A review and analysis of personal and ambient PM2.5 measurements: Implications for epidemiology studies.

BACKGROUND: In epidemiology studies, ambient measurements of PM2.5 are often used as surrogates for personal exposures. However, it is unclear the degree to which ambient PM2.5 reflects personal exposures. OBJECTIVE: In order to examine potential sources of bias in epidemiology studies, we conducted a review and meta-analysis of studies to determine the extent to which short-term measurements of ambient PM2.5 levels are related to short-term measurements of personal PM2.5 levels. METHODS: We conducted a literature search of studies reporting both personal and ambient measurements of PM2.5 published in the last 10 years (2009-2019) and incorporated studies published prior to 2009 from reviews. RESULTS: Seventy-one studies were identified. Based on 17 studies reporting slopes, a meta-analysis revealed an overall slope of 0.56 µg/m3 (95% CI: [0.39, 0.73]) personal PM2.5 per µg/m3 increase in ambient PM2.5. Slopes for summer months were higher (slope = 0.73, 95% CI: [0.64, 0.81]) than for winter (slope = 0.46, 95% CI: [0.36, 0.57]). Based on 44 studies reporting correlations, we calculated an overall personal-ambient PM2.5 correlation of 0.63 (95% CI: [0.55, 0.71]). Correlations were stronger in studies conducted in Canada (r = 0.86, 95% CI: [0.67, 0.94]) compared to the USA (r = 0.60, 95% CI: [0.49, 0.70]) and China (r = 0.60, 95% CI: [0.46, 0.71]). Correlations also were stronger in urban areas (r = 0.53, 95% CI: [0.43, 0.62]) vs. suburban areas (r = 0.36, 95% CI: [0.21, 0.49]). SIGNIFICANCE: Our results suggest a large degree of variability in the personal-ambient PM2.5 association and the potential for exposure misclassification and measurement error in PM2.5 epidemiology studies.

Cryogenic C-band wavelength division multiplexing system using an AIM Photonics Foundry process design kit.

Cryogenic environments make superconducting computing possible by reducing thermal noise, electrical resistance and heat dissipation. Heat generated by the electronics and thermal conductivity of electrical transmission lines to the outside world constitute two main sources of thermal load in such systems. As a result, higher data rates require additional transmission lines which come at an increasingly higher cooling power cost. Hybrid or monolithic integration of silicon photonics with the electronics can be the key to higher data rates and lower power costs in these systems. We present a 4-channel wavelength division multiplexing photonic integrated circuit (PIC) built from modulators in the AIM Photonics process development kit (PDK) that operate at 25 Gbps at room temperature and 10 Gbps at 40 K. We further demonstrate 2-channel operation for 20 Gbps aggregate data rate at 40 K using two different modulators/wavelengths, with the potential for higher aggregate bit rates by utilizing additional channels.

Silicon photonic transceiver circuit for high-speed polarization-based discrete variable quantum key distribution.

We demonstrate a silicon photonic transceiver circuit for high-speed discrete variable quantum key distribution that employs a common structure for transmit and receive functions. The device is intended for use in polarization-based quantum cryptographic protocols, such as BB84. Our characterization indicates that the circuit can generate the four BB84 states (TE/TM/45°/135° linear polarizations) with >30 dB polarization extinction ratios and gigabit per second modulation speed, and is capable of decoding any polarization bases differing by 90° with high extinction ratios.

Uninterrupted use of continuous positive airway pressure after endoscopic endonasal approach for pituitary tumors.

KEY POINTS: Resumption of continuous positive airway pressure (CPAP) in the immediate postoperative period after endoscopic endonasal approaches (EEA) for pituitary adenomas can be safe.

Health effects research and regulation of diesel exhaust: an historical overview focused on lung cancer risk.

