bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood supply to the human sternocleidomastoid muscle and its clinical implications for mandible reconstruction
Authors: Leclère Franck Marie , Vacher Christian , Benchaa Tarik
Published: September 2012

Objectives/Hypothesis:

The use of the sternocleidomastoid (SCM) flap for reconstructive surgery of the mandible seems to be a practicable although underestimated option.

Study Design:

This study was conducted on 15 cadavers that had been neoprene–latex injected in the middle and inferior pedicles.

Methods:

Lengths of the SCM were equally divided into upper, middle, and lower thirds. Each third was then subdivided into numbered quadrants. This procedure defined six levels in the SCM, each corresponding to two quadrants: one medial and the other lateral. For each third of the SCM, the origin of the main pedicles was recorded. The quadrants where neoprene–latex was detected were reported in the dissection book.

Results:

The upper third of the SCM muscle was constantly supplied by branches of the occipital artery. The middle third of the SCM muscle received its blood supply from a branch of the superior thyroid artery (right SCM/left SCM: 53%/53%), the external carotid artery (27%/20%), or branches of both (20%/27%). The lower third of the muscle was supplied by a branch arising from the suprascapular artery (73%/73%), the transverse cervical artery (7%/13%), the thyrocervical trunk (13%/13%), or the superficial cervical artery (7%/0%). The neoprene–latex injected into the subclavian artery reached the four lower levels in all SCMs studied (the middle third of the SCM). In 13% of the SCMs, this injection also reached level II (the upper third of the SCM). With a double injection (inferior and middle pedicles), levels I and II were reached in 100% of the cases.

Conclusions:

This study shows that, used alone, the lower pedicle does not have the ability to ensure the full vascularization of the SCM muscle. A composite flap might be safely raised only if the integrity of both inferior and middle pedicles is respected.
Outcomes following transoral robotic surgery: Supraglottic laryngectomy
Authors: Mendelsohn Abie H. , Remacle Marc , Van Der Vorst Sebastien , Bachy Vincent , Lawson Georges
Published: September 2012

Objectives/Hypothesis:

To describe a single center outcomes following transoral robotic surgery for supraglottic laryngectomy (TORS–SL).

Study Design:

Prospective data collection.

Methods:

Patient records receiving TORS–SL for squamous cell carcinoma (SCCA) with at least 12 months follow‐up fit inclusion for this study. Two patients with previous SCCA were excluded.

Results:

18 patients (14 male, 4 female) were included in the study, having a mean follow‐up time of 28.1 months (SD = 12.1). All patients had negative margins confirmed on final pathology. Nine (50%) patients received postoperative chemoradiation therapy for advanced neck disease. No (0%) patients received tracheostomy or gastrostomy tubes. There were no (0%) local recurrences, and three (16.7%) regional recurrences. Five (27.8%) patients experienced temporary postoperative complications. Overall 2‐year outcomes reached 83%, 100%, and 89% for locoregional control, disease‐specific survival, and overall survival respectively.

Conclusions:

Initial outcomes for TORS–SL are encouraging and are comparable to previously described treatment modalities. Larger studies are encouraged. Laryngoscope, 2013
Morbidity and mortality following transarterial liver chemoembolization in patients with hepatocellular carcinoma and synthetic hepatic dysfunction
Authors: Garwood Elisabeth R. , Fidelman Nicholas , Hoch Sarah E. , Kerlan Robert K. , Yao Francis Y.
Published: September 2012

The purpose of this study was to determine the rate and risk factors for the development of irreversible hepatotoxicity after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) and synthetic hepatic dysfunction. Two hundred fifty-one consecutive patients with HCC and hepatic dysfunction who underwent 443 TACE procedures from 2005 to 2010 were retrospectively reviewed. The included patients met one of the following criteria: a pre-TACE bilirubin level ≥ 2 mg/dL, an international normalized ratio (INR) > 1.5, a creatinine level > 1.2 mg/dL, a platelet count ≤ 60,000/mL, a Model for End-Stage Liver Disease (MELD) score > 15, Child-Turcotte-Pugh class B or C, ascites, or portal vein thrombosis. Hepatotoxicity was defined as new or worsening ascites, encephalopathy, or grade 3 or 4 toxicity (bilirubin, aspartate aminotransferase, alanine aminotransferase, creatinine, or INR) according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The rate and risk factors for death or urgent liver transplantation within 6 weeks of TACE and irreversible hepatotoxicity were determined with a generalized estimating equation analysis. Reversible hepatotoxicity developed after 90 procedures (20%) in 78 patients (31%). Irreversible hepatotoxicity developed after 41 procedures (9%) in 37 patients (15%). Six patients (2%) underwent urgent liver transplantation, and 11 (4%) died within 6 weeks of TACE. Patients at increased risk for procedure-related mortality or urgent liver transplantation within 6 weeks of TACE had a baseline serum bilirubin level ≥ 4.0 mg/dL (P = 0.01), an elevated INR (P < 0.001), hypoalbuminemia with an albumin level < 2.0 g/L (P = 0.01), a serum creatinine level > 2.0 mg/dL (P = 0.02), large ascites (P = 0.002), encephalopathy (P = 0.005), or a MELD score ≥ 20 (P < 0.001). In conclusion, TACE can be performed safely in patients with baseline hepatic dysfunction. However, a poor hepatic reserve increases the risk of irreversible hepatotoxicity, which may lead to death or the need for urgent liver transplantation. Liver Transpl 19:164–173, 2013. © 2012 AASLD.
Impact of estimated liver volume and liver weight on gender disparity in liver transplantation
Authors: Mindikoglu Ayse L. , Emre Sukru H. , Magder Laurence S.
Published: September 2012

