Bacteria-to-Human Protein Networks Reveal Origins of Endogenous DNA Damage.

DNA damage provokes mutations and cancer and results from external carcinogens or endogenous cellular processes. However, the intrinsic instigators of endogenous DNA damage are poorly understood. Here, we identify proteins that promote endogenous DNA damage when overproduced: the DNA "damage-up" proteins (DDPs). We discover a large network of DDPs in Escherichia coli and deconvolute them into six function clusters, demonstrating DDP mechanisms in three: reactive oxygen increase by transmembrane transporters, chromosome loss by replisome binding, and replication stalling by transcription factors. Their 284 human homologs are over-represented among known cancer drivers, and their RNAs in tumors predict heavy mutagenesis and a poor prognosis. Half of the tested human homologs promote DNA damage and mutation when overproduced in human cells, with DNA damage-elevating mechanisms like those in E. coli. Our work identifies networks of DDPs that provoke endogenous DNA damage and may reveal DNA damage-associated functions of many human known and newly implicated cancer-promoting proteins.

PIK3CA variants selectively initiate brain hyperactivity during gliomagenesis.

Glioblastoma is a universally lethal form of brain cancer that exhibits an array of pathophysiological phenotypes, many of which are mediated by interactions with the neuronal microenvironment1,2. Recent studies have shown that increases in neuronal activity have an important role in the proliferation and progression of glioblastoma3,4. Whether there is reciprocal crosstalk between glioblastoma and neurons remains poorly defined, as the mechanisms that underlie how these tumours remodel the neuronal milieu towards increased activity are unknown. Here, using a native mouse model of glioblastoma, we develop a high-throughput in vivo screening platform and discover several driver variants of PIK3CA. We show that tumours driven by these variants have divergent molecular properties that manifest in selective initiation of brain hyperexcitability and remodelling of the synaptic constituency. Furthermore, secreted members of the glypican (GPC) family are selectively expressed in these tumours, and GPC3 drives gliomagenesis and hyperexcitability. Together, our studies illustrate the importance of functionally interrogating diverse tumour phenotypes driven by individual, yet related, variants and reveal how glioblastoma alters the neuronal microenvironment.

Bioisosteric analogs of MDMA: Improving the pharmacological profile?

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is re-emerging in clinical settings as a candidate for the treatment of specific neuropsychiatric disorders (e.g. post-traumatic stress disorder) in combination with psychotherapy. MDMA is a psychoactive drug, typically regarded as an empathogen or entactogen, which leads to transporter-mediated monoamine release. Despite its therapeutic potential, MDMA can induce dose-, individual-, and context-dependent untoward effects outside safe settings. In this study, we investigated whether three new methylenedioxy bioisosteres of MDMA improve its off-target profile. In vitro methods included radiotracer assays, transporter electrophysiology, bioluminescence resonance energy transfer and fluorescence-based assays, pooled human liver microsome/S9 fraction incubations, metabolic stability studies, isozyme mapping, and liquid chromatography coupled to high-resolution mass spectrometry. In silico methods included molecular docking. Compared with MDMA, all three MDMA bioisosteres (ODMA, TDMA, and SeDMA) showed similar pharmacological activity at human serotonin, dopamine, and norepinephrine transporters (hSERT, hDAT, and hNET, respectively) but decreased agonist activity at 5-HT2A/2B/2C receptors. Regarding their hepatic metabolism, they differed from MDMA, with N-demethylation being the only metabolic route shared, and without forming phase II metabolites. In addition, TDMA showed an enhanced intrinsic clearance in comparison to its congeners. Additional screening for their interaction with human organic cation transporters (hOCTs) and plasma membrane monoamine transporter (hPMAT) revealed a weaker interaction of the MDMA analogs with hOCT1, hOCT2, and hPMAT. Our findings suggest that these new MDMA bioisosteres might constitute appealing therapeutic alternatives to MDMA, sparing the primary pharmacological activity at hSERT, hDAT, and hNET, but displaying a reduced activity at 5-HT2A/2B/2C receptors and alternative hepatic metabolism. Whether these MDMA bioisosteres may pose lower risk alternatives to the clinically re-emerging MDMA warrants further studies.

