bluuebunny/crossref_metadata_2025 huggingface dataset:
Thioredoxin 1 Is Essential for Sodium Sulfide–Mediated Cardioprotection in the Setting of Heart Failure
Authors: Nicholson Chad K. , Lambert Jonathan P. , Molkentin Jeffery D. , Sadoshima Junichi , Calvert John W.
Published: January 2013

Objective—

The aim of this study was to determine whether thioredoxin 1 (Trx1) mediates the cardioprotective effects of hydrogen sulfide (H
2
S) in a model of ischemic-induced heart failure (HF).

Approach and Results—

Mice with a cardiac-specific overexpression of a dominant negative mutant of Trx1 and wild-type littermates were subjected to ischemic-induced HF. Treatment with H
2
S as sodium sulfide (Na
2
S) not only increased the gene and protein expression of Trx1 in the absence of ischemia but also augmented the HF-induced increase in both. Wild-type mice treated with Na
2
S experienced less left-ventricular dilatation, improved left-ventricular function, and less cardiac hypertrophy after the induction of HF. In contrast, Na
2
S therapy failed to improve any of these parameters in the dominant negative mutant of Trx1 mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na
2
S therapy inhibited HF-induced apoptosis signaling kinase-1 signaling and nuclear export of histone deacetylase 4 in a Trx1-dependent manner.

Conclusions—

These findings provide novel information that the upregulation of Trx1 by Na
2
S therapy in the setting of HF sets into motion events, such as the inhibition of apoptosis signaling kinase-1 signaling and histone deacetylase 4 nuclear export, which ultimately leads to the attenuationof left-ventricular remodeling.
Molecular and phylogenetic studies on Pratylenchidae from Iran with additional data on Pratylenchus delattrei, Pratylenchoides alkani and two unknown species of Hirschmanniella and Pratylenchus
Authors: Majd Taheri Zahra , Majd Taheri Zahra , Tanha Maafi Zahra , Majd Taheri Zahra , Tanha Maafi Zahra , Subbotin Sergei A. , Majd Taheri Zahra , Tanha Maafi Zahra , Subbotin Sergei A. , Pourjam Ebrahim , Majd Taheri Zahra , Tanha Maafi Zahra , Subbotin Sergei A. , Pourjam Ebrahim , Eskandari Ali
Published: January 2013

Thirteen species of Pratylenchidae: Pratylenchus coffeae, P. delattrei, P. loosi, P. neglectus, P. penetrans, P. pseudopratensis, P. thornei, P. vulnus, Pratylenchus sp., Pratylenchoides alkani, P. ritteri, Hirschmanniella sp. and Zygotylenchus guevarai were collected from different crops and plants throughout Iran. The specimens were identified using morphological and molecular methods. Morphometrics and morphology are given for Pratylenchus sp., P. delattrei, Pratylenchoides alkani and Hirschmanniella sp. The D2-D3 expansion segments of the 28S rRNA gene were amplified and sequenced for all 13 species studied. Diagnostic PCR-ITS-RFLP profiles are given for Pratylenchus delattrei, P. penetrans, P. pseudopratensis, Pratylenchus sp., Pratylenchoides alkani and P. ritteri. Pratylenchus neglectus and P. thornei, collected from cereal fields, P. loosi from tea plantations, P. coffeae from banana, P. penetrans from ornamental plants, P. vulnus from pines and Z. guevarai from almonds showed a high level of similarity in the D2-D3 sequences with corresponding GenBank sequences. Nucleotide differences between Iranian populations and reference species were in the intraspecific range. Pratylenchus delattrei, found in vegetable fields, and Pratylenchus sp. from palm rhizosphere, formed a highly supported clade with P. zeae, the two former species being morphologically very close to the latter except in tail shape. Pratylenchus pseudopratensis, from cereal fields, clustered with P. vulnus with low support. Phylogenetic relationships within Pratylenchus species were mainly congruent with those obtained in previous studies. Despite the morphological similarities between P. ritteri and P. alkani, the D2-D3 of 28S rRNA gene sequences differed by 5 bp. Hirschmanniella sp., from a rice field, formed a clade with H. loofi and H. kwazuna.
The Contested Sea: Regimes of Maritime Violence in the Pre-Modern Indian Ocean
Authors: Prange Sebastian R.
Published: January 2013

Abstract

Rulers on the Indian Ocean littoral are generally portrayed as having been uninterested in the pursuit of sea power until the coming of the Europeans. This article examines a series of case studies from this earlier period to argue that maritime violence had long been a part of expansionist political projects centered on the control of trade routes and coastal waters. In their sum, they show the Indian Ocean to have been an arena of active political competition and legal contestation, which were waged through private and semi-private agents commonly denoted as pirates.
The Importance of Resolving Mesoscale Latent Heating in the North Atlantic Storm Track
Authors: Willison Jeff , Robinson Walter A. , Lackmann Gary M.
Published: January 2013