Although lower Model for End-Stage Liver Disease (MELD) scores due to lower levels of serum creatinine in women might account for some of the gender disparity in liver transplantation (LT) rates, even within MELD scores, women undergo transplantation at lower rates than men. It is unclear what causes this disparity, but transplant candidate/donor liver size mismatch may be a factor. We analyzed Organ Procurement and Transplantation Network data for patients with end-stage liver disease on the waiting list. A pooled conditional logistic regression analysis was used to assess the association between gender and LT and to determine the degree to which this association was explained by lower MELD scores or liver size. In all, 28,866 patients and 424,001 person-months were included in the analysis. The median estimated liver volume (eLV) and the median estimated liver weight (eLW) were significantly lower for women versus men on the LT waiting list (P < 0.001). When we controlled for the region and the blood type, women were 25% less likely to undergo LT in a given month in comparison with men (P < 0.001). When the MELD score was included in the model, the odds ratio (OR) for gender increased to 0.84, and this suggested that 9 percentage points of the 25% gender disparity were due to the MELD score. When eLV was added to the model, there was an additional 3% increase in the OR for gender, and this suggested that transplant candidate/donor liver size mismatch was an underlying factor for the lower LT rates in women versus men (OR = 0.87, P < 0.001). In conclusion, lower LT rates among women on the waiting list can be explained in part by lower MELD scores, eLVs, and eLWs in comparison with men. However, at least half of the gender disparity still remains unexplained. Liver Transpl 19:89–95, 2013. © 2012 AASLD.
Interleukin-28B polymorphism in hepatitis C and liver transplantation
Authors: Duarte-Rojo Andres , Deneke Matthew G. , Charlton Michael R.
Published: September 2012

The discovery of interleukin-28B (IL-28B) single-nucleotide polymorphisms has opened an important new area of research in liver transplantation (LT) for hepatitis C virus (HCV). Both recipient- and donor-derived IL-28B genotypes affect the post-LT treatment response, with sustained virological response (SVR) rates oscillating from >50% in homozygotes for the favorable allele (up to 90% when this is present in both the recipient and the donor) to <15% in homozygotes for the unfavorable allele and from 30% to 50% in heterozygotes. Other key posttransplant outcomes affected by the IL-28B genotype are the time to histological recurrence, HCV RNA and alanine aminotransferase levels, histological variables (including the rate of fibrosis progression), and hepatocellular carcinoma. Interactions between donor and recipient IL-28B genotypes are complex and may affect outcomes not directly related to HCV infections, such as acute cellular rejection (ACR) and metabolic diseases. A preferential allocation system in which livers from donors homozygous for the favorable allele are given to HCV patients might be postulated to improve SVR rates and post-LT outcomes in recipients with HCV infections (a 25% increase in SVR and an 8% decrease in mortality at 5 years). Although negative effects from this are difficult to predict, they could include an accelerated progression of fibrosis in patients with failed HCV eradication and an increase in ACR in non-HCV patients. Our knowledge of the precise role of IL-28B genotypes in the course of post-LT HCV is evolving, but existing knowledge suggests the possibility of exploring strategies that use IL-28B genotyping to reduce the impact of post-LT adverse outcomes. Liver Transpl 19:49–58, 2013. © 2012 AASLD.
Preparation of Pixantrone/Poly(γ‐glutamic acid) Nanoparticles through Complex Self‐Assembly for Oral Chemotherapy
Authors: Meng Lili , Ji Bing , Huang Wei , Wang Dali , Tong Gangsheng , Su Yue , Zhu Xinyuan , Yan Deyue
Published: September 2012

A facile and green approach is reported to construct pixantrone/poly(γ‐glutamic acid) nanoparticles (PIX/γ‐PGA NPs) as an oral drug delivery system through the complex self‐assembly of polyelectrolyte γ‐PGA and the anticancer drug pixantrone dimaleate (PDM). The complex self‐assembly behavior is investigated in detail. The results demonstrate that PDM can interact with γ‐PGA to conveniently form NPs and the size of NPs can be controlled by adjusting the solution volume ratio of PDM to γ‐PGA. These NPs illustrate their pH‐dependent release behavior, efficient cellular uptake and enhanced drug efficacy through an in vitro release study, flow cytometry, CLSM analysis and the MTT assay. In summary, PIX/γ‐PGA NPs may serve as a promising oral drug delivery system for cancer therapy.

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Bioinspired Bioadhesive Polymers: Dopa‐Modified Poly(acrylic acid) Derivatives
Authors: Laulicht Bryan , Mancini Alexis , Geman Nathanael , Cho Daniel , Estrellas Kenneth , Furtado Stacia , Hopson Russell , Tripathi Anubhav , Mathiowitz Edith
Published: September 2012

The one‐step synthesis and characterization of novel bioinspired bioadhesive polymers that contain Dopa, implicated in the extremely adhesive byssal fibers of certain gastropods, is reported. The novel polymers consist of combinations of either of two polyanhydride backbones and one of three amino acids, phenylalanine, tyrosine, or Dopa, grafted as side chains. Dopa‐grafted hydrophobic backbone polymers exhibit as much as 2.5× the fracture strength and 2.8× the tensile work of bioadhesion of a commercially available poly(acrylic acid) derivative as tested on live, excised, rat intestinal tissue.

