Ultrasensitive mass sensor fully integrated with complementary metal-oxide-semiconductor circuitry

Nanomechanical resonators have been monolithically integrated on preprocessed complementary metal-oxide-semiconductor(CMOS) chips. Fabricatedresonatorsystems have been designed to have resonance frequencies up to 1.5 MHz. The systems have been characterized in ambient air and vacuum conditions and display ultrasensitive mass detection in air. A mass sensitivity of 4ag/Hz has been determined in air by placing a single glycerine drop, having a measured weight of 57 fg, at the apex of a cantilever and subsequently measuring a frequency shift of 14.8 kHz. CMOS integration enables electrostatic excitation, capacitive detection, and amplification of the resonance signal directly on the chip

Light emission from a scanning tunneling microscope: Fully retarded calculation

The light emission rate from a scanning tunneling microscope (STM) scanning a noble metal surface is calculated taking retardation effects into account. As in our previous, non-retarded theory [Johansson, Monreal, and Apell, Phys. Rev. B 42, 9210 (1990)], the STM tip is modeled by a sphere, and the dielectric properties of tip and sample are described by experimentally measured dielectric functions. The calculations are based on exact diffraction theory through the vector equivalent of the Kirchoff integral. The present results are qualitatively similar to those of the non-retarded calculations. The light emission spectra have pronounced resonance peaks due to the formation of a tip-induced plasmon mode localized to the cavity between the tip and the sample. At a quantitative level, the effects of retardation are rather small as long as the sample material is Au or Cu, and the tip consists of W or Ir. However, for Ag samples, in which the resistive losses are smaller, the inclusion of retardation effects in the calculation leads to larger changes: the resonance energy decreases by 0.2-0.3 eV, and the resonance broadens. These changes improve the agreement with experiment. For a Ag sample and an Ir tip, the quantum efficiency is $\approx$ 10$^{-4}$ emitted photons in the visible frequency range per tunneling electron. A study of the energy dissipation into the tip and sample shows that in total about 1 % of the electrons undergo inelastic processes while tunneling.Comment: 16 pages, 10 figures (1 ps, 9 tex, automatically included); To appear in Phys. Rev. B (15 October 1998

Assessment of ePrescription quality: an observational study at three mail-order pharmacies

<p>Abstract</p> <p>Background</p> <p>The introduction of electronic transfer of prescriptions (ETP) or ePrescriptions in ambulatory health care has been suggested to have a positive impact on the prescribing and dispensing processes. Thereby, implying that ePrescribing can improve safety, quality, efficiency, and cost-effectiveness. In December 2007, 68% of all new prescriptions were transferred electronically in Sweden. The aim of the present study was to assess the quality of ePrescriptions by comparing the proportions of ePrescriptions and non-electronic prescriptions necessitating a clarification contact (correction, completion or change) with the prescriber at the time of dispensing.</p> <p>Methods</p> <p>A direct observational study was performed at three Swedish mail-order pharmacies which were known to dispense a large proportion of ePrescriptions (38–75%). Data were gathered on all ePrescriptions dispensed at these pharmacies over a three week period in February 2006. All clarification contacts with prescribers were included in the study and were classified and assessed in comparison with all drug prescriptions dispensed at the same pharmacies over the specified period.</p> <p>Results</p> <p>Of the 31225 prescriptions dispensed during the study period, clarification contacts were made for 2.0% (147/7532) of new ePrescriptions and 1.2% (79/6833) of new non-electronic prescriptions. This represented a relative risk (RR) of 1.7 (95% CI 1.3–2.2) for new ePrescriptions compared to new non-electronic prescriptions. The increased RR was mainly due to 'Dosage and directions for use', which had an RR of 7.6 (95% CI 2.8–20.4) when compared to other clarification contacts. In all, 89.5% of the suggested pharmacist interventions were accepted by the prescriber, 77.7% (192/247) as suggested and an additional 11.7% (29/247) after a modification during contact with the prescriber.</p> <p>Conclusion</p> <p>The increased proportion of prescriptions necessitating a clarification contact for new ePrescriptions compared to new non-electronic prescriptions indicates the need for an increased focus on quality aspects in ePrescribing deployment. ETP technology should be developed towards a two-way communication between the prescriber and the pharmacist with automated checks of missing, inaccurate, or ambiguous information. This would enhance safety and quality for the patient and also improve efficiency and cost-effectiveness within the health care system.</p

Physicians' attitudes towards ePrescribing – evaluation of a Swedish full-scale implementation

