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Primary osteoporosis is rare in children and adolescents and its optimal pharmacological management is uncertain. Bisphosphonates are commonly used while denosumab has only been administered to a few children with osteogenesis imperfecta. We studied a treatment-naive 13.5-year-old boy with severe osteoporosis and multiple vertebral deformities who presented with back pain and difficulty in walking. Causes of secondary osteoporosis were excluded and there were no abnormalities in genes known to cause bone fragility. He was treated with denosumab 60 mg subcutaneously every 3 months for 30 months, and he was pain-free within 6 weeks after the first injection. Lumbar spine BMD and femoral neck BMD increased with treatment by 65.6% and 25.3%, respectively, and deformed vertebrae regained their normal shape; linear growth was not impaired. During the second year of treatment, transient hypercalcemia (maximum 3.09 mmol/l) before the denosumab injection was observed. In conclusion, denosumab was highly effective in this case of primary pediatric osteoporosis, with remarkable clinical and radiological response. Transient hypercalcemia was probably due to amplification of the effect of growth spurt and puberty on bone remodeling by the transient, short-term discontinuation of the drug. Furthermore, our data suggest that mobilization of calcium from treatment-induced sclerotic transverse lines in bone metaphyses may contribute to the development of hypercalcemia.

Background. HER2+/HR+ BC is heterogeneous and subgroups with different treatment sensitivities need to be identified. We previously reported a PAM50-based CES in HR+/HER2-negative BC (Prat et al. CCR 2016). Here, we evaluated the association of CES with pathologic complete response (pCR) following anti-HER2-based therapy in HR+/HER2+ BC across 6 NA studies. Methods. Intrinsic subtype and clinico-pathological data were obtained from 6 NA clinical studies (CHERLOB, OptiHERHEART[OHH], PAMELA, LPT109096, ICO and CALGB 40601 [CALGB is part of the Alliance for Clinical Trials in Oncology]). All patients (pts) received chemotherapy (CT) and trastuzumab, except for pts in the PAMELA study who did not receive CT. A second anti-HER2 agent (lapatinib or pertuzumab) was included in the NA of all pts in OHH and PAMELA and in one of the treatment arms in CHERLOB, LPT and C40601. CES was evaluated as a continuous variable, and categorically (CES-E[endocrine-sensitive], CES-U[uncertain] and CES-C[chemo-sensitive]) using the previously reported cut-offs. In all studies, except CHERLOB and C40601, ERBB2 mRNA levels were measured using the nCounter platform. pCR in the breast was the endpoint. We first performed statistical analyses in each dataset individually, and then in a dataset with combined patient-level data. Univariate and multivariable logistic regressions analyses were used. Results. A total of 345 pts were included in the analysis. In the combined cohort, CES-E, CES-U and CES-C were identified in 27.5%, 23.7% and 48.6% of the pts, respectively. Table 1 summarizes the distribution and pCR rates by CES groups. In the combined cohort, CES-C was associated with higher pCR rates compared to CES-U and CES-E independent of tumor size, nodal status, anti-HER2 treatment (single vs. dual HER2 blockade), intrinsic subtype (HER2-enriched [HER2E] versus not) and study (Table 2). In the PAMELA trial (no CT), CES-C was also found associated with higher pCR rates compared to CES-E (31.6% vs. 0%). Concordant with this finding, CES-C tumors showed higher ERBB2 mRNA levels than non-CES-C (P Conclusion. CES shows clinical validity for predicting CT/HER2-targeting sensitivity in HER2+/HR+ BC beyond intrinsic subtype and clinicopathologic characteristics. HER2+/HR+/CES-E tumors, which represent ˜20% of all HER2+ tumors, show low sensitivity to anti-HER2 regimens (with and without CT); other treatment strategies might be needed for this group. Support: U10CA180882;U10CA180821;U24CA196171;P50-CA58823;BCRF;Komen. Table 1. Distribution and pCR rates of CES-E, CES-U and CES-C groups across studies.n(%pCR)LPTCHERLOBOHHICOPAMELAC40601TOTALCES-E00/9(0)1/5(20)0/7(0)0/14(0)16/60(27)17/95 (18)CES-U0/1(0)4/15(27)5/7(71)4/13(30)2/25(8)10/21(47)25/82 (30)CES-C20/29(69)12/32(37)22/28(78)15/29(52)12/38(32)3/6(50)84/162(52)P0.330.080.040.03 Table 2. Association of CES, intrinsic subtype, clinicopathologic variables and study with pCR in a multivariable model (including type of study). OR95% CIPCES CES-E1 CES-U2.91.2-7.0 Citation Format: Pascual T, Tanioka M, Dieci MV, Pernas S, Gavila J, Guarnieri V, Cortes J, Llombart A, Conte P, Oliveira M, Paré L, Galván P, Perou CM, Prat A, Carey L. Independent validation of the PAM50-based chemo-endocrine score (CES) in hormonal receptor positive (HR+)/HER2+ breast cancer (BC) treated with neoadjuvant (NA) anti-HER2-based therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-05.

