Heat shock protein paradigms in cancer progression: future therapeutic perspectives.

Heat-shock proteins (HSPs), also known as stress proteins, are ubiquitously present in all forms of life. They play pivotal roles in protein folding and unfolding, the formation of multiprotein complexes, the transportation and sorting of proteins into their designated subcellular compartments, the regulation of the cell cycle, and signalling processes. These HSPs encompass HSP27, HSP40, HSP70, HSP60, and HSP90, each contributing to various cellular functions. In the context of cancer, HSPs exert influence by either inhibiting or activating diverse signalling pathways, thereby impacting growth, differentiation, and cell division. This article offers an extensive exploration of the functions of HSPs within the realms of pharmacology and cancer biology. HSPs are believed to play substantial roles in the mechanisms underlying the initiation and progression of cancer. They hold promise as valuable clinical markers for cancer diagnosis, potential targets for therapeutic interventions, and indicators of disease progression. In times of cellular stress, HSPs function as molecular chaperones, safeguarding the structural and functional integrity of proteins and aiding in their proper folding. Moreover, HSPs play a crucial role in cancer growth, by regulating processes such as angiogenesis, cell proliferation, migration, invasion, and metastasis.

Temporal population genetic structure of Phormia regina (Diptera: Calliphoridae).

The genetic structure of forensically important blow fly (Brauer & Bergenstamm) (Diptera: Calliphoridae) populations has remained elusive despite high relatedness within wild-caught samples. This research aimed to determine if the implementation of a high-resolution spatiotemporal sampling design would reveal latent genetic structure among blow fly populations and to elucidate any environmental impacts on observed patterns of genetic structure. Adult females of the black blow fly, Phormia regina (Meigen) (Diptera: Calliphoridae), were collected from 9 urban parks in Indiana, USA over 3 yr and genotyped at 6 polymorphic microsatellite loci. The data analysis involved 3 clustering methods: principal coordinate analysis (PCoA), discriminant analysis of principal components (DAPC), and STRUCTURE. While the PCoA did not uncover any discernible clustering patterns, the DAPC and STRUCTURE analyses yielded significant results, with 9 and 4 genetic clusters, respectively. Visualization of the STRUCTURE bar plot revealed N = 11 temporal demarcations indicating barriers to gene flow. An analysis of molecular variance of these STRUCTURE-inferred populations supported strong temporally driven genetic differentiation (FST = 0.048, F'ST = 0.664) relative to geographic differentiation (FST = 0.009, F'ST = 0.241). Integrated Nested Laplace Approximation and Boosted Regression Tree analyses revealed that collection timepoint and 4 main abiotic factors (temperature, humidity, precipitation, and wind speed) were associated with the genetic subdivisions observed for P. regina. A complex interplay between environmental conditions, the unique reproductive strategies of the blow fly, and the extensive dispersal abilities of these organisms likely drives the strong genetic structure of P. regina in the Midwestern US.

Escalating costs of self-injury mortality in the 21st century United States: an interstate observational study.

