Qualitative exploration of perceived benefits of care and barriers influencing HIV care in trans Nzoia, Kenya.

BACKGROUND: Substantial efforts have been made to ensure people living with HIV (PLHIV) are linked to and retained in care but many challenges deter care utilization. We report perceived benefits of seeking HIV care and barriers to HIV care that were identified through a formative assessment conducted to advise the development of an alternative care model to deliver antiretroviral treatment therapy (ART) in Trans Nzoia County, Kenya. METHODS: Data were collected in 2015 through key informant interviews (KIIs), in-depth interviews (IDIs), and focus group discussions (FGDs). The study involved 55 participants of whom 53% were female. Ten KIIs provided community contextual information and viewpoints on the HIV epidemic in Trans Nzoia County while 20 PLHIV (10 male and 10 female) participated in IDIs. Twenty-five individuals living with HIV participated in four FGDs - two groups for men and two for women. Key informants were purposively selected, while every third patient above 18 years at the Kitale HIV Clinic was invited to share their HIV care experience through IDIs or FGDs. Trained research assistants moderated all sessions and audio recordings were transcribed and analyzed thematically. RESULTS: Findings showed that PLHIV in Trans Nzoia County used both conventional and complementary alternative care for HIV; however, public health facilities were preferred. Popular perceived benefits of adopting care were relief from symptoms and the chance to live longer. Benefits of care uptake included weight gain, renewed energy, and positive behavior change. Individual-level barriers to HIV care included lack of money and food, use of alternative care, negative side effects of ART, denial, and disclosure difficulties. At the community level, stigma, limited social support for conventional HIV treatment, and poor means of transport were reported. The health system barriers were limited supplies and staff, long distance to conventional HIV care, and unprofessional providers. CONCLUSIONS: Diverse individual, community and health system barriers continue to affect HIV care-seeking efforts in Kenya. Appreciation of context and lived experiences allows for development of realistic care models.

The relation of local order to material properties in relaxor ferroelectrics.

Correlating electromechanical and dielectric properties with nanometre-scale order is the defining challenge for the development of piezoelectric oxides. Current lead (Pb)-based relaxor ferroelectrics can serve as model systems with which to unravel these correlations, but the nature of the local order and its relation to material properties remains controversial. Here we employ recent advances in diffuse scattering instrumentation to investigate crystals that span the phase diagram of PbMg1/3Nb2/3O3-xPbTiO3 (PMN-xPT) and identify four forms of local order. From the compositional dependence, we resolve the coupling of each form to the dielectric and electromechanical properties observed. We show that relaxor behaviour does not correlate simply with ferroic diffuse scattering; instead, it results from a competition between local antiferroelectric correlations, seeded by chemical short-range order, and local ferroic order. The ferroic diffuse scattering is strongest where piezoelectricity is maximal and displays previously unrecognized modulations caused by anion displacements. Our observations provide new guidelines for evaluating displacive models and hence the piezoelectric properties of environmentally friendly next-generation materials.

Spin Stripe Order in a Square Planar Trilayer Nickelate.

Trilayer nickelates, which exhibit a high degree of orbital polarization combined with an electron count (d^{8.67}) corresponding to overdoped cuprates, have been identified as a promising candidate platform for achieving high-T_{c} superconductivity. One such material, La_{4}Ni_{3}O_{8}, undergoes a semiconductor-insulator transition at ∼105 K, which was recently shown to arise from the formation of charge stripes. However, an outstanding issue has been the origin of an anomaly in the magnetic susceptibility at the transition and whether it signifies the formation of spin stripes akin to single layer nickelates. Here we report single crystal neutron diffraction measurements (both polarized and unpolarized) that establish that the ground state is indeed magnetic. The ordering is modeled as antiferromagnetic spin stripes that are commensurate with the charge stripes, the magnetic ordering occurring in individual trilayers that are essentially uncorrelated along the crystallographic c axis. A comparison of the charge and spin stripe order parameters reveals that, in contrast to single-layer nickelates such as La_{2-x}Sr_{x}NiO_{4} as well as related quasi-2D oxides including manganites, cobaltates, and cuprates, these orders uniquely appear simultaneously, thus demonstrating a stronger coupling between spin and charge than in these related low-dimensional correlated oxides.

Observation of a Charge Density Wave Incommensuration Near the Superconducting Dome in Cu_{x}TiSe_{2}.

