Cumulative All-Cause Mortality in Diverse Hispanic/Latino Adults : A Prospective, Multicenter Cohort Study.

BACKGROUND: All-cause mortality among diverse Hispanic/Latino groups in the United States and factors underlying mortality differences have not been examined prospectively. OBJECTIVE: To describe cumulative all-cause mortality (and factors underlying differences) by Hispanic/Latino background, before and during the COVID-19 pandemic. DESIGN: Prospective, multicenter cohort study. SETTING: Hispanic Community Health Study/Study of Latinos. PARTICIPANTS: 15 568 adults aged 18 to 74 years at baseline (2008 to 2011) of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other backgrounds from the Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California. MEASUREMENTS: Sociodemographic, acculturation-related, lifestyle, and clinical factors were assessed at baseline, and vital status was ascertained through December 2021 (969 deaths; 173 444 person-years of follow-up). Marginally adjusted cumulative all-cause mortality risks (11-year before the pandemic and 2-year during the pandemic) were examined using progressively adjusted Cox regression. RESULTS: Before the pandemic, 11-year cumulative mortality risks adjusted for age and sex were higher in the Puerto Rican and Cuban groups (6.3% [95% CI, 5.2% to 7.6%] and 5.7% [CI, 5.0% to 6.6%], respectively) and lowest in the South American group (2.4% [CI, 1.7% to 3.5%]). Differences were attenuated with adjustment for lifestyle and clinical factors. During the pandemic, 2-year cumulative mortality risks adjusted for age and sex ranged from 1.1% (CI, 0.6% to 2.0%; South American) to 2.0% (CI, 1.4% to 3.0%; Central American); CIs overlapped across groups. With adjustment for lifestyle factors, 2-year cumulative mortality risks were highest in persons of Central American and Mexican backgrounds and lowest among those of Puerto Rican and Cuban backgrounds. LIMITATION: Lack of data on race and baseline citizenship status; correlation between Hispanic/Latino background and site. CONCLUSION: Differences in prepandemic mortality risks across Hispanic/Latino groups were explained by lifestyle and clinical factors. Mortality patterns changed during the pandemic, with higher risks in persons of Central American and Mexican backgrounds than in those of Puerto Rican and Cuban backgrounds. PRIMARY FUNDING SOURCE: National Institutes of Health.

Significant Changes in Resting Metabolic Rate Over a Competitive Match Week Are Accompanied by an Absence of Nutritional Periodization in Male Professional Soccer Players.

Resting metabolic rate (RMR) is an important component of total daily energy expenditure; however, it is currently not understood how it varies across a typical competitive match week in professional soccer players. For the first time, we aimed to assess RMR throughout an in-season competitive week in professional soccer players. Additionally, we aimed to assess energy and carbohydrate intake across the same week. Twenty-four professional soccer players from an English Premier League club (age: 18 ± 1.6 years) completed the study. RMR was assessed each morning of a typical competitive match week (match day [MD] -3, -2, -1, +1, +2, and + 3), and dietary intake (including MD) was assessed daily via the remote food photography method and 24-hr recall. Daily training load was quantified using Global Positioning System, daily muscle soreness ratings were recorded, and body composition was assessed via dual-energy X-ray absorptiometry. There was a significant (p = .0004) increase in mean RMR of ∼261 kcal/day on MD + 1, compared with MD - 1. Additionally, volume of oxygen consumed significantly increased at MD + 1 (p = .0002) versus MD - 1. There were no significant differences in daily energy or carbohydrate intake across the competitive week (p > .05), with inadequate carbohydrate intakes on MD - 1 (∼3.9 g/kg body mass), MD (∼4.2 g/kg body mass), and MD + 1 (∼3.6 g/kg body mass) in relation to current recommendations. We report, for the first time, that RMR is significantly increased following a competitive match in professional soccer players. In addition, we confirm previous findings to reinforce that players exhibit inadequate nutrition periodization practices, which may impair physical performance and recovery.

Risk factors associated with occupational noise-induced hearing loss in the Hispanic community health study/study of Latinos: A cross-sectional epidemiologic investigation.

