The public health exposome and pregnancy-related mortality in the United States: a high-dimensional computational analysis.

BACKGROUND: Racial inequities in maternal mortality in the U.S. continue to be stark. METHODS: The 2015-2018, 4-year total population, county-level, pregnancy-related mortality ratio (PRM; deaths per 100,000 live births; National Center for Health Statistics (NCHS), restricted use mortality file) was linked with the Public Health Exposome (PHE). Using data reduction techniques, 1591 variables were extracted from over 62,000 variables for use in this analysis, providing information on the relationships between PRM and the social, health and health care, natural, and built environments. Graph theoretical algorithms and Bayesian analysis were applied to PHE/PRM linked data to identify latent networks. RESULTS: PHE variables most strongly correlated with total population PRM were years of potential life lost and overall life expectancy. Population-level indicators of PRM were overall poverty, smoking, lack of exercise, heat, and lack of adequate access to food. CONCLUSIONS: In this high-dimensional analysis, overall life expectancy, poverty indicators, and health behaviors were found to be the strongest predictors of pregnancy-related mortality. This provides strong evidence that maternal death is part of a broader constellation of both similar and unique health behaviors, social determinants and environmental exposures as other causes of death.

Hexavalent chromium exposures and exposure-control technologies in American enterprise: results of a NIOSH field research study.

The National Institute for Occupational Safety and Health (NIOSH) conducted 21 field surveys in selected industries to characterize workers' exposures to hexavalent chromium-containing airborne particulate and to evaluate existing technologies for controlling these exposures. Hexavalent chromium Cr(VI) is a respiratory irritant and chronic inhalation may cause lung cancer. Primary evaluation methods included collection of full work shift, personal breathing-zone (PBZ) air samples for Cr(VI), measurement of ventilation system parameters, and documentation of processes and work practices. This study emphasized evaluation of engineering exposure control measures, so PBZ exposures were measured on the outside of personal protective equipment, for example, respirators. Field surveys were conducted in two chromium electroplating facilities, including one where full-shift PBZ exposures to Cr(VI) ranged from 3.0 to 16 times the 1 micro g/m(3)NIOSH recommended exposure limit (REL) despite several engineering controls on the plating tanks. At a painting and coating facility that used Cr(VI)-containing products, full-shift exposures of painters and helpers (2.4 to 55 micro g/m(3)) exceeded the REL, but LEV effectiveness was limited. Other operations evaluated included welding in construction; metal cutting operations on chromium-containing materials in ship breaking; chromate-paint removal with abrasive blasting; atomized alloy-spray coating; foundry operations; printing; and the manufacture of refractory brick, colored glass, prefabricated concrete products, and treated wood products. NIOSH researchers concluded that, in many of the evaluated processes, Cr(VI) exposures at or below the current NIOSH REL are achievable. However, for some processes, it is unclear whether controlling exposures to this range is consistently achievable without respirator use. Some operations involving the application of coatings and finishes may be among those most difficult to control to this range. Most operations judged to be moderately difficult to control to this range involve joining and cutting metals with relatively high chromium content. Nonetheless, exposures in a wide variety of other processes were judged more easily controllable to the current REL or below, or were found to be minimal, including some operations meeting the general descriptions named above but with different specific operating parameters producing lower Cr(VI) exposures.

The cemented custom femoral stem--a 10 year review.

We report a series of 706 patients (759 hip implants) with an average follow up of 10.5 years (range, 10-11 years) following total hip replacement (THR) using a cemented custom-made femoral stem and a cemented HDP acetabular component. The fate of every implant is known. One hundred and seventy-four patients (23%) were deceased at the time of their 10-year review all died with a functioning THR in situ. Four hundred and sixty-two patients (61%) were subsequently reviewed. One hundred and twenty three patients (16%) were assessed by telephone review, as they were too ill or unwilling to attend. Kaplan-Meier survival analysis (all components) demonstrated a median survival at 10 years of 96.05% or 95% Confidence Intervals (CI) for median survival of (94.41% to 97.22%). Revision surgery occurred in 30 cases (3.9%). Seventeen had full revisions (2.2%) and 13 (1.7%) socket revisions only. Twenty-one out of 30 revisions were for infection or dislocation. There were 2 cases (0.3%) of revision for aseptic loosening of the stem. The 10-year results of the custom femoral titanium stem are encouraging and compare well with other cemented systems.

Junctional biases in the naive TCR repertoire control the CTL response to an immunodominant determinant of HSV-1.