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Effect of Branched Side Chains on the Physicochemical and Photovoltaic Properties of Poly(3‐hexylthiophene) Isomers
Authors: Cui Chaohua , Sun Yeping , Zhang Zhi‐Guo , Zhang Maojie , Zhang Jing , Li Yongfang
Published: September 2012

Two P3HT isomers with branched alkyl side chains, P3EBT and P3MPT, are synthesized. The HOMO energy levels of P3EBT and P3MPT are −5.35 and −5.24 eV, respectively, which are significantly lower than that of P3HT with a linear side chain. The absorption edges of the two P3HT isomer films, especially those of P3EBT, are blue‐shifted in comparison with that of P3HT. A PSC based on P3EBT:IC60BA (2:1 w/w) shows a high open‐circuit voltage of 0.98 V, which is the highest Voc reported so far for polythiophene‐based PSCs. A PSC based on P3MPT:IC70BA (2:1 w/w) exhibits a power conversion efficiency of 3.62% with a Voc of 0.91 V. P3MPT is suitable for the application in tandem PSCs.
Finely Tuned Fluorescence Emission of Polydiphenylacetylene Films Obtained by Copolymerization
Authors: Lee Wang‐Eun , Han Dong‐Cheul , Sakaguchi Toshikazu , Kim Yong‐Bae , Lee Chang‐Lyoul , Kwak Giseop
Published: September 2012

PDPAs containing longer (octadecyl, C18) and shorter (methyl, C1) alkyl side chains in the same backbone are synthesized. The copolymerization of C1 and C18 monomers at a range of feed ratios afford high‐molecular‐weight (Mw > 106) copolymers almost quantitatively. As the content of longer alkyl chain units in the copolymers increases, the emission band in the bulk film shifts to shorter wavelengths and the emission intensity increases. The lamellar layer distance increases with increasing C18 content. The excited species with shorter lifetimes decrease gradually with increasing C18 content, whereas the longer‐lasting emission increases. Fine tuning of the FL emission of PDPAs is achieved by simple copolymerization of monomers with different alkyl side‐chain lengths.
Plasticizing and Reinforcing Features of Siloxane Domains in Amine‐Cured Epoxy/Silica Hybrids
Authors: Piscitelli Filomena , Lavorgna Marino , Buonocore Giovanna G. , Verdolotti Letizia , Galy Jocelyne , Mascia Leno
Published: September 2012

Organic/inorganic hybrid materials comprising an amine‐epoxide network and siloxane domains are produced by the sol/gel method. The presence of both plasticizing flexible linear siloxane sequences and reinforcing nanosized silica particles and branched silsesquioxanes (SSQO) structures is confirmed by 29Si NMR and SAXS analysis. The hybrids display simultaneously a monotonical reduction in Tg and an increase in rubbery plateau modulus with increasing siloxane content. At the same time, nanoindentation tests reveal an improved resistance to plastic deformation. The effect of siloxane content on the values of the rubbery plateau modulus is evaluated through the EBM model for blends and composites exhibiting the characteristic co‐continuity of the two constituent phases.

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Non‐Stoichiometric Polycondensations and the Synthesis of High Molar Mass Polycondensates
Authors: Kricheldorf Hans R. , Zolotukhin Mikhail G. , Cárdenas Jorge
Published: September 2012

This report presents a general overview of non‐stoichiometric step‐growth polymerizations (polycondensations). Three kinds of non‐stoichiometric polycondensations are defined and discussed for a2 + b2 monomer combinations. Depending on the kinetic scenario and on the experimental conditions, the excess of one monomer either strongly reduces or strongly enhances the average degree of polymerization (DP) relative to a stoichiometric polycondensation under identical conditions. As a result, telechelic oligomers or extremely high molar mass polymers (DPs > 1000) may be formed. Stoichiometric imbalance has in all cases the consequence that cyclization is largely suppressed in early stages of a polycondensation. Finally, non‐ stoichiometric “a2 + bn” polycondensations are discussed.
Forming of bulk metallic glasses: ideal superplasticity?
Authors: Gravier S. , Blandin J. J.
Published: September 2012

Due to their brittleness, bulk metallic glasses (BMG) are generally difficult to form at room temperature. A fruitful way to get components is to deform them in their supercooled liquid region (SLR). In this region, BMG generally exhibit particularly large strain capacities. This behaviour is sometimes reported as superplasticity since several requirements of superplasticity are fulfilled. For instance, particularly large m values (up to 1) can be measured and consequently one can wonder if such forming conditions of BMG can be considered as “ideal” superplasticity. In this paper, we report studies dealing with high temperature deformation of various BMGs. Similarities and differences between high temperature deformation of BMGs and superplasticity of fine grained alloys are discussed.
Superplastic forming of AZ31 magnesium alloy with controlled microstructure
Authors: Cusick M. , Abu‐Farha F. , Lours P. , Maoult Y. , Bernhart G. , Khraisheh M.
Published: September 2012

