The impact of punctal occlusion on soft contact lens wearing comfort and the tear film.
The purpose of this report is to describe the impact of punctal occlusion in symptomatic dry eye contact lens wearers and the relation between subjective and objective outcomes. This study was a randomized, controlled, double-masked, single center clinical trial. A previously described dry-eye questionnaire was used to determine subject eligibility. Tear interferometry was performed to evaluate prelens tear film thickness, contact lens center thickness, and postlens tear film thickness. Each subject was randomly assigned to receive the punctal plugs or a sham procedure. At the outcome examination, the subject completed the dry-eye questionnaire and answered one question rating the efficacy of the punctal plug treatment in addition to undergoing tear interferometry using an identical protocol as the first visit. Nineteen subjects completed both visits of this study. There was a significant improvement in the dry-eye questionnaire scores from baseline to the outcome visit for both the plug (Z = -2.52, P=0.01) and sham groups (Z = -2.93, P=0.003). A significant increase in prelens tear film thickness occurred within the sham group from baseline to the outcome visit (Z = -1.96, P=0.05), but not for the punctal plug group. No other layers measured by interferometry were shown to change significantly for either group. Results comparing the sham and plug groups were not significantly different from each other with regards to the questionnaire score and treatment benefit assessment, indicating either the treatment effect was not detected, although present, or punctal occlusion had no treatment effect at all.


Topical ivermectin: a new successful treatment for scabies.
Ivermectin is the only one of the avermectins that has been widely used in humans, since it is recommended as the treatment of choice for onchocerciasis, a filariasis that produces "river blindness," a parasitic endemic infestation in countries of West Equatorial Africa and in some areas of Central and South America. Also, ivermectin has been used for treating human endo- and ectoparasites with effective results and with almost no side effects. To study the efficacy of ivermectin for scabies, which is very common in Colombia, a trial with this drug that could be easily administered, with fast application and high efficacy, was undertaken. For this purpose, six complete families with active scabies, consisting of 12 adults and 20 children ranging in age from 1 to 10 years, were treated with 1% ivermectin in a solution of propylene glycol applied topically to the affected skin. The dose employed was 400 microg/kg, repeated once the following week. All patients were cured, tolerated the medication well, and there were no side effects or signs of recurrence 2, 4, or 6 weeks after therapy. In addition to its efficacy, easy administration, and lack of side effects, ivermectin is a low-cost medication.


Air Pollution, Greenhouse Gas, and Traffic Externality Benefits and Costs of Shifting Private Vehicle Travel to Ridesourcing Services.
On-demand ridesourcing services from transportation network companies (TNCs), such as Uber and Lyft, have reshaped urban travel and changed externality costs from vehicle emissions, congestion, crashes, and noise. To quantify these changes, we simulate replacing private vehicle travel with TNCs in six U.S. cities. On average, we find a 50-60% decline in air pollutant emission externalities from NOx, PM2.5, and VOCs due to avoided "cold starts" and relatively newer, lower-emitting TNC vehicles. However, increased vehicle travel from deadheading creates a ∼20% increase in fuel consumption and associated greenhouse gas emissions and a ∼60% increase in external costs from congestion, crashes, and noise. Overall, shifting private travel to TNCs increases external costs by 30-35% (adding 32-37 ¢ of external costs per trip, on average). This change in externalities increases threefold when TNCs displace transit or active transport, drops by 16-17% when TNC vehicles are zero-emission electric, and potentially results in reduced externalities when TNC rides are pooled.


Doxorubicin distribution in human breast cancer.
Using a high-performance liquid chromatographic method coupled with fluorimetric detection, we evaluated plasma pharmacokinetics of doxorubicin (DX) and tissue distribution in seven patients suffering from locally advanced breast cancer. Tumor biopsies were performed 30 minutes and 24 hours after DX injection. In addition at 48 hours, during surgery, biopsies were obtained from primary breast cancer, nodes, and other accessible tissues, and DX concentrations were analyzed. A triexponential equation gave the best fit for plasma levels and the values (mean +/- SE) were: elimination half-life, 37.6 +/- 4.9 hours; volume of distribution, 605 +/- 61 L/m2; and clearance 200 +/- 27 ml/min/m2. There was greater interindividual variability in tumor DX concentrations than in plasma concentrations. DX reached much higher (range at 48 hrs, 1.54-14.17 micrograms/g) and longer-lasting concentrations in tumor than in plasma. At 48 hours tumor concentrations were 55.2-337.4 times the plasma concentrations. DX concentrations in normal breast were lower or similar to those in breast carcinoma. DX levels were very low in fat and skin, slightly higher in muscle, and very high in normal or metastasized lymph nodes.


Defining the interleukin-8-binding domain of heparan sulfate.
Interleukin-8, a member of the CXC chemokine family, has been shown to bind to glycosaminoglycans. It has been suggested that heparan sulfate on cell surfaces could provide specific ligand sites on endothelial cells to retain the highly diffusible inflammatory chemokine for presentation to leukocytes. By using selectively modified heparin and heparan sulfate fragments in a nitrocellulose filter trapping system, we have analyzed sequence requirements for interleukin-8 binding to heparin/heparan sulfate. We demonstrate that the affinity of a monomeric interleukin-8 molecule for heparin/heparan sulfate is too weak to allow binding at physiological ionic strength, whereas the dimeric form of the protein mediates binding to two sulfated domains of heparan sulfate. These domains, each an N-sulfated block of approximately 6 monosaccharide units, are contained within an approximately 22-24-mer sequence and are separated by a region of </=14 monosaccharide residues that may be fully N-acetylated. Binding to interleukin-8 correlates with the occurrence of the di-O-sulfated disaccharide unit -IdceA(2-OSO3)-GlcNSO3(6-OSO3)-. We suggest that the heparan sulfate sequence binds in horseshoe fashion over two antiparallel-oriented helical regions on the dimeric protein.


Comparison study of broth macrodilution and microdilution antifungal susceptibility tests for the filamentous fungi.
An evaluation of broth dilution antifungal susceptibility tests was performed by determining both the micro- and macrodilution MICs of amphotericin B, fluconazole, ketoconazole, 5-fluorocytosine, miconazole, and itraconazole against representative species of opportunistic hyphomycetes (Fusarium spp. and Cladosporium [Cladophialophora] spp.) and ascomycetes (Chaetomium spp.). A total of 78 strains were tested, the majority of them twice and some three times on different days. Both methods were performed according to the recommendations of the National Committee for Clinical Laboratory Standards (Document M27-P), with the exception of the temperature of incubation, which was 25 degrees C in our case. A spectrophotometric method for inoculum preparation, RPMI 1640 medium buffered with morpholinepropanesulfonic acid (pH 7.0), and an additive drug dilution procedure were used. The MICs obtained by the two methods were read after 48, 72, and 96 h of incubation for Fusarium spp. and after 72, 96, and 120 h for the remaining isolates. The kappa test was used to calculate the degree of agreement. Considering the three fungal groups together, a good agreement between the results of both tests was observed with almost all the drugs at the different incubation times. There were no cases of poor agreement. The highest level (kappa index = 1) was observed with ketoconazole at the second-day reading. These results support the further evaluation of the broth microdilution test as an alternative to the reference broth macrodilution susceptibility test.


Evaluation of iron oxide nanoparticle micelles for magnetic particle imaging (MPI) of thrombosis.
Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis.


Site-specific protein cross-linking by peroxidase-catalyzed activation of a tyrosine-containing peptide tag.
Protein modification methods represent fundamental techniques that are applicable in many fields. In this study, a site-specific protein cross-linking based on the oxidative tyrosine coupling reaction was demonstrated. In the presence of horseradish peroxidase (HRP) and H(2)O(2), tyrosine residues undergo one-electron oxidation reactions and form radicals in their phenolic moieties, and these species subsequently react with each other to form dimers or further react to generate polymers. Here, a peptide-tag containing a tyrosine residue(s) (Y-tag, of which the amino acid sequences were either GGGGY or GGYYY) was genetically introduced at the C-terminus of a model protein, Escherichia coli alkaline phosphatase (BAP). Following the incubation of recombinant BAPs with HRP and H(2)O(2), Y-tagged BAPs were efficiently cross-linked with each other, whereas wild-type BAP did not undergo cross-linking, indicating that the tyrosine residues in the Y-tags were recognized by HRP as the substrates. To determine the site-specificity of the cross-linking reaction, the Y-tag was selectively removed by thrombin digestion. The resultant BAP without the Y-tag showed no reactivity in the presence of HRP and H(2)O(2). Conversely, Y-tagged BAPs cross-linked by HRP treatment were almost completely digested into monomeric BAP units following incubation with the protease. Moreover, cross-linked Y-tagged BAPs retained ∼95% of their native enzymatic activity. These results show that HRP catalyzed the site-specific cross-linking of BAPs through tyrosine residues positioned in the C-terminal Y-tag. The site-selective enzymatic oxidative tyrosine coupling reaction should offer a practical option for site-specific and covalent protein modifications.


Attitudes and behavior of peripheral arterial disease patients toward influencing their physician's prescription of cholesterol-lowering medication.
Among 355 peripheral arterial disease (PAD) patients with low density lipoprotein cholesterol (LDL-C) levels > or = 70 mg/dl, we assessed knowledge regarding optimal LDL levels and the importance of LDL-C-lowering therapy. We also assessed PAD participants' behaviors and attitudes regarding their engagement with their physician in treatment decisions for LDL-C lowering. The average baseline LDL-C level of participants was 103.4 mg/dl +/- 30.7 mg/dl. Seventy-six percent of participants were taking at least one cholesterol-lowering medication. Sixty-six percent were unable to define their optimal LDL-C. Only 47% strongly agreed that their own actions and decisions could reduce their LDL-C. Just 29.8% were aware that patients who request specific medications from their physician were more likely to receive them, and 16% had asked their physician whether they should be taking more cholesterol-lowering medication. These findings suggest that further study is needed to identify effective interventions to educate PAD patients and their physicians about the importance of cholesterol-lowering therapy and to encourage PAD patients to participate with their physician in decisions regarding cholesterol-lowering treatment. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00217919.


