bluuebunny/crossref_metadata_2025 huggingface dataset:
Eliciting preferences for waterpipe tobacco smoking using a discrete choice experiment: implications for product regulation
Authors: Salloum Ramzi G , Maziak Wasim , Hammond David , Nakkash Rima , Islam Farahnaz , Cheng Xi , Thrasher James F
Published: September 2015

Objectives

Waterpipe smoking is highly prevalent among university students, and has been increasing in popularity despite mounting evidence showing it is harmful to health. The aim of this study was to measure preferences for waterpipe smoking and determine which product characteristics are most important to smokers.

Setting

A large university in the Southeastern USA.

Participants

Adult waterpipe smokers attending the university (N=367).

Design

Participants completed an Internet-based discrete choice experiment to reveal their preferences for, and trade-offs between, the attributes of hypothetical waterpipe smoking sessions. Participants were presented with waterpipe lounge menus, each with three fruit-flavoured options and one tobacco flavoured option, in addition to an opt out option. Nicotine content and price were provided for each choice. Participants were randomised to either receive menus with a text-only health-warning message or no message.

Outcome measures

Multinomial and nested logit models were used to estimate the impact on consumer choice of attributes and between-subject assignment of health warnings respectively.

Results

On average, participants preferred fruit-flavoured varieties to tobacco flavour. They were averse to options labelled with higher nicotine content. Females and non-smokers of cigarettes were more likely than their counterparts to prefer flavoured and nicotine-free varieties. Participants exposed to a health warning were more likely to opt out.

Conclusions

Fruit-flavoured tobacco and lower nicotine content labels, two strategies widely used by the industry, increase the demand for waterpipe smoking among young adults. Waterpipe-specific regulation should limit the availability of flavoured waterpipe tobacco and require accurate labelling of constituents. Waterpipe-specific tobacco control regulation, along with research to inform policy, is required to curb this emerging public health threat.
Implementation research in emergency medicine: a systematic scoping review
Authors: Tavender Emma J , Bosch Marije , Fiander Michelle , Knott Jonathan C , Gruen Russell L , O'Connor Denise
Published: September 2015

Introduction

Implementation research aims to increase the uptake of research findings into clinical practice to improve the quality of healthcare. This scoping systematic study aims to assess the volume and scope of implementation research in emergency medicine (EM) to obtain an overview and inform future implementation research.

Methods

Studies were identified by searching electronic databases and reference lists of included studies for the years 2002, 2007 and 2012. Titles/abstracts were screened, full papers checked and data extracted by one author, with a random sample checked by a second author.

Results

A total of 3581 citations were identified with 197 eligible papers included. The number of papers significantly increased over time from 26 in 2002 to 77 in 2007 and 94 in 2012 (p<0.05). Eighty-two (42%) focused on identifying evidence–practice gaps, 77 (39%) evaluated the effectiveness of implementation interventions and 38 (19%) explored barriers and enablers to change. Only two papers explicitly stated that theory was used. Five of the 77 effectiveness studies used a randomised design and few provided sufficient detail about the intervention undergoing evaluation.

Conclusions

Although there was a significant increase in the number of implementation research papers, most studies focused on identifying evidence–practice gaps or used weak study designs to evaluate the effects of implementation interventions. Recommendations for improving implementation research in EM include identifying barriers and enablers to implementation, using theory in areas where proven important gaps exist, improving the reporting of the content of interventions and using rigorous study designs to evaluate their effectiveness.
The tectonic significance of the Early Cretaceous forearc-metamorphic assemblage in south-central Alaska based on detrital zircon U–Pb dating of sedimentary protoliths
Authors: Labrado Amanda , Pavlis Terry L. , Amato Jeffrey M. , Day Erik M.
Published: September 2015

A complex array of faulted arc rocks and variably metamorphosed forearc accretionary complex rocks form a mappable arc–forearc boundary in southern Alaska known as the Border Ranges fault (BRF). We use detrital U–Pb zircon dating of metasedimentary rocks within the Knik River terrane in the western Chugach Mountains to show that a belt of Early Cretaceous amphibolite-facies metamorphic rocks along the BRF was formed when older mélange rocks of the Chugach accretionary complex were reworked in a sinistral-oblique thrust reactivation of the BRF during a period of forearc plutonism. The metamorphic subterrane of the Knik River terrane has a maximum depositional age (MDA) of 156.5 ± 1.5 Ma and a detrital zircon age spectrum that is indistinguishable from the Potter Creek assemblage of the Chugach accretionary complex, supporting correlation of these units. These ages contrast strongly with new and existing data that show Triassic to earliest Jurassic detrital zircon ages from metamorphic screens in the plutonic subterrane of the Knik River terrane, a fragmented Early Jurassic plutonic assemblage generally interpreted as the basement of the Peninsular terrane. Based on these findings, we propose the following new terminology for the Knik River terrane: (1) “Carpenter Creek metamorphic complex” for the Early Cretaceous “metamorphic subterrane”, (2) “western Chugach trondhjemite suite” for the Early Cretaceous forearc plutons within the belt, (3) “Friday Creek assemblage” for a transitional mélange unit that contains blocks of the Carpenter Creek complex in a chert–argillite matrix, and (4) “Knik River metamorphic complex” in reference to metamorphic rocks engulfed by Early Jurassic plutons of the Peninsular terrane that represent the roots of the Talkeetna arc. The correlation of the Carpenter Creek metamorphic complex with the Chugach mélange indicates that the trace of the BRF lies ∼1–5 km north of the map trace shown on geologic maps, although, like other segments of the BRF, this boundary is blurred by local complexities within the BRF system. Ductile deformation of the mélange is sufficiently intense that few vestiges of its original mélange fabric exist, suggesting the scarcity of rocks described as mélange in the cores of many orogens may result from misidentification of rocks that have been intensely overprinted by younger, ductile deformation.
The Foucault pendulum viewed as a spherical pendulum placed in a rotating reference system
Authors: de Icaza-Herrera Miguel , Castaño Víctor Manuel
Published: September 2015

