Descriptive summary of fatal work-related injuries, Western States, 2011-2017.

Work-related deaths are a persistent occupational health issue that can be prevented. However, prevention opportunities can be hampered by a lack of adequate public health resources. The Western States Occupational Network (WestON) is a network of federal, state, and local occupational health professionals that includes a 19-state region of the United States. To encourage public health collaboration, WestON partners examined work-related fatalities within the region. Fatality counts (numerators) were obtained from the U.S. Bureau of Labor Statistics (BLS) Census of Fatal Occupational Injuries restricted-access research files for all workers ages ≥15 years and fatally injured in WestON states from 2011 through 2017. Estimates of full-time equivalent hours worked (FTE) (denominators) were retrieved from the BLS Current Population Survey. Annual average fatality rates were calculated as number of fatalities per 100,000 FTE over the study period. Rates were stratified by state, select demographics, industry sector, and event/exposure types. Pearson chi-squared tests and rate ratios with 95% confidence probability limits were used to assess rate differences. All analyses were conducted using SAS v.9.4. From 2011 through 2017, the annual average overall occupational fatality rate for the WestON region was 3.5 fatalities per 100,000 FTE, comparable to the overall U.S. fatality rate. Male workers had a fatality rate almost 10 times higher than female workers in the region. Fatality rates increased with successive age groups. Alaska and New Mexico had significantly higher fatality rates for all racial/ethnic groups compared to respective regional rates. Wyoming, North Dakota, and Montana had the three highest occupational fatality rates among foreign-born workers. Agriculture/forestry/fishing, mining/oil/gas extraction, and transportation/warehousing/utilities were industry sector groups with the three highest fatality rates regionally. Transportation-related incidents were the most frequent event type associated with occupational fatalities for all 19 states. Work-related fatalities are a crosscutting occupational public health priority. This analysis can be an impetus for collaborative multistate initiatives among a dynamic and varied occupational public health network to better meet the needs of a rapidly changing workforce.

Characteristics and Outcomes of Contacts of COVID-19 Patients Monitored Using an Automated Symptom Monitoring Tool - Maine, May-June 2020.

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is spread from person to person (1-3). Quarantine of exposed persons (contacts) for 14 days following their exposure reduces transmission (4-7). Contact tracing provides an opportunity to identify contacts, inform them of quarantine recommendations, and monitor their symptoms to promptly identify secondary COVID-19 cases (7,8). On March 12, 2020, Maine Center for Disease Control and Prevention (Maine CDC) identified the first case of COVID-19 in the state. Because of resource constraints, including staffing, Maine CDC could not consistently monitor contacts, and automated technological solutions for monitoring contacts were explored. On May 14, 2020, Maine CDC began enrolling contacts of patients with reported COVID-19 into Sara Alert (MITRE Corporation, 2020),* an automated, web-based, symptom monitoring tool. After initial communication with Maine CDC staff members, enrolled contacts automatically received daily symptom questionnaires via their choice of e-mailed weblink, text message, texted weblink, or telephone call until completion of their quarantine. Epidemiologic investigations were conducted for enrollees who reported symptoms or received a positive SARS-CoV-2 test result. During May 14-June 26, Maine CDC enrolled 1,622 contacts of 614 COVID-19 patients; 190 (11.7%) eventually developed COVID-19, highlighting the importance of identifying, quarantining, and monitoring contacts of COVID-19 patients to limit spread. In Maine, symptom monitoring was not feasible without the use of an automated symptom monitoring tool. Using a tool that permitted enrollees to specify a method of symptom monitoring was well received, because the majority of persons monitored (96.4%) agreed to report using this system.

Investigation of the Interaction between Cdc42 and Its Effector TOCA1: HANDOVER OF Cdc42 TO THE ACTIN REGULATOR N-WASP IS FACILITATED BY DIFFERENTIAL BINDING AFFINITIES.