X-ray diffraction was employed to study the evolution of the charge density wave (CDW) in Cu_{x}TiSe_{2} as a function of copper intercalation in order to clarify the relationship between the CDW and superconductivity. The results show a CDW incommensuration arising at an intercalation value coincident with the onset of superconductivity at around x=0.055(5). Additionally, it was found that the charge density wave persists to higher intercalant concentrations than previously assumed, demonstrating that the CDW does not terminate inside the superconducting dome. A charge density wave peak was observed in samples up to x=0.091(6), the highest copper concentration examined in this study. The phase diagram established in this work suggests that charge density wave incommensuration may play a role in the formation of the superconducting state.

The effects of gold nanoparticles functionalized with ß-amyloid specific peptides on an in vitro model of blood-brain barrier.

We studied the effect of gold nanoparticle (AuNP) size, surface charge, concentration and morphology on the integrity of the blood-brain barrier (BBB) in a well-established in vitro model set-up. We focused on the effect of peptide functionalized hollow gold nanospheres and gold nanorods, which selectively bind to amyloidogenic ß-amyloid structures. These AuNP conjugates have already been successfully tested as photothermal absorbers for potential application in Alzheimer's disease (AD) therapy in an in vitro set-up, but may exhibit a low passage through the BBB due to their overall negative charge. Our results show that: (i) small (1.4 nm) AuNPs strongly affects the BBB integrity, (ii) negative surface charge impedes BBB passage, and (iii) this charge effect caused by the peptide is compensated by covalent coupling to a polyethylene glycol ligand stabilizing the particles in diluted manner.

Interplay of spin-orbit interactions, dimensionality, and octahedral rotations in semimetallic SrIrO(3).

We employ reactive molecular-beam epitaxy to synthesize the metastable perovskite SrIrO(3) and utilize in situ angle-resolved photoemission to reveal its electronic structure as an exotic narrow-band semimetal. We discover remarkably narrow bands which originate from a confluence of strong spin-orbit interactions, dimensionality, and both in- and out-of-plane IrO(6) octahedral rotations. The partial occupation of numerous bands with strongly mixed orbital characters signals the breakdown of the single-band Mott picture that characterizes its insulating two-dimensional counterpart, Sr(2)IrO(4), illustrating the power of structure-property relations for manipulating the subtle balance between spin-orbit interactions and electron-electron interactions.

Protein pheromone expression levels predict and respond to the formation of social dominance networks.

Communication signals are key regulators of social networks and are thought to be under selective pressure to honestly reflect social status, including dominance status. The odours of dominants and nondominants differentially influence behaviour, and identification of the specific pheromones associated with, and predictive of, dominance status is essential for understanding the mechanisms of network formation and maintenance. In mice, major urinary proteins (MUPs) are excreted in extraordinary large quantities and expression level has been hypothesized to provide an honest signal of dominance status. Here, we evaluate whether MUPs are associated with dominance in wild-derived mice by analysing expression levels before, during and after competition for reproductive resources over 3 days. During competition, dominant males have 24% greater urinary MUP expression than nondominants. The MUP darcin, a pheromone that stimulates female attraction, is predictive of dominance status: dominant males have higher darcin expression before competition. Dominants also have a higher ratio of darcin to other MUPs before and during competition. These differences appear transient, because there are no differences in MUPs or darcin after competition. We also find MUP expression is affected by sire dominance status: socially naive sons of dominant males have lower MUP expression, but this apparent repression is released during competition. A requisite condition for the evolution of communication signals is honesty, and we provide novel insight into pheromones and social networks by showing that MUP and darcin expression is a reliable signal of dominance status, a primary determinant of male fitness in many species.

Experimental viral evolution reveals major histocompatibility complex polymorphisms as the primary host factors controlling pathogen adaptation and virulence.

Using an experimental evolution approach, we recently demonstrated that the mouse-specific pathogen Friend virus (FV) complex adapted to specific major histocompatibility complex (MHC) genotypes, which resulted in fitness tradeoffs when viruses were exposed to hosts possessing novel MHC polymorphisms. Here we report the analysis of patterns of pathogen adaptation and virulence evolution from viruses adapting to one of three hosts that differ across the entire genome (A/WySn, DBA/2J and BALB/c). We found that serial passage of FV complex through these mouse genotypes resulted in significant increases in pathogen fitness (156-fold) and virulence (11-fold). Adaptive responses by post-passage viruses also resulted in host-genotype-specific patterns of adaptation. To evaluate the relative importance of MHC versus non-MHC polymorphisms as factors influencing pathogen adaptation and virulence, we compared the magnitude of fitness tradeoffs incurred by post-passage viruses when infecting hosts possessing either novel MHC polymorphisms alone or hosts possessing novel MHC and non-MHC polymorphisms. MHC polymorphisms alone accounted for 71% and 83% of the total observed reductions in viral fitness and virulence in unfamiliar host genotypes, respectively. Strikingly, these data suggest that genetic polymorphisms within the MHC, a gene region representing only -0.1% of the genome, are major host factors influencing pathogen adaptation and virulence evolution.

