bluuebunny/crossref_metadata_2025 huggingface dataset:
P64 High rates of rectalChlamydia trachomatisin women reporting anal sex in the GUM clinic
Authors: Simon S , Hassan-Ibrahim M , Soni S
Published: May 2012

Background

Nucleic acid amplification (NAAT) testing forNeisseria gonorrhoeae(GC) andChlamydia trachomatis(CT) is now widely available but not licensed for use at non-genital sites. Despite this, high rates of pharyngeal and rectal GC and CT have been demonstrated in MSM. Currently there is little data on the prevalence of infection at these sites in women reporting oral and anal sex.

Aim

To determine the prevalence of pharyngeal and rectal CT and GC in women attending GUM.

Methods

Between 1 June and 31 October 2011 all women reporting oral and anal sex were offered pharyngeal and blind rectal swabs as well as cervical testing for CT and GC. Samples were analysed using the BD ProbeTecTM CT/GC Qx Amplified DNA assay in the BD ViperTM system. All women with positive GC NAAT results had swabs sent for GC culture and sensitivities.

Results

Median age was 25 years (IQR 21–31) and most women were of white ethnicity. 2235 swabs were taken, 124 were excluded due to incomplete labelling. 2111 women had non-genital sampling: 165 rectal swabs only, 1652 pharyngeal swabs only, 147 both sites. In nine and five women the pharynx and rectum were the sole sites of CT infection respectively. In two women, the pharynx was the sole site of GC infection. All women were asymptomatic at throat and rectum (see abstract P64 table 1).

Abstract P64 Table 1

CT and GC prevalence at different sites

PharynxRectumCervixCT NAAT1.3% (23/1799)7.1% (22/312)6.1% (194/3073)GC NAAT0.28% (5/1799)0.32% (1/312)0.49% (15/3073)GC Culture0.17% (3/1799)0.32% (1/312)0.36% (11/3073)

Discussion

Rectal CT rates were high among women reporting anal sex. As the antibiotic treatment of cervical and rectal CT differs, this pool of infection could remain untreated. We recommend routinely asking about anal sex and testing where appropriate. Rates of pharyngeal CT were low but higher than GC overall. Although 11 women had pharyngeal CT/GC only, and would have been missed, the cost of detecting one of these infections was £1727 and this has precluded ongoing screening.
P68 Improving the management of chlamydia in non-GUM settings: it to the rescue!
Authors: Zhou C N C , Roberts J , Davies J , Longbone M , Dean G
Published: May 2012

Background

BASHH guidelines recommend all patients diagnosed withChlamydia trachomatis(CT) should be given a detailed explanation of the condition, managed with appropriate antibiotics and have effective partner notification (PN). Patients tested in non-GUM settings may receive sub-optimal management. Following a 2008 audit highlighting several untreated CT cases in the Gynaecology Department (GD) we introduced a bespoke IT lab-link allowing daily downloads of results to GUM health advisers (HA).

Objectives

To re-audit the management of females tested for CT in GD.

Methods

We performed a retrospective database analysis of all CT tests requested by any of the 11 Gynaecology consultants from June 11 to January 12. Demographic and clinical details were extracted from a prospectively collected lab. database and clinic records. Results were compared with the 2008 audit. Fisher's exact test was used to compare differences between proportions.

Results

889 tests {864 (97.2%) negative, 16 (1.8%) positive, 9 (1%) not tested—incorrect swab} were requested by GD over 29 weeks. HAs were notified of 100% of results in real time. Median time from notification of positive results to patient contact was 1 day (range 1–60). Median time from positive result to treatment was 7 days (range 1–70). This compares to an upper limit of 168 days in the 2008 audit. Recommended antibiotics were used in all cases. PN outcomes improved from 31% to 75% (p=0.02) and untreated cases decreased from 38% to 18.7% (p=0.2) (see abstract P68 table 1).

Abstract P68 Table 1

Management of chlamydia positive patients

YearSite 1/2 (%)Age: median (range) yearsCT positive (%)PN complete (%)Untreated (%)200880/2022 (19–40)13/647 (2)4/13 (31)5/13 (38)2011/201279/2233 (14–84)16/889 (1.8)12/16 (75)3/16 (18.7)

Discussion

Since the introduction of a referral pathway and automated IT lab-link, management of CT positive patients from GD has improved, in particular PN and proportion left untreated. GUM departments should have a clear pathway for the management of patients diagnosed with STIs in non-GUM settings.
P95 Attitudes to sexual history taking and STI screening in a non-sexual health delivered HIV service
Authors: Salter E F C , Magee E , Allstaff S L
Published: May 2012

Background

An audit within our HIV service failed to meet national sexual health targets. Barriers to sexual history (SHx) taking and STI screening include fear of causing offence. This may be more so in HIV services delivered by non-sexual health clinicians.

Aim

To determine patients' attitudes to SHx taking and STI screening in an infectious diseases-led HIV service.

Methods

An anonymous, semi-structured questionnaire was offered to all clinic attendees from September-December 2011. Data collected included demographics, HIV history, sexual history and attitudes to SHx taking and STI screening.

