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Biomarker identification through spatial proteomics for the characterization of indeterminate thyroid nodules.

PURPOSE: The identification of novel molecular biomarkers may assist in the characterization of indeterminate thyroid nodules, which pose significant diagnostic challenges. Here, we aimed to explore the potential of proteomic analyses to support biomarker discovery in challenging thyroid lesions. METHODS: Linear Discriminant Analysis (LDA) was applied to Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) data from 44 thyroid neoplasms to select the most impactful molecular features for the classification of different tumor histologies, as well as for the distinction between NRAS-mutant (mNRAS) and NRAS-wild-type (wtNRAS) tumors. Relevant peaks were subsequently identified through nanoscale liquid chromatography electrospray ionization tandem mass spectrometry (nLC-ESI-MS/MS). RESULTS: The LDA selected nine relevant molecular markers distinguishing noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) from other tumor histologies (balanced accuracy = 73%), as well as 19 relevant markers able to identify mNRAS cases (balanced accuracy = 84%). Nine differentially expressed proteins were putatively identified: among them, ATP-dependent RNA helicase DDX42 showed a similar distribution between NIFTPs and papillary thyroid carcinomas (PTCs) / follicular variant PTCs (FVPTCs), while the distribution of the Histone H4 signal was similar between NIFTPs and follicular adenomas (FAs). In addition, Protein disulfide-isomerase A1 and Complement C4-B were overexpressed in wtNRAS compared to mNRAS cases, regardless of histology. CONCLUSION: The LDA-selected features enable to distinguish NIFTPs from morphologically similar lesions and to discriminate between mNRAS and wtNRAS cases. The identified markers might complement genetic analyses and provide insights into the distinct pathogenic drivers behind the development of mNRAS compared to wtNRAS lesions.

Humans↗

High-affinity CD25-binding IL-2 mutants potently stimulate persistent T cell growth.

We have used directed evolution to construct IL-2 mutants that bind the IL-2 alpha receptor subunit (IL-2Ralpha, CD25) with affinities comparable to that of the IL-15-IL-15 alpha receptor subunit (IL-15Ralpha) interaction. T cells proliferate for up to 6 days following a 30 minute incubation with these IL-2 mutants, which may lead to potential applications for cancer and viral immunotherapy. Several alternative mechanisms have been proposed to explain the contrasting effects of IL-2 and IL-15 on T cell proliferation and death. These IL-2 mutants exhibit T cell growth response-receptor occupancy curves indistinguishable from that for IL-15, suggesting that much of the difference between wild-type IL-2 and IL-15 effects arises simply from their 1000-fold differing affinities for their private alpha receptor subunits.

Amino Acid Substitution↗

Transcriptome-based epigenetic screening identifies DNA hypermethylation signatures as prognostic biomarkers in oral squamous cell carcinoma.

Promoter DNA hypermethylation is a key epigenetic mechanism of gene silencing in cancer, yet the DNA hypermethylome of oral squamous cell carcinoma (OSCC) and its prognostic relevance remain poorly characterized. Here, we systematically identified and validated novel hypermethylated genes with prognostic significance in OSCC using a genome-wide discovery and multi-platform validation strategy. Candidate genes were first identified by pharmacologic demethylation combined with RNA sequencing across OSCC cell lines, then validated by quantitative RT-PCR, methylation-specific PCR, and bisulfite sequencing in OSCC cell lines, normal oral mucosa, and primary OSCC tumors, with independent confirmation in the TCGA-HNSC dataset. Immunohistochemistry confirmed protein-level silencing, and Kaplan-Meier survival analysis assessed prognostic significance across both cohorts. This pipeline identified five candidate genes, GPX3, ANG, CTGF, GPRC5B, and BAMBI, exhibiting cancer-specific promoter hypermethylation associated with transcriptional and protein silencing in OSCC. Validation in oral cavity tumor samples extracted from the TCGA-HNSC dataset confirmed tumor-specific hypermethylation and revealed significant inverse correlations between methylation and expression for GPX3, GPRC5B, and CTGF. Notably, CTGF hypermethylation was independently associated with poor overall survival in both cohorts (institutional cohort, p=0.03; oral tumor subset from TCGA-HNSC, p=0.01), and a combined ANG+CTGF methylation signature showed superior and reproducible prognostic performance across both platforms. Pathway analysis linked these genes to epithelial-mesenchymal transition and interferon response signaling. This study establishes the first validated DNA methylation biomarker panel for OSCC prognosis, identifying CTGF hypermethylation as a robust prognostic driver with translational potential for clinical risk stratification.

