bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternation-Trading Proofs, Linear Programming, and Lower Bounds
Authors: Williams Ryan
Published: July 2013

A fertile area of recent research has demonstrated concrete polynomial-time lower bounds for natural hard problems on restricted computational models. Among these problems are Satisfiability, Vertex Cover, Hamilton Path, MOD
6
-SAT, Majority-of-Majority-SAT, and Tautologies, to name a few. The proofs of these lower bounds follow a proof-by-contradiction strategy that we call
resource trading
or
alternation trading
. An important open problem is to determine how powerful such proofs can possibly be.

We propose a methodology for studying these proofs that makes them amenable to both formal analysis and automated theorem proving. We prove that the search for better lower bounds can often be turned into a problem of solving a large series of linear programming instances. Implementing a small-scale theorem prover based on these results, we extract new human-readable time lower bounds for several problems and identify patterns that allow for further generalization. The framework can also be used to prove concrete limitations on the current techniques.
On Approximating the Number of Relevant Variables in a Function
Authors: Ron Dana , Tsur Gilad
Published: July 2013

In this work we consider the problem of approximating the number of relevant variables in a function given query access to the function. Since obtaining a multiplicative factor approximation is hard in general, we consider several relaxations of the problem. In particular, we consider a relaxation of the property testing variant of the problem and we consider relaxations in which we have a promise that the function belongs to a certain family of functions (e.g., linear functions). In the former relaxation the task is to distinguish between the case that the number of relevant variables is at most
k
, and the case in which it is far from any function in which the number of relevant variables is more than (1 + 
γ
)
k
for a parameter
γ
. We give both upper bounds and almost matching lower bounds for the relaxations we study.
Increased ventricular stiffness and decreased cardiac function in Atlantic cod (Gadus morhua) at high temperatures
Authors: Syme Douglas A. , Gamperl A. Kurt , Nash Gordon W. , Rodnick Kenneth J.
Published: July 2013

We employed the work loop method to study the ability of ventricular and atrial trabeculae from Atlantic cod to sustain power production during repeated contractions at acclimation temperatures (10°C) and when acutely warmed (20°C). Oxygen tension (Po2) was lowered from 450 to 34% air saturation to augment the thermal stress. Preparations worked under conditions simulating either a large stroke volume (35 contractions/min rate, 8–12% muscle strain) or a high heart rate (70 contractions/min, 2–4% strain), with power initially equal under both conditions. The effect of declining Po2on power was similar under both conditions but was temperature and tissue dependent. In ventricular trabeculae at 10°C (and atria at 20°C), shortening power declined across the full range of Po2studied, whereas the power required to lengthen the muscle was unaffected. Conversely, in ventricular trabeculae at 20°C, there was no decline in shortening power but an increase in lengthening power when Po2fell below 100% air saturation. Finally, when ventricular trabeculae were paced at rates of up to 115 contractions/min at 20°C (vs. the maximum of 70 contractions/min in vivo), they showed marked increases in both shortening and lengthening power. Our results suggest that although elevated heart rates may not impair ventricular power as they commonly do isometric force, limited atrial power and the increased work required to expand the ventricle during diastole may compromise ventricular filling and hence, stroke volume in Atlantic cod at warm temperatures. Neither large strains nor high contraction rates convey an apparent advantage in circumventing this.
Whole body acid-base and fluid-electrolyte balance: a mathematical model
Authors: Wolf Matthew B.
Published: July 2013

A cellular compartment was added to our previous mathematical model of steady-state acid-base and fluid-electrolyte chemistry to gain further understanding and aid diagnosis of complex disorders involving cellular involvement in critically ill patients. An important hypothesis to be validated was that the thermodynamic, standard free-energy of cellular H+and Na+pumps remained constant under all conditions. In addition, a hydrostatic-osmotic pressure balance was assumed to describe fluid exchange between plasma and interstitial fluid, including incorporation of compliance curves of vascular and interstitial spaces. The description of the cellular compartment was validated by close comparison of measured and model-predicted cellular pH and electrolyte changes in vitro and in vivo. The new description of plasma-interstitial fluid exchange was validated using measured changes in fluid volumes after isoosmotic and hyperosmotic fluid infusions of NaCl and NaHCO3. The validated model was used to explain the role of cells in the mechanism of saline or dilutional acidosis and acid-base effects of acidic or basic fluid infusions and the acid-base disorder due to potassium depletion. A module was created that would allow users, who do not possess the software, to determine, for free, the results of fluid infusions and urinary losses of water and solutes to the whole body.
Measurement of glomerular filtration rate during flight in a migratory bird using a single bolus injection of FITC-inulin
Authors: Gerson Alexander R. , Guglielmo Christopher G.
Published: July 2013