Theoretical, observational, and modeling studies have established an important role for latent heating in midlatitude cyclone development. Models simulate some contribution from condensational heating to cyclogenesis, even with relatively coarse grid spacing (on the order of 100 km). Our goal is to more accurately assess the diabatic contribution to storm-track dynamics and cyclogenesis while bridging the gap between climate modeling and synoptic dynamics. This study uses Weather Research and Forecasting model (WRF) simulations with 120- and 20-km grid spacing to demonstrate the importance of resolving additional mesoscale features that are associated with intense precipitation and latent heat release within extratropical cyclones. Sensitivity to resolution is demonstrated first with a case study, followed by analyses of 10 simulated winters over the North Atlantic storm track. Potential vorticity diagnostics are employed to isolate the influences of latent heating on storm dynamics, and terms in the Lorenz energy cycle are analyzed to determine the resulting influences on the storm track. The authors find that the intensities of individual storms and their aggregate behavior in the storm track are strongly sensitive to horizontal resolution. An enhanced positive feedback between cyclone intensification and latent heat release is seen at higher resolution, resulting in a systematic increase in eddy intensity and a stronger storm track relative to the coarser simulations. These results have implications for general circulation models and their projections of climate change.
The Diffusion of Local Bill of Rights Resolutions to the States
Authors: Riverstone-Newell Lori
Published: January 2013

Local officials engage in activism by passing laws in defiance of state and/or federal authority. Their intent is to stimulate policy change or, at least, to force a higher government response. What effect, if any, do their actions have? This study employs event history analysis, seeking to determine whether there is a relationship between local activism and state response as it pertains to the local Bill of Rights movement. In this movement, some localities and states passed resolutions or ordinances in opposition to the USA PATRIOT Act. While legislative professionalism is related to state resolution activity, the stronger predictor is the breadth of diffusion among localities.
Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cells
Authors: van den Boom Vincent , Rozenveld-Geugien Marjan , Bonardi Francesco , Malanga Donatella , van Gosliga Djoke , Heijink Anne Margriet , Viglietto Giuseppe , Morrone Giovanni , Fusetti Fabrizia , Vellenga Edo , Schuringa Jan Jacob
Published: January 2013

Key Points

Knockdown of individual PRC1 members in human stem/progenitor cells revealed a lack of redundancy between various paralog family members. CBX2 was identified as an important regulator of p21/CDKN1A independent of BMI1/PCGF4.
Genome sequence reveals that Pseudomonas fluorescens F113 possesses a large and diverse array of systems for rhizosphere function and host interaction
Authors: Redondo-Nieto Miguel , Barret Matthieu , Morrissey John , Germaine Kieran , Martínez-Granero Francisco , Barahona Emma , Navazo Ana , Sánchez-Contreras María , Moynihan Jennifer A , Muriel Candela , Dowling David , O’Gara Fergal , Martín Marta , Rivilla Rafael
Published: January 2013

Background

Pseudomonas fluorescensF113 is a plant growth-promoting rhizobacterium (PGPR) isolated from the sugar-beet rhizosphere. This bacterium has been extensively studied as a model strain for genetic regulation of secondary metabolite production inP. fluorescens, as a candidate biocontrol agent against phytopathogens, and as a heterologous host for expression of genes with biotechnological application. The F113 genome sequence and annotation has been recently reported.

Results

Comparative analysis of 50 genome sequences of strains belonging to theP. fluorescensgroup has revealed the existence of five distinct subgroups. F113 belongs to subgroup I, which is mostly composed of strains classified asP. brassicacearum. The core genome of these five strains is highly conserved and represents approximately 76% of the protein-coding genes in any given genome. Despite this strong conservation, F113 also contains a large number of unique protein-coding genes that encode traits potentially involved in the rhizocompetence of this strain. These features include protein coding genes required for denitrification, diterpenoids catabolism, motility and chemotaxis, protein secretion and production of antimicrobial compounds and insect toxins.

Conclusions

The genome ofP. fluorescensF113 is composed of numerous protein-coding genes, not usually found together in previously sequenced genomes, which are potentially decisive during the colonisation of the rhizosphere and/or interaction with other soil organisms. This includes genes encoding proteins involved in the production of a second flagellar apparatus, the use of abietic acid as a growth substrate, the complete denitrification pathway, the possible production of a macrolide antibiotic and the assembly of multiple protein secretion systems.
Rearing in enriched environment increases parvalbumin-positive small neurons in the amygdala and decreases anxiety-like behavior of male rats
Authors: Urakawa Susumu , Takamoto Kouich , Hori Etsuro , Sakai Natsuko , Ono Taketoshi , Nishijo Hisao
Published: January 2013

Background

Early life experiences including physical exercise, sensory stimulation, and social interaction can modulate development of the inhibitory neuronal network and modify various behaviors. In particular, alteration of parvalbumin-expressing neurons, a gamma-aminobutyric acid (GABA)ergic neuronal subpopulation, has been suggested to be associated with psychiatric disorders. Here we investigated whether rearing in enriched environment could modify the expression of parvalbumin-positive neurons in the basolateral amygdala and anxiety-like behavior.