The purpose of this study was to estimate the prevalence of occupational noise exposure and risk factors of occupational noise-induced hearing loss (NIHL) in Hispanic/Latino adults included in the baseline wave of the Hispanic Community Health Study/Study of Latinos collected from 2008 to 2011. Sequential multiple linear regression modeled the relationship between occupational NIHL (defined as a 3-, 4-, 6-kHz pure-tone average [PTA]) and occupation type, self-reported noise exposure, cardiovascular disease (CVD) risk score, and hearing protective device (HPD) use. The final model controlled for sex, age, and recreational noise exposure. Among 12,851 included participants, approximately 40% (n = 5036) reported occupational noise exposure "Sometimes" (up to 50% of the time) or "Frequently" (75-100% of the time). In the final fitted model, longest-held occupation and CVD risk were associated with poorer hearing. Specifically, those in non-skilled, service, skilled, and military/police/other job categories had between 2.07- and 3.29-dB worse PTA than professional/office workers. Additionally, a shift in the CVD risk score category from low to medium was associated with a 2.25- and 8.20-dB worse PTA for medium and high CVD risk, respectively. Age and sex were also significantly associated with poorer hearing, such that men presented with 6.08 dB worse PTA than women, and for every one-year increase in age, PTA increased by 0.62 dB (ps < .001). No interactions were seen between noise*sometimes or frequent exposure to other ototoxic agents and PTA (ps = .33 & .92, respectively). The prevalence of occupational noise exposure was high in this cross-sectional investigation of adults from Hispanic/Latino backgrounds. Findings contribute to the extant literature by demonstrating that risk factors for occupational NIHL in adults from varying Hispanic/Latino backgrounds are consistent with those of other previously studied groups.

A comparative analysis of histologic types of thyroid cancer between career firefighters and other occupational groups in Florida.

BACKGROUND: Florida Firefighters experience a higher risk of thyroid cancer than non-firefighters. This study examines whether the histologic types and tumor stage of thyroid cancer is different among firefighters compared to other occupational groups. METHODS: Eligible cases were firefighters (n = 120) identified in a linkage of Florida Cancer Data System (FCDS) registry records (1981-2014) and Florida State Fire Marshal's Office employment and certification records, and non-firefighters classified into: blue-collar (n = 655), service (n = 834), white-collar (n = 4,893), and other (n = 1,789). Differences in thyroid histologic type (papillary, follicular, and rare/other less common forms of thyroid cancer), tumor stage, and age at diagnosis were evaluated using multinomial logistic regression models comparing blue-collar, service, white-collar, and other occupational groups with firefighters. Univariate odds ratios as well as odds ratios adjusted for age, gender, race, tumor stage, and year of diagnosis (aOR) and 95% confidence intervals (95%CI) were reported. RESULTS: Service (aOR = 4.12; 95%CI: 1.25-13.65), white-collar (aOR = 3.51; 95%CI: 1.08-11.36), and blue-collar (aOR = 4.59; 95%CI: 1.40-15.07) workers had significantly higher odds of being diagnosed with rare histologic types of thyroid cancer vs papillary type compared to firefighters. Service (aOR = 0.42; 95%CI: 0.27-0.66), white-collar (aOR = 0.39; 95%CI: 0.26-0.59), blue-collar (aOR = 0.36; 95%CI: 0.23-0.56), and other (aOR = 0.34; 95%CI: 0.22-0.53) occupational groups have a significantly lower odds of being diagnosed with rare vs papillary type at a younger age (30-49 years) vs 50-69 years compared to firefighters. However, stage at diagnosis was not significantly different among occupational groups. CONCLUSION: Firefighters diagnosed with thyroid cancer experience a higher odds of papillary compared to rare histologic types of thyroid cancer relative to other workers; there is no evidence of an increased odds of late-stage diagnosis in firefighters relative to other worker groups. Firefighters may benefit from routine screening and active surveillance of suspected thyroid tumors especially given the excellent treatment outcomes available for those diagnosed with early-stage papillary thyroid tumors.