Results

Of the 101 questionnaires returned; 68% were male and almost two thirds were aged 26–40. 30% were MSM. 35% were in sero-discordant regular relationships. 37% had one partner in the last year and 15% had >1. 35% had a previous STI. 94% agreed with regular syphilis and hepatitis B (HBV) testing. 40% would have declined STI screening if offered; 26% of these were MSM, 16% had >1 partner in the last year and 34% had ≥1 past STI. Only 62% recalled being asked about sex. Preferred sites for sexual health consultations are detailed in abstract P95 table 1.

Abstract P95 Table 1

Preferred site for delivery of sexual health care (respondents may have given multiple preferences)

Service offered (no of respondents)HIV clinic n (%)Sexual health clinic n (%)Primary care n (%)None/other n (%)SHx taking (n=90)70 (78)21 (23)25 (28)7 (8)STI screening (n=90)72 (80)17 (19)11 (12)4 (4)Contraception (n=27)15 (56)5 (19)11 (41)4 (15)Cervical cytology (n=27)7 (25)5 (19)17 (63)3 (11)

Conclusions

Most patients found regular HBV and syphilis testing acceptable, however 40% would decline STI screening indicating that they may be uninformed about STIs, be uncertain of their risk and misperceive the invasiveness of STI screening. Most patients found the HIV clinic a preferable site for both SHx taking and STI screening. Specific sexual health training should be delivered to clinicians in non-sexual health led HIV services in order to improve the sexual health of HIV patients.
P97 Women requiring emergency contraception are a high risk group for sexually transmitted infections in future
Authors: Varma R
Published: May 2012

Background

Women in UK are able to get emergency hormonal contraception from various sources including general practice, community contraception clinic, A&E, pharmacies and GUM services. Other than the GUM services most other providers are not offering integrated sexual health services so the screening and prevention of sexually transmitted disease (STI) may be inadequate.

Aim

The aim of this study was to find the incidence of STI in this group of clients requesting emergency contraception at the time of their visit for emergency contraception and in subsequent visits within 6 months of the index visit.

Methods

We did a retrospective review of all electronic consultations in which Levonelle was issued during 6 months from January 2011 to June 2011. 102 consultations were identified by electronic search using search term Levonelle. Data were collected on Excel spreadsheet and analysed.

Results

102 consultations were identified for 91 patients. Median age was 20 (range 15–42), 55% (50/91) were Black Caribbean. On the day of the index visit for emergency contraception, out of the 102 consultations 79 had STI screen (77%). We detected STI in six women (7.5%). Five women hadChlamydia trachomatisand one had gonorrhoea. In the subsequent 6 months, 59 out of the original 91 women (64%) returned to our services. Out of these 59 women, 52 (88%) underwent STI screen. 15 women out of the 52 tested (28.8%) had a positive diagnosis of STI. 9/52 (17.3%) hadChlamydia trachomatisinfection, 3/52(5.7%) had gonorrhoea; two patients had bothChlamydia trachomatisand gonorrhoea. The other STI diagnosed were trichomonas vaginalis 2/52(3.8%), first episode genital herpes infection 2/52(3.8%) and 1/52 (1.95%) had first episode genital warts.

Conclusion

Women who attend for emergency contraception are at high risk of contacting future sexually transmitted infections and should be advised to have screening for sexually transmitted infection at 3 and/or 6 months. More research is needed in this sub group of women to improve the sexual health of the community.
Interactive television news
Authors: Olsen Dan R. , Bunn Derek , Boulter Trent , Walz Robert
Published: May 2012

A new interactive television experience has been created for watching television news. The goal is to create a news experience that is similar to the way people watch television in their living rooms while giving viewers the power to make choices about what they see. We partnered with existing news organizations to create tools consistent with current news production practices. The viewer experience allows selection of the order of news content, skipping unwanted content and exploring stories in more depth. These tools were used to produce seven days of interactive commercial news that were viewed in ten homes.
Protecting against data breaches; living with mistakes
Authors: Hong Jason , Linden Greg
Published: May 2012

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

twitter

Follow us on Twitter at http://twitter.com/blogCACM

http://cacm.acm.org/blogs/blog-cacm

Jason Hong writes about security breaches and offers a three-pronged approach. Greg Linden discusses the differences between computers and the human brain and their tolerance of errors.
Analyzing medical data
Authors: Goth Gregory
Published: May 2012

Electronic patient records contain a treasure trove of data, and researchers are using natural language processing technology to mine the structured data and free text.
An influential theoretician
Authors: Hyman Paul
Published: May 2012

Sanjeev Arora, winner of the 2011 ACM-Infosys Award, discusses his pivotal role in theoretical computer science.
Modeling people and places with internet photo collections
Authors: Crandall David , Snavely Noah
Published: May 2012

Understanding the world from the sea of online photos.
The GCT program toward the
P
vs.
NP
problem
Authors: Mulmuley Ketan D.
Published: May 2012

Exploring the power and potential of geometric complexity theory.
Puzzled: Solutions and sources
Authors: Winkler Peter
Published: May 2012

Last month (May 2012) we posted a trio of brainteasers concerning designs on square grids. Here, we offer solutions to all three. How did you do?
Writing secure programs
Authors: Denning Peter J.
Published: May 2012

Protecting computing systems and networks from attackers and data theft is an enormously complicated problem. The individual operating systems are complex (typically more than 40 million lines of code), they are connected to an enormous Internet (on order of 1 billion hosts), and the whole network is heavily populated (more than 2.3 billion users). Hunting down and patching vulnerabilities is a losing game.
Report on the fourth workshop on exploiting semantic annotations in information retrieval (ESAIR'11)
Authors: Alonso Omar , Kamps Jaap , Karlgren Jussi
Published: May 2012