Results

Three-week-old male rats were divided into two groups: those reared in an enriched environment (EE rats) and those reared in standard cages (SE rats). After 5 weeks of rearing, the EE rats showed decreased anxiety-like behavior in an open field than the SE rats. Under another anxiogenic situation, in a beam walking test, the EE rats more quickly traversed an elevated narrow beam. Anxiety-like behavior in the open field was significantly and negatively correlated with walking time in the beam-walking test. Immunohistochemical tests revealed that the number of parvalbumin-positive neurons significantly increased in the basolateral amygdala of the EE rats than that of the SE rats, while the number of calbindin-D28k-positive neurons did not change. These parvalbumin-positive neurons had small, rounded soma and co-expressed the glutamate decarboxylase (GAD67). Furthermore, the number of parvalbumin-positive small cells in the basolateral amygdala tended to positively correlate with emergence in the center arena of the open field and negatively correlated with walking time in the beam walking test.

Conclusion

Rearing in the enriched environment augmented the number of parvalbumin-containing specific inhibitory neuron in the basolateral amygdala, but not that of calbindin-containing neuronal phenotype. Furthermore, the number of parvalbumin-positive small neurons in the basolateral amygdala was negatively correlated with walking time in the beam walking test and tended to be positively correlated with activity in the center arena in the open field test. The results suggest that rearing in the enriched environment augmented parvalbumin-positive specific neurons in the basolateral amygdala, which induced behavioral plasticity that was reflected by a decrease in anxiety-like behavior in anxiogenic situations.
Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors
Authors: da Silva Emerson Rodrigues , Pitrez Márcio Condessa Paulo , Arruda Eurico , Mattiello Rita , Sarria Edgar E , de Paula Flávia Escremim , Proença-Modena José Luis , Delcaro Luana Sella , Cintra Otávio , Jones Marcus H , Ribeiro José Dirceu , Stein Renato T
Published: January 2013

Background

Lower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting.

Methods

Patients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes.

Results

We analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use.

Conclusions

Although RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.
Inhaled corticosteroid use is associated with increased circulating T regulatory cells in children with asthma
Authors: Singh Anne Marie , Dahlberg Paul , Burmeister Kristjan , Evans Michael D , Gangnon Ronald , Roberg Kathy A , Tisler Christopher , DaSilva Douglas , Pappas Tressa , Salazar Lisa , Lemanske Robert F , Gern James E , Seroogy Christine M
Published: January 2013

Background

T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use.

Methods

Peripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry.

Results

Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma.

Conclusion

We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency.
Characterizing biobank organizations in the U.S.: results from a national survey
Authors: Henderson Gail E , Cadigan R Jean , Edwards Teresa P , Conlon Ian , Nelson Anders G , Evans James P , Davis Arlene M , Zimmer Catherine , Weiner Bryan J
Published: January 2013

Background

Effective translational biomedical research hinges on the operation of 'biobanks,' repositories that assemble, store, and manage collections of human specimens and related data. Some are established intentionally to address particular research needs; many, however, have arisen opportunistically, in a variety of settings and with a variety of expectations regarding their functions and longevity. Despite their rising prominence, little is known about how biobanks are organized and function beyond simple classification systems (government, academia, industry).

Methods

In 2012, we conducted the first national survey of biobanks in the U.S., collecting information on their origins, specimen collections, organizational structures, and market contexts and sustainability. From a list of 636 biobanks assembled through a multi-faceted search strategy, representatives from 456 U.S. biobanks were successfully recruited for a 30-minute online survey (72% response rate). Both closed and open-ended responses were analyzed using descriptive statistics.

Results

While nearly two-thirds of biobanks were established within the last decade, 17% have been in existence for over 20 years. Fifty-three percent listed research on a particular disease as the most important reason for establishment; 29% listed research generally. Other reasons included response to a grant or gift, and intent to centralize, integrate, or harmonize existing research structures. Biobank collections are extraordinarily diverse in number and types of specimens and in sources (often multiple) from which they are obtained, including from individuals, clinics or hospitals, public health programs, and research studies. Forty-four percent of biobanks store pediatric specimens, and 36% include postmortem specimens. Most biobanks are affiliated in one or multiple ways with other entities: 88% are part of at least one or more larger organizations (67% of these are academic, 23% hospitals, 13% research institutes). The majority of biobanks seem to fill a particular 'niche' within a larger organization or research area; a minority are concerned about competition for services, although many are worried about underutilization of specimens and long-term funding.