Risk factors for heat-related illness resulting in death or hospitalization in the oil and gas extraction industry.

Many oil and gas extraction (OGE) activities occur in high-heat environments, resulting in a significant risk of heat-related illness among outdoor workers in this industry. This report highlights cases of occupational heat-related illness that resulted in death and identifies common risk factors for heat-related fatalities and hospitalizations among OGE workers. Two databases maintained by the National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA) were reviewed to identify heat-related fatalities, hospitalizations, and associated risk factors among OGE workers. Nine fatalities and associated risk factors were identified during 2014-2019 from NIOSH's Fatalities in Oil and Gas Extraction (FOG) Database. Risk factors identified included those commonly associated with heat-related fatalities: new workers not acclimatized to heat, inadequate heat stress training, and underlying hypertension or cardiovascular disease. Of particular note, substance use was identified as a significant risk factor as more than half of the fatalities included a positive postmortem test for amphetamines or methamphetamines. Fifty heat-related hospitalizations were identified from OSHA's Severe Injury Report Database during January 2015-May 2021. Heat stress has been and will continue to be an important cause of fatality and adverse health effects in OGE as hot outdoor working conditions become more common and extreme. More emphasis on heat stress training, acclimatization regimens, medical screening, and implementation of workplace-supportive recovery programs may reduce heat-related fatalities and injuries in this industry.

Suicide Rates by Industry and Occupation - National Vital Statistics System, United States, 2021.

The suicide rate among the U.S. working-age population has increased approximately 33% during the last 2 decades. To guide suicide prevention strategies, CDC analyzed suicide deaths by industry and occupation in 49 states, using data from the 2021 National Vital Statistics System. Industry (the business activity of a person's employer or, if self-employed, their own business) and occupation (a person's job or the type of work they do) are distinct ways to categorize employment. The overall suicide rates by sex in the civilian noninstitutionalized working population were 32.0 per 100,000 among males and 8.0 per 100,000 among females. Major industry groups with the highest suicide rates included Mining (males = 72.0); Construction (males = 56.0; females = 10.4); Other Services (e.g., automotive repair; males = 50.6; females = 10.4); Arts, Entertainment, and Recreation (males = 47.9; females = 15.0); and Agriculture, Forestry, Fishing, and Hunting (males = 47.9). Major occupation groups with the highest suicide rates included Construction and Extraction (males = 65.6; females = 25.3); Farming, Fishing, and Forestry (e.g., agricultural workers; males = 49.9); Personal Care and Service (males = 47.1; females = 15.9); Installation, Maintenance, and Repair (males = 46.0; females = 26.6); and Arts, Design, Entertainment, Sports, and Media (males = 44.5; females = 14.1). By integrating recommended programs, practices, and training into existing policies, workplaces can be important settings for suicide prevention. CDC provides evidence-based suicide prevention strategies in its Suicide Prevention Resource for Action and Critical Steps Your Workplace Can Take Today to Prevent Suicide, NIOSH Science Blog.

Health conditions among male workers in mining and other industries reliant on manual labor occupations: National Health Interview Survey, 2007-2018.

