Substance use before or during pregnancy and the risk of child mortality, perinatal morbidities and congenital anomalies.

AIMS: We aimed to investigate child mortality, perinatal morbidities and congenital anomalies born by women with substance misuse during or before pregnancy (DP or BP). METHODS: Taiwan Birth Registration from 2004 to 2014 linking Integrated Illicit Drug Databases used to include substance misuse participates. Children born by mothers convicted of substance misuse DP or BP were the substance-exposed cohort. Two substance-unexposed comparison cohorts were established: one comparison cohort selected newborns from the rest of the population on a ratio of 1:1 and exact matched by the child's gender, child's birth year, mother's birth year and child's first use of the health insurance card; another comparison cohort matched newborns from exposed and unexposed mothers by their propensity scores calculated from logistic regression. RESULTS: The exposure group included 1776 DP, 1776 BP and 3552 unexposed individuals in exact-matched cohorts. A fourfold increased risk of deaths in children born by mothers exposed to substance during pregnancy was found compared to unexposed group (hazard ratio [HR] = 4.54, 95% confidence interval (CI): 2.07-9.97]. Further multivariate Cox regression models with adjustments and propensity matching substantially attenuated HRs on mortality in the substance-exposed cohort (aHR = 1.62, 95% CI: 1.10-2.39). Raised risks of perinatal morbidities and congenital anomalies were also found. CONCLUSIONS: Increased risks of child mortality, perinatal morbidities or congenital anomalies were found in women with substance use during pregnancy. From estimates before and after adjustments, our results showed that having outpatient visits or medical utilizations during pregnancy were associated with substantially attenuated HRs on mortality in the substance-exposed cohort. Therefore, the excess mortality risk might be partially explained by the lack of relevant antenatal clinical care. Our finding may suggest that the importance of early identification, specific abstinence program and access to appropriate antenatal care might be helpful in reducing newborn mortality. Adequate prevention policies may be formulated.

Engineering the gain and bandwidth in avalanche photodetectors.

Avalanche and Single-Photon Avalanche photodetectors (APDs and SPADs) rely on the probability of photogenerated carriers to trigger a multiplication process. Photon penetration depth plays a vital role in this process. In silicon APDs, a significant fraction of the short visible wavelengths is absorbed close to the device surface that is typically highly doped to serve as a contact. Most of the photogenerated carriers in this region can be lost by recombination, get slowly transported by diffusion, or multiplied with high excess noise. On the other hand, the extended penetration depth of near-infrared wavelengths requires thick semiconductors for efficient absorption. This diminishes the speed of the devices due to the long transit time in the thick absorption layer that is required for detecting most of these photons. Here, we demonstrate that it is possible to drive photons to a critical depth in a semiconductor film to maximize their gain-bandwidth performance and increase the absorption efficiency. This approach to engineering the penetration depth for different wavelengths in silicon is enabled by integrating photon-trapping nanoholes on the device surface. The penetration depth of short wavelengths such as 450 nm is increased from 0.25 µm to more than 0.62 µm. On the other hand, for a long-wavelength like 850 nm, the penetration depth is reduced from 18.3 µm to only 2.3 µm, decreasing the device transit time considerably. Such capabilities allow increasing the gain in APDs by almost 400× at 450 nm and by almost 9× at 850 nm. This engineering of the penetration depth in APDs would enable device designs requiring higher gain-bandwidth in emerging technologies such as Fluorescence Lifetime Microscopy (FLIM), Time-of-Flight Positron Emission Tomography (TOF-PET), quantum communications systems, and 3D imaging systems.

Avalanche photodetectors with photon trapping structures for biomedical imaging applications.