For a pendulum of a given length, installed at any fixed latitude, the motion depends on three variables: the total mechanical energy, connected with the maximum angular distance of the bob from the vertical; the projection of the angular momentum along the vertical, connected with the shape of its orbit along the surface of a sphere, which may be described as a veering ellipse recalling the orbit of Mercury; and the angular velocity, Ω, of the rotating reference system given by that of the Earth. When the value of one of these variables is negligible, the ensuing motion has already been calculated in analytical grounds: a plummet, a Foucault pendulum, or a spherical pendulum including as a special case the so-called plane pendulum. This paper offers a Lagrangian approach in the case when Ω is the sidereal angular velocity of the Earth. To our knowledge, these are the first analytical solutions for any boundary conditions. When the boundary conditions are such that the bob passes through the vertical (i.e., the direction defined by the plummet), the behavior of the pendulum is as expected: the veering velocity of the plane equals the angular velocity of the Earth times the sine of the latitude. This state is reached when the projection of its angular momentum along the vertical vanishes. However, if that projection takes any other value, the motion is produced along a veering ellipse and the time rate of advance of the major axis is the sum of the previous result plus the spherical pendulum contribution. Our solutions include, as special cases, those of the spherical pendulum, or the ideal Foucault pendulum with finite amplitude.
The Application of HIWO–SVM in Analog Circuit Fault Diagnosis
Authors: Hu Hongzhi , Tian Shulin , Guo Qing , Ouyang Aijia
Published: September 2015

The paper proposes a fault diagnosis model based on the HIWO–SVM algorithm given the fact that the basic support vector machines (SVM) cannot solve effectively the problem of fault diagnosis in analog circuit. First of all, the wavelet package technique is adopted for extracting the information of the faults from the test points in the analog circuit. The differential evolution (DE) algorithm is then integrated with the purpose of improving the performance of the basic IWO algorithm, i.e. a hybrid IWO (HIWO) algorithm. The HIWO algorithm is further used to optimize the parameters of SVM in order to avoid the randomness of the parameter selection, thereby improving the diagnosis precision and robustness. The experimental results on a filter circuit show that the method is more effective and reliable than the other methods for fault diagnosis.
Plastic Collapse Analysis of Mindlin–Reissner Plates Using a Stabilized Mesh-Free Method
Authors: Le C. V. , Chu T. Q.
Published: September 2015

This paper presents a numerical kinematic formulation for computation of collapse load of Mindlin–Reissner plates, that uses a stabilized mesh-free method in combination with second-order cone programming (SOCP). The kinematic formulation is discretized using a moving least squares approximation combined with a stabilized conforming nodal integration scheme, ensuring that shear locking problem at thin plate limit can be removed. The stabilized mesh-free based kinematic formulation is formulated as a conic problem so that it can be solved by an efficient primal-dual interior-point algorithm. To speed up computational progress, an adaptive refinement scheme using dissipation-based error indicator is also performed. The performance of the proposed numerical procedure is illustrated by examining several plates with arbitrary geometries and various boundary conditions.
Structural, magnetic behaviors and temperature-dependent Raman scattering spectra of Y and Zr codoped BiFeO3 ceramics
Authors: Zhang Cheng , Xie Dan , Xu Jianlong , Sun Yilin , Zang Yongyuan , Zhang Xiaowen , Gao Xingsen
Published: September 2015

Multiferroic [Formula: see text] (BFO) and Y, Zr codoped BFO [Formula: see text] ceramics were prepared and the influence of codoping on the crystal structure and magnetic properties were investigated in this work. Confirmed by the evolution of X-ray diffraction and Raman modes, the codoping has changed the crystal structure from rhombohedral to tetragonal in bulk BFO ceramics. The enhancement of magnetic behaviors is demonstrated by the damage of space-modulated spiral spin structure, and it can be attributed to the crystal structure change and size effects. Meanwhile, Raman spectra from 300 to 800 K demonstrates that lower frequency phonon modes show rapid softening near the Neel temperature.
Assessing the impact of orogenic inheritance on the architecture, timing and magmatic budget of the North Atlantic rift system: a mapping approach
Authors: Chenin Pauline , Manatschal Gianreto , Lavier Luc L. , Erratt Duncan
Published: September 2015