Transducer of Cdc42-dependent actin assembly protein 1 (TOCA1) is an effector of the Rho family small G protein Cdc42. It contains a membrane-deforming F-BAR domain as well as a Src homology 3 (SH3) domain and a G protein-binding homology region 1 (HR1) domain. TOCA1 binding to Cdc42 leads to actin rearrangements, which are thought to be involved in processes such as endocytosis, filopodia formation, and cell migration. We have solved the structure of the HR1 domain of TOCA1, providing the first structural data for this protein. We have found that the TOCA1 HR1, like the closely related CIP4 HR1, has interesting structural features that are not observed in other HR1 domains. We have also investigated the binding of the TOCA HR1 domain to Cdc42 and the potential ternary complex between Cdc42 and the G protein-binding regions of TOCA1 and a member of the Wiskott-Aldrich syndrome protein family, N-WASP. TOCA1 binds Cdc42 with micromolar affinity, in contrast to the nanomolar affinity of the N-WASP G protein-binding region for Cdc42. NMR experiments show that the Cdc42-binding domain from N-WASP is able to displace TOCA1 HR1 from Cdc42, whereas the N-WASP domain but not the TOCA1 HR1 domain inhibits actin polymerization. This suggests that TOCA1 binding to Cdc42 is an early step in the Cdc42-dependent pathways that govern actin dynamics, and the differential binding affinities of the effectors facilitate a handover from TOCA1 to N-WASP, which can then drive recruitment of the actin-modifying machinery.

Increased Gonorrhea Cases - Utah, 2009-2014.

Gonorrhea (caused by infection with Neisseria gonorrhoeae) is the second most commonly reported notifiable disease in the United States (1). Left untreated, gonorrhea is associated with serious long-term adverse health effects, including pelvic inflammatory disease, ectopic pregnancy, and infertility. Infection also facilitates transmission of human immunodeficiency virus (2,3). Effective gonorrhea control relies upon early detection and effective antimicrobial treatment. To assess gonorrhea rate trends in Utah, the Utah Department of Health (UDOH) analyzed Utah National Electronic Disease Surveillance System (UT-NEDSS) data for the state during 2009-2014. After declining during 2009-2011, the statewide gonorrhea rate increased fivefold to 49 cases per 100,000 population in 2014. During 2009-2014, the proportion of cases among women increased from 21% to 39% (decreasing among males from 79% to 61%). Among male patients, the proportion who identified as men who have sex with men (MSM) decreased from 67% to 42%. These demographic changes suggest that increased heterosexual transmission of gonorrhea in Utah might be occurring. Health departments need to work with providers to ensure populations at high risk are being screened and properly treated for gonorrhea. Clinicians need to be aware of increases in the risk for infection among women and non-MSM males when making screening and testing decisions and educate their patients regarding gonorrhea transmission and prevention practices.

Worker health and safety and climate change in the Americas: issues and research needs.

SYNOPSIS This report summarizes and discusses current knowledge on the impact that climate change can have on occupational safety and health (OSH), with a particular focus on the Americas. Worker safety and health issues are presented on topics related to specific stressors (e.g., temperature extremes), climate associated impacts (e.g., ice melt in the Arctic), and a health condition associated with climate change (chronic kidney disease of non-traditional etiology). The article discusses research needs, including hazards, surveillance, and risk assessment activities to better characterize and understand how OSH may be associated with climate change events. Also discussed are the actions that OSH professionals can take to ensure worker health and safety in the face of climate change.

Alcohol-attributable deaths and years of potential life lost--11 States, 2006-2010.

Excessive alcohol consumption, the fourth leading preventable cause of death in the United States, resulted in approximately 88,000 deaths and 2.5 million years of potential life lost (YPLL) annually during 2006-2010 and cost an estimated $223.5 billion in 2006. To estimate state-specific average annual rates of alcohol-attributable deaths (AAD) and YPLL caused by excessive alcohol use, 11 states analyzed 2006-2010 data (the most recent data available) using the CDC Alcohol-Related Disease Impact (ARDI) application. The age-adjusted median AAD rate was 28.5 per 100,000 population (range = 50.9 per 100,000 in New Mexico to 22.4 per 100,000 in Utah). The median YPLL rate was 823 per 100,000 (range = 1,534 YPLL per 100,000 for New Mexico to 634 per 100,000 in Utah). The majority of AAD (median = 70%) and YPLL (median = 82%) were among working-age (20-64 years) adults. Routine monitoring of alcohol-attributable health outcomes, including deaths and YPLL, in states could support the planning and implementation of evidence-based prevention strategies recommended by the Community Preventive Services Task Force to reduce excessive drinking and related harms. Such strategies include increasing the price of alcohol, limiting alcohol outlet density, and holding alcohol retailers liable for harms related to the sale of alcoholic beverages to minors and intoxicated patrons (dram shop liability).