<p>Abstract</p> <p>Background</p> <p>The penetration rate of Electronic Health Record (EHR) systems in health care is increasing. However, many different EHR-systems are used with varying ePrescription designs and functionalities. The aim of the present study was to evaluate experienced ePrescribers' attitudes towards ePrescribing for suggesting improvements.</p> <p>Methods</p> <p>Physicians (n = 431) from seven out of the 21 Swedish health care regions, using one of the six most widely implemented EHR-systems with integrated electronic prescribing modules, were recruited from primary care centers and hospital clinics of internal medicine, orthopaedics and surgery. The physicians received a web survey that comprised eight questions on background data and 19 items covering attitudes towards ePrescribing. Forty-two percent (n = 199) of the physicians answered the questionnaire; 90% (n = 180) of the respondents met the inclusion criteria and were included in the final analysis.</p> <p>Results</p> <p>A majority of the respondents regarded their EHR-system easy to use in general (81%), and for the prescribing of drugs (88%). Most respondents believed they were able to provide the patients better service by ePrescribing (92%), and regarded ePrescriptions to be time saving (91%) and to be safer (83%), compared to handwritten prescriptions. Some of the most frequently reported weaknesses were: not clearly displayed price of drugs (43%), complicated drug choice (21%), and the perception that it was possible to handle more than one patient at a time when ePrescribing (13%). Moreover, 62% reported a lack of receipt from the pharmacy after successful transmission of an ePrescription. Although a majority (73%) of the physicians reported that they were always or often checking the ePrescription a last time before transmitting, 25% declared that they were seldom or never doing a last check. The respondents suggested a number of improvements, among others, to simplify the drug choice and the cancellation of ePrescriptions.</p> <p>Conclusion</p> <p>The Swedish physicians in the group studied were generally satisfied with their specific EHR-system and with ePrescribing as such. However, identified weaknesses warrant improvements of the EHR-systems as well as of their implementation in the individual health care organisation.</p

Virus Capsid Dissolution Studied by Microsecond Molecular Dynamics Simulations

Dissolution of many plant viruses is thought to start with swelling of the capsid caused by calcium removal following infection, but no high-resolution structures of swollen capsids exist. Here we have used microsecond all-atom molecular simulations to describe the dynamics of the capsid of satellite tobacco necrosis virus with and without the 92 structural calcium ions. The capsid expanded 2.5% upon removal of the calcium, in good agreement with experimental estimates. The water permeability of the native capsid was similar to that of a phospholipid membrane, but the permeability increased 10-fold after removing the calcium, predominantly between the 2-fold and 3-fold related subunits. The two calcium binding sites close to the icosahedral 3-fold symmetry axis were pivotal in the expansion and capsid-opening process, while the binding site on the 5-fold axis changed little structurally. These findings suggest that the dissociation of the capsid is initiated at the 3-fold axis

Tissue architecture delineates field cancerization in BRAFV600E-induced tumor development

Cancer cells hijack developmental growth mechanisms but whether tissue morphogenesis and architecture modify tumorigenesis is unknown. Here, we characterized a new mouse model of sporadic thyroid carcinogenesis based on inducible expression of BRAF carrying a Val600 Glu (V600E) point mutation (BRAFV600E) from the thyroglobulin promoter (TgCreERT2). Spontaneous activation of this Braf-mutant allele due to leaky activity of the Cre recombinase revealed that intrinsic properties of thyroid follicles determined BRAF-mutant cell fate. Papillary thyroid carcinomas developed multicentrically within a normal microenvironment. Each tumor originated from a single follicle that provided a confined space for growth of a distinct tumor phenotype. Lineage tracing revealed oligoclonal tumor development in infancy and early selection of BRAFV600E kinase inhibitor-resistant clones. Somatic mutations were few, non-recurrent and limited to advanced tumors. Female mice developed larger tumors than males, reproducing the gender difference of human thyroid cancer. These data indicate that BRAFV600E-induced tumorigenesis is spatiotemporally regulated depending on the maturity and heterogeneity of follicles. Moreover, thyroid tissue organization seems to determine whether a BRAF- mutant lineage becomes a cancerized lineage. The TgCreERT2; BrafCA/+ sporadic thyroid cancer mouse model provides a new tool to evaluate drug therapy at different stages of tumor evolution

Visceral leishmaniasis caused by Leishmania infantum in a Spanish patient in Argentina: What is the origin of the infection? Case report

