cssi/SciSciGPT-SciSciNet huggingface dataset:
Risk of Ovarian Malignancy Algorithm (ROMA) through time and space: a meta-analysis

Objectives: Each year in the U.S. over two million women will be diagnosed with an ovarian cyst or pelvic mass of which approximately 200,000 will require surgery. Of these women, 22,000 (~11%) will ultimately be diagnosed with epithelial ovarian cancer (EOC). Multiple studies have demonstrated that women with EOC managed by a gynecologic oncologist and at high volume institutions for EOC have improved survival rates. Despite these facts, less than 50% of women diagnosed with EOC are cared for by gynecologic oncologists or at high volume institutions. The Risk of Ovarian Malignancy Algorithm (ROMA) was developed to assist in the triage of women at high risk for EOC to gynecologic oncologists. ROMA has been cleared by the FDA for risk assessment and triage in women presenting with an ovarian cyst or pelvic mass. The objective of this study was to demonstrate the performance of ROMA in a large population of women presenting with a pelvic mass. This is the largest collection of patients evaluated with ROMA to date. Methods: A meta-analysis was conducted by pooling data from 5 pelvic mass trials. This study was institutional review board (IRB)-exempt due to the secondary use of preexisting data. Data was combined into one cohort for analysis of ROMA. As per ROMA design, the sensitivity, PPV and NPV were calculated at a set specificity of ~75%. All samples were run on the Abbott ARCHITECT platform for both CA125 and HE4. Results: A total of 2,004 patients were included in the analysis (837 premenopausal and 1,167 postmenopausal). There were 448 EOCs (89 stage I, 45 stage II, 284 stage III, 24 stage IV and 6 unstaged), 83 Borderline/LMP tumors, 1,224 benign masses, 23 non-epithelial ovarian cancers, 165 other gynecological cancers, 59 non-gynecologic metastatic cancers, and 2 mesotheliomas. For the detection of benign vs EOC only in pre and postmenopausal women, at a specificity of 75.0%, ROMA achieved a sensitivity of 91.3%, a PPV of 57.2% and a NPV 95.9%. In postmenopausal women, there were 554 benign cases and 379 EOCs. At a specificity of 75.3%, ROMA achieved a sensitivity of 92.3%, a PPV of 71.9% and a NPV of 93.5%. In premenopausal patients, there were 670 benign cases and 69 EOCs. At a specificity of 74.8%, ROMA achieved a sensitivity of 85.5%, a PPV of 25.9% and a NPV of 98.0%. An analysis of the ability of ROMA to differentiate early stage EOC from benign in pre and post-menopausal women revealed a sensitivity of 76.1%, a specificity of 75.0%, a PPV of 25.0% a NPV of 96.6%. ROMA detected over 98% of all late stage III and IV EOCs. Conclusions: ROMA has been shown in multiple independent prospective trials to be an accurate tool for pelvic mass risk assessment. This is the largest collection to date to validate the performance characteristics of ROMA. ROMA should be used as one of the tools for pelvic mass risk assessment to assist in the triage of patients at high risk for EOC to gynecologic oncologists.
Homines Diversi: Heterogeneous Earner Behaviors in the Platform Economy

The platform economy has entered its second decade, and researchers are developing new theorizations of it as an economic form. One important feature is a heterogeneous labor force with respect to hours of work. In this paper, we identify another type of heterogeneity, which is the diversity of economic orientation of earners. Using in-depth interview data from 102 earners on three platforms (Airbnb, TaskRabbit, and StocksyUnited) we find that even within individual platforms, earners have different behavioral models. We have identified three — the maximizing homo economicus; sociologists’ relational homo socialis; and homo instrumentalis. We present evidence of these three types. We then discuss platform policies and how earner diversity aligns with their imperatives for growth.
Super-doses of dietary vitamin D3 intake in aged laying hens illustrates limitation of 24,25-dihydroxycholecalciferol conversion

Background: Humans take vitamin D supplements to reduce risk of vitamin D deficiency and reduce the risk of osteoporosis. However, it is unclear how dietary super-dose (10,000x greater than requirement) can affect vitamin D status in aged animals. Aged laying hens could potentially be a model to compare with women in peri- or postmenopausal stages of life because their bone health is physiologically taxed from egg production and they are highly susceptible to osteoporosis. Objective: We investigated dietary super-dose impacts of cholecalciferol (vitamin D3) on vitamin D status in aged laying hens in production. Methods: Forty-eight 68-wk old Hy-Line Brown laying hens were individually housed in cages with eight hens per dietary treatment for eleven weeks. Hens were randomly assigned to one of six groups of dietary vitamin D3 supplementation and fed ad libitum. Supplementation levels were 400 (recommended dosage for hens), 800, 7,400, 14,000, 20,000, and 36,000 IU D3/kg of feed. At termination of the study, all hens were euthanized and we collected blood, feces, and tibia and humerus bones. Ionized (free) blood calcium, fecal calcium, bone calcium, and plasma vitamin D metabolites were measured. Results: We did not discern any dietary effects in tissue and fecal calcium. We observed that increasing dietary vitamin D3 increased plasma vitamin D3, 25-hydroxycholecalciferol, and 24,25-dihydroxycholecalciferol concentrations (p
Does the Midline Peripheral Intravenous Catheter Have a Place in Critical Care