The mutagenicity of organic solvent extracts from diesel exhaust particulate (DEP), first noted more than 55 years ago, initiated an avalanche of diesel exhaust (DE) health effects research that now totals more than 6000 published studies. Despite an extensive body of results, scientific debate continues regarding the nature of the lung cancer risk posed by inhalation of occupational and environmental DE, with much of the debate focused on DEP. Decades of scientific scrutiny and increasingly stringent regulation have resulted in major advances in diesel engine technologies. The changed particulate matter (PM) emissions in "New Technology Diesel Exhaust (NTDE)" from today's modern low-emission, advanced-technology on-road heavy-duty diesel engines now resemble the PM emissions in contemporary gasoline engine exhaust (GEE) and compressed natural gas engine exhaust more than those in the "traditional diesel exhaust" (TDE) characteristic of older diesel engines. Even with the continued publication of epidemiologic analyses of TDE-exposed populations, this database remains characterized by findings of small increased lung cancer risks and inconsistent evidence of exposure-response trends, both within occupational cohorts and across occupational groups considered to have markedly different exposures (e.g. truckers versus railroad shopworkers versus underground miners). The recently published National Institute for Occupational Safety and Health (NIOSH)-National Cancer Institute (NCI) epidemiologic studies of miners provide some of the strongest findings to date regarding a DE-lung cancer association, but some inconsistent exposure-response findings and possible effects of bias and exposure misclassification raise questions regarding their interpretation. Laboratory animal studies are negative for lung tumors in all species, except for rats under lifetime TDE-exposure conditions with durations and concentrations that lead to "lung overload." The species specificity of the rat lung response to overload, and its occurrence with other particle types, is now well-understood. It is thus generally accepted that the rat bioassay for inhaled particles under conditions of lung overload is not predictive of human lung cancer hazard. Overall, despite an abundance of epidemiologic and experimental data, there remain questions as to whether TDE exposure causes increased lung cancers in humans. An abundance of emissions characterization data, as well as preliminary toxicological data, support NTDE as being toxicologically distinct from TDE. Currently, neither epidemiologic data nor animal bioassay data yet exist that directly bear on NTDE carcinogenic potential. A chronic bioassay of NTDE currently in progress will provide data on whether NTDE poses a carcinogenic hazard, but based on the significant reductions in PM mass emissions and the major changes in PM composition, it has been hypothesized that NTDE has a low carcinogenic potential. When the International Agency for Research on Cancer (IARC) reevaluates DE (along with GEE and nitroarenes) in June 2012, it will be the first authoritative body to assess DE carcinogenic health hazards since the emergence of NTDE and the accumulation of data differentiating NTDE from TDE.

Trimodal gadolinium-gold microcapsules containing pancreatic islet cells restore normoglycemia in diabetic mice and can be tracked by using US, CT, and positive-contrast MR imaging.

PURPOSE: To develop microcapsules that immunoprotect pancreatic islet cells for treatment of type I diabetes and enable multimodal cellular imaging of transplanted islet cells. MATERIALS AND METHODS: All animal experiments were approved by the institutional animal care and use committee. Gold nanoparticles functionalized with DTDTPA (dithiolated diethylenetriaminepentaacetic acid):gadolinium chelates (GG) were coencapsulated with pancreatic islet cells by using protamine sulfate as a clinical-grade alginate cross linker. Conventional poly-l-lysine-cross-linked microcapsules and unencapsulated islets were included as controls. The viability and glucose responsiveness of islet cells were assessed in vitro, and in vivo insulin (C-peptide) secretion was monitored for 6 weeks in (streptozotocin-induced) diabetic mice with (n = 7) or without (n = 8) intraabdominally engrafted islet cells. Five nondiabetic mice were included as controls. Differences between samples were calculated by using a nonparametric Wilcoxon Mann-Whitney method. To adjust for multiple comparisons, a significance level of P < .01 was chosen. Generalized estimating equations were used to model cell function over time. Three mice with engrafted capsules were imaged in vivo with high-field-strength (9.4-T) magnetic resonance (MR) imaging, micro-computed tomography (CT), and 40-MHz ultrasonography (US). RESULTS: Encapsulated human pancreatic islets were functional in vitro for at least 2 weeks after encapsulation. Blood glucose levels in the diabetic mice transplanted with GG-labeled encapsulated mouse ßTC6 insulinoma cells returned to normal within 1 week after transplantation, and normoglycemia was sustained for at least 6 weeks without the use of immunosuppressive drugs. GG microcapsules could be readily visualized with positive-contrast high-field-strength MR imaging, micro-CT, and US both in vitro and in vivo. CONCLUSION: Cell encapsulation with GG provides a means of trimodal noninvasive tracking of engrafted cells.

Measurement error in environmental epidemiology and the shape of exposure-response curves.

