Histologic examination of fixed renal tissue is widely used to assess morphology and the progression of disease. Commonly reported metrics include glomerular number and injury. However, ...characterization of renal histology is a time-consuming and user-dependent process. To accelerate and improve the process, we have developed a glomerular localization pipeline for trichrome-stained kidney sections using a machine learning image classification algorithm.
We prepared 4-
m slices of kidneys from rats of various genetic backgrounds that were subjected to different experimental protocols and mounted the slices on glass slides. All sections used in this analysis were trichrome stained and imaged in bright field at a minimum resolution of 0.92
m per pixel. The training and test datasets for the algorithm comprised 74 and 13 whole renal sections, respectively, totaling over 28,000 glomeruli manually localized. Additionally, because this localizer will be ultimately used for automated assessment of glomerular injury, we assessed bias of the localizer for preferentially identifying healthy or damaged glomeruli.
Localizer performance achieved an average precision and recall of 96.94% and 96.79%, respectively, on whole kidney sections without evidence of bias for or against glomerular injury or the need for manual preprocessing.
This study presents a novel and robust application of convolutional neural nets for the localization of glomeruli in healthy and damaged trichrome-stained whole-renal section mounts and lays the groundwork for automated glomerular injury scoring.
Rates of amyotrophic lateral sclerosis (ALS) have been reported to be higher among US military veterans, who currently number more than 21 million, but the causal factor(s) has not been identified. ...We conducted a review to examine the weight of evidence for associations between military service, deployments, and exposures and ALS etiology and survival. Thirty articles or abstracts published through 2013 were reviewed. Although the current evidence suggests a positive association with ALS etiology, it is too limited to draw firm conclusions regarding associations between military service and ALS etiology or survival. Some evidence suggests that deployment to the 1990-1991 Persian Gulf War may be associated with ALS etiology, but there is currently no strong evidence that any particular military exposure is associated with ALS etiology. Future studies should address the limitations of previous ones, such as reliance on mortality as a surrogate for incidence, a dearth of survival analyses, lack of clinical data, low statistical power, and limited exposure assessment. The Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis (GENEVA) Study is one such study, but additional research is needed to determine whether military-related factors are associated with ALS and to assess potential prevention strategies.
Carbon nanotubes and nanofibers (CNT/F) are increasingly used for diverse applications. Although animal studies suggest CNT/F exposure may cause deleterious health effects, human epidemiological ...studies have typically been small, confined to single workplaces, and limited in exposure assessment.
We conducted an industrywide cross-sectional epidemiological study of 108 workers from 12 U.S. sites to evaluate associations between occupational CNT/F exposure and sputum and blood biomarkers of early effect.
We assessed CNT/F exposure via personal breathing zone, filter-based air sampling to measure background-corrected elemental carbon (EC) (a CNT/F marker) mass and microscopy-based CNT/F structure count concentrations. We measured 36 sputum and 37 blood biomarkers. We used factor analyses with varimax rotation to derive factors among sputum and blood biomarkers separately. We used linear, Tobit, and unconditional logistic regression models to adjust for potential confounders and evaluate associations between CNT/F exposure and individual biomarkers and derived factors.
We derived three sputum and nine blood biomarker factors that explained 78% and 67%, respectively, of the variation. After adjusting for potential confounders, inhalable EC and total inhalable CNT/F structures were associated with the most sputum and blood biomarkers, respectively. Biomarkers associated with at least three CNT/F metrics were 72 kDa type IV collagenase/matrix metalloproteinase-2 (MMP-2), interleukin-18, glutathione peroxidase (GPx), myeloperoxidase, and superoxide dismutase (SOD) in sputum and MMP-2, matrix metalloproteinase-9, metalloproteinase inhibitor 1/tissue inhibitor of metalloproteinases 1, 8-hydroxy-2′-deoxyguanosine, GPx, SOD, endothelin-1, fibrinogen, intercellular adhesion molecule 1, vascular cell adhesion protein 1, and von Willebrand factor in blood, although directions of associations were not always as expected.
Inhalable rather than respirable CNT/F was more consistently associated with fibrosis, inflammation, oxidative stress, and cardiovascular biomarkers.