The enormous diversity of the T cell pool makes it difficult to determine whether inherent biases in the naive TCR repertoire can influence T cell responsiveness. In C57BL/6 mice the cytotoxic T lymphocyte response to an immunodominant HSV-1 determinant (gB) is characterized by a prominent bias in Vbeta element usage, associated with a conserved and preferentially D element-encoded CDR3 sequence. Comparison of naive and gB-specific T cell populations revealed a similar enrichment of germline D element-encoded CDR3 sequences in the preimmune repertoire. Strikingly, eliminating the germline coding of the gB-specific CDR3 sequence caused an almost complete loss of the dominant subset of gB-specific T cells, illustrating that CDR3 biases can significantly alter both the composition and strength of an immune response.

Comparison of three sampling and analytical methods for the determination of airborne hexavalent chromium.

A field study was conducted with the goal of comparing the performance of three recently developed or modified sampling and analytical methods for the determination of airborne hexavalent chromium (Cr(VI)). The study was carried out in a hard chrome electroplating facility and in a jet engine manufacturing facility where airborne Cr(VI) was expected to be present. The analytical methods evaluated included two laboratory-based procedures (OSHA Method ID-215 and NIOSH Method 7605) and a field-portable method (NIOSH Method 7703). These three methods employ an identical sampling methodology: collection of Cr(VI)-containing aerosol on a polyvinyl chloride (PVC) filter housed in a sampling cassette, which is connected to a personal sampling pump calibrated at an appropriate flow rate. The basis of the analytical methods for all three methods involves extraction of the PVC filter in alkaline buffer solution, chemical isolation of the Cr(VI) ion, complexation of the Cr(VI) ion with 1,5-diphenylcarbazide, and spectrometric measurement of the violet chromium diphenylcarbazone complex at 540 nm. However, there are notable specific differences within the sample preparation procedures used in three methods. To assess the comparability of the three measurement protocols, a total of 20 side-by-side air samples were collected, equally divided between a chromic acid electroplating operation and a spray paint operation where water soluble forms of Cr(VI) were used. A range of Cr(VI) concentrations from 0.6 to 960 microg m(-3), with Cr(VI) mass loadings ranging from 0.4 to 32 microg, was measured at the two operations. The equivalence of the means of the log-transformed Cr(VI) concentrations obtained from the different analytical methods was compared. Based on analysis of variance (ANOVA) results, no statistically significant differences were observed between mean values measured using each of the three methods. Small but statistically significant differences were observed between results obtained from performance evaluation samples for the NIOSH field method and the OSHA laboratory method.

The cytotoxic T-cell response to herpes simplex virus type 1 infection of C57BL/6 mice is almost entirely directed against a single immunodominant determinant.

Many virus infections give rise to surprisingly limited T-cell responses directed to very few immunodominant determinants. We have been examining the cytotoxic T-lymphocyte (CTL) response to herpes simplex virus type 1 (HSV-1) infection. Previous studies have identified the glycoprotein B-derived peptide from residues 498 to 505 (gB(498-505)) as one of at least three determinants recognized by HSV-1-specific CTLs isolated from C57BL/6 mice. We had previously found that in vitro-derived CTLs directed to gB(498-505) show a characteristic pattern of T-cell receptor (TCR) usage, with 60% of gB(498-505)-specific CD8(+) T cells expressing BV10(+) TCR beta chains and a further 20% expressing BV8S1. In this report, we confirm that this TCR V-region bias is also reflected in the ex vivo response to HSV-1 infection. A high proportion of activated CD8(+) draining lymph node cells were found to express these dominant V regions, suggesting that a substantial number of in vivo responding T cells were directed to this one viral determinant. The use of an HSV-1 deletion mutant lacking the gB(498-505) determinant in combination with accurate intracellular gamma interferon staining allowed us to quantify the extent of gB-specific T-cell dominance. Together, these results suggested that between 70 and 90% of all CD8(+) HSV-1-specific T cells target gB(498-505). While deletion of this determinant resulted in an attenuated CD8(+) T-cell response, it also permitted the emergence of one or more previously unidentified cryptic specificities. Overall, HSV-1 infection of C57BL/6 mice results in an extremely focused pattern of CD8(+) T-cell selection in terms of target specificity and TCR expression.

Caffeine dependence in schoolchildren?

Schoolchildren (N = 289) kept a log and calculated their habitual caffeine consumption (principally in soft drinks). On 2 successive days, they completed a 20-item checklist adapted from the Profile of Moods Scale. On Day 2, they abstained from caffeine. Complete data were obtained for 175 children. A low-consumption group (10 mg or less daily) was compared with a high-consumption group (50 mg or more daily). The high-consumption group reported more stimulation than did the low-consumption group on Day 1 and more dysphoric symptoms during abstinence on Day 2. The results of this open-label pilot trial suggest that a large-scale double-blind placebo-controlled trial would be worthwhile.