Humans↗

Third-generation whole-genome sequencing reveals the role of CNTNAP2 as a tumor suppressor gene in high-risk neuroblastomas.

BACKGROUND: Neuroblastoma is a common and aggressive pediatric sympathetic nervous system tumor. Genomic structural variants (SVs) contribute substantially to neuroblastoma, yet remain under-characterized in high-risk neuroblastomas. We aimed to elucidate neuroblastoma pathogenesis using third-generation whole-genome sequence high-risk cases to identify driver aberrations and explore potential therapeutic strategies. METHODS: We analyzed third-generation whole-genome sequencing data of 20 high-risk neuroblastoma samples and combined the findings with those obtained from the analysis of clinical samples, in vitro models, and public datasets. RESULTS: The contactin-associated protein-like 2 (CNTNAP2) gene was observed to be frequently aberrated because of structural variants in high-risk neuroblastoma samples. CNTNAP2 expression was significantly correlated with favorable histology and could be used to predict prognosis using clinical samples and neuroblastoma datasets. Overexpression and knockdown experiments and transcriptomic analysis revealed that CNTNAP2 was primarily involved in neuronal differentiation and axon guidance pathways; moreover, CNTNAP2 was required for neuroblastoma differentiation and affected cancer stemness. Immunoprecipitation and mass spectrometry revealed that CNTNAP2 interacted with cytoskeletal proteins like drebrin 1 (DBN1) and myosin-heavy chain 9 (MYH9). CNTNAP2 dynamically reorganises actin and microtubules for DBN1-mediated neuronal differentiation. CNTNAP2 also reduces CTNNB1 transcription and β-catenin pathway activation by inhibiting MYH9 nuclear translocation. CNTNAP2 overexpression in neuroblastoma cell lines resulted in cell cycle arrest, decreased cell proliferation and metastasis. CONCLUSIONS: The recurrent loss of CNTNAP2 in neuroblastoma contributes to an aggressive phenotype by impairing neuronal differentiation and increasing cancer stemness. These findings may serve as a foundation for developing therapeutic strategies to overcome barriers to differentiation.

Humans↗

[Neurological diseases and driving].

Traffic accidents (TA) are, after heart disease, cancer and stroke, the fourth death cause among the general population. Although the number of AT caused by diseases-excluding alcoholism- seems to be reduced, interaction between organic pathology and functional ability increases the importance of this problem. This paper revises the literature on the relation between AT and specific neurological diseases: epilepsy, obstructive sleep apnea syndrome (SAS), stroke, dementia and Parkinson disease. Also, the problems and the role of the neurologist in assessing driving ability in patients with brain damage is analyzed, with special reference to the legal condition in Spain. The insufficiency of diagnostic labels as predictors of driving ability is stressed; the group of patients affected by these pathologies does not present greater TA risk than young drivers twice that of the general population. In the cases of epilepsy, SAS and ECV, which can cause episodic driving inability, defining recurrence probabilities and finding regulation formulas is the task of clinical epidemiologists and the regulative authorities. In the case of dementia, Parkinson disease and ECV, causing psychomotor performance deterioration, the basic problem, complicated by the presence of comorbility in these patients, is the development of valid clinical scales for driving ability assessment. The regulative authorities need simple measures which are often difficult to develop. Meanwhile, it is the task of the neurologist, as part of the therapeutic intervention during the medical encounter, to discuss driving risks with each patient.

