Drug Delivery Micropump with Built-In Monitoring

AbstractWe report on the fabrication of the first MEMS micropump including an integrated pressure sensor. The signal of this sensor allows direct insight into the pump's operating dynamics and enables real-time self-monitoring. We demonstrate the changes in the sensor signal under different pumping conditions, including the presence of air in the pumping chamber and a downstream occlusions. Deviations from normal operating conditions create clear and characteristic deviations from the normal signal. These deviations will be exploited to detect extraordinary or faulty pumping conditions during use

Quantitative features of multifractal subtleties in time series

Based on the Multifractal Detrended Fluctuation Analysis (MFDFA) and on the Wavelet Transform Modulus Maxima (WTMM) methods we investigate the origin of multifractality in the time series. Series fluctuating according to a qGaussian distribution, both uncorrelated and correlated in time, are used. For the uncorrelated series at the border (q=5/3) between the Gaussian and the Levy basins of attraction asymptotically we find a phase-like transition between monofractal and bifractal characteristics. This indicates that these may solely be the specific nonlinear temporal correlations that organize the series into a genuine multifractal hierarchy. For analyzing various features of multifractality due to such correlations, we use the model series generated from the binomial cascade as well as empirical series. Then, within the temporal ranges of well developed power-law correlations we find a fast convergence in all multifractal measures. Besides of its practical significance this fact may reflect another manifestation of a conjectured q-generalized Central Limit Theorem

The SCOUT-O3 Darwin Aircraft Campaign: rationale and mateorology

An aircraft measurement campaign involving the Russian high-altitude aircraft M55 Geophysica and the German DLR Falcon was conducted in Darwin, Australia in November and December 2005 as part of the European integrated project SCOUT-O3. The overall objectives of the campaign were to study the transport of trace gases through the tropical tropopause layer (TTL), mechanisms of dehydration close to the tropopause, and the role of deep convection in these processes. In this paper a detailed roadmap of the campaign is presented, including rationales for each flight, and an analysis of the local and large-scale meteorological context in which they were embedded. The campaign took place during the pre-monsoon season which is characterized by a pronounced diurnal evolution of deep convection including a mesoscale system over the Tiwi Islands north of Darwin known as �\x83¢Â�Â�HectorâÂ�Â�. This allowed studying in detail the role of deep convection in structuring the tropical tropopause region, in situ sampling convective overshoots above storm anvils, and probing the structure of anvils and cirrus clouds by Lidar and a suite of in situ instruments onboard the two aircraft. The large-scale flow during the first half of the campaign was such that local flights, away from convection, sampled air masses downstream of the âÂ�Â�cold trapâÂ�Â� region over Indonesia. Abundant cirrus clouds enabled the study of active dehydration, in particular during two TTL survey flights. The campaign period also encompassed a Rossby wave breaking event transporting stratospheric air to the tropical middle troposphere and an equatorial Kelvin wave modulating tropopause temperatures and hence the conditions for dehydration

Talin1 and Rap1 are critical for osteoclast function

To determine talin1's role in osteoclasts, we mated TLN1(fl/fl) mice with those expressing cathepsin K-Cre (CtsK-TLN1) to delete the gene in mature osteoclasts or with lysozyme M-Cre (LysM-TLN1) mice to delete TLN1 in all osteoclast lineage cells. Absence of TLN1 impairs macrophage colony-stimulating factor (M-CSF)-stimulated inside-out integrin activation and cytoskeleton organization in mature osteoclasts. Talin1-deficient precursors normally express osteoclast differentiation markers when exposed to M-CSF and receptor activator of nuclear factor κB (RANK) ligand but attach to substrate and migrate poorly, arresting their development into mature resorptive cells. In keeping with inhibited resorption, CtsK-TLN1 mice exhibit an ∼5-fold increase in bone mass. Osteoclast-specific deletion of Rap1 (CtsK-Rap1), which promotes talin/β integrin recognition, yields similar osteopetrotic mice. The fact that the osteopetrosis of CtsK-TLN1 and CtsK-Rap1 mice is substantially more severe than that of those lacking αvβ3 is likely due to added failed activation of β1 integrins. In keeping with osteoclast dysfunction, mice in whom talin is deleted late in the course of osteoclastogenesis are substantially protected from ovariectomy-induced osteoporosis and the periarticular osteolysis attending inflammatory arthritis. Thus, talin1 and Rap1 are critical for resorptive function, and their selective inhibition in mature osteoclasts retards pathological bone loss