Clinical value of blood pressure variability.
Blood pressure (BP) is known to continuously fluctuate over time and both the amplitude and frequency of these changes have been reported to be clinically relevant. Indeed, it has been shown that the occurrence of pronounced BP changes at the time of the physician's visit may introduce errors in the diagnosis of hypertension and in the assessment of the efficacy of antihypertensive treatment. Moreover, several studies have provided evidence that the end organ damage of hypertension is not only more closely related to 24h average BP values than to casual BP readings, it is also significantly and independently related to the degree of BP variability during the day and night. Results from a recent follow-up study support the possibility that the degree of BP variability may also have prognostic relevance in hypertensive patients. Recent progress in technology has offered us non-invasive techniques for the assessment of beat-to-beat finger blood pressure variability and for the detailed quantification of all its frequency components from the fastest to the slowest ones. Their role as additional surrogate endpoints in essential hypertension needs to be addressed in future studies.


C-reactive protein as a prognostic marker of Plasmodiumfalciparum malaria severity.
Plasmodiumfalciparum malaria causes wide variety of clinical symptoms ranging from a mild febrile illness to life-threatening complications. For prevention of the severity and early diagnosis, evaluation of potential biomarkers is much needed. C-reactive protein (CRP) is an acute phase protein and well-recognized marker of inflammation in the body. It is synthesized by liver in response to pro-inflammatory responses and has correlation with complications associated with malaria. The study was aimed to assess, if it could serve as a predictive marker for malaria disease severity. In the present study, 74 P. falciparum patients and 22 healthy controls were enrolled. Turbidimetric immunoassay was used to measure the CRP in serum samples of all the study participants. Mann-Whitney U-test for continuous data and chi-square test for categorical data were used to compare all malaria cases vs. healthy control group and uncomplicated vs. severe malaria groups. Using receiver operating characteristic (ROC) analysis, best threshold value was determined for CRP in severe malaria patients. CRP level was significantly elevated in all malaria case groups (1.6 mg/dl IQ 1-2.6) as compared to healthy controls (0.10 mg/dl IQ 0.1-0.20), with p-value <0.0001. Further, CRP level was significantly higher in the severe malaria group (2 mg/dl IQ 1.8-3.9) as compared to the uncomplicated malaria group (1.4 mg/dl IQ 1-2.47) and healthy control group (0.10 mg/dl IQ 0.10-0.20), with p-value <0.05. The present study findings suggest that CRP level can be used to differentiate severe malaria from uncomplicated malaria. Elevated CRP level could be helpful in early prediction of the disease severity in patients infected with P. falciparum and may play an important role in diagnosis of falciparum malaria where improper initial test and clinical manifestations like fever may be absent even with a high load of parasite.


Selection Bias Tracking and Detailed Subset Comparison for High-Dimensional Data.
The collection of large, complex datasets has become common across a wide variety of domains. Visual analytics tools increasingly play a key role in exploring and answering complex questions about these large datasets. However, many visualizations are not designed to concurrently visualize the large number of dimensions present in complex datasets (e.g. tens of thousands of distinct codes in an electronic health record system). This fact, combined with the ability of many visual analytics systems to enable rapid, ad-hoc specification of groups, or cohorts, of individuals based on a small subset of visualized dimensions, leads to the possibility of introducing selection bias-when the user creates a cohort based on a specified set of dimensions, differences across many other unseen dimensions may also be introduced. These unintended side effects may result in the cohort no longer being representative of the larger population intended to be studied, which can negatively affect the validity of subsequent analyses. We present techniques for selection bias tracking and visualization that can be incorporated into high-dimensional exploratory visual analytics systems, with a focus on medical data with existing data hierarchies. These techniques include: (1) tree-based cohort provenance and visualization, including a user-specified baseline cohort that all other cohorts are compared against, and visual encoding of cohort "drift", which indicates where selection bias may have occurred, and (2) a set of visualizations, including a novel icicle-plot based visualization, to compare in detail the per-dimension differences between the baseline and a user-specified focus cohort. These techniques are integrated into a medical temporal event sequence visual analytics tool. We present example use cases and report findings from domain expert user interviews.


Characterizing the link between glycosylation state and enzymatic activity of the endo-β1,4-glucanase KORRIGAN1 from Arabidopsis thaliana.
Defects in N-glycosylation and N-glycan processing frequently cause alterations in plant cell wall architecture, including changes in the structure of cellulose, which is the most abundant plant polysaccharide. KORRIGAN1 (KOR1) is a glycoprotein enzyme with an essential function during cellulose biosynthesis in Arabidopsis thaliana. KOR1 is a membrane-anchored endo-β1,4-glucanase and contains eight potential N-glycosylation sites in its extracellular domain. Here, we expressed A. thaliana KOR1 as a soluble, enzymatically active protein in insect cells and analyzed its N-glycosylation state. Structural analysis revealed that all eight potential N-glycosylation sites are utilized. Individual elimination of evolutionarily conserved N-glycosylation sites did not abolish proper KOR1 folding, but mutations of Asn-216, Asn-324, Asn-345, and Asn-567 resulted in considerably lower enzymatic activity. In contrast, production of wild-type KOR1 in the presence of the class I α-mannosidase inhibitor kifunensine, which abolished the conversion of KOR1 N-glycans into complex structures, did not affect the activity of the enzyme. To address N-glycosylation site occupancy and N-glycan composition of KOR1 under more natural conditions, we expressed a chimeric KOR1-Fc-GFP fusion protein in leaves of Nicotiana benthamiana. Although Asn-108 and Asn-133 carried oligomannosidic N-linked oligosaccharides, the six other glycosylation sites were modified with complex N-glycans. Interestingly, the partially functional KOR1 G429R mutant encoded by the A. thaliana rsw2-1 allele displayed only oligomannosidic structures when expressed in N. benthamiana, indicating its retention in the endoplasmic reticulum. In summary, our data indicate that utilization of several N-glycosylation sites is important for KOR1 activity, whereas the structure of the attached N-glycans is not critical.


Neurons on nanometric topographies: insights into neuronal behaviors in vitro.
Topography, the physical characteristics of an environment, is one of the most prominent stimuli neurons can encounter in the body. Many aspects of neurons and neuronal behavior are affected by the size, shape, and pattern of the physical features of the environment. A recent increase in the use of nanometric topographies, due to improved fabrication techniques, has resulted in new findings on neuronal behavior and development. Factors such as neuron adhesion, neurite alignment, and even the rate of neurite formation have all been highlighted through nanotopographies as complex phenomena that are driven by intricate intracellular mechanisms. Nanotopographies are suitable platforms, not only for fundamental studies on neuronal development, but also in practical applications, including multielectrode array devices and neuro-regenerative medicine. We reviewed recent publications that address the effects of nanotopography on neurons and categorized the observed behaviors as adherence, directional guidance, or accelerated outgrowth. We also discussed possible biological mechanisms of the molecular and cellular responses to topography, and suggested future perspectives for this field.


Functional subdivisions in the left angular gyrus where the semantic system meets and diverges from the default network.
The left angular gyrus (AG) is reliably activated across a wide range of semantic tasks, and is also a consistently reported component of the so-called default network that it is deactivated during all goal-directed tasks. We show here that there is only partial overlap between the semantic system and the default network in left AG and the overlap defines a reliable functional landmark that can be used to segregate functional subdivisions within AG. In 94 healthy human subjects, we collected functional magnetic resonance imaging (fMRI) data during fixation and eight goal directed tasks that involved semantic matching, perceptual matching or speech production in response to familiar or unfamiliar stimuli presented in either verbal (letters) or nonverbal (pictures) formats. Our results segregated three different left AG regions that were all activated by semantic relative to perceptual matching: (1) a midregion (mAG) that overlapped with the default network because it was deactivated during all tasks relative to fixation; (2) a dorsomesial region (dAG) that was more activated by all tasks relative to fixation; and (3) a ventrolateral region (vAG) that was only activated above fixation during semantic matching. By examining the effects of task and stimuli in each AG subdivision, we propose that mAG is involved in semantic associations regardless of the presence or absence of a stimulus; dAG is involved in searching for semantics in all visual stimuli, and vAG is involved in the conceptual identification of visual inputs. Our findings provide a framework for reporting and interpreting AG activations with greater definition.


Computational identification of key residues regulating fluorescence emission in a red/green cyanobacteriochrome.
Cyanobacteriochromes (CBCRs) are linear tetrapyrrole bilin-binding photoreceptors of cyanobacteria that exhibit high spectral diversity, gaining attention in optogenetics and bioimaging applications. Several engineering studies on CBCRs were attempted, especially for designing near-infrared (NIR) fluorescent proteins with longer fluorescence wavelengths. However, despite continuous efforts, a key component regulating fluorescence emission property in CBCRs is still poorly understood. As a model system, we focused on red/green CBCR Slr1393g3, from the unicellular cyanobacterium Synechocystis sp. PCC 6803 to engineer Pr to get far-red light-emitting property. Energy profiling and pairwise structural comparison of Slr1393g3 variants effectively reveal the mutations that are critical to the fluorescence changes. H497 seems to play a key role in stabilizing the chromophore environment, especially the α3 helix, while H495, T499, and Q502 are potential key residues determining fluorescence emission peak wavelength. We also found that mutations of α2 and α4 helical regions are closely related to the chromophore binding stability and likely affect fluorescence properties. Taken together, our computational analysis suggests that the fluorescence of Slr1393g3 is mainly controlled by the stabilization of the chromophore binding pocket. The predicted key residues potentially regulating the fluorescence emission property of a red/green CBCR will be advantageous for designing improved NIR fluorescent protein when combined with in vitro molecular evolution approaches.