To investigate the impact of orogenic inheritance on the characteristics of the North Atlantic rift system we develop new mapping methods that highlight the first-order architecture and timing of rifts, as well as the distribution of heterogeneities inherited from the Palaeozoic Caledonian and Variscan orogenies. These maps demonstrate major differences in the behaviour of the North Atlantic rift system relative to the two orogens, with the Variscan front appearing to be an important boundary: the rift cuts through the Caledonian orogen and is parallel to its structural grain to the north, whereas it circumvents the core of the Variscides to the south. In addition, rifting is protracted and polyphase with break-up being magma-rich north of the Variscan front, as opposed to the south, where a single, apparently continuous extensional event led to magma-poor break-up in less than 50 myr. Also, the North Atlantic rift system reactivates sutures corresponding to large (>2000 km) former oceans, whereas sutures of small (<500–1000 km) oceanic basins are little affected in both the northern and southern North Atlantic. These observations point to a major influence of orogenic inheritance on the characteristics of rift systems.
Mechanisms of ammonia and ammonium transport by rhesus-associated glycoproteins
Authors: Caner Tolga , Abdulnour-Nakhoul Solange , Brown Karen , Islam M. Toriqul , Hamm L. Lee , Nakhoul Nazih L.
Published: September 2015

In this study we characterized ammonia and ammonium (NH3/NH4+) transport by the rhesus-associated (Rh) glycoproteins RhAG, Rhbg, and Rhcg expressed in Xenopus oocytes. We used ion-selective microelectrodes and two-electrode voltage clamp to measure changes in intracellular pH, surface pH, and whole cell currents induced by NH3/NH4+ and methyl amine/ammonium (MA/MA+). These measurements allowed us to define signal-specific signatures to distinguish NH3 from NH4+ transport and to determine how transport of NH3 and NH4+ differs among RhAG, Rhbg, and Rhcg. Our data indicate that expression of Rh glycoproteins in oocytes generally enhanced NH3/NH4+ transport and that cellular changes induced by transport of MA/MA+ by Rh proteins were different from those induced by transport of NH3/NH4+. Our results support the following conclusions: 1) RhAG and Rhbg transport both the ionic NH4+ and neutral NH3 species; 2) transport of NH4+ is electrogenic; 3) like Rhbg, RhAG transport of NH4+ masks NH3 transport; and 4) Rhcg is likely to be a predominantly NH3 transporter, with no evidence of enhanced NH4+ transport by this transporter. The dual role of Rh proteins as NH3 and NH4+ transporters is a unique property and may be critical in understanding how transepithelial secretion of NH3/NH4+ occurs in the renal collecting duct.
Increased systolic load causes adverse remodeling of fetal aortic and mitral valves
Authors: Tibayan Frederick A. , Louey Samantha , Jonker Sonnet , Espinoza Herbert , Chattergoon Natasha , You Fanglei , Thornburg Kent L. , Giraud George
Published: September 2015

While abnormal hemodynamic forces alter fetal myocardial growth, little is known about whether such insults affect fetal cardiac valve development. We hypothesized that chronically elevated systolic load would detrimentally alter fetal valve growth. Chronically instrumented fetal sheep received either a continuous infusion of adult sheep plasma to increase fetal blood pressure, or a lactated Ringer's infusion as a volume control beginning on day 126 ± 4 of gestation. After 8 days, mean arterial pressure was higher in the plasma infusion group (63.0 mmHg vs. 41.8 mmHg, P < 0.05). Mitral annular septal-lateral diameter (11.9 mm vs. 9.1 mm, P < 0.05), anterior leaflet length (7.7 mm vs. 6.4 mm, P < 0.05), and posterior leaflet length (P2; 4.0 mm vs. 3.0 mm, P < 0.05) were greater in the elevated load group. mRNA levels of Notch-1, TGF-β2, Wnt-2b, BMP-1, and versican were suppressed in aortic and mitral valve leaflets; elastin and α1 type I collagen mRNA levels were suppressed in the aortic valves only. We conclude that sustained elevated arterial pressure load on the fetal heart valve leads to anatomic remodeling and, surprisingly, suppression of signaling and extracellular matrix genes that are important to valve development. These novel findings have important implications on the developmental origins of valve disease and may have long-term consequences on valve function and durability.
Nonlinear identification of the total baroreflex arc
Authors: Moslehpour Mohsen , Kawada Toru , Sunagawa Kenji , Sugimachi Masaru , Mukkamala Ramakrishna
Published: September 2015

The total baroreflex arc [the open-loop system relating carotid sinus pressure (CSP) to arterial pressure (AP)] is known to exhibit nonlinear behaviors. However, few studies have quantitatively characterized its nonlinear dynamics. The aim of this study was to develop a nonlinear model of the sympathetically mediated total arc without assuming any model form. Normal rats were studied under anesthesia. The vagal and aortic depressor nerves were sectioned, the carotid sinus regions were isolated and attached to a servo-controlled piston pump, and the AP and sympathetic nerve activity (SNA) were measured. CSP was perturbed using a Gaussian white noise signal. A second-order Volterra model was developed by applying nonparametric identification to the measurements. The second-order kernel was mainly diagonal, but the diagonal differed in shape from the first-order kernel. Hence, a reduced second-order model was similarly developed comprising a linear dynamic system in parallel with a squaring system in cascade with a slower linear dynamic system. This “Uryson” model predicted AP changes 12% better ( P < 0.01) than a linear model in response to new Gaussian white noise CSP. The model also predicted nonlinear behaviors, including thresholding and mean responses to CSP changes about the mean. Models of the neural arc (the system relating CSP to SNA) and peripheral arc (the system relating SNA to AP) were likewise developed and tested. However, these models of subsystems of the total arc showed approximately linear behaviors. In conclusion, the validated nonlinear model of the total arc revealed that the system takes on an Uryson structure.
Differences in control of parasympathetic vasodilation between submandibular and sublingual glands in the rat
Authors: Sato Toshiya , Ishii Hisayoshi
Published: September 2015