•We evaluated carbon nanotube/nanofiber (CNT/F) exposure in relation to biomarkers.•We assessed CNT/F exposure via personal breathing zone, filter-based air sampling.•We measured fibrosis, inflammation, oxidative stress, cardiovascular biomarkers.•Inhalable rather than respirable CNT/F was more often associated with biomarkers.•Sixteen biomarkers were associated with at least three CNT/F exposure metrics.
Pesticide exposure may be positively associated with depression. Few previous studies have considered the episodic nature of depression or examined individual pesticides.
We evaluated associations ...between pesticide exposure and depression among male private pesticide applicators in the Agricultural Health Study.
We analyzed data for 10 pesticide classes and 50 specific pesticides used by 21,208 applicators enrolled in 1993-1997 who completed a follow-up telephone interview in 2005-2010. We divided applicators who reported a physician diagnosis of depression (n = 1,702; 8%) into those who reported a previous diagnosis of depression at enrollment but not follow-up (n = 474; 28%), at both enrollment and follow-up (n = 540; 32%), and at follow-up but not enrollment (n = 688; 40%) and used polytomous logistic regression to estimate odds ratios (ORs) and 95% CIs. We used inverse probability weighting to adjust for potential confounders and to account for the exclusion of 3,315 applicators with missing covariate data and 24,619 who did not complete the follow-up interview.
After weighting for potential confounders, missing covariate data, and dropout, ever-use of two pesticide classes, fumigants and organochlorine insecticides, and seven individual pesticides-the fumigants aluminum phosphide and ethylene dibromide; the phenoxy herbicide (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T); the organochlorine insecticide dieldrin; and the organophosphate insecticides diazinon, malathion, and parathion-were all positively associated with depression in each case group, with ORs between 1.1 and 1.9.
Our study supports a positive association between pesticide exposure and depression, including associations with several specific pesticides.
Amyotrophic lateral sclerosis (ALS) may be associated with low body mass index (BMI) at the time of diagnosis. However, the role of premorbid BMI in the development of ALS and survival after ...diagnosis remains unclear. In 2005-2010, we interviewed 467 patients with ALS from the US National Registry of Veterans with ALS and 975 frequency-matched veteran controls. In this sample, we evaluated the association of BMI and BMI change at different ages with ALS risk using unconditional logistic models and with survival after ALS diagnosis using Cox proportional hazards models. After adjustment for confounders, compared with a moderate increase in BMI between ages 25 and 40 years, stable or decreasing BMI was positively associated with ALS risk (odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.20, 2.16). A 1-unit increase in BMI at age 40 years (OR = 0.95, 95% CI: 0.91, 0.98) but not at age 25 years (OR = 0.99, 95% CI: 0.95, 1.03) was inversely associated with ALS. These associations were similar for bulbar and spinal ALS but stronger for those with a delay of less than 1 year between symptom onset and diagnosis. We found no association between prediagnosis BMI and survival. A decreasing BMI from early to middle age and a low BMI in middle age may be positively associated with ALS risk.
Military veterans may have higher rates of amyotrophic lateral sclerosis (ALS) mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships ...between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases.
We followed 616 medical record-confirmed cases from enrollment (2005-2010) in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment.
We observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months). Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73.
Although most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans.
Optical clocks are emerging as next-generation timekeeping devices with technological and scientific use cases. Simplified atomic sources such as vapor cells may offer a straightforward path to field ...use, but suffer from long-term frequency drifts and environmental sensitivities. Here, we measure a laboratory optical clock based on warm rubidium atoms and find low levels of drift on the month-long timescale. We observe and quantify helium contamination inside the glass vapor cell by gradually removing the helium via a vacuum apparatus. We quantify a drift rate of 4×10-15/day, a 10 day Allan deviation less than 5×10-15, and an absolute frequency of the Rb-87 two-photon clock transition of 385,284,566,371,190(1970) Hz. These results support the premise that optical vapor cell clocks will be able to meet future technology needs in navigation and communications as sensors of time and frequency.