Evaluation of exfoliative cytology in the diagnosis of oral premalignant and malignant lesions: A cytomorphometric analysis.
Many oral squamous cell carcinomas (OSCCs) arise within regions that previously had premalignant lesion. Early diagnosis and prompt treatment of premalignant lesions offers the best hope of improving the prognosis in patients with OSCC. Exfoliative cytology is a simple and non-invasive diagnostic technique that could be used for early detection of oral premalignant and malignant lesions. This study was undertaken to evaluate the quantitative changes in nuclear area (NA), cytoplasmic area (CA) and nuclear-to-cytoplasmic ratio (NA/CA) in cytological buccal smears of oral leukoplakia with dysplasia (OLD) and OSCC patients while comparing with normal healthy mucosa. A quantitative study was conducted over 90 subjects including 30 cases each of OLD, OSCC and clinically normal oral mucosa. The smears obtained were stained with Papanicolaou (PAP) stain and cytomorphological assessment of the keratinocytes was carried out. The statistical tools included arithmetic mean, standard deviation, Chi-square test, analysis of variance, Tukey multiple comparison. P < 0.001 was considered as significant. The mean NA of keratinocytes in the normal mucosa was 65.47 ± 4.77 μm(2) while for OLD it was 107.97 ± 5.44 μm(2) and 139.02 ± 8.10 μm(2) for that of OSCC. The differences show a statistically significant increment in NA (P < 0.001). There was significant reduction (P < 0.001) in the CA of keratinocytes from OSCC when compared with those from smears of OLD and normal mucosa with the values of 1535.80 ± 79.38 μm(2), 1078.51 ± 56.65 μm(2) and 769.70 ± 38.77 μm(2) respectively. The NA/CA ratio in the smears from normal oral mucosa, OLD and OSCC showed a mean value of 0.043 ± 0.004, 0.100 ± 0.008, 0.181 ± 0.015 respectively with a significant difference among the groups (P < 0.001). Evaluation of nuclear and CA of keratinocytes by cytomorphometry can serve as a useful adjunct in the diagnosis and prognosis of a dysplastic lesion which may lead to OSCC.


Homozygous deletion scanning in hepatobiliary tumor cell lines reveals alternative pathways for liver carcinogenesis.
Despite high rates of loss of heterozygosity affecting various chromosomes, the number of tumor suppressor genes (TSGs) found to be consistently involved in primary liver cancer is low. In the past decade, characterization of homozygous deletions (HDs) in tumors has become instrumental to identify new TSGs or to reveal the influence of a particular TSG on the development of a specific tumor type. We performed a detailed HD profiling at 238 critical loci on a collection of 57 hepatobiliary tumor cell lines (hepatocellular, cholangiocellular, and bile duct carcinomas, hepatoblastomas, and immortalized hepatocytes). We identified HDs at 9 independent loci, the analysis of which was extended to 17 additional hepatobiliary tumor cell lines. In total, 34 homozygous losses involving 9 distinct genes were detected in the 74 cell lines analyzed. Besides expected deletions at the p16-INK4A/p14-ARF, FHIT, AXIN1, and p53 genes, we detected HDs at the PTEN, NF2, STK11, BAX, and LRPDIT genes that were formerly not known to be implicated in human liver tumorigenesis. In conclusion, our data suggest that these genes may represent novel liver tumor suppressive targets. Additional tumorigenic pathways should be carefully considered in hepatocarcinogenesis.


Exploring the Influence of Social Norms on Complementary Feeding: A Scoping Review of Observational, Intervention, and Effectiveness Studies.
The influence of social norms on child feeding is recognized, but guidance is lacking on how to address norms and related perceptions that hinder or support positive nutrition practices. We reviewed recent peer-reviewed and grey literature to summarize social norms relevant to complementary feeding (CF), intervention approaches that address norms, and their impacts on social norms and CF outcomes. Many reports described various norms, customs, and perceptions related to appropriate foods for young children, parenting practices, gender, and family roles, but rarely explored how they motivated behavior. Community engagement and media interventions addressed norms through facilitated discussions, challenging negative norms, portraying positive norms, engaging emotions, and correcting misperceptions. Evaluations of norms-focused interventions reported improved CF practices, but few assessed impacts on social norms. Although multiple contextual factors influence CF practices, evidence suggests the feasibility and effectiveness of addressing social norms as one component of programs to improve CF practices.


Systematic review and meta-analysis of endoscopic ablative treatment of Barrett's esophagus.
Barrett's esophagus (BE) is the main risk factor for esophageal adenocarcinoma. Its therapeutic approach is controversial and surgical treatment in the presence of high-grade intraepithelial neoplasia may be indicated. Endoscopic approach is an alternative with lower mortality and morbidity rates and favorable results. To define the best option, according to literature, to treat Barrett's Esophagus. Systematic review of PUBMED, EMBASE, LILACS, and Cochrane Library databases was conducted and articles of randomized, controlled studies on BE endoscopic ablative treatment were selected. The systematic review through PUBMED retrieved results with higher evidence level and available recommendation grade regarding BE ablative therapy. Nine articles on randomized, controlled studies classified as A or B according to the Oxford table were selected. Cryotherapy, laser, photodynamic therapy (PDT), multipolar electrocoagulation (MPEC), and ablation through argon plasma coagulation (APC) and radiofrequency were considered ablation therapies. 649 patients from 10 different studies were analysed. PDT was found to present an increase in treatment failure compared with APC, NNH = -7. BE ablation through MPEC or APC was found to have similar risk for treatment failure in meta-analysis. PDT associated with proton pump inhibitor (PPI) is beneficial for BE ablation regarding PPI use alone, NNT = 2.Radiofrequency with PPI is an efficient method to reduce risk of treatment failure, NNT = 1. There are no studies demonstrating the benefit of indicating cryotherapy or laser therapy for BE endoscopic approach. APC ablation was found to have superior efficacy compared with PDT and ablation through APC and MPEC was found to present effective, similar results. Radiofrequency is the most recent approach requiring comparative studies for indication.


ADAM-17: a target to increase chemotherapeutic efficacy in colorectal cancer?
Chemotherapy-induced activation of ADAM-17 results in increased growth factor shedding and activation of growth factor receptor-mediated pro-survival response. Enhanced ADAM-17 activity and HER ligand shedding results in resistance to chemotherapy in CRC. Therapies that decrease ADAM-17 activity in conjunction with current treatments may enhance response rates in advanced CRC patients.


A new astrophysical setting for chondrule formation.
Chondrules in the metal-rich meteorites Hammadah al Hamra 237 and QUE 94411 have recorded highly energetic thermal events that resulted in complete vaporization of a dusty region of the solar nebula (dust/gas ratio of about 10 to 50 times solar). These chondrules formed under oxidizing conditions before condensation of iron-nickel metal, at temperatures greater than or equal to 1500 K, and were isolated from the cooling gas before condensation of moderately volatile elements such as manganese, sodium, potassium, and sulfur. This astrophysical environment is fundamentally different from conventional models for chondrule formation by localized, brief, repetitive heating events that resulted in incomplete melting of solid precursors initially residing at ambient temperatures below approximately 650 K.


[Lymphadenectomy in gastric carcinoma?].
Lymphadenectomy in gastric carcinoma is still discussed. Based on non-randomised and randomised studies D2-lymphadenectomy is indicated only in R0-resections. D2-lymph-node dissection requires great experience with this technique as well as for the management of possible postoperative complications. Survival advantages can be expected in patients with a limited nodal involvement, a favorable lymph node ratio between resected and involved nodes and in stage II disease. Therefore, survival improvement can be expected in 15-20 % of all R0-resections. Despite these limited prognostic advantages D2-lymphadenectomy should be performed in all R0-procedures since only the pathologic data of the resected specimen supply reliable prognostic parameter. If in the future sentinel lymphadenectomy allows selection criteria for a balanced indication for D2-lymphadenectomy in gastric carcinoma, needs to be awaited.


Placebos: our most effective therapy?
Placebos remain highly controversial therapies largely because of their widespread use in research as a comparator rather than a focus of analysis. While a recent systematic review of placebo versus no therapy arms in trials found no difference, the placebo effect in some areas of drug trial research is large and increasing. We attempt to explain this paradox and suggest how clinicians may use the placebo effect to advantage.


CSF levels of receptor-active endorphins in schizophrenic patients: correlations with symptomatology and monoamine metabolites.
Cerebrospinal fluid (CSF) levels of an opioid receptor-active, chromatographically separated endorphin fraction (Fraction I) were measured in 45 schizophrenic patients and 18 healthy volunteers. Significantly increased levels of Fraction I differentiated the patient group from controls, with no difference being found between newly admitted untreated and chronic previously neuroleptic-treated subjects. Fraction I levels did not correlate with age, weight, height, duration of illness, total time hospitalized, or age when symptoms first appeared. No differences were found between patients with or without a family history of schizophrenia. Fraction I levels were negatively correlated with "hallucinations" and "indecision" on the Comprehensive Psychopathological Rating Scale. Increased levels of Fraction I were associated with low levels of the dopamine metabolite homovanillic acid in drug-free schizophrenics. This relationship was not present after neuroleptic treatment or in healthy controls. No relationship was found between Fraction I and the serotonin metabolite 5-hydroxyindoleacetic acid. Neuroleptic treatment did not significantly change Fraction I levels; when only patients above the control range were considered, however, a significant decrease was observed. The data support our previous hypothesis of an increased opioid activity in schizophrenia and further indicate a concomitant dysfunction of brain endorphin and dopamine activity in schizophrenic patients.