Conclusions

Effective utilization of biobank collections and effective policies to govern their use will require understanding of the immense diversity found in organizational features, including the very different history and primary goals that many biobanks have.
Bat flight with bad wings: is flight metabolism affected by damaged wing membranes?
Authors: Voigt Christian C.
Published: January 2013

Infection of North American bats with the keratin-digesting fungus Geomyces destructans often result in holes and ruptures of wing membranes, yet it is unknown if flight performance and metabolism of bats are altered by such injuries. I conducted flight experiments in a circular flight arena in Myotis albescens and M. nigricans where I observed individuals with intact or ruptured trailing edge of one of the plagiopatagial membranes. In both species, individuals with damaged wings were lighter, had a higher aspect ratio (squared wing span divided by wing area) and an increased wing loading (weight divided by wing area) than conspecifics with intact wings. Bats with an asymmetric reduction of the wing area flew at similar speeds but performed less flight manoeuvres than conspecifics with intact wings. Individuals with damaged wings showed lower metabolic rates during flight than conspecifics with intact wings, even when controlling for body mass differences; the difference in mass-specific metabolic rates may be attributable to the lower number of flight manoeuvres (U-turns) by bats with damaged wings compared to conspecifics with intact wings. Possibly, bats compensated an asymmetric reduction in wing area by lowering their body mass and avoiding flight manoeuvres. In conclusion, bats may not suffer directly from moderate wing damages by experiencing increased metabolic rates but indirectly by a reduced manoeuvrability and foraging success. This could impede a bat's ability to gain sufficient body mass before hibernation.
Synthesis of Silyl-substituted Anthracene Derivatives via Birch-type Silylation
Authors: Kanno Ken-ichiro , Maemura Yumika , Kobayashi Naotaka , Kyushin Soichiro
Published: January 2013

The Birch-type silylation of anthracene gave hexasilylated hexahydroanthracene 1 as a single stereoisomer. Treatment of 1 with DDQ or TCNE furnished 1,3-disilylanthracene or 1,2,3,4-tetrasilyltetrahydroanthracene, respectively, in high yields.
Analytical Performance and Clinical Utility of a Bioassay for Thyroid-Stimulating Immunoglobulins
Authors: Leschik Johannes J. , Diana Tanja , Olivo Paul D. , König Jochem , Krahn Ulrike , Li Yunsheng , Kanitz Michael , Kahaly George J.
Published: January 2013

The analytical performance and the clinical utility of a thyrotropin receptor (TSHR)–stimulating immunoglobulin (TSI) bioassay were compared with those of a TSHR-binding inhibitory immunoglobulin (TBII) assay. Limits of detection (LoD) and quantitation (LoQ), assay cutoff, and the half-maximal effective concentration (EC50) were measured. Dilution analysis was performed in sera of hyperthyroid patients with Graves disease (GD) during antithyroid treatment (ATD). Titer was defined as the first dilution step at which measurement of TSI or TBII fell below the assay cutoff. The LoD, LoQ, cutoff, and EC50 of the bioassay were 251-, 298-, 814-, and 827-fold lower than for the TBII assay. There were 22%, 42%, 23%, and 14% more positive samples in the TSI bioassay at dilutions of 1:3, 1:9, 1:27, and 1:81 (P < .0001), respectively. Responders to ATD demonstrated marked differences in titers compared with nonresponders. The bioassay detected lower levels of TSHR autoantibodies, and the dilution analysis provided similar predictive values of both assays in GD.
Subject auxiliary inversion and linguistic generalization: Evidence for functional/cognitive motivation in language
Authors: Chen Rong
Published: January 2013

This paper provides a unified account of English subject-auxiliary inversion (SAI). It argues that SAIs, as have been called in the literature, belong to two semantically distinctive constructions. The first is the Auxiliary Subject Construction (ASC), one that merely reverses the subject and auxiliary order, without the fronting of another unit. It functions to mark non-indicative moods. The second SAI construction is the X Auxiliary Subject Construction (XASC), in which the auxiliary-subject (AS) order is accompanied by the fronting of a unit from its original, post-subject position in the canonical, SV order sentence. The XASC serves a different purpose from the ASC, i.e., to focus the fronted unit. As such, it shares both structural and functional affinity with full-verb inversion (Chen 2003), which is referred to hereafter as the X Verb Subject Construction (XVSC) for sake of consistency. The second purpose of this study is to address the issue of invertability of the subject auxiliary/verb order. Drawing on Deane (1992), I propose an Invertability Hypothesis, which applies to both the XASC and the XVSC. On this hypothesis, invertability depends on the strength of the linkage between the fronted unit and the auxiliary/verb that exists in the canonical sentence. The stronger the link, the more likely the order of the subject and the auxiliary/verb will be inversed once the unit is fronted. With this analysis – one that is decidedly different from previous accounts (e.g. Goldberg 2006) – I intend to demonstrate that the functional/cognitive approach to language is indeed capable of handling a complex construction such as inversion, the generalization of which generative linguists believe can only be stated formally (Newmeyer 1998; Borsley and Newmeyer 2009; Lidz and Williams 2009).
Variational principles for immersed surfaces with L2
-bounded second fundamental form
Authors: Rivière Tristan
Published: January 2013