Chiral phase transition in charge ordered 1T-TiSe2.

It was recently discovered that the low-temperature, charge-ordered phase of 1T-TiSe(2) has a chiral character. This unexpected chirality in a system described by a scalar order parameter could be explained in a model where the emergence of relative phase shifts between three charge density wave components breaks the inversion symmetry of the lattice. Here, we present experimental evidence for the sequence of phase transitions predicted by that theory, going from disorder to nonchiral and finally to chiral charge order. Employing x-ray diffraction, specific heat, and electrical transport measurements, we find that a novel phase transition occurs ~7 K below the main charge ordering transition in TiSe(2), in agreement with the predicted hierarchy of charge-ordered phases.

Susceptibility anisotropy in an iron arsenide superconductor revealed by x-ray diffraction in pulsed magnetic fields.

In addition to unconventional high-T(c) superconductivity, the iron arsenides exhibit strong magnetoelastic coupling and a notable electronic anisotropy within the a-b plane. We relate these properties by studying underdoped Ba(Fe(1-x)Co(x))2As2 by x-ray diffraction in pulsed magnetic fields up to 27.5 T. We exploit magnetic detwinning effects to demonstrate anisotropy in the in-plane susceptibility, which develops at the structural phase transition despite the absence of magnetic order. The degree of detwinning increases smoothly with decreasing temperature, and a single-domain condition is realized over a range of field and temperature. At low temperatures we observe an activated behavior, with a large hysteretic remnant effect. Detwinning was not observed within the superconducting phase for accessible magnetic fields.

Magnetoelastics of a spin liquid: X-ray diffraction studies of Tb2Ti2O7 in pulsed magnetic fields.

We report high resolution single crystal x-ray diffraction measurements of the frustrated pyrochlore magnet Tb2Ti2O7, collected using a novel low temperature pulsed magnet system. This instrument allows characterization of structural degrees of freedom to temperatures as low as 4.4 K, and in applied magnetic fields as large as 30 T. We show that Tb2Ti2O7 manifests intriguing structural effects under the application of magnetic fields, including strongly anisotropic giant magnetostriction, a restoration of perfect pyrochlore symmetry in low magnetic fields, and ultimately a structural phase transition in high magnetic fields. It is suggested that the magnetoelastic coupling thus revealed plays a significant role in the spin liquid physics of Tb2Ti2O7 at low temperatures.

Two-dimensional kagome correlations and field induced order in the ferromagnetic XY pyrochlore Yb2Ti2O7.

Neutron scattering measurements show the ferromagnetic XY pyrochlore Yb2Ti2O7 to display strong quasi-two-dimensional (2D) spin correlations at low temperature, which give way to long range order (LRO) under the application of modest magnetic fields. Rods of scattering along 111 directions due to these 2D spin correlations imply a magnetic decomposition of the cubic pyrochlore system into decoupled kagome planes. A magnetic field of approximately 0.5 T applied along the [110] direction induces a transition to a 3D LRO state characterized by long-lived, dispersive spin waves. Our measurements map out a complex low temperature-field phase diagram for this exotic pyrochlore magnet.

X-ray reflectivity of chemically vapor-deposited diamond single crystals in the Laue geometry.

The absolute X-ray reflectivity of chemically vapor-deposited (CVD) single-crystal diamond plates was measured in the Laue geometry in the double-crystal non-dispersive setting with an asymmetric Si beam-conditioner crystal. The measurements were supplemented by rocking-curve topography. The measured reflectivity curves are examined in the framework of the Darwin-Hamilton approach using a set of two independent parameters: the characteristic thickness of mosaic blocks and their average angular misorientation. Owing to strong extinction effects, the width of the reflectivity curves does not directly represent the average misorientation of the blocks. Two different sets of parameters were found for the 111 asymmetric reflection in the two different scattering configurations (beam compression and beam expansion). Analysis of the rocking-curve topographs shows that this discrepancy can be attributed to inhomogeneity of the diamond crystal microstructure.

