bluuebunny/crossref_metadata_2025 huggingface dataset:
Mortality and loss-to-follow-up during the pre-treatment period in an antiretroviral therapy programme under normal health service conditions in Uganda
Authors: Amuron Barbara , Namara Geoffrey , Birungi Josephine , Nabiryo Christine , Levin Jonathan , Grosskurth Heiner , Coutinho Alex , Jaffar Shabbar
Published: August 2009

Background

In many HIV programmes in Africa, patients are assessed clinically and prepared for antiretroviral treatment over a period of 4–12 weeks. Mortality rates following initiation of ART are very high largely because patients present late with advanced disease. The rates of mortality and retention during the pre-treatment period are not well understood. We conducted an observational study to determine these rates.

Methods

HIV-infected subjects presenting at The AIDS Support Clinic in Jinja, SE Uganda, were assessed for antiretroviral therapy (ART). Eligible subjects were given information and counselling in 3 visits done over 4–6 weeks in preparation for treatment. Those who did not complete screening were followed-up at home. Survival analysis was done using poisson regression.

Results

4321 HIV-infected subjects were screened of whom 2483 were eligible for ART on clinical or immunological grounds. Of these, 637 (26%) did not complete screening and did not start ART. Male sex and low CD4 count were associated independently with not completing screening. At follow-up at a median 351 days, 181 (28%) had died, 189 (30%) reported that they were on ART with a different provider, 158 (25%) were alive but said they were not on ART and 109 (17%) were lost to follow-up. Death rates (95% CI) per 100 person-years were 34 (22, 55) (n.18) within one month and 37 (29, 48) (n.33) within 3 months. 70/158 (44%) subjects seen at follow-up said they had not started ART because they could not afford transport.

Conclusion

About a quarter of subjects eligible for ART did not complete screening and pre-treatment mortality was very high even though patients in this setting were well informed. For many families, the high cost of transport is a major barrier preventing access to ART.
Prevalence of risk factors for non-communicable diseases in the Mekong Delta, Vietnam: results from a STEPS survey
Authors: Pham Luc H , Au Thuy B , Blizzard Leigh , Truong Nhan B , Schmidt Michael D , Granger Robert H , Dwyer Terence
Published: August 2009

Background

Despite the increasing burden of non-communicable diseases (NCD) in Vietnam, information on the prevalence of preventable risk factors for NCD is restricted to the main urban centres of Ha Noi, and Ho Chi Minh City (HCMC). This population-based survey aimed to describe the prevalence of risk factors for NCD in a rural Vietnamese sample.

Methods

This survey was conducted using the WHO "STEPwise approach to surveillance of non-communicable diseases" (STEPS) methodology. Participants (n = 1978) were residents of the Mekong Delta region selected by multi-stage sampling. Standardised international protocols were used to measure behavioural risk factors (smoking, alcohol consumption, fruit and vegetable consumption, physical activity), physical characteristics (weight, height, waist and hip circumferences, blood pressure – BP), fasting blood glucose (BG) and total cholesterol (TC). Data were analysed using complex survey analysis methods.

Results

In this sample, 8.8% of men and 12.6% of women were overweight (body mass index (BMI) ≥ 25 kg/m2) and 2.3% of men and 1.5% of women were obese (BMI ≥ 30 kg/m2). The prevalence of hypertension (systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, or taking medication for hypertension) was 27.3% for men and 16.2% for women. There were 1.0% of men and 1.1% of women with raised BG (defined as capillary whole BG of at least 6.1 mmol/L).

Conclusion

We provide the first NCD risk factor profile of people living in the Mekong Delta of Vietnam using standardised methodology. Our findings for this predominantly rural sample differ from previous studies conducted in Ha Noi and HCMC, and suggest that it is inappropriate to generalise findings from the big-city surveys to the other 80% of the population.
Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients
Authors: Yamada Hidetaka , Shinmura Kazuya , Goto Masanori , Iwaizumi Moriya , Konno Hiroyuki , Kataoka Hideki , Yamada Masami , Ozawa Takachika , Tsuneyoshi Toshihiro , Tanioka Fumihiko , Sugimura Haruhiko
Published: August 2009

Background

Germline mono-allelic promoter hypermethylation of the MLH1 or MSH2 gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor gene CDH1 (E-cadherin) might cause predisposition to gastric cancer.

Methods

We prepared two groups of samples, a group of blood samples from 22 patients with familial gastric cancer or early-onset gastric cancer selected from among 39 patients, and a group of non-cancerous gastric tissue samples from 18 patients with sporadic gastric cancer showing loss of CDH1 expression selected from among 159 patients. We then investigated the allele-specific methylation status of the CDH1 promoter by bisulfite sequencing of multiple clones.

Results

Although there was a difference between the methylation level of the two alleles in some samples, there was no mono-allelic promoter hypermethylation in any of the samples.