BACKGROUND The goals of infusion therapy are to preserve vascular health and safely deliver needed treatment. Achieving these goals is challenging in critical care because of the complexity of the treatment required. Daily justification of retaining an existing central venous catheter also creates urgency to change to a peripheral vascular access device. The midline catheter has had a resurgence in use because of the need for a long-term peripheral vascular access device not linked to central catheter-associated bloodstream infection risk. OBJECTIVE To review the characteristics of midline catheters, the benefits and risks of midline catheters, and current evidence regarding midline catheter use in critical care. RESULTS Research related to midline catheters has greatly expanded the body of knowledge regarding vascular access device selection and midline catheter use. DISCUSSION Although the quality and results of research on vascular access devices vary widely, a more accurate safety profile is emerging to illustrate how midline catheter use can support the goals of infusion therapy. CONCLUSIONS Optimizing vascular access device selection requires recognition that every vascular access device can cause patient harm. Although the midline catheter appears to fill an important niche in infusion therapy, use of the midline catheter should be carefully evaluated. Midline catheters should not be used as a catheter-associated bloodstream infection prevention strategy, should be inserted to administer peripherally compatible solutions, and should be considered for short-term continuous vesicant therapy only in emergent situations until more definitive vascular access can be achieved.
Mainstreaming Photo- and Video-Based Documentation as Method for Establishing a Level of Service Framework for the Mumbai Suburban Railway System:

The city of Mumbai has grown at an unprecedented rate, increasing the burden of mobility on its core public transport system, the Mumbai suburban railway network. The system is likely failing from ...
TU‐AB‐303‐08: GPU‐Based Software Platform for Efficient Image‐Guided Adaptive Radiation Therapy

Purpose: In this study, we develop an integrated software platform for adaptive radiation therapy (ART) that combines fast and accurate image registration, segmentation, and dose computation/accumulation methods. Methods: The proposed system consists of three key components; 1) deformable image registration (DIR), 2) automatic segmentation, and 3) dose computation/accumulation. The computationally intensive modules including DIR and dose computation have been implemented on a graphics processing unit (GPU). All required patient-specific data including the planning CT (pCT) with contours, daily cone-beam CTs, and treatment plan are automatically queried and retrieved from their own databases. To improve the accuracy of DIR between pCT and CBCTs, we use the double force demons DIR algorithm in combination with iterative CBCT intensity correction by local intensity histogram matching. Segmentation of daily CBCT is then obtained by propagating contours from the pCT. Daily dose delivered to the patient is computed on the registered pCT by a GPU-accelerated superposition/convolution algorithm. Finally, computed daily doses are accumulated to show the total delivered dose to date. Results: Since the accuracy of DIR critically affects the quality of the other processes, we first evaluated our DIR method on eight head-and-neck cancer cases and compared its performance. Normalized mutual-information (NMI) and normalized cross-correlation (NCC) computed as similarity measures, and our method produced overall NMI of 0.663 and NCC of 0.987, outperforming conventional methods by 3.8% and 1.9%, respectively. Experimental results show that our registration method is more consistent and roust than existing algorithms, and also computationally efficient. Computation time at each fraction took around one minute (30–50 seconds for registration and 15–25 seconds for dose computation). Conclusion: We developed an integrated GPU-accelerated software platform that enables accurate and efficient DIR, auto-segmentation, and dose computation, thus supporting an efficient ART workflow. This work was supported by NIH/NCI under grant R42CA137886.
Contingency Management in Substance Abuse Treatment. Stephen T. Higgins, Kenneth Silverman, and Sarah H. Heil (Eds.)

Treating persons with substance use problems is critical, but successful treatment has largely been dependent on the quality of the therapist–client relationship. Although important, qualitative as...
Superconductivity in fullerenes: buckyballs

The molecular orbits on a buckyball, C 60, are studied analytically. It is found that the LUMO level and the second LUMO level form a closely spaced parity doublet. The implications of this parity doublet on the polarizability of C 60 ions and the superconductivity pairing mechanism of the alkali doped C 60 crystals are analyzed.
Neonatal androgen injection changes open-field behavior of mice.