BACKGROUND: The question "Where have you been?" is a common one asked by doctors in Northern Europe and America when faced with clinical symptoms not typical of their country. This question must also arise in the clinics of developing countries in which non-autochthonous cases such as the one described here can appear. Important outbreaks of Leishmania infantum have been recorded in the last decade in several Latin American countries but its presence has not yet been recorded in Argentina. We report the first case of visceral leishmaniasis owing to L. infantum in this country. CASE PRESENTATION: A 71-year-old Spanish woman who has been living in Mendoza, Argentina, during the last 40 years presented with a history of high fever and shivering, anemia, leukopenia and splenomegaly over two years. Argentinian doctors did not suspect visceral leishmaniasis even when the histological analysis revealed the presence of "intracytoplasmatic spheroid particles compatible with fungal or parasitic infection". After a serious deterioration in her health, she was taken to Spain where she was evaluated and visceral leishmaniasis was established. Specific identification of the parasite was done by PCR-ELISA, isoenzyme electrophoresis and RAPD-PCR. CONCLUSION: We would like to point out that: i) cases such as the one described here, which appear in non-endemic areas, can pass unnoticed by the clinical physician. ii) in countries in which these introduced cases reside, in-depth parasitological studies are required into vectors and possible reservoirs to rule out the rare case of local infection and, once infection has taken place, to ensure that this does not spread by anthroponotic transmission or a competent reservoir

Mouse DRG Cell Line with Properties of Nociceptors

In vitro cell lines from DRG neurons aid drug discovery because they can be used for early stage, high-throughput screens for drugs targeting pain pathways, with minimal dependence on animals. We have established a conditionally immortal DRG cell line from the Immortomouse. Using immunocytochemistry, RT-PCR and calcium microfluorimetry, we demonstrate that the cell line MED17.11 expresses markers of cells committed to the sensory neuron lineage. Within a few hours under differentiating conditions, MED17.11 cells extend processes and following seven days of differentiation, express markers of more mature DRG neurons, such as NaV1.7 and Piezo2. However, at least at this time-point, the nociceptive marker NaV1.8 is not expressed, but the cells respond to compounds known to excite nociceptors, including the TRPV1 agonist capsaicin, the purinergic receptor agonist ATP and the voltage gated sodium channel agonist, veratridine. Robust calcium transients are observed in the presence of the inflammatory mediators bradykinin, histamine and norepinephrine. MED17.11 cells have the potential to replace or reduce the use of primary DRG culture in sensory, pain and developmental research by providing a simple model to study acute nociception, neurite outgrowth and the developmental specification of DRG neurons

The Pristine survey -- XXIII. Data Release 1 and an all-sky metallicity catalogue based on Gaia DR3 BP/RP spectro-photometry

We use the spectro-photometric information of ~219 million stars from Gaia's DR3 to calculate synthetic, narrow-band, metallicity-sensitive CaHK magnitudes that mimic the observations of the Pristine survey, a survey of photometric metallicities of Milky Way stars that has been mapping more than 6,500 deg^2 of the northern sky with the CFHT since 2015. These synthetic magnitudes are used for an absolute re-calibration of the deeper Pristine photometry and, combined with broadband Gaia information, synthetic and Pristine CaHK magnitudes are used to estimate photometric metallicities over the whole sky. The resulting metallicity catalogue is accurate down to [Fe/H]~-3.5 and is particularly suited for the exploration of the metal-poor Milky Way ([Fe/H]<-1.0). We make available here the catalogue of synthetic CaHK_syn magnitudes for all stars with BP/RP information in Gaia DR3, as well as an associated catalogue of more than ~30 million photometric metallicities for high S/N FGK stars. This paper further provides the first public DR of the Pristine catalogue in the form of higher quality recalibrated Pristine CaHK magnitudes and photometric metallicities for all stars in common with the BP/RP information in Gaia DR3. We demonstrate that, when available, the much deeper Pristine data greatly enhances the quality of the derived metallicities, in particular at the faint end of the catalogue (G_BP>16). Combined, both catalogues include more than 2 million metal-poor star candidates as well as more than 200,000 and ~8,000 very and extremely metal-poor candidates. Finally, we show that these metallicity catalogues can be used efficiently, among other applications, for Galactic archaeology, to hunt for the most metal-poor stars, and to study how the structure of the Milky Way varies with metallicity, from the flat distribution of disk stars to the spheroid-shaped metal-poor halo. (Shortened)Comment: 30 pages, 24 figures, submitted to A&A. First two authors are co-first author. The CaHK photometry catalogue and the two photometric metallicity catalogues are available, before acceptance, as large compressed csv files at: https://seafile.unistra.fr/d/ee0c0f05719d4368bcbb