CLPFFD-PEG functionalized NIR-absorbing hollow gold nanospheres and gold nanorods inhibit ß-amyloid aggregation.

Gold nanoparticles with specific optical properties in combination with the CLPFFD peptide that exhibits selectivity for ß-amyloid (Aß) aggregates are promising photothermal absorbers for application in Alzheimer's disease therapy. We report on hollow gold nanospheres (HAuNS) and gold nanorods (AuNR), which exhibit strong plasmonic near infrared (NIR) absorbance in the optical window of biological tissue and which are functionalized with CLPFFD in two different ways. Therefore the peptide was either directly bound to the particle surface or indirectly to a particle-protecting polyethylene glycol (PEG) ligand shell, thereby reducing the CLPFFD density on the surfaces of both types of particles. Fully PEGylated particles were used for comparison. The effects on cell viability and the fundamental suitability of the HAuNS and AuNR conjugates as photothermal absorbers to inhibit Aß-fibrillation are analysed in vitro. The positive influence of the use of PEG ligands on the reduced cytotoxicity of the conjugates and on the Aß-disaggregation is discussed.

Dobutamine-stress magnetic resonance microimaging in mice : acute changes of cardiac geometry and function in normal and failing murine hearts.

The aim of this study was to assess the capability of MRI to characterize systolic and diastolic function in normal and chronically failing mouse hearts in vivo at rest and during inotropic stimulation. Applying an ECG-gated FLASH-cine sequence, MRI at 7 T was performed at rest and after administration of 1.5 microgram/g IP dobutamine. There was a significant increase of heart rate, cardiac output, and ejection fraction and significant decrease of end-diastolic and end-systolic left ventricular (LV) volumes (P<0.01 each) in normal mice during inotropic stimulation. In mice with heart failure due to chronic myocardial infarction (MI), MRI at rest revealed gross LV dilatation. There was a significant decrease of LV ejection fraction in infarcted mice (29%) versus sham mice (58%). Mice with MI showed a significantly reduced maximum LV ejection rate (P<0.001) and LV filling rate (P<0.01) and no increase of LV dynamics during dobutamine action, indicating loss of contractile and relaxation reserve. In 4-month-old transgenic mice with cardiospecific overexpression of the beta(1)-adrenergic receptor, which at this early stage do not show abnormalities of resting cardiac function, LV filling rate failed to increase after dobutamine stress (transgenic, 0.19+/-0.03 microL/ms; wild type, 0.36+/-0.01 microL/ms; P<0.01). Thus, MRI unmasked diastolic dysfunction during dobutamine stress. Dobutamine-stress MRI allows noninvasive assessment of systolic and diastolic components of heart failure. This study shows that MRI can demonstrate loss of inotropic and lusitropic response in mice with MI and can unmask diastolic dysfunction as an early sign of cardiac dysfunction in a transgenic mouse model of heart failure.

Lack of correlation between induction of chemotactic peptide receptors and stimulus-induced actin polymerization in HL-60 cells treated with dibutyryl cyclic adenosine monophosphate or retinoic acid.

We used the promyelocytic leukemic cell line HL-60 to explore the molecular mechanisms regulating stimulus-induced actin polymerization in myeloid cells. HL-60 cells express very few chemotactic peptide receptors in their undifferentiated state and fail to undergo actin polymerization when stimulated with the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). However, when the cells were induced to differentiate with dibutyryl cyclic AMP (dbcAMP) or retinoic acid, they acquired the ability to undergo actin polymerization on stimulation with FMLP or phorbol myristate acetate. Kinetic experiments revealed that in the first 48 h of retinoic acid treatment there was no increase in the chemotactic peptide receptors on HL-60 cells, but the cells were capable of undergoing actin polymerization on stimulation with FMLP. Similarly, treatment with dbcAMP showed no increase in chemotactic peptide receptors until 24 h but stimulus-induced actin polymerization was demonstrable as early as 4 h after the treatment. In addition, with dbcAMP-treated cells the magnitude of stimulus-induced actin polymerization showed large variation depending on the duration of exposure to the drug. Dual-label studies using propidium iodide to measure DNA content and NBD-phallacidin to measure the F-actin content revealed that these variations were not related to the stages of cell cycle. Cells in all stages of the cell cycle responded to stimulus-induced actin polymerization, but the magnitude of the response appeared to be more in cells in G2/M phase. The observations reported here indicate that the small number of chemotactic peptide receptors present on HL-60 cells are adequate to mount an actin polymerization response, provided the required intracellular mechanisms exist. Differentiation-inducing agents, therefore, must cause changes within the cell, such as induction of actin-binding proteins, to cause actin polymerization following FMLP stimulation. The HL-60 system serves as a useful model for studying the molecular mechanisms regulating stimulus-induced actin polymerization in human neutrophils.

