Pigment-dispersing factors (PDFs) are octadeca-peptides widely distributed in insect optic lobes and brain. In this study, we have purified PDF and determined its amino acid sequence in the cricket Gryllus bimaculatus. Its primary structure was NSEIINSLLGLPKVLNDA-NH(2), homologous to other PDH family members so far reported. When injected into the optic lobe of experimentally blinded adult male crickets, Gryllus-PDF induced phase shifts in their activity rhythms in a phase dependent and dose dependent manner. The resulted phase response curve (PRC) showed delays during the late subjective night to early subjective day and advances during the mid subjective day to mid subjective night. The PRC was different in shape from those for light, serotonin and temperature. These results suggest that PDF plays a role in phase regulation of the circadian clock through a separate pathway from those of other known phase regulating agents.

BACKGROUND

We aimed to demonstrate the prognostic value of TGF-β1 in triple negative breast cancer (TNBC) and its association with clinicopathological characteristics of TNBC.

METHODS

A total of 180 women were randomly selected from non-metastatic invasive TNBC patients diagnosed at two hospitals between 2003 and 2012. Lmmunohistochemistry was performed to semi-quantify the expression of TGF-β1. Relationship between TGF-β1 expression and clinicopathological features was performed by Chi-square test. Univariate and multivariate survival analyses were performed to identify the prognostic role of TGF-β1 expression on survival outcomes.

RESULTS

Of the 180 women included in this study, 67 (37.2%) patients expressed high level of TGF-β1. High expression of cytoplasmic TGF-β1 was correlated with higher histologic tumor grade (P < 0.001) and lymph node status (P < 0.001), and more axillary lymph node dissection (P = 0.029). High cytoplasmic TGF-β1 expression was associated with reduced disease-free survival (DFS) and overall survival (OS) by log-rank test (PDFS<0.001, POS = 0.045). However, multivariate survival analyses showed that high TGF-β1 was marginally correlated with unfavorable DFS (hazard ratio (HR) 1.796, 95% CI 0.995-3.242, P = 0.052), while it was not significantly associated with OS (HR 0.747, 95% CI 0.367-1.522, P = 0.422).

CONCLUSIONS

This multi-centered retrospective study highlights the high expression of cytoplasmic TGF-β1 in TNBC is associated with higher histologic grade and lymph node status, more axillary lymph node dissection, as well as reduced DFS. Our observation that the prognostic role of TGF-β1 in TNBC suggests potential rationale for using therapeutic strategies based on targeting TGF-β1 in advanced tumors.

Drosophila melanogaster is a long-standing model organism in the circadian clock research. A major advantage is the relative small number of about 150 neurons, which built the circadian clock in Drosophila. In our recent work, we focused on the neuroanatomical properties of the lateral neurons of the clock network. By applying the multicolor-labeling technique Flybow we were able to identify the anatomical similarity of the previously described E2 subunit of the evening oscillator of the clock, which is built by the 5th small ventrolateral neuron (5th s-LNv ) and one ITP positive dorsolateral neuron (LNd ). These two clock neurons share the same spatial and functional properties. We found both neurons innervating the same brain areas with similar pre- and postsynaptic sites in the brain. Here the anatomical findings support their shared function as a main evening oscillator in the clock network like also found in previous studies. A second quite surprising finding addresses the large lateral ventral PDF-neurons (l-LNv s). We could show that the four hardly distinguishable l-LNv s consist of two subgroups with different innervation patterns. While three of the neurons reflect the well-known branching pattern reproduced by PDF immunohistochemistry, one neuron per brain hemisphere has a distinguished innervation profile and is restricted only to the proximal part of the medulla-surface. We named this neuron "extra" l-LNv (l-LNv x). We suggest the anatomical findings reflect different functional properties of the two l-LNv subgroups.

Animals have sophisticated homeostatic controls. While mammalian body temperature fluctuates throughout the day, small ectotherms, such as Drosophila achieve a body temperature rhythm (BTR) through their preference of environmental temperature. Here, we demonstrate that pigment dispersing factor (PDF) neurons play an important role in setting preferred temperature before dawn. We show that small lateral ventral neurons (sLNvs), a subset of PDF neurons, activate the dorsal neurons 2 (DN2s), the main circadian clock cells that regulate temperature preference rhythm (TPR). The number of temporal contacts between sLNvs and DN2s peak before dawn. Our data suggest that the thermosensory anterior cells (ACs) likely contact sLNvs via serotonin signaling. Together, the ACs-sLNs-DN2s neural circuit regulates the proper setting of temperature preference before dawn. Given that sLNvs are important for sleep and that BTR and sleep have a close temporal relationship, our data highlight a possible neuronal interaction between body temperature and sleep regulation.

