bluuebunny/crossref_metadata_2025 huggingface dataset:
Protocol for determining the diagnostic validity of physical examination maneuvers for shoulder pathology
Authors: Somerville Lyndsay , Bryant Dianne , Willits Kevin , Johnson Andrew
Published: February 2013

Background

Shoulder complaints are the third most common musculoskeletal problem in the general population. There are an abundance of physical examination maneuvers for diagnosing shoulder pathology. The validity of these maneuvers has not been adequately addressed. We propose a large Phase III study to investigate the accuracy of these tests in an orthopaedic setting.

Methods

We will recruit consecutive new shoulder patients who are referred to two tertiary orthopaedic clinics. We will select which physical examination tests to include using a modified Delphi process. The physician will take a thorough history from the patient and indicate their certainty about each possible diagnosis (certain the diagnosis is absent, present or requires further testing). The clinician will only perform the physical examination maneuvers for diagnoses where uncertainty remains. We will consider arthroscopy the reference standard for patients who undergo surgery within 8 months of physical examination and magnetic resonance imaging with arthrogram for patients who do not. We will calculate the sensitivity, specificity and positive and negative likelihood ratios and investigate whether combinations of the top tests provide stronger predictions of the presence or absence of disease.

Discussion

There are several considerations when performing a diagnostic study to ensure that the results are applicable in a clinical setting. These include, 1) including a representative sample, 2) selecting an appropriate reference standard, 3) avoiding verification bias, 4) blinding the interpreters of the physical examination tests to the interpretation of the gold standard and, 5) blinding the interpreters of the gold standard to the interpretation of the physical examination tests. The results of this study will inform clinicians of which tests, or combination of tests, successfully reduce diagnostic uncertainty, which tests are misleading and how physical examination may affect the magnitude of the confidence the clinician feels about their diagnosis. The results of this study may reduce the number of costly and invasive imaging studies (MRI, CT or arthrography) that are requisitioned when uncertainty about diagnosis remains following history and physical exam. We also hope to reduce the variability between specialists in which maneuvers are used during physical examination and how they are used, all of which will assist in improving consistency of care between centres.
Quinine controls body weight gain without affecting food intake in male C57BL6 mice
Authors: Cettour-Rose Philippe , Bezençon Carole , Darimont Christian , le Coutre Johannes , Damak Sami
Published: February 2013

Background

Quinine is a natural molecule commonly used as a flavouring agent in tonic water. Diet supplementation with quinine leads to decreased body weight and food intake in rats. Quinine is an in vitro inhibitor of Trpm5, a cation channel expressed in taste bud cells, the gastrointestinal tract and pancreas. The objective of this work is to determine the effect of diet supplementation with quinine on body weight and body composition in male mice, to investigate its mechanism of action, and whether the effect is mediated through Trpm5.

Results

Compared with mice consuming AIN, a regular balanced diet, mice consuming AIN diet supplemented with 0.1% quinine gained less weight (2.89 ± 0.30 g vs 5.39 ± 0.50 g) and less fat mass (2.22 ± 0.26 g vs 4.33 ± 0.43 g) after 13 weeks of diet, and had lower blood glucose and plasma triglycerides. There was no difference in food intake between the mice consuming quinine supplemented diet and those consuming control diet. Trpm5 knockout mice gained less fat mass than wild-type mice. There was a trend for a diet-genotype interaction for body weight and body weight gain, with the effect of quinine less pronounced in the Trpm5 KO than in the WT background. Faecal weight, energy and lipid contents were higher in quinine fed mice compared to regular AIN fed mice and in Trpm5 KO mice compared to wild type mice.

Conclusion

Quinine contributes to weight control in male C57BL6 mice without affecting food intake. A partial contribution of Trpm5 to quinine dependent body weight control is suggested.
Dental sealant knowledge, opinion, values and practice of Spanish dentists
Authors: San Martin Laura , Castaño Antonio , Bravo Manuel , Tavares Mary , Niederman Richard , Ogunbodede Eyitope O
Published: February 2013

Background

Multiple guidelines and systematic reviews recommend sealant use to reduce caries risk. Yet, multiple reports also indicate that sealants are significantly underutilized. This study examined the knowledge, opinions, values, and practice (KOVP) of dentists concerning sealant use in the southwest region of Andalusia, Spain. This is a prelude to the generation of a regional plan for improving children’s oral health in Andalusia.

Methods

The survey’s target population was dentists working in western Andalusia, equally distributed in the provinces of Seville, Cadiz, and Huelva (N=2,047). A convenience sample of meeting participants and meeting participant email lists (N=400) were solicited from the annual course on Community and Pediatric Dentistry. This course is required for all public health sector dentists, and is open to all private sector dentists. Information on the dentist’s KOVP of sealants was collected using four-part questionnaire with 31, 5-point Likert-scaled questions.

Results

The survey population demographics included 190 men (48%) and 206 women (52%) with an average clinical experience of 10.6 (± 8.4) years and 9.3 (± 7.5) years, respectively. A significant sex difference was observed in the distribution of place of work (urban/suburb) (p=0.001), but no sex differences between working sector (public/private). The mean ± SD values for each of the four KOVP sections for pit and fissure sealants were: knowledge = 3.57 ± 0.47; opinion = 2.48 ± 0.47; value = 2.74 ± 0.52; and practice = 3.48 ± 0.50. No sex differences were found in KOVP (all p >0.4). Independent of sex: knowledge statistically differed by years of experience and place of work; opinion statistically differed by years of experience and sector; and practice statistically differed by years of experience and sector. Less experienced dentists tended to have slightly higher scores (~0.25 on a Likert 1–5 scale). Statistically significant correlations were found between knowledge and practice (r=0.44, p=0.00) and between opinion and value (r=0.35, p=0.00).

