Adiabatic dynamics of edge waves in photonic graphene

The propagation of localized edge modes in photonic honeycomb lattices, formed from an array of adiabatically varying periodic helical waveguides, is considered. Asymptotic analysis leads to an explicit description of the underlying dynamics. Depending on parameters, edge states can exist over an entire period or only part of a period; in the latter case an edge mode can effectively disintegrate and scatter into the bulk. In the presence of nonlinearity, a 'time'-dependent one-dimensional nonlinear Schrödinger (NLS) equation describes the envelope dynamics of edge modes. When the average of the 'time varying' coefficients yields a focusing NLS equation, soliton propagation is exhibited. For both linear and nonlinear systems, certain long lived traveling modes with minimal backscattering are found; they exhibit properties of topologically protected states

Linear and nonlinear traveling edge waves in optical honeycomb lattices

Traveling unidirectional localized edge states in optical honeycomb lattices are analytically constructed. They are found in honeycomb arrays of helical waveguides designed to induce a periodic pseudomagnetic field varying in the direction of propagation. Conditions on whether a given pseudofield supports a traveling edge mode are discussed; a special case of the pseudofields studied agrees with recent experiments. Interesting classes of dispersion relations are obtained. Envelopes of nonlinear edge modes are described by the classical one-dimensional nonlinear Schrödinger equation along the edge. Nonlinear states termed edge solitons are predicted analytically and are found numerically

Using Qualitative Research to Inform Development of Professional Guidelines: A Case Study of the Society of Critical Care Medicine Family-Centered Care Guidelines.

OBJECTIVES: To explore the importance, challenges, and opportunities using qualitative research to enhance development of clinical practice guidelines, using recent guidelines for family-centered care in the ICU as an example. METHODS: In developing the Society of Critical Care Medicine guidelines for family-centered care in the neonatal ICU, PICU, and adult ICU, we developed an innovative adaptation of the Grading of Recommendations, Assessments, Development and Evaluations approach to explicitly incorporate qualitative research. Using Grading of Recommendations, Assessments, Development and Evaluations and the Council of Medical Specialty Societies principles, we conducted a systematic review of qualitative research to establish family-centered domains and outcomes. Thematic analyses were undertaken on study findings and used to support Population, Intervention, Comparison, Outcome question development. RESULTS: We identified and employed three approaches using qualitative research in these guidelines. First, previously published qualitative research was used to identify important domains for the Population, Intervention, Comparison, Outcome questions. Second, this qualitative research was used to identify and prioritize key outcomes to be evaluated. Finally, we used qualitative methods, member checking with patients and families, to validate the process and outcome of the guideline development. CONCLUSIONS: In this, a novel report, we provide direction for standardizing the use of qualitative evidence in future guidelines. Recommendations are made to incorporate qualitative literature review and appraisal, include qualitative methodologists in guideline taskforce teams, and develop training for evaluation of qualitative research into guideline development procedures. Effective methods of involving patients and families as members of guideline development represent opportunities for future work

The clinical utility of routine urinalysis in pregnancy: A prospective study

Objectives: To determine whether routine urinalysis in the antenatal period facilitates diagnosis of pre-eclampsia. Can routine urinalysis during pregnancy be discontinue in women with normal results of dipstick urinalysis and microscopy at the first antenatal visit? Design: Prospective observational study. Setting: A metropolitan public hospital and a private hospital in Sydney (NSW). Participants: One thousand women were enrolled at their first antenatal visit (March to November 1999), and 913 completed the study. Outcome measures: The primary outcome was a diagnosis of de novo hypertension (gestational hypertension, pre-eclampasia, or pre-eclampsia superimposed on chronic hypertension). Results: Thirty-five women had dipstick proteinuria at the first antenatal visit. In 25 (71%) of these women, further dipstick proteinuria was detected during pregnancy, and two (6%) were diagnosed with pre-eclampsia. Of the 867 without dipstick proteinuria at the first visit, 338 (39%) had dipstick proteinuria (> 1+) at some time during pregnancy. There were no statistically significant differences in the proportion of women with and without dipstick proteinuria at their first visit who developed hypertension during pregnancy. Only six women developed proteinuria before the onset of hypertension. Women who had an abnormal result of a midstream urine test at their first visit, compared with women with a normal result, were more likely to have a urinary tract infection diagnosed during pregnancy; however, the numbers were small. Conclusion: In the absence of hypertension, routine urinalysis during pregnancy is a poor predictor of pre-eclampsia. Therefore, after an initial screening urinalysis, routine urinalysis could be eliminated from antenatal care without adverse outcomes for women