We examined blood flow in the submandibular gland (SMGBF) and sublingual gland (SLGBF) during electrical stimulation of the central cut end of the lingual nerve (LN) in the urethane-anesthetized rats using a laser speckle imaging flow meter. LN stimulation elicited intensity- and frequency-dependent SMGBF and SLGBF increases, and the magnitude of the SMGBF increase was higher than that of the SLGBF increase. The increase in both glands was significantly inhibited by intravenous administration of the autonomic cholinergic ganglion blocker hexamethonium. The antimuscarinic agent atropine markedly inhibited the SMGBF increase and partly inhibited the SLGBF increase. The atropine-resistant SLGBF increase was significantly inhibited by infusion of vasoactive intestinal peptide (VIP) receptor antagonist, although administration of VIP receptor antagonist alone had no effect. The recovery time to the basal blood flow level was shorter after LN stimulation than after administration of VIP. However, the recovery time after LN stimulation was significantly delayed by administration of atropine in a dose-dependent manner to the same level as after administration of VIP. Our results indicate that 1) LN stimulation elicits both a parasympathetic SMGBF increase mainly evoked by cholinergic fibers and a parasympathetic SLGBF increase evoked by cholinergic and noncholinergic fibers, and 2) VIP-ergic mechanisms are involved in the noncholinergic SLGBF increase and are activated when muscarinic mechanisms are deactivated.
Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus
Authors: Abdul-Ghani Muhammad A. , Norton Luke , DeFronzo Ralph A.
Published: September 2015

Hyperglycemia is the primary factor responsible for the microvascular, and to a lesser extent macrovascular, complications of diabetes. Despite this well-established relationship, approximately half of all type 2 diabetic patients in the US have a hemoglobin A1c(HbA1c) ≥7.0%. This is associated in part with the side effects, i.e., weight gain and hypoglycemia, of currently available antidiabetic agents and in part with the failure to utilize medications that reverse the basic pathophysiological defects present in patients with type 2 diabetes. The kidney has been shown to play a central role in the development of hyperglycemia by excessive production of glucose throughout the sleeping hours and enhanced reabsorption of filtered glucose by the renal tubules secondary to an increase in the threshold at which glucose spills into the urine. Recently, a new class of antidiabetic agents, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, has been developed and approved for the treatment of patients with type 2 diabetes. In this review, we examine their mechanism of action, efficacy, safety, and place in the therapeutic armamentarium. Since the SGLT2 inhibitors have a unique mode of action that differs from all other oral and injectable antidiabetic agents, they can be used at all stages of the disease and in combination with all other antidiabetic medications.
Postnatal development attunes olfactory bulb mitral cells to high-frequency signaling
Authors: Yu Yiyi , Burton Shawn D. , Tripathy Shreejoy J. , Urban Nathaniel N.
Published: September 2015

Mitral cells (MCs) are a major class of principal neurons in the vertebrate olfactory bulb, conveying odor-evoked activity from the peripheral sensory neurons to olfactory cortex. Previous work has described the development of MC morphology and connectivity during the first few weeks of postnatal development. However, little is known about the postnatal development of MC intrinsic biophysical properties. To understand stimulus encoding in the developing olfactory bulb, we have therefore examined the development of MC intrinsic biophysical properties in acute slices from postnatal day (P)7–P35 mice. Across development, we observed systematic changes in passive membrane properties and action potential waveforms consistent with a developmental increase in sodium and potassium conductances. We further observed developmental decreases in hyperpolarization-evoked membrane potential sag and firing regularity, extending recent links between MC sag heterogeneity and firing patterns. We then applied a novel combination of statistical analyses to examine how the evolution of these intrinsic biophysical properties specifically influenced the representation of fluctuating stimuli by MCs. We found that immature MCs responded to frozen fluctuating stimuli with lower firing rates, lower spike-time reliability, and lower between-cell spike-time correlations than more mature MCs. Analysis of spike-triggered averages revealed that these changes in spike timing were driven by a developmental shift from broad integration of inputs to more selective detection of coincident inputs. Consistent with this shift, generalized linear model fits to MC firing responses demonstrated an enhanced encoding of high-frequency stimulus features by mature MCs.
Theta-rhythmic drive between medial septum and hippocampus in slow-wave sleep and microarousal: a Granger causality analysis
Authors: Kang D. , Ding M. , Topchiy I. , Shifflett L. , Kocsis B.
Published: September 2015

Medial septum (MS) plays a critical role in controlling the electrical activity of the hippocampus (HIPP). In particular, theta-rhythmic burst firing of MS neurons is thought to drive lasting HIPP theta oscillations in rats during waking motor activity and REM sleep. Less is known about MS-HIPP interactions in nontheta states such as non-REM sleep, in which HIPP theta oscillations are absent but theta-rhythmic burst firing in subsets of MS neurons is preserved. The present study used Granger causality (GC) to examine the interaction patterns between MS and HIPP in slow-wave sleep (SWS, a nontheta state) and during its short interruptions called microarousals (a transient theta state). We found that during SWS, while GC revealed a unidirectional MS→HIPP influence over a wide frequency band (2–12 Hz, maximum: ∼8 Hz), there was no theta peak in the hippocampal power spectra, indicating a lack of theta activity in HIPP. In contrast, during microarousals, theta peaks were seen in both MS and HIPP power spectra and were accompanied by bidirectional GC with MS→HIPP and HIPP→MS theta drives being of equal magnitude. Thus GC in a nontheta state (SWS) vs. a theta state (microarousal) primarily differed in the level of HIPP→MS. The present findings suggest a modification of our understanding of the role of MS as the theta generator in two regards. First, a MS→HIPP theta drive does not necessarily induce theta field oscillations in the hippocampus, as found in SWS. Second, HIPP theta oscillations entail bidirectional theta-rhythmic interactions between MS and HIPP.
Sensitivity of rat inferior colliculus neurons to frequency distributions
Authors: Herrmann Björn , Parthasarathy Aravindakshan , Han Emily X. , Obleser Jonas , Bartlett Edward L.
Published: September 2015