Conclusions

The results suggest that, similar to other countries, Andalusian dentists know that sealants are effective, have neutral to positive attitudes toward sealants; though, based on epidemiological studies, underuse sealants. Therefore, methods other than classical behavior change (eg: financial or legal mechanisms) will be required to change practice patterns aimed at improving children's oral health.
Economic burden to primary informal caregivers of hospitalized older adults in Mexico: a cohort study
Authors: López-Ortega Mariana , García-Peña Carmen , Granados-García Víctor , García-González José Juan , Pérez-Zepeda Mario Ulises
Published: February 2013

Background

The burden of out of pocket spending for the Mexican population is high compared to other countries. Even patients insured by social security institutions have to face the cost of health goods, services or nonmedical expenses related to their illness. Primary caregivers, in addition, experience losses in productivity by taking up responsibilities in care giving activities. This situation represents a mayor economic burden in an acute care setting for elderly population. There is evidence that specialized geriatric services could represent lower overall costs in these circumstances and could help reduce these burdens.

The aim of this study was to investigate economic burden differences in caregivers of elderly patients comparing two acute care services (Geriatric and Internal Medicine). Specifically, economic costs associated with hospitalization of older adults in these two settings by evaluating health care related out of pocket expenditures (OOPE), non-medical OOPE and indirect costs.

Methods

A comparative analysis of direct and indirect costs in hospitalised elderly patients (60-year or older) and their primary informal caregivers in two health care settings, using a prospective cohort was performed. Economic burden was measured by out of pocket expenses and indirect costs (productivity lost) due to care giving activities. The analysis included a two-part model, the first one allowing the estimation of the probability of observing any health care related and non-medical OOPE; and the second one, the positive observations or expenditures.

Results

A total of 210 subjects were followed during their hospital stay. Of the total number of subjects 95% reported at least one non-medical OOPE, being daily transportation the most common expense. Regarding medical OOPE, medicines were the most common expense, and the mean numbers of days without income were 4.12 days. Both OOPE and indirect costs were significantly different between type of services, with less overall economic burden to the caregivers of elderly hospitalized in the geriatric unit. The final model showed that type of service and satisfaction had the largest coefficients (-0.68 and 0.662 respectively, p<0.001).

Conclusions

This study allowed us to identify associated factors of economic burden in elderly hospitalized in acute care units. It opens as well, an issue that should not be overlooked in framing public policies regarding elderly health care.
RETRACTED ARTICLE: Intragastric exposure
to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by
physiological and gene expression modifications
Authors: Gui Suxin , Sang Xuezi , Zheng Lei , Ze Yuguan , Zhao Xiaoyang , Sheng Lei , Sun Qingqing , Cheng Zhe , Cheng Jie , Hu Renping , Wang Ling , Hong Fashui , Tang Meng
Published: February 2013

Background

Numerous studies have demonstrated that titanium dioxide
nanoparticles (TiO2 NPs) induced nephrotoxicity in animals.
However, the nephrotoxic multiple molecular mechanisms are not clearly
understood.

Methods

Mice were exposed to 2.5, 5 and 10 mg/kg
TiO2 NPs by intragastric administration for 90
consecutive days, and their growth, element distribution, and oxidative stress in
kidney as well as kidney gene expression profile were investigated using
whole-genome microarray analysis technique.

Results

Our findings suggest that TiO2 NPs
resulted in significant reduction of renal glomerulus number, apoptosis,
infiltration of inflammatory cells, tissue necrosis or disorganization of renal
tubules, coupled with decreased body weight, increased kidney indices, unbalance
of element distribution, production of reactive oxygen species and peroxidation of
lipid, protein and DNA in mouse kidney tissue. Furthermore, microarray analysis
showed significant alterations in the expression of 1, 246 genes in the 10 mg/kg
TiO2 NPs-exposed kidney. Of the genes altered, 1006 genes
were associated with immune/inflammatory responses, apoptosis, biological
processes, oxidative stress, ion transport, metabolic processes, the cell cycle,
signal transduction, cell component, transcription, translation and cell
differentiation, respectively. Specifically, the vital up-regulation of Bcl6, Cfi and Cfd
caused immune/ inflammatory responses, the significant alterations of Axud1, Cyp4a12a, Cyp4a12b, Cyp4a14, and Cyp2d9 expression resulted in severe oxidative stress,
and great suppression of Birc5, Crap2, and Tfrc
expression led to renal cell apoptosis.

Conclusions

Axud1, Bcl6, Cf1, Cfd, Cyp4a12a,
Cyp4a12b, Cyp2d9, Birc5, Crap2, and Tfrc may be potential biomarkers of kidney toxicity caused by
TiO2 NPs exposure.
Comparison of a drug-eluting balloon first and then bare metal stent with a drug-eluting stent for treatment of de novo lesions: study protocol of a randomized controlled trial
Authors: Park Sang-Don , Yoon Chang-Hwan , Oh Il-Young , Suh Jung-Won , Cho Young-Suk , Youn Tae-Jin , Choi Dong-Ju , Chae In-Ho
Published: February 2013

Background

The use of a drug-eluting balloon for the treatment of de novo coronary artery lesions remains to be evaluated. A previous trial in patients with stable and unstable angina comparing a bare metal stent mounted on a drug-eluting balloon with a sirolimus-eluting stent failed to meet the prespecified non-inferiority criteria versus the sirolimus-eluting stent. The stent struts of a bare metal stent pre-mounted on a drug-eluting balloon may prevent the appropriate delivery of drugs to the vessel wall and may result in reduced efficacy. In the present study we will therefore evaluate the efficacy of a drug-eluting balloon for treating de novo coronary artery lesions using a strategy designed to uniformly deliver drug to the vessel with a bare metal stent.