INTRODUCTION: Mining is an industry with diverse, demanding occupational exposures. Understanding the prevalence of chronic health conditions in working miners is an area of active research. Of particular interest is how the health of miners compares to that of workers in other industry sectors with a high proportion of manual labor occupations. By comparing similar industries, we can learn what health conditions may be associated with manual labor and with individual industries. This study analyzes the prevalence of health conditions in miners compared to workers employed in other manual-labor-reliant industries. METHODS: National Health Interview Survey public data were analyzed for the years 2007-2018. Mining and five other industry groups with a high proportion of manual labor occupations were identified. Female workers were excluded because of small sample sizes. The prevalence of chronic health outcomes was calculated for each industry group and compared to that of nonmanual labor industries. RESULTS: Currently-working male miners showed increased prevalence of hypertension (in those age <55 years), hearing loss, lower back pain, leg pain progressing from lower back pain, and joint pain, compared to nonmanual labor industries workers. Construction workers also demonstrated a high prevalence of pain. CONCLUSION: Miners demonstrated increased prevalence of several health conditions, even when compared to other manual labor industries. Given previous research on chronic pain and opioid misuse, the high pain prevalence found among miners suggests mining employers should reduce work factors that cause injury while also providing an environment where workers can address pain management and substance use.

Self-reported exposure to hazards and mitigation strategies among oil and gas extraction workers in three U.S. states.

Numerous health and safety hazards exist at U.S. onshore oil and gas extraction worksites. Higher fatal injury rates have been reported among drilling and servicing companies, which are more likely to employ workers in construction and extraction occupations, compared to operators that employ more workers in management and office and administrative support roles. However, there is little information describing the extent to which workers encounter these hazards, are provided hazard mitigation strategies by their employers, or use personal protective equipment (PPE). A cross-sectional survey of 472 U.S. oil and gas extraction workers was conducted to identify and characterize factors related to on-the-job fatalities, injuries, and illnesses and determine workers' health and safety concerns. Workers were employed by servicing companies (271/472, 57.4%), drilling contractors (106/472, 22.5%), and operators (95/472, 20.1%). The likelihood of contact with hazardous substances varied by substance and company type. Drilling and servicing employees had significantly higher odds of self-reported contact with pipe dope (ORdrilling = 10.07, 95% CI: 1.74-63.64; ORservicing = 5.95, 95% CI: 2.18-18.34), diesel exhaust (ORdrilling = 2.28, 95% CI: 1.15-5.05; ORservicing = 4.93, 95% CI: 2.73-10.32), and drilling mud (ORdrilling = 24.36, 95% CI: 4.45-144.69; ORservicing = 3.48, 95% CI: 1.24-12.20), compared to operators. Safety policies, programs, and trainings were commonly reported by workers, although substance-specific training (e.g., respirable crystalline silica hazards) was less common. Differences in self-reported employer PPE requirements and worker use of PPE when needed or required for safety highlight a need for novel strategies to improve the use of PPE. Overall, this study highlights differences in work conditions by company type and uncovers gaps in employer administrative controls and PPE use.

A Governance Framework to Integrate Longitudinal Clinical and Community Data in a Distributed Data Network: The Childhood Obesity Data Initiative.

CONTEXT: Integrating longitudinal data from community-based organizations (eg, physical activity programs) with electronic health record information can improve capacity for childhood obesity research. OBJECTIVE: A governance framework that protects individual privacy, accommodates organizational data stewardship requirements, and complies with laws and regulations was developed and implemented to support the harmonization of data from disparate clinical and community information systems. PARTICIPANTS AND SETTING: Through the Childhood Obesity Data Initiative (CODI), 5 Colorado-based organizations collaborated to expand an existing distributed health data network (DHDN) to include community-generated data and assemble longitudinal patient records for research. DESIGN: A governance work group expanded an existing DHDN governance infrastructure with CODI-specific data use and exchange policies and procedures that were codified in a governance plan and a delegated-authority, multiparty, reciprocal agreement. RESULTS: A CODI governance work group met from January 2019 to March 2020 to conceive an approach, develop documentation, and coordinate activities. Governance requirements were synthesized from the CODI use case, and a customized governance approach was constructed to address governance gaps in record linkage, a procedure to request data, and harmonizing community and clinical data. A Master Sharing and Use Agreement (MSUA) and Memorandum of Understanding were drafted and executed to support creation of linked longitudinal records of clinical- and community-derived childhood obesity data. Furthermore, a multiparty infrastructure protocol was approved by the local institutional review board (IRB) to expedite future CODI research by simplifying IRB research applications. CONCLUSION: CODI implemented a clinical-community governance strategy that built trust between organizations and allowed efficient data exchange within a DHDN. A thorough discovery process allowed CODI stakeholders to assess governance capacity and reveal regulatory and organizational obstacles so that the governance infrastructure could effectively leverage existing knowledge and address challenges. The MSUA and complementary governance documents can inform similar efforts.

