Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155818/1/Karagas_et_al_1998_Design_of_an_epidemiologic.pd

Design of an epidemiologic study of drinking water arsenic exposure and skin and bladder cancer risk in a U.S. population.

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic

Design of an Epidemiologic Study of Drinking Water Arsenic Exposure and Skin and Bladder Cancer Risk in a U.S. Population

Ingestion of arsenic-contaminated drinking water is associated with an increased risk of several cancers, including skin and bladder malignancies; but it is not yet clear whether such adverse effects are present at levels to which the U.S. population is exposed. In New Hampshire, detectable levels of arsenic have been reported in drinking water supplies throughout the state. Therefore, we have begun a population-based epidemiologic case-control study in which residents of New Hampshire diagnosed with primary squamous cell (n = 900) and basal cell (n = 1200) skin cancers are being selected from a special statewide skin cancer incidence survey; patients diagnosed with primary bladder cancers (n = 450) are being identified through the New Hampshire State Cancer Registry. Exposure histories of these patients will be compared to a control group of individuals randomly selected from population lists (n = 1200). Along with a detailed personal interview, arsenic and other trace elements are being measured in toenail clipping samples using instrumental neutron activation analysis. Household water samples are being tested on selected participants using a hydride generation technique with high-resolution inductively coupled plasma mass spectrometry. In the first 793 households tested arsenic concentrations ranged from undetectable (0.01 microgram/l) to 180 microgram/l. Over 10% of the private wells contained levels above 10 microgram/l and 2.5% were above 50 microgram/l. Based on our projected sample size, we expect at least 80% power to detect a 2-fold risk of basal cell or squamous cell skin cancer or bladder cancer among individuals with the highest 5% toenail concentrations of arsenic

Mechanical and structural properties of YOYO-1 complexed DNA

YOYO-1 is a fluorescent dye widely used for probing the statistical–mechanical properties of DNA. However, currently contradicting data exist how YOYO-1 binding alters the DNA structure and rigidity. Here, we systematically address this problem using magnetic tweezers. Remarkably, we find that the persistence length of DNA remains constant independent of the amount of bound YOYO-1, which contrasts previous assumptions. While the ionic conditions can considerably alter the stability of YOYO-1 binding, the DNA bending rigidity seems not to be affected. We furthermore determine important structural parameters such as the binding site size, the elongation, as well as the untwisting angle per bound YOYO-1 molecule. We expect that our assay, in which all the parameters are determined within a single experiment, will be beneficial for a large range of other DNA binding drugs

Markers of low level arsenic exposure for evaluating human cancer risks in a US population

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155831/1/Karagas_et_al_2001_Markers_of_low_level.pd

Efficient preparation of internally modified single-molecule constructs using nicking enzymes

Investigations of enzymes involved in DNA metabolism have strongly benefited from the establishment of single molecule techniques. These experiments frequently require elaborate DNA substrates, which carry chemical labels or nucleic acid tertiary structures. Preparing such constructs often represents a technical challenge: long modified DNA molecules are usually produced via multi-step processes, involving low efficiency intermolecular ligations of several fragments. Here, we show how long stretches of DNA (>50 bp) can be modified using nicking enzymes to produce complex DNA constructs. Multiple different chemical and structural modifications can be placed internally along DNA, in a specific and precise manner. Furthermore, the nicks created can be resealed efficiently yielding intact molecules, whose mechanical properties are preserved. Additionally, the same strategy is applied to obtain long single-strand overhangs subsequently used for efficient ligation of ss- to dsDNA molecules. This technique offers promise for a wide range of applications, in particular single-molecule experiments, where frequently multiple internal DNA modifications are required

Awareness and use of intertrochanteric osteotomies in current clinical practice. An international survey

Current literature shows that intertrochanteric osteotomies can produce excellent results in selected hip disorders in specific groups of patients. However, it appears that this surgical option is considered an historical one that has no role to play in modern practice. In order to examine current awareness of and views on intertrochanteric osteotomies among international hip surgeons, an online survey was carried out. The survey consisted of a set of questions regarding current clinical practice and awareness of osteotomies. The second part of the survey consisted of five clinical cases and sought to elicit views on preoperative radiological investigations and preferred (surgical) treatments. The results of our survey showed that most of these experts believe that intertrochanteric osteotomies should still be performed in selected cases. Only 56% perform intertrochanteric osteotomies themselves and of those, only 11% perform more than five per year. The responses to the cases show that about 30–40% recommend intertrochanteric osteotomies in young symptomatic patients. This survey shows that the role of intertrochanteric osteotomies is declining in clinical practice