Universal soliton pattern formations in passively mode-locked fiber lasers.
We investigate multiple-soliton pattern formations in a figure-of-eight passively mode-locked fiber laser. Operation in the anomalous dispersion regime with a double-clad fiber amplifier allows generation of up to several hundreds of solitons per round trip. We report the observation of remarkable soliton distributions: soliton gas, soliton liquid, soliton polycrystal, and soliton crystal, thus indicating the universality of such complexes.


Protein Structural Analysis of Calbindin D28k Function and Dysregulation: Potential Competition Between Ca(2+) and Zn(2.).
Calcium homeostasis is an essential physiological process requiring tight control in the normal cell. The dysregulation of calcium homeostasis may play a key role in the onset of Alzheimer's disease (AD) and other disorders, whether through the loss of calcium binding or calcium sensing capacity. Calbindin D28k (CB-D28k), a calcium binding protein composed of six EF-hands, four of which can bind Ca(2+), has been implicated in AD-related calcium dysregulation. In this study, docking and molecular dynamics calculations were employed to refine the protein data base model in order to understand the underlying structural variations between functional and non-functional EF-hands. Molecular modeling calculations improved the modelled protein structure: helix-loop-helix sequences were formed in all hands and most canonical interactions were formed in the four functional hands. The protein can also bind Zn(2+), potentially altering the Ca(2+) binding capability. Analysis of calculated structures of Zn(2+) bound protein showed that only half of the correct EF-hand canonical interactions of Ca(2+) were formed with loop residues. These results have important implications for the understanding of calcium dysregulation as well as for the development of novel therapeutic strategies in AD and other central nervous system disease processes, or in conditions of brain injury where calcium homeostasis is compromised.


Validity, reliability, and assessment sensitivity of the Japanese version of the short-form McGill pain questionnaire 2 in Japanese patients with neuropathic and non-neuropathic pain.
The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2-J). This is a cross-sectional study. The original SF-MPQ-2 was translated into Japanese to create the SF-MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF-MPQ-2-J was assessed using internal consistency, reliability coefficients (Cronbach's α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis (CFA) was also performed to test the theoretical structure of the SF-MPQ-2-J. The internal consistencies calculated included continuous pain, α=0.893; intermittent pain, α=0.875; predominantly neuropathic pain, α=0.917; affective descriptors, α=0.857; and total score, α=0.907. The reproducibility coefficients calculated included continuous pain, ρ=0.81; intermittent pain, ρ=0.78; predominantly neuropathic pain, ρ=0.85; affective descriptors, ρ=0.75; and total score, ρ=0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. These findings suggest that the reliability and validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross-cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain.


Substrate profiling of the metalloproteinase ovastacin uncovers specific enzyme-substrate interactions and discloses fertilization-relevant substrates.
The metalloproteinase ovastacin is released by the mammalian egg upon fertilization and cleaves a distinct peptide bond in zona pellucida protein 2 (ZP2), a component of the enveloping extracellular matrix. This limited proteolysis causes zona pellucida hardening, abolishes sperm binding, and thereby regulates fertility. Accordingly, this process is tightly controlled by the plasma protein fetuin-B, an endogenous competitive inhibitor. At present, little is known about how the cleavage characteristics of ovastacin differ from closely related proteases. Physiological implications of ovastacin beyond ZP2 cleavage are still obscure. In this study, we employed N-terminal amine isotopic labeling of substrates (N-TAILS) contained in the secretome of mouse embryonic fibroblasts to elucidate the substrate specificity and the precise cleavage site specificity. Furthermore, we were able to unravel the physicochemical properties governing ovastacin-substrate interactions as well as the individual characteristics that distinguish ovastacin from similar proteases, such as meprins and tolloid. Eventually, we identified several substrates whose cleavage could affect mammalian fertilization. Consequently, these substrates indicate newly identified functions of ovastacin in mammalian fertilization beyond zona pellucida hardening.


[Comparison of productivity of different vitamin green technologies under the space station conditions].
At present, fresh plant products for nutrition of the International space station (ISS) crews are delivered from Earth in small quantities. Regular supply of additional fresh greens could be positive for improvement as of nutrition, so psychophysical state of ISS crews. Vitamin greens can be produced with the use of various technologies: planting leaf cultures in greenhouses, forcing the greens from onions and root vegetables (onion, garlic, chicory, beet, parsley etc.), and germinating seeds. Purpose of this study was to compare productivity of these technologies in order to specify inputs for designers of a vitamin greenhouse to be mounted in the space station and a Martian vehicle. Based on comparison of the productivity of various technologies, specific productivity of different greenhouses per a unit of power consumption, and a volume unit it will be maximal if used for germinating seeds and minimal if used for growing leaf vegetables in a greenhouse with a cylindrical crop surface.


A novel role of astrocyte elevated gene-1 (AEG-1) in regulating nonalcoholic steatohepatitis (NASH).
Nonalcoholic steatohepatitis (NASH) is the most prevalent cause of chronic liver disease in the Western world. However, an optimum therapy for NASH is yet to be established, mandating more in-depth investigation into the molecular pathogenesis of NASH to identify novel regulatory molecules and develop targeted therapies. Here, we unravel a unique function of astrocyte elevated gene-1(AEG-1)/metadherin in NASH using a transgenic mouse with hepatocyte-specific overexpression of AEG-1 (Alb/AEG-1) and a conditional hepatocyte-specific AEG-1 knockout mouse (AEG-1ΔHEP ). Alb/AEG-1 mice developed spontaneous NASH whereas AEG-1ΔHEP mice were protected from high-fat diet (HFD)-induced NASH. Intriguingly, AEG-1 overexpression was observed in livers of NASH patients and wild-type (WT) mice that developed steatosis upon feeding HFD. In-depth molecular analysis unraveled that inhibition of peroxisome proliferator-activated receptor alpha activity resulting in decreased fatty acid β-oxidation, augmentation of translation of fatty acid synthase resulting in de novo lipogenesis, and increased nuclear factor kappa B-mediated inflammation act in concert to mediate AEG-1-induced NASH. Therapeutically, hepatocyte-specific nanoparticle-delivered AEG-1 small interfering RNA provided marked protection from HFD-induced NASH in WT mice. AEG-1 might be a key molecule regulating initiation and progression of NASH. AEG-1 inhibitory strategies might be developed as a potential therapeutic intervention in NASH patients. (Hepatology 2017;66:466-480).


Importance of achieving stringent complete response after autologous stem-cell transplantation in multiple myeloma.
To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study. One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007). Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories.


[Lymphocyte and neutrophil cytochemistry in the dynamics of different forms of diphtheria in adults].
The cytochemical study of lymphocytes and neutrophils isolated from fractionated blood of diphtheria patients and carriers has revealed that a decrease in the activity of lymphocyte succinic dehydrogenase and myeloperoxidase can be observed at all periods of the disease and in all its forms. A decrease in the activity of lymphocyte nonspecific esterase has been noted only in patients with toxic and subtoxic diphtheria and a decrease in the activity of neutrophil alkaline phosphatase, in carriers. The analysis of correlations between the parameters of five enzymes under study (lymphocyte succinic dehydrogenase, lymphocyte acid phosphatase, lymphocyte non-specific esterase, myeloperoxidase, neutrophil alkaline phosphatase) and enzymatic rosette parameters has been made. The analysis has revealed an essential increase in the number of correlations in comparison with donors, changes in the qualitative nature of these correlations and sometimes the reversion of the correlations. Carriers have shown the greatest number of correlations. By the end of the terms of observations no restoration of normal correlations has been observed.


Influence of relative size at birth on growth and glucose homeostasis in twin lambs during juvenile life.
The effect of differences in size at birth on growth and glucose homeostasis between female twin lambs during juvenile life was examined. Twenty-six sets of twins were entered into the study, of which ten were used for organ sampling at birth and 16 were studied over the first year of life. Eleven sets were defined as being mismatched for birthweight as the weight difference between twins was >25%, with light lambs weighing 4.1 +/- 0.3 kg and heavy lambs weighing 5.1 +/- 0.1 kg. All remaining twins were matched in bodyweight, weighing 4.6 +/- 0.5 kg. During the rapid period of juvenile growth (i.e. one, three and six months of age) and following stabilization of bodyweight (i.e. 12 months of age) glucose tolerance tests were performed by intravenously injecting 0.8 mg kg(-1) bodyweight glucose. This was followed the next day with an insulin tolerance test, performed by intravenously injecting 0.08 units kg(-1) bodyweight insulin. At birth there were no differences in organ weight as a fraction of total bodyweight between matched and mismatched twins, but the ratio of liver to brain weight was lower in light compared with heavy twins. Light lambs remained lighter than their twins up to six months of age, and crown-rump length was also shorter. At one and three months of age there were no differences in basal plasma glucose concentrations between the groups, but glucose tolerance was greater in light compared with heavy lambs at one and six months of age. Insulin tolerance was greater in light compared with matched lambs at one and six months of age. In conclusion, it has been shown that size at birth of one twin in relation to its co-twin is one factor determining glucose regulation during postnatal life. This not only affects glucose and insulin tolerance but also growth over the first six months of age.


