’s law and an extraction-voltage-limited region that does not undergo saturation but exhibits a Schottky-like behaviour similar to that of a vacuum diode. A switching technique to control the motion of individual beamlets is developed and the stopping potential determined. The beamlets are thereafter used to create localized micro-resistive patterns. The experimental results are compared with simulations and reasonably good agreement is obtained.
Reactivity enhancement of oxide skins in reversible Ti-doped NaAlH4
Authors: Delmelle Renaud , Gehrig Jeffrey C. , Borgschulte Andreas , Züttel Andreas
Published: December 2014

The reversibility of hydrogen sorption in complex hydrides has only been shown unambiguously for NaAlH4 doped with transition metal compounds. Despite a multitude of investigations of the effect of the added catalyst on the hydrogen sorption kinetics of NaAlH4, the mechanism of catalysis remains elusive so far. Following the decomposition of TiCl3-doped NaAlH4 by in-situ X-ray photoelectron spectroscopy (XPS), we link the chemical state of the dopant with those of the hydride and decomposition products. Titanium and aluminium change their oxidation states during cycling. The change of the formal oxidation state of Al from III to zero is partly due to the chemical reaction from NaAlH4 to Al. Furthermore, aluminium oxide is formed (Al2O3), which coexists with titanium oxide (Ti2O3). The interplay of metallic and oxidized Ti with the oxide skin might explain the effectiveness of Ti and similar dopants (Ce, Zr…).
A simplified HTc rf SQUID to analyze the human cardiac magnetic field
Authors: Zhang Chen , Tang Fakuan , Ma Ping , Gan Zizhao
Published: December 2014

We have developed a four-channel high temperature radio-frequency superconducting quantum interference device (HTc rf SQUID) in a simple magnetically shielded room (MSR) that can be used to analyze the cardiac magnetic field. It is more robust and compact than existing systems. To achieve the high-quality magnetocardiographic signal, we explored new adaptive software gradiometry technology constructed by the first-order axial gradiometer with a baseline of 80mm, which can adjust its performance timely with the surrounding conditions. The magnetic field sensitivity of each channel was less than 100fT/√Hz in the white noise region. Especially, in the analysis of MCG signal data, we proposed the total transient mapping (TTM) technique to visualize current density map (CDM), then we focused to observe the time-varying behavior of excitation propagation and estimated the underlying currents at T wave. According to the clear 3D imaging, isomagnetic field and CDM, the position and distribution of a current source in the heart can be visualized. It is believed that our four-channel HTc rf SQUID magnetometer based on biomagnetic system is available to detect MCG signals with sufficient signal-to-noise (SNR) ratio. In addition, the CDM showed the macroscopic current activation pattern, in a way, it has established strong underpinnings for researching the cardiac microscopic movement mechanism and opening the way for its use in clinical diagnosis.
TDP-43 N terminus encodes a novel ubiquitin-like fold and its unfolded form in equilibrium that can be shifted by binding to ssDNA
Authors: Qin Haina , Lim Liang-Zhong , Wei Yuanyuan , Song Jianxing
Published: December 2014

Significance

Transactivation response element (TAR) DNA-binding protein 43 (TDP-43) inclusion is a histological hallmark of FTLD-TDP and amyotrophic lateral sclerosis. Its N terminus was just revealed as a double-edged sword indispensable for both physiology and proteinopathy, but its structure remains unknown due to aggregation. Here we revealed (
i
) the TDP-43 N terminus encodes a well-folded structure in equilibrium with its unfolded form; (
ii
) despite previous failure in detecting sequence homology to ubiquitin, the folded state assumes a novel ubiquitin-like fold; and (
iii
) this ubiquitin-like fold could bind ssDNA, thus representing the first capable of directly binding nucleic acid. Taken together, our results provide a molecular mechanism rationalizing the functional dichotomy of TDP-43 and further imply one therapeutic strategy for TDP-43–causing diseases.
Quantum delocalization of protons in the hydrogen-bond network of an enzyme active site
Authors: Wang Lu , Fried Stephen D. , Boxer Steven G. , Markland Thomas E.
Published: December 2014