In this work we present new tools for studying the variations of the Willmore functional
of immersed surfaces into ℝ
m
. This approach gives for instance a new proof of the existence of a Willmore minimizing embedding of an arbitrary closed surface in arbitrary codimension. We explain how the same approach can solve constraint minimization problems for the Willmore functional. We show in particular that, for a given closed surface and a given conformal class for this surface, there is an immersion in ℝ
m
, away possibly from isolated branched points, which minimizes the Willmore energy among all possible Lipschitz immersions in ℝ
m
having an L2
-bounded second fundamental form and realizing this conformal class. This branched immersion is either a smooth conformal Willmore branched immersion or an isothermic branched immersion. We show that branched points do not exist whenever the minimal energy in the conformal class is less than 8π and that these immersions extend to smooth conformal Willmore embeddings or global isothermic embeddings of the surface in that case. Finally, as a by-product of our analysis, we establish that inside a compact subspace of the moduli space the following holds: the weak limit of Palais Smale Willmore sequences are conformal Willmore, the weak limits of Palais Smale sequences
of conformal Willmore are either conformal Willmore or global isothermic and finally
we observe also that weakly converging Palais Smale sequences of global isothermic immersions are global isothermic. The analysis developed along the paper – in particular these last results – opens the door to the possibility of constructing new critical saddle points of the Willmore functional without or with constraints using min-max methods.
The Effect of Pharmaceutical Innovation on Longevity: Patient Level Evidence from the 1996–2002 Medical Expenditure Panel Survey and Linked Mortality Public-use Files
Authors: Lichtenberg Frank R.
Published: January 2013

This study uses patient-level data to analyze the effect of technological change embodied in pharmaceuticals on the longevity of elderly Americans. Previous patient-level studies could not control for important patient attributes such as education, income, and race; they did not provide estimates of the effect of using newer drugs on life expectancy, or of the overall cost-effectiveness of new drugs relative to old drugs; and they were not based on nationally representative samples of individuals. Our data, primarily derived from the Medical Expenditure Panel Survey and the Linked Mortality Public-use Files, enable us to overcome those limitations.

We investigate the effect of the vintage (year of U.S. Food and Drug Administration approval) of the prescription drugs used by an individual on his or her survival and medical expenditure, controlling for a number of demographic characteristics and indicators and determinants of health status. When we control only for age, sex, and interview year, we estimate that a 1-year increase in drug vintage increases life expectancy by 0.52%. Controlling for a much more extensive set of other attributes (the mean year the person started taking his or her medications, and dummy variables for activity limitations, race, education, family income as a percent of the poverty line, insurance coverage, Census region, body mass index, smoking, and more than 100 medical conditions) has virtually no effect on the estimate of the effect of drug vintage on life expectancy. Between 1996 and 2003, the mean vintage of prescription drugs increased by 6.6 years. This is estimated to have increased the life expectancy of elderly Americans by 0.41–0.47 years. This suggests that not less than two-thirds of the 0.6-year increase in the life expectancy of elderly Americans during 1996–2003 was due to the increase in drug vintage. The 1996–2003 increase in drug vintage is also estimated to have increased annual drug expenditure per elderly American by $207, and annual total medical expenditure per elderly American by $218. This implies that the incremental cost-effectiveness ratio (cost per life-year gained) of pharmaceutical innovation was about $12,900. This estimate of the cost per life-year gained from the use of newer drugs is a small fraction of leading economists’ estimates of the value of (willingness to pay for) an additional year of life. It is also consistent with estimates from clinical trials.
Prospective study of carmustine wafers in combination with 6-month metronomic temozolomide and radiation therapy in newly diagnosed glioblastoma: preliminary results
Authors: Salmaggi Andrea , Milanesi Ida , Silvani Antonio , Gaviani Paola , Marchetti Marcello , Fariselli Laura , Solero Carlo Lazzaro , Maccagnano Carmelo , Casali Cecilia , Guzzetti Sara , Pollo Bianca , Ciusani Emilio , DiMeco Francesco
Published: January 2013

Object

Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide. A combination of carmustine wafers with the Stupp treatment regimen has only been investigated in retrospective studies.