Microfabrication of nanoporous gold patterns for cell-material interaction studies.
Nanostructured materials with feature sizes in tens of nanometers have enhanced the performance of several technologies, including fuel cells, biosensors, biomedical device coatings, and drug delivery tools. Nanoporous gold (np-Au), produced by a nano-scale self-assembly process, is a relatively new material that exhibits large effective surface area, high electrical conductivity, and catalytic activity. These properties have made np-Au an attractive material to scientific community. Most studies on np-Au employ macro-scale specimens and focus on fundamental science of the material and its catalytic and sensor applications. The macro-scale specimens limit np-Au's potential in miniaturized systems, including biomedical devices. In order to address these issues, we initially describe two different methods to micropattern np-Au thin films on rigid substrates. The first method employs manually-produced stencil masks for creating millimeter-scale np-Au patterns, while the second method uses lift-off photolithography to pattern sub-millimeter-scale patterns. As the np-Au thin films are obtained by sputter-deposition process, they are compatible with conventional microfabrication techniques, thereby amenable to facile integration into microsystems. These systems include electrically-addressable biosensor platforms that benefit from high effective surface area, electrical conductivity, and gold-thiol-based surface bioconjugation. We describe cell culture, immunostaining, and image processing techniques to quantify np-Au's interaction with mammalian cells, which is an important performance parameter for some biosensors. We expect that the techniques illustrated here will assist the integration of np-Au in platforms at various length-scales and in numerous applications, including biosensors, energy storage systems, and catalysts.


Pathologic and clinical characteristics of elderly patients with breast cancer: a retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology).
There is very little information about breast cancer characteristics, treatment choices, and survival among elderly patients. The purpose of this multicenter retrospective study was to examine the clinical, pathologic, and biologic characteristics of 620 breast cancer patients age 70 years or older. Between June 1991 and May 2012, 620 patients with breast cancer, recruited from 16 institutions, were enrolled in the retrospective study. Patients had smaller tumors at diagnosis; only 15% of patients had tumors larger than 5 cm. The number of patients who had no axillary lymph node involvement was 203 (32.7%). Ninety-three patients (15.0%) had metastatic disease at diagnosis. Patients were characterized by a higher fraction of pure lobular carcinomas (75.3%). The tumors of the elderly patients were also more frequently estrogen receptor (ER) positive (75.2%) and progesterone receptor (PR) positive (67.3%). The local and systemic therapies for breast cancer differed according to age. An association between age and overall survival has not been demonstrated in elderly patients with breast cancer. In conclusion, the biologic behavior of older patients with breast cancer differs from younger patients, and older patients receive different treatments.


Clausius inequality for finite baths reveals universal efficiency improvements.
We study entropy production in nanoscale devices, which are coupled to finite heat baths. This situation is of growing experimental relevance, but most theoretical approaches rely on a formulation of the second law valid only for infinite baths. We fix this problem by pointing out that Clausius' paper from 1865 already contains an adequate formulation of the second law for finite heat baths, which can be also rigorously derived from a microscopic quantum description. This Clausius inequality shows that nonequilibrium processes are less irreversible than previously thought. We use it to correctly extend Landauer's principle to finite baths and we demonstrate that any heat engine in contact with finite baths has a higher efficiency than previously thought. Importantly, our results are easy to study, requiring only the knowledge of the average bath energy.


Assessing the strength of evidence for genes implicated in fatty acid oxidation disorders using the ClinGen clinical validity framework.
Newborn screening is an incredibly useful tool for the early identification of many metabolic disorders, including fatty acid oxidation (FAO) disorders. In many cases, molecular tests are necessary to reach a final diagnosis, highlighting the need for a thorough evaluation of genes implicated in FAO disorders. Using the ClinGen (Clinical Genome Resource) clinical validity framework, thirty genes were analyzed for the strength of evidence supporting their association with FAO disorders. Evidence was gathered from the literature by biocurators and presented to disease experts for review in order to assign a clinical validity classification of Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Reported Evidence. Of the gene-disease relationships evaluated, 22/30 were classified as Definitive, three as Moderate, one as Limited, three as No Reported Evidence and one as Disputed. Gene-disease relationships with a Limited, Disputed, and No Reported Evidence were found on two, six, and up to four panels out of 30 FAO disorder-specific panels, respectively, in the National Institute of Health Genetic Testing Registry, while over 70% of the genes on panels are definitively associated with an FAO disorder. These results highlight the need to systematically assess the clinical relevance of genes implicated in fatty acid oxidation disorders in order to improve the interpretation of genetic testing results and diagnosis of patients with these disorders.


Genetic reassortment between two human rotaviruses having different serotype and subgroup specificities.
Two reassortant viruses were selected from a mixed infection of MA104 cells with human rotavirus strains Wa (serotype 1-subgroup II) and HN126 (serotype 2-subgroup I). Antigenic characterization and genotype analysis by polyacrylamide gel electrophoresis revealed that they were reassortants with novel antigenic compositions, i.e. serotype 1-subgroup I (C116) and serotype 2-subgroup II (C15). Furthermore one of them, C15, was considered to have a mosaic antigenicity defined by two serotype-specific antigens, namely the serotype 1-specific VP3 antigen and the serotype 2-specific VP7 antigen. Although this reassortant was shown to be a serotype 2 virus on the basis of its preferential reactivity in neutralization reactions with serotype 2 antiserum, unexpectedly the antiserum prepared against C15 equally neutralized both serotype 1 and serotype 2 strains.


Cell-surface expression, progestin binding, and rapid nongenomic signaling of zebrafish membrane progestin receptors alpha and beta in transfected cells.
Recently, a unique family of membrane progestin receptors (mPRalpha, mPRbeta, and mPRgamma) was identified, which may be responsible for mediating rapid, nongenomic actions of progestins in a variety of target tissues. In this study, the mPRalpha and mPRbeta isoforms from zebrafish were shown to be rapidly and specifically activated by the maturation-inducing steroid (MIS) of this species, 4-pregnen-17,20beta-diol-3-one (17,20beta-DHP). The zebrafish mPRalpha and a previously uncharacterized mPRbeta isoform were stably expressed in nuclear progesterone receptor-deficient mammalian breast cancer cells, MDA-MB-231. Expression and surface localization of the receptors were verified by flow cytometry, biotin surface labeling, and Western blotting. Plasma membrane proteins from mPRalpha- or mPRbeta-transfected cells showed high affinity (mPRalpha, K(d) 7 nM; mPRbeta, K(d) 12 nM), saturable, displaceable, single-binding sites specific for 17,20beta-DHP, whereas negligible specific 17,20beta-DHP binding was observed in nontransfected cells. Progestin treatment caused significant activation of mitogen-activated protein kinase (MAPK) within 5 min in cells transfected with either of the receptors as measured by western blotting and flow cytometry. The rank order of the potencies of several progestins in activating MAPK via mPRalpha and mPRbeta was the same (17,20beta-DHP>progesterone >4-pregnen-17,20beta,21-triol-3-one). Interestingly, the MIS in zebrafish, 17,20beta-DHP, was also the most potent inhibitor, among the progestins tested, of adenylyl cyclase activity in cells transfected with either of the receptors. This progestin significantly decreased cAMP levels in both mPRalpha- and mPRbeta-transfected cells in a dose-responsive and time-dependent manner. In addition, signaling of the zebrafish mPRalpha was blocked by pertussis toxin, implying activation of a G(i) protein, while sensitivity to pertussis or cholera toxin was not shown with mPRbeta-mediated signaling, possibly indicating that this receptor activates a different pertussis toxin-insensitive G protein. The results of this study suggest that zebrafish mPRalpha and mPRbeta signal similarly upon progestin binding resulting in rapid activation of MAPK and downregulation of adenylyl cyclase activity.


The analysis of directionality of honed cylinder liners surfaces.
Various methods describing the directionality of honed cylinder liner surface topography are compared. The procedure of deep valleys recognition and determination of angular spectra on the basis of ratio of valleys widths in perpendicular directions is described in detail. The applications of deep valleys analysis, power spectral density, and cross-correlation functions for measured plateau-honed cylinder surface topographies were studied. It was found that method based on the deep valleys study assured correct values of honing angle estimation. Procedure of sampling interval selection for this method application was developed. Usefulness of deep valleys analysis for obtaining parameters characterizing other features specific for cylinder liner surfaces is described.


Fluorodeoxyglucose uptake in the aortic wall at PET/CT: possible finding for active atherosclerosis.
To evaluate fluorine 18 fluorodeoxyglucose (FDG) uptake in the thoracic aortic wall at combined positron emission tomography (PET)/computed tomography (CT) and compare uptake with aortic wall calcification. Records of 85 consecutive cancer patients who underwent FDG PET/CT were evaluated retrospectively. One hour after FDG injection, CT followed by PET was performed from ear to middle of the thigh. CT, PET, and fused PET/CT images were generated. FDG uptake and calcification were evaluated visually and semiquantitatively. FDG uptake was graded according to intensity; calcification, according to thickness. Unpaired t test was used for comparison of patient age with and without FDG uptake and with and without calcification. The relationship between the score (sum of grades along all aortic segments) of positive FDG uptake and calcification and patient age was analyzed with Spearman rank correlation. Comparison of frequency of FDG uptake and calcification with age, sex, risk factors for cardiovascular disease (CVD), or history of CVD was performed with chi2 analysis. Fifty patients had at least one area of FDG uptake in thoracic aortic wall, 14 of whom showed focal FDG uptake. Intermediate to intense FDG uptake tended to be observed in the descending aorta. Forty-five patients had at least one measurable aortic calcification. Thick calcification was observed most often at the aortic arch. Twelve patients had 13 uptake areas at the calcification site. Patients with positive findings were on average older (P <.05 for both increased uptake and calcification); the older patient group had higher frequency of both aortic wall uptake (P <.005) and calcification (P <.001). The calcification score correlated with age (rho = 0.60, P <.001) but the FDG uptake score did not. Women, patients with hyperlipidemia, and patients with history of CVD tended to show increased FDG uptake (P =.073,.080, and.068, respectively), whereas patients with diabetes had significantly more calcifications (P <.05). PET/CT depicted FDG uptake commonly in the thoracic aortic wall. The FDG uptake site was mostly distinct from the calcification site and may possibly be located in areas of metabolic activity of atherosclerotic changes.


Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells.
Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain nonneuronal tumors with the effect based on the type of tumor. We investigated NGF and its receptors (TrkA and p75) in pancreatic cancer cells (PANC-1, MIA-PaCa-2, CAPAN-1, ASPC-1, and T3M4) by reverse transcription-PCR, Western blot analysis, NGF ELISA, and growth assays. NGF mRNA was present at comparable levels in all five pancreatic cancer cell lines. TrkA expression was relatively high in PANC-1 and MIA-PaCa-2 cells and low in CAPAN-1, ASPC-1, and T3M4 cells. p75 expression was high in PANC-1, MIA-PaCa-2, and T3M4 cells, moderate in CAPAN-1, and low in ASPC-1 cells. By ELISA assay, the intracellular NGF content in all cell lines was approximately 40 pg/10(6) cells. NGF content increased significantly in PANC-1 and MIA-PaCa-2 cells when these cells were cultured with serum-free media, whereas there was no change in the other cancer cell lines. PANC-1 and MIA-PaCa-2 cells but not the other cell lines released NGF in the culture media. Exogenous NGF stimulated the growth of PANC-1 and MIA-PaCa-2 cells, inhibited the growth of T3M4 and CAPAN-1 cells in a dose- and time-dependent manner, and did not affect the growth of ASPC-1 cells. NGF led to the phosphorylation of TrkA, mitogen-activated protein kinase (MAPK), and p38 MAPK but not stress-activated protein kinase/c-Jun NH2-terminal kinase in PANC-1 and MIA-PaCa-2 cells. In contrast, in the other pancreatic cancer cell lines none of these kinases were phosphorylated by NGF. In conclusion, the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p75 receptors. NGF-induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK. These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy.


Designing flexible energy and memory storage materials using cellulose modified graphene oxide nanocomposites.
The demand for flexible energy storage devices is ever increasing, and several polymer nanocomposites are widely used to fabricate them. Here, we present a cellulose based nanocomposite by incorporating graphene oxide (GO) nanoplatelets modified with hexamethylene diisocyanate grafting agent useful for such versatile applications. The simple method of casting/solvent evaporation is applied to prepare the nanocomposites and GO dispersion in the cellulose matrix was analyzed by Fourier transform infrared spectroscopy, X-ray diffraction studies and scanning electron microscopy. The dielectric and ferroelectric properties of the eco-friendly samples were checked with temperature and voltage variations, which can attribute to flexible energy and memory storage properties. Thus, the cellulose modified GO nanocomposite has turned to be environmentally stable and excellent next generation material for energy storage and electronic devices.


Wireless Sensor Networks for Long-Term Monitoring of Urban Noise.
Noise pollution in urban environments is becoming increasingly common and it has potential to negatively impact people's health and decrease overall productivity. In order to alleviate these effects, it is important to better quantify noise patterns and levels through data collection and analysis. Wireless sensor networks offer a method for achieving this with a higher level of granularity than traditional handheld devices. In this study, a wireless sensing unit (WSU) was developed that possesses the same functionality as a handheld sound level meter. The WSU is comprised of a microcontroller unit that enables on-board computations, a wireless transceiver that uses Zigbee protocol for data transmission, and an external peripheral board that houses the microphone transducer. The WSU utilizes on-board data processing techniques to monitor noise by computing equivalent continuous sound levels, LeqT, which effectively minimizes data transmission and increases the overall longevity of the node. Strategies are also employed to ensure real-time functionality is maintained on the sensing unit, with a focus on preventing bottlenecks between data acquisition, data processing, and wireless transmission. Four units were deployed in two weeks field validation test and were shown to be capable of monitoring noise for extended periods of time.


The spatial structure of autism in California, 1993-2001.
This article identifies significant high-risk clusters of autism based on residence at birth in California for children born from 1993 to 2001. These clusters are geographically stable. Children born in a primary cluster are at four times greater risk for autism than children living in other parts of the state. This is comparable to the difference between males and females and twice the risk estimated for maternal age over 40. In every year roughly 3% of the new caseload of autism in California arises from the primary cluster we identify-a small zone 20 km by 50 km. We identify a set of secondary clusters that support the existence of the primary clusters. The identification of robust spatial clusters indicates that autism does not arise from a global treatment and indicates that important drivers of increased autism prevalence are located at the local level.


Early transient radiation-induced brachial plexopathy in locally advanced head and neck cancer.
Early transient brachial plexopathy following radiotherapy (RT) in patients with head and neck cancer may be underreported and associated with a dose-response. Our purpose was to determine the incidence of early transient radiation-ınduced brachial plexopathy (RIBP) in patients receiving primary RT (± chemotherapy) for locally advanced head and neck cancer (HNC). Twenty-seven locally advanced HNC patients who have no finding of brachial plexopathy at the diagnosis were evaluated 3 times by a specifically developed 13-item questionnaire for determining early transient RIBP. The 54 brachial plexus in 27 patients were delineated and dose volume histograms were calculated. Median follow-up period was 28 (range: 15-40) months. The mean BP volume was 7.9 ±3.6 cm(3), and the mean and maximum doses to the BP were 45.3 (range: 32.3-59.3) Gy, and 59.4 (range: 41.4-70.3) Gy, respectively. Maximum dose to the BP was ≥ 70 Gy only in 2 nasopharyngeal cancer patients. Two (7%) early transient RIBP were reported at 7(th) and 8(th) month after RT under maximum 67.17 and 55.37 Gy, and mean 52.95 and 38.60 Gy RT doses. Two (7%) early RIBP were seen in the patient group, although brachial plexus maximum doses were ≥ 66 Gy in 75% of patients.


Market Readiness for Single-Use Cystoscopes According to Urologists and Procurement Managers Worldwide.
Single-use endoscopes have been subjected to increase awareness in recent years, and several new single-use cystoscopes (eg Ambu® aScope 4 Cysto) have entered the market. However, the market readiness for such single-use cystoscopes remains unknown. This study investigates the worldwide market readiness for single-use cystoscopes among urologists and procurement managers (PMs) from Europe, Japan, and the US. An online survey using QuestionPro® was distributed to urologists and PMs in France, Germany, Italy, Japan, Spain, the UK, and the US between March 10, 2020 and July 14, 2020. All surveys were translated into the respective local language. Statistical analyses were performed using the software package Stata/SE version 16.1, StataCorp. Fisher's exact test was used to analyze categorical variables and simple linear regression was applied to continuous variables. A total of 415 urologists and PMs completed the survey (343 [82.7%] urologists and 72 [17.3%] PMs). Seventy (16.9%) were from Japan, 100 (24.1%) were from the US, and 245 (59.0%) were evenly distributed across the following European countries: France, Germany, Italy, Spain, and the UK. On average, respondents indicated that they would consider converting to single-use in 44.5% of their cystoscopy procedures. Respondents anticipated significantly higher conversion (p<0.05) when they (1) used single-use ureteroscopes in their department, (2) were concerned about cystoscopy-related infection as a result of contaminated cystoscopes, (3) were members of their institution's value committee, or (4) considered cost-transparency to be important when purchasing cystoscopes. This study investigated the marked readiness for single-use cystoscopes according to urologists and PMs worldwide. Respondents indicated a willingness to convert to single-use cystoscopes in nearly half (44.5%) of their cystoscopy procedures. Respondents that were concerned about cystoscopy-related infections as a result of contaminated cystoscopes indicated a significantly higher anticipated conversion rate (p<0.05).


The effect of resin formulation on the degree of conversion and mechanical properties of dental restorative resins.
The goal of this study was to determine the effects of resin formulation variables, such as diluent concentration, catalyst type and concentration and cure mode, on the degree of conversion of carbon double bonds and mechanical properties of dental restorative resins. Diametral tensile strength, compressive strength, hardness, flexural modulus and strength, and dynamic mechanical properties were tested, and the results were correlated to the degree of conversion results obtained by infrared analysis. The results showed a significant correlation between increased mechanical properties and higher degrees of conversion. Enhanced conversions were achieved by incorporating higher diluent and lower inhibitor concentrations into the resins. Ambient temperature properties were similarly enhanced by lower inhibitor concentrations, but were not enhanced by higher diluent concentration. Dynamic mechanical properties testing at oral and elevated temperatures elucidated possible differences in resin microstructure and network quality. The storage moduli decreased over the dental temperature range and was lower at all temperatures for resins with lower conversions. The glass transition temperature was also lower in resins with poorer conversions, suggesting that these resins may be more unstable at oral temperatures than more highly converted resins. Dynamic mechanical properties were most closely correlated to degree of conversion in these polymeric systems.


Doublets, triplets, or quadruplets of novel agents in newly diagnosed myeloma?
The treatment of multiple myeloma is evolving rapidly. A plethora of doublet, triplet, and quadruplet combinations have been studied for the treatment of newly diagnosed myeloma. Although randomized trials have been conducted comparing older regimens such as melphalan-prednisone with newer regimens containing drugs such as thalidomide, lenalidomide, or bortezomib, there are few if any randomized trials that have compared modern combinations with each other. Even in the few trials that have done so, definitive overall survival or patient-reported quality-of-life differences have not been demonstrated. Therefore, there is marked heterogeneity in how newly diagnosed patients with myeloma are treated around the world. The choice of initial therapy is often dictated by availability of drugs, age and comorbidities of the patient, and assessment of prognosis and disease aggressiveness. This chapter reviews the current data on the most commonly used and tested doublet, triplet, and quadruplet combinations for the treatment of newly diagnosed myeloma and provides guidance on choosing the optimal initial treatment regimen.