Significance

Because of the low mass of the proton, nuclear quantum effects can dramatically alter the properties of hydrogen-bond networks, especially when short and strong hydrogen bonds occur. Here, we combine experiments and state-of-the-art simulations that include the quantum nature of both the electrons and nuclei to show that the enzyme ketosteroid isomerase contains a hydrogen-bond network in its active site that facilitates extensive quantum proton delocalization. This leads to a 10,000-fold increase in the acidity of an active-site residue compared with the limit where the nuclei are classical particles. This work opens up new avenues for understanding the interplay between quantum effects and hydrogen bonding in biological systems containing strong hydrogen bonds.
“Shop-lease Contract with Sar-qofli” in the Post-Iranian Revolution Era: Deletion of “Haqq-e kasb o pisheh o tejārat” from the Law of Lessor–Lessee Relationships
Authors: Iwasaki Yoko
Published: December 2014

In contemporary Iran, many shops are under the “shop-lease contract with sar-qofli.” In this contract, sar-qoflisar-qofli, a strong usufructuary right supported by intangible assets such as the shop’s reputation, is given to the tenant. The “shop-lease contract with sar-qofli” originated from a traditional merchants’ custom in Iran’s business quarters. After the 1979 Revolution, the Law of Lessor–Lessee Relationships, which provides a legal framework for the practice of “shop-lease contract with sar-qofli,” was completely revised, since Islamic jurists regarded haqq-e kasb o pisheh o tejārat as problematic. Haqq-e kasb o pisheh o tejārat, the legal designation of sar-qofli, was based on a heterogeneous value concept introduced into the Iranian legal system from abroad during World War II. As a result of this revision, another alternative for asset management was granted to shop owners. Nevertheless, “shop-lease contract with sar-qofli” remains the most widely employed form of lease in Iran’s property lease market.
When the Subject is the Object: Islamic Advice Literature Modes and the Treatment of Slavery in The Qābūs Nāmih and The Nasirean Ethics
Authors: Sadr Amin Azad
Published: December 2014

This paper investigates the difference of perspective which informs The Qābūs Nāmih’s and The Nasirean Ethics’ respective treatments of the topic of slavery. While in various parts of their discussions both works show an engagement with each side of the hybrid status of a slave’s existence as both subject and object, The Qābūs Nāmih deals with the issue almost entirely in terms of the slave’s status as an object, while The Nasirean Ethics engages this issue with clear acknowledgments to his/her status as a subject. It is possible that the divergent approaches of these two works are a reflection of the two distinct modes of the genre of Islamic advice literature in which they were respectively written.
Lack of Protection following Re-Exposure of Chinook Salmon to Ceratonova shasta (Myxozoa)
Authors: Hurst C. N. , Bartholomew J. L.
Published: December 2014

The recent identification of multiple genotypes of the salmonid parasite Ceratonova shasta with different virulence levels in Chinook Salmon Oncorhynchus tshawytscha suggests that it is possible to immunize fish against subsequent infection and disease. We hypothesized that exposure of Chinook Salmon to the less-virulent parasite genotype (II) prior to the more virulent parasite genotype (I) would decrease disease and/or result in fewer mature parasites compared with fish only infected with the more virulent genotype. To test this hypothesis, fish were challenged in a combination of field and laboratory exposures, and we measured infection prevalence, percent morbidity, and mature parasite production. Neither mortality nor mature parasite production were reduced when fish were exposed to genotype II prior to genotype I compared with fish exposed only to genotype I, suggesting that protection against C. shasta using a less-virulent genotype of the parasite does not occur.

