Bicyclist fatalities in New York City: 1996-2005.

OBJECTIVES: To describe bicyclist fatalities in a traffic-dense, urban environment. METHODS: Multiple New York City (NYC) agencies provided information on bicyclist deaths. Fatality Analysis Reporting System (FARS) data were used to compare NYC's bicyclist fatality rate involving motor vehicles with rates in comparable urban centers. RESULTS: Between 1996 and 2005, 225 bicyclists died in NYC. Most fatalities resulted from motor vehicle crashes (92%). Men in NYC had higher death rates than women, and no age group had higher risk. Most of NYC's bicyclist fatalities occurred at intersections (88%). Head injuries contributed to 77 percent of deaths; helmet use was rare (3%). Most fatal crashes (91%) involved motorist and bicyclist factors, such as inattention and unsafe speed. Alcohol was detected in 21 percent of bicyclists dying within 3 hours of a crash; motorist alcohol use was a contributing factor in 6 percent of crashes. Over half were on multi-lane roads (53%). Large vehicles were involved in 30 percent of crashes but comprise 5-17 percent of road vehicles. Bicyclist fatality rates involving motor vehicles in NYC were comparable to those of other cities. CONCLUSION: Findings suggest the merits of multipronged efforts to prevent crashes and to improve bicyclist safety in NYC and in other dense, urban environments. Motorists and bicyclists should be made aware of the risks of alcohol use and the benefits of helmet-wearing. Road users should pay attention to traffic control measures and travel at safe speeds. Interventions that control traffic at intersections and on multilane streets, that dedicate and demarcate routes for motorists and cyclists, and that improve visibility, especially for large vehicles, warrant consideration.

Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer.

BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. METHODS: By thorough molecular and clinical evaluation of 41 families, two different groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive families without mutations in these genes and without microsatellite instability in their corresponding tumours. RESULTS: Significant clinical differences between these two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours (median 43 v 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68% of the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14% in group 2 (p < 0.010). Thirdly, more synchronous and metachronous colorectal (p = 0.017) and extracolorectal tumours (p < 0.001) were found in group 1. Fourthly, a higher colorectal adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronous or metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower progression of adenomas to carcinomas. As three mutation negative tumours revealed chromosomal instability after comparative genomic hybridisation, these tumours may be caused by one or more highly penetrant disease alleles from the chromosomal instability pathway. CONCLUSION: These data show that HNPCC includes at least two entities with clinical and molecular differences. This will have implications for surveillance programmes and for cancer research.

Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms?

5-8% of all colorectal cancer cases are assumed to be due to germline mutations in DNA mismatch repair genes. Mutation analysis of these genes in affected families enables one to identify subjects with an inborn susceptibility to colorectal tumorogenesis and to offer presymptomatic testing to family members at risk, provided that the mutation detected is a truncating one or a missense mutation that has either been judged as disease causing in other families or segregates with the disease and results in a microsatellite instability of the corresponding tumor. Segregation analysis within the family or microsatellite analysis of the tumor is, however, not always possible. In these cases, assessment of the relevance of the sequence variation identified is very difficult. On the other hand, discrimination between inactivating mutations and innocuous sequence polymorphisms is of extreme importance for clinical and genetic counseling of affected families. Here we report 16 rare sequence variants of the hMLH1 and hMSH2 genes including 11 different missense variations found in a cohort of 254 suspected HNPCC patients. We provide evidence, that missense variations in hMLH1 do not necessarily result in microsatellite instability of the corresponding tumor DNA. These patients would have been missed had one followed the recommendations of using only microsatellite analysis for the selection of patients at high risk of hereditary non-polyposis colorectal cancer for mutation analysis.

Impediments to employment under welfare reform: the importance of physical health and psychosocial characteristics.

