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Sodium ion uptake into isolated plasma membrane vesicles: indirect effects of other ions.

Vesicles derived from plasma membrane of corneal endothelium were agitated to their minimum size distribution. When isotonic salt solutions surrounding the vesicles were changed there were alterations to the vesicle size distribution: the modal point of the logarithmic distribution did not change but the log variance did, indicating that substantial fission and fusion of vesicles occurred depending upon the nature of the surrounding solute. Orientation and total membrane area was conserved in the transformed population of vesicles. Although the ions added to the external isotonic salt solutions in the present series of experiments have no direct effect upon sodium membrane transporters in these membranes, kinetics of sodium accumulation into the vesicles were affected in a way that correlated with changes to the vesicle size distribution. Early-saturating (<1 min) intravesicular concentrations of sodium corresponded with apparently stable populations. Late-saturating (>1 min) intravesicular concentrations of sodium corresponded with significant vesicle distribution shifts and included a few seconds of delay. During the linear accumulation phase, both populations showed similar magnitudes of sodium transport. The significance of these data is discussed.

Animals↗

Attachment and maintenance of adult rabbit cardiac myocytes in primary cell culture.

The present observations demonstrate that quiescent calcium-tolerant adult rabbit cardiac myocytes can be isolated by collagenase-hyaluronidase perfusion and maintained in primary culture for at least 2 wk. Culturing large numbers of myocytes requires that the freshly isolated cells be attached to a suitable substratum such as laminin, type IV collagen, or fetal bovine serum. The cultured myocytes retain their rod-like morphology for approximately 7 days before gradually spreading into a flattened conformation by 14 days. During the 1st wk of culture, contaminating interstitial cells rapidly proliferate, making cultures unsuitable for long-term study. Pure myocyte populations can be established and maintained if freshly isolated cells are cultured in the presence of cytosine arabinoside (Ara-C, 10 microM). This antimetabolite does not appear to adversely affect high-energy phosphates, since ATP and creatine phosphate (CrP) content of the myocytes is maintained at levels normally found in biopsy samples of rabbit myocardium. These results illustrate that an energetically stable population of adult cardiac myocytes can be maintained in primary culture in sufficient numbers to make them useful for future investigations of myocyte function.

Adenosine Triphosphate↗

On generating birth rates from skeletal populations.

Sattenspiel and Harpending (1983, American Antiquity 48(3): 489-498) have stated that the life expectancy at birth (e0(0] which paleodemographers calculate from skeletal population data is actually the mean age at death (ad) of the population. Yet, only when a population is neither growing or declining (i.e., is stationary) are these two statistics equivalent. They further assert, that the mean age at the death (ad) is more accurately interpreted as a measure of the fertility of the population. While we support their statement that since paleodemographic calculations use skeletal evidence of death, these do not a priori produce life expectancy values, we disagree that the inverse of the birth rate is a substitute for the average age at death (ad). The following pages demonstrate that: 1) An exact expression for the relationship between ad and 1/b can be derived using standard stable population theory, wherein ad = 1/b is shown to be a special case. 2) There are only two cases when ad = 1/b is an identity. 3) Whereas empirically ad and 1/b appear to correspond closely, this is an artifact of heavy mortality at early ages, which is a characteristic of the populations being considered. 4) Without insights into the behavioral dynamics of the situation any assessment of the demographics of the population is questionable.

Birth Rate↗

Historical population dynamics and demography of the Eastern Atlantic pomacentrid Chromis limbata (Valenciennes, 1833).