Methods/Design

The Comparison of Drug-Eluting Balloon first study is a prospective, randomized, open-label trial designed to demonstrate the non-inferiority of first using a drug-eluting balloon (Sequent® please; B. Braun, Melsungen, Germany) followed by a bare metal stent (Coroflex® Blue; B. Braun) compared with using a drug-eluting stent (Resolute Integrity™; Boston Scientific, Natick, MA, USA) for de novo coronary artery lesions. The primary endpoint of the study is in-segment late loss at 9 months measured by quantitative coronary angiography. Secondary endpoints include angiographic findings such as angiographic success, device success, binary angiographic restenosis, and clinical outcomes such as procedural success, all-cause death, myocardial infarction, target vessel revascularization, target lesion revascularization, and stent thrombosis. A total of 180 patients will be enrolled in the study.

Discussion

The Comparison of Drug-Eluting Balloon first study will evaluate the clinical efficacy, angiographic outcomes and safety of a drug-eluting balloon first followed by a bare metal stent compared with a drug-eluting stent for the treatment of de novo coronary artery lesions.

Trial registration

Clinical Trials.gov: NCT01539603
Can network biology unravel the aetiology of congenital hyperinsulinism?
Authors: Stevens Adam , Cosgrove Karen E , Padidela Raja , Skae Mars S , Clayton Peter E , Banerjee Indraneel , Dunne Mark J
Published: February 2013

Congenital Hyperinsulinism is a condition with a number of genetic causes, but for the majority of patients, the underlying aetiology is unknown. We present here a rational argument for the use of computational biology as a valuable resource for identifying new candidate genes which may cause disease and for understanding the complex mechanisms which define the pathophysiology of this rare disease.
Thermal decomposition of [Co(en)3][Fe(CN)6]∙ 2H2O: Topotactic dehydration process, valence and spin exchange mechanism elucidation
Authors: Trávníček Zdeněk , Zbořil Radek , Matiková-Maľarová Miroslava , Drahoš Bohuslav , Černák Juraj
Published: February 2013

Background

The Prussian blue analogues represent well-known and extensively studied group of coordination species which has many remarkable applications due to their ion-exchange, electron transfer or magnetic properties. Among them, Co-Fe Prussian blue analogues have been extensively studied due to the photoinduced magnetization. Surprisingly, their suitability as precursors for solid-state synthesis of magnetic nanoparticles is almost unexplored.

In this paper, the mechanism of thermal decomposition of [Co(en)3][Fe(CN)6] ∙∙ 2H2O (1a) is elucidated, including the topotactic dehydration, valence and spins exchange mechanisms suggestion and the formation of a mixture of CoFe2O4-Co3O4(3:1) as final products of thermal degradation.

Results

The course of thermal decomposition of1ain air atmosphere up to 600°C was monitored by TG/DSC techniques,57Fe Mössbauer and IR spectroscopy. As first, the topotactic dehydration of1ato the hemihydrate [Co(en)3][Fe(CN)6] ∙∙ 1/2H2O (1b) occurred with preserving the single-crystal character as was confirmed by the X-ray diffraction analysis. The consequent thermal decomposition proceeded in further four stages including intermediates varying in valence and spin states of both transition metal ions in their structures, i.e. [FeII(en)2(μ-NC)CoIII(CN)4], FeIII(NH2CH2CH3)2(μ-NC)2CoII(CN)3] and FeIII[CoII(CN)5], which were suggested mainly from57Fe Mössbauer, IR spectral and elemental analyses data. Thermal decomposition was completed at 400°C when superparamagnetic phases of CoFe2O4and Co3O4in the molar ratio of 3:1 were formed. During further temperature increase (450 and 600°C), the ongoing crystallization process gave a new ferromagnetic phase attributed to the CoFe2O4-Co3O4nanocomposite particles. Their formation was confirmed by XRD and TEM analyses. In-field (5 K / 5 T) Mössbauer spectrum revealed canting of Fe(III) spin in almost fully inverse spinel structure of CoFe2O4.

Conclusions

It has been found that the thermal decomposition of [Co(en)3][Fe(CN)6] ∙∙ 2H2O in air atmosphere is a gradual multiple process accompanied by the formation of intermediates with different composition, stereochemistry, oxidation as well as spin states of both the central transition metals. The decomposition is finished above 400°C and the ongoing heating to 600°C results in the formation of CoFe2O4-Co3O4nanocomposite particles as the final decomposition product.
Automatic traveltime picking using instantaneous traveltime
Authors: Saragiotis Christos , Alkhalifah Tariq , Fomel Sergey
Published: February 2013

Event picking is used in many steps of seismic processing. We present an automatic event picking method that is based on a new attribute of seismic signals, instantaneous traveltime. The calculation of the instantaneous traveltime consists of two separate but interrelated stages. First, a trace is mapped onto the time-frequency domain. Then the time-frequency representation is mapped back onto the time domain by an appropriate operation. The computed instantaneous traveltime equals the recording time at those instances at which there is a seismic event, a feature that is used to pick the events. We analyzed the concept of the instantaneous traveltime and demonstrated the application of our automatic picking method on dynamite and Vibroseis field data.
Personalised intervention for people with depression and severe COPD
Authors: Alexopoulos George S. , Kiosses Dimitris N. , Sirey Jo Anne , Kanellopoulos Dora , Novitch Richard S. , Ghosh Samiran , Seirup Joanna K. , Raue Patrick J.
Published: February 2013