The monitoring of concentration of methane dissolved in water is important for the security of underwater pipelines, delineation of oil and gas fields, and optimization of proper location of oil and gas wells. The reported system consists of metal oxide gas sensor separated from water by hydrophobic pervaporation membrane. Methane MEMS sensor was based on multilayer SiO2/Si3N4 film equipped with platinum heater and coated with sensing layer made of nanoparticle SnO2/Pd (3 wt. %). Methane saturation of water leads to a decrease in sensor resistance by a factor of 6 – 7, the response time of the system is of 200–300 s.

The monitoring of concentration of methane dissolved in water is important for the security of underwater pipelines, delineation of oil and gas fields, and optimization of proper location of oil and gas wells. The reported system consists of metal oxide gas sensor separated from water by hydrophobic pervaporation membrane. Methane MEMS sensor was based on multilayer SiO 2 /Si 3 N 4 film equipped with platinum heater and coated with sensing layer made of nanoparticle SnO 2 /Pd (3 wt. %). Methane saturation of water leads to a decrease in sensor resistance by a factor of 6 – 7, the response time of the system is of 200–300 s.

A microsystem composed of a micromachined resistive flow sensor and a signal conditioning CMOS IC is proposed for biomedical applications. The device can be adapted to noninvasively monitor urinary dysfunctions in male patients. The flow sensor, thermally simulated with ANSYS, is based on the hot-film principle: A thin film of gold laid on a suspended micromachined silicon membrane is heated while the fluid under test flows through the duct mounted above the membrane. The flow rate is sensed by measuring the temperature difference between two of the four polysilicon temperature sensors realized on the membrane. Simulations of the flow sensor with flow rates within 0.1-18 ml/s evidence a maximum temperature difference of 20degC between the temperature sensors. Characterization of the fabricated flow sensor shows temperature coefficient of resistance (TCR) values of -1930 ppm/degC for the polysilicon resistors, i.e., a resistance variation of about 4% at high flow rates. The CMOS readout designed for the flow sensor is a resistive bridge-to-duty cycle converter based on a relaxation oscillator. The digital output of the circuit is duty-cycle modulated by the change in resistance of the flow sensor's elements. Experimental tests on the CMOS interface, conducted with a setup of 1% precision resistors, report a maximum nonlinearity below 0.9% and a resolution of 7 bits over the full range of 4% resistance variation. The CMOS integrated readout circuit, provided with a digital output, allows simple signal interfacing towards any standard PC for periodical data transfer and storage

Shielding is the only practical countermeasure for the exposure to cosmic radiation during space travel. It is well known that light, hydrogenated materials, such as water and polyethylene, provide the best shielding against space radiation. Kevlar and Nextel are two materials of great interest for spacecraft shielding because of their known ability to protect human space infrastructures from meteoroids and debris. We measured the response to simulated heavy-ion cosmic radiation of these shielding materials and compared it to polyethylene, Lucite (PMMA), and aluminum. As proxy to galactic nuclei we used 1 GeV n iron or titanium ions. Both physics and biology tests were performed. The results show that Kevlar, which is rich in carbon atoms (about 50% in number), is an excellent space radiation shielding material. Physics tests show that its effectiveness is close (80-90%) to that of polyethylene, and biology data suggest that it can reduce the chromosomal damage more efficiently than PMMA. Nextel is less efficient as a radiation shield, and the expected reduction on dose is roughly half that provided by the same mass of polyethylene. Both Kevlar and Nextel are more effective than aluminum in the attenuation of heavy-ion dose.

The growing interest in new under-water pipe lines for the delivery of natural gas (in Baltic Sea, Mediterranean region, Caspian Sea, Black Sea, etc.) needs a new instruments for the monitoring of leakage and/or possible destruction of the pipes, which could not only disturb fragile ecological systems of Baltic and other seas, but also can lead to the technological catastrophes. We plan to develop a prototype of the system consisting of pervaporation membrane and gas sensors. Overall system will be immersed into water and will be fabricated in two versions: as a stationary instrument dipped into sea water and as an instrument towed along the pipe line. Micromachined metal oxide semiconductor gas sensors used for the detection of methane concentrations is designed and fabricated using “nano-on-micro” approach. Overall system is optimized from the point of view of minimum power consumption, which is necessary to assure its long term operation under autonomous conditions.

The problem of gas analyzers compatible with wireless networks can be solved by using sensors based on the “nano-on-micro” technology. The basis of this technology consists in nano-composite sensing metal oxide semiconductor or thermocatalytic materials deposited on a microhotplate fabricated using silicon or alumina microelectronic technology. As a result, the sensor combines the advantages of both technologies: on the one hand, high stability and sufficient selectivity of nano-composite materials, and, on the other hand, microprocessor compatibility, low-cost, mass-production possibilities, and low power consumption of microelectronic substrates. Two methods for the fabrication of microhotplates are the most promising: the silicon based technology of silicon oxide/silicon nitride membranes and the CeraMEMS technology of thin alumina films (TAF). The first technology enables the fabrication of microheaters with a power consumption around 20 mW for an operating temperature below 450°C. Advantages of CeraMEMS platforms are: (1) operation at temperature up to 600°C and, potentially, up to 800°C; (2) robustness compared with silicon chip with thin membrane; (3) perfect Pt and sensing layer adhesion without any adhesive layers; (4) low cost of middle scale production (104–107 chips per year) compared with the silicon technology. The CeraMEMS platform can be used for the fabrication of semiconductor and thermocatalytic gas sensors, as a source of IR radiation for optical gas sensors and as bolometers. The sensor withstands ∼7 × 106 on-off cycles. Heater resistance drift is below 3% per year at 550°C.