Stimulus-specific adaptation refers to a neural response reduction to a repeated stimulus that does not generalize to other stimuli. However, stimulus-specific adaptation appears to be influenced by additional factors. For example, the statistical distribution of tone frequencies has recently been shown to dynamically alter stimulus-specific adaptation in human auditory cortex. The present study investigated whether statistical stimulus distributions also affect stimulus-specific adaptation at an earlier stage of the auditory hierarchy. Neural spiking activity and local field potentials were recorded from inferior colliculus neurons of rats while tones were presented in oddball sequences that formed two different statistical contexts. Each sequence consisted of a repeatedly presented tone (standard) and three rare deviants of different magnitudes (small, moderate, large spectral change). The critical manipulation was the relative probability with which large spectral changes occurred. In one context the probability was high (relative to all deviants), while it was low in the other context. We observed larger responses for deviants compared with standards, confirming previous reports of increased response adaptation for frequently presented tones. Importantly, the statistical context in which tones were presented strongly modulated stimulus-specific adaptation. Physically and probabilistically identical stimuli (moderate deviants) in the two statistical contexts elicited different response magnitudes consistent with neural gain changes and thus neural sensitivity adjustments induced by the spectral range of a stimulus distribution. The data show that already at the level of the inferior colliculus stimulus-specific adaptation is dynamically altered by the statistical context in which stimuli occur.
Management of Necrotizing Fasciitis and Fecal Peritonitis following Ostomy Necrosis and Detachment by Using NPT and Flexi-Seal
Authors: Yetışır Fahri , Şarer Akgün Ebru , Acar H. Zafer
Published: September 2015

Management of necrotizing fasciitis and severe faecal peritonitis following ostomy in elderly patient with comorbid disease is challenging. We would like to report management of frozen Open Abdomen (OA) with colonic fistula following ostomy necrosis and detachment in an elderly patient with comorbid disease and malignancy. 78-year-old woman with high stage rectum carcinoma was admitted to emergency department and underwent operation for severe peritonitis and sigmoid colonic perforation. Loop sigmoidostomy was performed. At postoperative 15th day, she was transferred to our clinic with necrotizing fasciitis and severe faecal peritonitis due to ostomy necrosis and detachment. Enteric effluent was removed from the OA wound by using the Flexi-Seal Fecal Management System (FMS) (ConvaTec) and pesser tube in deeply located colonic fistula in conjunction with Negative Pressure Therapy (NPT). Maturation of ostomy was facilitated by using second NPT on ostomy side. After source control, delayed abdominal closure was achieved by skin flap approximation.
NocardiaBrain Abscess and CD4+Lymphocytopenia in a Previously Healthy Individual
Authors: Adjamian Norair , Kikam Adeline , Wessell Kathryn Ruda , Casselman Jason , Toller-Artis Erin , Olasokan Olapeju , Hostoffer Robert W.
Published: September 2015

Nocardiabrain abscesses are a known occurrence in patients with immunocompromised conditions. Nocardial infection is commonly an unfortunate sequela to other complications which these patients are being followed up and treated for. The incidence of nocardial brain abscess in an otherwise healthy patient is extremely rare. We present a case ofNocardiabrain abscess in a previously healthy individual, who, upon workup for vision and gait abnormalities, was shown to have multiple brain abscesses and a decreased absolute CD4+lymphocyte count. Adding to the rarity of our case, the finding of lymphocytopenia in our patient was unrelated to any known predisposing condition or infectious state.
A Comparative Study Examining the Management of Bowen’s Disease in the United Kingdom and Australia
Authors: Morley G. L. , Matthews J. H. , Verpetinske I. , Thom G. A.
Published: September 2015

Background and Aim. The optimum management of Bowen’s Disease (BD) is undefined. A review of current practice is required to allow the development of best practice guidelines.Methods. All BD cases, diagnosed in one UK centre and one Australian centre over a year (1 July 2012–30 June 2013), were analysed retrospectively. Patients with BD were identified from histopathology reports and their medical records were analysed to collect demographic data, site of lesion, and treatment used.Results. The treatment of 155 lesions from the UK centre and 151 lesions from the Australian centre was analysed. At both centres BD was most frequently observed on the face: UK had 70 (45%) lesions and Australia had 83 (55%) lesions (P=0.08). The greatest number of lesions was managed by the plastic surgery department in the UK centre, 72 (46%), and the dermatology department in the Australian centre, 121 (80%). The most common therapy was surgical excision at both centres.Conclusions. In both UK and Australia, BD arises on sun-exposed sites and was most commonly treated with surgical excision despite a lack of robust evidence-based guidelines.
Association of IFN-γ : IL-10 Cytokine Ratio with Nonsegmental Vitiligo Pathogenesis
Authors: Ala Yaswanth , Pasha Mohammed Khalid , Rao Raja Narasimha , Komaravalli Prasanna Latha , Jahan Parveen
Published: September 2015