Chronic obstructive pulmonary disease (COPD) is often complicated by depression and exemplifies the challenge in managing chronic illnesses that require active patient participation in care. In a clinical trial (NCT00151372), we compared a novel personalised intervention for depression and COPD (PID-C) targeting treatment adherence with treatment as usual (TAU). In 138 patients with major depression and severe COPD, PID-C led to a higher remission rate and a greater reduction in depressive symptoms and in dyspnoea-related disability than TAU over 28 weeks and 6 months after the last session. If replicated, PID-C may serve as a care model for patients with both depression and medical illnesses with a deteriorating course.
The Coregulator, Repressor of Estrogen Receptor Activity (REA), Is a Crucial Regulator of the Timing and Magnitude of Uterine Decidualization
Authors: Zhao Yuechao , Park Sunghee , Bagchi Milan K. , Taylor Robert N. , Katzenellenbogen Benita S.
Published: February 2013

Successful implantation and maintenance of pregnancy require the transformation of uterine endometrial stromal cells into distinct decidualized cells. Although estrogen and progesterone (P4) receptors are known to be essential for decidualization, the roles of steroid receptor coregulators in this process remain largely unknown. In this study, we have established a key role for the coregulator, repressor of estrogen receptor activity (REA), in the decidualization of human endometrial stromal cells (hESCs) in vitro and of the mouse uterus in vivo. Our studies revealed that the level of REA normally decreases to half as hESC decidualization proceeds and that uterine reduction of REA in transgenic heterozygous knockout mice or small interfering RNA knockdown of REA in hESC temporally accelerated and strongly enhanced the differentiation process, as indicated by changes in cell morphology and increased expression of biomarkers of decidualization, including P4 receptor. Findings in hESC cultured in vitro with estradiol, P4, and 8-bromo-cAMP over a 10-day period mirrored observations of enhanced decidualization response in transgenic mice with heterozygous deletion of REA. Importantly, gene expression and immunohistochemical analyses revealed changes in multiple components of the Janus kinase/signal transducer and activator of transcription pathway, including marked up-regulation of signal transducer and activator of transcription 3 and IL-11, master regulators of decidualization, and the down-regulation of several suppressor of cytokine signaling family members, upon reduction of REA. The findings highlight that REA physiologically restrains endometrial stromal cell decidualization, controlling the timing and magnitude of decidualization to enable proper coordination of uterine differentiation with concurrent embryo development that is essential for implantation and optimal fertility.
Delayed Puberty but Normal Fertility in Mice With Selective Deletion of Insulin Receptors From Kiss1 Cells
Authors: Qiu Xiaoliang , Dowling Abigail R. , Marino Joseph S. , Faulkner Latrice D. , Bryant Benjamin , Brüning Jens C. , Elias Carol F. , Hill Jennifer W.
Published: February 2013

Pubertal onset only occurs in a favorable, anabolic hormonal environment. The neuropeptide kisspeptin, encoded by the Kiss1 gene, modifies GnRH neuronal activity to initiate puberty and maintain fertility, but the factors that regulate Kiss1 neurons and permit pubertal maturation remain to be clarified. The anabolic factor insulin may signal nutritional status to these neurons. To determine whether insulin sensing plays an important role in Kiss1 neuron function, we generated mice lacking insulin receptors in Kiss1 neurons (IRΔKiss mice). IRΔKiss females showed a delay in vaginal opening and in first estrus, whereas IRΔKiss males also exhibited late sexual maturation. Correspondingly, LH levels in IRΔKiss mice were reduced in early puberty in both sexes. Adult reproductive capacity, body weight, fat composition, food intake, and glucose regulation were comparable between the 2 groups. These data suggest that impaired insulin sensing by Kiss1 neurons delays the initiation of puberty but does not affect adult fertility. These studies provide insight into the mechanisms regulating pubertal timing in anabolic states.
Sex-specific retinal pigmentation results in sexually dimorphic long-wavelength-sensitive photoreceptors in the Eastern Pale Clouded Yellow butterfly,Colias erate
Authors: Ogawa Yuri , Kinoshita Michiyo , Stavenga Doekele G. , Arikawa Kentaro
Published: February 2013

The compound eyes of the Eastern Pale Clouded Yellow butterfly, Colias erate, contain three types of ommatidia (I, II and III), identifiable by the differing arrangements of pigment clusters around the rhabdoms. The pigment color is red in all ommatidial types except for type II ommatidia of females, where the pigment is orange. Intracellular recordings demonstrated that the spectral sensitivities of the proximal photoreceptors (R5-8) of all ommatidia in both sexes are strongly tuned by the perirhabdomal pigments. These pigments act as long-pass filters, shifting the peak sensitivities into the wavelength range above 600 nm. Due to the sex-specific pigments in type II ommatidia, the spectral sensitivities of the R5-8 photoreceptors of females peaked at 620 nm while those in males peaked at 660 nm. The measured spectral sensitivities could be well reproduced by an optical model assuming a long-wavelength-absorbing visual pigment with peak absorbance at 565 nm. Whereas the sexual dimorphism was unequivocally demonstrated for the ventral eye region, dimorphism in the dorsal region was not found. Presumably the ventral region is adapted for sexual behaviors such as courtship and oviposition.
Ablation of the ability to control the right-to-left cardiac shunt does not affect oxygen consumption, specific dynamic action or growth in rattlesnakes,Crotalus durissus
Authors: Leite Cleo A. C. , Taylor Edwin W. , Wang Tobias , Abe Augusto S. , de Andrade Denis O. V.
Published: February 2013