Methylmercury cycling in sediments on the continental shelf of southern New England

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 70 (2006): 918-930, doi:10.1016/j.gca.2005.10.020.Exposure of humans to monomethylmercury (MMHg) occurs primarily through consumption of marine fish, yet there is limited understanding concerning the bioaccumulation and biogeochemistry of MMHg in the biologically productive coastal ocean. We examined the cycling of MMHg in sediments at three locations on the continental shelf of southern New England in September 2003. MMHg in surface sediments is related positively to inorganic Hg (Hg(II)=total Hg-MMHg), the geographical distribution of which is influenced by organic material. Organic matter also largely controls the sediment-water partitioning of Hg species and governs the availability of dissolved Hg(II) for methylation. Potential gross rates of MMHg production, assayed by experimental addition of 200Hg to intact sediment cores, are correlated inversely with the distribution coefficient (KD) of Hg(II) and positively with the concentration of Hg(II), most probably as HgS0, in 0.2-µm filtered pore water of these low-sulfide deposits. Moreover, the efflux of dissolved MMHg to overlying water (i.e., net production at steady state) is correlated with the gross potential rate of MMHg production in surface sediments. These results suggest that the production and efflux of MMHg from coastal marine sediments is limited by Hg(II), loadings of which presumably are principally from atmospheric deposition to this region of the continental shelf. The estimated diffusive flux of MMHg from the shelf sediments averages 9 pmol m-2 d-1. This flux is comparable to that required to sustain the current rate of MMHg accumulation by marine fish, and may be enhanced by the efflux of MMHg from near-shore deposits contaminated more substantially with anthropogenic Hg. Hence, production and subsequent mobilization of MMHg from sediments in the coastal zone may be a major source of MMHg to the ocean and marine biota, including fishes consumed by humans.This research was supported by a STAR student fellowship (U91591801) and grant (R827635) from the U.S. Environmental Protection Agency, a graduate student fellowship and grant from the Hudson River Foundation for Environmental Research, and the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Doherty Foundation

Femoroacetabular impingement and classification of the cam deformity: the reference interval in normal hips

BACKGROUND AND PURPOSE: Most patients with femoroacetabular impingement (FAI) have a cam deformity, which may be quantified by measuring the alpha angle and anterior offset ratio (AOR). Knowledge of what constitutes a "normal" alpha angle and AOR is limited. We defined the reference intervals of these measurements from normal hips in the general population. PATIENTS AND METHODS: 157 individuals from the general population were reviewed clinically and radiographically. 74 individuals with clinical evidence of hip disease or radiographic evidence of osteoarthritis (OA) were excluded, leaving a study group of 83 individuals (mean age 46 (22-69) years, 44 females) with normal hips. The alpha angles and AORs were measured from cross-table lateral radiographs taken in 15 degrees internal rotation. A validation study consisting of a cadaver study and a measurement reliability study was also performed. RESULTS: The mean alpha angle was 48 degrees in men and 47 degrees in women. The mean AOR was 0.19, the same in men and women. Thus, sexes were combined to derive 95% confidence intervals for the population mean alpha angle (46-49 degrees ) and AOR (0.18-0.20). The 95% reference interval for the alpha angle was 32-62 degrees degrees, and for the AOR it was 0.14-0.24. The validation study confirmed that these measurements were resistant to a reasonable degree of variation in positioning and that the repeatability and reproducibility of the measurements was good. INTERPRETATION: These reference intervals indicate that clinically and radiographically normal hips may have alpha angles and AORs that have previously been considered "abnormal". The thresholds provided by this study will aid classification of individuals involved in longitudinal studies of FAI and OA, and may be of use to the practicing clinician in evaluating the young adult with hip pain

Three-dimensional mechanical evaluation of joint contact pressure in 12 periacetabular osteotomy patients with 10-year follow-up

Background and purpose Because of the varying structure of dysplastic hips, the optimal realignment of the joint during periacetabular osteotomy (PAO) may differ between patients. Three-dimensional (3D) mechanical and radiological analysis possibly accounts better for patient-specific morphology, and may improve and automate optimal joint realignment