Enhancing photon detection efficiency and time resolution in photodetectors in the entire visible range is critical to improve the image quality of time-of-flight (TOF)-based imaging systems and fluorescence lifetime imaging (FLIM). In this work, we evaluate the gain, detection efficiency, and timing performance of avalanche photodiodes (APD) with photon trapping nanostructures for photons with 450 nm and 850 nm wavelengths. At 850 nm wavelength, our photon trapping avalanche photodiodes showed 30 times higher gain, an increase from 16% to >60% enhanced absorption efficiency, and a 50% reduction in the full width at half maximum (FWHM) pulse response time close to the breakdown voltage. At 450 nm wavelength, the external quantum efficiency increased from 54% to 82%, while the gain was enhanced more than 20-fold. Therefore, silicon APDs with photon trapping structures exhibited a dramatic increase in absorption compared to control devices. Results suggest very thin devices with fast timing properties and high absorption between the near-ultraviolet and the near infrared region can be manufactured for high-speed applications in biomedical imaging. This study paves the way towards obtaining single photon detectors with photon trapping structures with gains above 106 for the entire visible range.

Modeling of nanohole siliconpin/nipphotodetectors: Steady state and transient characteristics.

Theory is proposed for nanohole siliconpin/nipphotodetector (PD) physics, promising devices in the future data communications and lidar applications. Photons and carriers have wavelengths of 1µm and 5 nm, respectively. We propose vertical nanoholes having 2D periodicity with a feature size of 1µm will produce photons slower than those in bulk silicon, but carriers are unchanged. Close comparison to experiments validates this view. First, we study steady state nanohole PD current as a function of illumination power, and results are attributed to the voltage drop partitions in the PD and electrodes. Nanohole PD voltage drop depends on illumination, but series resistance voltage drop does not, and this explains experiments well. Next, we study transient characteristics for the sudden termination of light illumination. Nanohole PDs are much faster than flat PDs, and this is because the former produces much less slow diffusion minority carriers. In fact, most photons have already been absorbed in thei-layer in nanohole PDs, resulting in much less diffusion minority carriers at the bottom highly doped layer. Why diffusion in PDs is slow and that in bipolar junction transistors is quick is discussed in appendix.

Author response to "lack of benefit from low dose computed tomography in screening for lung cancer".

We explain to Dr. Benjamin (corresponding author) about why low-dose computed tomography reduce lung cancer mortality without significantly reducing all-cause mortality. We also conduct an up-to-date meta-analysis to evaluate low-dose computed tomography clinical effectiveness compared with usual care of lung cancer screening.

Effects of low-dose computed tomography on lung cancer screening: a systematic review, meta-analysis, and trial sequential analysis.

BACKGROUND: The Nelson mortality results were presented in September 2018. Four other randomized control trials (RCTs) were also reported the latest mortality outcomes in 2018 and 2019. We therefore conducted a meta-analysis to update the evidence and investigate the benefits and harms of low-dose computed tomography (LDCT) in lung cancer screening. METHODS: Detailed electronic database searches were performed to identify reports of RCTs that comparing LDCT to any other type of lung cancer screening. Pooled risk ratios (RRs) were calculated using random effects models. RESULTS: We identified nine RCTs (n = 97,244 participants). In pooled analyses LDCT reduced lung cancer mortality (RR 0.83, 95% CI 0.76-0.90, I2 = 1%) but had no effect on all-cause mortality (RR 0.95, 95% CI 0.90-1.00). Trial sequential analysis (TSA) confirmed the results of our meta-analysis. Subgroup defined by high quality trials benefitted from LDCT screening in reducing lung cancer mortality (RR 0.82, 95% CI 0.73-0.91, I2 = 7%), whereas no benefit observed in other low quality RCTs. LDCT was associated with detection of a significantly higher number of early stage lung cancers than the control. No significant difference (RR 0.64, 95% CI 0.30-1.33) was found in mortality after invasive procedures between two groups. CONCLUSIONS: In meta-analysis based on sufficient evidence demonstrated by TSA suggests that LDCT screening is superiority over usual care in lung cancer survival. The benefit of LDCT is expected to be heavily influenced by the risk of lung cancer in the different target group (smoking status, Asian) being screened.