Profiles and predictors of healthcare utilization: using a cluster-analytic approach to identify typical users across conventional, allied and complementary medicine, and self-care.

INTRODUCTION: The identification of typologies of health care users and their specific characteristics can be performed using cluster analysis. This statistical approach aggregates similar users based on their common health-related behavior. This study aims to examine health care utilization patterns using cluster analysis; and the associations of health care user types with sociodemographic, health-related and health-system related factors. METHODS: Cross-sectional data from the 2012 National Health Interview Survey were used. Health care utilization was measured by consultations with a variety of medical, allied and complementary health practitioners or the use of several interventions (exercise, diet, supplementation etc.) within the past 12 months (used vs. not used). A model-based clustering approach based on finite normal mixture modelling, and several indices of cluster fit were determined. Health care utilization within the cluster was analyzed descriptively, and independent predictors of belonging to the respective clusters were analyzed using logistic regression models including sociodemographic, health- and health insurance-related factors. RESULTS: Nine distinct health care user types were identified, ranging from nearly non-use of health care modalities to over-utilization of medical, allied and complementary health care. Several sociodemographic and health-related characteristics were predictive of belonging to the respective health care user types, including age, gender, health status, education, income, ethnicity, and health care coverage. CONCLUSIONS: Cluster analysis can be used to identify typical health care utilization patterns based on empirical data; and those typologies are related to a variety of sociodemographic and health-related characteristics. These findings on individual differences regarding health care access and utilization can inform future health care research and policy regarding how to improve accessibility of different medical approaches.

Yap/Taz are required for establishing the cerebellar radial glia scaffold and proper foliation.

Yap/Taz are well-established downstream effectors of the Hippo pathway, known to regulate organ size by directing proliferation and apoptosis. Although the functions of Yap/Taz have been extensively studied, little is known about their role in brain development. Here, through genetic ablation, we show that Yap/Taz are required for cerebellar morphogenesis. Yap/Taz deletion in neural progenitors causes defects in secondary fissure formation, leading to abnormal folia development. Although they seemed very likely to serve an important function in the development of cerebellar granule cell precursors, Yap/Taz are dispensable for their proliferation. Furthermore, Yap/Taz loss does not rescue the medulloblastoma phenotype caused by constitutively active Smoothened. Importantly, Yap/Taz are highly expressed in radial glia and play a crucial role in establishing the radial scaffold and cellular polarity of neural progenitors during embryogenesis. We found that Yap/Taz are necessary to establish and maintain junctional integrity of cerebellar neuroepithelium as prominent junction proteins are not maintained at the apical junction in the absence of Yap/Taz. Our study identifies a novel function of Yap/Taz in cerebellar foliation and finds that they are required to establish the radial glia scaffold and junctional stability.

Finding incident cancer cases through outpatient oncology clinic claims data and integration into a state cancer registry.

Cancer data from population-based cancer registries under-report cancer cases, especially for cancers primarily diagnosed and treated in outpatient clinical settings, away from hospital-based cancer registrars. Previously, we developed alternative methods of cancer case capture including a claims-based method, which identified a large proportion of cancer cases missed by traditional population-based cancer registries. In this study, we adapted a claims-based method for statewide implementation of cancer surveillance in Florida. Between 2010 and 2017 the claims-based method identified 143,083 cancer abstracts, of which 42% were new and 58% were previously registered. The claims-based method led to the creation of 53,419 new cancer cases in the state cancer registry, which made up 9.3% of all cancer cases registered between 2010 and 2017. The types of cancers identified by the claims-based method were typical of the kinds primarily diagnosed and treated in outpatient oncology clinic settings, such as hematological malignancies, prostate cancer, melanoma, breast cancer, and bladder cancer. These cases were added to the Florida cancer registry and may produce an artefactual increase in cancer incidence, which is believed to be closer to the actual burden of cancer in the state.

National Estimates of Prevalence, Time-Trend, and Correlates of Smoking in US People Living with HIV (NHANES 1999-2016).