Ductal Carcinoma In Situ and Margins <2 mm: Contemporary Outcomes With Breast Conservation.
To determine the relationship between negative margin width and locoregional recurrence (LRR) in a contemporary cohort of ductal carcinoma in situ (DCIS) patients. Recent national consensus guidelines recommend an optimal margin width of 2 mm or greater for the management of DCIS; however, controversy regarding re-excision remains when managing negative margins <2 mm. One thousand four hundred ninety-one patients with DCIS who underwent breast-conserving surgery from 1996 to 2010 were identified from a prospectively managed cancer center database and analyzed using univariate and multivariate Cox proportional hazard models to determine the relationship between negative margin width and LRR with or without adjuvant radiation therapy (RT). A univariate analysis revealed that age <40 years (n = 89; P = 0.02), no RT (n = 298; P = 0.01), and negative margin width <2 mm (n = 120; P = 0.005) were associated with LRR. The association between margin width and LRR differed by adjuvant RT status (interaction P = 0.02). There was no statistical significant difference in LRR between patients with <2 mm and ≥2 mm negative margins who underwent RT (10-yr LRR rate, 4.8% vs 3.3%, respectively; hazard ratio, 0.8; 95% CI, 0.2-3.2; P = 0.72). For patients who did not undergo RT, those with margins <2 mm were significantly more likely to develop a LRR than were those with margins ≥2 mm (10-yr LRR rate, 30.9% vs 5.4%, respectively; hazard ratio, 5.5; 95% CI, 1.8-16.8, P = 0.003). Routine additional surgery may not be justified for patients with negative margins <2 mm who undergo RT but should be performed in patients who forego RT.


A systematic review and bibliometric study of Bertolotti's syndrome: clinical characteristics and global trends.
Bertolotti's syndrome is a prevalent congenital deformity. However, many physicians fail to include it in their differential diagnosis for low back pain (LBP), which results in missed diagnosis or misdiagnosis. There is still a lack of standardized treatment and management strategies for Bertolotti's syndrome. This study aimed to review the clinical characteristics and management of Bertolotti's syndrome and reports bibliometric insights in advancements in Bertolotti's syndrome research. Studies published until 30 September 2022 were systematically reviewed according to the PRISMA guidelines. Three independent reviewers extracted the data and assessed the quality and risk of bias of the studies based on the methodological index of non-randomized studies (MINORS). SPSS, VOS viewer, and the Citespace software were used for the systematic review, visual analysis, data mining, mapping, and clustering of the retrieved articles, which presented clear and visual presentations of the structural patterns of published research in graphs. A total of 118 articles, describing a total of 419 patients with Bertolotti's syndrome, were included. There was an upward trend with a steady increase in the number of publications. The world map distribution showed that most publications were predominantly from North America and Asia. The most cited articles were published in the following journals: Spine, J Bone Joint Surg, and Radiology. The mean age of the patients was 47.7 years, and 49.6% of them were male. A total of 159 (96.4%) patients had LBP symptoms. The mean symptom duration was 41.4 months (74.8%), and most of the patients had Castellvi type II. Disc degeneration was the most reported comorbid spinal diseases. The mean methodological index of non-randomized studies score was 4.16±3.95 points (range, 1-21). A total of 265 (68.3%) patients underwent surgical treatments. Minimally invasive surgical techniques, prevalence, image classification, and disc degeneration were the current main research areas of Bertolotti's syndrome. The steady increase in the number of publications demonstrated the increased attention of researchers on this topic. Our results showed a significant prevalence of Bertolotti's syndrome in patients with LBP and a long symptom duration before the initiation of treatment. Surgical treatments were commonly used to treat patients with Bertolotti's syndrome after a non-effective conservative treatment. Minimally invasive surgical techniques, prevalence, image classification, and disc degeneration are the major research areas of Bertolotti's syndrome.


Ciprofloxacin interaction with silicon-based and conventional hydrogel contact lenses.
Hydrogel contact lenses can be used as bandage lenses to protect the corneal surface after injury. The use of novel silicon-based hydrogel lens materials as bandage lenses has not gained widespread acceptance. As a first step toward advocating their usefulness as bandage lenses, their interaction with ocular pharmaceuticals must be understood because topical agents are often administered in conjunction with bandage lenses. The in vitro uptake and release of ciprofloxacin from silicone-based hydrogel (SH) and conventional pHEMA-based (CH) hydrogel contact lenses was examined by spectrophotometric evaluation of the drug concentration in saline solution. The hydrogel contact lenses tested showed similar drug uptake (average 1800 microg/lens) but different levels of drug release. Multiphoton laser microscopy indicated that ciprofloxacin was distributed throughout the lens thickness, with higher levels of drug at the surface owing to drug precipitation. The drug adsorption onto the lenses was partially reversible. The SH lenses released a lower amount of drug than CH lenses (72 vs. 168 microg/lens). Ionic lenses released less drug than non-ionic lenses (127 vs. 151 microg/lens). The differences in ciprofloxacin uptake and release between SH and CH materials may not be clinically significant because the amount of drug released from all lenses would be above the MIC(90) of ciprofloxacin for common ocular pathogens. These results indicate that material properties have a significant impact on drug-lens interactions.


Development of a Medication Safety and Quality Survey for Small Rural Hospitals.
We summarize the development and initial implementation of a survey tool to assess medication safety in small rural hospitals. As part of an ongoing rural hospital medication safety improvement program, we developed a survey tool in all 13 critical access hospitals (CAHs) in Florida. The survey was compiled from existing medication safety assessments and standards, clinical practice guidelines, and published literature. Survey items were selected based on considerations regarding practicality and relevance to the CAH setting.The final survey instrument included 134 items representing 17 medication safety domains. Overall hospital scores ranged from 41% to 95%, with a median of 59%. Most hospitals showed large variation in scores across domains, with 5 hospitals having at least 1 domain with scores less than 10%. Highest scores across all facilities were seen for safety procedures concerning high-alert or look-alike medications and the assembly of emergency carts. The lowest median scores included availability and consistent use of standardized order sets and the effective implementation of medication safety committees. Most hospitals used the survey results to identify and prioritize quality improvement activities. The survey can be used to conduct a short medication safety assessment specific to a limited number of areas and services in CAHs. It showed good ability to discriminate medication safety levels across participating sites and highlighted opportunities for improvement. It may need modification if case mix or services differ in other states or if the status quo of medication safety in CAHs or related standards advance. The described process of survey development might be helpful to support such modifications.


Impaired host defense against Sporothrix schenckii in mice with chronic granulomatous disease.
We compared the immune defense of mice with chronic granulomatous disease (CGD mice) with that of wild-type C57BL/6 mice for their response to Sporothrix schenckii. A subcutaneous injection of 5 x 10(4) CFU S. schenckii strain IFM41598 into CGD mice resulted in systemic infection and death within 84 days. In contrast, injected C57BL/6 mice did not develop systemic infection and were able to survive through 100 days of observation. Differences in host resistance were analyzed in vitro. Neutrophils and macrophages obtained from CGD mice were found to allow greater growth of this organism than did those obtained from C57BL/6 mice. Moreover, macrophages obtained from immunized CGD mice were able to simply inhibit the growth of this fungus whereas macrophages obtained from immunized C57BL/6 mice killed the fungus within 48 h after phagocytosis. These results suggest that (i) the lack of NADPH oxidase function is a risk factor for lethal S. schenckii infection and (ii) superoxide anion and its reactive oxidative metabolites produced by neutrophils and macrophages are involved in fungistatic and fungicidal activities.


Improving discharge data fidelity for use in large administrative databases.
Large administrative databases have assumed a major role in population-based studies examining health care delivery. Lumbar fusion surgeries specifically have been scrutinized for rising rates coupled with ill-defined indications for fusion such as stenosis and spondylosis. Administrative databases classify cases with the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). The ICD-9-CM discharge codes are not designated by surgeons, but rather are assigned by trained hospital medical coders. It is unclear how accurately they capture the surgeon's indication for fusion. The authors first sought to compare the ICD-9-CM code(s) assigned by the medical coder according to the surgeon's indication based on a review of the medical chart, and then to elucidate barriers to data fidelity. A retrospective review was undertaken of all lumbar fusions performed in the Department of Neurosurgery at the authors' institution between August 1, 2011, and August 31, 2013. Based on this review, the indication for fusion in each case was categorized as follows: spondylolisthesis, deformity, tumor, infection, nonpathological fracture, pseudarthrosis, adjacent-level degeneration, stenosis, degenerative disc disease, or disc herniation. These surgeon diagnoses were compared with the primary ICD-9-CM codes that were generated by the medical coders and submitted to administrative databases. A follow-up interview with the hospital's coders and coding manager was undertaken to review causes of error and suggestions for future improvement in data fidelity. There were 178 lumbar fusion operations performed in the course of 170 hospital admissions. There were 44 hospitalizations in which fusion was performed for tumor, infection, or nonpathological fracture. Of these, the primary diagnosis matched the surgical indication for fusion in 98% of cases. The remaining 126 hospitalizations were for degenerative diseases, and of these, the primary ICD-9-CM diagnosis matched the surgeon's diagnosis in only 61 (48%) of 126 cases of degenerative disease. When both the primary and all secondary ICD-9-CM diagnoses were considered, the indication for fusion was identified in 100 (79%) of 126 cases. Still, in 21% of hospitalizations, the coder did not identify the surgical diagnosis, which was in fact present in the chart. There are many different causes of coding inaccuracy and data corruption. They include factors related to the quality of documentation by the physicians, coder training and experience, and ICD code ambiguity. Researchers, policymakers, payers, and physicians should note these limitations when reviewing studies in which hospital claims data are used. Advanced domain-specific coder training, increased attention to detail and utilization of ICD-9-CM diagnoses by the surgeon, and improved direction from the surgeon to the coder may augment data fidelity and minimize coding errors. By understanding sources of error, users of these large databases can evaluate their limitations and make more useful decisions based on them.