Methods

In a single-institution prospective study, the authors assessed 12-month progression-free survival (PFS), toxicity, and overall survival in patients with glioblastoma treated with surgery, carmustine wafers, radiotherapy, and 6-month metronomic temozolomide chemotherapy. Thirty-five patients with de novo glioblastoma, between the ages of 18 and 70 years, and with Karnofsky Performance Scale scores of at least 70, were included in the study. Patients were followed monthly and assessed using MRI every 2 months.

Results

After a median follow-up of 15 months, the median time to tumor progression was 12.5 months and median survival was 17.8 months. Due to toxicity (mostly hematological), 7 patients had to prematurely stop temozolomide treatment. Twenty-two patients developed Grade 3 CD4+ lymphocytopenia. Three patients developed oral-esophageal candidiasis, 2 developed pneumonia, and 1 developed a dorsolumbar zoster. Early intracranial hypertension was observed in 1 patient, and 1 was treated empirically for suspected brain abscess. One patient died of Legionella pneumonia soon after repeat surgery.

Conclusions

Overall, this treatment schedule produced promising results in terms of PFS without a marked increase in toxicities as compared with the Stupp regimen. However, the gain in median survival using this schedule was less clear. Only prospective comparative trials will determine whether these preliminary results will translate into a long-term survival advantage with an acceptable toxicity profile.
Pediatric perimedullary arteriovenous fistula of the conus medullaris supplied by the artery of Desproges-Gotteron
Authors: Cohen José E. , Constantini Shlomo , Gomori John M. , Benifla Mony , Itshayek Eyal
Published: January 2013

The cone artery, or artery of Desproges-Gotteron, is sometimes seen arising from the internal iliac artery. The authors describe a case of a symptomatic perimedullary arteriovenous fistula (AVF) of the conus medullaris in an 8-year-old boy who presented with a protracted history of urinary difficulty and severe sudden-onset right lumbosciatic pain that evolved to severe paraparesis with compromise of the sphincter muscles. The spinal AVF, which was supplied by the cone artery and a thoracic radiculomedullary artery that joined at the fistula site in a large partially thrombosed varix, was completely occluded with Onyx liquid embolic. The patient's clinical condition improved rapidly after embolization. As shown in this patient, urgent endovascular embolization of spinal AVFs can be very rewarding, even in patients with severe neurological presentation. The artery of Desproges-Gotteron appears to be a rare arterial variation. To the authors' knowledge, this is the first pediatric case of a conal AVF supplied by this artery.
Intraventricular silicone oil
Authors: Chang Chih-Chen , Chang Hong-Shiu , Toh Cheng Hong
Published: January 2013

The authors report a case in which intravitreous silicone oil migrated into the ventricles. They note that intraventricular silicone oil can be misdiagnosed as intraventricular hemorrhage and neurosurgeons should be aware of this possibility.

This 58-year-old woman with a history of Type II diabetic mellitus and retinal detachment (resulting from diabetic retinopathy), which had been treated with intravitreous silicone tamponade, presented with dizziness and headache approximately 10 years after the intravitreous silicone treatment. Over the next 6 years she underwent 2 non–contrast-enhanced brain CT studies and 1 MRI study for evaluation of her symptoms. On CT scan, extension of the intraocular silicone along the optic nerve was evident. Two hyperdense nodules were observed freely floating in the right lateral and fourth ventricles, remaining in the nondependent portion of ventricles in both supine and prone positions. On T2-weighted MRI, the left orbital content and the intraventricular nodules all demonstrated chemical shift artifacts typically associated with silicone. The imaging findings were characteristic for intraventricular silicone after silicone oil tamponade. The patient's dizziness and headache were treated symptomatically and she was followed up at the outpatient department.

Migration of intravitreous silicone oil into the cerebral ventricles is a rare complication. Intraventricular silicone oil can mimic intraventricular hemorrhage. Radiographically, intraventricular silicone oil can be distinguished from hemorrhage as silicone oil tends to stay in the nondependent portion of the ventricle. Chemical shift artifacts on MRI may help establishing the diagnosis of intraventricular silicone oil. Currently, there is no consensus on surgical removal of intraventricular silicone oil, and in the majority of cases reported in the literature, the patients were asymptomatic.
Registration of ‘Tamrun OL11’ Peanut
Authors: Baring Michael R. , Simpson Charles E. , Burow Mark D. , Cason John M. , Ayers Jamie L.
Published: January 2013

