PCI-SS: MISO dynamic nonlinear protein secondary structure prediction

<p>Abstract</p> <p>Background</p> <p>Since the function of a protein is largely dictated by its three dimensional configuration, determining a protein's structure is of fundamental importance to biology. Here we report on a novel approach to determining the one dimensional secondary structure of proteins (distinguishing α-helices, β-strands, and non-regular structures) from primary sequence data which makes use of Parallel Cascade Identification (PCI), a powerful technique from the field of nonlinear system identification.</p> <p>Results</p> <p>Using PSI-BLAST divergent evolutionary profiles as input data, dynamic nonlinear systems are built through a black-box approach to model the process of protein folding. Genetic algorithms (GAs) are applied in order to optimize the architectural parameters of the PCI models. The three-state prediction problem is broken down into a combination of three binary sub-problems and protein structure classifiers are built using 2 layers of PCI classifiers. Careful construction of the optimization, training, and test datasets ensures that no homology exists between any training and testing data. A detailed comparison between PCI and 9 contemporary methods is provided over a set of 125 new protein chains guaranteed to be dissimilar to all training data. Unlike other secondary structure prediction methods, here a web service is developed to provide both human- and machine-readable interfaces to PCI-based protein secondary structure prediction. This server, called PCI-SS, is available at <url>http://bioinf.sce.carleton.ca/PCISS</url>. In addition to a dynamic PHP-generated web interface for humans, a Simple Object Access Protocol (SOAP) interface is added to permit invocation of the PCI-SS service remotely. This machine-readable interface facilitates incorporation of PCI-SS into multi-faceted systems biology analysis pipelines requiring protein secondary structure information, and greatly simplifies high-throughput analyses. XML is used to represent the input protein sequence data and also to encode the resulting structure prediction in a machine-readable format. To our knowledge, this represents the only publicly available SOAP-interface for a protein secondary structure prediction service with published WSDL interface definition.</p> <p>Conclusion</p> <p>Relative to the 9 contemporary methods included in the comparison cascaded PCI classifiers perform well, however PCI finds greatest application as a consensus classifier. When PCI is used to combine a sequence-to-structure PCI-based classifier with the current leading ANN-based method, PSIPRED, the overall error rate (Q3) is maintained while the rate of occurrence of a particularly detrimental error is reduced by up to 25%. This improvement in BAD score, combined with the machine-readable SOAP web service interface makes PCI-SS particularly useful for inclusion in a tertiary structure prediction pipeline.</p

Pediatricians' weight assessment and obesity management practices

<p>Abstract</p> <p>Background</p> <p>Clinician adherence to obesity screening guidelines from United States health agencies remains suboptimal. This study explored how personal and career demographics influence pediatricians' weight assessment and management practices.</p> <p>Methods</p> <p>A web-based survey was distributed to U.S. pediatricians. Respondents were asked to identify the weight status of photographed children and about their weight assessment and management practices. Associations between career and personal demographic variables and pediatricians' weight perceptions, weight assessment and management practices were evaluated using univariate and multivariate modeling.</p> <p>Results</p> <p>3,633 pediatric medical providers correctly identified the weight status of children at a median rate of 58%. The majority of pediatric clinicians were white, female, and of normal weight status with more than 10 years clinical experience. Experienced pediatric medical providers were less likely than younger colleagues to correctly identify the weight status of pictured children and were also less likely to know and use BMI criteria for assessing weight status. General pediatricians were more likely than subspecialty practitioners to provide diverse interventions for weight management. Non-white and Hispanic general practitioners were more likely than counterparts to consider cultural approaches to weight management.</p> <p>Conclusion</p> <p>Pediatricians' perceptions of children's weight and their weight assessment and management practices are influenced by career and personal characteristics. Objective criteria and clinical guidelines should be uniformly applied by pediatricians to screen for and manage pediatric obesity.</p