Background and Objectives. Cytokines regulate immune response and inflammation and play a crucial role in depigmentation process of vitiligo. The present study aimed to estimate the serum levels of pro- and anti-inflammatory cytokines, IFN-γand IL-10, and their ratios in nonsegmental vitiligo patients and healthy individuals from India.Methods. Blood samples were collected from 280 subjects and serum IFN-γand IL-10 levels were measured using standard ELISA.Results. Nonsegmental vitiligo patients showed increased levels of IFN-γ(12.4±3.2versus9.9±4.4 pg/mL) and decreased levels of IL-10 (9.3±1.7versus11.5±5 pg/mL) compared to controls. Ratio of IFN-γ : IL-10 differed significantly from patients to controls (p<0.05). IFN-γconcentrations and IFN-γ : IL-10 ratio varied significantly with respect to clinical variants, disease stability, and social habits (smoking and alcohol consumption) and showed a positive correlation with disease duration. Family history of vitiligo was significantly associated with IFN-γ : IL-10 ratio but not with their individual levels.Conclusion. The ratio of IFN-γ : IL-10 serum levels may be considered as one of the promising immunological markers in nonsegmental vitiligo. This is the first study considering multiple aspects in relation to ratio of cytokine levels. Similar studies with large samples are warranted to confirm our observations.
Analysis of a Model for Computer Virus Transmission
Authors: Qin Peng
Published: September 2015

Computer viruses remain a significant threat to computer networks. In this paper, the incorporation of new computers to the network and the removing of old computers from the network are considered. Meanwhile, the computers are equipped with antivirus software on the computer network. The computer virus model is established. Through the analysis of the model, disease-free and endemic equilibrium points are calculated. The stability conditions of the equilibria are derived. To illustrate our theoretical analysis, some numerical simulations are also included. The results provide a theoretical basis to control the spread of computer virus.
PD-1 Blockade in Advanced Melanoma in Patients with Hepatitis C and/or HIV
Authors: Davar Diwakar , Wilson Melissa , Pruckner Chelsea , Kirkwood John M.
Published: September 2015

On the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor ipilimumab or BRAF/MEK inhibitors (forBRAFmutated melanoma). Given hypothesized risk of triggering exacerbations of autoimmune diseases and/or chronic viral infections, clinical trials (including regulatory studies) evaluating checkpoint blocking antibodies PD-1 and CTLA-4 have excluded patients with autoimmune diseases, chronic hepatitis B/C virus (HBV/HCV), and/or human immunodeficiency virus (HIV) infections. Herein, we describe two patients with advanced melanoma and concomitant HCV/HIV infections treated with PD-1 inhibitor pembrolizumab. Patient 2 with HIV/HCV coinfection progressed after 2 doses of pembrolizumab. Patient 1 who had HCV alone was treated with pembrolizumab with initial partial response. HCV viral load remained stable after 9 cycles of pembrolizumab following which 12-week course of HCV-directed therapy was commenced, resulting in prompt reduction of HCV viral load below detectable levels. Response is ongoing and HCV viral load remains undetectable. In both patients, no significant toxicities were observed when pembrolizumab was initiated. We argue for the further investigation of checkpoint inhibition in cancer patients with underlying chronic viral infections in the context of carefully designed clinical trials.
Therapeutic Potential of Dietary Phenolic Acids
Authors: Saibabu Venkata , Fatima Zeeshan , Khan Luqman Ahmad , Hameed Saif
Published: September 2015

Although modern lifestyle has eased the quality of human life, this lifestyle’s related patterns have imparted negative effects on health to acquire multiple diseases. Many synthetic drugs are invented during the last millennium but most if not all of them possess several side effects and proved to be costly. Convincing evidences have established the premise that the phytotherapeutic potential of natural compounds and need of search for novel drugs from natural sources are of high priority. Phenolic acids (PAs) are a class of secondary metabolites spread throughout the plant kingdom and generally involved in plethora of cellular processes involved in plant growth and reproduction and also produced as defense mechanism to sustain various environmental stresses. Extensive research on PAs strongly suggests that consumption of these compounds hold promise to offer protection against various ailments in humans. This paper focuses on the naturally derived PAs and summarizes the action mechanisms of these compounds during disease conditions. Based on the available information in the literature, it is suggested that use of PAs as drugs is very promising; however more research and clinical trials are necessary before these bioactive molecules can be made for treatment. Finally this review provides greater awareness of the promise that natural PAs hold for use in the disease prevention and therapy.
Bioaccumulation of Antimony and Arsenic in Vegetables and Health Risk Assessment in the Superlarge Antimony-Mining Area, China
Authors: Zeng Defang , Zhou Saijun , Ren Bozhi , Chen Tengshu
Published: September 2015