Newborn female mice of the C57BL/6J and BALB/cJ inbred strains and their reciprocal F1 hybrids were injected either with testosterone or with oil vehicle alone. Both the repeatability and mean level of open-field activity scores over a 10-day test period increased in hormone-injected animals compared with controls. Increased activity due to hormonal treatment was greater in hybrid females than in inbred females. There was no consistent effect of hormonal treatment on open-field defecation.
Stochastic Recursive Algorithm with Modified SPR Condition

A new adaptive stochastic algorithm is introduced which guarantees the convergence when the passivity condition fails without a priori information about the unknown model. The proposed algorithm consists of three stages. In the first stage an autoregressive model is fitted to estimate the parameters of the autoregressive polynomial. In the second stage, a white noise dither signal is used to estimate the autoregressive part of the autoregressive moving average model. In the third stage, an estimate of the actual noise is generated to obtain an improved autoregressive moving average model. The simulation results given shows that the proposed algorithm compares favorably with the algorithm introduced by Mayne and Clark and also Landau.
Gleevec-mediated inactivation of Akt regulates ABCG2 function in head and neck squamous cell carcinoma

1268 The ATP binding cassette protein ABCG2 (ABCP/MXR/BCRP) has been suggested to be involved in the resistance against various anticancer drugs. Many cell lines selected for resistance to numerous chemotheurapeutic drugs have been shown to overexpress ABCG2. Recent studies show that Imatinib mesylate (Gleevec, STI571) reverses ABCG2-mediated drug resistance to topotecan and SN-38. In addition, we have previously reported that Gleeve down-regulates Akt (PKB) kinase activity, which is elevated in head and neck squamous cell carcinoma (HNSCC). Akt is a downstream target in the phosphatidylinositol 3-kinase (PI3K) pathway and has been shown to regulate cellular growth and survival, tumorigenesis and drug resistance. Akt recently has also been implicated in the translocation of ABCG2 from the cell surface in LLC-PK1 cells. Therefore, we investigated whether the reversal of ABCG2 mediated drug resistance by Gleevec is caused by the down-regulation of the Akt kinase. Hoechst 33342 dye or doxorubicin was incubated with the HNSCC cells, and flow cytometry was used to determine the levels of extrusion from the cells. Cells with high Hoechst extrusion are termed side population (SP) cells. Our results suggest that Gleevec may be regulating doxorubicin drug resistance through Akt. To investigate this, Akt kinase inhibitors LY294002 and 1L-6-Hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (1L-6), transfection with siRNA Akt or a dominant negative Akt plasmid, and the tyrosine kinase inhibitor Gleevec were used to show that these treatments resulted is at least a 50% decrease in SP for each treatment. Doxorubicin extrusion flow cytometry studies also demonstrate a significant decrease in doxorubicin efflux of HNSCC cells treated with Gleevec, 1L6, and transfection with si-RNA Akt. To examine a possible mechanism for this drug resistance, Western blot and immunofluorescence were performed to study ABCG2. Similar to previous reports, our data suggests ABCG2 translocation as the mechanism to which Gleevec and Akt regulate drug resistance. In order to demonstrate the cellular effects of the proposed regulation of drug resistance, a clonogenic survival assay was performed with incubation of Gleevec and doxorubicin. This resulted in a dose-dependent decrease in cell survival compared to cells in the control population, further confirming the reversal of drug resistance via the regulation of ABCG2. Taken together, our findings demonstrate that Gleevec confers greater doxorubicin retention presumably via inhibition of Akt which regulates ABCG2 function. Ultimately, elucidating the role of Akt in the regulation of ABCG2-mediated drug resistance may support future studies of Akt as regulator in other chemotherapeutic drug resistance.
Anti-HER2/neu peptide-conjugated iron oxide nanoparticles for targeted delivery of paclitaxel to breast cancer cells

Nanoparticles (NPs) for targeted therapy are required to have appropriate size, stability, drug loading and release profiles, and efficient targeting ligands. However, many of the existing NPs such as albumin, liposomes, polymers, gold NPs, etc. encounter size limit, toxicity and stability issues when loaded with drugs, fluorophores, and targeting ligands. Furthermore, antibodies are bulky and this can greatly affect the physicochemical properties of the NPs, whereas many small molecule-based targeting ligands lack specificity. Here, we report the utilization of biocompatible, biodegradable, small (∼30 nm) and stable iron oxide NPs (IONPs) for targeted delivery of paclitaxel (PTX) to HER2/neu positive breast cancer cells using an anti-HER2/neu peptide (AHNP) targeting ligand. We demonstrate the uniform size and high stability of these NPs in biological medium, their effective tumour targeting in live mice, as well as their efficient cellular targeting and selective killing in human HER2/neu-positive breast cancer cells.
Changes in Voiding Patterns in Patients With MS and Extended-Release Oxybutynin

We evaluated the effects and tolerability of extended-release oxybutynin chloride on the voiding and catheterization frequency of multiple sclerosis (MS) patients with neurogenic bladder. This was a 12-week, prospective, dose-titration study of extended-release oxybutynin (oxybutynin XL). MS patients were recruited for this study from the University of Pittsburgh School of Medicine's MS clinic. Entry criteria included a postvoid residual urine volume of less than 200 mL (in noncatheterized subjects). Previous urodynamic testing was not required. Exclusion criteria included individuals with urine results indicating pyuria in the presence of a positive urine culture. These tests were repeated at six and 12 weeks. After a seven-day washout period, patients recorded episodes of voiding or catheterization and incontinence for three consecutive days. Patients received initial daily doses of 10 mg oxybutynin XL in the first week. Doses were increased at weekly or biweekly intervals to a maximum of 30 mg/d. Toler...
Biochemical evidence for the orientation of cytochrome b in the yeast mitochondrial membrane in the eight-helix model.