RATIONALEMotivational dysfunctions related to effort exertion are common in psychiatric disorders. Dopamine systems regulate exertion of effort and effort-based choice in humans and ...rodents.OBJECTIVESPrevious rodent studies mainly employed male rats, and it is imperative to conduct studies in male and female rats.METHODSThe present studies compared the effort-related effects of IP injections of the dopamine antagonists ecopipam and haloperidol, and the vesicular monoamine transport-2 inhibitor tetrabenazine (TBZ), in male and female rats using the fixed ratio 5/chow feeding choice task.RESULTSEcopipam (0.05-0.2 mg/kg) and haloperidol (0.05-0.15 mg/kg) induced a low-effort bias, decreasing lever pressing and increasing chow intake in males and females in the same dose range. With lever pressing, there was a modest but significant dose x sex interaction after ecopipam injection, but there was no significant interaction after administration of haloperidol. In the first study with TBZ (0.25-1.0 mg/kg), there was a robust sex difference. TBZ shifted choice from lever pressing to chow intake in male rats, but was ineffective in females. In a second experiment, 2.0 mg/kg affected choice behavior in both males and females. TBZ increased accumbens c-Fos immunoreactivity in a sex-dependent manner, with males significantly increasing at 1.0 mg/kg, while females showed augmented immunoreactivity at 2.0 mg/kg.CONCLUSIONSThe neural and behavioral effects of TBZ differed across sexes, emphasizing the importance of conducting studies in male and female rats. This research has implications for understanding the effort-related motivational dysfunctions seen in psychopathology.
Recent animal studies have suggested the potential for wide-ranging health effects resulting from exposure to carbon nanotubes and nanofibers (CNT/F). To date, no studies in the US have directly ...examined the relationship between occupational exposure and potential human health effects.
Our goal was to measure CNT/F exposures among US workers with representative job types, from non-exposed to highly exposed, for an epidemiologic study relating exposure to early biologic effects.
108 participants were enrolled from 12 facilities across the US. Personal, full-shift exposures were assessed based on the mass of elemental carbon (EC) at the respirable and inhalable aerosol particle size fractions, along with quantitatively characterizing CNT/F and estimating particle size via transmission electron microscopy (TEM). Additionally, sputum and dermal samples were collected and analyzed to determine internal exposures and exposures to the hands/wrists.
The mean exposure to EC was 1.00 μg/m3 at the respirable size fraction and 6.22 μg/m3 at the inhalable fraction. Analysis by TEM found a mean exposure of 0.1275 CNT/F structures/cm3, generally to agglomerated materials between 2 and 10 μm. Internal exposures to CNT/F via sputum analysis were confirmed in 18% of participants while ∼70% had positive dermal exposures.
We demonstrated the occurrence of a broad range of exposures to CNT/F within 12 facilities across the US. Analysis of collected sputum indicated internal exposures are currently occurring within the workplace. This is an important first step in determining if exposures in the workforce have any acute or lasting health effects.
Household and ambient air pollution remain public health problems in much of the world. Brick kiln employees in Nepal may be particularly at risk of high air pollution exposures and resulting health ...effects due to high levels of outdoor air pollution, substandard housing, and indoor biomass cooking. We conducted a cross-sectional study of indoor and outdoor air pollution concentrations at workers' homes at four fixed chimney Bull's trench brick kilns in Bhaktapur, Kathmandu Valley, Nepal. We measured air concentrations of carbon monoxide (CO), carbon dioxide (CO
), nitrogen dioxide (NO
), sulfur dioxide (SO
), and respirable crystalline silica (SiO
; cristobalite, quartz, tridymite) using established methods and conducted a survey about characteristics of homes or samples that may be associated with air pollution concentrations. Geometric mean concentrations of CO, CO
, and SiO
(quartz) were 0.84 ppm, 1447.34 ppm, and 6.22 µg/m
, respectively, whereas concentrations of all other air pollutants measured below lower detection limits. Most characteristics of homes or samples were not associated with air pollution concentrations. We found a positive association between the variable how long lived in house and SiO
(quartz) concentrations, which may reflect sustained take-home exposure to SiO
(quartz) over time. Interventions should focus on administrative controls to reduce take-home exposure to SiO
(quartz) in this population.
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