Antigen-specific CD8+ T cell subset distribution in lymph nodes draining the site of herpes simplex virus infection.

Inoculation with replicating virus leads to an increase in T cell numbers within lymph nodes that drain the site of infection. This increase has been associated with a nonspecific proliferation of bystander cells, with only a minority thought to be directed to the infectious agent. Such an assumption is largely based on precursor cytotoxic T lymphocyte (CTL) estimations using limiting dilution analysis. Recently, studies using more advanced molecular approaches have suggested that such functionally derived precursor frequencies considerably underestimate the proportion of T cells specific for the antigen under investigation. We have defined T cell receptor sequences characteristic of CTL populations directed to a dominant determinant of the herpes simplex virus (HSV) glycoprotein B (gB). In this investigation, we used this receptor signature as a probe to directly monitor changes occurring within lymph nodes draining the sites of active infection with HSV. We found that although lymph node CD8+ T cell numbers increase as a consequence of HSV infection, the majority of these cells are small resting cells that are not enriched for gB-specific receptors. In contrast, a significant proportion of activated T cells are highly enriched for CTL bearing gB-specific receptors. Our results are therefore consistent with a nonspecific migration of CTL precursors into the lymph nodes draining the site of infection, followed by the activation and proliferation of the antigen-specific subset that normally makes up a small proportion of the naive T cell repertoire.

Canine epilepsy: a genetic counselling programme for keeshonds.

The predisposition of keeshonds (Dutch barge dogs) to an idiopathic epilepsy appears to be determined by a single autosomal recessive gene. The pedigrees of 15 litters which included animals diagnosed as epileptic ('fitters') were compared with those of 34 contemporary, normal animals. The pedigrees of all the fitters traced back, on both the paternal and maternal sides, to a common ancestor. Subsequently, further pedigrees and details of litters were gathered. If both parents of a fitter were heterozygous ('carriers'), the progeny (120 in number) of all known carrier x carrier matings would be expected to have a ratio of three phenotypically normal animals to one fitter, that is, 90:30. The ratio observed (91:29) was not significantly different. The Keeshond Club has published a list from which the identities of carriers can be inferred, with the intention that known carriers should be excluded from breeding. A genetic counselling programme has been in operation since 1989, which is based on advising breeders on the probability that the offspring of proposed matings would be fitters or carriers; advice has been given on 77 proposed matings. The mean probability that the proposed matings would result in carriers has declined significantly, and this is consistent with a decline in the frequency of the gene for this form of epilepsy in the breed.

Control of paint overspray in autobody repair shops.

Commercially available controls for reducing worker exposure to paint overspray were evaluated in six autobody shops and a spray-painting equipment manufacturer's test facility. Engineering control measures included spray-painting booths, vehicle preparation stations, and spray-painting guns. The controls were evaluated by measuring particulate overspray concentrations in the worker's breathing zone, visualizing the airflow in spray-painting booths and vehicle preparation stations, and measuring airflow volumes and velocities. In addition, respirator usage observations were collected at five of the autobody repair shops, and quantitative fit tests were conducted on existing respirators at three shops. Several conclusions were drawn from this study. Downdraft spray-painting booths provide lower particulate overspray concentrations measured on the worker than crossdraft and semidowndraft spray-painting booths. In the latter two booths, the spray-painting gun can disperse as much as half the paint overspray into the incoming fresh air, increasing worker overspray exposure. Vehicle preparation stations have no walls to contain the overspray and, commonly, a single exhaust fan removes air from the painting area. Airflow patterns suggest that these do not control the paint overspray. Switching from a conventional spray-painting gun to a high-volume low pressure spray-painting gun reduced the particulate overspray concentration by a factor of 2 at a manufacturer's test facility. However, this change did not significantly affect solvent concentrations. Finally, respirator usage in five of the six shops studied was inappropriate. Respirators were poorly maintained and/or did not fit the workers, perhaps due to the absence of a formal respirator program.

Tail short variable: characterization of a new mouse mutant, and its possible analogy to certain human vascular disruption defects.

A new mouse mutant, tail short variable (Tsv) produces a reduction deformity of the tail, growth retardation, and, in adults, a mild anemia. Genetic and embryological studies show that on all genetic backgrounds there is variable viability of Tsv/Tsv and Tsv/+ and phenotypic overlap within these and with +/+. A modifier is located to a short segment of chromosome 7, which alters the tail length of Tsv/+ mice up to 15%. The modifier, Tsv, and a coat texture mutant come from the same wild Peru mouse. The tail deformity is associated with, and may be caused by, a vascular disruption of the caudal aorta starting on day 11 of gestation. Thus Tsv appears to be different from each of the thirty known mouse mutants involving the tail. It is suggested that Tsv could be a mouse model for human conditions involving transverse terminal limb defects such as Moebius and de Lange syndromes.