OBJECTIVE: Approximately one in four deaths among people living with HIV (PLWH) in the United States can be attributed to cigarette smoking. Using a nationally representative sample of PLWH, this study examines the prevalence, time-trends, and correlates of current cigarette smoking among PLWH compared to people without HIV. DESIGN: Secondary analysis of population-based cross-sectional biobehavioral survey. METHODS: Data were pooled from the 1999-2016 National Health and Nutrition Examination Survey (NHANES). All adults (20-59 years) who self-reported their smoking status and were tested for HIV (HIV+ = 152; HIV- = 26 305) were included in the analysis. Prevalence with 95% confidence interval (95% CI), trend analysis by year and group (HIV+/HIV-), and multivariable logistic regression analyses were performed with the complex survey design adjustments. RESULTS: Overall, 47.0% of PLWH were current smokers compared to 25.5% of those without HIV. From 1999 to 2016, the decline in smoking in PLWH was comparable to those without HIV (10.7% vs. 8.0%). PLWH smokers were more likely than PLWH nonsmokers to be substance users (adjusted odds ratio [aOR] = 17.52; 95% CI = 2.04 to 27.8). Compared to smokers without HIV, PLWH smokers were more likely to be older (1.10; 1.06 to 1.14), males (7.96; 2.50 to 25.40), non-Hispanic Black (10.45; 4.13 to 26.45), with depression (Patient Health Questionnaire-9 sum score ≥5) (3.79; 1.22 to 11.79), and less likely to be gay (0.02; 0.00 to 0.07). CONCLUSION: Cigarette smoking among PLWH is a major public health problem in the United States. Targeted and tailored smoking cessation interventions that incorporate assessment and treatment of depression and co-occurring substance use are critical for PLWH, especially among those who are disproportionately affected by smoking and HIV (sexual minority). IMPLICATIONS: This study offers important research implications in four areas:1. The decline in smoking among PLWH over 18 years has been modest, and half of PLWH are still smokers.2. More resources and efforts should be allocated to reduce cigarette smoking among PLWH.3. There is a critical need to develop and test culturally tailored smoking cessation interventions for minority subgroups who are most impacted by HIV infection and smoking (non-Hispanic Blacks and men who have sex with men)4. Smoking cessation interventions designed for PLWH should incorporate assessment and treatment of depression and substance use.

Factors Associated With Self-Perceived Hearing Handicap in Adults From Hispanic/Latino Background: Findings From the Hispanic Community Health Study/Study of Latinos.

OBJECTIVES: We sought to determine what factors, including acculturation (language and social contact preferences), were associated with self-perceived hearing handicap among adults from Hispanic/Latino background. We utilized the Aday-Andersen behavioral model of health services utilization to frame our hypotheses that predisposing characteristics (age, sex, education, city of residence, Hispanic/Latino background, and acculturation), enabling resources (annual income and current health insurance coverage), and need (measured hearing loss and self-reported hearing loss) would be related to clinically-significant self-perceived hearing handicap as measured by the Hearing Handicap Inventory - Screening (HHI-S) version. DESIGN: We analyzed baseline data collected from 2008 to 2011 as part of the multisite Hispanic Community Health Study/Study of Latinos. Data were from 6585 adults with hearing loss (defined by a worse-ear 500, 1000, 2000, and 4000 Hz pure-tone average [PTA] of ≥25 dB HL and/or a 4000, 6000, and 8000 Hz high-frequency PTA of ≥25 dB HL) aged 18 to 74 years from various Hispanic/Latino backgrounds. We conducted a series of multivariable logistic regression models examining the roles of independent variables of interest representing predisposing, enabling, and need indicators on the occurrence of clinically-significant self-perceived hearing handicap (e.g., HHI-S score > 8). RESULTS: Among included participants, 953 (14.5%) had an HHI-S score >8. The final model revealed significant associations between predisposing characteristics, enabling resources, need, and HHI-S outcome. Predisposing characteristics and need factors were associated with higher odds of reporting self-perceived hearing handicap (HHI-S score >8) including acculturation as measured by the Short Acculturation Scale for Hispanics (odds ratio [OR] = 1.28, 95% confidence interval [CI]: 1.09-1.50), female sex (OR = 1.72, 95% CI: 1.27-2.33), and poorer worse ear 500, 1000, 2000, and 4000 Hz PTA (OR = 1.02, 95% CI: 1.01-1.03); suggesting that a 5-decibel increase in a person's PTA was consistent with 10% higher odds of a HHI-S score of >8. Greater enabling resources were associated with lower odds of reporting clinically-significant self-perceived hearing handicap: compared with individuals with income <$10,000/year, the multivariable-adjusted OR among individuals with income $40,000 to $7500/year was 0.55 (95% CI: 0.33-0.89) and among individuals with income >$75,000/year was 0.28 (95% CI: 0.13-0.59]; p-trend < 0.0001). CONCLUSIONS: Our findings suggest there are associations between predisposing, enabling and need variables consistent with the Aday-Andersen model and self-perceived hearing handicap among adults from Hispanic/Latino background. The influence of language and culture on perceived hearing loss and associated handicap is complex, and deserves more attention in future studies. Our findings warrant further investigation into understanding the role of language and language access in hearing health care utilization and outcomes, as the current body of literature is small and shows mixed outcomes.