Both classical and Berkson exposure measurement errors as encountered in environmental epidemiology data can result in biases in fitted exposure-response relationships that are large enough to affect the interpretation and use of the apparent exposure-response shapes in risk assessment applications. A variety of sources of potential measurement error exist in the process of estimating individual exposures to environmental contaminants, and the authors review the evaluation in the literature of the magnitudes and patterns of exposure measurement errors that prevail in actual practice. It is well known among statisticians that random errors in the values of independent variables (such as exposure in exposure-response curves) may tend to bias regression results. For increasing curves, this effect tends to flatten and apparently linearize what is in truth a steeper and perhaps more curvilinear or even threshold-bearing relationship. The degree of bias is tied to the magnitude of the measurement error in the independent variables. It has been shown that the degree of bias known to apply to actual studies is sufficient to produce a false linear result, and that although nonparametric smoothing and other error-mitigating techniques may assist in identifying a threshold, they do not guarantee detection of a threshold. The consequences of this could be great, as it could lead to a misallocation of resources towards regulations that do not offer any benefit to public health.

Particulate matter in new technology diesel exhaust (NTDE) is quantitatively and qualitatively very different from that found in traditional diesel exhaust (TDE).

Diesel exhaust (DE) characteristic of pre-1988 engines is classified as a "probable" human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC), and the U.S. Environmental Protection Agency has classified DE as "likely to be carcinogenic to humans." These classifications were based on the large body of health effect studies conducted on DE over the past 30 or so years. However, increasingly stringent U.S. emissions standards (1988-2010) for particulate matter (PM) and nitrogen oxides (NOx) in diesel exhaust have helped stimulate major technological advances in diesel engine technology and diesel fuel/lubricant composition, resulting in the emergence of what has been termed New Technology Diesel Exhaust, or NTDE. NTDE is defined as DE from post-2006 and older retrofit diesel engines that incorporate a variety of technological advancements, including electronic controls, ultra-low-sulfur diesel fuel, oxidation catalysts, and wall-flow diesel particulate filters (DPFs). As discussed in a prior review (T. W. Hesterberg et al.; Environ. Sci. Technol. 2008, 42, 6437-6445), numerous emissions characterization studies have demonstrated marked differences in regulated and unregulated emissions between NTDE and "traditional diesel exhaust" (TDE) from pre-1988 diesel engines. Now there exist even more data demonstrating significant chemical and physical distinctions between the diesel exhaust particulate (DEP) in NTDE versus DEP from pre-2007 diesel technology, and its greater resemblance to particulate emissions from compressed natural gas (CNG) or gasoline engines. Furthermore, preliminary toxicological data suggest that the changes to the physical and chemical composition of NTDE lead to differences in biological responses between NTDE versus TDE exposure. Ongoing studies are expected to address some of the remaining data gaps in the understanding of possible NTDE health effects, but there is now sufficient evidence to conclude that health effects studies of pre-2007 DE likely have little relevance in assessing the potential health risks of NTDE exposures.

COVID-19 Testing in the Era of Modern Neurosurgery: Mitigating Risk in Our Vulnerable Patient Populations.

BACKGROUND: The respiratory illness identified as coronavirus disease 2019 (COVID-19) has resulted in a pandemic illness that has changed the face of healthcare. As the COVID-19 pandemic continues, patients have continued to require neurosurgical interventions, and the endoscopic endonasal approach for surgery has continued to be a mainstay treatment of pituitary tumors and anterior skull base lesions. METHODS: We sought to highlight the current lack of recommendations regarding testing protocols for neurosurgical patients. RESULTS: We implemented a novel testing protocol for our patient populations at increased risk and have proposed a model that can be used at other institutions to mitigate the risk of complications associated with some forms of COVID-19 testing. CONCLUSION: Patients with anterior skull base defects may be at risk with current COVID-19 testing protocols, and may benefit from alternative specimen collection strategies.

Health-based evaluation of ambient air measurements of PM2.5 and volatile organic compounds near a Marcellus Shale unconventional natural gas well pad site and a school campus.