The impact of Connecticut's welfare reform program (Jobs First), physical and mental health status, personal resources and household violence on employment was examined 18 months after women were randomized to either the welfare reform or the older AFDC program. Multivariate analyses showed that although the Jobs First program was statistically significantly associated with women having worked sometime since assignment to the welfare reform program, the Jobs First program was not associated with women currently working or having worked at some point but no longer working. Rather, women were more likely to be working at the 18 month interview if they reported frequent help from their social networks (OR = 1.52; p = .009), they had at least a high school degree (OR = 1.65; p =.002) and they were in good physical health (OR = 3.41; p = .009). Women who had worked sometime since random assignment but were no longer working at the 18 month interview reported few social contacts (OR = 1.33; p = .042), did not pay rent or own their own homes (OR = 6.94; p = .025), reported receiving AFDC for 2 years or more prior to randomization (OR = 1.83; p = .035) and reported high levels of household violence (OR = 1.52; p = .035). The need for attention to be focused on the importance of health problems, household violence and personal resources for the successful transitioning from public income support to employment is discussed.

Preschool and school age children under welfare reform.

This study compared the behavioral and school problems of young children whose mothers participated in two different income support programs, Jobs First and AFDC. The analyses also included measures of maternal education, maternal health, maternal psychological factors, and family environment. There were no differences in child school or behavioral problems across the income support programs. Children, however, were more likely to have school problems if they were older or if their mothers received less than a high school education, reported child behavioral problems or made criteria for depression on the CIDI. Behavioral problems were more likely to occur if mothers reported violence in the home, many depressive symptoms on the CES-D, few child positive qualities, or if the child had repeated a grade. Several familial factors, then, must be addressed in order to ensure that children excel both academically and behaviorally.

Identification of violence in the home: pediatric and parental reports.

OBJECTIVES: To compare the rates of domestic violence reported by mothers with those identified by physicians, to compare the rates of harsh discipline practices reported by mothers with the rates of abuse identified by physicians, and to examine the relationship between reported domestic violence and harsh discipline practices. DESIGNS: Interviews with parents and pediatricians to compare pediatric detection of domestic violence and child abuse with parental reports of domestic violence and harsh discipline practices. SETTING: Community-based pediatric practices in the 13-town greater New Haven, Conn, area. PARTICIPANTS: Of the 23 practices invited, 19 agreed to participate. Of the 2,006 parents of eligible 4- to 8-year-olds asked to participate, 1,886 (94%) completed the Child Behavior' Checklist. Of those invited into the interview portion, 1,148 (83%) completed the 90-minute in-person interview. MAIN OUTCOME MEASURES: Percentages of cases of domestic violence identified by pediatricians and reported by mothers. Percentages of cases of child abuse detected by pediatricians and percentages of mothers reporting that they have hit their children and left a mark. RESULTS: Pediatricians detected domestic violence in 0.3% of the cases, but parents reported domestic violence in 4.2% kappa= 0.106 [95% confidence interval, -0.007 to 0.219]). Pediatricians identified physical abuse of children in 0.5% of the cases, while mothers reported hitting their children and leaving a mark in 21.6% (kappa = 0.003 [95% confidence interval, -0.018 to 0.024]). Mothers reporting domestic violence were significantly more likely to report hitting hard enough to leave a mark (relative risk, 1.6 ([95% confidence interval, 1.09-2.38]) compared with those not reporting domestic violence. Physicians identifying domestic violence were not significantly more likely to report child abuse than those not identifying domestic violence. CONCLUSIONS: Parents report more cases of violence than pediatricians detect. Pediatricians should ask parents directly about domestic violence and harsh discipline.

A unique drug treatment program for pregnant and postpartum substance-using women in New York City: results of a pilot project, 1990-1995.

In the 1980s, there was virtually no drug treatment for pregnant women in New York City, especially women who used crack cocaine. The purpose of the Parent and Child Enrichment (PACE) demonstration project was to assess the effectiveness of the one-stop shopping model of drug treatment for this population. Among PACE clients, 88% were primarily users of crack cocaine. The mean total length of stay was 100.0 days (median 55.5 days). Client retention 42 days after intake was 54.3%. This paper describes the essential components of this program model. "Long-stay" and "short-stay" clients were compared using urine toxicology tests and activity logs. In addition, the birth outcomes of clients were compared to two similar populations. A strong positive correlation was found between total length of stay and low rate of positive urine drug tests (UDTs). Infants of PACE long-stay clients had greater mean birth weight, less low birth weight, and less intrauterine growth retardation than the infants of the comparison groups. Fetal exposure to cocaine was decreased dramatically among women who were enrolled for 42 or more days during their pregnancy. This model of drug treatment for pregnant and postpartum women seems to improve mothers' lives, fetal drug exposure, and birth outcome significantly.