The Childhood Obesity Data Initiative: A Case Study in Implementing Clinical-Community Infrastructure Enhancements to Support Health Services Research and Public Health.

CONTEXT: We describe a participatory framework that enhanced and implemented innovative changes to an existing distributed health data network (DHDN) infrastructure to support linkage across sectors and systems. Our processes and lessons learned provide a potential framework for other multidisciplinary infrastructure development projects that engage in a participatory decision-making process. PROGRAM: The Childhood Obesity Data Initiative (CODI) provides a potential framework for local and national stakeholders with public health, clinical, health services research, community intervention, and information technology expertise to collaboratively develop a DHDN infrastructure that enhances data capacity for patient-centered outcomes research and public health surveillance. CODI utilizes a participatory approach to guide decision making among clinical and community partners. IMPLEMENTATION: CODI's multidisciplinary group of public health and clinical scientists and information technology experts collectively defined key components of CODI's infrastructure and selected and enhanced existing tools and data models. We conducted a pilot implementation with 3 health care systems and 2 community partners in the greater Denver Metro Area during 2018-2020. EVALUATION: We developed an evaluation plan based primarily on the Good Evaluation Practice in Health Informatics guideline. An independent third party implemented the evaluation plan for the CODI development phase by conducting interviews to identify lessons learned from the participatory decision-making processes. DISCUSSION: We demonstrate the feasibility of rapid innovation based upon an iterative and collaborative process and existing infrastructure. Collaborative engagement of stakeholders early and iteratively was critical to ensure a common understanding of the research and project objectives, current state of technological capacity, intended use, and the desired future state of CODI architecture. Integration of community partners' data with clinical data may require the use of a trusted third party's infrastructure. Lessons learned from our process may help others develop or improve similar DHDNs.

COVID-19 as an occupational disease.

The impact of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 permeates all aspects of society worldwide. Initial medical reports and media coverage have increased awareness of the risk imposed on healthcare workers in particular, during this pandemic. However, the health implications of COVID-19 for the global workforce are multifaceted and complex, warranting careful reflection and consideration to mitigate the adverse effects on workers worldwide. Accordingly, our review offers a framework for considering this topic, highlighting key issues, with the aim to prompt and inform action, including research, to minimize the occupational hazards imposed by this ongoing challenge. We address respiratory disease as a primary concern, while recognizing the multisystem spectrum of COVID-19-related disease and how clinical aspects are interwoven with broader socioeconomic forces.

Literature-based automated discovery of tumor suppressor p53 phosphorylation and inhibition by NEK2.

Scientific progress depends on formulating testable hypotheses informed by the literature. In many domains, however, this model is strained because the number of research papers exceeds human readability. Here, we developed computational assistance to analyze the biomedical literature by reading PubMed abstracts to suggest new hypotheses. The approach was tested experimentally on the tumor suppressor p53 by ranking its most likely kinases, based on all available abstracts. Many of the best-ranked kinases were found to bind and phosphorylate p53 (P value = 0.005), suggesting six likely p53 kinases so far. One of these, NEK2, was studied in detail. A known mitosis promoter, NEK2 was shown to phosphorylate p53 at Ser315 in vitro and in vivo and to functionally inhibit p53. These bona fide validations of text-based predictions of p53 phosphorylation, and the discovery of an inhibitory p53 kinase of pharmaceutical interest, suggest that automated reasoning using a large body of literature can generate valuable molecular hypotheses and has the potential to accelerate scientific discovery.

Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers.

RNA editing, a widespread post-transcriptional mechanism, has emerged as a new player in cancer biology. Recent studies have reported key roles for individual miRNA editing events, but a comprehensive picture of miRNA editing in human cancers remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of 8595 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified 19 adenosine-to-inosine (A-to-I) RNA editing hotspots. We independently validated 15 of them by perturbation experiments in several cancer cell lines. These miRNA editing events show extensive correlations with key clinical variables (e.g., tumor subtype, disease stage, and patient survival time) and other molecular drivers. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to the pattern observed for the wild-type miR-200b expression. We further experimentally showed that, in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets, including LIFR, a well-characterized metastasis suppressor. Our study highlights the importance of miRNA editing in gene regulation and suggests its potential as a biomarker for cancer prognosis and therapy.

Estimating the prevalence of congenital heart disease among adolescents and adults in Colorado adjusted for incomplete case ascertainment.

BACKGROUND: Congenital heart defects (CHDs), the most common type of birth defect in the United States, are increasing in prevalence in the general population. Though CHD prevalence at birth has been well described in the United States at about 1%, little is known about long-term survival and prevalence of CHDs beyond childhood. This study aimed to estimate the prevalence of CHDs among adolescents and adults in Colorado. METHODS: The prevalence of CHDs among adolescents and adults residing in Colorado during 2011 to 2013 was estimated using log-linear capture-recapture methods to account for incomplete case ascertainment. Five case-finding data sources were used for this analysis including electronic health record data from 4 major health systems and a state-legislated all payer claims database. RESULTS: Twelve thousand two hundred ninety-three unique individuals with CHDs (2481 adolescents and 9812 adults) were identified in one or more primary data sources. We estimated the crude prevalence of CHDs in adolescents and adults in Colorado to be 3.22 per 1000 individuals (95% CI 3.19-3.53). After accounting for incomplete case ascertainment, the final capture-recapture model yielded an estimated total adolescent and adult CHD population of 23,194 (95% CI 22,419-23,565) and an adjusted prevalence of 6.07 per 1000 individuals (95% CI 5.86-6.16), indicating 47% of the cases in the catchment area were not identified in the case-identifying data sources. CONCLUSION: This statewide study yielded new information on the prevalence of CHDs in adolescents and adults. These high prevalence rates underscore the need for additional specialized care facilities for this population with CHDs.

Disproportionate Incidence of COVID-19 Infection, Hospitalizations, and Deaths Among Persons Identifying as Hispanic or Latino - Denver, Colorado March-October 2020.

Persons identifying as Hispanic or Latino (Hispanic) represent the second largest racial/ethnic group in the United States (1), yet understanding of the impact of coronavirus disease 2019 (COVID-19) in this population is limited. To evaluate COVID-19 health disparities in the community and inform public health, health system, and community-based interventions, local public health authorities analyzed the sociodemographic characteristics of persons who were diagnosed, hospitalized, and who died with COVID-19 in Denver, Colorado. During the first 7 months of the COVID-19 epidemic in Denver (March 6-October 6, 2020) the majority of adult COVID-19 cases (54.8%), hospitalizations (62.1%), and deaths (51.2%) were among persons identifying as Hispanic, more than double the proportion of Hispanic adults in the Denver community (24.9%) (1). Systemic drivers that influence how Hispanic persons live and work increase their exposure risks: compared with non-Hispanic persons, Hispanic persons with COVID-19 in Denver reported larger household sizes and were more likely to report known exposures to household and close contacts with COVID-19, working in an essential industry, and working while ill. Reducing the disproportionate incidence of COVID-19 morbidity and mortality among Hispanic persons will require implementation of strategies that address upstream social and environmental factors that contribute to an increased risk for both infection and transmission and that facilitate improved access to culturally congruent care.

The Detection of Opioid Misuse and Heroin Use From Paramedic Response Documentation: Machine Learning for Improved Surveillance.