Mdivi-1, a mitochondrial fission inhibitor, modulates T helper cells and suppresses the development of experimental autoimmune encephalomyelitis.

BACKGROUND: Unrestrained activation of Th1 and Th17 cells is associated with the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). While inactivation of dynamin-related protein 1 (Drp1), a GTPase that regulates mitochondrial fission, can reduce EAE severity by protecting myelin from demyelination, its effect on immune responses in EAE has not yet been studied. METHODS: We investigated the effect of Mdivi-1, a small molecule inhibitor of Drp1, on EAE. Clinical scores, inflammation, demyelination and Drp1 activation in the central nervous system (CNS), and T cell responses in both CNS and periphery were determined. RESULTS: Mdivi-1 effectively suppressed EAE severity by reducing demyelination and cellular infiltration in the CNS. Mdivi-1 treatment decreased the phosphorylation of Drp1 (ser616) on CD4+ T cells, reduced the numbers of Th1 and Th17 cells, and increased Foxp3+ regulatory T cells in the CNS. Moreover, Mdivi-1 treatment effectively inhibited IFN-γ+, IL-17+, and GM-CSF+ CD4+ T cells, while it induced CD4+ Foxp3+ regulatory T cells in splenocytes by flow cytometry. CONCLUSIONS: Together, our results demonstrate that Mdivi-1 has therapeutic potential in EAE by modulating the balance between Th1/Th17 and regulatory T cells

Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types

Dosimetric Evaluation of a New Rotating Gamma System for Stereotactic Radiosurgery

Purpose: A novel rotating gamma stereotactic radiosurgery (SRS) system (Galaxy RTi) with real-time image guidance technology has been developed for high-precision SRS and frameless fractionated stereotactic radiotherapy (SRT). This work investigated the dosimetric quality of Galaxy by comparing both the machine treatment parameters and plan dosimetry parameters with those of the widely used Leksell Gamma Knife (LGK) systems for SRS. Methods: The Galaxy RTi system uses 30 cobalt-60 sources on a rotating gantry to deliver non-coplanar, non-overlapping arcs simultaneously while the LGK 4C uses 201 static cobalt-60 sources to deliver noncoplanar beams. Ten brain cancer patients were unarchived from our clinical database, which were previously treated on the LGK 4C. The lesion volume for these cases varied from 0.1 cm3 to 15.4 cm3. Galaxy plans were generated using the Prowess TPS (Prowess, Concord, CA) with the same dose constraints and optimization parameters. Treatment quality metrics such as target coverage (%volume receiving the prescription dose), conformity index (CI), cone size, shots number, beam-on time were compared together with DVH curves and dose distributions. Results: Superior treatment plans were generated for the Galaxy system that met our clinical acceptance criteria. For the 10 patients investigated, the mean CI and dose coverage for Galaxy was 1.77 and 99.24 compared to 1.94 and 99.19 for LGK, respectively. The beam-on time for Galaxy was 17.42 minutes compared to 21.34 minutes for LGK (both assuming dose rates at the initial installation). The dose fall-off is much faster for Galaxy, compared with LGK. Conclusion: The Galaxy RTi system can provide dose distributions with similar quality to that of LGK with less beam-on time and faster dose fall-off. The system is also capable of real-time image guidance at treatment position to ensure accurate dose delivery for SRS.Comment: 14 pages, 7 figure