Conclusion

These results suggest that germline mono-allelic hypermethylation of the CDH1 promoter is not a major predisposing factor for gastric cancer.
Selective entrainment of the Drosophilacircadian clock to daily gradients in environmental temperature
Authors: Currie Jake , Goda Tadahiro , Wijnen Herman
Published: August 2009

Background

Circadian clocks are internal daily time keeping mechanisms that allow organisms to anticipate daily changes in their environment and to organize their behavior and physiology in a coherent schedule. Although circadian clocks use temperature compensation mechanisms to maintain the same pace over a range of temperatures, they are also capable of synchronizing to daily temperature cycles. This study identifies key properties of this process.

Results

Gradually ramping daily temperature cycles are shown here to synchronize behavioral and molecular daily rhythms in Drosophila with a remarkable efficiency. Entrainment to daily temperature gradients of amplitudes as low as 4°C persisted even in the context of environmental profiles that also included continuous gradual increases or decreases in absolute temperature. To determine which elements of daily temperature gradients acted as the key determinants of circadian activity phase, comparative analyses of daily temperature gradients with different wave forms were performed. The phases of ascending and descending temperature acted together as key determinants of entrained circadian phase. In addition, circadian phase was found to be modulated by the relative temperature of release into free running conditions. Release at or close to the trough temperature of entrainment consistently resulted in phase advances. Re-entrainment to daily temperature gradients after large phase shifts occurred relatively slowly and required several cycles, allowing flies to selectively respond to periodic rather than anecdotal signals. The temperature-entrained phase relationship between clock gene expression rhythms and locomotor activity rhythms strongly resembled that previously observed for light entrainment. Moreover, daily temperature gradient and light/dark entrainment reinforced each other if the phases of ascending and descending temperature were in their natural alignment with the light and dark phases, respectively.

Conclusion

The present study systematically examined the entrainment of clock-controlled behavior to daily environmental temperature gradients. As a result, a number of key properties of circadian temperature entrainment were identified. Collectively, these properties represent a circadian temperature entrainment mechanism that is optimized in its ability to detect the time-of-day information encoded in natural environmental temperature profiles. The molecular events synchronized to the daily phases of ascending and descending temperature are expected to play an important role in the mechanism of circadian entrainment to daily temperature cycles.
A novel approach to inhibit HIV-1 infection and enhance lysis of HIV by a targeted activator of complement
Authors: Xu Yuanyong , Zhang Chuanfu , Jia Leili , Wen Cuirong , Liu Huihui , Wang Yong , Sun Yansong , Huang Liuyu , Zhou Yusen , Song Hongbin
Published: August 2009

Background

The complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells.

Presentation of the hypothesis

Previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2) linked to a complement-activating human IgG1 Fc domain (CR2-Fc), can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis.

Testing the hypothesis

Our hypothesis was tested using cell-free HIV-1 virions cultivatedin vitroand assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus.

Implications of the hypothesis

The targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.
Promoting smoking cessation in Bangladeshi and Pakistani male adults: design of a pilot cluster randomised controlled trial of trained community smoking cessation workers
Authors: Begh Rachna A , Aveyard Paul , Upton Penney , Bhopal Raj S , White Martin , Amos Amanda , Prescott Robin J , Bedi Raman , Barton Pelham , Fletcher Monica , Gill Paramjit , Zaidi Qaim , Sheikh Aziz
Published: August 2009

Background

The prevalence of smoking is higher among Pakistani and Bangladeshi males than among the general population. Smokers who receive behavioural support and medication quadruple their chances of stopping smoking, but evidence suggests that these populations do not use National Health Service run stop smoking clinics as frequently as would be expected given their high prevalence of smoking. This study aims to tackle some of the main barriers to use of stop smoking services and adherence to treatment programmes by redesigning service delivery to be more acceptable to these adult male populations. The study compares the effectiveness of trained Pakistani and Bangladeshi smoking cessation workers operating in an outreach capacity ('clinic + outreach') with standard care ('clinic only') to improve access to and success of National Health Service smoking cessation services.

Methods/design

This is a pilot cluster randomised controlled trial based in Birmingham, UK. Super output areas of Birmingham will be identified in which more than 10% of the population are of Pakistani and/or Bangladeshi origin. From these areas, 'natural geographical communities' will be identified. Sixteen aggregated agglomerations of super output areas will be identified, separating areas from each other using buffer regions in order to reduce potential contamination. These natural communities will be randomised to 'clinic + outreach' (intervention) or 'clinic only' (control) arms. The use of stop smoking services and the numbers of people quitting smoking (defined as prolonged self-reported abstinence at four weeks, three months and six months) will be assessed in each area. In addition, we will assess the impact of the intervention on adherence to smoking cessation treatments and patient satisfaction.