Received June 9, 2014; accepted September 19, 2014
Plasma Renin Activity and Resting Heart Rate in a Population of Community-Dwelling Japanese: The Tanushimaru Study
Authors: Adachi Hisashi , Enomoto Mika , Fukami Ako , Kumagai Eita , Nakamura Sachiko , Yoshimura Ayako , Obuchi Aya , Hori Kensuke , Nohara Yume , Nakao Erika , Fukumoto Yoshihiro
Published: December 2014

BACKGROUND

Heart rate is a strong predictor of mortality and development of obesity and diabetes. The renin–angiotensin–aldosterone system plays an important role in blood pressure control and volume homeostasis. Although many studies have indicated the association between aldosterone and hypertension or insulin resistance, epidemiological evidence of the association of heart rate with plasma renin activity (PRA) remains scant. Therefore, we investigated whether heart rate is associated with PRA.

METHODS

A total of 1,943 subjects were enrolled, who underwent a health examination in Tanushimaru in 2009. Plasma renin and aldosterone concentrations were measured by radioimmunoassay. PRA and the homeostasis model assessment (HOMA) were used by natural-log transformed. Resting heart rate was measured using electrocardiography.

RESULTS

We divided the subjects into four groups by heart rate (<60/min, 60–69/min, 70–79/min, ≥80/ min), and analyzed an association between PRA and heart rate by analysis of covariance after adjustments for age and sex. The adjusted mean PRA and HOMA index showed a significant trend (P < 0.01) as higher heart rate, although there was no significant trend between aldosterone and heart rate (P = 0.26). In multiple linear regression analysis adjusted for age, sex, systolic blood pressure, HOMA index, and hypertensive medication, PRA was positively and strongly associated with elevated heart rate (P < 0.01).

CONCLUSIONS

This epidemiological study demonstrated that PRA, but not aldosterone, is significantly and positively associated with higher resting heart rate in a general population.
Heme Oxygenase Improves Renal Function by Potentiating Podocyte-Associated Proteins in Nω-Nitro-l-Arginine-Methyl Ester (l-NAME)-Induced Hypertension
Authors: Ndisang Joseph Fomusi , Chibbar Rajni
Published: December 2014

BACKGROUND

Although heme-oxygenase (HO) is cytoprotective, its effects on podocyte regulators like podocalyxin, podocin, CD2-associated protein (CD2AP) in renal dysfunction in Nω-nitro-l-arginine-methyl ester (l-NAME) hypertension are largely unclear.

METHODS

Hypertension was induced in normotensive Sprague Dawley rats by administering l-NAME for 4 weeks. Enzyme immunoassay, enzyme-linked immunosorbent, histology/morphology, spectrophotometry, and western immunoblotting were used. HO was enhanced with heme-arginate (HA) or inhibited with chromium mesoporphyrin (CrMP).

RESULTS

Treatment with heme-arginate reduced several renal histo-pathological lesions including renal arteriolar thickening, glomerular abnormalities, tubular cast, tubular atrophy/fibrosis, and mononuclear cell infiltration in l-NAME-hypertensive rats. Similarly, HA abated the elevated levels of renal extracellular matrix/profibrotic proteins like collagen and fibronectin that deplete nephrin, a fundamental transmembrane protein that forms the scaffoldings of the podocyte slit diaphragm permitting small ions to filter, but not massive excretion of proteins, hence proteinuria. Correspondingly, HA enhanced the aberrant expression of nephrin alongside other important regulators of podocyte like podocalyxin, podocin, and CD2AP, and improved renal function by reducing albuminuria/proteinuria, while increasing creatinine clearance. The renoprotection by HA were accompanied by significant reduction of inflammatory/oxidative mediators including nuclear factor-kappaB, macrophage inflammatory protein-1-alpha, macrophage chemoattractant protein-1, tumor necrosis factor-alpha, interleukin (IL)-6, IL1β, 8-isoprostane, endothelin-1, and aldosterone. These were associated with increased levels of adiponectin, HO-1, HO activity, cyclic guanosine monophosphate, and atrial natriuretic peptide (ANP), whereas the HO inhibitor, CrMP annulled the renoprotection and exacerbated renal dysfunction.