Accidents, Traffic↗

Youth risk behavior surveillance--United States, 2001.

PROBLEM/CONDITION: Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. REPORTING PERIOD COVERED: This report covers data during February-December 2001. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults; these behaviors contribute to unintentional injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 34 state surveys, and 18 local surveys conducted among students in grades 9-12 during February-December 2001. RESULTS: In the United States, approximately three fourths of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2001 national Youth Risk Behavior Survey demonstrated that numerous high school students engage in behaviors that increase their likelihood of death from these four causes: 14.1% had rarely or never worn a seat belt during the 30 days preceding the survey; 30.7% had ridden with a driver who had been drinking alcohol; 17.4% had carried a weapon during the 30 days preceding the survey; 47.1% had drunk alcohol during the 30 days preceding the survey; 23.9% had used marijuana during the 30 days preceding the survey; and 8.8% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 2001, 45.6% of high school students had ever had sexual intercourse; 42.1% of sexually active students had not used a condom at last sexual intercourse; and 2.3% had ever injected an illegal drug. Two thirds of all deaths among persons aged > or = 25 years result from only two causes: cardiovascular disease and cancer. The majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 2001, 28.5% of high school students had smoked cigarettes during the 30 days preceding the survey; 78.6% had not eaten > or = 5 servings per day of fruits and vegetables during the 7 days preceding the survey; 10.5% were overweight; and 67.8% did not attend physical education class daily. PUBLIC HEALTH ACTIONS: Health and education officials at national, state, and local levels are using these YRBSS data to analyze and improve policies and programs to reduce priority health-risk behaviors among youth. The YRBSS data also are being used to measure progress toward achieving 16 national health objectives for 2010 and 3 of the 10 leading health indicators.

Adolescent↗

Youth Risk Behavior Surveillance--United States, 1999. State and local YRBSS Coordinators.

Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults--behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 33 state surveys, and 16 local surveys conducted among high school students during February through May 1999. In the United States, approximately three fourths of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1999 national Youth Risk Behavior Survey demonstrate that numerous high school students engage in behaviors that increase their likelihood of death from these four causes--16.4% had rarely or never worn a seat belt; during the 30 days preceding the survey, 33.1% had ridden with a driver who had been drinking alcohol; 17.3% had carried a weapon during the 30 days preceding the survey; 50.0% had drunk alcohol during the 30 days preceding the survey; 26.7% had used marijuana during the 30 days preceding the survey; and 7.8% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 1999, nationwide, 49.9% of high school students had ever had sexual intercourse; 42.0% of sexually active students had not used a condom at last sexual intercourse; and 1.8% had ever injected an illegal drug. Two thirds of all deaths among persons aged > or = 25 years result from only two causes--cardiovascular disease and cancer. The majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 1999, 34.8% of high school students had smoked cigarettes during the 30 days preceding the survey; 76.1% had not eaten > or = 5 servings/day of fruits and vegetables during the 7 days preceding the survey; 16.0% were at risk for becoming overweight; and 70.9% did not attend physical education class daily. These YRBSS data are already being used by health and education officials at national, state, and local levels to analyze and improve policies and programs to reduce priority health-risk behaviors among youth. The YRBSS data also are being used to measure progress toward achieving 16 national health objectives for 2010 and 3 of the 10 leading health indicators.

Adolescent↗

Youth risk behavior surveillance--United States, 2001.

Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. This report covers data during February-December 2001. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults; these behaviors contribute to unintentional injuries and violence; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection; unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 34 state surveys, and 18 local surveys conducted among students in grades 9-12 during February-December 2001. In the United States, approximately three-fourths of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 2001 national Youth Risk Behavior Survey demonstrated that numerous high school students engage in behaviors that increase their likelihood of death from these four causes: 14.1% had rarely or never worn a seat belt during the 30 days preceding the survey; 30.7% had ridden with a driver who had been drinking alcohol; 17.4% had carried a weapon during the 30 days preceding the survey; 47.1% had drunk alcohol during the 30 days preceding the survey; 23.9% had used marijuana during the 30 days preceding the survey; and 8.8% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 2001, 45.6% of high school students had ever had sexual intercourse; 42.1% of sexually active students had not used a condom at last sexual intercourse; and 2.3% had ever injected an illegal drug. Two-thirds of all deaths among persons aged > or = 25 years result from only two causes: cardiovascular disease and cancer. The majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 2001, 28.5% of high school students had smoked cigarettes during the 30 days preceding the survey; 78.6% had not eaten > or = 5 servings per day of fruits and vegetables during the 7 days preceding the survey; 10.5% were overweight; and 67.8% did not attend physical education class daily. Health and education officials at national, state, and local levels are using these YRBSS data to analyze and improve policies and programs to reduce priority health-risk behaviors among youth. The YRBSS data also are being used to measure progress toward achieving 16 national health objectives for 2010 and 3 of the 10 leading health indicators.

Adolescent↗

Youth risk behavior surveillance--United States, 1999.

PROBLEM/CONDITION: Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, are interrelated, and are preventable. REPORTING PERIOD: February-May 1999. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults --behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 33 state surveys, and 16 local surveys conducted among high school students during February-May 1999. RESULTS AND INTERPRETATION: In the United States, approximately three fourths of all deaths among persons aged 10-24 years result from only four causes: motor-vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1999 national Youth Risk Behavior Survey demonstrate that numerous high school students engage in behaviors that increase their likelihood of death from these four causes--16.4% had rarely or never worn a seat belt; during the 30 days preceding the survey, 33.1% had ridden with a driver who had been drinking alcohol; 17.3% had carried a weapon during the 30 days preceding the survey; 50.0% had drunk alcohol during the 30 days preceding the survey; 26.7% had used marijuana during the 30 days preceding the survey; and 7.8% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among young persons also result from unintended pregnancies and STDs, including HIV infection. In 1999, nationwide, 49.9% of high school students had ever had sexual intercourse; 42.0% of sexually active students had not used a condom at last sexual intercourse; and 1.8% had ever injected an illegal drug. Two thirds of all deaths among persons aged > or = 25 years result from only two causes--cardiovascular disease and cancer. The majority of risk behaviors associated with these two causes of death are initiated during adolescence. In 1999, 34.8% of high school students had smoked cigarettes during the 30 days preceding the survey; 76.1% had not eaten > or = 5 servings/day of fruits and vegetables during the 7 days preceding the survey; 16.0% were at risk for becoming overweight; and 70.9% did not attend physical education class daily. ACTIONS TAKEN: These YRBSS data are already being used by health and education officials at national, state, and local levelsto analyze and improve policies and programs to reduce priority health-risk behaviors among youth. The YRBSS data also are being used to measure progress toward achieving 16 national health objectives for 2010 and 3 of the 10 leading health indicators.

Adolescent↗

Parental occupations and childhood brain tumors: results of an international case-control study.

OBJECTIVE: To evaluate the role of parental occupations in the etiology of childhood brain tumors (CBT). METHODS: Population-based case-control studies were conducted concurrently in seven countries under the coordination of the International Agency for Research on Cancer, gathering 1,218 cases and 2,223 controls. We report here the findings related to parental occupations during the 5-year period before the child's birth. Risk estimates related to a number of paternal and maternal occupations were obtained by unconditional logistic regression adjusted for age, sex, year of birth, and center, for all types of CBT combined and for the subgroups of astroglial, primitive neuroectodermal tumors (PNET), and other glial tumors. RESULTS: An increased risk in relation with agricultural work was seen for all CBT combined and for other glial tumors. Increased risks for all tumors and PNET were seen for paternal occupation as an electrician; the same pattern held for maternal occupation when children under 5 were selected. Paternal occupation as a driver or mechanic, and maternal work in an environment related to motor-vehicles were associated with an increased risk for all CBT and astroglial tumors. More case mothers compared to control mothers were employed in the textile industry. CONCLUSION: Our study reinforces previous findings relative to the role of parental work in agriculture, electricity, or motor-vehicle related occupations and maternal work in the textile industry. It does not confirm previous associations with work environments including aerospace, the chemical industry, or the food industry, or with maternal occupation as a hairdresser, a nurse, or a sewing machinist, and paternal occupation as a welder.