[Noninvasive medical imaging system for tissue classification using RGB LED and micro-spectroscopy].

As skin is the exterior organ of human body, cosmetic industry advances year by year. To reveal the details of skin tissue, threedimensional medical imaging is required. Based on the idea of "readout instead of write", a new scheme named spectral classification imaging (SCI) is proposed in the present study to reduce the invasiveness by applying the reflection spectra of the sample points for three-dimensional medical imaging. Broad-band light source and the spectrometer were employed to collect the spectra curves of scanned region, which were classified into several tissue types by their cross-correlations. A colorful tissue tomography can finally be obtained by filling in each image pixel the color indicating the corresponding tissue type. The lateral/longitudinal resolutions and penetration depth were analyzed to characterize the SCI system. The lateral resolution is based on the source's diffraction limit, the longitudinal resolution is by its depth-of-focus, and the penetration depth is equivalent to its skin depth. The imaging results of an amethyst of 0.6 mm (chi-direction) x 0.6 mm (y-direction) with a total of 120 x 120 pixels per frame and a guppy fish of 3.2 mm (chi-direction) x 2.4 mm (y-direction) of 160 x 120 pixels, are presented to show the image quality. The effects of the cross-correlation coefficient and the number of source wavelengths on the imaging results were explored. The value of cross-correlation threshold determines the required time for imaging, the resulted number of tissue groups, and the variety of tissue colors in the imaging result. Owing to its virtual noninvasiveness and easy configuration, the SCI system is highly promising for practical uses. RGB LEDs possess merits of broad bandwidth, low cost, long lifetime, small volume, and are ready to be integrated into a multi-color source module. Replacing the wide-band light source and the spectrometer module with a composite RGB LED with discrete wavelengths and a micro-spectrometer for spectra retrieval, the system has great potential to be minimized as a hand-held product for noninvasive medical imaging. It leads to reduced use of non-eco-friendly cosmetics and extended advance of cosmetic dermatology.

Ultrafast modulation of optical metamaterials.

We show by pump-probe spectroscopy that the optical response of a fishnet metamaterial can be modulated on the femtosecond time scale. The modulation dynamics is dominated by pump-induced changes in the constituting dielectric medium, but the strength of modulation is dramatically enhanced through the plasmon resonance. The pump-induced spectral responses of the metamaterial provide understanding on how the resonance is modified by pump excitation. Our study suggests that metamaterials can be used as high-speed amplitude/phase modulators with terahertz-bandwidth.

Ultrasmooth silver thin films deposited with a germanium nucleation layer.

We demonstrate an effective method for depositing smooth silver (Ag) films on SiO(2)/Si(100) substrates using a thin seed layer of evaporated germanium (Ge). The deposited Ag films exhibit smaller root-mean-square surface roughness, narrower peak-to-valley surface topological height distribution, smaller grain-size distribution, and smaller sheet resistance in comparison to those of Ag films directly deposited on SiO(2)/Si(100) substrates. Optically thin ( approximately 10-20 nm) Ag films deposited with approximately 1-2 nm Ge nucleation layers show more than an order of magnitude improvement in the surface roughness. The presence of the thin layer of Ge changes the growth kinetics (nucleation and evolution) of the electron-beam-evaporated Ag, leading to Ag films with smooth surface morphology and high electrical conductivity. The demonstrated Ag thin films are very promising for large-scale applications as molecular anchors, optical metamaterials, plasmonic devices, and several areas of nanophotonics.

Sub-10 nm nanoimprint lithography by wafer bowing.

