Time-Dependent Evolution Study of Ar/N2 Plasma-Activated Cu Surface for Enabling Two-Step Cu-Cu Direct Bonding in a Non-Vacuum Environment

In this paper, a two-step copper-copper direct bonding process in a non-vacuum environment is reported. Time-dependent evolution of argon/nitrogen plasma-activated copper surface is carefully studied. A multitude of surface characterizations are performed to investigate the evolution of the copper surface, with and without argon/nitrogen plasma treatment, when it is exposed to the cleanroom ambient for a period of time. The results reveal that a thin layer of copper nitride is formed upon argon/nitrogen plasma activation on copper surface. It is hypothesized that the nitride layer could dampen surface oxidation. This allows the surface to remain in an “activated” state for up to 6 hours. Afterwards, the activated dies are physically bonded at room temperature in cleanroom ambient. Thereafter, the bonded dies are annealed at 300ºC for varying duration, which results in an improvement of the bond strength by a factor of 70 ~ 140 times. A sample bonded after plasma activation and 2-hour cleanroom ambient exposure demonstrates the largest shear strength (~5 MPa). The degradation of copper nitride layer at elevated temperature could aid in maintaining a localized inert environment for the initial diffusion of copper atoms across the interface. This novel bonding technique would be useful for high-throughput three-dimensional wafer bonding and heterogeneous packaging in semiconductor manufacturing.

Ambient and household PM2.5 pollution and adverse perinatal outcomes: A meta-regression and analysis of attributable global burden for 204 countries and territories

Background Particulate matter <2.5 micrometer (PM2.5) is associated with adverse perinatal outcomes, but the impact on disease burden mediated by this pathway has not previously been included in the Global Burden of Disease (GBD), Mortality, Injuries, and Risk Factors studies. We estimated the global burden of low birth weight (LBW) and preterm birth (PTB) and impacts on reduced birth weight and gestational age (GA), attributable to ambient and household PM2.5 pollution in 2019. Methods and findings We searched PubMed, Embase, and Web of Science for peer-reviewed articles in English. Study quality was assessed using 2 tools: (1) Agency for Healthcare Research and Quality checklist; and (2) National Institute of Environmental Health Sciences (NIEHS) risk of bias questions. We conducted a meta-regression (MR) to quantify the risk of PM2.5 on birth weight and GA. The MR, based on a systematic review (SR) of articles published through April 4, 2021, and resulting uncertainty intervals (UIs) accounted for unexplained between-study heterogeneity. Separate nonlinear relationships relating exposure to risk were generated for each outcome and applied in the burden estimation. The MR included 44, 40, and 40 birth weight, LBW, and PTB studies, respectively. Majority of the studies were of retrospective cohort design and primarily from North America, Europe, and Australia. A few recent studies were from China, India, sub-Saharan Africa, and South America. Pooled estimates indicated 22 grams (95% UI: 12, 32) lower birth weight, 11% greater risk of LBW (1.11, 95% UI: 1.07, 1.16), and 12% greater risk of PTB (1.12, 95% UI: 1.06, 1.19), per 10 μg/m3 increment in ambient PM2.5. We estimated a global population–weighted mean lowering of 89 grams (95% UI: 88, 89) of birth weight and 3.4 weeks (95% UI: 3.4, 3.4) of GA in 2019, attributable to total PM2.5. Globally, an estimated 15.6% (95% UI: 15.6, 15.7) of all LBW and 35.7% (95% UI: 35.6, 35.9) of all PTB infants were attributable to total PM2.5, equivalent to 2,761,720 (95% UI: 2,746,713 to 2,776,722) and 5,870,103 (95% UI: 5,848,046 to 5,892,166) infants in 2019, respectively. About one-third of the total PM2.5 burden for LBW and PTB could be attributable to ambient exposure, with household air pollution (HAP) dominating in low-income countries. The findings should be viewed in light of some limitations such as heterogeneity between studies including size, exposure levels, exposure assessment method, and adjustment for confounding. Furthermore, studies did not separate the direct effect of PM2.5 on birth weight from that mediated through GA. As a consequence, the pooled risk estimates in the MR and likewise the global burden may have been underestimated. Conclusions Ambient and household PM2.5 were associated with reduced birth weight and GA, which are, in turn, associated with neonatal and infant mortality, particularly in low- and middle-income countries.