BACKGROUND

Disparities in postpregnancy contraception utilization exist, with low-income women disproportionately undergoing sterilization. We assessed the impact of increased intrauterine device (IUD) availability on rates of female sterilization.

METHODS

Hospital billing records were used to identify women with an IUD placement or sterilization within 1 year of a pregnancy at a university hospital between Oct 2005 and Jun 2007. Demographic data were compared between women receiving either an IUD or sterilization.

RESULTS

There were 365 sterilizations and 223 IUD placements during the study period. IUD placements doubled over the study period from 6% to 12% of all deliveries, while sterilizations remained stable at 11% (p<.001). Demographic variables were examined for women with either public or private insurance who had financial access to both sterilization (n=253) and IUD (n=223). Women receiving sterilization were slightly older (mean age 31 years versus 30 years, p=.03), of higher parity (median three versus two, p<.01), more likely to have had cesarean delivery (69% versus 31%, p<.001) and more likely to have public insurance (77% versus 23%, p<.001) than women who received IUD. Approximately 45% of women delivering in Oregon in 2007 were publicly insured (2010 Maternal and Child Health Update: States Make Progress Towards Improving Systems of Care. National Governor's Association, Table 6. Available at http://www.nga.org/files/live/sites/NGA/files/pdf/MCHUPDATE2010.PDF, accessed Nov 2011). After adjusting for age, parity and type of delivery, women choosing sterilization were more likely to have public insurance than women choosing IUD (odds ratio 8.4, 95% confidence interval 4.7-14.9, p<.0001).

CONCLUSIONS

Women choosing sterilization are more likely to have public insurance than women choosing IUD and may represent a continued trend toward nonreversible contraception among women of lower socioeconomic status despite available long-acting reversible methods.

BACKGROUND

Practice guidelines (PGs) are systematically developed statements intended to assist in patient and practitioner decisions. The AGREE II is the revised tool for PG development, reporting, and evaluation, comprised of 23 items, two global rating scores, and a new User's Manual. In this study, we sought to develop, execute, and evaluate the impact of two internet interventions designed to accelerate the capacity of stakeholders to use the AGREE II.

METHODS

Participants were randomized to one of three training conditions. 'Tutorial'--participants proceeded through the online tutorial with a virtual coach and reviewed a PDF copy of the AGREE II. 'Tutorial + Practice Exercise'--in addition to the Tutorial, participants also appraised a 'practice' PG. For the practice PG appraisal, participants received feedback on how their scores compared to expert norms and formative feedback if scores fell outside the predefined range. 'AGREE II User's Manual PDF (control condition)'--participants reviewed a PDF copy of the AGREE II only. All participants evaluated a test PG using the AGREE II. Outcomes of interest were learners' performance, satisfaction, self-efficacy, mental effort, time-on-task, and perceptions of AGREE II.

RESULTS

No differences emerged between training conditions on any of the outcome measures.

CONCLUSIONS

We believe these results can be explained by better than anticipated performance of the AGREE II PDF materials (control condition) or the participants' level of health methodology and PG experience rather than the failure of the online training interventions. Some data suggest the online tools may be useful for trainees new to this field; however, this requires further study.

The neuropeptide pigment-dispersing factor (PDF) is a crucial component of the insect circadian clock, but the identity of its receptor has long remained a mystery. In this issue of Neuron, three papers (Hyun et al., Lear et al., and Mertens et al.) identify the PDF receptor.

In the simplest form of signal-detection theory (SDT), all stimuli give rise to equal-variance Gaussian probability density functions (PDFs) of sensation, with means proportional to stimulus intensity. As this simple SDT cannot accurately describe psychometric functions for two-alternative forced-choice (2AFC) detection experiments, it is commonly modified in one of two ways: with a non-linear transducer or intrinsic uncertainty. Most results can adequately be explained by either modification, but Swets et al.'s (1961) two-response 4AFC (2R4AFC) detection experiment is an exception. Simple SDT cannot predict the relationship between first- and second-response accuracies and non-linear transduction does not help. A previously unacknowledged facet of intrinsic uncertainty is that the same uncertainty required to fit 2AFC psychometric functions also produces an excellent fit to Swets et al.'s 2R4AFC results, without requiring any additional assumptions. This result is derived within the context of a primer on SDT.