Molecular analysis of the Acinetobacter baumannii biofilm-associated protein

Acinetobacter baumannii is a multidrug-resistant pathogen associated with hospital outbreaks of infection across the globe, particularly in the intensive care unit. The ability of A. baumannii to survive in the hospital environment for long periods is linked to antibiotic resistance and its capacity to form biofilms. Here we studied the prevalence, expression, and function of the A. baumannii biofilm-associated protein (Bap) in 24 carbapenem-resistant A. baumannii ST92 strains isolated from a single institution over a 10-year period. The bap gene was highly prevalent, with 22/24 strains being positive for bap by PCR. Partial sequencing of bap was performed on the index case strain MS1968 and revealed it to be a large and highly repetitive gene approximately 16 kb in size. Phylogenetic analysis employing a 1,948-amino-acid region corresponding to the C terminus of Bap showed that Bap(MS1968) clusters with Bap sequences from clonal complex 2 (CC2) strains ACICU, TCDC-AB0715, and 1656-2 and is distinct from Bap in CC1 strains. By using overlapping PCR, the bap(MS1968) gene was cloned, and its expression in a recombinant Escherichia coli strain resulted in increased biofilm formation. A Bap-specific antibody was generated, and Western blot analysis showed that the majority of A. baumannii strains expressed an similar to 200-kDa Bap protein. Further analysis of three Bap-positive A. baumannii strains demonstrated that Bap is expressed at the cell surface and is associated with biofilm formation. Finally, biofilm formation by these Bap-positive strains could be inhibited by affinity-purified Bap antibodies, demonstrating the direct contribution of Bap to biofilm growth by A. baumannii clinical isolates

Efficacy, Safety, and Tolerability of Three Regimens for Prevention of Malaria: A Randomized, Placebo-Controlled Trial in Ugandan Schoolchildren

BACKGROUND: Intermittent preventive treatment (IPT) is a promising malaria control strategy; however, the optimal regimen remains unclear. We conducted a randomized, single-blinded, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of a single course of sulfadoxine-pyrimethamine (SP), amodiaquine + SP (AQ+SP) or dihydroartemisinin-piperaquine (DP) among schoolchildren to inform IPT. METHODS: Asymptomatic girls aged 8 to 12 years and boys aged 8 to 14 years enrolled in two primary schools in Tororo, Uganda were randomized to receive one of the study regimens or placebo, regardless of presence of parasitemia at enrollment, and followed for 42 days. The primary outcome was risk of parasitemia at 42 days. Survival analysis was used to assess differences between regimens. RESULTS: Of 780 enrolled participants, 769 (98.6%) completed follow-up and were assigned a treatment outcome. The risk of parasitemia at 42 days varied significantly between DP (11.7% [95% confidence interval (CI): 7.9, 17.1]), AQ+SP (44.3% [37.6, 51.5]), and SP (79.7% [95% CI: 73.6, 85.2], p<0.001). The risk of parasitemia in SP-treated children was no different than in those receiving placebo (84.6% [95% CI: 79.1, 89.3], p = 0.22). No serious adverse events occurred, but AQ+SP was associated with increased risk of vomiting compared to placebo (13.0% [95% CI: 9.1, 18.5] vs. 4.7% [95% CI: 2.5, 8.8], respectively, p = 0.003). CONCLUSIONS: DP was the most efficacious and well-tolerated regimen tested, although AQ+SP appears to be a suitable alternative for IPT in schoolchildren. Use of SP for IPT may not be appropriate in areas with high-level SP resistance in Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00852371

Absorption closure in highly aged biomass burning smoke

This is the final version. Available from Copernicus Publications via the DOI in this record. Data availability. Airborne measurements are available from the Centre for Environmental Data Analysis (https://catalogue.ceda.ac.uk/uuid/38ab7089781a4560b067dd6c20af3769, Facility for Airborne Atmospheric Measurements et al., 2017).The optical properties of black carbon (BC) are a major source of uncertainty in regional and global climate studies. In the past, detailed investigation of BC absorption has been hampered by systematic biases in the measurement instrumentation. We present airborne measurements of aerosol absorption and black carbon microphysical properties in highly aged biomass burning plumes measured 4-8 d from their source over the southeast Atlantic Ocean during CLARIFY-2017, using a suite of novel photoacoustic spectrometers to measure aerosol absorption at 405, 514, and 655 nm and a single-particle soot photometer to measure the BC mass concentration, size, and mixing state. These measurements are of sufficient quality and detail to provide constraint on optical schemes used in climate models for the first time in biomass burning plumes far from their source-an aerosol environment that is one of the most important climatically. The average absorption Ångström exponents (AAE) were 1.38 over the wavelength range from 405 to 514 nm and 0.88 over the range from 514 to 655 nm, suggesting that brown carbon (BrC) contributed to 11±2 % of absorption at 405 nm. The effective organic aerosol (OA) mass absorption coefficient (MAC) was 0:31±0:09 m2 g-1 at 405 nm. The BC particles were universally thickly coated, and almost no externally mixed BC particles were detected. The average MAC of BC was 20 ± 4, 15 ± 3, and 12 ± 2 m2g-1 at wavelengths of 405, 514, and 655 nm respectively, with equivalent absorption enhancements of around 1:85 ± 0:45 at all three wavelengths, suggesting that the thick coatings acted as a lens that enhanced light absorption by the BC. We compared the measured MAC and AAE values with those calculated using several optical models and absorption parameterisations that took the measured BC mass and mixing state as inputs. Homogeneous grey-sphere Mie models were only able to replicate MAC for some low (real and imaginary) values of the complex BC refractive index (mBC) at the shortest wavelength, but they would have to use unrealistically low values of mBC to accurately replicate the AAE. A core-shell Mie model was able to generate good agreement for MAC in the green-red end of the visible spectrum for most values of mBC. However, there are no possible values of mBC that produce MAC values that agree with our observations at all three wavelengths, due to a wavelengthdependent underestimation of the MAC of the underlying BC core. Four semiempirical parameterisations from the literature were also tested, linking the BC mixing state to either the MAC or absorption enhancement. Two of these schemes produced results that agreed within a few percent with the measured MAC at all three wavelengths, and the AAE agreed well when discounting the effects of BrC. Our results uniquely demonstrate the validity of absorption parameterisations, as well as the failings of Mie calculations, in this highly aged environment. We recommend that future work should conduct similar analyses in environments where BC has different properties; future studies should also investigate the impact of implementing these types of schemes within climate models as well as the impact of developing equivalent schemes for light scattering by soot particles at visible wavelengths.Natural Environment Research Council (NERC