Multivalency of PEG-thiol ligands affects the stability of NIR-absorbing hollow gold nanospheres and gold nanorods.

In this work the effect of multivalency on the stability of NIR-absorbing HAuNSs and AuNRs functionalized by mono-, bi- and tridentate polyethyleneglycol (PEG) thiol ligands is reported. Comparison of commercially-available monodentate and self-synthesized bi- and tridentate methoxy terminated thiol-polyethyleneglycol ligands having molecular weights of around 5000 Da shows the stability increase of HAuNSs and AuNRs for bi- and tridentate ligands, attributed to the multivalency of the ligands. The stability was explored according to three different aspects: (1) stability towards competition reactions with the strong binding ligand dithiothreitol, (2) resistance towards oxidative Au dissolution with potassium cyanide, and (3) colloidal stability, tested by the addition of NaCl. Our PEGylation approach leads to AuNRs where the CTAB concentration is below the detection limit of the performed analytical methods, which is vital for any clinical applications. Furthermore, we found strikingly high biocompatibility after PEGylation for both particle types whereby we observed no significant difference in cytotoxicity comparing the mono-, bi- and tridentate PEGylated species.

Emergence of coherence in the charge-density wave state of 2H-NbSe2.

A charge-density wave (CDW) state has a broken symmetry described by a complex order parameter with an amplitude and a phase. The conventional view, based on clean, weak-coupling systems, is that a finite amplitude and long-range phase coherence set in simultaneously at the CDW transition temperature T(cdw). Here we investigate, using photoemission, X-ray scattering and scanning tunnelling microscopy, the canonical CDW compound 2H-NbSe2 intercalated with Mn and Co, and show that the conventional view is untenable. We find that, either at high temperature or at large intercalation, CDW order becomes short-ranged with a well-defined amplitude, which has impacts on the electronic dispersion, giving rise to an energy gap. The phase transition at T(cdw) marks the onset of long-range order with global phase coherence, leading to sharp electronic excitations. Our observations emphasize the importance of phase fluctuations in strongly coupled CDW systems and provide insights into the significance of phase incoherence in 'pseudogap' states.

Magnetic resonance imaging of coronary arteries and heart valves in a living mouse: techniques and preliminary results.

New investigations in MRI of a mouse heart showed high-contrast cardiac images and thereby the possibility of doing functional cardiac studies of in vivo mice. But is MRI, in addition, capable of visualizing microstructures such as the coronary arteries and the heart valves of a living mouse? To answer this question, 2D and 3D gradient echo sequences with and without flow compensation were used to image the coronary arteries. To increase signal-to-noise ratio, a birdcage resonator was optimized for mouse heart imaging. Contrast between blood and myocardium was achieved through the inflow effect. A segmented three-dimensional FLASH sequence acquired with a multiple overlap thin slab technique showed the best results. With this technique an isotropic resolution of 100 microm was achieved. The left coronary artery could be visualized up to the apex of the heart. This is demonstrated with short axis views and 3D surface reconstructions of the mouse heart. The four cardiac valves were also visible with the 3D method.

Origin of stable flies (Diptera: Muscidae) on west Florida beaches: electrophoretic analysis of dispersal.

Stable fly adults were collected from 16 locations within the state of Florida and from locations in six other states in an attempt to determine the source of stable fly populations along Florida beaches on the Gulf of Mexico. Electrophoretic analyses were made of a minimum of 10 enzymes in each of 37 separate populations. Extremely low heterozygosity resulted in an inability to use standard genetic identity and distance procedures for determining the divergence of allopatric populations to establish the source of flies captured from beach areas where reproduction was unlikely. Comparisons of rare alleles in populations grouped geographically, computations of number of possible migrants, and analysis of conditional average frequency of alleles led to the conclusion that flies captured on Florida beaches come from a variety of sites, with locations northwest of the beaches contributing the majority of flies in outbreaks.