OBJECTIVE

To determine whether electrogastrography (EGG) can discern sonographically demonstrated motility disorders in patients with progressive systemic sclerosis (SSc) and to evaluate EGG as a possible diagnostic tool.

METHODS

Prospective study with control group and testing for reliability.

METHODS

15 SSc patients [women aged 33-70 years (mean 53.3 years)] and 15 healthy volunteers.

METHODS

Bipolar cutaneous EGG was recorded to obtain the following parameters: period dominant frequency (PDF), percentage of gastric dysrhythmia and normogastria (defined as 2-4/min), period dominant power (PDP) and its change after a standardized meal of 500 kcal (2093 kJ), and instability coefficients of dominant frequency and power (DFIC, DPIC). Simultaneously, real-time sonography was performed in the aortomesenteric plane (3.5-MHz curved-array probe). In 10 patients and 13 control subjects, the distance from the anterior wall of the gastric antrum to the abdominal skin was measured.

RESULTS

Three patients (20%) showed hypomotility of the gastric antrum sonographically. The percentage of bradygastria was significantly lower in these patients, but the PDF, DFIC and DPIC values were not significantly different. The distance between the cutaneous electrodes and the antrum bore a greater relationship to the PDP values than did the sonographically demonstrated number of gastric contractions.

CONCLUSIONS

Although cutaneous EGG can be performed in SSc patients without apparent derangement in frequency and stability of the signal, it offers no advantage over sonography in diagnosis and follow-up.

OBJECTIVE

Despite widespread use of mobile technology in medical education, medical students' use of mobile technology for clinical decision support and learning is not well understood. Three key questions were explored in this extensive mixed methods study: 1) how medical students used mobile technology in the care of patients, 2) the mobile applications (apps) used and 3) how expertise and time spent changed overtime.

METHODS

This year-long (July 2012-June 2013) mixed methods study explored the use of the iPad, using four data collection instruments: 1) beginning and end-of-year questionnaires, 2) iPad usage logs, 3) weekly rounding observations, and 4) weekly medical student interviews. Descriptive statistics were generated for the questionnaires and apps reported in the usage logs. The iPad usage logs, observation logs, and weekly interviews were analyzed via inductive thematic analysis.

RESULTS

Students predominantly used mobile technology to obtain real-time patient data via the electronic health record (EHR), to access medical knowledge resources for learning, and to inform patient care. The top four apps used were Epocrates(®), PDF Expert(®), VisualDx(®), and Micromedex(®). The majority of students indicated that their use (71%) and expertise (75%) using mobile technology grew overtime.

CONCLUSIONS

This mixed methods study provides substantial evidence that medical students used mobile technology for clinical decision support and learning. Integrating its use into the medical student's daily workflow was essential for achieving these outcomes. Developing expertise in using mobile technology and various apps was critical for effective and efficient support of real-time clinical decisions.

The instantaneous noise-free linear mixing model in independent component analysis is largely a solved problem under the usual assumption of independent nongaussian sources and full column rank mixing matrix. However, with some prior information on the sources, like positivity, new analysis and perhaps simplified solution methods may yet become possible. In this letter, we consider the task of independent component analysis when the independent sources are known to be nonnegative and well grounded, which means that they have a nonzero pdf in the region of zero. It can be shown that in this case, the solution method is basically very simple: an orthogonal rotation of the whitened observation vector into nonnegative outputs will give a positive permutation of the original sources. We propose a cost function whose minimum coincides with nonnegativity and derive the gradient algorithm under the whitening constraint, under which the separating matrix is orthogonal. We further prove that in the Stiefel manifold of orthogonal matrices, the cost function is a Lyapunov function for the matrix gradient flow, implying global convergence. Thus, this algorithm is guaranteed to find the nonnegative well-grounded independent sources. The analysis is complemented by a numerical simulation, which illustrates the algorithm.

A compound probability density function (pdf) is presented to describe the envelope of the backscattered echo from tissue. This pdf allows local and global variation in scattering cross sections in tissue. The ultrasonic backscattering cross sections are assumed to be gamma distributed. The gamma distribution also is used to model the randomness in the average cross sections. This gamma-gamma model results in the compound scattering pdf for the envelope. The relationship of this compound pdf to the Rayleigh, K, and Nakagami distributions is explored through an analysis of the signal-to-noise ratio of the envelopes and random number simulations. The three parameter compound pdf appears to be flexible enough to represent envelope statistics giving rise to Rayleigh, K, and Nakagami distributions.