A recent study on post‐superplastic forming properties has shown that heating time prior to testing has a major effect on the post‐forming properties of superplastically‐formed AZ31 Magnesium alloy sheets. To this point, there has been very little examination into the effects of pre‐heating or annealing on superplastic forming. In this work, these effects are examined using AZ31 Mg alloy samples. Both tensile specimens and bulge sheets were superplastically‐stretched after undergoing different annealing routes. Multiple annealing temperatures and times were examined to produce specimens with grain sizes ranging from 8 to 15 μm, for comparison with traditional SPF results. The results show that annealing treatments can be suitable for the improvement of thinning and forming time of superplastically‐formed Magnesium alloys through the control of the microstructure.
Superplasticity of the aluminum alloys containing the Al3Ni eutectic particles
Authors: Mikhaylovskaya A. V. , Portnoy V. K.
Published: September 2012

The structures and parameters of superplasticity of aluminum alloys containing fine and coarse eutectic Al3Ni particles were investigated. Traditional hot and cold rolling were used for sheet producing. The research alloys have low‐ or high – alloying solid solution. Superplastisity characterization of the alloy with high‐alloying solid solution is much better beside alloys with low‐alloying solid solution. Alloying by zirconium improves superplasticity in some investigated alloys. Some alloys with partially recrystallized structure show d = 500–700% at T = 0.95 Tm with the constant strain rates to the range of (1·10 –3–1·10 –2) s–1.
Modelling of superplastic forming of hollow structures with goffered filler made of VT6 titanium alloy
Authors: Safiullin R.V. , Kruglov A.A. , Akhunova A.Kh. , Safiullin A.R. , Dmitriev S.V.
Published: September 2012

The superplastic forming process of the VT6 titanium alloy three‐layered hollow structures with goffered filler are investigated. Based on the results of experimental studies and on the results of finite element modeling, we determine rational parameters of the process such as gas pressure increase rate, when superplastic flow condition is satisfied for ribs, and the processing time is minimal.
Material characterization of duplex stainless steel by superplastic free bulging test
Authors: Yoon J.‐H. , Yi Y.‐M. , Lee H.‐S.
Published: September 2012

Macroscopic superplastic behaviour of metallic or non metallic materials is usually represented by the strain rate sensitivity, and it can be determined by tensile tests at elevated temperature. However, a uniaixal stress state occurs in the test whilst a multiaixal stress state is induced in actual superplastic forming processes. The difference of the stress state might affect the reliability of the strain rate sensitivity obtained from the tension test. In the current study, the material characterization of duplex stainless steel, UNS S31803, has been carried out to determine the strain rate sensitivity throughout superplastic free bulging test under constant pressure. The measured height of bulged plate during the test was transformed into strain rate and stress corresponding to height at each time by theoretical considerations. The strain rate sensitivities were calculated for each pressure level. After calculating the strain rate sensitivity and strength coefficient for each test case, the flow stress equations have been employed in the finite element simulation to verify the experiments. The bulged height obtained from the simulation showed a reasonable agreement with the experimental findings. In the future, if a study on the effect of fillet radius of test tool and microstructure evolution is carried out, it is thought that the reliability of the material characterization by superplastic free bulging test can be enhanced.
Olfactory dysfunction in fragile X tremor ataxia syndrome
Authors: Juncos Jorge L. , Lazarus Joash T. , Rohr Julia , Allen Emily G. , Shubeck Lisa , Hamilton Debra , Novak Gloria , Sherman Stephanie L.
Published: September 2012

Introduction:

We investigated olfactory defects in fragile X‐associated tremor/ataxia syndrome (FXTAS), a finding reported on in other neurodegenerative disorders with clinical features that overlap those of FXTAS.

Methods:

We measured olfactory identification capacity in 41 FMR1 premutation carriers and 42 controls using the University of Pennsylvania Smell Identification Test (UPSIT). Carriers received neurologic evaluations using motor rating scales for tremor, ataxia, and parkinsonism. Cognitive function was measured using the Montreal Cognitive Assessment test.

Results:

Frequency of olfactory defects was higher in carriers, compared to controls (61% versus 29%; P = 0.003). There was no statistically significant group difference in severity of olfaction defects, after accounting for differences in age, and in rates of head injury and smoking. However, both the frequency (odds ratio = 3.9; 95% confidence interval: 0.81–19.1) and severity (28.6 versus 33.4; P = 0.01) of these defects were greater in cognitively impaired, compared to cognitively intact, carriers. There was no correlation between UPSIT scores and the above‐mentioned motor rating scales.

Conclusions:

FMR1 premutation carriers are susceptible to olfactory identification defects. The severity of these defects is comparable to that reported in hereditary ataxias, but less than that in PD and Alzheimer's disease. This concurrence across neurodegenerative disorders suggests a shared system vulnerability that correlates with, but is not limited to, cognitive impairment, because it is also found in cognitively intact carriers. These results need to be corroborated in a larger prospective study of FMR1 premutation carriers that extends beyond olfactory identification to include measures of smell thresholds. © 2012 Movement Disorder Society
Living on the edge with too many mouths to feed: Why dopamine neurons die
Authors: Bolam J. Paul , Pissadaki Eleftheria K.
Published: September 2012