Metabolic Dysregulation and Cancer Risk Program (MeDOC): a transdisciplinary approach to obesity-associated cancers.

With the escalating prevalence of obesity, the association between obesity and cancer is a growing public health concern. Obesity will soon surpass tobacco smoking as the most important preventable cause of cancer. Obesity-driven mechanisms can alter cell functions to induce metabolic changes, chronic inflammation, and insulin resistance that are believed to contribute to cancer risk and development; yet the specific underlying biological mechanisms of obesity-related cancer development are largely unknown. The Metabolic Dysregulation and Cancer Risk Program: a transdisciplinary approach to obesity-associated cancers (MeDOC) is a trans-National Cancer Institute research initiative supported by the Division of Cancer Control and Population Sciences, the Division of Cancer Biology, the Division of Cancer Prevention, and the Center to Reduce Cancer Health Disparities. The overall purpose of the MeDOC Program is to advance our understanding of the underlying mechanisms that connect obesity, metabolic dysregulation, and increased obesity cancer risk as well as identify markers that will enhance cancer risk prediction, improve screening for high-risk individuals, and identify targets for preventive and therapeutic interventions for cancer interception or treatment. This report describes the funded research projects, the Coordinating Center, and the goals of the MeDOC program.

Menopausal hormone therapy and risk of gastrointestinal cancer: nested case-control study within a prospective cohort, and meta-analysis.

Use of menopausal hormone therapy (HT) has been associated with reduced risk of colorectal cancer; evidence for its effect on other gastrointestinal cancers is limited. We conducted a nested case-control study within a UK cohort, and meta-analyses combining our results with those from published studies. Our study included women aged 50+ in the UK General Practice Research Database (GPRD): 1,054 with oesophageal, 750 with gastric and 4,708 with colorectal cancer, and 5 age- and practice-matched controls per case. Relative risks (RRs) and 95% confidence intervals (CIs) for cancer in relation to prospectively-recorded HT prescriptions were estimated by conditional logistic regression. Women prescribed HT had a reduced risk of oesophageal cancer (adjusted RR for 1+ vs. no HT prescriptions, 0.68, 95% CI 0.53-0.88; p = 0.004), gastric cancer (0.75, 0.54-1.05; p = 0.1) and colorectal cancer (0.81, 0.73-0.90; p < 0.001). There were no significant differences in cancer risk by HT type, estimated duration of HT use or between past and current users. In meta-analyses, risks for ever vs. never use of HT were significantly reduced for all three cancers (summary RR for oesophageal cancer, 0.68, 0.55-0.84, p < 0.001; for gastric cancer, 0.78, 0.65-0.94, p = 0.008; for colorectal cancer, 0.84, 0.81-0.88, p < 0.001). In high-income countries, estimated incidence over 5 years of these three cancers combined in women aged 50-64 was 2.9/1,000 in HT users and 3.6/1,000 in never users. The absolute reduction in risk of these cancers in HT users is small compared to the HT-associated increased risk of breast cancer.

Direct visualisation of collateral ventilation in COPD with hyperpolarised gas MRI.

BACKGROUND: Collateral ventilation has been proposed as a mechanism of compensation of respiratory function in obstructive lung diseases but observations of it in vivo are limited. The assessment of collateral ventilation with an imaging technique might help to gain insight into lung physiology and assist the planning of new bronchoscopic techniques for treating emphysema. OBJECTIVE: To obtain images of delayed ventilation that might be related to collateral ventilation over the period of a single breath-hold in patients with chronic obstructive pulmonary disease (COPD). METHODS: Time-resolved breath-hold hyperpolarised (3)He MRI was used to obtain images of the progressive influx of polarised gas into initially non-ventilated defects. RESULTS: A time-series of images showed that (3)He moves into lung regions which were initially non-ventilated. Ventilation defects with delayed filling were observed in 8 of the 10 patients scanned. CONCLUSIONS: A method for direct imaging of delayed ventilation within a single breath-hold has been demonstrated in patients with COPD. Images of what is believed to be collateral ventilation and slow filling of peripheral airspaces due to increased flow resistance are presented. The technique provides 3D whole-lung coverage with sensitivity to regional information, and is non-invasive and non-ionising.

