Northern Ireland farm-level management factors for recurrent bovine tuberculosis herd breakdowns.

Bovine tuberculosis (bTB) is a chronic, infectious and zoonotic disease of domestic and wild animals caused mainly by Mycobacterium bovis. This study investigated farm management factors associated with recurrent bTB herd breakdowns (n = 2935) disclosed in the period 23 May 2016 to 21 May 2018 and is a follow-up to our 2020 paper which looked at long duration bTB herd breakdowns. A case control study design was used to construct an explanatory set of farm-level management factors associated with recurrent bTB herd breakdowns. In Northern Ireland, a Department of Agriculture Environment and Rural Affairs (DAERA) Veterinarian investigates bTB herd breakdowns using standardised guidelines to allocate a disease source. In this study, source was strongly linked to carryover of infection, suggesting that the diagnostic tests had failed to clear herd infection during the breakdown period. Other results from this study associated with recurrent bTB herd breakdowns were herd size and type (dairy herds 43% of cases), with both these variables intrinsically linked. Other associated risk factors were time of application of slurry, badger access to silage clamps, badger setts in the locality, cattle grazing silage fields immediately post-harvest, number of parcels of land the farmer associated with bTB, number of land parcels used for grazing and region of the country.

Northern Ireland farm-level management factors for prolonged bovine tuberculosis herd breakdowns.

This study determined farm management factors associated with long-duration bovine tuberculosis (bTB) breakdowns disclosed in the period 23 May 2016 to 21 May 2018; a study area not previously subject to investigation in Northern Ireland. A farm-level epidemiological investigation (n = 2935) was completed when one or more Single Intradermal Comparative Cervical Test (SICCT) reactors or when one or more confirmed (positive histological and/or bacteriological result) lesion at routine slaughter were disclosed. A case-control study design was used to construct an explanatory set of management factors associated with long-duration bTB herd breakdowns; with a case (n = 191) defined as an investigation into a breakdown of 365 days or longer. Purchase of infected animal(s) had the strongest association as the most likely source of infection for long-duration bTB herd breakdowns followed by badgers and then cattle-to-cattle contiguous herd spread. However, 73.5% (95% CI 61.1-85.9%) of the herd type contributing to the purchase of infection source were defined as beef fattening herds. This result demonstrates two subpopulations of prolonged bTB breakdowns, the first being beef fattening herds with main source continuous purchase of infected animals and a second group of primary production herds (dairy, beef cows and mixed) with risk from multiple sources.

Hemodynamic Parameters and Early Intimal Thickening in Branching Blood Vessels.

Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.

Early vertebral trabecular bone loss in normal premenopausal women.

The precise timing for the onset of trabecular bone loss in women is a matter of controversy. To address this issue, we studied the relationship between age and vertebral trabecular bone density (measured by computed tomography) in 74 healthy premenopausal women from 18 to 48 years old. We also measured radial cortical bone density (by single photon absorptiometry) in 28 of these subjects. Trabecular bone density levels (milligrams per milliliter, mean +/- standard error of the mean, SEM) were significantly (p less than 0.05) higher in the second (178 +/- 8) and third (171 +/- 6) decades than in the fourth (158 +/- 4) or fifth (140 +/- 12) decades, and were inversely correlated with age (r = -0.39, p = 0.0006), diminishing at a rate of 1.3 mg/ml (0.73%) per year. Radial cortical bone density levels (grams per square centimeter) were similar in the third (0.711 +/- 0.021), fourth (0.721 +/- 0.012), and fifth (0.736 +/- 0.012) decades and were not related to age (r = 0.17, p = 0.39). We conclude that vertebral trabecular bone loss in women commences during or prior to the third decade. In contrast, radial cortical bone density does not decline during the premenopausal years.

Determinants of peak trabecular bone density in women: the role of androgens, estrogen, and exercise.