Although genes, protein aggregates, environmental toxins, and other factors associated with Parkinson's disease (PD) are widely distributed in the nervous system and affect many classes of neurons, a consistent feature of PD is the exceptional and selective vulnerability of dopamine (DA) neurons of the SNc. What is it about these neurons, among all other neurons in the brain, that makes them so susceptible in PD? We hypothesize that a major contributory factor is the unique cellular architecture of SNc DA neuron axons. Their large, complex axonal arbour puts them under such a tight energy budget that it makes them particularly susceptible to factors that contribute to cell death, including unique molecular characteristics associated with SNc DA neurons and nonspecific, nervous‐system–wide factors. © 2012 Movement Disorder Society
Brain activation pattern related to gait disturbances in Parkinson's disease
Authors: Crémers Julien , D'Ostilio Kevin , Stamatakis Julien , Delvaux Valérie , Garraux Gaëtan
Published: September 2012

Gait disturbances represent a therapeutic challenge in Parkinson's disease (PD). To further investigate their underlying pathophysiological mechanisms, we compared brain activation related to mental imagery of gait between 15 PD patients and 15 age‐matched controls using a block‐design functional MRI experiment. On average, patients showed altered locomotion relatively to controls, as assessed with a standardized gait test that evaluated the severity of PD‐related gait disturbances on a 25‐m path. The experiment was conducted in the subjects as they rehearsed themselves walking on the same path with a gait pattern similar as that during locomotor evaluation. Imagined walking times were measured on a trial‐by‐trial basis as a control of behavioral performance. In both groups, mean imagined walking time was not significantly different from that measured during real gait on the path used for evaluation. The between‐group comparison of the mental gait activation pattern with reference to mental imagery of standing showed hypoactivations within parieto‐occipital regions, along with the left hippocampus, midline/lateral cerebellum, and presumed pedunculopontine nucleus/mesencephalic locomotor area, in patients. More specifically, the activation level of the right posterior parietal cortex located within the impaired gait‐related cognitive network decreased proportionally with the severity of gait disturbances scored on the path used for gait evaluation and mental imagery. These novel findings suggest that the right posterior parietal cortex dysfunction is strongly related to the severity of gait disturbances in PD. This region may represent a target for the development of therapeutic interventions for PD‐related gait disturbances. © 2012 Movement Disorder Society
Maternal B vitamin status in pregnancy week 18 according to reported use of folic acid supplements
Authors: Bjørke‐Monsen Anne Lise , Roth Christine , Magnus Per , Midttun Øivind , Nilsen Roy M. , Reichborn‐Kjennerud Ted , Stoltenberg Camilla , Susser Ezra , Vollset Stein Emil , Ueland Per Magne
Published: September 2012

Scope

Epidemiological studies on the association between pregnancy outcomes and use of periconceptional folic acid are often based on maternal reported intake. Use of folic acid during pregnancy is associated with a higher socioeconomic status known to have an impact on diet quality. We have studied plasma B vitamin status according to reported use of folic acid supplements during the periconceptional period in Norwegian women.

Methods and results

Plasma levels of folate, cobalamin, pyridoxal 5′‐phosphate (vitamin B6), riboflavin, and the metabolic markers total homocysteine, methylmalonic acid and 3‐hydro‐xykynurenine were measured in pregnancy week 18 and related to reported intake of folic acid from 4 weeks prior to conception throughout week 18 in 2911 women from the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health.

Being a folic acid user during the periconceptional period was associated with a better socioeconomic status, and a higher intake of several micronutrients, including vitamins, trace‐metals, and omega 3 fatty acids. Folic acid users had a significantly better plasma B vitamin status.

Conclusion

Epidemiological data based on maternal reported intake of folic acid supplements during pregnancy, should take into account the numerous nutritional implications, in addition to higher blood folate levels, of being a folic acid user.
Differential gene expression and methylation in the retinoid/PPARA pathway and of tumor suppressors may modify intestinal tumorigenesis induced by low folate in mice
Authors: Leclerc Daniel , Cao Yuanhang , Deng Liyuan , Mikael Leonie G. , Wu Qing , Rozen Rima
Published: September 2012

Scope

Inadequate folate intake increases risk for colorectal cancer. We previously showed that low‐folate diets induced intestinal tumors in BALB/c mice, but not in C57BL/6 mice. We suggested that DNA damage, altered methylation, and reduced apoptosis could contribute to tumorigenesis in this model.

Methods and results

To identify genes involved in tumorigenesis, we compared gene expression profiles in preneoplastic intestine of BALB/c and C57BL/6 mice‐fed low folate. We identified 74 upregulated and 90 downregulated genes in BALB/c compared to C57BL/6 mice. We validated decreased expression of Bcmo1 and increased expression of Aldh1a, which would be expected to upregulate the peroxisome proliferator‐activated receptor alpha (PPARA) pathway, and confirmed the expected upregulation of several Ppara downstream genes. We verified, in BALB/c mice, reduced expression of Sprr2a, a gene that increases resistance to oxidative damage, and of two oncosuppressors (Bmp5 and Arntl). Low folate increased Ppara and Aldh1a1 expression, and decreased Bcmo1, Sprr2a, and Bmp5 expression in BALB/c, compared to BALB/c on control diets. Bcmo1, Ppara, and Bmp5 showed differential DNA methylation related to strain, diet, and/or Mthfr genotype.