The morphologically undivided ventricle of the heart in non-crocodilian reptiles permits the mixing of oxygen-rich blood returning from the lungs and oxygen-poor blood from the systemic circulation. A possible functional significance for this intra-cardiac shunt has been debated for almost a century. Unilateral left vagotomy rendered the single effective pulmonary artery of the South American rattlesnake, Crotalus durissus, unable to adjust the magnitude of blood flow to the lung. The higher constant perfusion of the lung circulation and the incapability of adjusting R-L shunt in left-denervated snakes persisted over time, providing a unique model for investigation of the long-term consequences of cardiac shunting in a squamate. Oxygen uptake recorded at rest, during spontaneous and forced activity, was not affected by removing control of the cardiac shunt. Furthermore, metabolic rate and energetic balance during the post-prandial metabolic increment, plus the food conversion efficiency and growth rate were all similarly unaffected. These results show that control of cardiac shunting is not associated with a clear functional advantage in adjusting metabolic rate, effectiveness of digestion or growth rates.
Topology of the Interconversion Pathway Networks of Cycloheptane Conformations and Those of Related n-Membered Rings
Authors: Goto Satoru , Komatsu Kazushi , Terada Hiroshi
Published: February 2013

We, a collaboration group of mathematician and chemists, previously reported that the configuration space of n-membered alicyclic compounds (n = 5, 6, and 7) is diffeomorphic to (n − 4)-dimensional surface Sn−4 (S. Goto, K. Komatsu, Hiroshima Mathematical Journal201242, 115–126). In the present work, we spread concrete conformations and their interconversion pathway networks over a conformational scattering manifold, stochastically computing the optimized conformations of the alicyclic compounds (cyclopentane, cyclohexane, and cycloheptane). The conformational scattering manifold, namely “world map” of conformation, of these compounds depends on the degree of freedom in the endocyclic torsion angles. The present computational study confirmed that the world map of cyclohexane consists of a compact two-dimensional surface S2 equivalent to a traditional ring-puckering coordinate space. We then claim the world map of cycloheptane exists in a compact three-dimensional surface S3 (3-manifold). Since these series of studies rationalizes the world map of transformation of the cyclic compound containing small-, medium-, and large-size ring portions and their various connections, it might give an opportunity to improve such medicinal resources.
Individual vs. Aggregate Preferences: The Case of a Small Fish in a Big Pond
Authors: Blackburn Douglas W. , Ukhov Andrey D.
Published: February 2013

We study the relationship between the risk preferences of individuals and the risk preferences of the aggregate economy. To emphasize the vast differences that can occur between individual and market preferences brought about through aggregation, we assume an economy consisting entirely of risk seekers. We show that such individuals can lead to an aggregate economy that is risk averse. The converse is also true. An aggregate economy that exhibits risk aversion does not imply an economy of individual risk averters. An economy demanding a risk premium can be formed from individuals who do not demand such compensation. Understanding the relationship between the preferences of individuals and the preferences of the aggregate economy is crucial for understanding the connection between the behavioral finance literature, which focuses on individual preferences, and the asset-pricing literature, which focuses on aggregate prices. We discuss empirical implications of these results.

This paper was accepted by Wei Xiong, finance.
Pirfenidone: A Novel Agent for the Treatment of Idiopathic Pulmonary Fibrosis
Authors: Potts Jason , Yogaratnam Dinesh
Published: February 2013

OBJECTIVE

To evaluate the published clinical literature on the role of pirfenidone for the treatment of idiopathic pulmonary fibrosis (IPF).

DATA SOURCES

A systematic literature search was performed using the key words pirfenidone or Esbriet, alone and in combination, with IPF or idiopathic pulmonary fibrosis (expanded using MESH terminology). MEDLINE (1948-September 2012) was the primary database used for search purposes. In addition, all available articles and abstracts referenced by the articles identified via literature search were included.

STUDY SELECTION AND DATA EXTRACTION

The search was limited to English-language publications. All available clinical trials of pirfenidone pertinent to its pharmacology, pharmacokinetics, efficacy, and safety were included.

DATA SYNTHESIS

Pirfenidone is the first agent specifically developed for the treatment of IPF. It has been approved for use in Europe and Japan, but not in the US. Although Phase 3 trials have shown pirfenidone to improve certain clinical (6-minute walk test) and functional (change in forced vital capacity) outcomes in patients with IPF, an independent benefit on either mortality or acute exacerbation rates has yet to be demonstrated. Until more definitive supportive data are available, international guidelines have recommended against using pirfenidone to treat most patients with IPF.

CONCLUSIONS

Although pirfenidone appears to be an effective treatment for IPF, additional clinical trials are needed to better delineate its risk-benefit profile.
Cycloadditions in heterocycle and alkaloid synthesis
Authors: Wipf Peter , Fang Zhenglai , Ferrié Laurent , Ueda Masafumi , Walczak Maciej A. A. , Yan Yongzhao , Yang Michael
Published: February 2013

Intramolecular cycloadditions of bicyclo[1.1.0]butylalkyl-amines represent a rich source of novel heterocyclic scaffolds. As a function of the side chain attached to the amine, formal ene- or [2 + 2] cycloaddition products can be obtained in moderate to high yields. By suitable further functionalizations, a library of 3-azatricyclo[5.1.1.01,5]-nonanes was prepared and interrogated in 450 biological assays. This discovery collection was found to generate high hit rates and yet the individual samples demonstrated sufficient selectivity to fulfill robust lead criteria. These applications of bicyclo[1.1.0]butanes demonstrate that new synthetic chemistry and novel architectures are promising starting points for the generation of high-value discovery libraries.
Young Women's Perceptions of the Benefits Of Childbearing: Associations with Contraceptive Use and Pregnancy
Authors: Rocca Corinne H. , Harper Cynthia C. , Raine‐Bennett Tina R.
Published: February 2013

Context

High unintended pregnancy rates, and inconsistencies between reported pregnancy intentions and contraceptive behaviors, have been well documented among young U.S. women. Women's beliefs about the benefits of childbearing and motherhood may be related to the apparent disconnect between pregnancy intentions and reproductive outcomes.