BACKGROUND: Estimating the economic costs of self-injury mortality (SIM) can inform health planning and clinical and public health interventions, serve as a basis for their evaluation, and provide the foundation for broadly disseminating evidence-based policies and practices. SIM is operationalized as a composite of all registered suicides at any age, and 80% of drug overdose (intoxication) deaths medicolegally classified as 'accidents,' and 90% of corresponding undetermined (intent) deaths in the age group 15 years and older. It is the long-term practice of the United States (US) Centers for Disease Control and Prevention (CDC) to subsume poisoning (drug and nondrug) deaths under the injury rubric. This study aimed to estimate magnitude and change in SIM and suicide costs in 2019 dollars for the United States (US), including the 50 states and the District of Columbia. METHODS: Cost estimates were generated from underlying cause-of-death data for 1999/2000 and 2018/2019 from the US Centers for Disease Control and Prevention's (CDC's) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Estimation utilized the updated version of Medical and Work Loss Cost Estimation Methods for CDC's Web-based Injury Statistics Query and Reporting System (WISQARS). Exposures were medical expenditures, lost work productivity, and future quality of life loss. Main outcome measures were disaggregated, annual-averaged total and per capita costs of SIM and suicide for the nation and states in 1999/2000 and 2018/2019. RESULTS: 40,834 annual-averaged self-injury deaths in 1999/2000 and 101,325 in 2018/2019 were identified. Estimated national costs of SIM rose by 143% from $0.46 trillion to $1.12 trillion. Ratios of quality of life and work losses to medical spending in 2019 US dollars in 2018/2019 were 1,476 and 526, respectively, versus 1,419 and 526 in 1999/2000. Total national suicide costs increased 58%-from $318.6 billion to $502.7 billion. National per capita costs of SIM doubled from $1,638 to $3,413 over the observation period; costs of the suicide component rose from $1,137 to $1,534. States in the top quintile for per capita SIM, those whose cost increases exceeded 152%, concentrated in the Great Lakes, Southeast, Mideast and New England. States in the bottom quintile, those with per capita cost increases below 70%, were located in the Far West, Southwest, Plains, and Rocky Mountain regions. West Virginia exhibited the largest increase at 263% and Nevada the smallest at 22%. Percentage per capita cost increases for suicide were smaller than for SIM. Only the Far West, Southwest and Mideast were not represented in the top quintile, which comprised states with increases of 50% or greater. The bottom quintile comprised states with per capita suicide cost increases below 24%. Regions represented were the Far West, Southeast, Mideast and New England. North Dakota and Nevada occupied the extremes on the cost change continuum at 75% and - 1%, respectively. CONCLUSION: The scale and surge in the economic costs of SIM to society are large. Federal and state prevention and intervention programs should be financed with a clear understanding of the total costs-fiscal, social, and personal-incurred by deaths due to self-injurious behaviors.

Association of State Social and Environmental Factors With Rates of Self-injury Mortality and Suicide in the United States.

Importance: Self-injury mortality (SIM) combines suicides and the preponderance of drug misuse-related overdose fatalities. Identifying social and environmental factors associated with SIM and suicide may inform etiologic understanding and intervention design. Objective: To identify factors associated with interstate SIM and suicide rate variation and to assess potential for differential suicide misclassification. Design, Setting, and Participants: This cross-sectional study used a partial panel time series with underlying cause-of-death data from 50 US states and the District of Columbia for 1999-2000, 2007-2008, 2013-2014 and 2018-2019. Applying data from the Centers for Disease Control and Prevention, SIM includes all suicides and the preponderance of unintentional and undetermined drug intoxication deaths, reflecting self-harm behaviors. Data were analyzed from February to June 2021. Exposures: Exposures included inequity, isolation, demographic characteristics, injury mechanism, health care access, and medicolegal death investigation system type. Main Outcomes and Measures: The main outcome, SIM, was assessed using unstandardized regression coefficients of interstate variation associations, identified by the least absolute shrinkage and selection operator; ratios of crude SIM to suicide rates per 100 000 population were assessed for potential differential suicide misclassification. Results: A total of 101 325 SIMs were identified, including 74 506 (73.5%) among males and 26 819 (26.5%) among females. SIM to suicide rate ratios trended upwards, with an accelerating increase in overdose fatalities classified as unintentional or undetermined (SIM to suicide rate ratio, 1999-2000: 1.39; 95% CI, 1.38-1.41; 2018-2019: 2.12; 95% CI, 2.11-2.14). Eight states recorded a SIM to suicide rate ratio less than 1.50 in 2018-2019 vs 39 states in 1999-2000. Northeastern states concentrated in the highest category (range, 2.10-6.00); only the West remained unrepresented. Least absolute shrinkage and selection operator identified 8 factors associated with the SIM rate in 2018-2019: centralized medical examiner system (ß = 4.362), labor underutilization rate (ß = 0.728), manufacturing employment (ß = -0.056), homelessness rate (ß = -0.125), percentage nonreligious (ß = 0.041), non-Hispanic White race and ethnicity (ß = 0.087), prescribed opioids for 30 days or more (ß = 0.117), and percentage without health insurance (ß = -0.013) and 5 factors associated with the suicide rate: percentage male (ß = 1.046), military veteran (ß = 0.747), rural (ß = 0.031), firearm ownership (ß = 0.030), and pain reliever misuse (ß = 1.131). Conclusions and Relevance: These findings suggest that SIM rates were associated with modifiable, upstream factors. Although embedded in SIM, suicide unexpectedly deviated in proposed social and environmental determinants. Heterogeneity in medicolegal death investigation processes and data assurance needs further characterization, with the goal of providing the highest-quality reports for developing and tracking public health policies and practices.