During migration, passerine birds typically complete a series of multi-hour flights, each followed by a period of stopover. During flight, rates of respiratory water loss are high, yet these birds show no signs of dehydration after flights. During stopover, birds become hyperphagic to replenish fat reserves, often consuming food with high water content, such as fruit. Thus migratory birds seem to face an osmoregulatory challenge; they must reduce water losses during flight but retain the ability to excrete large quantities of water while maintaining osmotic balance at stopover. Our goal was to measure glomerular filtration rate (GFR) and fractional water reabsorption (FWR) of a migratory bird in free flight, at rest, and during feeding to assess the role of the kidney in maintaining water balance during migration. We used FITC-inulin and one- and two-phase exponential decay models to first validate a technique and then measure GFR in the Swainson's thrush, a small (∼30 g) songbird. Single-phase exponential decay models and the modified slope intercept method overestimated GFR by 26% compared with two-phase exponential decay models. We found no differences in GFR among fed, resting and flying birds, but FWR was significantly higher in resting and flying birds relative to feeding birds. There was no effect of the rate of respiratory water loss on GFR or FWR in flight. These data support the idea that birds in flight do not dramatically alter GFR but rely on increased FWR to minimize excretory water losses.
Injured kidney endothelium is only marginally repopulated by cells of extrarenal origin
Authors: Schirutschke Holger , Vogelbacher Regina , Stief Andrea , Parmentier Simon , Daniel Christoph , Hugo Christian
Published: July 2013

The role of bone marrow marrow-derived cells after kidney endothelial injury is controversial. In this study, we investigated if and to what extent extrarenal cells incorporate into kidney endothelium after acute as well as during chronic endothelial injury. Fischer F-344 wt (wild type) rat kidney grafts were transplanted into R26- hPAP (human placental alkaline phosphatase) transgenic Fischer F-344 recipient rats to allow identification of extrarenal cells by specific antibody staining. A severe model of renal thrombotic microangiopathy was induced via graft perfusion with antiglomerular endothelial cell (GEN) antibody and resulted in eradication of 85% of the glomerular and 69% of the peritubular endothelium (GEN group). At week 4 after injury, renal endothelial healing as well as recovery of the kidney function was seen. Endothelial chimerism was evaluated by double staining for hPAP and endothelial markers RECA-1 or JG-12. Just 0.25% of the glomerular and 0.1% of the peritubular endothelium was recipient derived. In a second experiment, chronic endothelial injury was induced by combination of kidney transplantation with 5/6 nephrectomy (5/6 Nx group). After 14 wk, only 0.86% of the peritubular and 0.05% of the glomerular endothelium was of recipient origin. In summary, despite demonstration of extensive damage and loss as well as excellent regeneration, just a minority of extrarenal cells were incorporated into kidney endothelium in rat models of acute and chronic renal endothelial cell injury. Our results highlight that kidney endothelial regeneration after specific and severe injury is almost exclusively of renal origin.
Participation of a persistent sodium current and calcium-activated nonspecific cationic current to burst generation in trigeminal principal sensory neurons
Authors: Tsuruyama Kentaro , Hsiao Chie-Fang , Chandler Scott H.
Published: July 2013

The properties of neurons participating in masticatory rhythmogenesis are not clearly understood. Neurons within the dorsal trigeminal principal sensory nucleus (dPrV) are potential candidates as components of the masticatory central pattern generator (CPG). The present study examines in detail the ionic mechanisms controlling burst generation in dPrV neurons in rat (postnatal day 8–12) brain stem slices using whole cell and perforated patch-clamp methods. Nominal extracellular Ca2+ concentration transformed tonic discharge in response to a maintained step pulse of current into rhythmical bursting in 38% of nonbursting neurons. This change in discharge mode was suppressed by riluzole, a persistent Na+ current ( INaP) antagonist. Veratridine, which suppresses the Na+ channel inactivation mechanism, induced rhythmical bursting in nonbursting neurons in normal artificial cerebrospinal fluid, suggesting that INaP contributes to burst generation. Nominal extracellular Ca2+ exposed a prominent afterdepolarizing potential (ADP) following a single spike induced by a 3-ms current pulse, which was suppressed, but not completely blocked, by riluzole. Application of BAPTA, a Ca2+ chelator, intracellularly, or flufenamic acid, a Ca2+-activated nonspecific cationic channel ( ICAN) antagonist, extracellularly to the bath, suppressed rhythmical bursting and the postspike ADP. Application of drugs to alter Ca2+ release from endoplasmic reticulum also suppressed bursting. Finally, voltage-clamp methods demonstrated that nominal Ca2+ facilitated INaP and induced ICAN. These data demonstrate for the first time that the previously observed induction in dPrV neurons of rhythmical bursting in nominal Ca2+ is mediated by enhancement of INaP and onset of ICAN, which are dependent on intracellular Ca2+.
Are Onconeural Antibodies a Clinical Phenomenology in Paraneoplastic Limbic Encephalitis?
Authors: Zhang Hongliang , Zhou Chunkui , Wu Limin , Ni Fengming , Zhu Jie , Jin Tao
Published: July 2013

Paraneoplastic neurological syndromes (PNSs) occur in patients with cancer and can cause clinical symptoms and signs of dysfunction of the nervous system that are not due to a local effect of the tumor or its metastases. Most of these clinical syndromes in adults are associated with lung cancer, especially small cell lung cancer (SCLC), lymphoma, and gynecological tumors. The finding of highly specific antibodies directed against onconeural antigens has revolutionized the diagnosis and promoted the understanding of these syndromes and led to the current hypothesis of an autoimmune pathophysiology. Accumulating data strongly suggested direct pathogenicity of these antibodies. The field of PNS has expanded rapidly in the past few years with the discovery of limbic encephalitis associated with glutamic acid decarboxylase (GAD) 65, the voltage (VGKC-gated potassium channel) complex, the methyl (N-NMDA-D-aspartate), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and gamma aminobutyric acid (GABA) (B) receptors, and so forth. Despite this, the clinical spectrum of these diseases has not yet been fully investigated. The clinical importance of these conditions lies in their frequent response to immunotherapies and, less commonly, their association with distinctive tumors. This review provides an overview on the pathogenesis and diagnosis of PNS, with emphasis on the role of antibodies in limbic encephalitis.
The Influence of Gene-Gene and Gene-Environment Interactions on the Risk of Asbestosis
Authors: Franko A. , Dolžan V. , Arnerić N. , Dodič-Fikfak M.
Published: July 2013