‘Tamrun OL11’ (Reg. No. CV‐118, PI 665017) is a high‐yielding, high‐oleic, runner‐type peanut (Arachis hypogaea L. subsp. hypogaea var. hypogaea) cultivar that has resistance to Sclerotinia minor Jaggar) and improved grade attributes over previously released runner‐type cultivars that are resistant to S. minor. It was tested under the experimental designation Tx055308 and released by Texas AgriLife Research at College Station, TX on 21 July 2011. Tamrun OL11 was derived from a single cross between Tx977116 F2:8, which has a high oleic‐oil content and resistance to Tomato spotted wilt virus, and the cultivar Tamrun 98, which has a normal oleic‐oil content and a high percentage of total sound mature kernels (TSMKs). Early selections were practiced using the pedigree selection technique. Initial yield testing began in the F3:5 generation in 2006 and continued through 2009 for a total of 25 multiple location trials. Tamrun OL11 performed equally as well as Tamrun OL07, which is resistant to S. minor, and was superior to the widely grown Flavorunner 458 cultivar for yield and disease resistance under high incidence of S. minor. Tamrun OL11 also performed equally as well as Flavor Runner 458 and was superior to Tamrun OL07 for the percentage of TSMKs. The objective of releasing this line is to provide growers with a cultivar that will yield and grade the same as the currently grown Flavor Runner 458 cultivar while reducing grower risk by maintaining the level of resistance to S. minor that the recently released Tamrun OL07 cultivar provides.
Registration of Three Germplasm Lines of Cotton Derived from Gossypium barbadense L. Accession GB713 with Resistance to the Reniform Nematode
Authors: McCarty J. C. , Jenkins J. N. , Wubben M. J. , Gutierrez O. A. , Hayes R. W. , Callahan F. E. , Deng D.
Published: January 2013

Three upland cotton (Gossypium hirsutum L.) germplasm lines, M713 Ren1 (Reg. No. GP‐958, PI 665928), M713 Ren2 (Reg. No. GP‐959, PI 665929), and M713 Ren5 (Reg. No. GP‐960, PI 665930) resistant to the reniform nematode, Rotylenchulus reniformis Linford and Oliveria were developed and jointly released by the USDA‐ARS and the Mississippi Agricultural and Forestry Experiment Station in 2012. The day‐neutral, reniform‐resistant germplasm lines originated from the photoperiodic G. barbadense L. accession GB713 and were selected using the tightly linked simple sequence repeat (SSR) markers GH 132, BNL 3279, and BNL 569. Egg production of the reniform nematode was suppressed to approximately 90% below that of the susceptible check, ‘Deltapine 61’ in greenhouse tests. The lines exhibit considerable differences for agronomic and fiber traits such as length, strength and micronaire, and with their high level of resistance they should be valuable to cotton breeding programs. The successful use of marker assisted selection for these specific SSR markers further validates their use in the selection of resistant plants in segregating generations.
Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes
Authors: Cellier Mathieu
Published: January 2013

The Natural resistance-associated macrophage protein 1 (Nramp1 or Solute carrier 11 member 1, Slc11a1) transports divalent metals across the membrane of late endosomes and lysosomes in professional phagocytes. Nramp1 represents an ancient eukaryotic cell-autonomous defense whereas the gene duplication that yielded Nramp1 and Nramp2 predated the origin of Sarcopterygians (lobe-finned fishes and tetrapods). SLC11A1 genetic polymorphisms associated with human resistance to tuberculosis consist of potential regulatory variants. Herein, current knowledge of the regulation of SLC11A1 gene expression is reviewed and comprehensive analysis of ENCODE data available for hematopoietic cell-types suggests a hypothesis for the regulation of SLC11A1 expression during myeloid development and phagocyte functional polarization. SLC11A1 is part of a 34.6 kb CTCF-insulated locus scattered with predicted regulatory elements: a 3' enhancer, a large 5' enhancer domain and four elements spread around the transcription start site (TSS), including several C/EBP and PU.1 sites. SLC11A1 locus ends appear mobilized by ETS-related factors early during myelopoiesis; activation of both 5' and 3' enhancers in myelo-monocytic cells correlate with transcription factor binding at the TSS. Characterizing the corresponding cis/trans determinants functionally will establish the mechanisms involved and possibly reveal genetic variation that impacts susceptibility to infectious or immune diseases.
Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid
Authors: Kim Jong , Campbell Bruce , Chan Kathleen , Mahoney Noreen , Haff Ronald
Published: January 2013

Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA), a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H2O2), tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H2O2 was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H2O2 against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization.
Systems Modeling at Multiple Levels of Regulation: Linking Systems and Genetic Networks to Spatially Explicit Plant Populations
Authors: Kitchen James , Allaby Robin
Published: January 2013