Coordinated airborne studies in the tropics (CAST)

This is the final version of the article. It first appeared from the American Meteorological Society via http://dx.doi.org/10.1175/BAMS-D-14-00290.1Abstract The main field activities of the Coordinated Airborne Studies in the Tropics (CAST) campaign took place in the west Pacific during January–February 2014. The field campaign was based in Guam (13.5°N, 144.8°E), using the U.K. Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 atmospheric research aircraft, and was coordinated with the Airborne Tropical Tropopause Experiment (ATTREX) project with an unmanned Global Hawk and the Convective Transport of Active Species in the Tropics (CONTRAST) campaign with a Gulfstream V aircraft. Together, the three aircraft were able to make detailed measurements of atmospheric structure and composition from the ocean surface to 20 km. These measurements are providing new information about the processes influencing halogen and ozone levels in the tropical west Pacific, as well as the importance of trace-gas transport in convection for the upper troposphere and stratosphere. The FAAM aircraft made a total of 25 flights in the region between 1°S and 14°N and 130° and 155°E. It was used to sample at altitudes below 8 km, with much of the time spent in the marine boundary layer. It measured a range of chemical species and sampled extensively within the region of main inflow into the strong west Pacific convection. The CAST team also made ground-based measurements of a number of species (including daily ozonesondes) at the Atmospheric Radiation Measurement Program site on Manus Island, Papua New Guinea (2.1°S, 147.4°E). This article presents an overview of the CAST project, focusing on the design and operation of the west Pacific experiment. It additionally discusses some new developments in CAST, including flights of new instruments on board the Global Hawk in February–March 2015.CAST is funded by NERC and STFC, with grant NE/ I030054/1 (lead award), NE/J006262/1, NE/J006238/1, NE/J006181/1, NE/J006211/1, NE/J006061/1, NE/J006157/1, NE/J006203/1, NE/J00619X/1, and NE/J006173/1. N. R. P. Harris was supported by a NERC Advanced Research Fellowship (NE/G014655/1). P. I. Palmer acknowledges his Royal Society Wolfson Research Merit Award. The BAe-146-301 Atmospheric Research Aircraft is flown by Directflight Ltd and managed by the Facility for Airborne Atmospheric Measurements, which is a joint entity of the Natural Environment Research Council and the Met Office. The authors thank the staff at FAAM, Directflight and Avalon Aero who worked so hard toward the success of the aircraft deployment in Guam, especially for their untiring efforts when spending an unforeseen 9 days in Chuuk. We thank the local staff at Chuuk and Palau, as well as the authorities in the Federated States of Micronesia for their help in facilitating our research flights. Special thanks go to the personnel associated with the ARM facility at Manus, Papua New Guinea without whose help the ground-based measurements would not have been possible. Thanks to the British Atmospheric Data Centre (BADC) for hosting our data and the NCAS Atmospheric Measurement Facility for providing the radiosonde and ground-based ozone equipment. Chlorophyll-a data used in Figure 1 were extracted using the Giovanni online data system, maintained by the NASA GES DISC. We acknowledge the MODIS mission scientists and associated NASA personnel for the production of this data set. Finally we thank many individuals associated with the ATTREX and CONTRAST campaigns for their help in the logistical planning, and we would like to single out Jim Bresch for his excellent and freely provided meteorological advice

Relationship between Tumor DNA Methylation Status and Patient Characteristics in African-American and European-American Women with Breast Cancer