This study investigated the influence of gene-gene and gene-environment interactions on the risk of developing asbestosis. The study comprised 262 cases with asbestosis and 265 controls with no asbestos-related disease previously studied forMnSOD,ECSOD,CAT,GSTT1,GSTM1,GSTP1, andiNOSpolymorphisms. Data on cumulative asbestos and smoking were available for all subjects. To assess gene-gene and gene-environmental interactions, logistic regression was used. The associations betweenMnSODAla −9Val polymorphism and the risk of asbestosis and betweeniNOSgenotypes and asbestosis were modified byCAT–262 C > T polymorphism (P=0.038;P=0.031). A strong interaction was found betweenGSTM1-null polymorphism and smoking (P=0.007),iNOS(CCTTT)npolymorphism and smoking (P=0.054), and betweeniNOS(CCTTT)npolymorphism and cumulative asbestos exposure (P=0.037). The findings of this study suggest that the interactions between different genotypes, genotypes and smoking, and between genotypes and asbestos exposure have an important influence on the development of asbestosis and should be seriously considered in future research on occupational/environmental asbestos-related diseases.
Hyperglycemia Induces Altered Expressions of Angiogenesis Associated Molecules in the Trophoblast
Authors: Chang Shu-Chun , Vivian Yang Wei-Chung
Published: July 2013

We previously reported that the increased level of perlecan with altered glycosaminoglycan (GAG) substitution was present in the placenta with gestational diabetes mellitus (GDM) and in the trophoblasts cultured under hyperglycemic condition. Trophoblast is the first cell lineage to differentiate, invasive, and migrate into the vessel tissues of placenta and fetal membrane during pregnancy. Therefore, active matrix remodeling and vessel formation must occur during placentation. In this study, we further investigated whether hyperglycemia-induced alterations of perlecan in the extracellular matrix (ECM) affect the proliferation and the expressions of angiogenesis-related growth factors and cytokines in the trophoblasts. 3A-Sub-E trophoblastic cells cultured in high glucose medium were conducted to mimic the hyperglycemic condition. Results showed that the hyperglycemia-induced GAG alterations in the cell surface perlecan as well as in the ECM indeed upregulated the expressions of IL-6, IL-8, and MCP-1 and the activities of MMP-2 and MMP-9 and downregulated the expressions of TIMP-2. A regulatory molecular mechanism of hyperglycemia-induced alterations of the cell surface proteoglycans and the ECM remodeling on the expressions of angiogenesis-related cytokines and growth factors in trophoblasts was proposed. This mechanism may contribute to the aberrant placental structure and the maternal and fetal complications during development.
A Scientific Validation of Antihyperglycemic and Antihyperlipidemic Attributes of Trichosanthes dioica
Authors: Rai Prashant Kumar , Gupta Sharad Kumar , Srivastava Amrita Kumari , Gupta Rajesh Kumar , Watal Geeta
Published: July 2013

The present study was undertaken to scientifically validate the antidiabetic activity of aqueous fruit extract of Trichosanthes dioica Roxb. (Family: Cucurbitaceae) which has been traditionally used for managing diabetes mellitus. This plant commonly known as “Sespadula” in English has not been explored scientifically so far for its glycemic potential except by our research group. The study was conducted with variable doses on normal, mild, and severe diabetics models, and several biochemical parameters including blood glucose level (BGL) were assessed. Maximum fall in BGL of 23.8% in normal rats and of 31.3% in mild diabetic rats was observed during their fasting blood glucose (FBG) and glucose tolerance test (GTT) with the dose of 1000 mg kg−1. In severely diabetic animals after 4 weeks treatment with FBG, postprandial glucose, total cholesterol, and triglyceride levels were reduced by 28.7, 30.7, 57.2, and 18.5%, whereas high density lipoprotein, total protein, hemoglobin, and body weight were increased by 33.0, 36.7, 15.7 and 16.7%, respectively. Moreover, urine sugar was reduced from +4 to +1. Thus, the study scientifically validates the traditional use of T. diocia in diabetes management and could be developed as an effective oral agent for treating diabetes mellitus and complications associated with it.
Land Cover Mapping Based on Multisource Spatial Data Mining Approach for Climate Simulation: A Case Study in the Farming-Pastoral Ecotone of North China
Authors: Wu Feng , Zhan Jinyan , Yan Haiming , Shi Chenchen , Huang Juan
Published: July 2013