Abstract The topographical localization of the N-terminus of cytochrome b in the inner mitochondrial membrane was determined by mild proteolysis of the yeast mitochondrial cytochrome bc1, complex and identification of the proteolytic fragments derived from subunits of the complex with an established orientation in the inner membrane. The cytochrome bc1 complex was incorporated into proteoliposomes which were separated by cytochrome c affinity chromatography into two populations in either the mitochondrial or the submitochondrial orientation. Core protein I which protrudes from the matrix side of the inner membrane was digested by proteinase K only in proteoliposomes with the submitochondrial orientation and not in those with the mitochondrial orientation. By contrast, cytochrome c1 which protrudes from the cytoplasmic side of the inner membrane was digested by proteinase K only in proteoliposomes with the mitochondrial orientation and not in those with the submitochondrial orientation. Cytochrome b was digested by SV8 protease only in proteoliposomes with the mitochondrial orientation to yield two aggregating fragments of 25.6 and 24.5 kDa. These peptides were isolated by preparative gel chromatography and sequenced to establish that the cleavage of cytochrome b by SV8 protease occurred at glutamate residues 59 and 66. These residues are localized in the extramembranous loop between the two hydrophobic membrane-spanning helices A and B and thus face the cytoplasmic side of the inner mitochondrial membrane. These results indicate that the N-terminus of yeast cytochrome b protrudes from the matrix side of the inner membrane consistent with the eight-helix model for the orientation of cytochrome b in the membrane.
Agoraphobia and hyperthyroidism.

T he association of thyroid disease and emotional lability has been noted since the 1800s [1,2]. Although nonspecific anxiety, irritability, and emotional fragility are common in hyperthyroidism [3-91, the association of agoraphobia with thyrotoxicosis is less well recognized [lO,ll]. Clinical descriptions of agoraphobia have been provided by Westphal [12] and Marks and Herst [13]. Common features of this disorder include fear of crowded or confined places, difficulty traveling away from home or places of “safety,” and the development of panic attacks. The diagnosis of agoraphobia requires identification of a situational context for the fear because the absence of this component suggests anxiety neurosis rather than agoraphobia [14]. When agoraphobia is encountered, it is important to consider the possibility that the patient may also have a coexistent disorder that initiates or accentuates the phobia. This point is illustrated by this report describing four patients with agoraphobia and hyperthyroidism. The agoraphobia, which led to a significant delay in the diagnosis of thyroid dysfunction and impaired the patients’ ability to comply with therapy, was significantly improved with restoration of a euthyroid state.
Optimization of input patterns and neuronal properties to evoke motor neuron synchronization

The study used a computational approach to identify combinations of synaptic input timing and strength superimposed on a variety of active dendritic conductances that could evoke similar levels of motor unit synchronization in model motor neurons. Two motor neurons with low recruitment thresholds but different passive properties were modeled using GENESIS software. The timing and strength of synaptic inputs and the density of dendritic ion channels were optimized with a genetic algorithm to produce a set of target discharge times. The target times were taken from experimental recordings made in a human subject and had the synchronization characteristics that are commonly observed in hand muscles. The main finding was that the two parameters with the highest association to output synchrony were the ratio of inward-to-outward ionic conductances (r = 0.344; P = 0.003) and the degree of correlation in inhibitory inputs (r = 0.306; P = 0.009). Variation in the amount of correlation in the excitatory input was not positively correlated with variation in output synchrony. Further, the variability in discharge rate of the model neurons was positively correlated with the density of N-type calcium channels in the dendritic compartments (r = 0.727; P < 0.001 and r = 0.533; P < 0.001 for the two cells). This result suggests that the experimentally observed correlation between discharge variability and synchronization is caused by an increase in fast inward ionic conductances in the dendrites. Given the moderate level of correlation between output synchrony and each of the model parameters, especially at moderate levels of synchrony (E < 0.09 and CIS < 1.0), the results suggest caution in ascribing mechanisms to observations of motor unit synchronization.
Epidermal growth factor binding and trafficking dynamics in fibroblasts: relationship to cell proliferation