There is an increasing amount of structure on the Web as a result of modern Web languages, user tagging and annotation, and emerging robust NLP tools. These meaningful, semantic, annotations hold the promise to significantly enhance information access, by increasing the depth of analysis of today's systems. Currently, we have only started to explore the possibilities and only begun to understand how these valuable semantic cues can be put to fruitful use. The workshop had an interactive format consisting of keynotes, boasters and posters, breakout groups and reports, and a final discussion, which was prolonged into the evening. There was a strong feeling that we made substantial progress. Specifically, each of the breakout groups contributed to our understanding of the way forward. First, annotations and use cases come in many different shapes and forms depending on the domain at hand, but at a higher level there are remarkable commonalities in annotation tools, indexing methods, user interfaces, and general methodology. Second, we got insights in the "exploitation" aspects, leading to a clear separation between the low-level annotations giving context or meaning to small units of information (e.g., NLP, sentiments, entities), and annotations bringing out the structure inherent in the data (e.g., sources, data schema's, document genres). Third, the plan to enrich ClueWeb with various document level (e.g., pagerank and spam scores, but also reading level) and lower level (e.g., named entities or sentiments) annotations was embraced by the workshop as a concrete next step to promote research in semantic annotations.
Time-aware approaches to information retrieval
Authors: Kanhabua Nattiya
Published: May 2012

In this thesis, we address major challenges in searching temporal document collections. In such collections, documents are created and/or edited over time. Examples of temporal document collections are web archives, news archives, blogs, personal emails and enterprise documents. Unfortunately, traditional IR approaches based on term-matching only can give unsatisfactory results when searching temporal document collections. The reason for this is twofold: the contents of documents are strongly time-dependent, i.e., documents are about events happened at particular time periods, and a query representing an information need can be time-dependent as well, i.e., a temporal query.

Our contributions in this thesis are different time-aware approaches within three topics in IR: content analysis, query analysis, and retrieval and ranking models. In particular, we aim at improving the retrieval effectiveness by 1) analyzing the contents of temporal document collections, 2) performing an analysis of temporal queries, and 3) explicitly modeling the time dimension into retrieval and ranking.

Leveraging the time dimension in ranking can improve the retrieval effectiveness if information about the creation or publication time of documents is available. In this thesis, we analyze the contents of documents in order to determine the time of non-timestamped documents using temporal language models. We subsequently employ the temporal language models for determining the time of implicit temporal queries, and the determined time is used for re-ranking search results in order to improve the retrieval effectiveness.

We study the effect of terminology changes over time and propose an approach to handling terminology changes using time-based synonyms. In addition, we propose different methods for predicting the effectiveness of temporal queries, so that a particular query enhancement technique can be performed to improve the overall performance. When the time dimension is incorporated into ranking, documents will be ranked according to both textual and temporal similarity. In this case, time uncertainty should also be taken into account. Thus, we propose a ranking model that considers the time uncertainty, and improve ranking by combining multiple features using learning-to-rank techniques.

Through extensive evaluation, we show that our proposed time-aware approaches outperform traditional retrieval methods and improve the retrieval effectiveness in searching temporal document collections.

Available online at: http://www.idi.ntnu.no/research/doctor_theses/nattiya.pdf.
Acute saline expansion increases nephron filtration and distal flow rate but maintains tubuloglomerular feedback responsiveness: role of adenosine A1 receptors
Authors: Blantz Roland C. , Singh Prabhleen , Deng Aihua , Thomson Scott C. , Vallon Volker
Published: May 2012

Temporal adaptation of tubuloglomerular feedback (TGF) permits readjustment of the relationship of nephron filtration rate [single nephron glomerular filtration rate (SNGFR)] and early distal tubular flow rate (VED) while maintaining TGF responsiveness. We used closed-loop assessment of TGF in hydropenia and after acute saline volume expansion (SE; 10% body wt over 1 h) to determine whether 1) temporal adaptation of TGF occurs, 2) adenosine A1 receptors (A1R) mediate TGF responsiveness, and 3) inhibition of TGF affects SNGFR, VED, or urinary excretion under these conditions. SNGFR was evaluated in Fromter-Wistar rats by micropuncture in 1) early distal tubules (ambient flow at macula densa), 2) recollected from early distal tubules while 12 nl/min isotonic fluid was added to late proximal tubule (increased flow to macula densa), and 3) from proximal tubules of same nephrons (zero flow to macula densa). SE increased both ambient SNGFR and VED compared with hydropenia, whereas TGF responsiveness (proximal-distal difference in SNGFR, distal SNGFR response to adding fluid to proximal tubule) was maintained, demonstrating TGF adaptation. A1R blockade completely inhibited TGF responsiveness during SE and made VED more susceptible to perturbation in proximal tubular flow, but did not alter ambient SNGFR or VED. Greater urinary excretion of fluid and Na+ with A1R blockade may reflect additional effects on the distal nephron in hydropenia and SE. In conclusion, A1R-independent mechanisms adjust SNGFR and VED to higher values after SE, which facilitates fluid and Na+ excretion. Concurrently, TGF adapts and stabilizes early distal delivery at the new setpoint in an A1R-dependent mechanism.
Anti-Myeloma Effects of the Novel Anthracycline Derivative INNO-206
Authors: Sanchez Eric , Li Mingjie , Wang Cathy , Nichols Cydney M. , Li Jennifer , Chen Haiming , Berenson James R.
Published: May 2012

Purpose: Doxorubicin has shown efficacy especially in combination treatment for the treatment of multiple myeloma; however, its side effects limit its use. INNO-206 is an albumin-binding prodrug of doxorubicin, which is released from albumin under acidic conditions. Because INNO-206 has not been previously evaluated in any hematologic malignancy, we determined its anti–multiple myeloma effects.