Trial registration

Current Controlled Trials ISRCTN 82127540.
Modeling genetic imprinting effects of DNA sequences with multilocus polymorphism data
Authors: Wen Sheron , Wang Chenguang , Berg Arthur , Li Yao , Chang Myron M , Fillingim Roger B , Wallace Margaret R , Staud Roland , Kaplan Lee , Wu Rongling
Published: August 2009

Single nucleotide polymorphisms (SNPs) represent the most widespread type of DNA sequence variation in the human genome and they have recently emerged as valuable genetic markers for revealing the genetic architecture of complex traits in terms of nucleotide combination and sequence. Here, we extend an algorithmic model for the haplotype analysis of SNPs to estimate the effects of genetic imprinting expressed at the DNA sequence level. The model provides a general procedure for identifying the number and types of optimal DNA sequence variants that are expressed differently due to their parental origin. The model is used to analyze a genetic data set collected from a pain genetics project. We find that DNA haplotype GAC from three SNPs, OPRKG36T (with two alleles G and T), OPRKA843G (with alleles A and G), and OPRKC846T (with alleles C and T), at the kappa-opioid receptor, triggers a significant effect on pain sensitivity, but with expression significantly depending on the parent from which it is inherited (p = 0.008). With a tremendous advance in SNP identification and automated screening, the model founded on haplotype discovery and statistical inference may provide a useful tool for genetic analysis of any quantitative trait with complex inheritance.
The Revised Fibromyalgia Impact Questionnaire (FIQR): validation and psychometric properties
Authors: Bennett Robert M , Friend Ronald , Jones Kim D , Ward Rachel , Han Bobby K , Ross Rebecca L
Published: August 2009

Introduction

The Fibromyalgia Impact Questionnaire (FIQ) is a commonly used instrument in the evaluation of fibromyalgia (FM) patients. Over the last 18 years, since the publication of the original FIQ, several deficiencies have become apparent and the cumbersome scoring algorithm has been a barrier to widespread clinical use. The aim of this paper is to describe and validate a revised version of the FIQ: the FIQR.

Methods

The FIQR was developed in response to known deficiencies of the FIQ with the help of a patient focus group. The FIQR has the same 3 domains as the FIQ (that is, function, overall impact and symptoms). It differs from the FIQ in having modified function questions and the inclusion of questions on memory, tenderness, balance and environmental sensitivity. All questions are graded on a 0–10 numeric scale. The FIQR was administered online and the results were compared to the same patient's online responses to the 36-Item Short Form Health Survey (SF-36) and the original FIQ.

Results

The FIQR was completed online by 202 FM patients, 51 rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) patients (31 RA and 20 SLE), 11 patients with major depressive disorder (MDD) and 213 healthy controls (HC). The mean total FIQR score was 56.6 ± 19.9 compared to a total FIQ score of 60.6 ± 17.8 (P < 0.03). The total scores of the FIQR and FIQ were closely correlated (r = 0.88, P < 0.001). Each of the 3 domains of the FIQR correlated well with the 3 related FIQ domains (r = 0.69 to 0.88, P < 0.01). The FIQR showed good correlation with comparable domains in the SF-36, with a multiple regression analysis showing that the three FIQR domain scores predicted the 8 SF-36 subscale scores. The FIQR had good discriminant ability between FM and the 3 other groups; total FIQR scores were HC (12.1 ± 11.6), RA/SLE (28.6 ± 21.2) and MDD (17.3 ± 11.8). The patient completion time was 1.3 minutes; scoring took about 1 minute.

Conclusions

The FIQR is an updated version of the FIQ that has good psychometric properties, can be completed in less than 2 minutes and is easy to score. It has scoring characteristics comparable to the original FIQ, making it possible to compare past FIQ results with future FIQR results.
Liver X receptors interfere with cytokine-induced proliferation and cell survival in normal and leukemic lymphocytes
Authors: Geyeregger René , Shehata Medhat , Zeyda Maximilian , Kiefer Florian W , Stuhlmeier Karl M , Porpaczy Edit , Zlabinger Gerhard J , Jäger Ulrich , Stulnig Thomas M
Published: August 2009

A novel role for Liver X receptors in lymphocytic cells is described with potential application in immunosuppression and anti-leukemia therapy.

Liver X receptors (LXRs) are nuclear receptors regulating lipid and cholesterol metabolism. Recent data indicate an additional role of LXR in immunity by controlling dendritic cell and T-cell function and in breast and prostate cancer cells. Here, we show that LXR activation interferes with IL-2 and IL-7-induced proliferation and cell cycle progression of human T-cell blasts mainly through inhibited phosphorylation of the retinoblastoma protein and decreased expression of the cell cycle protein cyclin B. Comparable results were obtained with IL-2-dependent chronic lymphoblastic leukemia (CLL) T cells. Furthermore, we show for B-CLL cells that LXR are functionally active and inhibit expression of survival genes bcl-2 and MMP-9, and significantly reduce cell viability, suggesting an interference of LXR with cytokine-dependent CLL cell survival. In conclusion, our data reveal LXR as a potent modulator of cytokine-dependent proliferation and survival of normal and malignant T and B lymphocytes. This novel LXR action could find clinical application in immunosuppressive and antileukemic therapies.
Mechanism underlying activity-dependent insertion of TrkB into the neuronal surface
Authors: Zhao Ling , Sheng Ai-Li , Huang Shu-Hong , Yin Yu-Xia , Chen Bing , Li Xue-Zhi , Zhang Yun , Chen Zhe-Yu
Published: August 2009