Conclusion

Disturbed regulation of the retinoid/PPARA pathway, which influences oxidative damage, and altered expression of tumor suppressors may contribute to intestinal tumorigenesis induced by low‐folate intake.
Myocardial T2‐mapping and velocity mapping: Changes in regional left ventricular structure and function after heart transplantation
Authors: Markl Michael , Rustogi Rahul , Galizia Mauricio , Goyal Amita , Collins Jeremy , Usman Asad , Jung Bernd , Foell Daniela , Carr James
Published: September 2012

Monitoring post cardiac transplant (TX) status relies on frequent invasive techniques such as endomyocardial biopsies and right heart cardiac catheterization. The aim of this study was to noninvasively evaluate regional myocardial structure, function, and dyssynchrony in TX patients. Myocardial T2‐mapping and myocardial velocity mapping of the left ventricle (basal, midventricular, and apical short‐axis locations) was applied in 10 patients after cardiac transplantation (49 ± 13years, n = 2 with signs of mild rejection, time between TX and MRI = 1–64 months) and compared to healthy controls (n = 20 for myocardial velocity mapping and n = 14 for T2). Segmental analysis based on the 16‐segment American Heart Association model revealed increased T2 (P = 0.0003) and significant (P < 0.0001) reductions in systolic and diastolic radial and long‐axis peak myocardial velocities in TX patients without signs of rejection compared to controls. Multiple comparisons of individual left ventricular segments demonstrated reductions of long‐axis peak velocities in 50% of segments (P < 0.001) while segmental T2 values were not significantly different. Systolic radial as well as diastolic radial and long‐axis dyssynchrony were significantly (P < 0.04) increased in TX patients indicating less coordinated contraction, expansion, and lengthening. Correlation analysis revealed moderate but significant (P < 0.010) inverse relationships between myocardial T2 and long‐axis peak velocities suggesting a structure–function relationship between altered T2 and myocardial function. Magn Reson Med 70:517–526, 2013. © 2012 Wiley Periodicals, Inc.
Quantitative Bayesian model‐based analysis of amide proton transfer MRI
Authors: Chappell Michael A. , Donahue Manus J. , Tee Yee Kai , Khrapitchev Alexandre A. , Sibson Nicola R. , Jezzard Peter , Payne Stephen J.
Published: September 2012

Amide Proton Transfer (APT) reports on contrast derived from the exchange of protons between amide groups and water. Commonly, APT contrast is quantified by asymmetry analysis, providing an ensemble contrast of both amide proton concentration and exchange rate. An alternative is to sample the off‐resonant spectrum and fit an exchange model, permitting the APT effect to be quantified, correcting automatically for confounding effects of spillover, field inhomogeneity, and magnetization transfer. Additionally, it should permit amide concentration and exchange rate to be independently quantified. Here, a Bayesian method is applied to this problem allowing pertinent prior information to be specified. A three‐pool model was used incorporating water protons, amide protons, and magnetization transfer effect. The method is demonstrated in simulations, creatine phantoms with varying pH and in vivo (n = 7). The Bayesian model‐based approach was able to quantify the APT effect accurately (root‐mean‐square error < 2%) even when subject to confounding field variation and magnetization transfer effect, unlike traditional asymmetry analysis. The in vivo results gave approximate APT concentration (relative to water) and exchange rate values of 3 × 10−3 and 15 s−1. A degree of correlation was observed between these parameter making the latter difficult to quantify with absolute accuracy, suggesting that more optimal sampling strategies might be required. Magn Reson Med 70:556–567, 2013. © 2012 Wiley Periodicals, Inc.
Experimental and theoretical investigation of the high‐pressure, undrained response of a cohesionless sand
Authors: Martin B.E. , Cazacu O.
Published: September 2012

Key in predicting stability in sands during dynamic events is gaining a fundamental understanding of the physics of its deformation and failure at high pressures. In this paper are reported results of an experimental investigation into the high‐pressure (up to 700 MPa) mechanical response of Quikrete sand. During all triaxial compression tests, the material exhibited hardening up to failure while both compressibility and dilatancy regimes of the volumetric response were observed. Furthermore, the transition from compressibility to dilatancy was found to be highly dependent on confining pressure. By performing triaxial compression tests with several creep stages followed by unloading–reloading cycles, the time influence of the overall response was detected. Using the experimental data, a new model that captures both compressibility and dilatancy has been developed. Comparison between model predictions and data showed that the proposed model describes well the main characteristics of the high‐pressure response of sand. Copyright © 2012 John Wiley & Sons, Ltd.
Emerging philanthropy markets
Authors: Michon Richard , Tandon Atul
Published: September 2012

Entrepreneurs are not the only ones to salivate at the call of emerging markets. Major nonprofit organizations that raise money in high‐income Organisation for Economic Co‐operation and Development countries for redistribution in developing countries are also looking for new sources of funds. Some of the countries that benefited from private philanthropy not too long ago are now in a position to help. The contribution of this paper is two‐prong. First, it introduces a robust market screening methodology to determine countries' capacities to give on the basis of macroeconomic and infrastructure indicators. Second, it identifies cross‐cultural predictors for charitable donations taken from the World Value Survey. A logistic regression calibrated on already successful fundraising operation scores countries on their propensity for private philanthropy. Research findings receive theoretical support from Max Weber's Protestant Ethic and the Spirit of Capitalism. Top countries for private philanthropy are of Protestant tradition and are at the origin of capitalism, as we know it today. Confucian countries that share a similar ethic and have opted for capitalist economies are first class candidates for private philanthropy.