Experimental Design: The anti–multiple myeloma effect of INNO-206 at different pH levels on multiple myeloma cell proliferation using multiple myeloma cell lines with the MTS assay and antiangiogenic activity using the chorioallantoic membrane/feather bud assay were determined. The anti–multiple myeloma effects and toxicity of INNO-206 were also compared with conventional doxorubicin and PEGylated liposomal doxorubicin (PLD) alone, and in combination with bortezomib, using our multiple myeloma xenograft models.

Results: INNO-206 inhibited blood vessel formation and reduced multiple myeloma cell growth in a pH-dependent fashion. INNO-206 alone produced marked anti–multiple myeloma effects in vivo at doses that doxorubicin was toxic, and the combination of INNO-206 plus bortezomib produced increased anti–multiple myeloma effects compared with either agent alone. In contrast, all mice receiving bortezomib with doxorubicin or PLD died.

Conclusions: These findings show that INNO-206 produces anti–multiple myeloma effects in vitro and in vivo. It also enhances the antitumor effects of bortezomib. These results suggest that INNO-206 may provide patients with multiple myeloma with an anthracycline that may be administered safely at higher doses compared with free doxorubicin, resulting in superior efficacy compared with the currently available anthracyclines to treat this B-cell malignancy. Clin Cancer Res; 18(14); 3856–67. ©2012 AACR.
Embryonic Pretreatment with Bromodeoxyuridine Blocks Regeneration and Functional Recovery from Perinatal Medial Frontal Lesions in Rats
Authors: Kolb Bryan , Pedersen Brian , Gibb Robbin
Published: May 2012

Removal of the midline frontal cortex on postnatal day 10 is followed by apparent regeneration of the part of the lost cortex, correlated with substantial recovery of function in adulthood. The spontaneous regrowth of the medial frontal cortex after midline frontal lesions on postnatal day 10 was blocked by pretreatment with bromodeoxyuridine (BrdU) on embryonic days 11, 12, 13, 15, or 17. BrdU pretreatment on embryonic day 21 or postnatal day 10 did not block either functional recovery or cortical regrowth. These results demonstrate a teratological effect of BrdU and are consistent with the claim that functional recovery after midline frontal removal on postnatal day 10 is supported by the generation of new midline frontal tissue.
Comparison of the Kidney Fungal Burden in Experimental Disseminated Candidiasis by Species of the Candida parapsilosis Complex Treated with Fluconazole, Amphotericin B and Caspofungin in a Temporarily Neutropenic Murine Model
Authors: Szilágyi J. , Földi R. , Gesztelyi R. , Bayegan S. , Kardos G. , Juhász B. , Majoros L.
Published: May 2012

Background: The efficacy of fluconazole (FLU), amphotericin B (AMB) and caspofungin (CAS) was tested against three Candida orthopsilosis, three C. metapsilosis and two C. parapsilosis sensu stricto isolates in neutropenic mice. Methods: Mice were immunosuppressed by 200 mg/kg cyclophosphamide. Five-day intraperitoneal treatment was started 24 h after infection. Kidney burden was analyzed using the Kruskal-Wallis test. Results: FLU 10 and 20 mg/kg as well as AMB 1 mg/kg significantly decreased the fungal burden (p < 0.05) for all eight isolates of the three species. CAS 2 and 5 mg/kg were efficacious against all C. orthopsilosis and C. metapsilosis isolates (p < 0.05), but only 5 mg/kg CAS was effective against C. parapsilosis isolates (p < 0.05). Conclusions: The efficacy of FLU and AMB against the three species was comparable. Though the activity of CAS was higher against C. orthopsilosis and C. metapsilosis, the current treatment guidelines for C. parapsilosis sensu stricto seem to be applicable to other ‘psilosis’ species.
Neutrophil Gelatinase-Associated Lipocalin: A Novel Marker of Contrast Nephropathy Risk
Authors: McCullough Peter A. , Williams Frances J. , Stivers David N. , Cannon Louis , Dixon Simon , Alexander Patrick , Runyan Danielle , David Shukri
Published: May 2012