Activity-dependent insertion of tyrosine kinase receptor type 2 (TrkB receptor) into the plasma membrane can explain, in part, the preferential effect of brain-derived neurotrophic factor (BDNF) on active neurons; however, the detailed cellular and molecular mechanisms underlying this process are still unclear. In our study, we developed a fluorescence ratiometric assay for surface TrkB receptors to investigate the mechanisms of recruitment of TrkB to the plasma membrane following chemical long-term potentiation (cLTP) induction. We found that, in hippocampal neurons, the effect of cLTP-induced TrkB surface-recruitment occurred predominantly on neurites with rapid kinetics (t1/2 of ∼2.3 minutes) and was dependent on an intact cytoskeleton structure. Mutagenesis studies revealed that the juxtamembrane domain of TrkB is necessary and sufficient for its activity-dependent insertion into the plasma membrane. Moreover, we found that the phosphorylation of TrkB receptor at the Ser478 site by cyclin-dependent kinase 5 (Cdk5) is essential for cLTP-induced TrkB insertion into the neuronal surface. Finally, the degree of cLTP-induced TrkB surface-recruitment is higher in postsynaptic regions, which provides a potential mechanism for rapid enhancement of postsynaptic sensitivity to incoming BDNF signaling. Our studies provide new insights regarding neuronal activity-dependent surface delivery of TrkB receptor, which will advance our understanding of the modulatory role of TrkB in synaptic plasticity.
In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction
Authors: Osakada Fumitaka , Jin Zi-Bing , Hirami Yasuhiko , Ikeda Hanako , Danjyo Teruko , Watanabe Kiichi , Sasai Yoshiki , Takahashi Masayo
Published: August 2009

The use of stem-cell therapy to treat retinal degeneration holds great promise. However, definitive methods of retinal differentiation that do not depend on recombinant proteins produced in animal or Escherichia coli cells have not been devised. Here, we report a defined culture method using low-molecular-mass compounds that induce differentiation of human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells into retinal progenitors, retinal pigment epithelium cells and photoreceptors. The casein kinase I inhibitor CKI-7, the ALK4 inhibitor SB-431542 and the Rho-associated kinase inhibitor Y-27632 in serum-free and feeder-free floating aggregate culture induce retinal progenitors positive for RX, MITF, PAX6 and CHX10. The treatment induces hexagonal pigmented cells that express RPE65 and CRALBP, form ZO1-positive tight junctions and exhibit phagocytic functions. Subsequent treatment with retinoic acid and taurine induces photoreceptors that express recoverin, rhodopsin and genes involved in phototransduction. Both three-factor (OCT3/4, SOX2 and KLF4) and four-factor (OCT3/4, SOX2, KLF4 and MYC) human iPS cells could be successfully differentiated into retinal cells by small-molecule induction. This method provides a solution to the problem of cross-species antigenic contamination in cell-replacement therapy, and is also useful for in vitro modeling of development, disease and drug screening.
BLM helicase stimulates the ATPase and chromatin-remodeling activities of RAD54
Authors: Srivastava Vivek , Modi Priyanka , Tripathi Vivek , Mudgal Richa , De Siddharth , Sengupta Sagar
Published: August 2009

Mutation of BLM helicase results in the autosomal recessive disorder Bloom syndrome (BS). Patients with BS exhibit hyper-recombination and are prone to almost all forms of cancer. BLM can exhibit its anti-recombinogenic function either by dissolution of double Holliday junctions or by disruption of RAD51 nucleofilaments. We have now found that BLM can interact with the pro-recombinogenic protein RAD54 through an internal ten-residue polypeptide stretch in the N-terminal region of the helicase. The N-terminal region of BLM prevented the formation of RAD51-RAD54 complex, both in vitro and in vivo. Using the fluorescence recovery after photobleaching (FRAP) technique, we found that RAD54 and BLM rapidly and concurrently, yet transiently, bound to the chromatinized foci. Presence of BLM enhanced the mobility of both soluble and chromatinized RAD51 but not RAD54. The BLM-RAD54 interaction could occur even in absence of functional RAD51. The N-terminal 1-212 amino acids of BLM or an ATPase-dead mutant of the full-length helicase enhanced the ATPase and chromatin-remodeling activities of RAD54. These results indicate that apart from its dominant function as an anti-recombinogenic protein, BLM also has a transient pro-recombinogenic function by enhancing the activity of RAD54.
The effects of shear deformation on the free vibration of elastic beams with general boundary conditions
Authors: Li J , Hua H
Published: August 2009

Free vibration characteristics of shear deformable elastic beams subjected to different sets of boundary conditions are investigated. The analysis is based on a unified one-dimensional shear deformation beam theory. The governing equations of the elastic beams are obtained by means of Hamilton's principle. Four different boundary conditions are considered. The natural frequencies and mode shapes are obtained by applying the dynamic stiffness method, where the elements of the exact dynamic stiffness matrix are derived by using the analytical solutions of the governing equations of the beam in free vibration. The numerical results for the particular beams with different slenderness ratios are presented and compared with those available in the literature.
Dual surface beamforming and acoustical holography for sound field visualization in reverberant environments
Authors: Cho Yong Thung , Roan M J , Bolton J Stuart
Published: August 2009