CONCLUSIONS

HA improves renal function by attenuating histopathological lesions, suppressing inflammatory/oxidative mediators, abating profibrotic/extracellular matrix proteins, and reducing albuminuria/proteinuria, while concomitantly potentiating the HO-adiponectin-ANP axis, enhancing nephrin, podocin, podocalyxin, CD2AP and increasing creatinine clearance. Our study underscores the benefit of potentiating the HO-adiponectin-ANP against nephropathy.
Elevated Homocysteine Levels Are Associated With the Metabolic Syndrome and Cardiovascular Events in Hypertensive Patients
Authors: Catena Cristiana , Colussi Gianluca , Nait Francesca , Capobianco Frine , Sechi Leonardo A.
Published: December 2014

BACKGROUND

Hyperhomocysteinemia and the metabolic syndrome are established cardiovascular risk factors and are frequently associated with hypertension. The relationship of plasma homocysteine (Hcy) with the metabolic syndrome and insulin resistance, however, is debated and studies in hypertensive patients are limited. In this study, we have investigated the association of Hcy with the metabolic syndrome and cerebro- cardiovascular events in hypertension.

METHODS

In 562 essential hypertensive patients who underwent accurate assessment of fasting and postload glucose metabolism, insulin sensitivity, and renal function, we measured plasma levels of Hcy, vitamin B12, folate, and fibrinogen and assessed the prevalence of the metabolic syndrome and of coronary heart and cerebrovascular disease (CVD).

RESULTS

Patients with the metabolic syndrome had significantly higher plasma Hcy levels. After correction for covariates, increasing Hcy levels were associated with an increasing prevalence of the metabolic syndrome, coronary heart disease, and CVD. Plasma Hcy was directly correlated with age, waist circumference, fasting glucose, triglyceride, uric acid, and fibrinogen levels, and homeostatic model assessment index and inversely with creatinine clearance and high-density lipoprotein cholesterol, vitamin B12, and folate levels. Logistic regression analysis showed an independent association of Hcy levels with age, male gender, vitamin B12 and folate levels, and the metabolic syndrome. Logistic regression indicated also an independent association of Hcy with cerebro-cardiovascular disease that was independent of the metabolic syndrome.

CONCLUSIONS

Elevated plasma Hcy is associated with the metabolic syndrome in hypertensive patients. Prevalence of events increases with increasing plasma Hcy levels suggesting a contribution of Hcy to cerebro-cardiovascular diseases in these patients.
Subtherapeutic concentrations of first-line anti-TB drugs in South African children treated according to current guidelines: the PHATISA study
Authors: Hiruy Hiwot , Rogers Zoe , Mbowane Chris , Adamson John , Ngotho Lihle , Karim Farina , Gumbo Tawanda , Bishai William , Jeena Prakash
Published: December 2014

Objectives

There is a paucity of evidence regarding the optimal dosing of anti-TB drugs in children. The aim of this study was to identify the pharmacokinetic parameters of first-line anti-TB drugs and the concentrations achieved after implementation of the 2010 WHO-recommended paediatric dosages.

Methods

We conducted a prospective, observational pharmacokinetic study in children 10 years old or younger who were on isoniazid, rifampicin, pyrazinamide and ethambutol therapy in Durban, KwaZulu-Natal, South Africa. Blood was collected at six timepoints over a 24 h period, chosen using optimal sampling theory. The drug concentrations were simultaneously modelled to identify the compartmental pharmacokinetics of each drug in each child, using the ADAPT program.

Results

The best six sampling timepoints in children were identified as 0 (pre-dose) and 0.42, 1.76, 3.37, 10.31 and 24 h post-dose. Thirty-one children were recruited and blood was drawn at these timepoints. Rifampicin, ethambutol and pyrazinamide were best described using a one-compartment model, while isoniazid was best described with a two-compartment model. Only 2/31 (6%), 20/31 (65%), 17/31 (55%) and 2/13 (15%) of children attained the WHO 2 h target therapeutic concentrations of rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. Moreover, only 24/31 (77%), 6/31 (19%) and 8/31 (26%) achieved the AUCs associated with an optimal clinical response to rifampicin, pyrazinamide and isoniazid, respectively. No single risk factor was significantly associated with below-normal drug levels.