Background: Neutrophil gelatinase-associated lipocalin (NGAL, siderocalin) is a protein secreted by the kidney in the setting of acute kidney injury in an attempt to regulate and bind the release of catalytic iron from injured cells. We sought to evaluate the relationships between baseline NGAL, renal filtration function, and the degree of injury reflected by further increases in NGAL. Methods: This study was a prospective, blinded assessment of blood samples taken from patients with estimated glomerular filtration rate (eGFR) <75 ml/min/1.73 m2 undergoing non-urgent coronary angiography and intervention using iodinated contrast. Renal transplant recipients, dialysis patients, and administration of iodinated contrast in the prior 30 days were exclusion criteria. Plasma NGAL was measured using the Alere™ assay. Serum creatinine (Cr) was measured using calibrated methods at a core laboratory. Samples were obtained at baseline, 1, 2, 4, 6, 12, 24, and 48 h after contrast administration. Results: A total of 63 subjects were enrolled with a mean age of 69.4 ± 9.1 years, 73% male, 35% with diabetes, and a mean eGFR of 47.82 ± 15.46 ml/min/1.73 m2. The correlation between eGFR and NGAL was r = –0.61, 95% CI –0.74 to –0.44, p < 0.001. When stratified by baseline NGAL tertile, the peak NGAL observed for each group occurred at 29.0 ± 22.2 h and there was a twofold increase in the mean and peak change in NGAL across the tertiles. NGAL began to rise 6 h after contrast exposure and followed a similar course to serum Cr and at 48 h the overall mean NGAL was still rising. Only 2 patients sustained a rise in Cr of >25% or ≥0.5 mg/dl. Multivariate regression revealed that baseline NGAL (p < 0.001) and not eGFR (p = 0.95) was independently associated with the NGAL value at 48 h. Conclusions: Baseline NGAL is strongly correlated with eGFR in patients with reduced renal filtration function undergoing coronary angiography. The magnitude of rise in NGAL is positively associated with the baseline value and is analogous to the time course of Cr in blood after contrast exposure. NGAL and not eGFR is an independent predictor of changes in the post-procedure NGAL. A baseline NGAL level is necessary for the interpretation of NGAL levels in the evaluation of acute kidney injury.
Do Pharmacokinetics Explain Persistent Restenosis Inhibition by a Single Dose of Paclitaxel?
Authors: Speck Ulrich , Cremers Bodo , Kelsch Bettina , Biedermann Melanie , Clever Yvonne P. , Schaffner Silvio , Mahnkopf Dirk , Hanisch Uli , Böhm Michael , Scheller Bruno
Published: May 2012

Background—

The purpose of this study was to investigate the elimination of paclitaxel from the arterial wall after a single short administration with a coated balloon.

Methods and Results—

Slightly oversized paclitaxel-coated balloons (dose 3 or 9 μg/mm
2
) without or with premounted stents were inflated in nonatherosclerotic coronary arteries of either young domestic pigs or adult Goettingen minipigs. The paclitaxel content of plasma, arterial segments, and residual hearts (without treated arteries) was measured for up to 180 days using high-performance liquid chromatography/ultraviolet detection or mass spectrometry. Angiograms were evaluated for lumen narrowing. The paclitaxel concentration in plasma remained <10 ng/mL. In arteries of domestic pigs and minipigs treated with paclitaxel-coated balloons with premounted stents, 10%±5% or 21%±8% of dose, respectively, was initially detected and decreased to 3.5%±3.1% of dose (domestic pig) by Day 7. Within 6 months it fell with a half-life of 1.9 months to 0.40%±0.35%. After 3 months the concentration in the arterial wall was 17±11 μmol/L. Without a stent, drug transfer to the vessel wall was somewhat reduced and elimination faster. Immediately after treatment up to 26%±4% of dose was detected in the residual whole hearts. It dropped with a half-life of 45 days to 1.5%±0.6% of dose (0.3 μmol/L) within 6 months.

Conclusions—

After a single local administration with coated balloons, paclitaxel stays in the vessel wall of pigs long enough to explain persistent inhibition of neointimal proliferation. The pharmacokinetics of paclitaxel does, however, not exclude other reasons for sustained efficacy such as early blocking of processes initiating excessive and prolonged neointimal proliferation.
Use of an Intrapericardial, Continuous-Flow, Centrifugal Pump in Patients Awaiting Heart Transplantation
Authors: Aaronson Keith D. , Slaughter Mark S. , Miller Leslie W. , McGee Edwin C. , Cotts William G. , Acker Michael A. , Jessup Mariell L. , Gregoric Igor D. , Loyalka Pranav , Frazier O.H. , Jeevanandam Valluvan , Anderson Allen S. , Kormos Robert L. , Teuteberg Jeffrey J. , Levy Wayne C. , Naftel David C. , Bittman Richard M. , Pagani Francis D. , Hathaway David R. , Boyce Steven W.
Published: May 2012

Background—

Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes.

Methods and Results—

We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (
P
<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly.

Conclusions—

A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00751972.
Differential Brain Activity during Emotional versus Nonemotional Reversal Learning
Authors: Nashiro Kaoru , Sakaki Michiko , Nga Lin , Mather Mara
Published: May 2012

The ability to change an established stimulus–behavior association based on feedback is critical for adaptive social behaviors. This ability has been examined in reversal learning tasks, where participants first learn a stimulus–response association (e.g., select a particular object to get a reward) and then need to alter their response when reinforcement contingencies change. Although substantial evidence demonstrates that the OFC is a critical region for reversal learning, previous studies have not distinguished reversal learning for emotional associations from neutral associations. The current study examined whether OFC plays similar roles in emotional versus neutral reversal learning. The OFC showed greater activity during reversals of stimulus–outcome associations for negative outcomes than for neutral outcomes. Similar OFC activity was also observed during reversals involving positive outcomes. Furthermore, OFC activity is more inversely correlated with amygdala activity during negative reversals than during neutral reversals. Overall, our results indicate that the OFC is more activated by emotional than neutral reversal learning and that OFC's interactions with the amygdala are greater for negative than neutral reversal learning.
Influences of Precipitation on Water Mass Transformation and Deep Convection
Authors: Spall Michael A.
Published: May 2012