The land use and land cover change (LUCC) is one of the prime driving forces of climate change. Most attention has been paid to the influence of accuracy of the land cover data in numerous climate simulation projects. The accuracy of the temporal land use data from Chinese Academy of Sciences (CAS) is higher than 90%, but the high-precision land cover data is absent. We overlaid land cover maps from different sources, and the grids with consistent classification were selected as the sample grids. By comparing the results obtained with different decision tree classifiers with the WEKA toolkit for data mining, it was found that the C4.5 algorithm was more suitable for converting land use data of CAS classification to land cover data of IGBP classification. We reset the decision rules with Net Primary Productivity (NPP) and Normalized Difference Vegetation Index (NDVI) as the indicators. The accuracy of the reclassified land cover data was proven to reach 83.14% through comparing with the Terrestrial Ecosystem Monitoring Sites and high resolution images. Therefore, it is feasible to produce the temporal land cover data with this method, which can be used as the parameters of dynamical downscaling in the regional climate simulation.
Pseudoaneurysm of the Anterior Tibial Artery following Tibio-Talar-Calcaneum Fusion with a Retrograde Nail: A Rare Case and Literature Review
Authors: Craxford Simon , Karuppiah Saravana V. , Milner Stephen
Published: July 2013

This study reports the case of an 87-year-old woman who presented with a nonresolving haematoma 13 weeks following tibiotalar arthrodesis surgery on her right ankle using a retrograde nail. This was revealed by angiography to be a pseudoaneurysm of the anterior tibial artery. The patient subsequently underwent endovascular stenting of the pseudoaneurysm and has had a successful recovery. This case highlights the need for awareness of both the normal arterial supply to the leg and ankle as well as the potential for anatomical variations. Arterial variation may be as high as 6.7% based on published findings from cadaveric studies. As pseudoaneurysm is a rare complication, a high index of suspicion is needed in order to avoid a missed or delayed diagnosis. We urge surgeons to keep in mind the potential for pseudoaneurysm when a patient presents with a nonresolving haematoma and arrange appropriate further investigations as needed.
Proximate Analysis of Five Wild Fruits of Mozambique
Authors: Magaia Telma , Uamusse Amália , Sjöholm Ingegerd , Skog Kerstin
Published: July 2013

Mozambique is rich in wild fruit trees, most of which produce fleshy fruits commonly consumed in rural communities, especially during dry seasons. However, information on their content of macronutrients is scarce. Five wild fruit species (Adansonia digitata, Landolphia kirkii, Sclerocarya birrea, Salacia kraussii, and Vangueria infausta) from different districts in Mozambique were selected for the study. The contents of dry matter, fat, protein, ash, sugars, pH, and titratable acidity were determined in the fruit pulps. Also kernels of A. digitata and S. birrea were included in the study. The protein content in the pulp was below 5 g/100 g of dry matter, but a daily intake of 100 g fresh wild fruits would provide up to 11% of the recommended daily intake for children from 4 to 8 years old. The sugar content varied between 2.3% and 14.4% fresh weight. The pH was below 3, except for Salacia kraussii, for which it was slightly below 7. Kernels of A. digitata contained, on average, 39.2% protein and 38.0% fat, and S. birrea kernels 32.6% protein and 60.7% fat. The collection of nutritional information may serve as a basis for increased consumption and utilization.
Epidural Catheter Placement in Morbidly Obese Parturients with the Use of an Epidural Depth Equation prior to Ultrasound Visualization
Authors: Singh Sukhdip , Wirth Keith M. , Phelps Amy L. , Badve Manasi H. , Shah Tanmay H. , Sah Neera , Vallejo Manuel C.
Published: July 2013

Background. Previously, Balki determined the Pearson correlation coefficient with the use of ultrasound (US) was 0.85 in morbidly obese parturients. We aimed to determine if the use of the epidural depth equation (EDE) in conjunction with US can provide better clinical correlation in estimating the distance from the skin to the epidural space in morbidly obese parturients.
Methods. One hundred sixty morbidly obese (≥40 kg/m2) parturients requesting labor epidural analgesia were enrolled. Before epidural catheter placement, EDE was used to estimate depth to the epidural space. This estimation was used to help visualize the epidural space with the transverse and midline longitudinal US views and to measure depth to epidural space. The measured epidural depth was made available to the resident trainee before needle insertion. Actual needle depth (ND) to the epidural space was recorded. Results. Pearson’s correlation coefficients comparing actual (ND) versus US estimated depth to the epidural space in the longitudinal median and transverse planes were 0.905 (95% CI: 0.873 to 0.929) and 0.899 (95% CI: 0.865 to 0.925), respectively. Conclusion. Use of the epidural depth equation (EDE) in conjunction with the longitudinal and transverse US views results in better clinical correlation than with the use of US alone.
Synthesis of Coral‐Like, Straw‐Tied‐Like, and Flower‐Like Antimony Sulfides by a Facile Wet‐Chemical Method
Authors: Kavinchan Jutarat , Thongtem Titipun , Thongtem Somchai , Saksornchai Eksuree
Published: July 2013

Antimony sulfide (Sb2S3) was successfully synthesized from antimony chloride (SbCl3) and sodium thiosulfate pentahydrate (Na2S2O3·5H2O) in ethylene glycol (EG) without using any template by a facile wet‐chemical method. X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) show that the products were orthorhombic Sb2S3 nanorods forming the coral‐like, straw‐tied‐like, and flower‐like architectures with the nanorods growing along the [001] direction. The energy gap (Eg) was determined by UV‐visible absorption to be 1.52 eV.
A 22-Year-Old Female with Invasive Epithelioid Angiomyolipoma and Tumor Thrombus into the Inferior Vena Cava: Case Report and Literature Review
Authors: Grant Campbell , Lacy John M. , Strup Stephen E.
Published: July 2013