Adolescent↗

A 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes.

Amplification of 8p11-12 is a well-known alteration in human breast cancers but the driving oncogene has not been identified. We have developed a high-resolution comparative genomic hybridization array covering 8p11-12 and analysed 33 primary breast tumors, 20 primary ovarian tumors and 27 breast cancer cell lines. Expression analysis of the genes in the region was carried out by using real-time quantitative PCR and/or oligo-microarray profiling. In all, 24% (8/33) of the breast tumors, 5% (1/20) of the ovary tumors and 15% (4/27) of the cell lines showed 8p11-12 amplification. We identified a 1 Mb segment of common amplification that excludes previously proposed candidate genes. Some of the amplified genes did not show overexpression, whereas for others, overexpression was not specifically attributable to amplification. The genes FLJ14299, C8orf2, BRF2 and RAB11FIP, map within the 8p11-12 minimal amplicon, two have a putative function consistent with an oncogenic role, these four genes showed a strong correlation between amplification and overexpression and are therefore the best candidate driver oncogenes at 8p12.

Breast Neoplasms↗

The Landscape of Genomic and Socioeconomic Variables in Patients with Colorectal Cancer Based on Genetic Ancestry.

BACKGROUND: Despite differences in tumor alterations across genetic ancestries, investigations of the colorectal cancer molecular landscape have used self-reported ethnicity instead of genetic ancestry. METHODS: We used tumor and matched normal whole-exome sequencing data from 16,388 patients with stage I to IV colorectal cancer to investigate colorectal cancer's germline and somatic molecular landscape and the potential influence of socioeconomic factors (Distressed Communities Index, DCI) across diverse genetic ancestries. Genetic ancestry determined via supervised local ancestry inference included African (AFR, N = 1,697), Native American (AMR, N = 1,291), East Asian (EAS, N = 2,247), European (EUR, N = 9,726), Levantine Middle Eastern (LME, N = 1,192), and South Asian (SAS, N = 184). RESULTS: Microsatellite instability (MSI) was the most common form of hypermutation (80.8%), higher in the EUR genetic ancestry than in the AFR, AMR, and EAS genetic ancestry. Among germline findings, positive results were most common in high-penetrance genes associated with Lynch syndrome. Enrichment patterns included MLH1 (SAS) and PMS2 (AFR). There were significant differences in the frequency of driver mutations in APC, BRAF, KRAS, TP53, and PIK3CA between the EUR and other ancestry groups in both MSI and microsatellite stable tumors. Mutational signatures suggested enrichment of reactive oxygen species and POLE in AFR, colibactin in EAS, and aflatoxin and NTHL1 in SAS. DCI scores differed by ancestry (higher distress in AFR/AMR than in EUR), but driver mutation frequencies did not vary across DCI quintiles. CONCLUSIONS: Genetic ancestry shapes hereditary risk, tumor biology, and environmental exposures. IMPACT: These findings suggest that incorporating ancestry into screening, trials, and precision oncology may improve equity, though outcome-linked prospective studies and implementation research are warranted.

Aged↗

Youth risk behavior surveillance. National Alternative High School Youth Risk Behavior Survey, United States, 1998.