Selection and adaptation of individuals to their underlying environments are highly dynamical processes, encompassing interactions between the individual and its seasonally changing environment, synergistic or antagonistic interactions between individuals and interactions amongst the regulatory genes within the individual. Plants are useful organisms to study within systems modeling because their sedentary nature simplifies interactions between individuals and the environment, and many important plant processes such as germination or flowering are dependent on annual cycles which can be disrupted by climate behavior. Sedentism makes plants relevant candidates for spatially explicit modeling that is tied in with dynamical environments. We propose that in order to fully understand the complexities behind plant adaptation, a system that couples aspects from systems biology with population and landscape genetics is required. A suitable system could be represented by spatially explicit individual-based models where the virtual individuals are located within time-variable heterogeneous environments and contain mutable regulatory gene networks. These networks could directly interact with the environment, and should provide a useful approach to studying plant adaptation.
A New Method for Flow Rate Measurement in Millimeter-Scale Pipes
Authors: Ji Haifeng , Gao Xuemin , Wang Baoliang , Huang Zhiyao , Li Haiqing
Published: January 2013

Combining the Capacitively Coupled Contactless Conductivity Detection (C4D) technique and the principle of cross correlation flow measurement, a new method for flow rate measurement in millimeter-scale pipes was proposed. The research work included two parts. First, a new five-electrode C4D sensor was developed. Second, with two conductivity signals obtained by the developed sensor, the flow rate measurement was implemented by using the principle of cross correlation flow measurement. The experimental results showed that the proposed flow rate measurement method was effective, the developed five-electrode C4D sensor was successful, and the measurement accuracy was satisfactory. In five millimeter-scale pipes with different inner diameters of 0.5, 0.8, 1.8, 3.0 and 3.9 mm respectively, the maximum relative difference of the flow rate measurement between the reference flow rate and the measured flow rate was less than 5%.
Lipid Profile of Patients with Acute Myocardial Infarction and its Correlation with Systemic Inflammation
Authors: Khan Haseeb A. , Alhomida Abdullah S. , Sobki Samia H.
Published: January 2013

The biomarker potential of using various lipids fractions for predicting risk of acute myocardial infarction (AMI) is controversial. We therefore compared the lipid profiles, including serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TG), in 67 AMI patients. Patients included 28 STEMI (ST-elevated myocardial infarction) patients, 39 NSTEMI (non-ST-elevated myocardial infarction) patients and 25 patients with chest pain. Control group included 54 age- and gender-matched normal subjects. We also studied the correlation between lipid profile and systemic inflammation in these subjects. There were significant decreases in TC, LDL and HDL levels in both STEMI and NSTEMI patients as compared to normal subjects; however, patients with chest pain did not show any significant change in these lipids. Serum TG levels did not differ significantly among the study groups. There were significant increases in serum high-sensitive C-reactive protein (hs-CRP) levels in STEMI and NSTEMI patients, as compared to control group. Serum hs-CRP showed significant inverse correlation with HDL; however, hs-CRP was not correlated with TC, LDL, and TG. In conclusion, our findings suggest that reduction in serum TC does not prevent the risk of AMI, whereas a decrease in serum HDL and increase in hs-CRP strongly predisposes the risky individuals to an AMI event. We emphasize the importance of HDL and CRP measurements for the assessment of a combined lipid-inflammation risk factor that could be a useful predictor of high risk individuals, as well as a prognostic marker in AMI patients.
HIRESSS: a physically based slope stability simulator for HPC applications
Authors: Rossi G. , Catani F. , Leoni L. , Segoni S. , Tofani V.
Published: January 2013

Abstract. HIRESSS (HIgh REsolution Slope Stability Simulator) is a physically based distributed slope stability simulator for analyzing shallow landslide triggering conditions in real time and on large areas using parallel computational techniques. The physical model proposed is composed of two parts: hydrological and geotechnical. The hydrological model receives the rainfall data as dynamical input and provides the pressure head as perturbation to the geotechnical stability model that computes the factor of safety (FS) in probabilistic terms. The hydrological model is based on an analytical solution of an approximated form of the Richards equation under the wet condition hypothesis and it is introduced as a modeled form of hydraulic diffusivity to improve the hydrological response. The geotechnical stability model is based on an infinite slope model that takes into account the unsaturated soil condition. During the slope stability analysis the proposed model takes into account the increase in strength and cohesion due to matric suction in unsaturated soil, where the pressure head is negative. Moreover, the soil mass variation on partially saturated soil caused by water infiltration is modeled. The model is then inserted into a Monte Carlo simulation, to manage the typical uncertainty in the values of the input geotechnical and hydrological parameters, which is a common weak point of deterministic models. The Monte Carlo simulation manages a probability distribution of input parameters providing results in terms of slope failure probability. The developed software uses the computational power offered by multicore and multiprocessor hardware, from modern workstations to supercomputing facilities (HPC), to achieve the simulation in reasonable runtimes, compatible with civil protection real time monitoring. A first test of HIRESSS in three different areas is presented to evaluate the reliability of the results and the runtime performance on large areas.