Conclusions

The drug concentrations of all first-line anti-TB drugs were markedly below the target therapeutic concentrations in most South African children who received the revised WHO-recommended paediatric weight-based dosages.
Multifaceted intervention to optimize antibiotic use for intra-abdominal infections
Authors: Popovski Zagorka , Mercuri Mathew , Main Cheryl , Sne Niv , Walsh Kate , Sung Melani , Rice Timothy , Mertz Dominik
Published: December 2014

Objectives

Implementing evidence-based practice guidelines is challenging. We used a multifaceted, continuous educational approach to disseminate an up-to-date internal guideline adapted from published guidelines for management of intra-abdominal infections (IAI).

Patients and methods

The intervention consisted of continuing educational sessions, internal guideline pocket cards and posters with collaboration among all key stakeholders starting in December 2010. We emphasized risk stratification and the use of ceftriaxone/metronidazole for treatment of low-risk IAI, and discouraged the use of fluoroquinolones due to the high local resistance rates. We then compared patients with IAI before the intervention (April–November 2010) to those after implementation of the guideline (April–November 2011) in a surgical unit at a tertiary care teaching hospital in Hamilton, Ontario, Canada. Antibiotic use was measured in in-hospital days of antibiotic therapy (DOT) per 1000 patient days (PD).

Results

152 and 145 patients with IAI were included in the pre- and post-intervention periods, respectively. There was a significant reduction in the proportion of patients who received ciprofloxacin therapy from 74% to 34% (OR 0.18, 95% CI 0.11–0.31) and in DOT/1000 PD from 221 to 74 (OR 0.3, 95% CI 0.2–0.3). Also, a reduction in the DOT/1000 PD for piperacillin/tazobactam was seen (from 116 to 67; OR 0.6, 95% CI 0.5–0.7). There was an increase in the use of ceftriaxone from 1.3% to 53% of patients (OR 85, 95% CI 20–515) and from 6 to 92 DOT/1000 PD (OR 17, 95% CI 10–25). This change in practice was sustained over >2 years since the end of the active intervention, as shown in the unit-wide antimicrobial utilization data.

Conclusions

A multifaceted intervention aimed at all key stakeholders resulted in a high adherence to evidence-based treatment guidelines for IAI and has initiated a sustained culture change in prescribing of antibiotics.
Histoplasmosis in Patients With Cell-Mediated Immunodeficiency: Human Immunodeficiency Virus Infection, Organ Transplantation, and Tumor Necrosis Factor-α Inhibition
Authors: Luckett Keith , Dummer J. Stephen , Miller Geraldine , Hester Sydney , Thomas Lora
Published: December 2014

Background.  Histoplasmosis causes severe disease in patients with defects of cell-mediated immunity. It is not known whether outcomes vary related to the type of immunodeficiency or class of antifungal treatment.

Methods.  We reviewed cases of active histoplasmosis that occurred at Vanderbilt University Medical Center from July 1999 to June 2012 in patients with human immunodeficiency virus (HIV) infection, a history of transplantation, or tumor necrosis factor (TNF)-α inhibitor use. These groups were compared for differences in clinical presentation and outcomes. In addition, outcomes were related to the initial choice of treatment.

Results.  Ninety cases were identified (56 HIV, 23 transplant, 11 TNF-α inhibitor). Tumor necrosis factor-α patients had milder disease, shorter courses of therapy, and fewer relapses than HIV patients. Histoplasma antigenuria was highly prevalent in all groups (HIV 88%, transplant 95%, TNF-α 91%). Organ transplant recipients received amphotericin B formulation as initial therapy less often than other groups (22% vs 57% HIV vs 55% TNF-α; P = .006). Treatment failures only occurred in patients with severe disease. The failure rate was similar whether patients received initial amphotericin or triazole therapy. Ninety-day histoplasmosis-related mortality was 9% for all groups and did not vary significantly with choice of initial treatment.