Alternative high schools serve approximately 280,000 students nationwide who are at high risk for failing or dropping out of regular high school or who have been expelled from regular high school because of illegal activity or behavioral problems. Such settings provide important opportunities for delivering health promotion education and services to these youth and young adults. However, before this survey, the prevalence of health-risk behaviors among students attending alternative high schools nationwide was unknown. The Youth Risk Behavior Surveillance System (YRBSS) monitors the following six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The national Alternative High School Youth Risk Behavior Survey (ALT-YRBS) is one component of the YRBSS; it was conducted in 1998 to measure priority health-risk behaviors among students at alternative high schools. The 1998 ALT-YRBS used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 in the United States who attend alternative high schools. The school response rate was 81.0%, and the student response rate was 81.9%, resulting in an overall response rate of 66.3%. This report summarizes results from the 1998 ALT-YRBS. The reporting period is February-May 1998. In the United States, 73.6% of all deaths among youth and young adults aged 10-24 years results from only four causes--motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1998 ALT-YRBS demonstrate that many students at alternative high schools engage in behaviors that increase their likelihood of death from these four causes. During the 30 days preceding the survey, 51.9% had ridden with a driver who had been drinking alcohol, 25.1% had driven a vehicle after drinking alcohol, 32.9% had carried a weapon, 64.5% had drunk alcohol, and 53.0% had used marijuana. During the 12 months preceding the survey, 15.7% had attempted suicide, and 29.0% had rarely or never worn a seat belt. Substantial morbidity among school-aged youth and young adults also results from unintended pregnancies and STDs, including HIV infection. ALT-YRBS results indicate that in 1998, a total of 87.8% of students at alternative high schools had had sexual intercourse, 54.1% of sexually active students had not used a condom at last sexual intercourse, and 5.7% had ever injected an illegal drug. Among adults aged > or = 25 years, 66.5% of all deaths result from two causes--cardiovascular disease and cancer. Most risk behaviors associated with these causes of death are initiated during adolescence. In 1998, a total of 64.1% of students at alternative high schools had smoked cigarettes during the 30 days preceding the survey, 38.3% had smoked a cigar during the 30 days preceding the survey, 71.2% had not eaten > or = 5 servings of fruits and vegetables during the day preceding the survey, and 81.0% had not attended physical education (PE) class daily. Comparing ALT-YRBS results with 1997 national YRBS results demonstrates that the prevalence of most risk behaviors is higher among students attending alternative high schools compared with students at regular high schools. Some risk behaviors are more common among certain sex and racial/ethnic subgroups of students. ALT-YRBS data can be used nationwide by health and education officials to improve policies and programs designed to reduce risk behaviors associated with the leading causes of morbidity and mortality among students attending alternative high schools.

Adolescent↗

A 39-year follow-up of the U.K. oil refinery and distribution center studies: results for kidney cancer and leukemia.

This paper presents briefly some of the principal results of a mortality analysis of a cohort of workers employed for at least 1 year between 1950 and 1975 at eight oil refineries and approximately 750 distribution centers in the U.K., together with detailed results for kidney cancer and leukemia. Over 99% of the workers were successfully traced. Their mortality was compared with that of all males in the national population. The mortality from all causes of death is lower than that of the comparison population in both studies, and reduced mortality is also found for many of the major nonmalignant causes of death. In the refinery study, some increased mortality patterns are found for diseases of the arteries, and no healthy worker effect is found in the distribution center study for ischemic heart disease. Mortality from all neoplasms is lower than expected overall in both studies, largely due to a deficit of deaths from malignant neoplasm of the lung. Mortality from malignant neoplasm of the kidney is increased overall in the distribution center study, and in drivers in particular. The mortality from this disease increases with increased time since first exposure. The observed deaths from leukemia are slightly less than expected in the refinery study and slightly more than expected in the distribution center study. One refinery shows increased mortality due to in myeloid leukemia, and mortality is increased among refinery operators. Mortality is also raised in distribution center drivers, particularly for myeloid leukemias, including acute myeloid leukemia.

Cause of Death↗

Youth Risk Behavior Surveillance--National Alternative High School Youth Risk Behavior Survey, United States, 1998.