Activation by NarL at the Escherichia coli ogt promoter.

The Escherichia coli NarX/NarL two-component response-regulator system regulates gene expression in response to nitrate ions and the NarL protein is a global transcription factor, which activates transcript initiation at many target promoters. One such target, the E. coli ogt promoter, which controls the expression of an O6-alkylguanine-DNA-alkyltransferase, is dependent on NarL binding to two DNA targets centred at positions -44.5 and -77.5 upstream from the transcript start. Here, we describe ogt promoter derivatives that can be activated solely by NarL binding either at position -44.5 or position -77.5. We show that NarL can also activate the ogt promoter when located at position -67.5. We present data to argue that NarL-dependent activation of transcript initiation at the ogt promoter results from a direct interaction between NarL and a determinant in the C-terminal domain of the RNA polymerase α subunit. Footprinting experiments show that, at the -44.5 promoter, NarL and the C-terminal domain of the RNA polymerase α subunit bind to opposite faces of promoter DNA, suggesting an unusual mechanism of transcription activation. Our work suggests new organisations for activator-dependent transcription at promoters and future applications for biotechnology.

Comparing cancer risk estimates using occupational record linkage approaches in male Florida firefighters.

BACKGROUND: Firefighters have an increased risk of cancer, but variations in reported results could be due to differences in occupational case ascertainment. This study compares cancer risk estimates generated by identifying firefighters from their occupational title available in the Florida Cancer Data System (FCDS) versus identification by a linkage method between the FCDS and the Florida State Fire Marshal's Office. METHODS: Florida firefighter employment records (1972-2012; n = 109,009) were linked with FCDS data (1981-2014; ~3.3 million records), identifying 3760 primary cancers in male firefighters. Using the FCDS occupational data field we identified 1831 male cancer cases in those classified as firefighters, first-line supervisors of firefighting and prevention workers, fire inspectors, emergency medical technicians, or paramedics. Age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals for firefighters versus non-firefighters were calculated for both groups. RESULTS: For skin cancers the risk estimate for FCDS-indentified firefighters was substantially lower than in the employment-record-linked firefighters (aOR = 1.06; 0.87-1.29 vs. 1.54; 1.37-1.73), but for endocrine system cancers it was greater (aOR = 2.36; 1.77-3.14 vs. 2.08; 1.71-2.53). Remaining cancer risk estimates were in the same direction for the two samples except for lymphoma (aOR = 1.10; 0.90-1.34 vs. 0.86; 0.75-0.99). CONCLUSION: Reliance on occupational title in cancer registry records to characterize firefighter cancer risk may result in estimates that are over- or underestimated depending on cancer site. The authors recommend moving toward national linkages between cancer registries and certification or other administrative records, which are a vital resource for firefighter cancer research.

Mechanisms Driving Immune-Related Adverse Events in Cancer Patients Treated with Immune Checkpoint Inhibitors.