The influences of precipitation on water mass transformation and the strength of the meridional overturning circulation in marginal seas are studied using theoretical and idealized numerical models. Nondimensional equations are developed for the temperature and salinity anomalies of deep convective water masses, making explicit their dependence on both geometric parameters such as basin area, sill depth, and latitude, as well as on the strength of atmospheric forcing. In addition to the properties of the convective water, the theory also predicts the magnitude of precipitation required to shut down deep convection and switch the circulation into the haline mode. High-resolution numerical model calculations compare well with the theory for the properties of the convective water mass, the strength of the meridional overturning circulation, and also the shutdown of deep convection. However, the numerical model also shows that, for precipitation levels that exceed this critical threshold, the circulation retains downwelling and northward heat transport, even in the absence of deep convection.
Tuning AutoNowcaster Automatically
Authors: Lakshmanan Valliappa , Crockett John , Sperow Kenneth , Ba Mamoudou , Xin Lingyan
Published: May 2012

AutoNowcaster (ANC) is an automated system that nowcasts thunderstorms, including thunderstorm initiation. However, its parameters have to be tuned to regional environments, a process that is time consuming, labor intensive, and quite subjective. When the National Weather Service decided to explore using ANC in forecast operations, a faster, less labor-intensive, and objective mechanism to tune the parameters for all the forecast offices was sought. In this paper, a genetic algorithm approach to tuning ANC is described. The process consisted of choosing datasets, employing an objective forecast verification technique, and devising a fitness function. ANC was modified to create nowcasts offline using weights iteratively generated by the genetic algorithm. The weights were generated by probabilistically combining weights with good fitness, leading to better and better weights as the tuning process proceeded.The nowcasts created by ANC using the automatically determined weights are compared with the nowcasts created by ANC using weights that were the result of manual tuning. It is shown that nowcasts created using the automatically tuned weights are as skilled as the ones created through manual tuning. In addition, automated tuning can be done in a fraction of the time that it takes experts to analyze the data and tune the weights.
Knockdown of the Adipokinetic Hormone Receptor Increases Feeding Frequency in the Two-Spotted Cricket Gryllus bimaculatus
Authors: Konuma Takahiro , Morooka Nobukatsu , Nagasawa Hiromichi , Nagata Shinji
Published: May 2012

Adipokinetic hormone (AKH) is a peptide hormone that regulates the nutritional state in insects by supporting the mobilization of lipids. In the present study, we manipulated AKH signaling to evaluate how metabolic state regulates feeding in an orthopteran insect, the two-spotted cricket, Gryllus bimaculatus. This was accomplished by RNA interference (RNAi) targeting the receptor gene for AKH [G. bimaculatus AKHR (GrybiAKHR)]. We found that the knockdown of GrybiAKHR by AKHR-double-stranded RNA treatment decreased the levels of 1,2-diacylglycerol and trehalose in the hemolymph, whereas it increased the level of triacylglycerol in the fat body. In addition, the knockdown of GrybiAKHR enhanced starvation resistance and increased food intake. Furthermore, direct observation of GrybiAKHRRNAi crickets revealed that the knockdown of GrybiAKHR increased feeding frequency but did not alter meal duration, whereas locomotor activity decreased. The increased frequency of feeding by GrybiAKHRRNAi crickets eventually resulted in an increase of food intake. These data demonstrate that the regulation of the metabolic state by AKH signaling affects feeding frequency, probably through nutritional control.
Identification of Permissive Insertion Sites for Generating Functional Fluorescent Mineralocorticoid Receptors
Authors: Aguilar-Sánchez Cristina , Hernández-Díaz Iván , Lorenzo-Díaz Fabián , Navarro Juan F. , Hughes Thom E. , Giraldez Teresa , Alvarez de la Rosa Diego
Published: May 2012

The mineralocorticoid receptor (MR), a member of the nuclear receptor superfamily of transcription factors, is activated by aldosterone and mediates its natriferic action in tight epithelia. MR is also expressed in nonepithelial tissues. Importantly, it mediates the deleterious effects of inappropriately high aldosterone levels in the heart, in which it induces the development of cardiac fibrosis. Antagonism of MR in humans is useful in the treatment of severe cardiac failure and some forms of hypertension. Despite the important pathophysiological and pharmacological role of this receptor, many important questions about its cellular biology and functional roles remain unanswered. A major challenge in the study of MR is the unavailability of fully functional fluorescent derivatives of the receptor. In this study we have created a library of MR mutants with insertions of the yellow fluorescent protein in various internal locations in the receptor using a random-insertion transposon-based technique. Screening of this library using a transactivation assay allowed us to identify several fluorescent constructs that retain functionality. Detailed characterization of one of these construct showed that it induces aldosterone-target genes such as the epithelial Na+ channel subunits and the serum and glucocorticoid-induced kinase 1 at physiological concentrations of aldosterone to an equal extent than the wild-type receptor. Furthermore, aldosterone affinity, hormone-induced nuclear translocation, DNA binding and regulation of nongenomic pathways are all indistinguishable from the wild-type receptor. This new set of fluorescent MR derivatives provides a useful tool for studying the cell biology of the receptor.
Hepatic Src Homology Phosphatase 2 Regulates Energy Balance in Mice
Authors: Nagata Naoto , Matsuo Kosuke , Bettaieb Ahmed , Bakke Jesse , Matsuo Izumi , Graham James , Xi Yannan , Liu Siming , Tomilov Alexey , Tomilova Natalia , Gray Susan , Jung Dae Young , Ramsey Jon J. , Kim Jason K. , Cortopassi Gino , Havel Peter J. , Haj Fawaz G.
Published: May 2012