To elucidate determinants of peak trabecular bone density, we studied the role of androgens, estrogen, and aerobic exercise in 30 women from 18 to 22 years old. The women were divided into three groups: Sedentary, 11 normal women who did not exercise regularly; eumenorrheic, 10 athletes with normal menstrual function; and oligomenorrheic, 9 athletes with exercise-induced oligomenorrhea. All athletes participated in aerobic sports that did not involve selective resistance loading of the back. Serum free and albumin-bound testosterone (fab T), androstenedione (A), and estradiol (E2) were measured on four separate occasions at consecutive 7 day intervals and averaged. Trabecular density was measured by quantitative computed tomography of the lumbar spine. Peak trabecular bone density was related to fab T (r = 0.48, p = 0.007), A (r = 0.40, p = 0.03), and E2 (r = 0.40, p = 0.04). When taken in combination, androgens and estrogen each accounted independently for significant portions of the variance in bone density [fab T and E2 (R2 = 0.38, p = 0.002) and A and E2 (R2 = 0.27, p = 0.01)]. Bone density (mg/ml, mean +/- standard error of the mean, SEM) in the sedentary group (174 +/- 6) was not significantly different from that in the eumenorrheic (183 +/- 12, p = 0.47) or oligomenorrheic (161 +/- 11, p = 0.32) subjects. We conclude that androgens and estrogen function as independent and additive determinants of peak trabecular bone density in young women. The quantitative impact of aerobic exercise (without resistance loading) and exercise-induced menstrual dysfunction appears to be less important than that of the hormones.

Effect of excess endogenous androgens on bone density in young women.

To determine whether endogenous androgens influence bone density in young women, we studied 27 normal women and 19 women with androgen excess, as defined by increased serum bioavailable testosterone (bio T) concentrations. The women ranged from 21-48 yr of age. The 2 groups were comparable with respect to age, anthropomorphic measures, nutrition, gynecological history, and serum cortisol and estradiol levels. Trabecular (lumbar) and cortical (radial) bone density were quantitated by computerized tomography and single photon absorptiometry, respectively. Serum obtained during the follicular phase of the cycle was assayed for bio T, total T, dehydroepiandrosterone sulfate, androstenedione (Adione), and 3 alpha-androstanediol glucuronide (3-Adiol-G). Trabecular bone density was significantly higher in the androgen excess group [172 +/- 7 (+/- SE) vs. 153 +/- 5 mg/mL; P = 0.03]; controlling for serum Adione (but not for serum bio T, total T, dehydroepiandrosterone sulfate, or 3 alpha-androstanediol glucuronide, or 3-Adiol-G) abolished this difference. Similarly, serum Adione correlated more strongly than the other androgens with trabecular bone density (r = 0.31; P = 0.03). Average cortical bone density was not higher in the androgen excess group (0.740 +/- 0.014 vs. 0.722 +/- 0.008 g/cm2; P = 0.27). Among the 27 normal women, cortical density was correlated to serum bio T (r = 0.47; P = 0.01) and total T (r = 0.53; P = 0.004), but not to the other androgens. We conclude that supraphysiological levels of endogenous androgens are associated with increased trabecular bone density in young women. Serum Adione appeared to be the best marker for the impact of androgen on trabecular density. Among normal women, cortical bone density was related to serum T.

Determination of peak trabecular bone density: interplay of dietary fiber, carbohydrate, and androgens.

To elucidate mechanisms linking nutrition and sex hormones to magnitude of peak trabecular bone density, we studied 11 normal women aged 19-21 y. Trabecular bone density was related inversely to dietary fiber (r = -0.69, p = 0.02) and carbohydrate (r = -0.70, p = 0.02) and directly to serum free-and-albumin-bound testosterone (fab T) (r = -0.70, p = 0.02) and total testosterone (total T) (r = 0.66, p = 0.03). Dietary fiber was correlated negatively with fab T (r = -0.74, p = 0.009), total T (r = -0.70, p = 0.02), and androstenedione (Adione) (r = -0.72, p = 0.01). Controlling for the effect of fab T or Adione weakened the relationship between dietary fiber and bone density and the relationship was no longer statistically significant. Conversely, controlling for sex hormones did not abolish the effect of carbohydrate on bone density. The contributions of fab T and carbohydrate to bone density were independent. These results suggest that dietary fiber may depress serum androgens which in turn decrease trabecular bone density. Carbohydrate may also depress bone density but independently of sex steroid hormones.