BACKGROUND: Limited air monitoring studies with long-term measurements during all phases of development and production of natural gas and natural gas liquids have been conducted in close proximity to unconventional natural gas well pads. OBJECTIVE: Conducted in an area of Washington County, Pennsylvania, with extensive Marcellus Shale development, this study investigated whether operations at an unconventional natural gas well pad may contribute to ambient air concentrations of potential health concern at a nearby school campus. METHODS: Almost 2 years of air monitoring for fine particulate matter (PM2.5) and volatile organic compounds (VOCs) was performed at three locations between 1000 and 2800 feet from the study well pad from December 2016 to October 2018. PM2.5 was measured continuously at one of the three sites using a beta attenuation monitor, while 24-h stainless steel canister samples were collected every 6 days at all sites for analysis of 58 VOCs. RESULTS: Mean PM2.5 concentrations measured during the different well activity periods ranged from 5.4 to 9.5 µg/m3, with similar levels and temporal changes as PM2.5 concentrations measured at a regional background location. The majority of VOCs were either detected infrequently or not at all, with measurements for a limited number of VOCs indicating the well pad to be a source of small and transient contributions. SIGNIFICANCE: All measurement data of PM2.5 and 58 VOCs, which reflect the cumulative contributions of emissions from the study well pad and other local/regional air pollutant sources (e.g., other well pads), were below health-based air comparison values, and thus do not provide evidence of either 24-hour or long-term air quality impacts of potential health concern at the school.

Self-referenced characterization of optical frequency combs and arbitrary waveforms using a simple, linear, zero-delay implementation of spectral shearing interferometry.

We discuss a simple, linear, zero-delay implementation of spectral shearing interferometry for amplitude and phase characterization of optical frequency comb sources and arbitrary waveforms. We demonstrate this technique by characterizing two different high repetition rate (approximately 10 GHz) frequency comb sources, generated respectively by strong external and intracavity phase modulation of a continuous-wave laser. This technique is easy to implement, requiring only an intensity modulator and an optical spectrum analyzer (OSA), and is demonstrated to work at average power levels down to 100 nW (10 aJ/pulse at 10 GHz). By exploiting the long coherence lengths of these frequency combs and the self-referenced nature of the measurement, we also demonstrate a simple single-ended measurement of dispersion and dispersion slope in long lengths of fiber (>25 km).

Photonically enabled agile rf waveform generation by optical comb shifting.

We present a photonically enabled rf arbitrary waveform generator that can rapidly switch between two output waveforms. This method is based on line-by-line shaping of an optical comb and then converting the optical pulses to rf waveforms with a fast photodetector. It uses a single diode laser as the optical source and selects different patterns preprogrammed into an optical pulse shaper by shifting the laser frequency. We demonstrate minimum update delay times of 0.45 ns.

Generation of very flat optical frequency combs from continuous-wave lasers using cascaded intensity and phase modulators driven by tailored radio frequency waveforms.

We demonstrate a scheme based on a cascade of lithium niobate intensity and phase modulators driven by specially tailored RF waveforms to generate an optical frequency comb with very high spectral flatness. In this Letter, we demonstrate a 10 GHz comb with 38 comb lines within a spectral power variation below 1 dB. The number of comb lines that can be generated is limited by the power handling capability of the phase modulator, and this can be scaled without compromising the spectral flatness. Furthermore, the spectral phase of the generated combs in our scheme is almost purely quadratic, which, as we will demonstrate, allows for high-quality pulse compression using only single-mode fiber.

Diesel exhaust particulate (DEP) and nanoparticle exposures: what do DEP human clinical studies tell us about potential human health hazards of nanoparticles?

Engineered nanoparticles (ENPs) are increasingly tested in cellular and laboratory-animal experiments for hazard potential, but there is a lack of health effects data for humans exposed to ENPs. However, human data for another source of nanoparticle (NP) exposure are available, notably for the NPs contained in diesel exhaust particulate (DEP). Studies of human volunteers exposed to diesel exhaust (DE) in research settings report DEP-NP number concentrations (i.e., >10(6) particles/cm(3)) that exceed number concentrations reported for worst-case exposure conditions for workers manufacturing and handling ENPs. Recent human DE exposure studies, using sensitive physiological instrumentation and well-characterized exposure concentrations and durations, suggest that elevated DE exposures from pre-2007 engines may trigger short-term changes in, for example, lung and systemic inflammation, thrombogenesis, vascular function, and brain activity. Considerable uncertainty remains both as to which DE constituents underlie the observed responses (i.e., DEP NPs, DEP mass, DE gases), and as to the implications of the observed short-term changes for the development of disease. Even so, these DE human clinical data do not give evidence of a unique toxicity for NPs as compared to other small particles. Of course, physicochemical properties of toxicological relevance may differ between DEP NPs and other NPs, yet overall, the DE human clinical data do not support the idea that elevated levels of NPs per se (at least in the DEP context) must be acutely toxic by virtue of their nano-sized nature alone.

Optical arbitrary waveform characterization using linear spectrograms.