Comparison of broadband and monochromatic photopic negative response in eyes of patients with diabetes with no diabetic retinopathy and different stages of diabetic retinopathy.

PURPOSE: To evaluate the change in broadband (W/W), red on blue (R/B), and blue on yellow (B/Y) photopic negative response (PhNR) in patients with diabetes mellitus with no diabetic retinopathy (no DR) and different stages of DR and compare it with age-matched controls. This study was performed to provide a single PhNR protocol that can be used for early diagnosis of DR. METHODS: It was a cross-sectional case-control study done in a hospital setup. Patients with diabetes with no DR and different stages of DR with no other associated ocular pathologies were included. Age-matched controls with no retinal pathologies were also included for comparison. All subjects underwent detailed ophthalmic examination and W/W, R/B, and B/Y electroretinography. Fifty control eyes and 52 treatment naïve eyes of 52 patients with diabetes [no DR = 11, mild nonproliferative diabetic retinopathy (NPDR) =11, moderate NPDR = 10, severe NPDR = 9, and proliferative DR = 11] were included in the study. RESULTS: On comparing the ERG responses in patients with diabetes and age-matched controls, a significant reduction (P < 0.05) was noted in the amplitudes of a-wave (39.78 ± 11.34 µV vs. 67.28 ± 12.88 µV), b-wave (116.25 ± 45.25 vs. 134.39 ± 28.78 µV), W/W PhNR (33.86 ± 17.33 vs. 67.18 ± 15.99 µV), R/B PhNR (28.77 ± 15.85 vs. 53.48 ± 14.15 µV), and B/Y PhNR (55.04 ± 32.63 vs. 104.79 ± 24.37 µV). Post hoc analysis revealed that all the eyes in the diabetic group, including those with no DR, had a significantly reduced PhNR amplitude (P < 0.05) when compared with controls. PhNR was found to reduce in amplitude with increasing severity of DR (P < 0.05), with more significance in B/Y. Receiver operating characteristic showed highest area under the curve in B/Y PhNR (94%, P < 0.001), with maximum sensitivity and specificity of 88% and 87%, respectively. CONCLUSION: Changes in the amplitude and implicit time of ERG can reflect the severity of DR. PhNR amplitudes, especially B/Y PhNR, appear to be significantly reduced even in eyes with no DR.

Fatal self-injury in the United States, 1999-2018: Unmasking a national mental health crisis.

BACKGROUND: Suicides by any method, plus 'nonsuicide' fatalities from drug self-intoxication (estimated from selected forensically undetermined and 'accidental' deaths), together represent self-injury mortality (SIM)-fatalities due to mental disorders or distress. SIM is especially important to examine given frequent undercounting of suicides amongst drug overdose deaths. We report suicide and SIM trends in the United States of America (US) during 1999-2018, portray interstate rate trends, and examine spatiotemporal (spacetime) diffusion or spread of the drug self-intoxication component of SIM, with attention to potential for differential suicide misclassification. METHODS: For this state-based, cross-sectional, panel time series, we used de-identified manner and underlying cause-of-death data for the 50 states and District of Columbia (DC) from CDC's Wide-ranging Online Data for Epidemiologic Research. Procedures comprised joinpoint regression to describe national trends; Spearman's rank-order correlation coefficient to assess interstate SIM and suicide rate congruence; and spacetime hierarchical modelling of the 'nonsuicide' SIM component. FINDINGS: The national annual average percentage change over the observation period in the SIM rate was 4.3% (95% CI: 3.3%, 5.4%; p<0.001) versus 1.8% (95% CI: 1.6%, 2.0%; p<0.001) for the suicide rate. By 2017/2018, all states except Nebraska (19.9) posted a SIM rate of at least 21.0 deaths per 100,000 population-the floor of the rate range for the top 5 ranking states in 1999/2000. The rank-order correlation coefficient for SIM and suicide rates was 0.82 (p<0.001) in 1999/2000 versus 0.34 (p = 0.02) by 2017/2018. Seven states in the West posted a ≥ 5.0% reduction in their standardised mortality ratios of 'nonsuicide' drug fatalities, relative to the national ratio, and 6 states from the other 3 major regions a >6.0% increase (p<0.05). INTERPRETATION: Depiction of rising SIM trends across states and major regions unmasks a burgeoning national mental health crisis. Geographic variation is plausibly a partial product of local heterogeneity in toxic drug availability and the quality of medicolegal death investigations. Like COVID-19, the nation will only be able to prevent SIM by responding with collective, comprehensive, systemic approaches. Injury surveillance and prevention, mental health, and societal well-being are poorly served by the continuing segregation of substance use disorders from other mental disorders in clinical medicine and public health practice. FUNDING: This study was partially funded by the National Centre for Injury Prevention and Control, US Centers for Disease Control and Prevention (R49CE002093) and the US National Institute on Drug Abuse (1UM1DA049412-01; 1R21DA046521-01A1).