Interrelationships of diet, athletic activity, menstrual status, and bone density in collegiate women.

We undertook a case-control study to examine the effect of nutritional factors on menstrual function and bone density in collegiate athletes. Three groups, matched with respect to age, height, and weight, were studied: eumenorrheic collegiate athletes, oligomenorrheic collegiate athletes, and eumenorrheic sedentary collegiate control subjects. Menarche was delayed in the eumenorrheic (13.1 y) and oligomenorrheic (14.3 y) athletic groups compared with the sedentary control subjects (12.2 y) (p less than 0.05). Average bone density tended (p = 0.10) to be lower in the oligomenorrheic athletes (158 mg/mL) compared with the eumenorrheic athletes (184 mg/mL) or sedentary control subjects (173 mg/mL). Dietary fiber intake was significantly elevated (p less than 0.05) in the oligomenorrheic athletes (5.74 g/d) compared with the eumenorrheic athletes (3.62 g/d) or sedentary control subjects (2.97 g/d). We conclude that increased dietary fiber intake is associated with menstrual dysfunction of these collegiate athletes. These factors may contribute to decreased bone density.

Relation between non-uniform hemodynamics and sites of altered permeability and lesion growth at the rabbit aorto-celiac junction.

Using the rabbit's aorto-celiac junction as a representative atherosclerotic model, the hemodynamics of a bifurcating blood vessel are numerically simulated and three hemodynamic parameters are compared. The wall shear stress (WSS), the oscillatory shear index (OSI), and the spatial wall shear stress gradient (WSSG) are considered in this study. Locally enhanced wall permeabilities and intimal macrophages are generally considered to be involved in atherogenesis, and here the primary concern is with the hemodynamic influence on these early stages of the disease process. In comparing the segmental averages of the indicator functions and previously published intimal white blood cell densities, only the WSSG shows a statistically significant correlation. All three indicators have selective strengths in determining sites of early lesion growth around the aorto-celiac flow divider. At the proximal end of the flow divider on the lateral side of the orifice, there are elevated values of the OSI as well as WSSG and low WSS values. Regions of elevated wall permeabilities compare with the regions of elevated WSSG along the lateral and distal portions of the flow divider. Largely dependent upon the present input pulse with reverse flow, the OSI indicates relatively high values throughout the flow domain, however, it is important when utilized in conjunction with low WSS regions. This study presents a rationale for further quantitative correlative studies in the rabbit model based on additional histological data sets.

Purpose and guidelines for toxicokinetic studies within the National Toxicology Program.

Toxicokinetic studies undertaken within the National Toxicology Program are intended to aid the design of toxicology and carcinogenicity studies, help interpret the results of toxicology and carcinogenicity studies with respect to the relationship between toxic effects and external exposure, and define the parameters of dose, distribution, metabolism, and elimination that can be used in human risk assessment. Descriptions of two study designs presented here represent the possible extremes in approaches to toxicokinetic studies. The comprehensive approach is geared toward the development of physiology based pharmacokinetic models that relate external exposure to target organ dosimetry and addresses the questions: Is the chemical absorbed? How is the chemical metabolized? Where are the chemical and/or metabolites distributed in the body? What are the elimination rate and route of the chemical? What is the effect of dose on absorption, distribution, metabolism, and elimination? The minimal study design is more limited in scope than the comprehensive design and addresses primarily the issues of absorption, distribution, and elimination of the parent chemical. Study protocols for most chemicals lie somewhere between these two extreme approaches. An increased understanding of the relationships between external exposure, target organ dosimetry, and adverse effects should provide greater confidence in making low-dose extrapolations of human risk. This paper focuses on the collection of data from animal toxicokinetic studies. The construction of comparable models to characterize target organ dosimetry in exposed humans would certainly require the use of human parameter values obtained from human tissue samples and volunteers.