The Src homology 2 domain-containing protein-tyrosine phosphatase Src homology phosphatase 2 (Shp2) is a negative regulator of hepatic insulin action in mice fed regular chow. To investigate the role of hepatic Shp2 in lipid metabolism and energy balance, we determined the metabolic effects of its deletion in mice challenged with a high-fat diet (HFD). We analyzed body mass, lipid metabolism, insulin sensitivity, and glucose tolerance in liver-specific Shp2-deficient mice (referred to herein as LSHKO) and control mice fed HFD. Hepatic Shp2 protein expression is regulated by nutritional status, increasing in mice fed HFD and decreasing during fasting. LSHKO mice gained less weight and exhibited increased energy expenditure compared with control mice. In addition, hepatic Shp2 deficiency led to decreased liver steatosis, enhanced insulin-induced suppression of hepatic glucose production, and impeded the development of insulin resistance after high-fat feeding. At the molecular level, LSHKO exhibited decreased hepatic endoplasmic reticulum stress and inflammation compared with control mice. In addition, tyrosine and serine phosphorylation of total and mitochondrial signal transducer and activator of transcription 3 were enhanced in LSHKO compared with control mice. In line with this observation and the increased energy expenditure of LSHKO, oxygen consumption rate was higher in liver mitochondria of LSHKO compared with controls. Collectively, these studies identify hepatic Shp2 as a novel regulator of systemic energy balance under conditions of high-fat feeding.
Redox implications of AMPK-mediated signal transduction beyond energetic clues
Authors: Cardaci Simone , Filomeni Giuseppe , Ciriolo Maria Rosa
Published: May 2012

Since the discovery of AMP-dependent protein kinase (AMPK), its fundamental role in regulating metabolic pathways and the molecular mechanism underlying the regulation of its activity by adenine nucleotides has been widely studied. AMPK is not only an energy-responsive enzyme, but it also senses redox signals. This review aims at recapitulating the recent lines of evidence that demonstrate the responsiveness of this kinase to metabolic and nitroxidative imbalance, thus providing new insights into the intimate networks of redox-based signals upstream of AMPK. In particular, we discuss its well-recognized activation downstream of mitochondrial dysfunction, debate the recent findings that AMPK is directly targeted by pro-oxidant species, and question alternative redox pathways that allow AMPK to be included into the large class of redox-sensing proteins. The possible therapeutic implications of the role of AMPK in redox-associated pathologies, such as cancer and neurodegeneration, are also discussed in light of recent advances that suggest a role for AMPK in the tuning of redox-dependent processes, such as apoptosis and autophagy.
Flexural stiffness and composition of the batoid propterygium as predictors of punting ability
Authors: Macesic Laura J. , Summers Adam P.
Published: May 2012

Elasmobranchs (sharks, skates and rays) perform at the extremes of locomotion and feeding (i.e. long migrations, high-speed swimming and durophagy). However, very little is known about their cartilaginous skeletal structure and composition in response to loading regimes. In this study, we investigated a batoid (skate and ray) appendicular skeletal element, the propterygium, and its response to forces experienced during punting (benthic pelvic fin locomotion). Punting places a flexural load on this thin, rod-like element. The goals for our study were to determine: (1) the mechanical and compositional properties of the propterygium and (2) whether these properties correlate with punting ability. Using five batoid species of varying punting ability, we employed a three-point bending test and found that propterygium flexural stiffness (33.74–180.16 Nm2) was similar to values found in bone and could predict punting ability. Variation in flexural stiffness resulted from differences in mineral content (24.4–48.9% dry mass) and the second moment of area. Propterygia material stiffness (140–2533 MPa) approached the lower limit of bone despite having less than one-third of its mineral content. This drastically lower mineral content is reflected in the radius-to-thickness ratio of the cross-section (mean ± s.e.m.=5.5±0.44), which is comparatively much higher than bony vertebrates. This indicates that elasmobranchs may have evolved skeletal elements that increase buoyancy without sacrificing mechanical properties. Our results highlight the functional parallels between a cartilaginous and bony skeleton despite dramatic compositional differences, and provide insight into how environmental factors may affect cartilaginous skeletal development.
High e-vector acuity in the polarisation vision system of the fiddler crabUca vomeris
Authors: How Martin J. , Pignatelli Vincenzo , Temple Shelby E. , Marshall N. Justin , Hemmi Jan M.
Published: May 2012