Impacts of confounding roadway characteristics on estimates of associations between alcohol outlet densities and alcohol-related motor vehicle crashes.

INTRODUCTION AND AIMS: Previous research on alcohol-related motor vehicle crashes (AMVC) share a substantial limitation: sources of geographic variations in background crash risks may confound estimated spatial relationships between alcohol outlets and AMVCs. The aim of this study was to address this concern by examining, spatial-temporally, relationships between alcohol outlets and AMVCs adjusting for a set of six roadway characteristics that may be, independently, related to crash risks. While most similar studies focus on one metropolitan area, we use a unique sample of 50 cities. DESIGN AND METHODS: The spatial sample for this study consisted of 8726 Census 2000 block groups representing 50 mid-sized California cities. Dependent measures were counts of crashes located within Census block groups. Independent measures included socio-demographics, social disadvantage, alcohol outlets and roadway characteristics. We assessed relationships of crashes to independent measures using hierarchical generalised linear models. RESULTS: Greater roadway length, greater percentage of highways, greater average speeds, fewer T-intersections, greater curviness and less fragmentation were related to greater numbers of crashes as was alcohol outlet density. DISCUSSION: Above and beyond alcohol outlet type and density, we found that roadway characteristics were related to AMVC risks across a sample of 50 mid-sized cities. Measures of roadway characteristics are an essential component of any model of motor vehicle crashes that attempts to assess impacts of alcohol outlets on motor vehicle crashes risks.

Clinical and electrophysiological characteristics of Efavirenz-induced macular toxicity.

Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, is commonly used to treat HIV-infected individuals. We report a case of painless, progressive and bilateral blurring of vision in an HIV-positive 54-year-old lady within months of treatment with anti-retro viral therapy including Efavirenz. On presentation, her visual acuity was 6/18; N24 and 6/9; N10 in both eyes with mottling of the retinal pigment epithelial at the macula with corresponding scotomas on HVF 30-2 and loss of ellipsoid layer on spectral domain optical coherence topography (OCT). Though full field ERG was normal, multifocal ERG revealed reduced foveal and parafoveal amplitudes. Our case emphasizes the need of periodic ocular examination of these patients on long-term EFV.

Female Blow Flies As Vertebrate Resource Indicators.

Rapid vertebrate diversity evaluation is invaluable for monitoring changing ecosystems worldwide. Wild blow flies naturally recover DNA and chemical signatures from animal carcasses and feces. We demonstrate the power of blow flies as biodiversity monitors through sampling of flies in three environments with varying human influences: Indianapolis, IN and two national parks (the Great Smoky Mountains and Yellowstone). Dissected fly guts underwent vertebrate DNA sequencing (12S and 16S rRNA genes) and fecal metabolite screening. Integrated Nested Laplace Approximation (INLA) was used to determine the most important abiotic factor influencing fly-derived vertebrate richness. In 720 min total sampling time, 28 vertebrate species were identified, with 42% of flies containing vertebrate resources: 23% DNA, 5% feces, and 14% contained both. The species of blow fly used was not important for vertebrate DNA recovery, however the use of female flies versus male flies directly influenced DNA detection. Temperature was statistically relevant across environments in maximizing vertebrate detection (mean = 0.098, sd = 0.048). This method will empower ecologists to test vertebrate community ecology theories previously out of reach due practical challenges associated with traditional sampling.

Enhanced S-cone syndrome: Clinical spectrum in Indian population.