Determinants of atraumatic vertebral fracture rates in menopausal women: biologic v mechanical factors.

In menopausal women, the susceptibility to atraumatic vertebral fractures is thought to be governed by both mechanical factors (as represented by bone density) and by biologic factors such as age, body size, and dietary calcium. Whether these biologic factors independently influence fracture rates beyond the effect of bone density is a matter of controversy. To compare the relative importance of mechanical and biologic factors on vertebral fractures, we elucidated the determinants of atraumatic compression fractures in 63 menopausal women who had no chronic diseases other than osteopenia. Trabecular bone density was determined by quantitative computerized tomography of the spine. Fracture frequency was expressed as the number of compressed vertebrae per person between T5 and L4. The analysis showed that fracture frequency, bone density, and the biologic factors were closely interrelated. Fracture frequency was inversely correlated to bone density [R2 (spline model) = .40, P less than .0001], body size (r = -.26, P = .05), and dietary calcium (r = -.28, P = .04), and directly correlated with age (r = .46, P = .0002). Bone density decreased with age (r = -.65, P less than .0001), increased with body size (r = .37, P = .004), and tended to increase with dietary calcium (r = .24, P = .08). After controlling for bone density, there was no perceptible residual relationship between fracture frequency and any of these biologic factors. We conclude that mechanical factors overshadow age, body size, and dietary calcium as determinants of vertebral fracture frequency. The apparent influence of these biologic factors on fracture frequency is explained by their surrogate effects on bone density.

Interaction between parathyroid hormone and endogenous estrogen in normal women.

It has been hypothesized that estrogens conserve bone substance by blocking the resorbing effect of parathyroid hormone (PTH). We evaluated this hypothesis by examining the relation of circulating PTH to endogenous estrogen fluctuation during four quarters of a single menstrual cycle in 20 normal women. The hypothesis predicts that PTH should vary directly with estrogen, since PTH should increase following estrogen elevation to satisfy physiologic demands for calcium. Contrary to the predicted direct variation, PTH remained constant throughout the menstrual cycle despite sharply fluctuating estrogen levels. Furthermore, PTH was negatively associated with estrone during the early follicular (r = -.65, P less than 0.005) and late follicular (r = -.84, P less than 0.0001) phases. We attempted to determine whether this unexpected relationship between estrone and PTH signified a direct physiologic link, by excluding factors which could have spuriously engendered the inverse correlation. Stepwise multiple regression and partial correlation showed that estrone contributed significantly to circulating PTH independent of the effects of dietary calcium, 25-hydroxyvitamin D, serum calcium, 1,25-dihydroxyvitamin D, phosphate, estradiol, progesterone, and body weight. Therefore, it is possible that the inverse correlation between estrone and PTH signified a direct physiologic link, as an artifactual cause for the relationship could not be identified. These data imply that estrone interacts with PTH, but not by blocking PTH-mediated bone resorption. We conclude that estrone is associated with reduced circulating PTH through an as yet undetermined mechanism.

Collegiate women athletes with irregular menses during adolescence have decreased bone density.

We studied six eumenorrheic and 13 oligomenorrheic collegiate women athletes who were matched in all respects other than menstrual histories. There was a significant (P less than .05) association between menstrual regularity and bone density. The severely oligomenorrheic subjects had modestly decreased plasma estrogen levels. These findings support the notion that plasma estrogen levels during adolescence play a significant role in the development of peak adult bone density in women.