A 22-year-old female presented with back pain and was discovered to have a right-sided abdominal mass. Computed tomography (CT) scan revealed a 9 cm enhancing right upper pole renal mass with suspicion for tumor thrombus into the right renal vein and possibly the inferior vena cava (IVC). Magnetic resonance imaging (MRI) confirmed tumor thrombus into the inferior vena cava approximately 3 cm below the hepatic venous confluence. Open right radical nephrectomy with inferior vena cava thrombectomy was performed with removal of right kidney and tumor thrombus en bloc. Pathology revealed malignant epithelioid angiomyolipoma (EAML or PEComa). Epithelioid angiomyolipoma is a rare tumor of mesenchymal tissue that has the potential for local invasion and disease progression. Diagnosis of EAML was confirmed by pathology and immunohistochemistry. She was referred to medical oncology for discussion of surveillance versus potential adjuvant therapy and ultimately opted for close surveillance.
Spectral Galerkin Method in Space and Time for the 2Dg-Navier-Stokes Equations
Authors: Quyet Dao Trong
Published: July 2013

We prove theH2-stability andL2-error analysis of the spectral Galerkin method in space and time with the implicit/explicit Euler scheme for the 2Dg-Navier-Stokes equations in bounded domains when the initial data belong toH1.
Common Fixed Points for JH-Operators and Occasionally Weakly g-Biased Pairs under Relaxed Condition on Probabilistic Metric Space
Authors: Bhatt Arvind , Chandra Harish
Published: July 2013

We obtain some fixed point theorems for JH-operators and occasionally weakly g-biased maps on a setXtogether with the functionF:X×X→Δwithout using the triangle inequality and without using the symmetric condition. Our results extend the results of Bhatt et al. (2010).
Akt SUMOylation Regulates Cell Proliferation and Tumorigenesis
Authors: Li Rong , Wei Jie , Jiang Cong , Liu Dongmei , Deng Lu , Zhang Kai , Wang Ping
Published: July 2013

Proto-oncogene Akt plays essential roles in cell proliferation and tumorigenesis. Full activation of Akt is regulated by phosphorylation, ubiquitination, and acetylation. Here we report that SUMOylation of Akt is a novel mechanism for its activation. Systematically analyzing the role of lysine residues in Akt activation revealed that K276, which is located in a SUMOylation consensus motif, is essential for Akt activation. Ectopic or endogenous Akt1 could be modified by SUMOylation. RNA interference–mediated silencing of UBC9 reduced Akt SUMOylation, which was promoted by SUMO E3 ligase PIAS1 and reversed by the SUMO-specific protease SENP1. Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity. Interestingly, the cancer-derived mutant E17K in Akt1 that occurs in various cancers was more efficiently SUMOylated than wild-type Akt. Moreover, SUMOylation loss dramatically reduced Akt1 E17K–mediated cell proliferation, cell migration, and tumorigenesis. Collectively, our findings establish that Akt SUMOylation provides a novel regulatory mechanism for activating Akt function. Cancer Res; 73(18); 5742–53. ©2013 AACR.
Mitochondrial DNA Copy Number and Exposure to Polycyclic Aromatic Hydrocarbons
Authors: Pavanello Sofia , Dioni Laura , Hoxha Mirjam , Fedeli Ugo , Mielzynska-Švach Danuta , Baccarelli Andrea A.
Published: July 2013

Background: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic response to mtDNA damage and dysfunction, predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens and may cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA (nDNA) genotoxic effects are linked with increased mtDNAcn has never been evaluated.

Methods: We investigated the effect of chronic exposure to PAHs on mtDNAcn in peripheral blood lymphocytes (PBLs) of 46 Polish male noncurrent smoking coke-oven workers and 44 matched controls, who were part of a group of 94 study individuals examined in our previous work. Subjects' PAH exposure and genetic alterations were characterized through measures of internal dose (urinary 1-pyrenol), target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)–DNA adduct], genetic instability (micronuclei and telomere length), and DNA methylation (p53 promoter) in PBLs. mtDNAcn (MT/S) was measured using a validated real-time PCR method.

Results: Workers with PAH exposure above the median value (>3 μmol 1-pyrenol/mol creatinine) showed higher mtDNAcn [geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared with controls [GM 0.89 (unadjusted); 0.89 (age-adjusted); (P = 0.029 and 0.016)], as well as higher levels of genetic and chromosomal [i.e., anti-BPDE–DNA adducts (P < 0.001), micronuclei (P < 0.001), and telomere length (P = 0.053)] and epigenetic [i.e., p53 gene-specific promoter methylation (P < 0.001)] alterations in the nDNA. In the whole study population, unadjusted and age-adjusted mtDNAcn was positively correlated with 1-pyrenol (P = 0.043 and 0.032) and anti-BPDE–DNA adducts (P = 0.046 and 0.049).

Conclusions: PAH exposure and PAH-related nDNA genotoxicity are associated with increased mtDNAcn.