PURPOSE: Enhanced S-cone syndrome (ESCS), a rare disorder, is often misdiagnosed as other forms of retinal degenerations, which have a poorer prognosis than ESCS. The aim of this study is to report the varied clinical features of ESCS and distinguish it from other similar disorders. METHODS: We retrospectively scrutinized the records of patients with confirmed diagnosis of ESCS and analyzed the findings. RESULTS: We included 14 patients (age range 4-39 years) who were confirmed to have ESCS according to pathognomonic electroretinography (ERG) showing reduced photopic, combined responses, and 30 Hz flicker with reduced L, M cone responses and supernormal S cone responses. The disease presented in the 1st decade with night blindness and was almost stationary or minimally progressive. Mid-peripheral fundus changes in form of nummular pigmentary alterations, yellow punctate lesions, and macular schisis were noted. The vision ranged from 6/6 to 6/36 with follow-up ranging from 1month to 22 years. CONCLUSION: ESCS shows varied clinical features ranging from unremarkable fundus to pigment clumping and atrophic lesions. It has good prognosis with patients mostly maintaining their vision. ERG is diagnostic. More awareness and knowledge about this entity can help to differentiate it from other forms of night blindness.

Comparison between broadband and monochromatic photopic negative response in full-field electroretinogram in controls and subjects with primary open-angle glaucoma.

PURPOSE: A prospective, cross-sectional, case-control study was conducted to investigate the role of broadband and monochromatic photopic negative response (PhNR) of the full-field flash electroretinogram (ERG) in the evaluation of ganglion cell damage in primary open-angle glaucoma (POAG) subjects. METHODS: Subjects with POAG and age-matched normal subjects were recruited from the outpatient department of a tertiary eye care center in South India. A total of 25 patients with POAG and 50 age-matched normal subjects were recruited. ERG was recorded using broadband (3.5 cd.s/m2 white stimulus on 10 cd/m2 white background) and monochromatic (3.5 cd.s/m2 red stimulus on 10 cd/m2 blue background and 1 cd.s/m2 blue stimulus on 10 cd/m2 yellow background) stimuli. RESULTS: The reduction in PhNR amplitude in POAG compared to normal individuals was higher in red-on-blue PhNR [26.37 µV; p < 0.001, confidence interval (CI) 19.34 to 33.4] as compared to broadband stimuli (16.41 µV; p < 0.001, CI 8.68 to 24.13), and blue on yellow (21.96 µV; p < 0.001, CI 10.12 to 33.8). Red-on-blue PhNR amplitudes correlated better with mean deviation (MD; r = - 0.66, p < 0.05), pattern standard deviation (PSD; r = - 0.4, p = 0.04), visual field index (VFI; r = - 0.58, p < 0.05), and retinal nerve fiber layer thickness (r = - 0.67, p < 0.05) in comparison with broadband and monochromatic blue-on-yellow PhNR. Receiver operating characteristic curve revealed largest area under the curve (0.89) in red-on-blue PhNR compared to broadband (0.76) and blue on yellow (0.74). The sensitivity and specificity was also higher in red-on-blue PhNR (72% and 80%, respectively) as compared to the other stimuli (sensitivity and specificity of broadband 0.68 and 0.7, blue on yellow 0.64 and 0.7, respectively). CONCLUSION: Correlation of PhNR with Humphrey visual field parameters and retinal nerve fiber layer thickness showed that red-on-blue PhNR can be a useful additional tool for clinical assessment of retinal ganglion cell dysfunction in glaucoma patients. Red-on-blue PhNR was more sensitive as compared to white-on-white and blue-on-yellow PhNR in identifying ganglion cell dysfunction and correlates well with other structural and functional tests for glaucoma such as MD, PSD, VFI, and RNFL thickness.

Aqueous misdirection in thyroid eye disease.

Secondary glaucoma in thyroid eye disease (TED) is attributed either to raised episcleral venous pressure or to mechanical compression induced trabecular meshwork damage by mucopolysaccharide deposition. While the mechanism for raised intraocular pressure (IOP) in TED is largely mechanical and is often evident during its active stage, our case presented with aqueous misdirection in the left eye during the inactive stage. Appropriate diagnostic tests should be ordered to diagnose cause of raised IOP, which would help determine appropriate treatment for the cause for secondary glaucoma in TED.

The iatrogenic epidemic of prescription drug abuse: county-level determinants of opioid availability and abuse.