Methods

Perceived benefits of childbearing and feelings about a potential pregnancy were assessed among 1,377 women aged 15–24 (most of them black or Latina) participating in a longitudinal study in 2005–2008. The women, who were initiating hormonal contraception at public family planning clinics and did not want to become pregnant for one year, were followed for 12 months. Differences in perceived benefits of childbearing by participant characteristics were examined with linear regression, using a new multi‐item measure. Cox proportional hazard regression was used to investigate the association of perceived benefits of childbearing with subsequent contraceptive discontinuation and pregnancy.

Results

Perceptions of the benefits of childbearing decreased with increasing age (coefficient, –0.04), and white women perceived fewer benefits to childbearing than blacks (−0.2). As women's perception of the benefits of childbearing increased, their one‐year pregnancy rates increased, after demographic characteristics and feelings about a potential pregnancy were controlled for (hazard ratio, 1.2). Benefits of childbearing were not associated with contraceptive discontinuation.

Conclusions

To better assess pregnancy risk among young women wanting to avoid pregnancy, it may be useful to acknowledge that they hold not only explicit pregnancy desires, but also beliefs about the benefits of childbearing, which may influence sexual behavior and pregnancy.
Altered Expression of Endogenous Soluble Vascular Endothelial Growth Factor Receptor-2 Is Involved in the Progression of Esophageal Squamous Cell Carcinoma
Authors: Wu Zhi-Yong , Chen Tao , Zhao Qing , Huang Jian-Hao , Chen Jie-Xin , Zheng Chun-Peng , Xu Xiu-E , Wu Jian-Yi , Xu Li-Yan , Li En-Min
Published: February 2013

Endogenous soluble vascular endothelial growth factor receptor-2 (esVEGFR-2), a new splicing variant of VEGFR-2, was shown to be the first endogenous specific inhibitor of lymphatic vessel growth. The expression of esVEGFR-2 and its clinicopathological roles in esophageal squamous cell carcinoma (ESCC) are unclear. In this article, quantitative RT-PCR was employed to detect the mRNA levels of esVEGFR-2 and VEGF-C in 90 paired primary ESCC tissues, along with immunohistochemical staining to measure esVEGFR-2 protein in 182 ESCC primary tissues. Correlations between esVEGFR-2 expression and clinicopathological features were also analyzed. Compared with the corresponding non-neoplastic esophageal mucosa tissues, the mRNA level of esVEGFR-2 was decreased, whereas the mRNA level of VEGF-C was increased in ESCCs. Downregulation of esVEGFR-2 mRNA level was significantly correlated with pTNM stages (χ2 = 7.790, p=0.02). Immunohistochemical staining of esVEGFR-2 was inclined to be reduced in ESCC tissues; lower esVEGFR-2 protein expression was related to better prognosis (χ2 = 6.366, p=0.012), whereas higher esVEGFR-2 protein accumulation in ESCC tissues was an independent prognostic factor for poor survival of patients (hazard ratio, 1.606; 95% confidence interval, 1.042–2.476; p=0.032). Taken together, altered expression of esVEGFR-2 is correlated with progression of ESCC. esVEGFR-2 might serve as a new independent prognostic marker for ESCC patients.
Targeting the Circulating MicroRNA Signature of Obesity
Authors: Ortega Francisco José , Mercader Josep María , Catalán Victoria , Moreno-Navarrete José María , Pueyo Neus , Sabater Mónica , Gómez-Ambrosi Javier , Anglada Roger , Fernández-Formoso José Antonio , Ricart Wifredo , Frühbeck Gema , Fernández-Real José Manuel
Published: February 2013

BACKGROUND

Genomic studies have yielded important insights into the pathogenesis of obesity. Circulating microRNAs (miRNAs) are valuable biomarkers of systemic diseases and potential therapeutic targets. We sought to define the circulating pattern of miRNAs in obesity and examine changes after weight loss.

METHODS

We assessed the genomewide circulating miRNA profile cross-sectionally in 32 men and after surgery-induced weight loss in 6 morbidly obese patients. The most relevant miRNAs were cross-sectionally validated in 80 men and longitudinally in 22 patients (after surgery-induced weight loss). We evaluated the effects of diet-induced weight loss in 9 obese patients. Thirty-six circulating miRNAs were associated with anthropometric variables in the initial sample.

RESULTS

In the validation study, morbidly obese patients showed a marked increase of miR-140-5p, miR-142-3p (both P < 0.0001), and miR-222 (P = 0.0002) and decreased levels of miR-532–5p, miR-125b, miR-130b, miR-221, miR-15a, miR-423-5p, and miR-520c-3p (P < 0.0001 for all). Interestingly, in silico targets leukemia inhibitory factor receptor (LIFR) and transforming growth factor receptor (TGFR) of miR-140-5p, miR-142-3p, miR-15a, and miR-520c-3p circulated in association with their corresponding miRNAs. Moreover, a discriminant function of 3 miRNAs (miR-15a, miR-520c-3p, and miR-423-5p) was specific for morbid obesity, with an accuracy of 93.5%. Surgery-induced (but not diet-induced) weight loss led to a marked decrease of miR-140-5p, miR-122, miR-193a-5p, and miR-16-1 and upregulation of miR-221 and miR-199a-3p (P < 0.0001 for all).