Near-field acoustical holography is a technique that has been widely used to visualize noise sources from pressure measurements in spaces that can be assumed to be anechoic or semi-anechoic. Previously, a dual surface acoustical holography procedure based on making measurements on two surfaces between the source and a reflecting surface was introduced to remove the effects of reverberation. Little work has been performed in which beamforming has been used to visualize sources based on dual surface, near-field measurements in a reverberant environment: such a procedure is described here. Because many practical measurement environments are not completely anechoic, the source resolution accuracy of dual surface acoustical holography and beamforming procedures in reverberant environments is compared here by using numerical simulations. It has been found that dual surface acoustical holography provides the clearest representation of the source location when sound waves radiating from the source and the reflected waves are propagating in the opposite directions and when the measurement surfaces are conformal with the source geometry. However, it has also been found that dual surface beamforming provides more consistent source resolution performance regardless of the relative direction of wave propagation of the source and reflected waves.
An inverse design of a double-pitch passage for an infinite cascade model experiment
Authors: Cho C-H , Cho S-Y , Gorrell S E , Ahn K-Y , Kim Y-C
Published: August 2009

In this study, sidewalls of a turbine cascade experimental apparatus are designed to satisfy periodic flow conditions with two blades without any flow control or tailboards. Generally, the turbine cascade experimental apparatus needs removing fluid from the cascade walls or adjusting tailboards located downstream of the cascade to establish periodic flow conditions through the cascade blades. If a linear turbine cascade often consists of only a few blades within a passage, advantages to this experimental arrangement are increased from using larger turbine cascades, a lower mass flowrate and corresponding decrease in required power, and easier optical access within the cascade passage. However, fewer blades in the cascade make it difficult to establish periodic flow conditions between blades compared to infinite cascade flow conditions. In order to test a turbine cascade with a few blades without flow control devices, only two turbine blades are installed within a double-pitch passage. Sidewall shape is designed with 12 geometric design variables using a gradient-based optimization method, and surface isentropic Mach number distribution on the blades is chosen for the existence of periodic flow conditions. The computed result shows periodic flow conditions obtained by modifying only the sidewalls of the double-pitch passage as a cascade experimental apparatus.
The effect of carbon fibre surface oxidation on the friction and wear properties of polytetrafluoroethylene composites under oil-lubricated conditions
Authors: Li J , Su Y H
Published: August 2009

In this study, the effect of air oxidation and ozone surface treatment of carbon fibres (CFs) on tribological properties of CF-reinforced polytetrafluoroethylene (PTFE) composites under oil-lubricated condition was investigated. Experimental results revealed that ozone-treated CF-reinforced PTFE (CF/PTFE) composite had the lowest friction coefficient and wear compared with untreated and air-oxidated composites. An X-ray photoelectron spectroscopy study of the CF surface showed that, after ozone treatment, oxygen concentration was obviously increased, and the amount of oxygen-containing groups on CF surfaces was largely increased. The increase in the amount of oxygen-containing groups enhanced interfacial adhesion between CF and PTFE matrix. With strong interfacial adhesion of the composite, CFs were strongly bonded with PTFE matrix, and large-scale rubbing-off of PTFE was prevented; therefore, the tribological properties of the composite was improved.
Non-isothermal and electrochemical modelling of the multi-cell module performance in the integrated-planar solid oxide fuel cell
Authors: Mounir H , El Gharad A , Belaiche M , Boukalouch M
Published: August 2009

This article presents a performance analysis of a multi-cell integrated-planar solid oxide fuel cell (IP-SOFC) fuelled by pure hydrogen. A non-isothermal electrochemical model, taking into account the temperature variation produced by electrochemical reactions, air, and fuel flow, is used to predict the characteristics of the multi-cell module. The model results show good agreement with the experimental data obtained from a full-size IP-SOFC module prototype for both a first- and a second-generation hybrid application. In this study, a simulation model of individual cell voltage loss indicates that ohmic and activation losses dominate the performance. Sensitivity analyses of the multi-cell show that decreasing the electrolyte thickness can improve cell performance. An increase in operating temperature causes a decrease in ohmic loss and ameliorates the voltage and power cell. Further, increasing the operating pressure produces a weak increase in cell performance.
Stabilization of carbon nanotube field emitters
Authors: Mann M , Teo K B K , Milne W I , El Gomati M M , Wells T , Tessner T , Ovsyanko M
Published: August 2009

Carbon nanotubes (CNTs) have been determined to be field emitters of high quality, but CNTs produced by chemical vapour deposition can produce emission currents with high instability and noise. This work finds that adsorbates and amorphous carbon deposited during the growth process are the primary contributors to field emission instability, and shows that burning off the amorphous carbon in air at 450°C removes the amorphous carbon, resulting in stabilities of better than 3 per cent over 1 h. This work removes one of the major barriers to the use of CNTs in field emission devices.
A novel short-course regimen of intramuscular iron therapy for anaemic pregnant women
Authors: Thirunavukkarasu Sumangali , Bhandary Amritha
Published: August 2009

This study was conducted in anaemic pregnant women to investigate the efficacy and feasibility of intramuscular iron therapy as a short-course regimen and also to show the usefulness of such a regimen in women intolerable or non-compliant to oral iron.
‘Frozen finger’ in anal fissures
Authors: Chintamani  , Tandon Megha , Khandelwal Rohan
Published: August 2009