BACKGROUND: Opioid use and abuse in the United States continues to expand at an alarming rate. In this study, we examine the county-level determinants of the availability and abuse of prescription opioids to better understand the socio-ecological context, and in particular the role of the healthcare delivery system, on the prescription drug abuse epidemic. METHODS: We use community-level information, data from Indiana's prescription drug monitoring program in 2011, and geospatial regression methods to identify county-level correlates of the availability and abuse of prescription opioids among Indiana's 92 counties. RESULTS: The findings suggest that access to healthcare generally, and to dentists and pharmacists in particular, increases the availability of prescription opioids in communities, which, in turn, is associated with higher rates of opioid abuse. CONCLUSIONS: The results suggest that the structure of the local healthcare system is a major determinant of community-level access to opioids adding to a growing body of evidence that the problem of prescription opioid abuse is, at least in part, an "iatrogenic epidemic."

Assessing the built environment using omnidirectional imagery.

Observational audits commonly are used in public health research to collect data on built environment characteristics that affect health-related behaviors and outcomes, including physical activity and weight status. However, implementing in-person field audits can be expensive if observations are needed over large or geographically dispersed areas or at multiple points in time. A reliable and more efficient method for observational audits could facilitate extendibility (i.e., expanded geographic and temporal scope) and lead to more standardized assessment that strengthens the ability to compare results across different regions and studies. The purpose of the current study was to evaluate the degree of agreement between field audits and audits derived from interpretation of three types of omnidirectional imagery. Street segments from St. Louis MO and Indianapolis IN were stratified geographically to ensure representation of neighborhoods with different socioeconomic characteristics in both cities. Audits were conducted in 2008 and 2009 using four methods: field audits, and interpretation of archived imagery, new imagery, and Google Street View™ imagery. Agreement between field audits and image-based audits was assessed using observed agreement and the prevalence-adjusted bias-adjusted kappa statistic (PABAK). Data analysis was conducted in 2010. When measuring the agreement between field audits and audits from the different sources of imagery, the mean PABAK statistic for all items on the instrument was 0.78 (archived); 0.80 (new); and 0.81 (Street View imagery), indicating substantial to nearly perfect agreement among methods. It was determined that image-based audits represent a reliable method that can be used in place of field audits to measure several key characteristics of the built environment important to public health research.

Drinking patterns and myocardial infarction: a linear dose-response model.

BACKGROUND: The relation of alcohol intake to cardiovascular health is complex, involving both protective and harmful effects, depending on the amount and pattern of consumption. Interpretation of data available on the nature of these relations is limited by lack of well-specified, mathematical models relating drinking patterns to alcohol-related consequences. Here we present such a model and apply it to data on myocardial infarction (MI). METHODS: The dose-response model derived assumes: (1) each instance of alcohol use has an effect that either increases or decreases the likelihood of an alcohol-related consequence, and (2) greater quantities of alcohol consumed on any drinking day add linearly to these increases or decreases in risk. Risk was reduced algebraically to a function of drinking frequency and dosage (volume minus frequency, a measure of the extent to which drinkers have more than 1 drink on days when they drink). In addition to estimating the joint impact of frequency and dosage, the model provides a method for calculating the point at which risk related to alcohol consumption is equal to background risk from other causes. A bootstrapped logistic regression based on the dose-response model was conducted using data from a case-control study to obtain the predicted probability of MI associated with current drinking patterns, controlling for covariates. RESULTS: MI risk decreased with increasing frequency of drinking, but increased as drinking dosage increased. Rates of increasing MI risk associated with drinking dosage were twice as high among women as they were among men. Relative to controls, lower MI risk was associated with consuming < 4.55 drinks per drinking day for men (95% CI: 2.77 to 7.18) and < 3.08 drinks per drinking day for women (95% CI: 1.35 to 5.16), increasing after these cross-over points were exceeded. CONCLUSIONS: Use of a well-specified mathematical dose-response model provided precise estimates for the first time of how drinking frequency and dosage each contribute linearly to the overall impact of a given drinking pattern on MI risk in men and women.

The spatial distribution of underage tobacco sales in Los Angeles.