CONCLUSIONS

Circulating miRNAs are deregulated in severe obesity. Weight loss–induced changes in this profile and the study of in silico targets support this observation and suggest a potential mechanistic relevance.
The Levenberg–Marquardt iteration for numerical inversion of the power density operator
Authors: Bal Guillaume , Naetar Wolf , Scherzer Otmar , Schotland John
Published: February 2013

In this paper we develop a convergence analysis in an infinite dimensional setting of the Levenberg–Marquardt iteration
for the solution of a hybrid conductivity imaging problem. The problem consists in determining the spatially varying conductivity σ
from a series of measurements of power densities for various voltage inductions. Although this problem has been very well studied in the literature, convergence and regularizing properties of iterative algorithms in an
infinite dimensional setting are still rudimentary. We provide a partial result under the assumptions that the
derivative of the operator, mapping conductivities to power densities, is injective and the data is noise-free. Moreover, we implemented the Levenberg–Marquardt algorithm and tested it on simulated data.
Regulation of Central Na+Detection Requires the Cooperative Action of the NaXChannel and α1 Isoform of Na+/K+-ATPase in the Na+-Sensor Neuronal Population
Authors: Berret Emmanuelle , Nehmé Benjamin , Henry Mélaine , Toth Katalin , Drolet Guy , Mouginot Didier
Published: February 2013

The median preoptic nucleus (MnPO) holds a strategic position in the hypothalamus. It is adjacent to the third ventricle; hence, it can directly access the ionic composition of the CSF. MnPO neurons play a critical role in hydromineral homeostasis regulation by acting as central sensors of extracellular Na+concentration ([Na+]ext). The mechanism underlying Na+sensing involves the atypical Na+channel, NaX. Here we sought to determine whether Na+influx in Na+sensors is actively regulated via interaction with other membrane proteins involved in cellular Na+homeostasis, such as Na+/K+-ATPase.

The Na+/K+-ATPase role was investigated using patch-clamp recordings in rat MnPO dissociated neurons. Na+current evoked with hypernatriuric solution was diminished in the absence of ATP/GTP, indicating that Na+/K+-ATPase play a central role in [Na+]extdetection. Specific blockers of α1 and α3 isoforms of Na+/K+-ATPase, ouabain or strophanthidin, inhibited this Na+current. However, strophanthidin, which selectively blocks the α1 isoform, was more effective in blocking Na+current, suggesting that the Na+/K+-ATPase-α1 isoform is specifically involved in [Na+]extdetection. Although strophanthidin did not alter either the membrane resistance or the Na+reversal potential, the conductance and the permeability of the NaXchannel decreased significantly. Our results suggest that Na+/K+-ATPase interacts with the NaXchannel and regulates the high [Na+]ext-evoked Na+current via influencing the Na+influx rate. This study describes a novel intracellular regulatory pathway of [Na+]extdetection in MnPO neurons. The α1 isoform of Na+/K+-ATPase acts as a direct regulatory partner of the NaXchannel and influences Na+influx via controlling the Na+permeability of the channel.
Rich Services — A SOA Pattern for Dynamic Change in Cyber-physical Systems
Authors: Krüger Ingolf
Published: February 2013

Cyber-physical systems (CPS) are changing the way we interact with the physical world. From automotive to manufacturing to logistics to power-grid to virtual command and control, we now see widespread application of integrated, software-intensive systems of sensor/actuator networks connected to backbone cyber-infrastructures. In this document we develop Rich Services as an architectural pattern suitable for systematically designing and implementing CPS, with particular emphasis on dynamic change.
Search and Learning in the Immune System: Models of Immune Surveillance and Negative Selection
Authors: Textor Johannes
Published: February 2013

To protect our bodies against malicious antigens, our immune system needs to solve several difficult information processing problems. We propose algorithmic models of how the immune system finds intruding antigen as quickly and robustly as possible (a search problem) and how it reliably distinguishes proteins of foreign origin from normal host proteins (a classification problem). The analysis of these models provides novel qualitative and quantitative insights into the workings of the immune system, and yields predictions that can be tested experimentally.
Crystal structure of meso-1,4-bis-(N-(endo-himoyl)-valinate)benzene hexane- hemisolvate, C34H36N2O8·0.5C6H14, C37H43N2O8
Authors: Zhang Jing , Chu Gang , Yan Song
Published: February 2013

C37H43N2O8, triclinic, P1̄ (no. 2), a = 10.161(2) Å, b = 10.246(2) Å, c = 17.629(4) Å, α = 86.012(4)°, β = 78.092(4)°, γ = 73.458(4)°, V = 1721.4 Å3, Z = 2, Rgt(F) = 0.0748, wRref(F2) = 0.2160, T = 293 K.
Crystal structure of 2-methyl-4-(pyridin-3-yl)but-3-yn-2-ol, C10H11NO
Authors: Liu Qiao-Ru , Zhang Xiao-Li , Ma Wei , Yang Wei-Chun
Published: February 2013

C10H11NO, monoclinic, P21/c (no. 14), a = 5.901(2) Å, b = 13.380(4) Å, c = 11.537(3) Å, β = 95.760(5)°, V = 906.3 Å3, Z = 4, Rgt(F) = 0.0488, wRref(F2) = 0.1222, T = 298 K.
The cortisol awakening response is blunted in patients with active Cushing's disease
Authors: Ruiz Roa Silvia Liliana , Elias Paula Conde Lamparelli , Castro Margaret , Moreira Ayrton Custodio
Published: February 2013

Introduction

Cortisol awakening response (CAR) is a rapid increase of cortisol levels within 30–45 min after awakening.