Heavy metal pollution in soils caused by mining and smelting has attracted worldwide attention for its potential health risks to residents. This paper studies the concentrations and accumulations of Sb and As in both soils and vegetables and the human health risks of Sb and As in vegetables from Xikuangshan (XKS) Sb mine, Hunan, China. Results showed that the soils were severely polluted by Sb and As; Sb and As have significant positive correlation. Sb and As concentrations in vegetables were quite different:Coriandrum sativumL. was the highest in Sb,Allium fistulosumL. was the highest in As, andBrassica pekinensisL. was the lowest in both Sb and As;Daucus carotaL. andCoriandrum sativumL. showed advantage in accumulating Sb and As;Coriandrum sativumL. had higher capacity of redistributing Sb and As within the plant. Health risk assessment results showed that the hazard quotient (HQ) values of Sb and As in vegetables were in the ranges of 1.61–3.33 and 0.09–0.39, respectively; the chronic daily intake (CDI) and hazard quotient (HQ) values of Sb were over the safe limit recommended by FAO and WHO, indicating that long-term consumption of vegetables from the surrounding soils of XKS mine may bring health risks to residents.
Electrical Stimulation of the Amygdala Modifies the Negative Feedback Effect of Glucocorticoids on the Adrenocortical Responses to Stress
Authors: Weidenfeld Joseph , Itzik Anna , Ovadia Haim
Published: September 2015

Objective: The amygdala (AMG) plays a facilitatory role in the hypothalamic-pituitary-adrenal (HPA) axis. The effect of the AMG on the negative feedback exerted by glucocorticoids (GC) is not clear. We investigated the effect of repeated electrical stimulation of the AMG on the feedback action of GC upon the adrenocortical (AC) response to stressful stimuli. Methods: Rats received electrical stimulation into the central amygdalar nucleus once daily for 4 days. At days 5 and 12 after the onset of stimulation, rats were treated with dexamethasone (Dex) or vehicle and were exposed to either photic or acoustic stress stimuli, and serum corticosterone (CS) was measured. In another group of rats, we measured the binding of Dex to the hippocampal cytosol at 5 and 12 days after the AMG stimulation. Results: At 5 and 12 days after the onset of stimulation or a sham control, stress increased the serum CS level. In the sham group, Dex completely inhibited the CS response, but at 5 days after stimulation, it was significantly less effective in doing this. At day 12, Dex was as effective as in the control group. AMG stimulation delayed the return of CS response to basal levels and caused a significant decrease in the binding capacity of Dex to hippocampal cytosol. Conclusion: Electrical stimulation of the AMG caused a transient impairment of the feedback action of GC upon the stress response. This effect may be due to the decrease in hippocampal corticosteroid receptors. This suggests that the impaired GC feedback caused by AMG stimulation may be involved in the facilitatory effect of the AMG on the function of the AC axis.
Catecholaminergic Fiber Innervation of the Vocal Motor System Is Intrasexually Dimorphic in a Teleost with Alternative Reproductive Tactics
Authors: Ghahramani Zachary N. , Timothy Miky , Kaur Gurpreet , Gorbonosov Michelle , Chernenko Alena , Forlano Paul M.
Published: September 2015

Catecholamines, which include the neurotransmitters dopamine and noradrenaline, are known modulators of sensorimotor function, reproduction, and sexually motivated behaviors across vertebrates, including vocal-acoustic communication. Recently, we demonstrated robust catecholaminergic (CA) innervation throughout the vocal motor system in the plainfin midshipman fish Porichthys notatus, a seasonal breeding marine teleost that produces vocal signals for social communication. There are 2 distinct male reproductive morphs in this species: type I males establish nests and court females with a long-duration advertisement call, while type II males sneak spawn to steal fertilizations from type I males. Like females, type II males can only produce brief, agonistic, grunt type vocalizations. Here, we tested the hypothesis that intrasexual differences in the number of CA neurons and their fiber innervation patterns throughout the vocal motor pathway may provide neural substrates underlying divergence in reproductive behavior between morphs. We employed immunofluorescence (-ir) histochemistry to measure tyrosine hydroxylase (TH; a rate-limiting enzyme in catecholamine synthesis) neuron numbers in several forebrain and hindbrain nuclei as well as TH-ir fiber innervation throughout the vocal pathway in type I and type II males collected from nests during the summer reproductive season. After controlling for differences in body size, only one group of CA neurons displayed an unequivocal difference between male morphs: the extraventricular vagal-associated TH-ir neurons, located just lateral to the dimorphic vocal motor nucleus (VMN), were significantly greater in number in type II males. In addition, type II males exhibited greater TH-ir fiber density within the VMN and greater numbers of TH-ir varicosities with putative contacts on vocal motor neurons. This strong inverse relationship between the predominant vocal morphotype and the CA innervation of vocal motor neurons suggests that catecholamines may function to inhibit vocal output in midshipman. These findings support catecholamines as direct modulators of vocal behavior, and differential CA input appears reflective of social and reproductive behavioral divergence between male midshipman morphs.
Determining the Role of Dynamic Hyperinflation in Patients with Severe Chronic Obstructive Pulmonary Disease
Authors: Klooster Karin , ten Hacken Nick H.T. , Hartman Jorine E. , Sciurba Frank C. , Kerstjens Huib A.M. , Slebos Dirk-Jan
Published: September 2015