The efficacy and tolerability of two novel H(1)/H(3) receptor antagonists in seasonal allergic rhinitis.

BACKGROUND: A therapeutic role for histamine H(3) receptor antagonism in allergic rhinitis has been proposed and may be complimentary to the well-known benefits of H(1) receptor antagonism. Combined H(1)/H(3) blockade has therefore been investigated as a novel therapeutic approach that may enhance symptom relief, particularly nasal blockage. METHODS: Two novel H(1)/H(3) dual receptor antagonists were investigated in phase I and II safety and efficacy studies. One molecule (GSK1004723) was designed for intranasal administration as a suspension or solution and the other molecule (GSK835726) for oral administration. In phase I and II studies, both molecules were compared with an active control and/or placebo in randomised studies. In phase II studies, efficacy was assessed in an environmental allergen challenge chamber (ECC). Subjects with seasonal allergic rhinitis were exposed to allergen to induce symptoms. Efficacy and safety was measured over 4, 7 and 20-24 h post-dose. The endpoints included total nasal symptom score and nasal blockage. RESULTS: Intranasal suspension of GSK1004723 and oral GSK835726 were well tolerated. Single-dose intranasal suspensions of GSK1004723 (220, 1,100 µg) failed to demonstrate clinically significant attenuation of symptoms of allergic rhinitis induced in the ECC. Single (10, 50, 100 mg) and 3-day repeat (10 mg) dose oral GSK835726 demonstrated clinically significant attenuation of symptoms in the ECC comparable to cetirizine 10 mg. Three-day repeat dosing of the intranasal solution GSK1004723 1,000 µg also demonstrated a statistically significant attenuation of nasal symptoms, but was less than seen with cetirizine and GSK835726 and caused initial nasal discomfort. CONCLUSIONS: Combined H(1)/H(3) antagonism did not show differentiation from H(1) antagonism in reducing total nasal symptom score or nasal blockage.

Analysis of human CYP1A1 and CYP1A2 genes and their shared bidirectional promoter in eight world populations.

The human CYP1A1_CYP1A2 locus comprises the CYP1A1 (5,988 bp) and CYP1A2 (7,759 bp) transcribed regions, oriented head-to-head, sharing a bidirectional promoter of 23,306 bp. The older CYP1A1 gene appears more conserved and responsible for critical life function(s), whereas the younger CYP1A2 gene might have evolved more rapidly due to environmental (dietary) pressures. A population genetics study might confirm this premise. We combined 60 CYP1A1_CYP1A2 SNPs found in the present study (eight New Guinea Highlanders, eight Samoans, four Dogrib, four Teribe, four Pehuenche, and one Caucasian) with those found in a previous study (six West Africans, four Han Chinese, six Germans, four Samoans, and four Dogrib), yielding a total of 106 SNPs in 106 chromosomes. Resequencing of Oceanians plus Amerindians in the present study yielded 21 New World SNPs ( approximately 20%), of which 17 are not previously reported in any SNP database. Various tests revealed selective pressures for both genes and both haploblocks; unfortunately, differences in rates of evolution between the two genes were undetectable. Fay & Wu's H test revealed a "hitchhiking event" centered around four SNPs in the CYP1A1 3'-UTR; a study in silico identified different microRNA-binding patterns in the hitchhiked region, when the mutations were present compared with the mutations absent.

Workers' compensation injury claims of aviation industry worker injuries in Alaska, 2014-2015.

Aviation operations in Alaska often occur in remote locations and during inclement weather. Limited infrastructure and staff in some locations often requires aviation workers to perform tasks outside of their specific job descriptions. Researchers identified workers' compensation claims as a valuable data source to characterise nonfatal injuries among Alaskan aviation workers. Keyword searches of injury claim narrative fields and industry codes were used to identify potentially aviation-related workers' compensation claims during 2014-2015. These claims were manually reviewed to verify whether aviation related and manually coded according to the US Bureau of Labour Statistics' Occupational Injury and Illness Classification System. There were 875 aviation-related injury claims accepted during 2014-2015. Ramp/baggage/cargo agents incurred the most injuries (35%), followed by mechanics/maintenance workers (15%). Among all workers, Overexertion and Bodily Reaction (40%) was most often cited as the injury event, followed by Contact with Objects and Equipment (28%), and Falls, Slips, Trips (22%). Sprains, strains, tears were the most frequent nature of injury (55%). Cargo/freight/luggage was the most frequent source of injury (24%). The 3 most frequently identified injury event types were responsible for over 90% of all injuries, which indicates that preventive interventions should be directed towards tasks rather than occupational groups.