Dual leadership in a hospital practice.
Purpose Despite the practice of dual leadership in many organizations, there is relatively little research on the topic. Dual leadership means two leaders share the leadership task and are held jointly accountable for the results of the unit. To better understand how dual leadership works, this study aims to analyse three different dual leadership pairs at a Danish hospital. Furthermore, this study develops a tool to characterize dual leadership teams from each other. Design/methodology/approach This is a qualitative study using semi-structured interviews. Six leaders were interviewed to clarify how dual leadership works in a hospital context. All interviews were transcribed and coded. During coding, focus was on the nine principles found in the literature and another principle was found by looking at the themes that were generic for all six interviews. Findings Results indicate that power balance, personal relations and decision processes are important factors for creating efficient dual leaderships. The study develops a categorizing tool to use for further research or for organizations, to describe and analyse dual leaderships. Originality/value The study describes dual leadership in the hospital context and develops a categorizing tool for being able to distinguish dual leadership teams from each other. It is important to reveal if there are any indicators that can be used for optimising dual leadership teams in the health-care sector and in other organisations.


Growth stimulants in plant extracts for Leuconostoc citrovorum.
The growth of Leuconostoc citrovorum ML 34, an isolate associated with the malo-lactic fermentation of wine, was stimulated in part by grape, orange, cabbage, and tomato juices. The stimulatory activity of tomato serum was associated with the carbohydrate fraction. Further purification of the fraction showed that fructose was the factor responsible for initiating growth. In addition to fructose, the organism required CO(2) for establishing growth. Saturated CO(2) atmosphere and catalytic amounts of fructose served as substitutes for plant extracts in a complex glucose medium.


Stepping down backwards as a means of detecting biomechanical differences between healthy older and younger adults.
Changes in sensory- motor systems that occur with age result in a decrease in postural equilibrium, which has been linked with an increased risk of falling in the elderly. Stepping down backwards from a step perturbs dynamic postural equilibrium, thus offering an opportunity to analyze the biomechanical parameters underlying the control of balance. The aim of this study was to analyze modifications in motor patterns used by older adult subjects to control equilibrium under the environmental constraint of a backward stepping-down movement. Ten healthy young adult and 10 healthy older adult subjects with no previous history of falls stepped down backward from a stable position on a force plate 7 cm high, at a spontaneous velocity. Each subject performed five trials, and the mean of all trials was used for subsequent analyses. An ANOVA was performed, with temporal parameters defining the phases of the stepping-down backward movement, center of mass velocity, vertical ground reaction force, impulse, and slope as dependent variables, and subject group as independent variable. Older adult subjects had a longer total movement duration, a longer phase of anticipatory postural adjustments, and a longer weight-transfer phase than young adult subjects (p<0.05). In contrast, older adults had a shorter relative swing phase than the young adults (p<0.05) and a lower center of mass velocity, impulse and slope (p<0.05) than young adults. To counterbalance the perturbation of postural equilibrium created by the backward stepping-down movement, older adults decreased the intensity of ground reaction forces and spent correspondingly more time in double-support phases than young adults.


Improving driver alertness through music selection using a mobile EEG to detect brainwaves.
Driving safety has become a global topic of discussion with the recent development of the Smart Car concept. Many of the current car safety monitoring systems are based on image discrimination techniques, such as sensing the vehicle drifting from the main road, or changes in the driver's facial expressions. However, these techniques are either too simplistic or have a low success rate as image processing is easily affected by external factors, such as weather and illumination. We developed a drowsiness detection mechanism based on an electroencephalogram (EEG) reading collected from the driver with an off-the-shelf mobile sensor. This sensor employs wireless transmission technology and is suitable for wear by the driver of a vehicle. The following classification techniques were incorporated: Artificial Neural Networks, Support Vector Machine, and k Nearest Neighbor. These classifiers were integrated with integration functions after a genetic algorithm was first used to adjust the weighting for each classifier in the integration function. In addition, since past studies have shown effects of music on a person's state-of-mind, we propose a personalized music recommendation mechanism as a part of our system. Through the in-car stereo system, this music recommendation mechanism can help prevent a driver from becoming drowsy due to monotonous road conditions. Experimental results demonstrate the effectiveness of our proposed drowsiness detection method to determine a driver's state of mind, and the music recommendation system is therefore able to reduce drowsiness.


Block-Row Sparse Multiview Multilabel Learning for Image Classification.
In image analysis, the images are often represented by multiple visual features (also known as multiview features), that aim to better interpret them for achieving remarkable performance of the learning. Since the processes of feature extraction on each view are separated, the multiple visual features of images may include overlap, noise, and redundancy. Thus, learning with all the derived views of the data could decrease the effectiveness. To address this, this paper simultaneously conducts a hierarchical feature selection and a multiview multilabel (MVML) learning for multiview image classification, via embedding a proposed a new block-row regularizer into the MVML framework. The block-row regularizer concatenating a Frobenius norm (F-norm) regularizer and an l(2,1)-norm regularizer is designed to conduct a hierarchical feature selection, in which the F-norm regularizer is used to conduct a high-level feature selection for selecting the informative views (i.e., discarding the uninformative views) and the l(2,1)-norm regularizer is then used to conduct a low-level feature selection on the informative views. The rationale of the use of a block-row regularizer is to avoid the issue of the over-fitting (via the block-row regularizer), to remove redundant views and to preserve the natural group structures of data (via the F-norm regularizer), and to remove noisy features (the l(2,1)-norm regularizer), respectively. We further devise a computationally efficient algorithm to optimize the derived objective function and also theoretically prove the convergence of the proposed optimization method. Finally, the results on real image datasets show that the proposed method outperforms two baseline algorithms and three state-of-the-art algorithms in terms of classification performance.


Treatment of a landfill leachate containing compounds of pharmaceutical origin.
Paper reports the results of landfill leachate treatment with membrane bioreactor, nanofiltration and ozonation. Investigated leachate encompasses a number of specific compounds of pharmaceutical origin, including a suite of by-products deriving from the production of vitamin C and propyphenazone. Low biodegradability was observed in MBR (16%) for propyphenazone, while the removal of intermediates from the vitamin C-synthesis was moderate, reaching 30% for diacetone sorbose (DAS) and 69% for diacetone alpha-keto-gulonic acid (DAG). Ozonation almost completely removed propyphenazone but failed to significantly oxidise intermediates from the vitamin C-synthesis. Nanofiltration of the leachate succeeded to remove 99% of DAG and 79% of propyphenazone which made it the most efficient among techniques used.


Retrograde coronary artery flow in aortic valve disease.
Retrograde coronary artery flow was observed angiographically in 43 patients with aortic stenosis and/or regurgitation. In the 24 patients with pure or predominant aortic stenosis, retrograde flow was seen in all 24 during end-systole. In the eight patients with pure aortic regurgitation, retrograde flow was seen mainly during end-diastole (6/8). Among the 11 patients with stenosis and regurgitation, retrograde flow was both end-systolic and enddiastolic. Dominant left coronary arteries were seen in 13 patients; 13 showed retrograde flow in the dominant arteries. Dominant right coronary arteries were seen in 25 patients: all 25 showed retrograde flow equally in the right and left coronary. Five of the 43 patients could not be evaluated for dominance because of coronary artery occlusions. The severity of retrograde flow did not correlate with usual clinical, hemodynamic or tension-stress parameters: angina, electrocardiographic abnormality, end-diastolic pressure or volume, end-systolic pressure or volume, ejection fraction, severity of aortic regurgitation, peak or mean valve gradient, aortic valve area, myocardial tension and stress calculations, or DPTI:SPTI. In summary, retrograde coronary artery flow was seen in all 43 patients with severe aortic valve disease. The time in the cardiac cycle when retrograde flow occurred was related to the type of valve disease. Retrograde flow was seen mainly in the coronary arteries supplying the left ventricle and may result from increased regional myocardial stresses.


Chitosan-graft-polyaniline-based hydrogels: elaboration and properties.
Intrinsically conducting polymers are of great interest for a large number of applications. But among the major drawbacks are their low solubility in common solvents and their poor mechanical properties. Elaboration of composites associating a matrix, bringing its mechanical properties, and polyaniline, as the conducting polymer, is a way of overcoming these disadvantages. Chitosan-graft-polyaniline copolymers were synthesized by simple oxidative method. The grafting reaction was quite complete, and it was found that the copolymers cross-linked to yield a composite hydrogel in which the polyaniline was homogeneously embedded. The conductivity of precursor (block copolymer) and gels was found to be larger than 10(-2) S x cm(-1). The composite gels were characterized in terms of swelling and rheological properties. They can be classified as "superabsorbent" hydrogels, and the swelling is reversible. The composite gels were then successfully used as actuators.


Predicting the protein-protein interactions using primary structures with predicted protein surface.
Many biological functions involve various protein-protein interactions (PPIs). Elucidating such interactions is crucial for understanding general principles of cellular systems. Previous studies have shown the potential of predicting PPIs based on only sequence information. Compared to approaches that require other auxiliary information, these sequence-based approaches can be applied to a broader range of applications. This study presents a novel sequence-based method based on the assumption that protein-protein interactions are more related to amino acids at the surface than those at the core. The present method considers surface information and maintains the advantage of relying on only sequence data by including an accessible surface area (ASA) predictor recently proposed by the authors. This study also reports the experiments conducted to evaluate a) the performance of PPI prediction achieved by including the predicted surface and b) the quality of the predicted surface in comparison with the surface obtained from structures. The experimental results show that surface information helps to predict interacting protein pairs. Furthermore, the prediction performance achieved by using the surface estimated with the ASA predictor is close to that using the surface obtained from protein structures. This work presents a sequence-based method that takes into account surface information for predicting PPIs. The proposed procedure of surface identification improves the prediction performance with an F-measure of 5.1%. The extracted surfaces are also valuable in other biomedical applications that require similar information.