Impact: The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(10); 1722–9. ©2013 AACR.
Modified Technique for Inducing Posterior Vitreous Detachment through the Posterior Precortical Vitreous Pocket during Microincision Vitreous Surgery with a Wide-Angle Viewing System
Authors: Sato Taku , Kishi Shoji , Otani Tomohiro , Hashimoto Hideaki , Watanabe Goro
Published: July 2013

Purpose: To introduce a simple technique to create a posterior vitreous detachment (PVD) through the posterior precortical vitreous pocket (PPVP) during microincision vitreous surgery using a wide-angle viewing system (WAVS). Methods: This study included 20 eyes of 20 consecutive patients (mean age, 65.6 years; range, 56-76) with a stage 2 or 3 idiopathic macular hole who underwent 25-gauge microincision vitreous surgery using a WAVS and phacoemulsification surgery. A triamcinolone suspension was injected into the vitreous cavity. The triamcinolone facilitated visualization of the posterior wall of the PPVP. Using a vitreous cutter, we suctioned the outer margin of the PPVP. After a resultant small break of the posterior hyaloid membrane developed and enlarged rapidly, a PVD easily expanded at the periphery. Results: Using this technique, we induced a PVD without close proximity to the optic disk and macula. Conclusion: This technique is an easy and safe method for creating a PVD during microincision vitreous surgery using a WAVS.
Variability of Raltegravir Plasma Levels in the Clinical Setting
Authors: Fortuna Serena , Fabbiani Massimiliano , Digiambenedetto Simona , Ragazzoni Enzo , Lisi Lucia , Cauda Roberto , Navarra Pierluigi
Published: July 2013

Therapeutic drug monitoring of raltegravir Ctrough levels was carried out in the setting of the Raltegravir Switch for Toxicity or Adverse events (RASTA) trial, a randomized pilot study exploring a 48-week safety and efficacy of treatment switch to raltegravir associated with tenofovir/emtricitabine or abacavir/lamivudine in patients with regimens with optimal virologic control. Blood sampling for measurement of raltegravir plasma levels was carried out at weeks 4, 12, 24, 36 and 48. Plasma samples were analysed by a recently developed and validated UPLC-MS method. A total of 164 samples from 39 patients were assayed. Analysis for intra- and inter-subject variability was restricted to those patients with 4 or more determinations, including 30 patients and 142 determinations. The intra- and inter-subject variability measures were 85.9 and 124.6%, respectively, with an intra-/inter-subject variability ratio of 69%. We also analysed data from a subset of patients with well-documented adherence to protocol, defined as protocol compliant population, including 21 patients and 93 determinations. In this subpopulation, we estimated intra- and inter-subject variability of 79.87% and 110%, respectively, with an intra-/inter-subject variability ratio of 72.6%. This study confirms the notion that raltegravir is a highly variable drug according to the European Medicines Agency criteria. While this condition does not favour the adoption of therapeutic drug monitoring in the clinical practice, the latter is deemed useful in patients with drug plasma concentrations below or near the threshold level of efficacy (since intracellular raltegravir levels might be as low as 5% of the corresponding plasma levels), or to identify drug-drug interactions of potential clinical relevance.
Paradoxical Hypoglycaemia Associated with Diazoxide Therapy for Hyperinsulinaemic Hypoglycaemia
Authors: Ponmani Caroline , Gannon Hannah , Hussain Khalid , Senniappan Senthil
Published: July 2013

Background/Aims: Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of severe and persistent hypoglycaemia in the neonatal period. Diazoxide, a KATP channel activator, is the first line of treatment for patients with HH. Methods: We present 2 cases diagnosed with HH in the neonatal period. Both were started on diazoxide as the first line of treatment and the dose was titrated in order to achieve euglycaemia. Results: When the dose of diazoxide was increased to 15 mg/kg/day, we noted that both infants had increased frequency of hypoglycaemic episodes associated with an increase in the intravenous glucose infusion rate required to maintain normoglycaemia. When the diazoxide was stopped, the intravenous glucose infusion rate decreased and the frequency of hypoglycaemic episodes significantly reduced. The period between the increase in the dose of diazoxide and the onset of increased episodes of hypoglycaemia varied from 12 to 48 h. Conclusion: We report for the first time that diazoxide can cause paradoxical hypoglycaemia when used in moderate to high doses in infants with HH. Our clinical observations support the recent in vitro observations on pancreatic tissue isolated from patients with HH, where diazoxide caused an unanticipated increase in insulin secretion. These observations have important implications for managing patients with HH.
Why have studies of tailored anti-platelet therapy failed so far?
Authors: Siller-Matula Jolanta M. , Jilma Bernd
Published: July 2013

Published data linking clopidogrel non-responsiveness to adverse ischaemic events lead to the suggestion that the magnitude of platelet inhibition by clopidogrel can be monitored and individually adjusted. This has been tested in randomised clinical trials (ARCTIC, GRAVITAS and TRIGGER-PCI), but despite reducing platelet reactivity, a strategy of therapy adjustment based on platelet function monitoring did not reduce the incidence of cardiac ischaemic events. Several critical issues regarding the design of these trials, which might in part have led to negative results, are discussed in this article.
A Novel Method for Determining the Phase of T-Wave Alternans
Authors: Sayadi Omid , Merchant Faisal M. , Puppala Dheeraj , Mela Theofanie , Singh Jagmeet P. , Heist E. Kevin , Owen Chris , Armoundas Antonis A.
Published: July 2013

Background—

T-wave alternans (TWA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. However, to estimate and suppress TWA effectively, the phase of TWA must be accurately determined.