Using Workers' Compensation Claims Data to Describe Nonfatal Injuries among Workers in Alaska.

BACKGROUND: To gain a better understanding of nonfatal injuries in Alaska, underutilized data sources such as workers' compensation claims must be analyzed. The purpose of the current study was to utilize workers' compensation claims data to estimate the risk of nonfatal, work-related injuries among occupations in Alaska, characterize injury patterns, and prioritize future research. METHODS: A dataset with information on all submitted claims during 2014-2015 was provided for analysis. Claims were manually reviewed and coded. For inclusion in this study, claims had to represent incidents that resulted in a nonfatal acute traumatic injury, occurred in Alaska during 2014-2015, and were approved for compensation. RESULTS: Construction workers had the highest number of injuries (2,220), but a rate lower than the overall rate (34 per 1,000 construction workers, compared to 40 per 1,000 workers overall). Fire fighters had the highest rate of injuries on the job, with 162 injuries per 1,000 workers, followed by law enforcement officers with 121 injuries per 1,000 workers. The most common types of injuries across all occupations were sprains/strains/tears, contusions, and lacerations. CONCLUSION: The successful use of Alaska workers' compensation data demonstrates that the information provided in the claims dataset is meaningful for epidemiologic research. The predominance of sprains, strains, and tears among all occupations in Alaska indicates that ergonomic interventions to prevent overexertion are needed. These findings will be used to promote and guide future injury prevention research and interventions.

Factors associated with crewmember survival of commercial fishing vessel sinkings in Alaska.

Occupational fatality surveillance has identified that fishing vessel disasters, such as sinkings and capsizings, continue to contribute to the most deaths among crewmembers in the US fishing industry. When a fishing vessel sinks at sea, crewmembers are at risk of immersion in water and subsequent drowning. This study examined survival factors for crewmembers following cold water immersion after the sinking of decked commercial fishing vessels in Alaskan waters during 2000-2014. Two immersion scenarios were considered separately: immersion for any length of time, and long-term immersion defined as immersion lasting over 30 minutes. Logistic regression was used to predict the odds of crewmember survival. Of the 617 crewmembers onboard 187 fishing vessels that sank in Alaska during 2000-2014, 557 (90.3%) survived and 60 died. For crewmembers immersed for any length of time, the significant adjusted predictors of survival were: entering a life-raft, sinking within three miles of shore, the sinking not being weather-related, and working as a deckhand. For crewmembers immersed for over 30 minutes, the significant adjusted predictors of survival were: wearing an immersion suit, entering a life-raft, working as a deckhand, and the sinking not being weather-related. The results of this analysis demonstrate that in situations where cold water immersion becomes inevitable, having access to well-maintained, serviceable lifesaving equipment and the knowledge and skills to use it properly are critical.

The effect of mammographic screening and hormone replacement therapy use on breast cancer incidence in England and Wales.

DESIGN: An extended age-period-cohort model was used to estimate the effect of mammographic screening and hormone replacement therapy on breast cancer incidence in England and Wales between 1971 and 2001. RESULTS: Incidence of breast cancer increased noticeably in women attending screening for the first time compared with nonattenders [rate ratio (RR), 1.73; 95% confidence interval (95% CI), 1.67-1.80]. Incidence was also 18% to 35% higher in attenders relative to nonattenders in subsequent screening rounds. In the first 3 years after women left the screening program, rates of breast cancer were reduced (RR, 0.88; 95% CI, 0.86-0.90), but by 7 to 9 years after screening, the rates had returned to the expected level (RR, 0.97; 95% CI, 0.94-1.00). The estimated RR of hormone replacement therapy on breast cancer incidence was 1.55 (95% CI, 1.37-1.75). Screening is estimated to increase a woman's lifetime risk of being diagnosed with breast cancer from 7.8% to 8.6%. CONCLUSIONS: It is estimated that in the absence of screening, rates of breast cancer incidence would have continued to increase. A study at the individual subject level would be beneficial to assess the level of overdiagnosis associated with breast cancer screening.