We introduce the concept of wafer bowing to affect nanoimprinting. This approach allows a design that can fit the key imprinting mechanism into a compact module, which we have constructed and demonstrated with an overlay and resolution of <0.5 microm and <10 nm, respectively. In the short term, this wafer bowing approach makes nanoimprint lithography much more accessible to a broad range of researchers. More importantly, this approach eliminates machine movement other than wafer bowing and shortens the mechanical path; these will enable the achievement of excellent patterning and overlay at a much lower cost. In the long term, wafer bowing is extensible to step-and-repeat printing for volume manufacturing.

Circuit fabrication at 17 nm half-pitch by nanoimprint lithography.

High density metal cross bars at 17 nm half-pitch were fabricated by nanoimprint lithography. Utilizing the superlattice nanowire pattern transfer technique, a 300-layer GaAs/AlGaAs superlattice was employed to produce an array of 150 Si nanowires (15 nm wide at 34 nm pitch) as an imprinting mold. A successful reproduction of the Si nanowire pattern was demonstrated. Furthermore, a cross-bar platinum nanowire array with a cell density of approximately 100 Gbit/cm(2) was fabricated by two consecutive imprinting processes.

Cross-linked polymer replica of a nanoimprint mold at 30 nm half-pitch.

This letter reports the demonstration of a photocurable polymer process for replicating the master mold for nanoimprint lithography. The cross-linked polymer mold was fabricated directly with high fidelity from a master by imprinting and photocuring a low viscosity liquid prepolymer film spun onto a substrate. The surface of the cross-linked polymer mold can be treated using an O(2) plasma, and then vapor primed with a low surface energy mold release layer for repeatable imprinting. The imprinting results demonstrated that the cross-linked polymer mold could be faithfully used for both thermal and photocurable nanoimprint lithography.

Vapor-phase self-assembled monolayer for improved mold release in nanoimprint lithography.

Resist adhesion to the mold is one of the challenges for nanoimprint lithography. The main approach to overcoming it is to apply a self-assembled monolayer of an organosilane release agent to the mold surface, either in the solution phase or vapor phase. We compared the atomic force microscopy, ellipsometry, reflection-absorption infrared spectroscopy, and contact angle results collected from substrates treated by two different application processes and found that the vapor-phase process was superior. The vapor-treated substrates had fewer aggregates of the silane molecules on the surface, because the lower density of the agent in the vapor phase was not conducive to aggregation formation, and received a superior coating of the releasing agent, because the vapor was more effective than the solution in penetrating into the nanoscale gaps of the mold. A pattern transfer of 20 parallel nanowires with a line width of 40 nm at 100 nm pitch-size was performed faithfully with the vapor-treated mold without any resist adhesion.

Radiation exposure during transmission measurements: comparison between CT- and germanium-based techniques with a current PET scanner.

In positron emission tomographic (PET) scanning, transmission measurements for attenuation correction are commonly performed by using external germanium-68 rod sources. Recently, combined PET and computed tomographic (CT) scanners have been developed in which the CT data can be used for both anatomical-metabolic image formation and attenuation correction of the PET data. The purpose of this study was to evaluate the difference between germanium- and CT-based transmission scanning in terms of their radiation doses by using the same measurement technique and to compare the doses that patients receive during brain, cardiac and whole-body scans. Measurement of absorbed doses to organs was conducted by using a Rando Alderson phantom with thermoluminescent dosimeters. Effective doses were calculated according to the guidelines in the International Commission on Radiation Protection Publication Number 60. Compared with radionuclide doses used in routine 2-[fluorine-18]-fluoro-2-deoxy-D-glucose PET imaging, doses absorbed during germanium-based transmission scans were almost negligible. On the other hand, absorbed doses from CT-based transmission scans were significantly higher, particularly with a whole-body scanning protocol. Effective doses were 8.81 mSv in the high-speed mode and 18.97 mSv in the high-quality mode for whole-body CT-based transmission scans. These measurements revealed that the doses received by a patient during CT-based transmission scanning are more than those received in a typical PET examination. Therefore, the radiation doses represent a limitation to the generalised use of CT-based transmission measurements with current PET/CT scanner systems.