Abstract We provide a mathematical model, with accompanying quantitative experimental data, for binding and trafficking properties of the epidermal growth factor (EGF) receptor on B82 fibroblasts, and propose a theoretical dependence of cell proliferation rate on these properties. The signal for cell proliferation is generated by intrinsic EGF-receptor (EGFR) tyrosine kinase activation via EGF binding at the cell surface, and terminated by receptor/growth factor complex internalization and degradation. Our model consists of kinetic equations which describe the binding, internalization, and recycling of EGF and EGFR, along with a simple expression relation the dependence of cell cycle progression on EGFR dynamics. We show that, with key model parameters determined independently from EGF/fibroblast binding and internalization experiments, our model successfully predicts, as a first step, kinetic data for EGF binding to and internalization by B82 cells at 37°C.
Comparison of Particle Size Distributions and Elemental Partitioning from the Combustion of Pulverized Coal and Residual Fuel Oil

U.S. Environmental Protection Agency (EPA) research examining the characteristics of primary PM generated by the combustion of fossil fuels is being conducted in efforts to help determine mechanisms controlling associated adverse health effects. Transition metals are of particular interest, due to the results of studies that have shown cardiopulmonary damage associated with exposure to these elements and their presence in coal and residual fuel oils. Further, elemental speciation may influence this toxicity, as some species are significantly more water-soluble, and potentially more bio-available, than others. This paper presents results of experimental efforts in which three coals and a residual fuel oil were combusted in three different systems simulating process and utility boilers. Particle size distributions (PSDs) were determined using atmospheric and low-pressure impaction as well as electrical mobility, time-of-flight, and light-scattering techniques. Size-classified PM samples from this study are also being utilized by colleagues for animal instillation experiments. Experimental results on the mass and compositions of particles between 0.03 and > 20 microns in aerodynamic diameter show that PM from the combustion of these fuels produces distinctive bimodal and trimodal PSDs, with a fine mode dominated by vaporization, nucleation, and growth processes. Depending on the fuel and combustion equipment, the coarse mode is composed primarily of unburned carbon char and associated inherent trace elements (fuel oil) and fragments of inorganic (largely calcium-alumino-silicate) fly ash including trace elements (coal). The three coals also produced a central mode between 0.8- and 2.0-micron aerodynamic diameter. However, the origins of these particles are less clear because vapor-to-particle growth processes are unlikely to produce particles this large. Possible mechanisms include the liberation of micron-scale mineral inclusions during char fragmentation and burnout and indicates that refractory transition metals can contribute to PM < 2.5 microns without passing through a vapor phase. When burned most efficiently, the residual fuel oil produces a PSD composed almost exclusively of an ultrafine mode (approximately 0.1 micron). The transition metals associated with these emissions are composed of water-soluble metal sulfates. In contrast, the transition metals associated with coal combustion are not significantly enriched in PM < 2.5 microns and are significantly less soluble, likely because of their association with the mineral constituents. These results may have implications regarding health effects associated with exposure to these particles.
What Will Drive Genomics Over the Next 10 Years

When the announcement was made that teams led by Francis Collins and J. Craig Venter had jointly produced a rough map of the human genome, I was way in the back of a room crowded with a starry-eyed horde of media, NIH officials, representatives from the White House, and a variety of university and corporate scientists. I am fairly certain I was the only person at that press conference from the field of ethics. In the decade since the human genome map was published, efforts to apply that knowledge to human health have greatly and appropriately increased the presence of ethics in the world of human genomics. Most thought that the ability to predict an individual's risk of developing diseases would drive the use of genomic information. That did not turn out to be so. Efforts to move personalized risk-testing to the Internet and into pharmacies did quickly follow the publication of the map and the creation of better array-based technology. A variety of companies jumped on the “spitomics” bandwagon—encouraging individuals to spit in a cup in order to find out whether they were at risk for cancer, diabetes, and drug dependency; to gain insight into the identity of their forebears; or to find out if their kids were likely to have food allergies or become star athletes. These activities met with little enthusiasm. The lack of standards about the accuracy and sensitivity of claims about genetic tests, the absence of serious efforts to ensure competent counseling, and indifference to simply having information about risk slowed the growth of interest in personal risk assessment. Fear of repercussions has been an obstacle as well. Only in the past few years, with the enactment of the Genetic Information Nondiscrimination Act of 2008 and the Patient Protection and Affordable Care Act last year, has the requisite ethical and legal infrastructure for personal genetic risk analysis been created. It is not the analysis of risk factors that shows the most immediate promise for human genomics but the application of genetic information to permit the safer and more efficacious use of drugs. Pharmacogenomics is poised to capture the promise of the discovery and publication of our genome. Cure, not diagnosis, is the value driving human genetics and is likely to do so into the future.
Cytogenetic analysis of a juvenile granulosa cell tumor

We report chromosomal changes in a juvenile granulosa cell tumor with complex chromosomal rearrangements. These tumors have not been subjected previously to cytogenetic analysis.
As they see US: the Americanization of a Japanese multinational in the USA