Acute anal fissures are usually managed by various invasive and non-invasive modalities ranging from simple lifestyle changes to chemical and surgical sphincterotomies. Frozen finger, prepared using a water-filled ordinary rubber glove, was successfully used in one hundred patients, thus providing a cost-effective and simple solution to the problem.
Primary amoebic meningoencephalitis: two new cases from Pakistan
Authors: Saleem Taimur , Rabbani Madiha , Jamil Bushra
Published: August 2009

Naegleria fowleri causes a fatal infection of the central nervous system. Only one case of N. fowleri meningoencephalitis has previously been reported from Pakistan. We describe two cases of primary amoebic meningoencephalitis. A 24-year-old man presented with a two-day history of high grade fever, headaches and vomiting. He was put on intrathecal amphotericin B, fluconazole and rifampicin when motile trophozoites were identified on a wet mount of cerebrospinal fluid. The patient did not improve and died on the sixth day of admission. The second case was a 30-year-old man who presented with a three-day history of high grade fever, vomiting and agitation. His clinical course was marked by a rapid deterioration. He received intrathecal amphotericin B, fluconazole and broad spectrum antibiotics when motile trophozoites on wet mount were observed. Again, the patient's condition did not improve and he died on the eighth day of admission.
Time Continuity and Nonadditive Expected Utility
Authors: Teper Roee
Published: August 2009

Information consisting of probabilities of some (but possibly not all) events induces an integral with respect to a probability specified on a subalgebra. A decision maker evaluates the alternatives using only the available information and completely ignoring unavailable information. Assume now that the decision maker assesses the worth of a different lottery at each point in a discrete time. Assume also that each such lottery is preferred to some fixed alternative lottery. Now, consider the situation where the sequence of lotteries converges in some sense. If the limiting lottery is preferred to the fixed alternative, then the preference order is referred to as time continuous. This paper studies time continuity for two preference functionals: the Choquet integral and the integral with respect to a probability specified on a subalgebra. The integral with respect to probability specified on a subalgebra is determined by the structure of the available information. By relating it to the Choquet integral, we characterize the structure of available information that would yield time continuity.
Ustekinumab: Treatment of Adult Moderate-to-Severe Chronic Plaque Psoriasis
Authors: Scanlon James V , Exter Benjamin P , Steinberg Michael , Jarvis Courtney I
Published: August 2009

Objective:

To systematically review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of ustekinumab to inform pharmacists and other healthcare professionals of this new biologic therapy for psoriasis.

Data Sources:

A search of PubMed/MEDLINE, EMBASE, and International Pharmaceutical Abstracts was performed through July 2009, limited to publications in English, using the search terms CNTO-1275, ustekinumab, interleukin-12, interleukin-23, and/or psoriasis to identify literature sources. References from the retrieved articles were also evaluated to identify relevant literature. An abstract from a Congress of the European Academy of Dermatology and Venereology and unpublished Phase 3 clinical trials in progress (using www.clinicaltrials.gov ) were also reviewed. The Food and Drug Administration, European Medicines Agency, and Health Canada Web sites were used to retrieve product monographs, regulatory guidances, and advisory committee briefing packets.

Study Selection and Data Extraction:

All available studies relevant to the pharmacology, pharmacokinetics, and clinical safety/efficacy of ustekinumab for the treatment of psoriasis were included, with preference for human data.

Data Synthesis:

Ustekinumab, an anti-interleukin-12/23 monoclonal antibody, achieved the primary endpoint of 75% reduction in the Psoriasis Area and Severity Index score in a large proportion of patients in the Phase 3 PHOENIX trials. Commensurate improvements were also seen in the Physician's Global Assessment and Dermatology Life Quality Index scores. These efficacy results were reproduced in the ACCEPT trial, demonstrating superiority of ustekinumab to etanercept. The frequency of adverse events was similar between ustekinumab and placebo; common adverse events reported included nasopharyngitis, upper respiratory tract infection, headache, arthralgia, cough, and injection site reactions. Phase 3 studies indicate that the optimal dosing appears to be 45 mg for patients weighing less than 100 kg or 90 mg for patients weighing more than 100 kg, with both doses administered subcutaneously. In these studies, the second dose was given 4 weeks after the first and then every 8–12 weeks thereafter, based upon response.

Conclusions:

Ustekinumab, a promising new therapy, reduces the extent and severity of psoriasis and was well tolerated in clinical trials. Ongoing clinical trials will allow clinicians to further assess the efficacy/safety profile of this novel biologic.
The Geometry of Perisaccadic Visual Perception
Authors: Richard Alby , Churan Jan , Guitton Daniel E. , Pack Christopher C.
Published: August 2009

