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New Methods for Personal Exposure Monitoring for Airborne Particles
Airborne particles have been associated with a range of adverse cardiopulmonary outcomes, which has driven its monitoring at stationary central sites throughout the world. Individual exposures, however, can differ substantially from concentrations measured at central sites due to spatial variability across a region and sources unique to the individual, such as cooking or cleaning in homes, traffic emissions during commutes, and widely varying sources encountered at work. Personal monitoring with small, battery-powered instruments enables the measurement of an individual’s exposure as they go about their daily activities. Personal monitoring can substantially reduce exposure misclassification and improve the power to detect relationships between particulate pollution and adverse health outcomes. By partitioning exposures to known locations and sources, it may be possible to account for variable toxicity of different sources. This review outlines recent advances in the field of personal exposure assessment for particulate pollution. Advances in battery technology have improved the feasibility of 24-h monitoring, providing the ability to more completely attribute exposures to microenvironment (e.g., work, home, commute). New metrics to evaluate the relationship between particulate matter and health are also being considered, including particle number concentration, particle composition measures, and particle oxidative load. Such metrics provide opportunities to develop more precise associations between airborne particles and health and may provide opportunities for more effective regulations.
Journal Article
Chief joy officer : how great leaders elevate human energy and eliminate fear
\"The founder of Menlo Innovations and author of the business culture cult classic Joy, Inc offers an inspirational guide to leaders seeking joy in the challenge of leading others. Rich Sheridan's Joy, Inc. told the story of how his tiny software company in Ann Arbor, Michigan achieved success and renown by embracing offbeat culture and human-centered values. In Chief Joy Officer, he turns his attention from culture to leadership, and draws on his experience running Menlo and consulting elsewhere to offer a wise, provocative guide on how anyone can build leadership capacity for joy within their own organization. Chief Joy Officer offers sage, hard-won advice to any manager or leader who yearns to make more of an impact on the lives of others, including: *Self-understanding is the cornerstone for every virtue of leadership: authenticity, trust, humility, and optimism. *Good leaders make more leaders: Learn to judge your performance not on whether people are doing what they're told, but whether they're developing independent leadership capacity. *Influencing up is just as important is influencing down: how to encourage different thinking in those above you in your organizations. Filled with colorful anecdotes from Sheridan's personal journey and wisdom from many leadership mentors, Chief Joy Officer offers an approachable, down-to-earth philosophy and practice that will help even the most disillusioned of middle managers bring a renewed sense of purpose to their work building others\"-- Provided by publisher.
Book
Relation Between Age, Comorbidity, and Complications in Patients Undergoing Major Surgery for Head and Neck Cancer
Background
Multiple factors have been identified as predictors of complication after head and neck surgery. However, little is known about the exact role of different comorbid conditions in the development of postoperative complications. This question is especially interesting in the elderly population. The aim of this study was to investigate the association between comorbidity and types of postoperative complications with special attention to age differences.
Methods
A retrospective analysis was performed of 1,201 major surgical interventions for head and neck malignancies in a tertiary referral center between 1995 and 2010. The Adult Comorbidity Evaluation 27 (ACE-27) index was used to analyze severity (mild, moderate, and severe comorbidity) and type (12 different organ systems) of comorbidity. The Clavien–Dindo index was used to evaluate grade and type of complications after treatment.
Results
In univariate analysis gender, comorbidity, stage, mandibulectomy, total laryngectomy, neck dissection, and length of surgery significantly predicted grade of complication. In a multivariate analysis, complication was predicted by age, stage, length of surgery, and various comorbidities. After specification of the complications, age was only a predictor of medical complications; tumor stage was a significant factor in surgical complications. Length of surgery was the only significant variable in all types of complications.
Conclusions
Specific comorbidities are associated with specific complications; however, age itself seems not to be a contraindication for major head and neck surgery. With careful preoperative assessment and risk analysis, physicians can better individualize treatment recommendations.
Journal Article
Low-Cost, Distributed Environmental Monitors for Factory Worker Health
An integrated network of environmental monitors was developed to continuously measure several airborne hazards in a manufacturing facility. The monitors integrated low-cost sensors to measure particulate matter, carbon monoxide, ozone and nitrogen dioxide, noise, temperature and humidity. The monitors were developed and tested in situ for three months in several overlapping deployments, before a full cohort of 40 was deployed in a heavy vehicle manufacturing facility for a year of data collection. The monitors collect data from each sensor and report them to a central database every 5 min. The work includes an experimental validation of the particle, gas and noise monitors. The R2 for the particle sensor ranges between 0.98 and 0.99 for particle mass densities up to 300 μg/m3. The R2 for the carbon monoxide sensor is 0.99 for concentrations up to 15 ppm. The R2 for the oxidizing gas sensor is 0.98 over the sensitive range from 20 to 180 ppb. The noise monitor is precise within 1% between 65 and 95 dBA. This work demonstrates the capability of distributed monitoring as a means to examine exposure variability in both space and time, building an important preliminary step towards a new approach for workplace hazard monitoring.