Tracking Devices for Pets: Health Risk Assessment for Exposure to Radiofrequency Electromagnetic Fields

Every year, approximately 3% of cats and dogs are lost. In addition to passive methods for identifying pets, radiofrequency tracking devices (TDs) are available. These TDs can track a pet’s geographic position, which is transmitted by radio frequencies. The health risk to the animals from continuous exposure to radiofrequency electromagnetic fields (RF-EMFs) was reviewed. Fourteen out of twenty-one commercially available TDs use 2G, 3G, or 4G mobile networks, and the others work with public frequencies, WLAN, Bluetooth, etc. The exposure of pets to RF-EMFs was assessed, including ambient exposure (radios, TVs, and base stations of mobile networks), exposure from indoor devices (DECT, WLAN, Bluetooth, etc.), and the exposure from TDs. The exposure levels of the three areas were found to be distinctly below the International Commission on Non-Ionising Radiation Protection (ICNIRP) reference levels, which assure far-reaching protection from adverse health effects. The highest uncertainty regarding the exposure of pets was related to that caused by indoor RF-emitting devices using WLAN and DECT. This exposure can be limited considerably through a reduction in the exposure time and an increase in the distance between the animal and the RF-emitting device. Even though the total RF-EMF exposure level experienced by pets was found to be below the reference limits, recommendations were derived to reduce potential risks from exposure to TDs and indoor devices.

Association between exposure to ambient air pollution and occurrence of inflammatory acne in the adult population

Background Acne vulgaris is one of the most prevalent skin diseases responsible for dermatological consultations. Several internal and external factors can affect acne occurrence and severity. Outdoor air pollution is an external factor discussed to trigger inflammation of the skin. The objective of this study was to find a link between the exposure to ambient air pollution and inflammatory acne occurrence in the Lebanese adult population. Methods A cross-sectional study was conducted, using an online questionnaire to collect the required data from different Lebanese regions. The survey covered pollution exposure questions as well as queries on several factors known to have a role on acne occurrence. Results A total of 372 participants were included in the study, aged 18 to 55 years old. The results of a logistic regression taking the presence/absence of acne as the dependent variable, showed that female gender (aOR = 4.39), younger age (aOR = 1.05), using hydrating cream (aOR = 4.30), working near a power plant vs not (aOR = 3.07), having a severe NO2 exposure compared to none (aOR = 8.24), a higher number of family members with acne or history of acne (aOR = 1.48) were significantly associated with higher odds of having acne, whereas having a dry skin compared to normal (aOR = 0.20) was significantly associated with lower odds of having acne. Conclusion The occurrence of inflammatory acne in Lebanese adults was found to be associated with ambient exposure to high levels of NO2 and employment near a power plant known to emit CO2, CO, SO2, NO2 and PM. Therefore, our findings can serve as a first step towards implementing awareness on a skin care routine suitable for highly polluted areas.

Environmental Exposure to Volatile Organic Compounds is Associated with Endothelial Injury