PROBLEM/CONDITION: Alternative high schools serve approximately 280,000 students nationwide who are at high risk for failing or dropping out of regular high school or who have been expelled from regular high school because of illegal activity or behavioral problems. Such settings provide important opportunities for delivering health promotion education and services to these youth and young adults. However, before this survey, the prevalence of health-risk behaviors among students attending alternative high schools nationwide was unknown. REPORTING PERIOD: February-May 1998. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors the following six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The national Alternative High School Youth Risk Behavior Survey (ALT-YRBS) is one component of the YRBSS; it was conducted in 1998 to measure priority health-risk behaviors among students at alternative high schools. The 1998 ALT-YRBS used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 in the United States who attend alternative high schools. The school response rate was 81.0%, and the student response rate was 81.9%, resulting in an overall response rate of 66.3%. This report summarizes results from the 1998 ALT-YRBS. RESULTS AND INTERPRETATION: In the United States, 73.6% of all deaths among youth and young adults aged 10-24 years results from only four causes--motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1998 ALT-YRBS demonstrate that many students at alternative high schools engage in behaviors that increase their likelihood of death from these four causes. During the 30 days preceding the survey, 51.9% had ridden with a driver who had been drinking alcohol, 25.1% had driven a vehicle after drinking alcohol, 32.9% had carried a weapon, 64.5% had drunk alcohol, and 53.0% had used marijuana. During the 12 months preceding the survey, 15.7% had attempted suicide, and 29.0% had rarely or never worn a seat belt. Substantial morbidity among school-aged youth and young adults also results from unintended pregnancies and STDs, including HIV infection. ALT-YRBS results indicate that in 1998, a total of 87.8% of students at alternative high schools had had sexual intercourse, 54.1% of sexually active students had not used a condom at last sexual intercourse, and 5.7% had ever injected an illegal drug. Among adults aged > or =25 years, 66.5% of all deaths result from two causes--cardiovascular disease and cancer. Most risk behaviors associated with these causes of death are initiated during adolescence. In 1998, a total of 64.1% of students at alternative high schools had smoked cigarettes during the 30 days preceding the survey, 38.3% had smoked a cigar during the 30 days preceding the survey, 71.2% had not eaten > or =5 servings of fruits and vegetables during the day preceding the survey, and 81.0% had not attended physical education (PE) class daily. Comparing ALT-YRBS results with 1997 national YRBS results demonstrates that the prevalence of most risk behaviors is higher among students attending alternative high schools compared with students at regular high schools. Some risk behaviors are more common among certain sex and racial/ethnic subgroups of students. PUBLIC HEALTH ACTION: ALT-YRBS data can be used nationwide by health and education officials to improve policies and programs designed to reduce risk behaviors associated with the leading causes of morbidity and mortality among students attending alternative high schools.

Adolescent↗

Medical costs associated with non-Hodgkin's lymphoma in the United States during the first two years of treatment.

OBJECTIVES: To determine the direct costs of medical care associated with aggressive and indolent non-Hodgkin's lymphoma (NHL) in the United States; to show how costs for aggressive NHL change over time by examining costs related to initial, secondary and palliative treatment phases; and to evaluate the economic consequences of treatment failure in aggressive NHL. PATIENTS AND METHODS: A retrospective cohort analysis of 1999 - 2000 direct costs in newly diagnosed NHL patients and controls (subjects without any cancer) was conducted using the MarketScan medical and drug claims database of large employers across the United States. Treatment failure analysis was conducted for aggressive NHL patients, and was defined by the need for secondary treatment or palliative care after initial therapy. Cost of treatment failure was calculated as difference in regression-adjusted costs between patients with initial therapy only and patients experiencing initial treatment failure. RESULTS: Patients with aggressive (n = 356) and indolent (n = 698) NHL had significantly greater health service utilization and associated costs (all P < 05) than controls (n = 1068 for aggressive, n = 2094 for indolent). Mean monthly costs were 5871 dollars for aggressive NHL vs. 355 dollars for controls (P < 0001) and 3833 dollars for indolent NHL vs. 289 dollars for controls (P < 0001). The primary cost drivers were hospitalization (aggressive NHL = 44% of total costs, indolent NHL = 50%) and outpatient office visits (aggressive NHL = 39%, indolent NHL = 34%). For aggressive NHL, mean monthly initial treatment phase costs (10,970 dollars) and palliative care costs (9836 dollars) were higher than costs incurred during secondary phase (3302 dollars). The mean cost of treatment failure in aggressive NHL was 14,174 dollars per month, and 85,934 dollars over the study period. CONCLUSION: The treatment of NHL was associated with substantial health care costs. Patients with aggressive lymphomas tended to accrue higher costs, compared with those with indolent lymphomas. These costs varied over time, with the highest costs occurring during the initial treatment and palliative care phases. Treatment failure was the most expensive treatment pattern. New strategies to prevent or delay treatment failure in aggressive NHL could help reduce the economic burden of NHL.