Objective

This study evaluates CAR compared with cortisol circadian rhythm in active and in remission Cushing's disease (CD).

Materials and methods

We evaluated healthy controls (HC, n=19), obese (OB, n=10), in remission (n=08), and active CD patients (n=10). Salivary free cortisol (SF) was determined at 0800, 1100, 1700, 2000, and 2300 h on the first day. CAR was obtained the next morning immediately upon awakening and at 15, 30, 45, and 60-min post-wake up.

Results

We observed differences in SF levels throughout the day in HC, OB, and in remission CD (ANOVA P=0.0001) but not in active CD (P=0.2). We demonstrated SF increment after awakening in HC, OB, and in remission CD (ANOVA P=0.007), with no effect of time on SF in active CD. The relative increment of SF obtained at the peak after awakening (CARi%) in the active CD (67±57%) was lower than in HC (154±107%), OB (240±188%), and in remission CD (186±184%) patients (P=0.009). There was a negative correlation between the SF at awakening and the CARi% in HC (r=−0.8), OB (r=−0.78), and in remission CD (r=−0.74) but not in active CD (r=−0.35; P=0.31).

Conclusion

This study originally described a blunted CAR in active CD in contrast to its presence in HC, OB, and in remission CD. This subtle dysfunction of the hypothalamus–pituitary–adrenal axis may represent a distinct and additional physiopathological phenomenon superimposing the dysregulated cortisol circadian rhythm in this disease.
Compositional Effects on the Degradation of PVD-Tisin
Authors: McArthur W. F. , Deng F. , Ring K. , Pattison P. M. , Kavanagh K. L.
Published: February 2013

PVD-TixSiyNzfilms formed by reactive RF-magnetron co-sputtering of Ti and Si in Ar/N2are evaluated as a diffusion barrier between Cu and Si. A complete range of compositions are obtained by Ti targets inlaid with Si. Film composition is controlled by the target ratio of titanium to silicon and N2partial pressure. Electrical results versus thermal history for films of∼6–18% Si as well as the composition and microstructure as determined by Rutherford back scattering (RBS), TEM and electron diffraction are reported. These films are an amorphous matrix with imbedded nanocrystals of titanium nitride as-deposited and undergo phase separation to yield titanium nitride and silicon nitride after a 1000°C anneal. As-deposited compositions which lie above the TiN-Si3N4phase line yield crystals of TiN. Compositions below the TiN-Si3N4phase line yield crystals of Ti2N. Bulk resistivity as-deposited (<400μω-cm) is acceptable for use as a contact liner/barrier material and improves with annealing. Si pn-diodes metallized with 20nm Ti40Si15N45and Cu show no significant increase in reverse leakage current at anneal temperatures below 700°C.
Highly efficient electrode catalysts prepared with ordered nanoporous carbons with tunable pore sizes as catalyst supports
Authors: Chai Geun Seok , Yu Jong-Sung
Published: February 2013

Ordered uniform nanoporous carbons with pore sizes in the range of 10 – 600 nm were synthesized against removable colloidal crystalline templates by carbonization of phenol and formaldehyde as a carbon precursor. The porous carbons have high surface areas, large pore volumes, and three-dimensionally interconnected uniform pore structures, and thus were used as a support of a Pt(50)-Ru(50) alloy catalyst to study their effect on the anodic performance of the catalyst in direct methanol fuel cell. The use of the ordered uniform porous carbon allowed higher degree of dispersion of the catalysts and efficient diffusion of reagents, resulting in much improved catalytic activity for methanol oxidation in the fuel cell. In general, the smaller pore sizes the porous carbons have, the higher surface areas and the better catalytic activity for methanol oxidation they showed.
Potassium Fertilization in Rice–Wheat System across Northern India: Crop Performance and Soil Nutrients
Authors: Singh Vinod K. , Dwivedi Brahma S. , Buresh Roland J. , Jat M. L. , Majumdar Kaushik , Gangwar Babooji , Govil Vidhi , Singh Susheel K.
Published: February 2013

Rice (Oryza sativa L.)–wheat (Triticum aestivum L.) cropping in South Asia is under stress due to widespread removal of plant nutrients in excess of their application. We evaluated K, S, and Zn application to rice and wheat in 60 farmer’s fields in five districts across northern India. We compared the existing farmer’s fertilizer practice (FFP), which in most cases did not include application of K, S, or Zn, with application of K only, S + Zn, or K + S + Zn. Application of K increased rice yields by 0.6 to 1.2 Mg ha−1 and wheat yields by 0.2 to 0.7 Mg ha−1 across the locations varying in soil texture, soil K, climate, and irrigation. Application of S and Zn with K further increased yields. Added net return from fertilization with only K, as compared to FFP, ranged from U.S.$ 114 to 233 ha−1 for rice and U.S.$ 29 to 214 ha−1 for wheat. Added net return further increased when S and Zn were combined with K. Total plant K per unit of grain yield was comparable for mature rice and wheat (22 kg Mg grain−1). Soil exchangeable and non‐exchangeable K decreased without K application during one rice–wheat cropping cycle. Rice and wheat yields increased with application of K across the range in exchangeable soil K from 60 to 162 mg kg−1. Approaches are needed to reliably predict fertilizer K requirements when crops respond relatively uniformly to K across a wide range in exchangeable K.