In this work we describe the design implementation, validated by experimental results, of an innovative gas sensor array for wine quality monitoring. The main innovation of this integrated array deals with the simultaneous outputs, from a single chip on custom SMD socket, of eight different signals coming from a WO 3 thin film structure heated in a linear temperature gradient mode, allowing an overall evaluation of gas sensing properties of the material in a 100 °C-wide window, typically from 300 to 400 °C. The implemented sensitive layer is a WO 3 film deposed by RF-sputtering. Preliminary tests of gas sensing showed good responses to the target analytes for the specific application (1-heptanol, 3-methylbutanol, benzaldehyde and ethyl-hexanoate).

In this work, we describe the design implementation, validated by experimental results, of an innovative gas sensor array for wine quality monitoring. The main innovation of this integrated array deals with the simultaneous outputs, from a single chip on TO-12 socket, of 8 different signals coming from a WO3 thin film structure heated in a linear temperature gradient mode, allowing an overall evaluation of gas sensing properties of the material in a 100°C-wide window, typically from 300 to 400°C. The implemented sensitive layer is a WO3 film deposed by RF-sputtering. Preliminary tests of gas sensing showed good responses to the target analytes for the specific application (1-heptanol, 3-methyl butanol, benzaldehyde and ethyl-hexanoate).

A novel prototype of low-power thick-film gas sensor deposited by screen-printing onto a micromachined hotplate is presented. The micro-heater is designed to maintain a film temperature of 400°C with less than 30 mW of input power. The fabrication process involves a combination of standard, VLSI-compatible, micromachining procedures and computer-aided screen-printing. A dielectric membrane of Si 3 N 4 and SiO 2 has been obtained with an embedded poly-Si resistor acting as a heating element. The bonding pad and contacts have been realised by a Ti/TiN/Cr/Au structure and the sensing film has been deposited by a screen-printing technique. Here follows a characterisation of a device, based on SnO 2 sensing film, at working conditions together with the response curve for CH 4 and NO 2 . We will also address some important improvements to the micro-hotplate structure, which leads to an increased flexibility of the device.

We report on the design, implementation and characterisation of a thick-film gas sensor deposited for the first time by screen-printing technique onto a micromachined hotplate, the microheater maintains a film temperature as high as 400°C with 2 was achieved by computer-aided screen-printing. The films were then fired through the microheater itself to guarantee thermodynamic stability for long time exploitation. The response of the device to CO, CH 4 and NO 2 at concentrations typical for indoor and outdoor applications was recorded by measuring the film resistance through ultra high impedance CMOS circuit.

We report on the design, fabrication, and characterization of a microheater module for chemoresistive, metal-oxide semiconductor gas sensors, consisting of a dielectric stacked membrane, micromachined from bulk silicon and with an embedded polysilicon resistor heater. Fabricated structures exhibit excellent heating efficiency, requiring only 30 mW to achieve a temperature of 500 C. Measured electrothermal characteristics are in good agreement with the outcomes of 3D numerical simulations.

Tetra-methyl ammonium hydroxide (TMAH) is an anisotropic silicon etchant that is gaining considerable use in silicon sensor micromachining due to its excellent compatibility with CMOS processing, selectivity, anisotropy and relatively low toxicity, as compared to the more used KOH and EDP etchants. In this paper, the influence of temperature and concentration of the TMAH solution together with oxidizer additions is studied in order to optimize the anisotropic silicon etching for MEMS fabrication. In particular this optimized etchant formulation has been employed at ITC-Irst in the development of a basic fabrication process for piezoresistive pressure sensors based on a silicon membrane and four resistors connected in a Weatherstone bridge configuration. The active element of the sensor, i.e. the thin silicon membrane, is formed by etching anisotropically from the backside of the wafer. Both process and etching have to be tuned and matched in order to obtain an optimum fabrication sequence. Some improvements such as higher etch rate and better surface finish have been obtained by the addition of ammonium peroxidsulfate as oxidizing agent under different conditions. This simplifies both the post processing and the tech set-up. The process parameters and the thermo-electro-mechanical characteristics of the pressure sensors were tested and are compared with the analytical and numerical simulations.

We report developing a SnO2 thick-film gas sensor deposited by screen printing onto a micromachined dielectric stacked membrane equipped with an embedded polysilicon microheater and two resistors for temperature measurement. The microheaters were designed to enable an operating temperature of 400 °C at about 30 mW power consumption. A newly developed scheme for temperature measurement was adopted for on-line adjustment of the film temperature through a conventional low-power feedback circuit. The electrical response of the prototypes to CO and CH4 is discussed, and their performance is compared to traditional devices fabricated via thick-film methods.