Examines the culturally‐conditioned localization process of a Japanese multinational in the United States. Analyses the case of a dialogical relationship between Americanism and Japanism as perceived and executed by organizational sub‐groups that paralleled the functional degradation process of a Japanese‐English technical translation task. While different organizational sub‐groups used different cultural markers such as “insider/outsider”, “woman”, and “Asian” as “legitimate” categories of people in the firm, their contending rhetoric against the others became remarkably similar in purpose and binary opposition. Advocates more sensitivity to multiple processes of intra‐ and inter‐subjective dialogues and schema creation, and to the ingenuity of social agents who attempt to push for their vested interest versus those of the others in the global, capitalistic, post‐colonial world order. Multiple interpretations of Asian businesses in the United States are part of this new “structuation” process.
First‐Order geometrical response equations for state‐averaged multiconfigurational self‐consistent field (SA‐MCSCF) wave functions

The first-order geometrical response equations for a state-averaged multiconfigurational self-consistent field (SA-MCSCF) calculation are derived. This derivation is carried through from first principles to final working equations suited for computer implementation. The final equations are expressed such that the energies and wave functions must be known only for the internalSA-MCSCF states. In the derivation, the special but important case where two or more internal states have equal weighting factors is treated in a manner fully consistent with all other cases. Except for introducing extra equations that are straightforward to solve, the case where two or more internal states have equal weighting factors introduces no new complications.
Periodic solutions to non-autonomous second-order systems

Abstract We establish the existence of periodic solution of a class of non-autonomous second-order systems, x + μ x + V ( t , x ) = 0 , where V ( t , x ) = ( v 1 ( t , x ) , … , v n ( t , x ) ) , if lim | x | → ∞ v i ( t , x ) | x | = 0 , i = 1 , … , n , uniformly in t and V is bounded below or above for appropriate ranges of μ .
Microfluidic technologies as platforms for performing quantitative cellular analyses in an in vitro environment

Quite often, important cellular events occur in environments that are either not amenable to implanted sensors or other types of molecular probes. In such cases, a viable alternative to taking the sensor or probe to the biological sample of interest is to bring the sample of interest out of its natural environment to one that is more conducive to the measurement scheme. The disadvantage of the latter approach is that the sample may not behave in the same manner in vitro as it does in vivo, or that the agonists and other stimuli to which the sample is subjected to in vivo are no longer present. In this Tutorial Review, the authors attempt to provide some guidance, based on their own experiences and those of other scientists, to performing cellular measurements in a quantitative manner under in vitro conditions. Due to the expansive literature on analyses involving cells, the authors have limited this Tutorial Review to those methods involving microfluidic technologies, both in microbore tubing and in microfabricated channels. Initial reports of analyses involving cells in microbore tubing were first reported nearly two decades ago, while those in microfabricated fluidic devices appeared over a decade ago. However, more recently, the complexity of cell analyses using fabricated microfluidic devices (as opposed to microbore tubing) has increased due in part to the improvements in fabrication technologies, fluid handling and delivery capabilities, advances in coatings of the channels within the microfluidic device, and integrated detection schemes. Examples of cellular analyses in microbore tubing and in fabricated microfluidic devices will be given, as well as associated advantages and challenges. Finally, the authors' thoughts on cellular analyses are presented here using the classical steps in an analysis as a guide.
FINE STRUCTURAL ALTERATIONS OF INTERPHASE NUCLEI OF LYMPHOCYTES STIMULATED TO GROWTH ACTIVITY IN VITRO

This report describes fine structural changes of interphase nuclei of human peripheral blood lymphocytes stimulated to growth by short-term culture with phytohemagglutinin. Chromatin is found highly labile, its changes accompanying the sequential increases of RNA and DNA synthesis which are known to occur in lymphocyte cultures. In "resting" lymphocytes, abundant condensed chromatin appears as a network of large and small aggregates. Early in the response to phytohemagglutinin, small aggregates disappear during increase of diffuse chromatin regions. Small aggregates soon reappear, probably resulting from disaggregation of large masses of condensed chromatin. Loosened and highly dispersed forms then appear prior to the formation of prophase chromosomes. The loosened state is found by radioautography to be most active in DNA synthesis. Small nucleoli of resting lymphocytes have concentric agranular, fibrillar, and granular zones with small amounts of intranucleolar chromatin. Enlarging interphase nucleoli change chiefly (1) by increase in amount of intranucleolar chromatin and alteration of its state of aggregation and (2) by increase in granular components in close association with fibrillar components.
Evaluating DNA barcoding criteria using African duiker antelope (Cephalophinae) as a test case