Conclusions.  Histoplasmosis caused milder disease in patients receiving TNF-α inhibitors than patients with HIV or solid organ transplantation. Treatment failures and mortality only occurred in patients with severe disease and did not vary based on type of immunosuppression or choice of initial therapy.
Transmission of Respiratory Syncytial Virus Infection Within Families
Authors: Heikkinen Terho , Valkonen Heikki , Waris Matti , Ruuskanen Olli
Published: December 2014

Background.  Because the production of an effective respiratory syncytial virus (RSV) vaccine for infants is challenging, vaccination of other family members is one viable alternative to prevent severe RSV illnesses in infants.

Methods.  In a prospective study, we enrolled all family members of children who were hospitalized with RSV infection. Nasal swabs for RSV detection were obtained from all participating family members. Data on respiratory symptoms in the family members prior to and after the child's admission were collected using standardized questionnaires.

Results.  At the time of or within 1 week after the index child's hospitalization, RSV was detected in 40 (77%) of the 52 families and in 60 (47%) of 129 family members. Forty-nine (82%) of RSV detections in the family members were associated with respiratory symptoms. A sibling or a parent was the probable primary case of RSV in 30 (58%) families. Respiratory syncytial virus loads in the nasal swabs were significantly higher (107.7) in index children than in their parents (105.1, P < .0001).

Conclusions.  In most cases, the likely source of an infant's RSV infection is an older sibling or a parent. These findings support the strategy of reducing the burden of RSV in infants by vaccination of their family members.
Glycocaulis
alkaliphilus sp. nov., a dimorphic prosthecate bacterium isolated from crude oil
Authors: Geng Shuang , Pan Xin-Chi , Mei Ran , Wang Ya-Nan , Liu Xue-Ying , Wang Xing-Biao , Tang Yue-Qin , Wu Xiao-Lei
Published: December 2014

A bacterial strain designated 6B-8T was isolated from crude oil from Daqing oilfield, China. Cells of strain 6B-8T were Gram-negative, aerobic, dimorphic and reproduced by means of binary fission. Strain 6B-8T could grow at 20–37 °C, pH 8–10 and 1–5 % (w/v) NaCl. Its genomic DNA G+C content was 62.0 mol%. The predominant cellular fatty acids were C18 : 1ω7c, C17 : 0, C18 : 0 and 11-methyl C18 : 1ω7c and the main hydroxy fatty acids were C12 : 0 3-OH and C12 : 1 3-OH when grown on marine agar 2216. The major quinone was Q-10 and the major polar lipids were three unidentified glycolipids. Phylogenetic analysis revealed that strain 6B-8T was a member of the family

Hyphomonadaceae

, sharing 99.6 and 99.4 % 16S rRNA gene sequence similarity with

Glycocaulis abyssi

LMG 27140T and

Glycocaulis albus

SLG210-30A1T, respectively, and less than 94.4 % similarity with the type strains of other members of the family

Hyphomonadaceae

. However, the DNA–DNA relatedness between strain 6B-8T and related strains

G. abyssi

LMG 27140T and

G. albus

SLG210-30A1T was 36±5 and 42±5 %, respectively. In addition, several phenotypic and genotypic features allowed differentiation of strain 6B-8T from

G. abyssi

LMG 27140T and

G. albus

SLG210-30A1T. Therefore, strain 6B-8T represents a novel species of genus

Glycocaulis

, for which the name Glycocaulis alkaliphilus sp. nov. is proposed. The type strain is 6B-8T ( = CGMCC 1.12428T = LMG 27410T).
The Avian RNAseq Consortium: a community effort to annotate the chicken genome
Authors: Smith Jacqueline , Burt David W. ,   the Avian RNAseq Consortium
Published: December 2014

Here we describe how members of the chicken research community have come together as the “Avian RNAseq Consortium” to provide chicken RNAseq data with a view to improving the annotation of the chicken genome. The data was used by Ensembl in their release 71 gene_build to help provide the most up-to-date annotation of Galgal4, which is still in current use. The data has also been used to predict many ncRNAs, particularly lncRNAs, and it continues to be used as a resource for annotation of other avian genomes along with continued gene discovery in the chicken. This article is submitted as part of the Third Report on Chicken Genes and Chromosomes which will be published in Cytogenetic and Genome Research
Mouse conventional dendritic cells can be universally classified based on the mutually exclusive expression of XCR1 and SIRPα
Authors: Gurka Stephanie , Becker Martina , Hartung Evelyn , Kroczek Richard A.
Published: December 2014