Polarisation vision is used by a variety of species in many important tasks, including navigation and orientation (e.g. desert ant), communication and signalling (e.g. stomatopod crustaceans), and as a possible substitute for colour vision (e.g. cephalopod molluscs). Fiddler crabs are thought to possess the anatomical structures necessary to detect polarised light, and occupy environments rich in polarisation cues. Yet little is known about the capabilities of their polarisation sense. A modified polarisation-only liquid crystal display and a spherical rotating treadmill were combined to test the responses of fiddler crabs to moving polarisation stimuli. The species Uca vomeris was found to be highly sensitive to polarised light and detected stimuli differing in e-vector angle by as little as 3.2 deg. This represents the most acute behavioural sensitivity to polarised light yet measured for a crustacean. The occurrence of null points in their discrimination curve indicates that this species employs an orthogonal (horizontal/vertical) receptor array for the detection of polarised light.
Inducible tolerance to dietary protease inhibitors inDaphnia magna
Authors: von Elert Eric , Zitt Anja , Schwarzenberger Anke
Published: May 2012

Daphnia has been shown to acquire tolerance to cyanobacterial toxins within an animals' lifetime and to transfer this tolerance to the next generation. Here we used a strain of the cyanobacterium Microcystis aeruginosa, which contained two chymotrypsin inhibitors (BN920 and CP954), the green alga Scenedesmus obliquus as reference food and a clone of D. magna to investigate the physiological mechanism of acquired tolerance to these cyanobacterial toxins. The intracellular concentrations of CP954 and BN920 were 1550 and 120 μmol l–1, respectively. When food suspensions of the green alga contained >60% M. aeruginosa, growth rates of D. magna were reduced. When grown on the green alga, three chymotrypsins ranging in mass from 16 to 22 kDa were distinguished in D. magna. Purified BN920 and CP954 specifically inhibited D. magna chymotrypsins. Feeding with encapsulated BN920 resulted in growth depression in D. magna and replacement of the chymotrypsins by three chymotrypsins with smaller molecular mass. With just 20% M. aeruginosa, the same changes in the chymotrypsin pattern as with the pure inhibitor were observed. IC50 values for inhibition of chymotrypsins of D. magna growing on the green alga were 5.4 nmol l–1 (BN920) and 7.4 nmol l–1 (CP954). When D. magna was grown on 20% M. aeruginosa, 2.2-fold higher IC50 values were observed. This indicated that increased tolerance to these dietary inhibitors was acquired within an animal's lifetime by remodelling the digestive chymotrypsins, which in turn serves as an intra-generational defence against these cyanobacterial inhibitors. This mechanism might be relevant for the transfer of tolerance to the next generation through maternal effects.
Seasonal variation in metabolic rate, flight activity and body size of Anopheles gambiae in the Sahel
Authors: Huestis Diana L. , Yaro Alpha S. , Traoré Adama I. , Dieter Kathryne L. , Nwagbara Juliette I. , Bowie Aleah C. , Adamou Abdoulaye , Kassogué Yaya , Diallo Moussa , Timbiné Seydou , Dao Adama , Lehmann Tovi
Published: May 2012

Malaria in Africa is vectored primarily by the Anopheles gambiae complex. Although the mechanisms of population persistence during the dry season are not yet known, targeting dry season mosquitoes could provide opportunities for vector control. In the Sahel, it appears likely that M-form A. gambiae survive by aestivation (entering a dormant state). To assess the role of eco-physiological changes associated with dry season survival, we measured body size, flight activity and metabolic rate of wild-caught mosquitoes throughout 1 year in a Sahelian locality, far from permanent water sources, and at a riparian location adjacent to the Niger River. We found significant seasonal variation in body size at both the Sahelian and riparian sites, although the magnitude of the variation was greater in the Sahel. For flight activity, significant seasonality was only observed in the Sahel, with increased flight activity in the wet season when compared with that just prior to and throughout the dry season. Whole-organism metabolic rate was affected by numerous biotic and abiotic factors, and a significant seasonal component was found at both locations. However, assay temperature accounted completely for seasonality at the riparian location, while significant seasonal variation remained after accounting for all measured variables in the Sahel. Interestingly, we did not find that mean metabolic rate was lowest during the dry season at either location, contrary to our expectation that mosquitoes would conserve energy and increase longevity by reducing metabolism during this time. These results indicate that mosquitoes may use mechanisms besides reduced metabolic rate to enable survival during the Sahelian dry season.
Room-temperature Fast Synthesis of Composition-adjustable Pt–Pd Alloy Sub-10-nm Nanoparticle Networks with Improved Electrocatalytic Activities
Authors: Hou Shuangxia , Xu You , Liu Yang , Xu Rui , Zhang Bin
Published: May 2012

Pt–Pd alloy nanoparticle networks (Pt–Pd NN) with adjustable composition have been fast synthesized through a one-step room-temperature coreduction method in a water/ethylene glycol (EG) system. It was found that the Pt–Pd NN exhibited enhanced electrocatalytic activity toward ethanol oxidation reaction (EOR) compared with Pt nanoparticle networks (Pt NN) and commercially available Pt black.
The Effects of Charges at the N- and C-Termini of Short Peptides on Their Secondary and Self-assembled Structures
Authors: Tomizaki Kin-ya , Ikawa Tomoyo , Ahn Soo-Ang , Yamazoe Seiji , Imai Takahito
Published: May 2012

Self-assembly of small molecules (i.e., synthetic peptides) into nanostructures is an attractive template for fabrication of nanoscaled organic–inorganic composites. In order to increase the diversity of morphologies of template nanostructures, we designed, synthesized, and characterized four different nonapeptides, and examined the effects of charge(s) at the N- and/or C-termini of the peptides on their secondary and assembled structures in water.