African duikers in the subfamily Cephalophinae (genera Cephalophus, Philantomba and Sylvicapra) constitute an important target for DNA barcoding efforts because of their importance to the bushmeat trade and protection under the Convention for International Trade in Endangered Species (CITES). Duikers also make a challenging test case of barcoding methods due to their recent diversification, substantial intra-specific genetic variation and high species richness. However, no study to date has evaluated how well DNA barcoding methods can be used to delineate all of the taxa within this group. To address this question, cytochrome c oxidase subunit 1 (COX1) sequences from all eighteen species within this subfamily and an outgroup taxon (genus Tragelaphus) were used to build a neighbor-joining tree, identify species-specific diagnostic synapomorphies, and determine whether species exceed a given pair-wise genetic distance threshold commonly employed in DNA barcoding studies. Tree-based analyses of the data indicate that several species within two clusters of closely related taxa consistently failed to form reciprocally monophyletic clades and similarly lack species-specific synapomorphies. Furthermore, one additional taxon failed to constitute a diagnosable clade and another occupied an unresolved position in the tree. Of the two genetic distance criteria evaluated, the 3% threshold was far more effective in delimiting species than a threshold level based on the ratio of inter- to intra-specific distances. However, neither approach could effectively delineate all sister species. While the taxonomy of this group might be open to question, the fact that barcodes consistently failed to differentiate several currently recognized sister taxa challenges the routine application of this approach in forensic studies of duiker species. Future barcoding work of this group should always include a complete taxonomic sampling and strive to include a broader geographic sampling of sequence diversity than has been carried out to date. Lastly, this work highlights the need to re-examine the taxonomy of this group, which may illuminate why some barcoding criteria fail to reliably differentiate species.
Educational Theory as Theory of Culture: A Vichian Perspective on the Educational Theories of John Dewey and Kieran Egan.

At the center of every well‐constructed theory of education is a philosophical anthropology‐reasoned speculation as to the origins on man's conditions in the history of culture, especially the particular phenomenon of consciousness that underlies historical periods. Using the lens of one of the most significant theories of culture produced, we examine the philosophical anthropological accounts reflected in the theories of John Dewey and Kieran Egan, which are responsible for their divergent educational plans.
Review of Major Directions in Non-Equilibrium Atmospheric Plasma Treatments in Medical, Biological, and Bioengineering Applications

Plasma Medicine is the newest and rapidly expanding area of engineering medicine and bioengineering focused on direct applications of plasma for treatment of different diseases, blood coagulation control, wound management, and wound healing, as well as improving patient care through sterilization, medical implants, biomaterial engineering, and tissue engineering. The number of medical engineering professionals, researchers, upper undergraduate, and graduate university students involved today in plasma medicine is already large and growing; there is also an exponentially growing number of publications in this new field. All these students and professionals need the ability to find these publications to aid them in getting started and to advance in their research in plasma medicine. This determines the main purpose of this review, focused on, first of all, summarizing the major directions of fundamental plasma medicine and providing an extensive guide to specific diseases with current plasma-bioengineering solutions, as well as providing a relevant, up-to-date bibliography.
Specificity in Protein–DNA Interactions: Energetic Recognition by the (Cytosine-C5)-methyltransferase from HhaI

Sequence-specific interactions between proteins and DNA are essential for a variety of biological functions. The (cytosine-C5)-methyltransferase from HhaI (M.HhaI) specifically modifies the second base in GCGC sequences, employing a base flipping mechanism to access the target base being chemically modified. The mechanism of sequence-specific recognition of M.HhaI is not evident based on crystallographic structures, leading to the suggestion that recognition is linked to the flipping event itself, a process that may be referred to as energetic recognition. Using computational methods, it is shown that the free energy barriers to flipping are significantly higher in non-cognate versus the cognate sequence, supporting the energetic recognition mechanism. Energetic recognition is imparted by two protein "selectivity filters" that function via a "web" of protein-DNA interactions in short-lived, high energy states present along the base flipping pathway. Other sequence-specific DNA binding proteins whose function involves significant distortion of DNA's conformation may use a similar recognition mechanism.
Oral bisphosphonates and upper gastrointestinal toxicity: a study of cancer and early signals of esophageal injury.

Summary We evaluated the association between bisphosphonate use and (1) upper gastrointestinal cancer, (2) upper endoscopy, (3) incident Barrett’s esophagus, and (4) prescription antacid initiation among Medicare beneficiaries. We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett’s association.
Correlation of ureteric length with anthropometric variables of surface body habitus

Authors from the USA describe a method of correlating anthropometric variables of body habitus with ureteric length; they found height to be the variable that correlated most closely with ureteric length, but ureteric length was nevertheless difficult to predict. OBJECTIVE To evaluate the association of variables of body habitus with direct measurements of ureteric length, as the correct choice of ureteric stent length might help to prevent complications and improve stent tolerance, and to date there are limited data correlating height or other body variables with ureteric length. PATIENTS AND METHODS We prospectively measured pelvi-ureteric junction to vesico-ureteric junction length in 100 patients by placing a ruled 5 F ureteric catheter. Ureteric length was then correlated with patient height, weight, body mass index, and distance from the shoulder (acromium process) to the wrist (head of the ulna; S–W), the elbow (olecranon process) to the wrist (head of the ulna), xyphoid process to umbilicus, xyphoid process to pubis (X–P), umbilicus to pubis, and anterior iliac spine to anterior iliac spine. Patients with pathology affecting the ureteric length were excluded. The results were analysed statistically using a multiple linear regression model with stepwise selection of variables, and a paired t-test. RESULTS The mean right and left ureteric lengths were similar (P = 0.61); height (P < 0.01), weight (P = 0.02), X–P (P = 0.01), and S–W (P = 0.02) distances all correlated with ureteric length. On multivariate regression analysis, weight, height and male gender were associated with mean ureteric length. From these data a formula was constructed to predict ureteric length. CONCLUSIONS It is a challenge to predict ureteric length from body habitus, but height, X–P distance and S–W distance can be used to predict ureteric length.
Allosteric Manipulation of Photoexcited State Relaxation in a Series of RuII(bpy)2(bipyridine−crown ethers)