ABSTRACTObjectiveVolatile organic compounds (VOCs) are airborne toxicants abundant in outdoor and indoor air. High levels of VOCs are also present at various Superfund and other hazardous waste sites; however, little is known about the cardiovascular effects of VOCs. We hypothesized that ambient exposure to VOCs exacerbate cardiovascular disease (CVD) risk by depleting circulating angiogenic cells (CACs).Approach and ResultsIn this cross-sectional study, we recruited 603 participants with low-to-high CVD risk and measured 15 subpopulations of CACs by flow cytometry and 16 urinary metabolites of 12 VOCs by LC/MS/MS. Associations between CAC and VOC metabolite levels were examined using generalized linear models in the total sample, and separately in non-smokers. In single pollutant models, metabolites of ethylbenzene/styrene and xylene, were negatively associated with CAC levels in both the total sample, and in non-smokers. The metabolite of acrylonitrile was negatively associated with CD45dim/CD146+/CD34+/AC133+ cells and CD45+/CD146+/AC133+, and the toluene metabolite with AC133+ cells. In analysis of non-smokers (n=375), multipollutant models showed a negative association with metabolites of ethylbenzene/styrene, benzene, and xylene with CD45dim/CD146+/CD34+ cells, independent of other VOC metabolite levels. Cumulative VOC risk score showed a strong negative association with CD45dim/CD146+/CD34+ cells, suggesting that total VOC exposure has a cumulative effect on pro-angiogenic cells. We found a non-linear relationship for benzene, which showed an increase in CAC levels at low, but depletion at higher levels of exposure. Sex and race, hypertension, and diabetes significantly modified VOC associated CAC depletion.ConclusionLow-level ambient exposure to VOCs is associated with CAC depletion, which could compromise endothelial repair and angiogenesis, and exacerbate CVD risk.

Chemical Vapor Deposition of N-Doped Graphene through Pre-Implantation of Nitrogen Ions for Long-Term Protection of Copper

Nitrogen-doped graphene (NG) was synthesized through the chemical vapor deposition (CVD) of graphene on Cu substrates, which were pre-implanted with N ions by the ion implantation method. The pre-implanted N ions in the Cu substrate could dope graphene by the substitution of C atoms during the CVD growth of graphene, forming NG. Based on this, NG’s long-term protection properties for Cu were evaluated by ambient exposure for a corrosion test. The results showed that NG can obviously reduce the natural oxidation of Cu in the long-term exposure compared with the case of pristine graphene (PG) coated on Cu. Moreover, with the increase in pre-implanted N dose, the formed NG’s long-term protection for Cu improved. This indicates that the modification of graphene by N doping is an effective way to improve the corrosion resistance of the PG coating owing to the reduction in its conductivity, which would inhibit galvanic corrosion by cutting off electron transport across the interface in their long-term protection. These findings provide insight into corrosion mechanisms of the graphene coating and correlate with its conductive nature based on heteroatoms doping, which is a potential route for improving the corrosion resistance of graphene as an effective barrier coating for metals.

Dietary Synbiotics Can Help Relieve the Impacts of Deltamethrin Toxicity of Nile Tilapia Reared at Low Temperatures

The optimal water temperature for the normal growth of Nile tilapia is between 26 and 28 °C, and the toxicity of pesticides is strongly related to water temperature. An alternate approach to augmenting the resistance of fish to ambient water toxicity and low water temperature via synbiotic feeding was proposed. In this study, fish were allocated into four groups with 10 fish in each replicate, where they were fed a basal diet or synbiotics (550 mg/kg) and kept at a suboptimal water temperature (21 ± 2 °C). The prepared diets were fed to Nile tilapia for 30 days with or without deltamethrin (DMT) ambient exposure (15 μg/L). The groups were named control (basal diet without DMT toxicity), DMT (basal diet with DMT toxicity), synbiotic (synbiotics without DMT toxicity), and DMT + synbiotic (synbiotics with DMT toxicity). The results displayed upregulated transcription of catalase, glutathione peroxidase, and interferon (IFN-γ) genes caused by DMT exposure and synbiotic feeding when compared with the controls. Moreover, HSP70 and CASP3 genes displayed increased transcription caused by DMT exposure without synbiotic feeding. However, fish fed with synbiotics showed downregulated HSP70 and CASP3 gene expressions. The transcription of IL-1β and IL-8 genes were also decreased by DMT exposure, while fish fed synbiotics showed upregulated levels. DMT exposure resulted in irregular histopathological features in gills, intestine, spleen, and liver tissues, while fish fed synbiotics showed regular, normal, and protected histopathological images. Our results indicated that dietary synbiotics ameliorated histopathological damages in DMT-exposed tilapia through alleviation of oxidative stress and inflammation as well as enhancing the immunity.