Aberrant DNA methylation is critical for development and progression of breast cancer. We investigated the association of CpG island methylation in candidate genes and clinicopathological features in 65 African-American (AA) and European-American (EA) breast cancer patients. Quantitative methylation analysis was carried out on bisulfite modified genomic DNA and sequencing (pyrosequencing) for promoter CpG islands of p16, ESR1, RASSF1A, RARβ2, CDH13, HIN1, SFRP1 genes and the LINE1 repetitive element using matched paired non-cancerous and breast tumor specimen (32 AA and 33 EA women). Five of the genes, all known tumor suppressor genes (RASSF1A, RARβ2, CDH13, HIN1 and SFRP1), were found to be frequently hypermethylated in breast tumor tissues but not in the adjacent non-cancerous tissues. Significant differences in the CDH13 methylation status were observed by comparing DNA methylation between AA and EA patients, with more obvious CDH13 methylation differences between the two patient groups in the ER- disease and among young patients (age<50). In addition, we observed associations between CDH13, SFRP1, and RASSF1A methylation and breast cancer subtypes and between SFRP1 methylation and patient's age. Furthermore, tumors that received neoadjuvant therapy tended to have reduced RASSF1A methylation when compared with chemotherapy naïve tumors. Finally, Kaplan Meier survival analysis showed a significant association between methylation at 3 loci (RASSF1A, RARβ2 and CDH13) and reduced overall disease survival. In conclusion, the DNA methylation status of breast tumors was found to be significantly associated with clinicopathological features and race/ethnicity of the patients

The LRRK2 Arg1628Pro variant is a risk factor for Parkinson's disease in the Chinese population

The c.G4883C variant in the leucine-rich repeat kinase 2 (LRRK2) gene (protein effect: Arg1628Pro) has been recently proposed as a second risk factor for sporadic Parkinson's disease in the Han Chinese population (after the Gly2385Arg variant). In this paper, we analyze the Arg1628Pro variant and the associated haplotype in a large sample of 1,337 Han subjects (834 patients and 543 controls) ascertained from a single referral center in Taiwan. In our sample, the Arg1628Pro allele was more frequent among patients (3.8%) than among controls (1.8%; p = 0.004, OR 2.13, 95% CI 1.29-3.52). Sixty heterozygous and two homozygous carriers of the Arg1628Pro variant were identified among the patients, of which only one was also a carrier of the LRRK2 Gly2385Arg variant. We also show that carriers of the Arg1628Pro variant share a common, extended haplotype, suggesting a founder effect. Parkinson's disease onset age was similar in patients who carried the Arg1628Pro variant and in those who did not carry it. Our data support the contention that the Arg1628Pro variant is a second risk factor for Parkinson's disease in the Han Chinese population. Adding the estimated effects of Arg1628Pro (population attributable risk [PAR] ∼4%) and Gly2385Arg variants (PAR ∼6%) yields a total PAR of ∼10%

Evaluating the Impact of a ‘Virtual Clinic’ on Patient Experience, Personal and Provider Costs of Care in Urinary Incontinence: A Randomised Controlled Trial.

Objective: To evaluate the impact of using a ‘virtual clinic’ on patient experience and cost in the care of women with urinary incontinence. Materials and Methods: Women, aged > 18 years referred to a urogynaecology unit were randomised to either (1) A Standard Clinic or (2) A Virtual Clinic. Both groups completed a validated, web-based interactive, patient-reported outome measure (ePAQ-Pelvic Floor), in advance of their appointment followed by either a telephone consultation (Virtual Clinic) or face-to-face consultation (Standard Care). The primary outcome was the mean ‘short-term outcome scale’ score on the Patient Experience Questionnaire (PEQ). Secondary Outcome Measures included the other domains of the PEQ (Communications, Emotions and Barriers), Client Satisfaction Questionnaire (CSQ), Short-Form 12 (SF-12), personal, societal and NHS costs. Results: 195 women were randomised: 98 received the intervention and 97 received standard care. The primary outcome showed a non-significant difference between the two study arms. No significant differences were also observed on the CSQ and SF-12. However, the intervention group showed significantly higher PEQ domain scores for Communications, Emotions and Barriers (including following adjustment for age and parity). Whilst standard care was overall more cost-effective, this was minimal (£38.04). The virtual clinic also significantly reduced consultation time (10.94 minutes, compared with a mean duration of 25.9 minutes respectively) and consultation costs compared to usual care (£31.75 versus £72.17 respectively), thus presenting potential cost-savings in out-patient management. Conclusions: The virtual clinical had no impact on the short-term dimension of the PEQ and overall was not as cost-effective as standard care, due to greater clinic re-attendances in this group. In the virtual clinic group, consultation times were briefer, communication experience was enhanced and personal costs lower. For medical conditions of a sensitive or intimate nature, a virtual clinic has potential to support patients to communicate with health professionals about their condition