A series of ruthenium(II) crown ether complexes containing 4-, 5-, or 6-oxygen crowns tethered to a bipyridine at the 3,3′ position were prepared and examined for their ability to act as luminescent sensors. The complexes [(bpy)2Ru(2,2′-bipyridine-3,3′-16-crown-4)](PF6)2 and [(bpy)2Ru(2,2′-bipyridine-3,3′-19-crown-5)](PF6)2 were characterized by X-ray crystallography. The 4-oxygen crown crystallizes in the P space group. The 5-oxygen crown crystallizes in the P space group. In both complexes, the inter-pyridine ring angle in the tethered bipyridine is twisted substantially away from 0°. Coordination of a heavy metal ion such as Pb2+ by the crown ether, and the geometric changes that result, were examined by UV/Vis, luminescence and NMR spectroscopy. The results show that there is a weak allosteric interaction between the Pb2+ ion and the Ru complexes, and that this interaction alters the luminescent behavior of the Ru complexes. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Soft Chemical Conversion of Layered Double Hydroxides to Superparamagnetic Spinel Platelets

We report the synthesis of a wide range of single-crystal spinel platelets with exposed (111) faces, lateral dimensions in the micrometer range, and thicknesses of 20–50 nm, prepared by soft chemical dehydration of well crystallized layered precursors. This method enables the synthesis of the metastable composition NiCoAlO4, which cannot be prepared by conventional solid state synthesis. Because of their nanoscale thickness, mosaic structure, shape anisotropy, and surface porosity, NiCoAlO4 and NiCo2O4 platelets exhibit room-temperature superparamagnetism (TB = 40 and 250 K, respectively) despite the fact that they have micrometer-size lateral dimensions. The accessibility of a wide range of superparamagnetic spinel platelets (as opposed to cubes or spheres) should be useful for studies in ferrofluids and related composite magnetic materials.
Does a multifaceted environmental intervention alter the effect of asthma among inner-city children?

Abstract Rationale To reduce asthma symptoms in 5-12 year old children through a multifaceted environmental/educational intervention. Methods Changes in indoor allergen levels and asthma severity scores (summary score of symptoms, activity limitations, medication use, hospitalization and emergency department [ED] use) were compared over 14 months between an intervention and delayed intervention ("control") groups in a prospective, randomized field trial. Intervention group households had dust mite covers put on the child's sleeping surfaces, received a professional house cleaning, had roach bait and trays placed appropriately along with instructions in their monitoring, and received customized information about common allergens avoidance. Results Of 981 eligible subjects presenting to the ED, 410 (42%) were enrolled; 161 (40%) completed baseline activities and were randomized: 84 to intervention and 77 to control. At study's end, control children compared to baseline had a 163% increase in dust mite levels, while the intervention group levels were stable. There was no change in the overall asthma severity scores, however, relative to baseline, the median functional severity score (FSS) component declined more in the intervention (33% versus 20%) than the control group. The median FSS for the intervention group showed a 25% improvement compared to the control group (p Conclusions Dust mite allergen levels did not increase for the intervention group and the FSS indicated improvement without changing the overall asthma severity score. The interventions probably contributed to improvements in the allergenic environment and the function of the children.
Are opioids effective in relieving neuropathic pain

The purpose of this review is to identify important issues and to review the data that underlie the controversial effectiveness of opioids in relieving neuropathic pain. This controversy seems related to the use of multiple definitions of neuropathic pain together with its distinct mechanisms in both experimental animal models and human neuropathic pain syndromes, methodological shortcomings in available randomized controlled clinical trials, different methods of pain assessment, the inappropriate use of terms like efficacy and responsiveness, differential responses in spontaneous versus evoked pains, interindividual differences to specific opioids and opioid doses, and duration of follow-up. New randomized controlled clinical trials with opioids in neuropathic pain are still needed. These studies should include larger patient samples with rigorously defined homogeneous neuropathic pain syndromes. Active placebo's mimicking side-effects should be included in the double-blind design, and control of unmasking should be performed. Individual titration of the opioid dose and active management of side-effects in long-term follow-up studies need to measure both pain relief and quality of life.
Transdermal deferoxamine prevents pressure-induced diabetic ulcers

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.