Copyright © 2012 John Wiley & Sons, Ltd.
Survey of patients on an alcohol in‐patient unit in relation to group therapeutic factors
Authors: Ogilvie Sheena S , Blair Sheena EE , Paul Anna Louise
Published: September 2012

This study was prompted by the clinical research of Lovett and Lovett (1991) and Yalom's theory of group therapy (Yalom, 1985). The investigators examined perceptions of therapeutic factors in groups, in relation to outcome measures. Twenty‐one patients admitted consecutively to an Alcohol Problems clinic engaged in a three‐week programme, led by an interdisciplinary treatment team, including occupational therapy‐led groups, were interviewed using an ‘important events’ questionnaire in the second and third week. A modified version of Yalom's therapeutic factor questionnaire was used at the end of the programme and patients were also asked if they had additional comments. Outcome factors were assessed at three months after discharge from reports by key workers and self‐report. Results indicated that patients most valued existential factors, self‐understanding, cohesiveness and catharsis. Existential factors were not identified as helpful by the group who were unchanged and continued to drink. The implications for occupational therapy in the treatment of alcohol problems were discussed.
Harnessing monocyte‐derived macrophages to control central nervous system pathologies: no longer ‘if’ but ‘how’
Authors: Shechter Ravid , Schwartz Michal
Published: September 2012

The central nervous system (CNS) tissues, including the brain, the eye, and the spinal cord, are immune‐privileged, secluded from the circulation by a complex of barriers, and equipped with their own myeloid cell population, the resident microglia. Based on the classical perspective of immune–brain interactions and on the contribution of such interactions to the progression of multiple sclerosis, an autoimmune inflammatory disease of the CNS, infiltrating macrophages were traditionally viewed as an enemy of the nervous system. However, over the past two decades, research has revealed the pivotal role of monocyte‐derived macrophages in CNS repair, and opened up a new era in understanding and treating CNS pathologies. Here, we gather current knowledge regarding macrophage broad spectrum of activities in the CNS, whose two poles correspond to the classical pro‐inflammatory M1 and the ‘alternatively‐activated’ M2 cells previously described in various non‐CNS pathologies, and their diverse, multi‐functional contribution in various neurological conditions, ranging from acute traumas to neurodegenerative disorders, and autoimmune diseases. The diverse functions are manifested by induction and resolution of inflammation as well as their involvement in neural tissue regeneration and renewal, matrix remodelling, debris clearance, and angiogenesis. A special focus is devoted to current evidence suggesting that resident microglia and infiltrating monocyte‐derived macrophages are functionally non‐redundant cell types. Taken together, these recent advances reveal a dramatic therapeutic opportunity for controlled harnessing of macrophages for repair of the damaged CNS following acute insults, in neurodegenerative conditions, and in psychiatric disorders.
Hanging in the balance: endogenous anti‐inflammatory mechanisms in tissue repair and fibrosis
Authors: Ariel Amiram , Timor Orly
Published: September 2012

Inflammation is the physiological response to tissue injury caused by pathogens or trauma. Nevertheless, inflammation should be resolved in a timely manner, resulting in elimination of the inflammatory cells and mediators from the injured tissue, to avoid its deleterious consequences. Uncontrolled inflammation can lead to inflammatory, autoimmune, and cancerous disorders that are the result of improper resolution. The healing of the injured tissue during the termination of inflammation must also be tightly controlled since excessive tissue repair can lead to fibrosis and scarring of the affected organ. In the last three decades, it has been revealed that the resolution of inflammation is tightly orchestrated by specific cells, protein, and lipid mediators that are produced at proper timing and distinct locations. The bioactivity of these anti‐inflammatory, pro‐resolving, and immunoregulatory agents results in clearance of the tissue from inflammatory leukocytes and their products, and the return of homeostatic tissue architecture and function. Here, we will survey the current endogenous mechanisms governing the resolution of inflammation and directing it towards injury healing and halting of acquired immune responses while preventing excessive tissue repair and fibrosis. We focus on the role played by apoptotic polymorphonuclear cells (PMNs), 15‐lipoxygenase (LO)‐derived lipid mediators, and TGFβ in this macrophage‐governed decision‐making process and suggest new modes of action for fibrosis prevention and return to homeostasis.
Transcriptome and small RNA deep sequencing reveals deregulation of miRNA biogenesis in human glioma
Authors: Moore Lynette M , Kivinen Virpi , Liu Yuexin , Annala Matti , Cogdell David , Liu Xiuping , Liu Chang‐Gong , Sawaya Raymond , Yli‐Harja Olli , Shmulevich Ilya , Fuller Gregory N , Zhang Wei , Nykter Matti
Published: September 2012

Altered expression of oncogenic and tumour‐suppressing microRNAs (miRNAs) is widely associated with tumourigenesis. However, the regulatory mechanisms underlying these alterations are poorly understood. We sought to shed light on the deregulation of miRNA biogenesis promoting the aberrant miRNA expression profiles identified in these tumours. Using sequencing technology to perform both whole‐transcriptome and small RNA sequencing of glioma patient samples, we examined precursor and mature miRNAs to directly evaluate the miRNA maturation process, and examined expression profiles for genes involved in the major steps of miRNA biogenesis. We found that ratios of mature to precursor forms of a large number of miRNAs increased with the progression from normal brain to low‐grade and then to high‐grade gliomas. The expression levels of genes involved in each of the three major steps of miRNA biogenesis (nuclear processing, nucleo‐cytoplasmic transport, and cytoplasmic processing) were systematically altered in glioma tissues. Survival analysis of an independent data set demonstrated that the alteration of genes involved in miRNA maturation correlates with survival in glioma patients. Direct quantification of miRNA maturation with deep sequencing demonstrated that deregulation of the miRNA biogenesis pathway is a hallmark for glioma genesis and progression. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
A novel blueprint for ‘top down’ differentiation defines the cervical squamocolumnar junction during development, reproductive life, and neoplasia
Authors: Herfs Michael , Vargas Sara O , Yamamoto Yusuke , Howitt Brooke E , Nucci Marisa R , Hornick Jason L , Mckeon Frank D , Xian Wa , Crum Christopher P
Published: September 2012