Heat Exposure and Multiple Sclerosis—A Regional and Temporal Analysis

Multiple sclerosis (MS) is a neurological disorder that progressively distorts the myelination of axons within the central nervous system (CNS). Increased core body temperature or metabolism as a result of exercise are common causes of short-term exacerbations of neurological symptoms in MS. About 60–80% of patients with MS experience a worsening of their symptoms when exposed to heat. In comparison, less data are available on the relationship between ambient meteorological conditions (e.g., temperature and relative humidity (RH)) and fluctuations in such variables in relation to MS symptoms. Thus, this study examined associations between time-lagged exposure to meteorological conditions and risk of a clinic visit due to MS among US veterans between 2010 and 2013. This study leveraged data from the Veterans Affairs (VA) and National Climactic Data Center (NCDC) for the continental US, partitioned into eight climate zones. We used a case crossover design to assess the risk of a MS clinic visit with respect to several meteorological conditions. Location-specific time-lagged daily (ambient) exposure to temperature, RH, and temperature variations (standard deviation (SD) of temperature) were computed (up to 30 days) for each case (i.e., day of MS visit) and control (a randomly assigned date ± 90–270 days prior to visit). Statistical analyses were conducted to examine independent associations between the selected meteorological conditions and risk of MS visits at the national and regional levels. A total of 533,066 patient visits received a MS diagnosis (International Classifications of Diseases (ICD)-9 code = 340). The Northeast (NE) and Upper Midwest (UMW) regions reported the highest frequency of clinic visits due to MS. Clinic visits were 9% more likely to occur in the spring, summer, and fall months (March–October) than in the winter (OR = 1.089; 95% CI = 1.076–1.103; p < 0.01). In the univariate analyses, the SD of temperature, temperature, and temperature–RH interaction were positively associated with an elevated risk of a MS clinic visit, while the RH was negatively associated with the risk for a clinic visit. In multivariate analyses, the strongest association of a MS clinic visit was observed with the SD of the temperature (OR = 1.012; 95% CI 1.008–1.017; p < 0.01). These associations between MS clinic visits and meteorological conditions varied across climate regions, with the strongest associations being observed in the LMW, UMW, DSW, and NE zones. The SD of the temperature was again the strongest associated predictor when examined regionally. Temperature variations and temperature–RH interactions (a proxy of the heat index) showed significant associations with MS clinic visits. These associations varied across climate regions when examined geographically. Our findings have implications for the management of MS in severe or recurrent cases, especially considering the impending changes in the daily temperature variations and intensity of the heatwaves expected with the intensification of global warming.

Maternal Ambient Exposure to Atmospheric Pollutants during Pregnancy and Offspring Term Birth Weight in the Nationwide ELFE Cohort

Background: Studies have reported associations between maternal exposure to atmospheric pollution and lower birth weight. However, the evidence is not consistent and uncertainties remain. We used advanced statistical approaches to robustly estimate the association of atmospheric pollutant exposure during specific pregnancy time windows with term birth weight (TBW) in a nationwide study. Methods: Among 13,334 women from the French Longitudinal Study of Children (ELFE) cohort, exposures to PM2.5, PM10 (particles < 2.5 µm and <10 µm) and NO2 (nitrogen dioxide) were estimated using a fine spatio-temporal exposure model. We used inverse probability scores and doubly robust methods in generalized additive models accounting for spatial autocorrelation to study the association of such exposures with TBW. Results: First trimester exposures were associated with an increased TBW. Second trimester exposures were associated with a decreased TBW by 17.1 g (95% CI, −26.8, −7.3) and by 18.0 g (−26.6, −9.4) for each 5 µg/m3 increase in PM2.5 and PM10, respectively, and by 15.9 g (−27.6, −4.2) for each 10 µg/m3 increase in NO2. Third trimester exposures (truncated at 37 gestational weeks) were associated with a decreased TBW by 48.1 g (−58.1, −38.0) for PM2.5, 38.1 g (−46.7, −29.6) for PM10 and 14.7 g (−25.3, −4.0) for NO2. Effects of pollutants on TBW were larger in rural areas. Conclusions: Our results support an adverse effect of air pollutant exposure on TBW. We highlighted a larger effect of air pollutants on TBW among women living in rural areas compared to women living in urban areas.