Methods and Results—

We developed a method that computes the beat-by-beat integral of the T-wave morphology, over time points within the T-wave with positive alternans. Then, we estimated the signed derivative of the T-wave integral sequence, which allows the classification of each beat to a binary phase index. In animal studies, we found that this method was able to accurately identify the T-wave phase in artificially induced alternans (
P
<0.0001). The coherence of the phase increased consistently after acute ischemia induction in all body-surface and intracardiac leads (
P
<0.0001). Also, we developed a phase-resetting detection algorithm that enhances the diagnostic utility of TWA. We further established an algorithm that uses the phase of TWA to deliver appropriate polarity-pacing pulses (all interventions compared with baseline,
P
<0.0001 for alternans voltage;
P
<0.0001 for K
score
), to suppress TWA. Finally, we demonstrated that using the phase of TWA we can suppress spontaneous TWA during acute ischemia; 77.6% for alternans voltage (
P
<0.0001) and 92.5% for K
score
(
P
<0.0001).

Conclusions—

We developed a method to quantify the temporal variability of the TWA phase. This method is expected to enhance the utility of TWA in predicting ventricular arrhythmias and sudden cardiac death and raises the possibility of using upstream therapies to abort a ventricular tachyarrhythmia before its onset.
Nicotinamide Adenine Dinucleotide Phosphate Oxidase 4 Mediates the Differential Responsiveness of Atrial Versus Ventricular Fibroblasts to Transforming Growth Factor-β
Authors: Yeh Yung-Hsin , Kuo Chi-Tai , Chang Gwo-Jyh , Qi Xiao-Yan , Nattel Stanley , Chen Wei-Jan
Published: July 2013

Background—

Atrial fibrosis, a common feature of atrial fibrillation, is thought to originate from the differential response of atrium versus ventricle to pathological insult. However, detailed mechanisms underlying the regional differences remain unclear. The aim of this study was to investigate the related factor(s) in mediating atrial vulnerability to fibrotic processes.

Methods and Results—

We first compared the response of cultured atrial versus ventricular fibroblasts with transforming growth factor-β (TGF-β), a key mediator of myocardial fibrosis. Atrial fibroblasts showed a stronger response to TGF-β1 in producing extracellular matrix protein (collagen and fibronectin) than ventricular fibroblasts. Furthermore, TGF-β1 activated its downstream signaling (Smads) and induced pronounced oxidative stress, including up-regulation of nicotinamide adenine dinucleotide phosphate oxidase in atrial fibroblasts, and to a lesser extent in ventricular fibroblasts. Nicotinamide adenine dinucleotide phosphate oxidase inhibitors and small-interfering RNA for Nox4 eliminated TGF-β–induced difference between atrial and ventricular fibroblasts, suggesting the crucial role of Nox4 in mediating the atrial-ventricular discrepancy. Small-interfering RNA for Smad3 also suppressed the differential responsiveness of atrial versus ventricular fibroblasts to TGF-β1, including Nox4 activation, implicating a crosstalk between nicotinamide adenine dinucleotide phosphate oxidases and Smad. In vivo, the increased TGF-β1 responsiveness and Nox4 expression were documented in the atria of transgenic mice with cardiac overexpression of TGF-β1.

Conclusions—

Atrial fibroblasts show greater fibrotic and oxidative responses to TGF-β1 than ventricular fibroblasts. Nox4-derived reactive oxygen species production mediates the susceptibility of atrial fibroblasts to TGF-β1 via activating TGF-β1/Smad signaling cascade, which provides a novel insight into the pathogenesis of atrial fibrosis.
“I'm Not Just a Heart, I'm a Whole Person Here”: A Qualitative Study to Improve Sexual Outcomes in Women With Myocardial Infarction
Authors: Abramsohn Emily M. , Decker Carole , Garavalia Brian , Garavalia Linda , Gosch Kensey , Krumholz Harlan M. , Spertus John A. , Lindau Stacy Tessler
Published: July 2013

Background

Little is known about recovery of female sexual function following an acute myocardial infarction (
MI
). Interventions to improve sexual outcomes in women are limited.

Methods and Results

Semistructured, qualitative telephone interviews were conducted with 17 partnered women (aged 43 to 75 years) purposively selected from the Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients’ Health Status Registry to deepen knowledge of recovery of female sexual function following an acute myocardial infarction (
MI
) and to improve sexual outcomes in women. Sixteen women had a monogamous relationship with a male spouse; 1 had a long‐term female partner. Most women resumed sexual activity within 4 weeks of their
MI
. Sexual problems and concerns were prevalent, including patient and/or partner fear of “causing another heart attack.” Few women received counseling about sexual concerns or the safety of returning to sex. Most women who discussed sex with a physician initiated the discussion themselves. Inquiry about strategies to improve sexual outcomes elicited key themes: need for privacy, patient‐centeredness, and information about the timing and safe resumption of sexual activity. In addition, respondents felt that counseling should be initiated by the treating cardiologist, who “knows whether your heart is safe,” and then reinforced by the care team throughout the rehabilitation period.