Women at high risk of HIV infection from drug use.

The purpose of this project was to study women at high risk for contracting AIDS from intravenous drug use or from sexual contact with addicts. Characteristics of the population, differences between HIV+ and HIV- women, substance abuse in primary caretakers of this high risk population, and changes in drug use when learning of HIV status were investigated. Subjects were mothers at high risk for contracting HIV, whose children were referred to a pediatric AIDS clinic of a large urban hospital because of AIDS risk factors. HIV testing revealed that 27 women were HIV+ and 13 were HIV-. The most common source of infection reported by the HIV+ women was sexual contact (17 subjects), with the remainder reporting that they were unsure of the source or reported intravenous drug use as their source of infection. There were significant differences between HIV+ and HIV- mothers with regard to the presence and impact of substance abuse in their own primary caretakers before age 16. Substance abuse in the parents of subjects was apparently reflected in behaviors reflecting health risk in subsequent generations. Subjects did not report changes in AIDS risk behavior when informed of their own HIV status or that of their children.

Remodelling of angular deformity after femoral shaft fractures in children.

We reviewed 28 children with unilateral middle-third fractures of the femoral shaft who had an angular deformity after union of 10 degrees to 26 degrees. At an average follow-up of 45 months (20 to 66), we measured remodelling of the proximal physis, the distal physis and the femoral shaft. The average correction was 85% of the initial deformity. We found that 74% of correction occurred at the physes and only 26% at the fracture site. Neither the direction nor the magnitude of the angulation much influenced the degree of remodelling. Younger children remodelled only a little better than older children. We conclude that in children under 13 years of age, malunion of as much as 25 degrees in any plane will remodel enough to give normal alignment of the joint surfaces.

Sertoli-Leydig cell tumor of the ovary: a rare cause of amenorrhea.

A 15-year-old girl presented to a primary care clinic with secondary amenorrhea, masculinization, and rapidly increasing abdominal girth. Evaluation revealed a large pelvic mass, which was found at laparotomy to be a bilateral Sertoli-Leydig cell tumor producing androgens and high levels of alpha-fetoprotein (AFP). The patient underwent bilateral salpingo-oophorectomy. Other pelvic structures were uninvolved. The postoperative course was unremarkable, with testosterone and AFP levels in the normal range. A thorough literature search revealed no cases in which bilateral Sertoli-Leydig cell tumors were associated with high AFP levels. This case was unusual in its pathology, dramatic in its presentation, and valuable in its implications regarding the work-up of amenorrhea in young women.

Recognition of 'trembler', a hypomyelinating condition in the Bernese mountain dog.

An account is given of a hypomyelinating condition, 'trembler', in the Bernese mountain dog. The condition is manifested clinically as a tremor of the limbs and head which becomes more intense with excitement or stress and which disappears with sleep. The tremor, which is first noticeable between two and eight weeks old, may persist throughout life but decline with age. Examination of plastic embedded tissue obtained post mortem from two, nine-week-old animals showed hypomyelination of the spinal cord. Preliminary examination of breeding data suggests that the condition may be inherited as an autosomal recessive.

Chubby: a new autosomal recessive skeletal mutation producing dwarfism in the mouse.

The chubby (cby) mutant is a previously undescribed skeletal mutation in the mouse. Breeding experiments showed that cby is a recessive mutant with complete viability, full penetrance and fertility in both sexes. Tests for allelism showed that the cby mutant is genetically unlike the somewhat similar mutants, stumpy (stm), pituitary dwarf (dw), spondylometaphyseal chondrodysplasia (smc), brachymorphic (bm), and achondroplasia (cn). The defects seem to occur mainly in growth cartilage. Microradiography revealed increased height of the epiphyseal growth plate and irregular bone trabeculae in the metaphysis. Light microscopy showed disturbed columnar organization of proliferative chondrocytes and pronounced signs of cellular disintegration. The hypertrophic zone, however, contained normally shaped chondrocytes arranged in regular columns. In spite of the normal cellular hypertrophy the pattern of cartilage mineralization was disturbed. The electron microscopy studies revealed very high amounts of matrix vesicles and numerous larger membrane coated structures in the extracellular matrix. Biochemical analysis of the affected growth cartilage revealed a slightly modified pattern of proteoglycan subpopulations and considerably longer chondroitin sulfate chains when compared with controls. From the present study it can be concluded that the cby mutant is a genetically and morphologically distinct condition with characteristic, somewhat rickets-like stigmata. The pathogenetic mechanism underlying the condition remains to be clarified.