PURPOSE OF REVIEW: In the past decade, immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer treatment. With the continuing rise in the number of cancer patients eligible for ICIs, a corresponding rise in immune-related adverse events (irAEs) is occurring. IrAEs are inflammatory reactions against normal, healthy tissue that occur due to ICI-induced activation of the immune system. Although the exact immune pathogenesis driving irAE development remains unknown, we review the main proposed mechanisms, highlighting how they may inform irAE prediction and treatment. RECENT FINDINGS: IrAEs are common and diverse, varying in incidence, timing, and severity. The possible mechanisms driving irAEs include (1) activation of cytotoxic T cells; (2) activation of B cells and increased autoantibody production; (3) direct molecular mimicry and off-target toxicity; (4) activation of intracellular signaling and pro-inflammatory cytokine production; and (5) environmental modifiers of immune system activation, including composition of the host gut microbiome. These mechanisms may help identify predictive biomarkers and targeted treatment strategies. IrAEs are driven by multiple components of the immune system. More research is needed to understand their immunopathogenesis so that clinicians across all specialties may more effectively monitor and manage these increasingly common conditions.

Chronic condition patterns in the US population and their association with health related quality of life.

This study aims to identify chronic disease patterns and their relationship to health-related quality of life (HRQL) in the US population. This cross-sectional study used data from 86,745 participants aged 18 years and older of the Medical Expenditure Panel Survey (MEPS) 2010-2015, we employed latent class analysis (LCA) to identify subgroups of participants with different combinations of 23 chronic conditions which had medical utilization during the past 12 months. Derived chronic condition latent classes were used to predict the 12-Item Short Form Survey physical component score (PCS), mental component score (MCS) in addition to overall HRQL (SF-6D) while controlling for covariates. LCA identified five unique multi-morbidity groups: "healthy" (62.5%), "vascular risk" (18.9%), "anxiety" (12.2%), "heart disease" (2.9%), and "severely-impaired" (3.5%). Covariate-adjusted mean SF-6D scores varied significantly among classes: healthy (0.85), vascular risk (0.77), anxiety (0.67), heart disease group (0.65), and severely-impaired (0.56). The anxiety group, proportionately younger and female, had high PCS (46.3) but low MCS (41.9). The heart disease group, although older and in poor physical health (PCS = 33.2), had higher MCS scores (46.9). Our results demonstrate multi-morbidity significantly impacts HRQL. The relationship between physical and mental health functioning varied across different multi-morbidity groups, and the discordance was more pronounced in younger ages and females. Our research also identified an older age group that was mentally robust and maintained a strong HRQL. Findings can inform the development of targeted interventions to improve physical and mental health functioning in vulnerable populations.

Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals.

IL-1, generally considered an amplifier of adaptive immune responses, has been proposed for use as adjuvant during immunization with weak immunogens. However, its effects on memory T cell function remain largely undefined. Using the murine model of acute viral infection, in this paper, we show that in addition to augmenting the size of the Ag-specific pool, IL-1 signals act directly on CD8 T cells to promote the quality of effector and memory responses. Ablation of IL-1R1 or MyD88 signaling in T cells led to functional impairment; both the ability to produce multiple cytokines on a per cell basis (polyfunctionality) and the potential for recall proliferation in response to antigenic restimulation were compromised. IL-1 supplementation during priming augmented the expansion of Ag-specific CD8 T cells through the MyD88-IRAK1/4 axis, resulting in a larger memory pool capable of robust secondary expansion in response to rechallange. Together, these findings demonstrate a critical role of the IL-1-MyD88 axis in programming the quantity and quality of memory CD8 T cell responses and support the notion that IL-1 supplementation may be exploited to enhance adoptive T cell therapies against cancers and chronic infections.

Effects of Food on Bioavailability of Analgesics; Resulting Dosage and Administration Recommendations.