This editorial highlights the problem of language barrier in scientific communication in spite of the recent success of Open Access Movement. Four options for English-language journals to overcome the language barrier are suggested: 1) abstracts in alternative languages provided by authors, 2) Wiki open translation, 3) international board of translator-editors, and 4) alternative language version of the journal. The Emerging Themes in Epidemiology announces that with immediate effect, it will accept translations of abstracts or full texts by authors as Additional files. Editorial note: In an effort towards overcoming the language barrier in scientific publication, ETE will accept translations of abstracts or the full text of published articles. Each translation should be submitted separately as an Additional File in PDF format. ETE will only peer review English-language versions. Therefore, translations will not be scrutinized in the review-process and the responsibility for accurate translation rests with the authors.

The retina and the first optic neuropil (lamina) of Drosophila show circadian rhythms in various processes. To learn about the regulation of circadian rhythms in the retina and lamina and in two cell types, glial and the lamina L2 interneurons, we examined expression of the following clock genes; per, tim, clk, and cry and clock-controlled genes (ccgs); Atpα, nrv2, brp, Pdfr. We found that the expression of gene studied is specific for the retina and lamina. The rhythms of per and tim expression in the retina and glial cells are similar to that observed in the whole head and in clock neurons, while they differ in the lamina and L2 cells. In both the retina and lamina, CRY seems to be a repressor of clk expression. In L2 interneurons per expression is not cyclic indicating the other function of PER in those cells than in the circadian molecular clock. In contrast to per and tim, the pattern of clk and cry expression is similar in both the retina and lamina. The retina holds the autonomous oscillators but the expression of cry and ccgs, Atpα and nrv2, is also regulated by inputs from the pacemaker transmitted by PDF and ITP neuropeptides.

BACKGROUND

Business Architecture Models (BAMs) describe what a business does, who performs the activities, where and when activities are performed, how activities are accomplished and which data are present. The purpose of a BAM is to provide a common resource for understanding business functions and requirements and to guide software development. The cancer Biomedical Informatics Grid (caBIG®) Life Science BAM (LS BAM) provides a shared understanding of the vocabulary, goals and processes that are common in the business of LS research.

RESULTS

LS BAM 1.1 includes 90 goals and 61 people and groups within Use Case and Activity Unified Modeling Language (UML) Diagrams. Here we report on the model's current release, LS BAM 1.1, its utility and usage, and plans for future use and continuing development for future releases.

METHODS

The LS BAM is freely available as UML, PDF and HTML (https://wiki.nci.nih.gov/x/OFNyAQ).

Genetic variation provides a basis upon which populations can be genetically improved. Management of animal genetic resources in order to minimize loss of genetic diversity both within and across breeds has recently received attention at different levels, e.g., breed, national and international levels. A major need for sustainable improvement and conservation programs is accurate estimates of population parameters, such as rate of inbreeding and effective population size. A software system (POPREP) is presented that automatically generates a typeset report. Key parameters for population management, such as age structure, generation interval, variance in family size, rate of inbreeding, and effective population size form the core part of this report. The report includes a default text that describes definition, computation and meaning of the various parameters. The report is summarized in two pdf files, named Population Structure and Pedigree Analysis Reports. In addition, results (e.g., individual inbreeding coefficients, rate of inbreeding and effective population size) are stored in comma-separate-values files that are available for further processing. Pedigree data from eight livestock breeds from different species and countries were used to describe the potential of POPREP and to highlight areas for further research.

The International Centre for Diffraction Data (ICDD) is responding to the changing needs in powder diffraction and materials analysis by developing the Powder Diffraction File (PDF) in a very flexible relational database (RDB) format. The PDF now contains 136,895 powder diffraction patterns. In this paper, an attempt is made to give an overview of the PDF-4, search/match methods and the advantages of having the PDF-4 in RDB format. Some case studies have been carried out to search for crystallization trends, properties, frequencies of space groups and prototype structures. These studies give a good understanding of the basic structural aspects of classes of compounds present in the database. The present paper also reports data-mining techniques and demonstrates the power of a relational database over the traditional (flat-file) database structures.