Female↗

Potential-years-life-lost from motor vehicle crashes in Israel: an epidemiologic analysis.

Motor Vehicle Crashes (MVC) were the 7th ranking specific cause of mortality (Israel 1975) after ischaemic heart disease (ISHD), cerebrovascular disease, respiratory disease, various types of cancer, and accidents other than MVC, but were the top ranking single cause (in males, next to accidents of all kinds) of Potential-Years-Life-Lost (PYLL) ages 1-65 among men and women and men 1-70 and 2nd ranking cause of PYLL age 1-75 among men. Many young male deaths from MVC and few from non-traumatic causes below age 40 account for these high PYLL rankings for MVC. Israeli age-specific death rates from MVC below age 40 were lower than those of USA, but higher among the elderly (reason: pedestrian deaths). Both Israel's PYLL rate (PYLL per 100 000 persons) from MVC and crude mortality rates are only slightly lower than those of USA. Trends in Israel point to a growing number of drivers among young and poorer groupings, who have been shown elsewhere to be at high-risk for MVC mortality. PYLL from MVC in Israel can be expected to increase, even if crude death rates remain stable or decline. Swift low-cost preventive measures could arrest or reverse these predicted trends.

Accident Prevention↗

Youth risk behavior surveillance--United States, 1995.

Priority health-risk behaviors that contribute to the leading causes of mortality, morbidity, and social problems among youth and adults often are established during youth, extend into adulthood, and are interrelated. The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries, tobacco use, alcohol and other drug use, sexual behaviors, unhealthy dietary behaviors, and physical inactivity. The YRBSS includes both a national school-based survey conducted by CDC and state and local school-based surveys conducted by state and local education agencies. This report summarizes results from the national survey, 35 state surveys, and 16 local surveys conducted among high school students from February through May 1995. In the United States, 72% of all deaths among school-age youth and young adults result from four causes: motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1995 YRBSS suggest that many high school students practice behaviors that may increase their likelihood of death from these four causes: 21.7% had rarely or never used a safety belt, 38.8% had ridden with a driver who had been drinking alcohol during the 30 days preceding the survey, 20.0% had carried a weapon during the 30 days preceding the survey, 51.6% had drunk alcohol during the 30 days preceding the survey, 25.3% had used marijuana during the 30 days preceding the survey, and 8.7% had attempted suicide during the 12 months preceding the survey. Substantial morbidity and social problems among school-age youth and young adults also result from unintended pregnancies and sexually transmitted diseases, including HIV infection. YRBSS results indicate that in 1995, 53.1% of high school students had experienced sexual intercourse, 45.6% of sexually active students had not used a condom at last sexual intercourse, and 2.0% had ever injected an illegal drug. Among adults, 65% of all deaths result from three causes: heart disease, cancer, and stroke. Most of the risk behaviors associated with these causes of death are initiated during adolescence. In 1995, 34.8% of high school students had smoked cigarettes during the 30 days preceding the survey, 39.5% had eaten more than two servings of foods typically high in fat content during the day preceding the survey, and only 25.4% had attended physical education class daily. YRBSS data are being used nationwide by health and education officials to improve national, state, and local policies and programs designed to reduce risks associated with the leading causes of mortality and morbidity. YRBSS data also are being used to measure progress toward achieving 21 national health objectives and one of eight National Education Goals.

Adolescent↗