Breast-feeding initiation in New York City, 1979 to 1996.

OBJECTIVES: The purpose of this study was to explore changes in breast-feeding initiation from 1979 to 1996 among infants born in New York City hospitals. METHODS: All New York City hospitals were surveyed every 2 years. Hospital staff reported feeding method at newborn discharge. RESULTS: New York City breast-feeding initiation rates increased consistently from 1979 to 1996 (from 29% to 58%, P < .0001), including 1984 to 1990, when rates decreased nationally. CONCLUSIONS: A 1984 New York State regulation requiring each hospital to designate a lactation coordinator may have been associated with the continuing increases in breast-feeding initiation.

Evaluation of educational programs: an affiliate survey.

PIP: The Planned Parenthood Federation of America (PPFA) conducted a survey in 1996 to investigate the use of educational program evaluation among its affiliates. Of the 153 surveys mailed out, 55 (36%) were returned. Evaluations of school-based educational programs were conducted consistently by 19% of respondents and occasionally by 72%; non-school-based programs were evaluated consistently by 31% of associations and occasionally by 64%. In both types of presentations, evaluations were likely to consist of pre- and post-testing, post-tests alone, or informal discussions with participants. The outcome variables most often measured were participant satisfaction with the presentation, knowledge gained, and behavioral change. 75% of educational directors recognized the value of evaluations for purposes such as program planning, providing a baseline, and procuring funding; 80% were interested in doing more evaluations. However, directors identified numerous obstacles to evaluation: insufficient time, lack of expertise or models, problems conducting meaningful impact evaluations, limited funds for this purpose, and fear that results would be disappointing. Despite its low response rate, this survey identified a need for PPFA's Education Department to promote program evaluation among its affiliates, provide staff training, and develop meaningful program impact measures.^ieng

Disseminated hypopigmented keratoses.

We present two cases of asymptomatic, widespread keratotic eruptions in young female patients. Clinically, the lesions are well-demarcated, small, hypopigmented, flat-topped papules occurring on the trunk and extremities in a uniform distribution. Skin biopsy specimens from one patient revealed hyperorthokeratosis, papillomatosis, and a normal amount of melanin. We suggest that this is a newly recognized dermatologic entity that may be descriptively termed disseminated hypopigmented keratoses. Disseminated hypopigmented keratoses may be distinguished by clinical and histologic criteria from similar keratotic eruptions. Since the lesions of disseminated hypopigmented keratoses are both inconspicuous and asymptomatic, it is likely that the disorder is more prevalent than our two cases would suggest.

Endothelial expression of intercellular adhesion molecule (ICAM-1) is unaffected by marrow aplasia-inducing chemotherapy.

Sequential skin biopsies were obtained from five patients receiving chemotherapy for acute myelocytic leukemia. The first specimen was taken on the fourth day of initial chemotherapy and subsequent specimens were obtained at weekly intervals thereafter, until discharge. In all cases, clinically normal skin was selected as the biopsy site. A panel of monoclonal antibodies was applied to frozen tissue sections, including anti-intercellular adhesion molecule-1 (ICAM-1), anti-lymphocyte function-associated antigen-1 (LFA-1), and anti-HLA-DR. Bound antibody was detected using the avidin-biotin complex method. Endothelial cell expression of ICAM-1 and lymphocyte expression of LFA-1 were unaffected over the course of the ensuing, profound marrow aplasia. This finding suggests that this mechanism of lymphocyte trafficking in the skin remains operational despite the administration of antileukemic agents.

The photoaggravated dermatoses.