OBJECTIVES: To evaluate currently approved analgesics, that is, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and serotonin and norepinephrine reuptake inhibitors (SNRIs) used as analgesics, for 1) differences in pharmacokinetic parameters under fed vs fasting conditions and 2) factors involved in dosage recommendations in relation to food. DESIGN: Systematic review. RESULTS: Food effect on the rate, extent of absorption, or shape of concentration-time profile can alter the onset of action, duration of action, or tolerability of a medication. Based on 79 analgesic products reviewed, food effect dosage recommendations depend on whether an analgesic will be dosed on a regular interval around-the-clock vs on an as-needed basis, the shape of concentration-time profile, steady-state concentrations, the type of meals used in the pharmacokinetic study, and drug administration with regard to food in clinical trials. Overall, most opioids do not have food restriction and are taken without regard to food, with the exception of OPANA products and XTAMPZA ER. For many NSAIDs, food does not affect absorption characteristics, with the exception of ZORVOLEX and CELEBREX. Although NSAIDs are commonly to be taken without regard to food, prescribers recommend administering them with food to reduce their propensity for gastrointestinal adverse events. A larger percentage of anticonvulsants and SNRIs used as analgesics are taken with food to improve their tolerability. Of all analgesic products, seven NSAIDs and six opioids lack food effect information, maybe due to their approval before Food and Drug Administration food effect guidance. CONCLUSIONS: Overall, because food effects could alter the onset and/or duration of pain relief, analgesic medication should be used as per labeled recommendations for proper pain management.

Cancer risk among career male and female Florida firefighters: Evidence from the Florida Firefighter Cancer Registry (1981-2014).

BACKGROUND: Firefighters are at increased risk for select cancers. However, many studies are limited by relatively small samples, with virtually no data on the cancer experience of female firefighters. This study examines cancer risk in over 100,000 career Florida firefighters including 5000 + females assessed over a 34-year period. METHODS: Florida firefighter employment records (n = 109 009) were linked with Florida Cancer Data System registry data (1981-2014; ~3.3 million records), identifying 3760 male and 168 female-linked primary cancers. Gender-specific age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals for firefighters vs non-firefighters were calculated. RESULTS: Male firefighters were at increased risk of melanoma (aOR = 1.56; 1.39-1.76), prostate (1.36; 1.27-1.46), testicular (1.66; 1.34-2.06), thyroid (2.17; 1.78-2.66) and late-stage colon cancer (1.19;1.00-1.41). Female firefighters showed significantly elevated risk of brain (2.54; 1.19-5.42) and thyroid (2.42; 1.56-3.74) cancers and an elevated risk of melanoma that approached statistical significance (1.68; 0.97-2.90). Among male firefighters there was additional evidence of increased cancer risk younger than the age of 50 vs 50 years and older for thyroid (2.55; 1.96-3.31 vs 1.69; 1.22-2.34), prostate (1.88; 1.49-2.36 vs 1.36; 1.26-1.47), testicular (1.60; 1.28-2.01 vs 1.47; 0.73-2.94), and melanoma (1.87; 1.55-2.26 vs 1.42; 1.22-1.66) cancers. CONCLUSION: Male career firefighters in Florida are at increased risk for five cancers with typically stronger associations in those diagnosed younger than the age of 50, while there was evidence for increased thyroid and brain cancer, and possibly melanoma risk in female firefighters. Larger cohorts with adequate female representation, along with the collection of well-characterized exposure histories, are needed to more precisely examine cancer risk in this occupational group.

Analysis of musculoskeletal radiology fellowship websites.

OBJECTIVE: Due to the relative lack of standardization in the fellowship application processes for musculoskeletal radiology, program websites are of paramount importance as application resources. This study evaluates the comprehensiveness of these websites and the potential effects of program ACGME accreditation, region, and size on website comprehensiveness. MATERIALS AND METHODS: The websites of musculoskeletal fellowship programs listed on the Society of Skeletal Radiology website were assigned a validated comprehensiveness score based on the presence of 19 specific informative components pertaining to the program's characteristics. The correlations of comprehensiveness scores with program ACGME accreditation, region, and size were evaluated. RESULTS: A total of 90 musculoskeletal radiology fellowship program websites were reviewed, yielding a mean comprehensiveness score of 55.1% (10.5 out of 19 criteria). Only 3 of the 19 criteria-application information (88.9%), stand-alone webpage (87.8%), and affiliated hospital information (84.4%)-were present in more than 80% of all websites. Eleven criteria, most notably away rotation information (6.7% presence) and case log (0.0% presence), were absent from at least 50% of all websites. Program ACGME accreditation was correlated with significantly higher website comprehensiveness scores compared with non-accreditation (p = 0.087). CONCLUSION: There is lack of sufficient, useful information and standardization on the websites of MSK fellowship programs throughout the country. According to our review and analysis, addition of specific information regarding each fellowship program and implementing some type of standardization may optimize fellowship matching for both applicants and the programs.