Hemodynamic parameters and early intimal thickening in branching blood vessels.

Intimal thickening due to atherosclerotic lesions or intimal hyperplasia in medium to large blood vessels is a major contributor to heart disease, the leading cause of death in the Western World. Balloon angioplasty with stenting, bypass surgery, and endarterectomy (with or without patch reconstruction) are some of the techniques currently applied to occluded blood vessels. On the basis of the preponderance of clinical evidence that disturbed flow patterns play a key role in the onset and progression of atherosclerosis and intimal hyperplasia, it is of interest to analyze suitable hemodynamic wall parameters that indicate susceptible sites of intimal thickening and/or favorable conditions for thrombi formation. These parameters, based on the wall shear stress, wall pressure, or particle deposition, are applied to interpret experimental/clinical observations of intimal thickening. Utilizing the parameters as "indicator" functions, internal branching blood vessel geometries are analyzed and possibly altered for different purposes: early detection of possibly highly stenosed vessel segments, prediction of future disease progression, and vessel redesign to potentially improve long-term patency rates. At the present time, the focus is on the identification of susceptible sites in branching blood vessels and their subsequent redesign, employing hemodynamic wall parameters. Specifically, the time-averaged wall shear stress (WSS), its spatial gradient (WSSG), the oscillatory shear index (OSI), and the wall shear stress angle gradient (WSSAG) are compared with experimental data for an aortoceliac junction. Then, the OSI, wall particle density (WPD), and WSSAG are segmentally averaged for different carotid artery bifurcations and compared with clinical data of intimal thickening. The third branching blood vessel under consideration is the graft-to-vein anastomosis of a vascular access graft. Suggested redesigns reduce several hemodynamic parameters (i.e., the WSSG, WSSAG, and normal pressure gradient [NPG]), thereby reducing the likelihood of restenosis, especially near the critical toe region.

Resources and limitations of medical centers in the United States.

A profile is provided of the range of opportunities and limitations for foreign nationals who seek access to the U.S. health care education and training system. The system is complicated, and entry depends on numerous variables. Facility in the English language is considered a prerequisite. Among opportunities, clinical training is probably most sought in the form of either residencies or clinical fellowships. Many major medical centers are eager to host earnest students and trainees from abroad. Yet such opportunities are limited, since most programs are unable to accept additional trainees once the first year of the program has been filled. Additional residency positions are not likely to be created and funded. In general, the larger academic medical centers tend to be the first to introduce new technologies and newer diagnostic and therapeutic modalities. Other settings may offer better, or at least equally good, environments for other kinds of post-M.D.-degree training. U.S. educational opportunities also exist in health policy and health systems education, nursing education, allied health and non-physician education, and research. All those seeking to study in the United States are urged to consult one of the several agencies that are knowledgeable about the opportunities and requirements for entering the programs offered.

The past as prologue.

What has the Association of American Medical Colleges (AAMC) accomplished in the last 25 years in its efforts to advance medical education, biomedical research, and health delivery in this country? Can the AAMC's past accomplishments help predict how it will respond to future challenges? To answer these questions, the author traces in detail the recent history of the AAMC, focusing on the expansion of the association's role and constituencies and how these and other changes were precipitated by recommendations in the AAMC's 1965 "Coggeshall Report." He also recounts how the AAMC has responded to the pressures and needs of recent years (such as fostering an increase in the number of practicing physicians) and describes in detail the organization and functions of the AAMC's staff, with emphasis on its six divisions and the fact that many of the complex issues that confront the AAMC transcend the boundaries of governance councils and staff divisions and dictate that association policy be based on broad consensus. Looking ahead, he sees at least four important activities that the AAMC will continue to be involved with: fostering the education of more minority students; promoting health services research; finding an appropriate role in the evolution of health care reform; and addressing the need for academic medicine to be more socially responsive. The author concludes that the AAMC's highly regarded record, its organization, and its financial stability all indicate that it will do well as it tackles the issues on the horizon and others not yet in view.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of the risk of vertebral fracture in menopausal osteopenia and other metabolic disturbances.