Background: Dynamic hyperinflation due to increased respiratory frequency during exercise is associated with limitations in exercise capacity in patients with moderately severe chronic obstructive pulmonary disease (COPD). Objectives: The present study assessed whether the manually paced tachypnea (MPT) test, sitting at rest, induces dynamic hyperinflation correlating with exercise capacity in patients with very severe COPD. Methods: Dynamic hyperinflation was induced by the MPT test, using a breathing frequency of 40/min for 1 min. Dynamic hyperinflation was defined as a ‘change' in inspiratory capacity (IC) before and directly after the MPT test. At baseline, static hyperinflation by body plethysmography was measured, as well as the 6-min walking test and spirometry. Results: We studied 74 patients with severe COPD (age 59 ± 9 years, FEV1 28 ± 10% predicted). All patients tolerated the MPT test well. It induced a significant decrease in IC: -0.65 ± 0.33 liters, p < 0.001, correlating with the 6-min walking distance (rho = -0.246, p = 0.034). Static hyperinflation [IC/total lung capacity (TLC)] at baseline correlated stronger with the 6-min walking distance (r = 0.582, p < 0.001). Multiple regression analysis showed that IC/TLC, but not dynamic hyperinflation, was the only independent predictor of walking distance. Conclusions: In patients with very severe COPD, dynamic hyperinflation measurement by the MPT test is feasible and contributes less importantly to exercise performance than static hyperinflation.
In Nonobese Girls, Waist Circumference as a Predictor of Insulin Resistance Is Comparable to MRI Fat Measures and Superior to BMI
Authors: Wolfgram Peter M. , Connor Ellen L. , Rehm Jennifer L. , Eickhoff Jens C. , Zha Wei , Reeder Scott B. , Allen David B.
Published: September 2015

Objective: The aim of this study was to investigate the degree to which waist circumference (WC), body mass index (BMI), and magnetic resonance imaging (MRI)-measured abdominal fat deposition predict insulin resistance (IR) in nonobese girls of diverse racial and ethnic backgrounds. Methods: Fifty-seven nonobese girls (12 African-American, 16 Hispanic White, and 29 non-Hispanic White girls) aged 11-14 years were assessed for WC, MRI hepatic proton density fat fraction, visceral and subcutaneous adipose tissue volume, BMI Z-score, fasting insulin, homeostasis model of assessment (HOMA)-IR, adiponectin, leptin, sex hormone-binding globulin, high-density lipoprotein cholesterol, and triglycerides. Results: Univariate and multivariate analyses adjusted for race and ethnicity indicated that only WC and visceral adipose tissue volume were independent predictors of fasting insulin and HOMA-IR, while hepatic proton density fat fraction, BMI Z-score, and subcutaneous adipose tissue volume were dependent predictors. Hispanic White girls showed significantly higher mean fasting insulin and HOMA-IR and lower sex hormone-binding globulin than non-Hispanic White girls (p < 0.01). Conclusions: In nonobese girls of diverse racial and ethnic backgrounds, WC, particularly when adjusted for race or ethnicity, is an independent predictor of IR comparable to MRI-derived measurements of fat and superior to the BMI Z-score.
Treatment Progress of Paroxysmal Sympathetic Hyperactivity after Acquired Brain Injury
Authors: Feng Ying , Zheng Xiang , Fang Zhicheng
Published: September 2015

Paroxysmal sympathetic hyperactivity (PSH) is a common complication of various acquired brain injuries such as traumatic brain injury, subarachnoid hemorrhage, anoxic brain injury, intracerebral hemorrhage, and others. It is manifested by tachycardia, hypertension, tachypnea, diaphoresis, and dystonic posturing. The development of PSH can prolong hospitalization and lead to secondary brain injury and even death. Despite the awareness of the serious clinical impact, there is no consensus on diagnostic criteria. Thus, misdiagnosis and delayed recognition is very common. Most of the current treatment programs come from case reports and small case series; there are very few large-scale randomized controlled trials. Generally accepted medications are opioids, β-blockers and gabapentin (usually used in combination). However, the efficacy of these drugs has not been systematically assessed. The purpose of this review is to determine the treatment strategies and drugs commonly used for PSH at the overall level.
Dabigatran use in elderly patients with atrial fibrillation
Authors: Avgil-Tsadok Meytal , Jackevicius Cynthia , Essebag Vidal , Eisenberg Mark J. , Rahme Elham , Behlouli Hassan , Pilote Louise
Published: September 2015

In elderly patients (≥75 years), evidence of dabigatran efficacy is lacking and increased vigilance is warranted. We aimed to assess dabigatran effectiveness and safety in elderly patients in real-world practice. We conducted a population-based study using administrative databases, in Quebec (1999–2013). Dabigatran users (110/150 mg) were compared with matched warfarin users with regard to stroke and bleeding events. Age was categorised into < 75 or ≥ 75 years. Propensity score adjusted models were used. The cohort consisted of 15,918 dabigatran users and 47,192 matched warfarin users, with 67.3 % being elderly patients. The elderly predominantly used the lower dose (80.1 %) while younger patients mainly used the higher dose (80.0 %). In multivariable analyses adjusted for propensity score, the risk of stroke in elderly patients using dabigatran, was no different than the risk in warfarin users (HR 1.05, 95 % CI: 0.93, 1.19) regardless of dabigatran dose. However, dabigatran was associated with lower rates of intracranial haemorrhage (HR 0.60, 95 % CI: 0.47–0.76) and higher rates of gastrointestinal bleeding (HR 1.30 95 % CI: 1.14–1.50) when compared to warfarin. Based on real-life experience, dabigatran can offer an alternative to warfarin in elderly patients, with fewer intracranial bleeding events. However, caution is warranted for gastrointestinal bleeding.