Conclusions

Partnered women commonly resume sexual activity soon after an
MI
with fear but without directed counseling from their physicians. Proactive attention to women's concerns related to sexual function and the safety of sexual activity following an
MI
could improve post‐
MI
outcomes for women and their partners.
First record of the genus Abrhexosa Freeman from Mexico, with the description a new species, and two new species and new records of the genus Swammerdamella Enderlein (Diptera: Scatopsidae)
Authors: HUERTA HERON , DZUL FELIPE
Published: July 2013

The genus Abrhexosa Freeman is reported for the first time from Mexico, with the description of a new species, A. patriciae sp. nov., very close to A. panamensis (Cook, 1956). Two new species of the genus Swammerdamella Enderlein, 1912 from Mexico are described and illustrated: Swammerdamella amorimi sp. nov. and S. amacuzacae sp. nov. Swammerdamella mojingae Cook, 1956 is reported for the first time for Mexico, and new records are included for S. marginata Cook, 1956. A key for the species of Swammerdamella of Mexico is provided.
Dehumidification over Tropical Continents Reduces Climate Sensitivity and Inhibits Snowball Earth Initiation
Authors: Fiorella Richard P. , Poulsen Christopher J.
Published: July 2013

The enigmatic Neoproterozoic geological record suggests the potential for a fully glaciated “snowball Earth.” Low-latitude continental position has been invoked as a potential snowball Earth trigger by increasing surface albedo and decreasing atmospheric CO2 concentrations through increased silicate weathering. Herein, climate response to the reduction of total solar irradiance (TSI) and CO2 concentration is tested using four different land configurations (aquaplanet, modern, Neoproterozoic, and low-latitude supercontinent) with uniform topography in the NCAR Community Atmosphere Model, version 3.1 (CAM3.1), GCM with a mixed layer ocean. Despite a lower surface albedo at 100% TSI, the threshold for global glaciation decreases from 92% TSI in the aquaplanet configuration to 85% TSI with a low-latitude supercontinent. The difference in thresholds is principally because of the partitioning of local longwave cooling relative to poleward energy transport. Additionally, dehumidification of the troposphere over large tropical continents in CAM3.1 increases direct heating by decreasing cloud cover. Continental heating intensifies the Walker circulation, enhancing surface evaporation and moistening the marine troposphere. Topography also provides an important control on snowball Earth initiation. Modern topography in the modern continental arrangement eases snowball initiation, requiring a 2% smaller reduction in TSI relative to a modern continental arrangement without topography. In the absence of potential silicate weathering feedbacks, large tropical landmasses raise the barrier to initiation of snowball events. More generally, these simulations demonstrate the substantial influence of geography on climate sensitivity and challenge the notion that the reduced continental area early in Earth history might provide a solution to the faint young Sun paradox.
Client-centred occupational therapy in Canada: Refocusing on core values / Recentrer l’ergothérapie au Canada sur les valeurs fondamentales de la pratique centrée sur le client
Authors: Hammell Karen R. Whalley
Published: July 2013

Background.

The Canadian occupational therapy profession has proclaimed its allegiance to client-centred practice for three decades. However, official definitions of client-centred practice have been inconsistent, and its defining features, underlying assumptions, and power relations have been subjected to little critical reflection.

Purpose.

The aim was to reflect critically on Canadian conceptions of client-centred practice and its core values.

Key issues.

Definitions of client-centred practice have evolved and changed, suggesting that the occupational therapy profession in Canada may have abandoned those values that originally underpinned its vision of client-centred practice by electing to focus on the enabling skills of therapists. However, evidence suggests that clients value those qualities of client-centred practice that underpinned the profession’s original vision.

Implications.

This paper proposes a renewed focus on respect—respect for clients; respect for clients’ strengths, experience, and knowledge; respect for clients’ moral right to make choices concerning their lives—and on fostering respectful, supportive relationships with clients.
Translating the Triumph: Reading Mark’s Cruciﬁxion Narrative against a Roman Ritual of Power
Authors: Georgia Allan T.
Published: July 2013

Traces of the Roman triumph have been identiﬁed in the procession narratives in Mk 11 and 15, but how its themes should be understood to function in Mark’s telling has never achieved consensus. Reading these narratives alongside evidence for the Roman triumph demonstrates how the ritual logic of the triumph allowed Mark to exploit the degradation of Jesus’ passion, undermine the performance of Roman power and portray Jesus as a king, and a threat to Rome. The Roman triumph paradoxically magnified triumphal victims, presented kings as ideal victims, and drew a close parallel between the victim’s kingly status and the conqueror’s grandeur. Mark employs the logic of the triumph to transform Jesus’ status as victim into an assertion of his authority, so that Jesus’ execution by Roman agents emerges as a ritualized assertion of Jesus’ Davidic kingship. In this article, Mark emerges as a cultural bricoleur who co-opts Roman spectacle in order to naturalize Rome’s dominant language, symbols and practices, thereby translating them to the purposes of gospel.
Rethinking the Ethics of John: A Review Article
Authors: Koester Craig R.
Published: July 2013

The essays in Rethinking the Ethics of John, edited by Jan G. van der Watt and Ruben Zimmermann, make a signiﬁcant contribution to the study of Johannine ethics. They show that the Gospel’s narrative form with its character portrayal, speciﬁc directives, and images, provides critical reflection on human action. The command to ‘love one another’ need not be understood in a narrow sense, for it forms community and engages the world. Themes of ‘life’ and ‘truth’ work together with ‘love’ to create a multifaceted ethical perspective. The Gospel afﬁrms values included in Jewish law, while centering ethical reflection on the action of God in Jesus, which evokes a human response. The critical stance toward opponents in the Johannine epistles stands in tension with the love command, but references to God’s action on behalf of the world opens up possibilities for positive reading.