Solid solutions of felodipine with EUDRAGIT E and EUDRAGIT E/NE were shown to dramatically increase the dissolution rate of felodipine in biorelevant media. Of the two polymer systems, extrudates containing 5% EUDRAGIT NE showed a faster dissolution rate and less recrystallization (no precipitation within 2 h). Although differential scanning calorimetry (DSC) and conventional X-ray powder diffraction (XRPD) were able to verify the amorphous state of the drug after melt extrusion, it was not possible to differentiate the two extrudate compositions further with these methods. We then applied pair distribution function (PDF) analysis to investigate extrudates. It was possible to more closely characterize the solid state of the amorphous extrudates in terms of local structural order: PDF analysis revealed that addition of minor amounts of EUDRAGIT NE to the main component EUDRAGIT E during extrusion changed the local structure of EUDRAGIT E in a nonadditive way. We conclude that local ordering can be important to the release characteristics of extrudates, even when the components are present in the amorphous state.

The finite size effects of nanoparticles on the atomic pair distribution functions (PDF) are discussed by calculating the radial distribution functions (RDF) on nanoparticles with various shapes, such as sheet, belt, rod, tube and sphere, assuming continua. Their characteristics are shown depending on the shapes and the sizes of the nanoparticles. The formulas of a PDF analysis which take account of such effects are presented and are found to reproduce the experimental data.

The use of protein templates to direct the formation of inorganic nanostructures offers a novel bio-inspired route to nanomaterial synthesis that avoids the use of harsh reaction conditions and offers unique functionalities including biocompatibility and hierarchical assembly. Pair distribution function (PDF) analysis from total X-ray scattering has been used to determine the structure of TiO2 nanoparticles grown within an icosahedral virus capsid. The protein-TiO2 composites are similar to nanocrystalline anatase and show photocatalytic activity. PDF analysis is ideally suited to the study of protein-inorganic nanocomposites, and may be able to provide information about the hard/soft interface.

BACKGROUND

Vascular complications in renal transplant recipients are uncommon but important causes of graft dysfunction and graft loss after kidney transplantation.

OBJECTIVE

To document vascular complications that occurred following kidney transplantations in order to assess the incidence of these complications at our center as well as to identify possible treatment approach.

METHODS

103 kidney transplantations were performed in the period from 1 January 2008 to 31 December 2009. All patients after kidney transplantation underwent ultrasound examination (included colour Doppler flow and duplex Doppler ultrasound) immediately after surgery--especially in condition of anuria, then regularly according to an internal schedule and always in patients with worsened graft function.

RESULTS

We detected renal vein thrombosis in 3 cases (2.9%), artery thrombosis in 4 cases (3.9%), one time intrarenal pseudoaneurysm (1%) and renal artery stenosis in 10 patients (9.7%). There was no extrarenal pseudoaneurysm or arteriovenous fistula in our group of patients.

CONCLUSIONS

The incidence of vascular complications in our department correlates with the incidence of these complications referred in literature. We confirmed the importance of established immediate diagnosis and fast intervention once the diagnosis of vascular complication is established (Fig. 8, Ref. 12). Full Text in free PDF www.bmj.sk.

An assay was developed to determine the activity of peptide deformylase (PDF) inhibitors under conditions as close as possible to the physiological situation. The assay principle is the detection of N-terminal [35S]methionine labeling of a protein that contains no internal methionine. If PDF is active, the deformylation of the methionine renders the peptide a substrate for methionine aminopeptidase, resulting in the removal of the N-terminal methionine label. In the presence of a PDF inhibitor, the deformylation is blocked so that the N-formylated peptide is not processed and the label is detected. Using this assay, it is possible to determine the PDF activity under near-physiological conditions in a cell-free transcription-translation system as well as in intact bacterial cells.

In situ pair distribution function (PDF) analyses and density functional theory (DFT) computations are used to probe local structural transitions of M6O8 nodes found in two metal organic frameworks (MOFs), NU-1000 and UiO-66, for M = Zr, Hf. Such transitions are found to occur without change to the global framework symmetry at temperatures within a range relevant to many potential MOF applications. For the particular M6(O)8 nodes studied here, the observed distortions can be mapped to polymorphic forms known for bulk ZrO2. In the MOF framework, however, node distortions are found to occur at substantially lower temperature than analogous distortions in bulk ZrO2 owing to the nanoscale nature of the former.

In this paper, we compare nonparametric kernel estimates with smoothed histograms as methods for displaying logarithmically transformed dwell-time distributions. Kernel density plots provide a simpler means for producing estimates of the probability density function (pdf) and they have the advantage of being smoothed in a well-specified, carefully controlled manner. Smoothing is essential for multidimensional plots because, with realistic amounts of data, the number of counts per bin is small. Examples are presented for a 2-dimensional pdf and its associated dependency-difference plot that display the correlations between successive dwell times.