BACKGROUND: Timely, precise, and localized surveillance of nonfatal events is needed to improve response and prevention of opioid-related problems in an evolving opioid crisis in the United States. Records of naloxone administration found in prehospital emergency medical services (EMS) data have helped estimate opioid overdose incidence, including nonhospital, field-treated cases. However, as naloxone is often used by EMS personnel in unconsciousness of unknown cause, attributing naloxone administration to opioid misuse and heroin use (OM) may misclassify events. Better methods are needed to identify OM. OBJECTIVE: This study aimed to develop and test a natural language processing method that would improve identification of potential OM from paramedic documentation. METHODS: First, we searched Denver Health paramedic trip reports from August 2017 to April 2018 for keywords naloxone, heroin, and both combined, and we reviewed narratives of identified reports to determine whether they constituted true cases of OM. Then, we used this human classification as reference standard and trained 4 machine learning models (random forest, k-nearest neighbors, support vector machines, and L1-regularized logistic regression). We selected the algorithm that produced the highest area under the receiver operating curve (AUC) for model assessment. Finally, we compared positive predictive value (PPV) of the highest performing machine learning algorithm with PPV of searches of keywords naloxone, heroin, and combination of both in the binary classification of OM in unseen September 2018 data. RESULTS: In total, 54,359 trip reports were filed from August 2017 to April 2018. Approximately 1.09% (594/54,359) indicated naloxone administration. Among trip reports with reviewer agreement regarding OM in the narrative, 57.6% (292/516) were considered to include information revealing OM. Approximately 1.63% (884/54,359) of all trip reports mentioned heroin in the narrative. Among trip reports with reviewer agreement, 95.5% (784/821) were considered to include information revealing OM. Combined results accounted for 2.39% (1298/54,359) of trip reports. Among trip reports with reviewer agreement, 77.79% (907/1166) were considered to include information consistent with OM. The reference standard used to train and test machine learning models included details of 1166 trip reports. L1-regularized logistic regression was the highest performing algorithm (AUC=0.94; 95% CI 0.91-0.97) in identifying OM. Tested on 5983 unseen reports from September 2018, the keyword naloxone inaccurately identified and underestimated probable OM trip report cases (63 cases; PPV=0.68). The keyword heroin yielded more cases with improved performance (129 cases; PPV=0.99). Combined keyword and L1-regularized logistic regression classifier further improved performance (146 cases; PPV=0.99). CONCLUSIONS: A machine learning application enhanced the effectiveness of finding OM among documented paramedic field responses. This approach to refining OM surveillance may lead to improved first-responder and public health responses toward prevention of overdoses and other opioid-related problems in US communities.

Analyzing Somatic Genome Rearrangements in Human Cancers by Using Whole-Exome Sequencing.

Although exome sequencing data are generated primarily to detect single-nucleotide variants and indels, they can also be used to identify a subset of genomic rearrangements whose breakpoints are located in or near exons. Using >4,600 tumor and normal pairs across 15 cancer types, we identified over 9,000 high confidence somatic rearrangements, including a large number of gene fusions. We find that the 5' fusion partners of functional fusions are often housekeeping genes, whereas the 3' fusion partners are enriched in tyrosine kinases. We establish the oncogenic potential of ROR1-DNAJC6 and CEP85L-ROS1 fusions by showing that they can promote cell proliferation in vitro and tumor formation in vivo. Furthermore, we found that ∼4% of the samples have massively rearranged chromosomes, many of which are associated with upregulation of oncogenes such as ERBB2 and TERT. Although the sensitivity of detecting structural alterations from exomes is considerably lower than that from whole genomes, this approach will be fruitful for the multitude of exomes that have been and will be generated, both in cancer and in other diseases.

Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma.