Since the identification of mouse dendritic cells (DC) in the early 70s, all attempts to consistently classify the identified functional DC subpopulations according to their surface molecule expression failed. In the absence of DC lineage markers, a great variety of non-congruent surface molecules were used instead. Recent advances in the understanding of the involvement of transcription factors in the differentiation of DC subpopulations, together with the identification of a lineage marker for cross-presenting DC, have now allowed to establish a consistent and unified DC classification in the mouse. We demonstrate in the present article that all conventional DC in the mouse can be universally subdivided into either XCR1+cross-presenting DC or SIRPα+DC, irrespective of their activation status. This advancement will greatly facilitate future work on the biology of mouse DC. We discuss this new classification in view of current DC classification systems in the mouse and the human.
Pre-synaptic inhibition of afferent feedback in the macaque spinal cord does not modulate with cycles of peripheral oscillations around 10 Hz
Authors: Galán Ferran , Baker Stuart N
Published: December 2014

Spinal interneurons are partially phase-locked to physiological tremor around 10Hz. The phase of spinal interneuron activity is approximately opposite to descending drive to motoneurons, leading to partial phase cancellation and tremor reduction. Pre-synaptic inhibition of afferent feedback modulates during voluntary movements, but it is not known whether it tracks more rapid fluctuations in motor output such as during tremor.

In this study, dorsal root potentials (DRPs) were recorded from the C8 and T1 roots in two macaque monkeys following intra-spinal micro-stimulation (random inter-stimulus interval 1.5-2.5 s, 30-100μA), whilst the animals performed an index finger flexion task which elicited peripheral oscillations around 10Hz. Forty one responses were identified with latency <5ms; these were narrow (mean width 0.59 ms), and likely resulted from antidromic activation of afferents following stimulation near terminals. Significant modulation during task performance occurred in 16/41 responses, reflecting terminal excitability changes generated by pre-synaptic inhibition (Wall’s excitability test). Stimuli falling during large-amplitude 8-12Hz oscillations in finger acceleration were extracted, and sub-averages of DRPs constructed for stimuli delivered at different oscillation phases. Although some apparent phase-dependent modulation was seen, this was not above the level expected by chance.

We conclude that although terminal excitability reflecting pre-synaptic inhibition of afferents modulates over the timescale of a voluntary movement, it does not follow more rapid changes in motor output. This suggests that pre-synaptic inhibition is not part of the spinal systems for tremor reduction described previously, and that it plays a role in overall – but not moment-by-moment – regulation of feedback gain.
HISAT: Hierarchical Indexing for Spliced Alignment of Transcripts
Authors: Kim Daehwan , Langmead Ben , Salzberg Steven L.
Published: December 2014

HISAT is a new, highly efficient system for alignment of sequences from RNA sequencing experiments that achieves dramatically faster performance than previous methods. HISAT uses a new indexing scheme, hierarchical indexing, which is based on the Burrows-Wheeler transform and the Ferragina-Manzini (FM) index. Hierarchical indexing employs two types of indexes for alignment: (1) a whole-genome FM index to anchor each alignment, and (2) numerous local FM indexes for very rapid extensions of these alignments. HISAT’s hierarchical index for the human genome contains 48,000 local FM indexes, each representing a genomic region of ~64,000 bp. The algorithm includes several customized alignment strategies specifically designed for mapping RNA-seq reads across multiple exons. In tests on a variety of real and simulated data sets, we show that HISAT is the fastest system currently available, approximately 50 times faster than TopHat2 and 12 times faster than GSNAP, with equal or better accuracy than any other method. Despite its very large number of indexes, HISAT requires only 4.3 Gigabytes of memory to align reads to the human genome. HISAT supports genomes of any size, including those larger than 4 billion bases. HISAT is available as free, open-source software fromhttp://www.ccb.jhu.edu/software/hisat.
An annotated consensus genetic map forPinus taedaL. and extent of linkage disequilibrium in three genotype-phenotype discovery populations
Authors: Westbrook Jared W. , Chhatre Vikram E. , Wu Le-Shin , Chamala Srikar , Neves Leandro Gomide , Muñoz Patricio , Martínez-García Pedro J. , Neale David B. , Kirst Matias , Mockaitis Keithanne , Nelson C. Dana , Peter Gary F. , Davis John M. , Echt Craig S.
Published: December 2014