We demonstrate the first application of linear spectrogram methods based on electro-optic phase modulation to characterize optical arbitrary waveforms generated under spectral line-by-line control. This approach offers both superior sensitivity and self-referencing capability for retrieval of periodic high repetition rate optical arbitrary waveforms.

Optimizing Diffusion Imaging Protocols for Structural Connectomics in Mouse Models of Neurological Conditions.

Network approaches provide sensitive biomarkers for neurological conditions, such as Alzheimer's disease (AD). Mouse models can help advance our understanding of underlying pathologies, by dissecting vulnerable circuits. While the mouse brain contains less white matter compared to the human brain, axonal diameters compare relatively well (e.g., ~0.6 µm in the mouse and ~0.65-1.05 µm in the human corpus callosum). This makes the mouse an attractive test bed for novel diffusion models and imaging protocols. Remaining questions on the accuracy and uncertainty of connectomes have prompted us to evaluate diffusion imaging protocols with various spatial and angular resolutions. We have derived structural connectomes by extracting gradient subsets from a high-spatial, high-angular resolution diffusion acquisition (120 directions, 43-µm-size voxels). We have simulated protocols with 12, 15, 20, 30, 45, 60, 80, 100, and 120 angles and at 43, 86, or 172-µm voxel sizes. The rotational stability of these schemes increased with angular resolution. The minimum condition number was achieved for 120 directions, followed by 60 and 45 directions. The percentage of voxels containing one dyad was exceeded by those with two dyads after 45 directions, and for the highest spatial resolution protocols. For the 86- or 172-µm resolutions, these ratios converged toward 55% for one and 39% for two dyads, respectively, with <7% from voxels with three dyads. Tractography errors, estimated through dyad dispersion, decreased most with angular resolution. Spatial resolution effects became noticeable at 172 µm. Smaller tracts, e.g., the fornix, were affected more than larger ones, e.g., the fimbria. We observed an inflection point for 45 directions, and an asymptotic behavior after 60 directions, corresponding to similar projection density maps. Spatially downsampling to 86 µm, while maintaining the angular resolution, achieved a subgraph similarity of 96% relative to the reference. Using 60 directions with 86- or 172-µm voxels resulted in 94% similarity. Node similarity metrics indicated that major white matter tracts were more robust to downsampling relative to cortical regions. Our study provides guidelines for new protocols in mouse models of neurological conditions, so as to achieve similar connectomes, while increasing efficiency.

Optical properties of photonic crystal heterostructure cavity lasers.

We design, fabricate, and test photonic crystal heterostructure cavity lasers in the InP material system. A heterostructure cavity is formed by interfacing two different photonic crystals such that a dispersion maximum of the inner lattice lies within the band gap of the surrounding lattice. Feedback to slow light modes of the central region results in a lower threshold and single mode operation. The use of a kagome lattice as the inner defect area increases the semiconductor volume as well as the modal overlap with the gain material. We use a simulation technique to verify experimentally observed single mode operation as well as to quantify the effects of the heterostructure cavity formation.

Non-cancer health effects of diesel exhaust: a critical assessment of recent human and animal toxicological literature.

We reviewed laboratory and clinical studies bearing on the non-cancer health effects of diesel exhaust (DE) published since the 2002 release of the US EPA Health Assessment Document for Diesel Engine Exhaust. We critically evaluated over 100 published articles on experimental research, focusing on their value for predicting the risk of non-cancer health effects in humans exposed to DE. Human controlled-exposure studies provide new evidence of lung inflammatory effects and thrombogenic and ischemic effects of inhaled DE, albeit for older-model diesel engines and concentrations that are much higher (approximately 300 microg/m(3)) than typical ambient or even occupational levels. Recent animal studies provide insight into the potential mechanisms underlying observed respiratory and cardiovascular health responses; however, because of unrealistically high DE concentrations, the mechanisms elucidated in these studies may not be relevant at lower DE exposure levels. Although larger in number, and suggestive of possible mechanisms for non-cancer health effects at elevated DE levels, interpretation of this recent group of clinical-study findings and laboratory-animal results remains hindered by inconsistencies and variability in outcomes, potentially irrelevant DE-exposure compositions, limitations in exposure protocols and pathways, and uncertainties in extrapolation and generalization. A mechanism of action that allows reliable prediction of adverse health effects at DE-exposure levels typical of the present-day ambient and occupational environment has not emerged. Because of changing diesel-engine technology, inhalation studies using realistic environmental and occupational exposures of new-technology diesel exhaust are of critical importance.