When it escapes early detection, malignant melanoma becomes a highly lethal and treatment-refractory cancer. Melastatin is greatly downregulated in metastatic melanomas and is widely believed to function as a melanoma tumor suppressor. Here we report that tumor suppressive activity is not mediated by melastatin but instead by a microRNA (miR-211) hosted within an intron of melastatin. Increasing expression of miR-211 but not melastatin reduced migration and invasion of malignant and highly invasive human melanomas characterized by low levels of melastatin and miR-211. An unbiased network analysis of melanoma-expressed genes filtered for their roles in metastasis identified three central node genes: IGF2R, TGFBR2, and NFAT5. Expression of these genes was reduced by miR-211, and knockdown of each gene phenocopied the effects of increased miR-211 on melanoma invasiveness. These data implicate miR-211 as a suppressor of melanoma invasion whose expression is silenced or selected against via suppression of the entire melastatin locus during human melanoma progression.

Assessment of tobacco heating product THP1.0. Part 2: Product design, operation and thermophysical characterisation.

A novel tobacco heating product, THP1.0, that heats tobacco below 245 °C is described. It was designed to eliminate tobacco combustion, while heating tobacco to release nicotine, tobacco volatiles and glycerol to form its aerosol. The stewardship assessment approach behind the THP 1.0 design was based on established toxicological principles. Thermophysical studies were conducted to examine the extent of tobacco thermal conversion during operation. Thermogravimetric analysis of the tobacco material revealed the major thermal behaviour in air and nitrogen up to 900 °C. This, combined with the heating temperature profiling of the heater and tobacco rod, verified that the tobacco was not subject to combustion. The levels of tobacco combustion markers (CO, CO2, NO and NOx) in the aerosol of THP1.0 were significantly lower than the levels if there were any significant pyrolysis or combustion. Quantification of other tobacco thermal decomposition and evaporative transfer markers showed that these levels were, on average, reduced by more than 90% in THP1.0 aerosol as compared with cigarette smoke. The physical integrity of the tobacco consumable rod showed no ashing. Taken together, these data establish that the aerosol generated by THP1.0 is produced mainly by evaporation and distillation, and not by combustion or pyrolysis.

Early labor force exit subsequent to permanently impairing occupational injury or illness among workers 50-64 years of age.

BACKGROUND: Severity of workplace injury tends to increase with age. Whether older workers who experience a workplace injury or illness exit the labor force sooner than comparable peers is not established. METHODS: A case-cohort study design and complementary log-log model were used to identify factors associated with average time to early substantial labor force exit among workers' compensation claimants 50-64 years of age with permanent impairment from an occupational injury or illness. Analysis was based on Ontario's workers' compensation claimant data from 1998 to 2006 linked with Canadian tax files. RESULTS: Workers with permanent impairment left the labor force earlier, on average, than peers without claims. Early retirement was associated with older age in the injury/illness year, greater impairment, lower pre-claim income, physically demanding jobs, and soft-tissue injuries. CONCLUSIONS: Policies aiming to extend older adults' working lives should account for the potentially disparate impacts on older workers of occupational injury and illness.

Same-level fall injuries in US workplaces by age group, gender, and industry.

BACKGROUND: As the workforce ages, occupational injuries from falls on the same level will increase. Some industries may be more affected than others. METHODS: We conducted a cross-sectional study using data from the Bureau of Labor Statistics to estimate same-level fall injury incidence rates by age group, gender, and industry for four sectors: 1) healthcare and social assistance; 2) manufacturing; 3) retail; and 4) transportation and warehousing. We calculated rate ratios and rate differences by age group and gender. RESULTS: Same-level fall injury incidence rates increase with age in all four sectors. However, patterns of rate ratios and rate differences vary by age group, gender, and industry. Younger workers, men, and manufacturing workers generally have lower rates. CONCLUSIONS: Variation in incidence rates suggests there are unrealized opportunities to prevent same-level fall injuries. Interventions should be evaluated for their effectiveness at reducing injuries, avoiding gender- or age-discrimination and improving work ability.