A consensus genetic map forPinus taeda(loblolly pine) was constructed by merging three previously published maps with a map from a pseudo-backcross betweenP. taedaandP. elliottii(slash pine). The consensus map positioned 4981 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.48 centiMorgans and total map length was 2372 centiMorgans. Functional predictions for 4762 markers for expressed sequence tags were improved by alignment to full-lengthP. taedatranscripts. Alignments to theP. taedagenome mapped 4225 scaffold sequences onto linkage groups. The consensus genetic map was used to compare the extent of genome-wide linkage disequilibrium in an association population of distantly relatedP. taedaindividuals (ADEPT2), a multiple-family pedigree used for genomic selection studies (CCLONES), and a full-sib quantitative trait locus mapping population (BC1). Weak linkage disequilibrium was observed in CCLONES and ADEPT2. Average squared correlations, R2, between genotypes at SNPs less than one centiMorgan apart was less than 0.05 in both populations and R2did not decay substantially with genetic distance. By contrast, strong and extended linkage disequilibrium was observed among BC1 full-sibs where average R2decayed from 0.8 to less than 0.1 over 53 centiMorgans. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association and quantitative trait locus mapping between genotype-phenotype discovery populations.
Model checking to assess T-helper cell plasticity
Authors: Abou-Jaoudé Wassim , Monteiro Pedro T. , Naldi Aurélien , Grandclaudon Maximilien , Soumelis Vassili , Chaouiya Claudine , Thieffry Denis
Published: December 2014

Computational modeling constitutes a crucial step towards the functional understanding of complex cellular networks. In particular, logical modeling has proven suitable for the dynamical analysis of large signaling and transcriptional regulatory networks. In this context, signaling input components are generally meant to convey external stimuli, or environmental cues. In response to such external signals, cells acquire specific gene expression patterns modeled in terms of attractors (e.g.stable states). The capacity for cells to alter or reprogram their differentiated states upon changes in environmental conditions is referred to as cell plasticity.

In this article, we present a multivalued logical framework along with computational methods recently developed to efficiently analyze large models. We mainly focus on a symbolic model checking approach to investigate switches between attractors subsequent to changes of input conditions.

As a case study, we consider the cellular network regulating the differentiation of T-helper cells, which orchestrate many physiological and pathological immune responses. To account for novel cellular subtypes, we present an extended version of a published model of T-helper cell differentiation. We then use symbolic model checking to analyze reachability properties between T-helper subtypes upon changes of environmental cues. This allows for the construction of a synthetic view of T-helper cell plasticity in terms of a graph connecting subtypes with arcs labeled by input conditions. Finally, we explore novel strategies enabling specific T-helper cell polarizing or reprograming events.
Testing for genetic associations in arbitrarily structured populations
Authors: Song Minsun , Hao Wei , Storey John D.
Published: December 2014

We present a new statistical test of association between a trait and genetic markers, which we theoretically and practically prove to be robust to arbitrarily complex population structure. The statistical test involves a set of parameters that can be directly estimated from large-scale genotyping data, such as that measured in genome-wide association studies (GWAS). We also derive a new set of methodologies, called a genotype-conditional association test (GCAT), shown to provide accurate association tests in populations with complex structures, manifested in both the genetic and environmental contributions to the trait. We demonstrate the proposed method on a large simulation study and on the Northern Finland Birth Cohort study. In the Finland study, we identify several new significant loci that other methods do not detect. Our proposed framework provides a substantially different approach to the problem from existing methods, such as the linear mixed model and principal component approaches.