The cervical squamocolumnar (SC) junction is the site of a recently discovered ‘embryonic’ cell population that was proposed as the cell of origin for cervical cancer and its precursors. How this population participates in cervical remodelling and neoplasia is unclear. In the present study, we analysed the SC junction immunophenotype during pre‐ and post‐natal human and mouse development and in the adult, processes of metaplastic evolution of the SC junction, microglandular change, and early cervical neoplasia. Early in life, embryonic cervical epithelial cells were seen throughout the cervix and subsequently diminished in number to become concentrated at the SC junction in the adult. In all settings, there was a repetitive scenario in which cuboidal embryonic/SC junction cells gave rise to subjacent metaplastic basal/reserve cells with a switch from the SC junction positive to negative immunophenotype. This downward or basal (rather than upward or apical) evolution from progenitor cell to metaplastic progeny was termed reverse or ‘top down’ differentiation. A similar pattern was noted in high‐grade squamous intraepithelial lesions (HSILs), suggesting that HPV infection of the cuboidal SC junction cells initiated outgrowth of basally‐oriented neoplastic progeny. The progressive loss of the embryonic/SC junction markers occurred with ‘top down’ differentiation during development, remodelling, and early neoplasia. Interestingly, most low‐grade SILs were SC junction‐negative, implying infection of metaplastic progeny rather than the original SC junction cells. This proposed model of ‘top down’ differentiation resolves the mystery of how SC junction cells both remodel the cervix and participate in neoplasia and provides for a second population of metaplastic progeny (including basal and reserve cells), the infection of which is paradoxically less likely to produce a biologically aggressive precursor. It also provides new targets in animal models to determine why the SC junction is uniquely susceptible to carcinogenic HPV infection. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prevalence and correlates of exceeding the labeled maximum dose of acetaminophen among adults in a U.S.‐based internet survey
Authors: Kaufman David W , Kelly Judith P , Rohay Jeffrey M , Malone Mary Kathryn , Weinstein Rachel B , Shiffman Saul
Published: September 2012

Purpose

Acetaminophen is a commonly used analgesic; excessive doses can lead to liver damage. We sought to determine the proportion of acetaminophen users exceeding the recommended maximum daily dose of 4 g and identify correlates of such behavior.

Methods

U.S. adults were recruited from an internet panel in summer 2010, oversampling past 30‐day acetaminophen users. Among 47 738 starting the study, 5649 completed all phases; individuals with low education were underrepresented. Subjects completed a 7‐day daily diary online, reporting intake of acetaminophen products selected from a comprehensive list; total daily dose was computed from product names. An exit survey elicited: attitudes/knowledge related to product ingredients, label reading, dosing behavior; demographics, medical history, general physical, and mental health status. Unconditional logistic regression identified variables independently associated with use exceeding 4 g.

Results

Among 3618 acetaminophen users, 163 took >4 g on ≥1 day (4.5%); the median dose was 5.5 g; 26 took >8 g (0.7%). >4‐g users were characterized by chronic pain, poor physical status, and heavy use of medical care. Knowledge of ingredients and recommended OTC doses for all products taken was inversely associated with >4‐g use (multivariable odds ratios [ORs] = 0.5–0.6), as was the attitude to start with the lowest dose (OR = 0.6). The attitude that users could choose their own dose was positively associated (OR = 1.3).

Conclusions

The results estimate the proportion of acetaminophen users exceeding 4 g in a group of U.S. adults, identify potentially modifiable attitudes and knowledge associated with such use, and characterize subpopulations at higher risk. Copyright © 2012 John Wiley & Sons, Ltd.
Survey of the camel urinary proteome by shotgun proteomics using a multiple database search strategy
Authors: Alhaider Abdulqader A. , Bayoumy Nervana , Argo Evelyn , Gader Abdel G. M. A. , Stead David A.
Published: September 2012

We report the first survey of the dromedary camel urinary proteome. Proteins retained from ultrafiltration of urine were analysed by GeLC‐MS/MS (SDS‐PAGE followed by LC‐MS/MS). In the absence of a complete camel genome sequence, the number of protein identifications was maximised by searching three primary sequence databases: Swiss‐Prot, alpaca and camel EST. This search strategy enabled the identification of 1274 peptide sequences, of which 735 were found in at least two independent samples. Functional annotations for proteins identified from alpaca and camel EST sequences were mapped from basic local alignment search tool (protein) searches. These 735 peptides, which included many novel sequences found only in the camel EST database, were grouped to 147 protein descriptors. Gene ontology term analysis of human proteins with sequence similarity showed that camel urine may be particularly enriched in proteins from extracellular compartments and vesicles, and with functions that include carbohydrate‐binding and peptidase inhibitor activities. If their biological functions are conserved between species, many of the camel urinary proteins could be involved in various stress and immune responses, and some may have antimicrobial activities.