OBJECTIVE: Underage tobacco sales is considered a serious public health problem in Los Angeles. Anecdotally, rates have been thought to be quite high. In this paper, using spatial statistical techniques, we describe underage tobacco sales, identifying areas with high levels of sales and hot spots controlling for sociodemographic measures. METHODS: Six hundred eighty-nine tobacco outlets were investigated throughout the city of Los Angeles in 2001. We consider the factors that explain vendor location of illegal sales of tobacco to underage youth and focus on those areas with especially high rates of illegal sales when controlling for other independent measures. Using data from the census, the LA City Attorney's Office, and public records on school locations in Los Angeles, we employ general least-squares (GLS) estimators in order to avoid biased estimates. MAIN OUTCOME MEASURE: vendor location of underage tobacco compliance checks, violators, and nonviolators. RESULTS: Underage tobacco sales in Los Angeles were very high (33.5%) for the entire city in 2001. In many zip codes this rate is considerably higher (60%-100%). When conducting spatial modeling, lower income and ethnicity were strongly associated with increases in underage tobacco sales. Hotspot areas of underage tobacco sales also had much lower mean family income and a much higher percentage of foreign born and greater population density. CONCLUSIONS: Spatial techniques were used to better identify areas where vendors sell tobacco to underage youth. Lower income areas were much more likely to both have higher rates of underage tobacco sales and to be a hot spot for such sales. Population density is also significantly associated with underage tobacco sales. The study's limitations are noted.

Occupational correlates of smoking among urban transit operators: a prospective study.

BACKGROUND: Workers in blue-collar and service occupations smoke at higher rates than workers in white-collar and professional occupations. Occupational stress may explain some of the occupational class differences in smoking and quitting behavior. The purpose of this study is to investigate the contribution of occupational factors to smoking behavior over a ten year period among a multiethnic cohort of urban transit operators, while accounting for demographic factors and alcohol. METHODS: The sample consists of 654 San Francisco Municipal Railway (MUNI) transit operators who participated in two occupational health studies and biennial medical examinations during 1983-85 and 1993-95. Workers who had initiated, increased, or maintained their smoking over the ten year period were compared to workers who remained non-smokers. Occupational factors included self-rated frequency of job problems (e.g., difficulties with equipment, passengers, traffic), job burnout (i.e., the emotional exhaustion subscale of the Maslach Burnout Inventory), time needed to unwind after work, and years employed as a transit operator. A series of logistic regression models were developed to estimate the contribution of occupational factors to smoking behavior over time. RESULTS: Approximately 35% of the workers increased, initiated, or maintained their smoking over the ten-year period. Frequency of job problems was significantly associated with likelihood of smoking increase, initiation, or maintenance (OR = 1.30; 95% CI 1.09, 1.55). Black operators were significantly more likely to have smoked over the ten-year period compared to operators in other racial/ethnic groups. CONCLUSION: Understanding the role of work-related stress vis-à-vis smoking behavior is of critical importance for crafting workplace smoking prevention and cessation interventions that are applicable to blue-collar work settings, and for developing policies that mitigate occupational stress.

Temporal changes in the spatial pattern of disease rates incorporating known risk factors.

Examining the geographical pattern of temporal changes in infant mortality rates illustrates the methodological problems of documenting and understanding temporal changes in any spatial pattern of disease. Early research on geographical differences in infant mortality rates showed strong ecological correlations with socio-economic factors such as poverty rates. More recent research established relationships between individual-level socio-economic values and probabilities of death. With geographic information available at the level of individuals, it is possible to estimate the probabilities of death on a person-by-person basis from knowledge of the relationships between individual factors and socio-economic measures. These estimated probabilities provide an expected geographic pattern of deaths. The difference between the observed spatial pattern and the expected pattern is the remaining spatial variation adjusted for this knowledge. For the study area, individual factors and some socio-economic measures were available for each year of the study period. Using data from the Iowa Birth Defects Registry and the Iowa Department of Public Health (USA), I tested the stability and continuity of these cross-sectional relationships and investigated whether any temporal lags in these variables relate to the unexplained spatial variations in infant mortality rates that remain. I accounted for the 'Change of Support Problem' [Gotway C. A. & Young L. J. (2002). Combining incompatible spatial data. Journal of the American Statistical Association, 97458, 632-648] inherent in frame-based geographical analysis. The analysis involved a generalized linear model (GLM) to estimate individual risks and a Monte Carlo simulation model to generate the non-linear probability density functions for disease rates whose densities are theoretically intractable. Results show the temporal changes in the observed spatial pattern and the expected spatial pattern differ by geographic location. In conclusion such differences are the result of a combination of unexplained place-based risk and unmeasured individual risks.