Our ability to explore our surroundings requires a combination of high-resolution vision and frequent rotations of the visual axis toward objects of interest. Such gaze shifts are themselves a source of powerful retinal stimulation, and so the visual system appears to have evolved mechanisms to maintain perceptual stability during movements of the eyes in space. The mechanisms underlying this perceptual stability can be probed in the laboratory by briefly presenting a stimulus around the time of a saccadic eye movement and asking subjects to report its position. Under such conditions, there is a systematic misperception of the probes toward the saccade end point. This perisaccadic compression of visual space has been the subject of much research, but few studies have attempted to relate it to specific brain mechanisms. Here, we show that the magnitude of perceptual compression for a wide variety of probe stimuli and saccade amplitudes is quantitatively predicted by a simple heuristic model based on the geometry of retinotopic representations in the primate brain. Specifically, we propose that perisaccadic compression is determined by the distance between the probe and saccade end point on a map that has a logarithmic representation of visual space, similar to those found in numerous cortical and subcortical visual structures. Under this assumption, the psychophysical data on perisaccadic compression can be appreciated intuitively by imagining that, around the time of a saccade, the brain confounds nearby oculomotor and sensory signals while attempting to localize the position of objects in visual space.
Shift from Hippocampal to Neocortical Centered Retrieval Network with Consolidation
Authors: Takashima Atsuko , Nieuwenhuis Ingrid L.C. , Jensen Ole , Talamini Lucia M. , Rijpkema Mark , Fernández Guillén
Published: August 2009

The standard model of system-level consolidation posits that the hippocampus is part of a retrieval network for recent memories. According to this theory, the memories are gradually transferred to neocortical circuits with consolidation, where the connections within this circuit grow stronger and reorganized so that redundant and/or contextual details may be lost. Thus, remote memories are based on neocortical networks and can be retrieved independently of the hippocampus. To test this model, we measured regional brain activity and connectivity during retrieval with functional magnetic resonance imaging. Subjects were trained on two sets of face–location association and were tested with two different delays, 15 min and 24 h including a whole night of sleep. We hypothesized that memory traces of the locations associated with specific faces will be linked through the hippocampus for the retrieval of recently learned association, but with consolidation, the activity and the functional connectivity between the neocortical areas will increase. We show that posterior hippocampal activity related to high-confidence retrieval decreased and neocortical activity increased with consolidation. Moreover, the connectivity between the hippocampus and the neocortical regions decreased and in turn, cortico-cortical connectivity between the representational areas increased. The results provide mechanistic support for a two-level process of the declarative memory system, involving initial representation of new associations in a network including the hippocampus and subsequent consolidation into a predominantly neocortical network.
Corticotropin-Releasing Factor Receptor Antagonism within the Dorsal Raphe Nucleus Reduces Social Anxiety-Like Behavior after Early-Life Social Isolation
Authors: Lukkes Jodi , Vuong Shawn , Scholl Jamie , Oliver Harvey , Forster Gina
Published: August 2009

Social isolation of rats during the early part of development increases social anxiety-like behavior in adulthood. Furthermore, early-life social isolation increases the levels of corticotropin-releasing factor (CRF) receptors in the serotonergic dorsal raphe nucleus (dRN) of adult rats. Interactions between serotonin and CRF systems are thought to mediate anxiety behavior. Therefore, we investigated the effects of CRF receptor antagonism within the dRN on social anxiety-like behavior after early-life social isolation. Male rats were reared in isolation or in groups from weaning until midadolescence, and rehoused in groups and allowed to develop into adulthood. Adult rats underwent surgery to implant a drug cannula into the dRN. After recovery from surgery and acclimation to the testing arena, rats were infused with vehicle or the CRF receptor antagonistd-Phe-CRF(12-41)(50 or 500 ng) into the dRN before a social interaction test. Isolation-reared rats pretreated with vehicle exhibited increased social anxiety-like behavior compared with rats reared in groups. Pretreatment of the dRN withd-Phe-CRF(12-41)significantly reduced social anxiety-like behaviors exhibited by isolation-reared rats. Overall, this study shows that early-life social stress results in heightened social anxiety-like behavior, which is reversed by CRF antagonism within the dRN. These data suggest that CRF receptor antagonists could provide a potential treatment of stress-related social anxiety.
TRPC Channels Mediate a Muscarinic Receptor-Induced Afterdepolarization in Cerebral Cortex
Authors: Yan Hai-Dun , Villalobos Claudio , Andrade Rodrigo
Published: August 2009