Cdc42 in actin dynamics: An ordered pathway governed by complex equilibria and directional effector handover.

The small GTPase, Cdc42, is a key regulator of actin dynamics, functioning to connect multiple signals to actin polymerization through effector proteins of the Wiskott-Aldrich syndrome protein (WASP) and Transducer of Cdc42-dependent actin assembly (TOCA) families. WASP family members serve to couple Cdc42 with the actin nucleator, the Arp2/3 complex, via direct interactions. The regulation of these proteins in the context of actin dynamics has been extensively studied. Studies on the TOCA family, however, are more limited and relatively little is known about their roles and regulation. In this commentary we highlight new structural and biophysical insight into the involvement of TOCA proteins in the pathway of Cdc42-dependent actin dynamics. We discuss the biological implications of the low affinity interactions between the TOCA family and Cdc42, as well as probing the sequential binding of TOCA1 and the WASP homolog, N-WASP, to Cdc42. We place our current research in the context of the wealth of biophysical, structural and functional data from earlier studies pertaining to the Cdc42/N-WASP/Arp2/3 pathway of actin polymerization. Finally, we describe the molecular basis for a sequential G protein-effector handover from TOCA1 to N-WASP.

Epilepsy in adults with intellectual disabilities: prevalence, associations and service implications.

STATEMENT OF THE PROBLEM: The prevalence of epilepsy in people with an intellectual disability (ID) is apparently higher than in the general population. The outlook for individuals with both epilepsy and ID depends on the presence of any associated conditions. However, there have been few epidemiological studies of the prevalence of epilepsy and associated problems within a representative adult ID population to inform the development of policy. METHOD: This was a population-based prevalence study using the Leicestershire Learning Disability Register. Prevalence was estimated from the number of individuals with reported epilepsy identified from structured home interviews with carers. Associations with epilepsy were investigated for a range of defined physical, mental and skill attributes. Logistic regression was done with and without adjustment for age, sex and level of understanding to identify specific and holistic links respectively. RESULTS: The prevalence of epilepsy was 26%. Among those with epilepsy, 68% experienced seizures despite anti-epileptic medication. Epilepsy showed a significant association with low levels of understanding. Specific morbid associations included wetting (adjusted odds ratio 2.7), soiling (2.2), walking (2.5), daily living skills (1.6), poor speech (2.2), lack of empathy (1.5), mood swings (1.5), being uncooperative (1.6), seeking attention (1.7) and disturbing others at night (1.9). Holistic associations included a wider range of physical and mental problems and global skills deficits. CONCLUSIONS: The high prevalence, associated morbidities and global skills deficits make epilepsy care for adults with ID important and complex. Specialist epilepsy services for this population need a multidisciplinary skills mix.

(1)H, (13)C and (15)N resonance assignments of the Cdc42-binding domain of TOCA1.

TOCA1 is a downstream effector protein of the small GTPase, Cdc42. It is a multi-domain protein that includes a membrane binding F-BAR domain, a homology region 1 (HR1) domain, which binds selectively to active Cdc42 and an SH3 domain. TOCA1 is involved in the regulation of actin dynamics in processes such as endocytosis, filopodia formation, neurite elongation, cell motility and invasion. Structural insight into the interaction between TOCA1 and Cdc42 will contribute to our understanding of the role of TOCA1 in actin dynamics. The (1)H, (15)N and (13)C NMR backbone and sidechain resonance assignment of the HR1 domain (12 kDa) presented here provides the foundation for structural studies of the domain and its interactions.

Live surgery at conferences - Clinical benefits and ethical dilemmas.

Live surgical broadcasts (LSBs) are becoming increasingly popular in urological conferences. These activities can provide excellent training opportunities, as they allow the audience to view an operation conducted by world-renowned surgeons, and have the ability to interact with them in real time. However, several ethical considerations have been raised with this practice, which the participating surgeons and conference organisers must appreciate and address carefully. In this article we highlight the ethical considerations related to LSBs and advise on how these should be addressed. We also present the latest recommendations made by the European Association of Urology Live Surgery Committee and discuss alternatives to LSB.