Journal Article
An orally available, brain penetrant, small molecule lowers huntingtin levels by enhancing pseudoexon inclusion
Huntington’s Disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the huntingtin (
HTT
) gene. The mutant HTT (mHTT) protein causes neuronal dysfunction, causing progressive motor, cognitive and behavioral abnormalities. Current treatments for HD only alleviate symptoms, but cerebral spinal fluid (CSF) or central nervous system (CNS) delivery of antisense oligonucleotides (ASOs) or virus vectors expressing RNA-induced silencing (RNAi) moieties designed to induce mHTT mRNA lowering have progressed to clinical trials. Here, we present an alternative disease modifying therapy the orally available, brain penetrant small molecule branaplam. By promoting inclusion of a pseudoexon in the primary transcript, branaplam lowers mHTT protein levels in HD patient cells, in an HD mouse model and in blood samples from Spinal Muscular Atrophy (SMA) Type I patients dosed orally for SMA (NCT02268552). Our work paves the way for evaluating branaplam’s utility as an HD therapy, leveraging small molecule splicing modulators to reduce expression of dominant disease genes by driving pseudoexon inclusion.
Huntington’s disease (HD) results from the abnormal expansion of CAG repeats in exon 1 of the HTT gene. Here, the authors show that orally available, brain penetrant molecule branaplam lowers HTT transcript by promoting inclusion of a poison exon or pseudoexon.
Journal Article
Chemical Characterization of Outdoor and Subway Fine (PM2.5–1.0) and Coarse (PM10–2.5) Particulate Matter in Seoul (Korea) by Computer-Controlled Scanning Electron Microscopy (CCSEM)
Outdoor and indoor (subway) samples were collected by passive sampling in urban Seoul (Korea) and analyzed with computer-controlled scanning electron microscopy coupled with energy dispersive x-ray spectroscopy (CCSEM-EDX). Soil/road dust particles accounted for 42%–60% (by weight) of fine particulate matter larger than 1 µm (PM2.5–1.0) in outdoor samples and 18% of PM2.5–1.0 in subway samples. Iron-containing particles accounted for only 3%–6% in outdoor samples but 69% in subway samples. Qualitatively similar results were found for coarse particulate matter (PM10–2.5) with soil/road dust particles dominating outdoor samples (66%–83%) and iron-containing particles contributing most to subway PM10–2.5 (44%). As expected, soil/road dust particles comprised a greater mass fraction of PM10–2.5 than PM2.5–1.0. Also as expected, the mass fraction of iron-containing particles was substantially less in PM10–2.5 than in PM2.5–1.0. Results of this study are consistent with known emission sources in the area and with previous studies, which showed high concentrations of iron-containing particles in the subway compared to outdoor sites. Thus, passive sampling with CCSEM-EDX offers an inexpensive means to assess PM2.5–1.0 and PM10-2.5 simultaneously and by composition at multiple locations.
Journal Article
Would government compensation of living kidney donors exploit the poor? An empirical analysis
Government compensation of kidney donors would likely increase the supply of kidneys and prevent the premature deaths of tens of thousands of patients with kidney failure each year. The major argument against it is that it would exploit the poor who would be more likely to accept the offers of compensation. This overlooks the fact that many poor patients desperately need a kidney transplant and would greatly benefit from an increased supply of kidneys. The objective of this study is to empirically test the hypothesis that government compensation of kidney donors would exploit the poor. Exploitation is defined by economists and several noted ethicists as paying donors less than the fair market value of their kidney. Exploitation is expressed in monetary terms and compared with the economic benefit recipients receive from a transplant. Data are from the Scientific Registry of Transplant Recipients and the United States Renal Data System annual data reports. Educational attainment is used as a proxy for income. We estimate that if the government rewards living donors with a package of non-cash benefits worth $75,000 per kidney, donors would not be exploited. Much more important, this compensation would likely end the kidney shortage, enabling many more patients with kidney failure to obtain transplants and live longer and healthier lives. The value of kidney transplantation to a U.S. recipient is about $1,330,000, which is an order of magnitude greater than any purported exploitation of a living donor (zero to $75,000). Consequently, the aggregate net benefit to the poor alone from kidney transplantation would increase to about $12 billion per year from $1 billion per year currently. Most of the benefit would accrue to poor kidney recipients. But poor donors would receive the fair market value of their kidney, and hence would not be exploited. If the government wanted to ensure that donors also received a net benefit, it could easily do so by increasing the compensation above $75,000 per donor.
Journal Article
Metabolic and Hormonal Changes After Laparoscopic Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: a Randomized, Prospective Trial
Background
The mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood.
Methods
In this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)).
Results
In both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels (
p
< 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations (
p
< 0.012 vs. LRYGB).
Conclusions
Bypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms.
Journal Article