Activation of muscarinic cholinergic receptors on pyramidal cells of the cerebral cortex induces the appearance of a slow afterdepolarization that can sustain autonomous spiking after a brief excitatory stimulus. Accordingly, this phenomenon has been hypothesized to allow for the transient storage of memory traces in neuronal networks. Here we investigated the molecular basis underlying the muscarinic receptor-induced afterdepolarization using molecular biological and electrophysiological strategies. We find that the ability of muscarinic receptors to induce the inward aftercurrent underlying the slow afterdepolarization is inhibited by expression of a Gαq-11dominant negative and is also markedly reduced in a phospholipase C β1 (PLCβ1) knock-out mouse. Furthermore, we show, using a genetically encoded biosensor, that activation of muscarinic receptor induces the breakdown of phosphatidylinositol 4,5-bisphosphate in pyramidal cells. These results indicate that the Gαq-11/PLCβ1 cascade plays a key role in the ability of muscarinic receptors to signal the inward aftercurrent. We have shown previously that the muscarinic afterdepolarization is mediated by a calcium-activated nonselective cation current, suggesting the possible involvement of TRPC channels. We find that expression of a TRPC dominant negative inhibits, and overexpression of wild-type TRPC5 or TRPC6 enhances, the amplitude of the muscarinic receptor-induced inward aftercurrent. Furthermore, we find that coexpression of TRPC5 and T-type calcium channels is sufficient to reconstitute a muscarinic receptor-activated inward aftercurrent in human embryonic kidney HEK-293 cells. These results indicate that TRPC channels mediate the muscarinic receptor-induced slow afterdepolarization seen in pyramidal cells of the cerebral cortex and suggest a possible role for TRPC channels in mnemonic processes.
Best1Is a Gene Regulated by Nerve Injury and Required for Ca2+-Activated Cl−Current Expression in Axotomized Sensory Neurons
Authors: Boudes Mathieu , Sar Chamroeun , Menigoz Aurélie , Hilaire Cécile , Péquignot Marie O. , Kozlenkov Alexei , Marmorstein Alan , Carroll Patrick , Valmier Jean , Scamps Frédérique
Published: August 2009

We investigated the molecular determinants of Ca2+-activated chloride current (CaCC) expressed in adult sensory neurons after a nerve injury. Dorsal root ganglia express the transcripts of three gene families known to induce CaCCs in heterologous systems: bestrophin, tweety, and TMEM16. We found with quantitative transcriptional analysis andin situhybridization that nerve injury induced upregulation of solely bestrophin-1 transcripts in sensory neurons. Gene screening with RNA interference in single neurons demonstrated that mouseBest1is required for the expression of CaCC in injured sensory neurons. Transfecting injured sensory neurons with bestrophin-1 mutants inhibited endogenous CaCC. Exogenous expression of the fusion protein green fluorescent protein–Bestrophin-1 in naive neurons demonstrated a plasma membrane localization of the protein that generates a CaCC with biophysical and pharmacological properties similar to endogenous CaCC. Our data suggest thatBest1belongs to a group of genes upregulated by nerve injury and supports functional CaCC expression in injured sensory neurons.
Visual Processing in the Central Bee Brain
Authors: Paulk Angelique C. , Dacks Andrew M. , Phillips-Portillo James , Fellous Jean-Marc , Gronenberg Wulfila
Published: August 2009

Visual scenes comprise enormous amounts of information from which nervous systems extract behaviorally relevant cues. In most model systems, little is known about the transformation of visual information as it occurs along visual pathways. We examined how visual information is transformed physiologically as it is communicated from the eye to higher-order brain centers using bumblebees, which are known for their visual capabilities. We recorded intracellularlyin vivofrom 30 neurons in the central bumblebee brain (the lateral protocerebrum) and compared these neurons to 132 neurons from more distal areas along the visual pathway, namely the medulla and the lobula. In these three brain regions (medulla, lobula, and central brain), we examined correlations between the neurons' branching patterns and their responses primarily to color, but also to motion stimuli. Visual neurons projecting to the anterior central brain were generally color sensitive, while neurons projecting to the posterior central brain were predominantly motion sensitive. The temporal response properties differed significantly between these areas, with an increase in spike time precision across trials and a decrease in average reliable spiking as visual information processing progressed from the periphery to the central brain. These data suggest that neurons along the visual pathway to the central brain not only are segregated with regard to the physical features of the stimuli (e.g., color and motion), but also differ in the way they encode stimuli, possibly to allow for efficient parallel processing to occur.
Spikes and Membrane Potential Oscillations in Hair Cells Generate Periodic Afferent Activity in the Frog Sacculus
Authors: Rutherford Mark A. , Roberts William M.
Published: August 2009

To look for membrane potential oscillations that may contribute to sensory coding or amplification in the ear, we made whole-cell and perforated-patch recordings from hair cells and postsynaptic afferent neurites in the explanted frog sacculus, with mechanoelectrical transduction (MET) blocked. Small depolarizing holding currents, which may serve to replace thein vivoresting MET current, evoked all-or-none calcium spikes (39–75 mV amplitude) in 37% of hair cells tested, and continuous membrane potential oscillations (14–28 mV; 15–130 Hz) in an additional 14% of cells. Spiking hair cells were on average taller and thinner than nonspiking hair cells, and had smaller outward currents through delayed rectifier channels (IKV) and noninactivating calcium-activated potassium channels (IBK,steady), and larger inward rectifier currents (IK1). Some spiking hair cells fired only a brief train at the onset of a current step, but others could sustain repetitive firing (3–70 Hz). Partial blockade ofIBKchanged the amplitude and frequency of oscillations and spikes, and converted some nonspiking cells into spiking cells. Oscillatory hair cells preferentially amplified sinusoidal stimuli at frequencies near their natural oscillation frequency. Postsynaptic recordings revealed regularly timed bursts of EPSPs in some afferent neurites. EPSP bursts were able to trigger afferent spikes, which may be initiated at the sodium channel cluster located adjacent to the afferent axon's most peripheral myelin segment. These results show that some frog saccular hair cells can generate spontaneous rhythmic activity that may drive periodic background activity in afferent axons.