Pre-exposure prophylaxis for preventing acquisition of HIV: A cross-sectional study of patients, prescribers, uptake, and spending in the United States, 2015-2016

BACKGROUND: In 2015, there were approximately 40,000 new HIV diagnoses in the United States. Pre-exposure prophylaxis (PrEP) is an effective strategy that reduces the risk of HIV acquisition; however, uptake among those who can benefit from it has lagged. In this study, we 1) compared the characteristics of patients who were prescribed PrEP with individuals newly diagnosed with HIV infection, 2) identified the specialties of practitioners prescribing PrEP, 3) identified metropolitan statistical areas (MSAs) within the US where there is relatively low uptake of PrEP, and 4) reported median amounts paid by patients and third-party payors for PrEP. METHODS AND FINDINGS: We analyzed prescription drug claims for individuals prescribed PrEP in the Integrated Dataverse (IDV) from Symphony Health for the period of September 2015 to August 2016 to describe PrEP patients, prescribers, relative uptake, and payment methods in the US. Data were available for 75,839 individuals prescribed PrEP, and findings were extrapolated to approximately 101,000 individuals, which is less than 10% of the 1.1 million adults for whom PrEP was indicated. Compared to individuals with newly diagnosed HIV infection, PrEP patients were more likely to be non-Hispanic white (45% versus 26.2%), older (25% versus 19% at ages 35-44), male (94% versus 81%), and not reside in the South (30% versus 52% reside in the South).Using a ratio of the number of PrEP patients within an MSA to the number of newly diagnosed individuals with HIV infection, we found MSAs with relatively low uptake of PrEP were concentrated in the South. Of the approximately 24,000 providers who prescribed PrEP, two-thirds reported primary care as their specialty. Compared to the types of payment methods that people living with diagnosed HIV (PLWH) used to pay for their antiretroviral treatment in 2015 to 2016 reported in the Centers for Disease Control and Prevention (CDC) HIV Surveillance Special Report, PrEP patients were more likely to have used commercial health insurance (80% versus 35%) and less likely to have used public healthcare coverage or a publicly sponsored assistance program to pay for PrEP (12% versus 45% for Medicaid). Third-party payors covered 95% of the costs of PrEP. Overall, we estimated the median annual per patient out-of-pocket spending on PrEP was approximately US$72. Limitations of this study include missing information on prescription claims of patients not included in the database, and for those included, some patients were missing information on patient diagnosis, race/ethnicity, educational attainment, and income (34%-36%). CONCLUSIONS: Our findings indicate that in 2015-2016, many individuals in the US who could benefit from being on PrEP were not receiving this HIV prevention medication, and those prescribed PrEP had a significantly different distribution of characteristics from the broader population that is at risk for acquiring HIV. PrEP patients were more likely to pay for PrEP using commercial or private insurance, whereas PLWH were more likely to pay for their antiretroviral treatment using publicly sponsored programs. Addressing the affordability of PrEP and otherwise promoting its use among those with indications for PrEP represents an important opportunity to help end the HIV epidemic

Mean-field Study of Charge, Spin, and Orbital Orderings in Triangular-lattice Compounds ANiO2 (A=Na, Li, Ag)

We present our theoretical results on the ground states in layered triangular-lattice compounds ANiO2 (A=Na, Li, Ag). To describe the interplay between charge, spin, orbital, and lattice degrees of freedom in these materials, we study a doubly-degenerate Hubbard model with electron-phonon couplings by the Hartree-Fock approximation combined with the adiabatic approximation. In a weakly-correlated region, we find a metallic state accompanied by \sqroot3x\sqroot3 charge ordering. On the other hand, we obtain an insulating phase with spin-ferro and orbital-ferro ordering in a wide range from intermediate to strong correlation. These phases share many characteristics with the low-temperature states of AgNiO2 and NaNiO2, respectively. The charge-ordered metallic phase is stabilized by a compromise between Coulomb repulsions and effective attractive interactions originating from the breathing-type electronphonon coupling as well as the Hund's-rule coupling. The spin-orbital-ordered insulating phase is stabilized by the cooperative effect of electron correlations and the Jahn-Teller coupling, while the Hund's-rule coupling also plays a role in the competition with other orbital-ordered phases. The results suggest a unified way of understanding a variety of low-temperature phases in ANiO2. We also discuss a keen competition among different spin-orbital-ordered phases in relation to a puzzling behavior observed in LiNiO2