The risk of atraumatic compression fracture in postmenopausal women increases as vertebral trabecular bone density decreases. To determine whether the risk is similar for patients who have other metabolic disorders, we compared eight-nine patients who had various disturbances affecting bone and sixty-three postmenopausal women who had no evidence of underlying disease. Trabecular bone density was measured by quantitative computed tomography of the lumbar spine. The relationship between frequency of fracture and bone density was modeled mathematically with spline threshold, quadratic polynomial, and decaying exponential functions. Analysis of covariance showed that the diagnostic category did not influence the relationship between frequency of fracture and bone density in any of the three models. We concluded that the risk of atraumatic compression fracture, as assessed by measurement of vertebral trabecular bone density using quantitative computerized tomography, is independent of the underlying metabolic disturbance.

Management strategy for prevention of avascular necrosis during treatment of congenital dislocation of the hip.

We retrospectively analyzed the cases of fifty children with unilateral congenital dislocation of the hip in an attempt to determine what factors in treatment were associated with the prevention of avascular necrosis of the femoral head. All children were less than thirty-six months old at the initiation of treatment, had no other anomalies, had their entire treatment rendered at the same institution, and were followed for at least one year after reduction. Avascular necrosis occurred in 36% of the patients; in all cases definite roentgenographic signs were apparent within twelve months of reduction. No patient whose hip had grown normally during the first twelve months after reduction later had avascular necrosis. The management strategy for congenital dislocation of the hip in the child who is less than thirty-six months old should include a minimum two-week period of traction until achievement of the +2 traction station and immobilization in the so-called human position following reduction. Skeletal traction, gradually increased over several weeks to an average of 39% of body weight, usually was required to attain the +2 station. Observation of these principles should decrease the incidence of avascular necrosis and increase the probability of obtaining a normal hip.

Assessment of the risk of vertebral fracture in menopausal women.

The decision to institute prophylaxis in women with menopausal osteopenia is hampered by the absence of quantitative criteria for appraising the risk of fracture in the individual. We have developed standards for assessing the risk of fracture by relating the prevalence of atraumatic vertebral compression fractures to bone density in sixty-five menopausal women, forty-nine to ninety-two years old. To define the upper limit of the spectrum of bone density, we also studied thirty-one young women, seventeen to twenty-two years old. The density of trabecular bone in a vertebral body was determined by quantitative computed tomography and expressed in terms of milligrams per milliliter of dipotassium hydrogen phosphate. Twenty-five of the menopausal women exhibited at least one fracture (range, one to six fractures), and forty had no fracture. The bone density ranged from -9 to sixty-nine milligrams per milliliter in those with fractures and from twelve to 122 milligrams per milliliter in those without a fracture. The densities in the young women averaged 173 milligrams per milliliter and ranged from ninety-five to 248 milligrams per milliliter. The percentage of subjects with fractures increased as the bone density decreased. It was zero per cent in women with a density of seventy milligrams per milliliter or more, 38 per cent in women with a density between fifty and less than seventy milligrams per milliliter, 71 per cent in those with a density between thirty and less than fifty milligrams per milliliter, and 82 per cent in women with a density of less than thirty milligrams per milliliter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal androgens, sex-hormone binding globulin and bone density in osteoporotic menopausal women: is there a relationship?

The relationships among sex steroids, sex hormone binding globulin (SHBG) and vertebral bone density as measured by computerized tomography were studied in 18 post-menopausal women. A significant negative correlation was found between SHBG binding capacity (SHBG-BC) and bone density. Bone density and the adrenal androgen dehydroepiandrosterone sulfate (DHEAS) declined with age, and SHBG-BC was correlated significantly with DHEAS concentrations. The relationship between SHBG-BC and bone density may be affected by adrenal androgen output.