The photoaggravated dermatoses are diverse diseases adversely affected by sunlight or artificial ultraviolet (UV) exposure. The role of UVR is often well-recognized, as in lupus erythematosus (LE) and bullous pemphigoid (BP). Immunologic theories for the cause of the photosensitivity in lupus erythematosus are the production of UV-DNA antibodies with subsequent immune complex formation, a partial defect in DNA repair following UV exposure, and the release or stimulation of potent cutaneous immunologic mediators. However, mechanisms are still not fully elucidated. Photosensitivity has also been described in erythema multiforme, actinic lichen planus, viral exanthems, cutaneous T-cell lymphoma, eczema, and psoriasis. Treatment is restriction of light exposure, use of high protection sunscreens, and treatment of the underlying disorder.

Photochemotherapy of generalized granuloma annulare.

Various forms of treatment for generalized granuloma annulare have been employed with little success. The results of treatment with topical and intralesional corticosteroids, as well as systemic therapy with corticosteroids, salicylates, aspirin, niacinamide, and chloroquine, have been generally disappointing. We describe five patients with generalized granuloma annulare of several years' duration who were treated with oral psoralen plus ultraviolet A irradiation. Lesions were present on the extremities, buttocks, and trunk in the form of macules, papules, and plaques. One patient also had perforating lesions on her thighs. Flattening of the lesions with decreased erythema and pigmentation was noted as early as 1 month after initiation of treatment. Complete clearance was achieved in all patients. Maintenance therapy has been required, resulting in prolonged disease-free intervals. Although the mechanism of action of oral psoralen plus ultraviolet A irradiation in granuloma annulare is unclear, one possibility is selective elimination of the cells that are responsible for initiating the disease.

Site-directed mutagenesis of core sequence elements 9R', 9L, 9R, and 2 in self-splicing Tetrahymena pre-rRNA.

The intron within the Tetrahymena thermophila nuclear large rRNA precursor is the best studied example of group I self-splicing introns. In this paper, we examine the structural and functional roles of four internal sequence elements which are characteristic of group I introns in the RNA-catalyzed processing reactions. Oligonucleotide-directed mutagenesis was used to generate mutations in sequence elements 9R', 9L, 9R and 2 of the Tetrahymena intervening sequence. Self-splicing activities of variant precursor RNAs were characterized by in vitro splicing following transcription with T7 or SP6 RNA polymerase. First, we confirm the proposed base pairing of sequence elements 9R and 9R' by construction and analysis of compensatory mutations. Mutations in elements 9R (G272A C274G) and 9R' (G100C C102U) each disrupt the pairing and eliminate self-splicing activity. A compensatory 9R/9R' mutation (G100C C102U G272A C274G) restores pairing and normal splicing activity. We conclude that 9R X 9R' pairing is a requirement for self-splicing. Second, we show that self-splicing activity is very sensitive to both nucleotide sequence and RNA secondary structure in the pairing segments of elements 9L and 2. Mutations within these regions at positions 266, 268, 307, and 309 can increase as well as decrease activity relative to wild type. Third, a mutation in the highly conserved nonpairing segment of element 9L (U259A A261C) increases KM for GTP from 29 to 120 microM, but does not otherwise affect splicing activity. The primary consequence of this mutation is a decrease in GTP binding energy of approximately 0.9 kcal/mol. Last, we show that a mutation in the highly conserved nonpairing segment of element 2 (A301C A302G G303C) eliminates transesterification activity, but does not affect 3' splice site hydrolysis.

Role of conserved sequence elements 9L and 2 in self-splicing of the Tetrahymena ribosomal RNA precursor.

Oligonucleotide-directed mutagenesis has been used to alter highly conserved sequences within the intervening sequence (IVS) of the Tetrahymena large ribosomal RNA precursor. Mutations within either sequence element 9L or element 2 eliminate splicing activity under standard in vitro splicing conditions. A double mutant with compensatory base changes in elements 9L and 2 has accurate splicing activity restored. Thus, the targeted nucleotides of elements 9L and 2 base-pair with one another in the IVS RNA, and pairing is important for self-splicing. Mutant splicing activities are restored by increased magnesium ion concentrations, supporting the conclusion that the role of the targeted bases in splicing is primarily structural. Based on the temperature dependence, we propose that a conformational switch involving pairing and unpairing of elements 9L and 2 is required for splicing.