Resistance of New Zealand Provenance Leptospermum scoparium, Kunzea robusta, Kunzea linearis, and Metrosideros excelsa to Austropuccinia psidii.

Resistance to the pandemic strain of Austropuccinia psidii was identified in New Zealand provenance Leptospermum scoparium, Kunzea robusta, and K. linearis plants. Only 1 Metrosideros excelsa-resistant plant was found (of the 570 tested) and no resistant plants of either Lophomyrtus bullata or L. obcordata were found. Three types of resistance were identified in Leptospermum scoparium. The first two, a putative immune response and a hypersensitive response, are leaf resistance mechanisms found in other myrtaceous species while on the lateral and main stems a putative immune stem resistance was also observed. Both leaf and stem infection were found on K. robusta and K. linearis plants as well as branch tip dieback that developed on almost 50% of the plants. L. scoparium, K. robusta, and K. linearis are the first myrtaceous species where consistent infection of stems has been observed in artificial inoculation trials. This new finding and the first observation of significant branch tip dieback of plants of the two Kunzea spp. resulted in the development of two new myrtle rust disease severity assessment scales. Significant seed family and provenance effects were found in L. scoparium, K. robusta, and K. linearis: some families produced significantly more plants with leaf, stem, and (in Kunzea spp.) branch tip dieback resistance, and provenances provided different percentages of resistant families and plants. The distribution of the disease symptoms on plants from the same seed family, and between plants from different seed families, suggested that the leaf, stem, and branch tip dieback resistances were the result of independent disease resistance mechanisms.

Position effects on promoter activity in Escherichia coli and their consequences for antibiotic-resistance determinants.

The activity of any bacterial promoter is generally supposed to be set by its base sequence and the different transcription factors that bind in the local vicinity. Here, we review recent data indicating that the activity of the Escherichia coli lac operon promoter also depends upon its chromosomal location. Factors that affect promoter activity include the binding of nucleoid-associated proteins to neighbouring sequences, supercoiling and the activity of neighbouring promoters. We suggest that many bacterial promoters might be susceptible to similar position-dependent effects and we review recent data showing that the expression of mobile genes encoding antibiotic-resistance determinants is also location-dependent, both when carried on a bacterial chromosome or a conjugative plasmid.

Comparison of host susceptibilities to native and exotic pathogens provides evidence for pathogen-imposed selection in forest trees.

The extent to which spatial structuring of host resistance in wild plant populations reflects direct pathogen-imposed selection is a subject of debate. To examine this issue, genetic susceptibilities to an exotic and a coevolved native fungal pathogen were compared using two Australian host tree species. Damage to common host germplasm of Corymbia citriodora ssp. variegata (CCV) and Eucalyptus globulus, caused by recently introduced (Austropuccinia psidii) and native (Quambalaria pitereka and Teratosphaeria sp.) pathogens was evaluated in common-garden experiments. There was significant additive genetic variation within host species for susceptibility to both the exotic and native pathogens. However, susceptibility to A. psidii was not genetically correlated with susceptibility to either native pathogen, providing support for pathogen-specific rather than general mechanisms of resistance. Population differentiation (QST ) for susceptibility to the native pathogens was greater than neutral expectations (molecular FST ), arguing for divergent selection. Coupled with lower native, but not exotic, pathogen susceptibility in host populations from areas climatically more prone to fungal proliferation, these findings suggest that pathogen-imposed selection has contributed directly to a geographic mosaic of host resistance to native pathogens.