Recent studies have focused on the relationship between the marine fauna of the Eastern Atlantic and the Mediterranean Sea, but within the Atlantic, little is known about genetic relationships between populations of the Macaronesian islands. In this study, we tested whether the paleo-climatology and paleo-oceanography of the region could predict the genetic relationships among three Eastern Atlantic populations (Azores, Madeira, and Canaries) of a damselfish, Chromis limbata, and compared our results with its Mediterranean and adjacent Atlantic sister species, Chromis chromis. We combined phylogeographic and coalescent approaches using the fast evolving mitochondrial control region gene. No population structure was found for the three archipelagos. The coalescence time estimated for C. limbata (0.857-1.17 Mya) was much greater than that estimated for C. chromis. We propose that this difference reflects differences in glaciating extents in the Northeastern Atlantic and the Mediterranean. Diversity indexes (Hd and genetic distances) together with historical demographic parameters of C. limbata (Theta and g) revealed a more stable population history when compared to C. chromis. Our results suggest that the Macaronesian populations of C. limbata have probably been less affected by the last glaciation than the Mediterranean populations of C. chromis. Migration across the three archipelagos was estimated and a prevailing northwest trend was detected. This result supports the idea of a colonization of the Azores by warm water fish from Madeira or the westernmost Canary islands which acted as major glacial refugia for the tropical and subtropical marine fauna during the glaciations.

Animals↗

Genetic variability in sensitivity to population density affects the dynamics of simple ecological models.

Many 1-dimensional discrete time ecological models contain a sensitivity parameter that does not affect the dynamic complexity of these models. We show that genetic variability in this parameter can have a strong effect on population dynamics. We incorporate ecological dynamics in two different population genetic models with one locus and two alleles. The first is the classical model of a randomly mating population in Hardy-Weinberg equilibrium, and the second is a model of differential selection in males and females. In populations in Hardy-Weinberg equilibrium, variability in the sensitivity parameter can be maintained by overdominance. In this case, the dynamics of the polymorphic population tend to be much simpler than those of monomorphic populations. In the model with different selection in males and females, polymorphisms can be maintained in various ways, e.g., by opposing directional selection in males and females. Polymorphism in the sensitivity parameter tends to simplify population dynamics in the model with different selection in males and females as well. A number of interesting dynamic effects can be observed, e.g., multiple attractors with complicated basins of attraction. Then the final state of the system after a successful invasion by mutant alleles may depend on the mutation rate and on the distribution of mutational steps. In addition, there are situations in which genetic variability destabilizes a stable population dynamic equilibrium in the monomorphic model. There is an analogy between genetic variability and variability imposed by the environment. If differences in sensitivity are caused by the environment, dynamic effects similar to those in the genetic models can be observed. In addition, source-sink structures that are known to occur in spatially structured models can be seen in the genetic model if one of the genotypes is inviable. The results suggest that combining ecological and population genetic models can lead to a number of new insights. More work is needed, e.g., with fertility models, in which fitnesses are not assigned to individuals, but to mating pairs.

Alleles↗

The NCI All Ireland Cancer Conference.

The National Cancer Institute (NCI) has recently decided to embark on an international partnership with the developing cancer programs on the Island of Ireland (Northern Ireland and the Republic of Ireland) in an attempt to further improve the quality and range of cancer services available for patients. This Transatlantic Partnership called the All Ireland-NCI Cancer Consortium offers exciting opportunities in cancer treatment, education and research as the cancer-caring communities from both the Republic of Ireland and Northern Ireland prepare to join with the U.S. NCI in this major endeavor. The inaugural event of the partnership will be the NCI All Ireland Cancer Conference to be held in Belfast, October 3-6, 1999. (See www.allirelandcancer.com, for information on the conference.) Cancer is a significant cause of mortality and morbidity on the Island of Ireland. There are approximately 28,000 new cases and approximately 11,000 deaths from cancer each year. Therefore, Northern Ireland and the Republic of Ireland have among the highest cancer incidence and mortality rates in the Western World. In recent years there has been a major restructuring of cancer services in both parts of the Island. This is the result of several government reports such as the Campbell Report in Northern Ireland and the National Strategy Document for Cancer in the Republic of Ireland. The National Strategy Document proposes that cancer treatment services should be centered around primary care services, regional services, supra-regional centers and a national coordinating structure whereby the supra-regional centers deliver specialist surgery, medical and radiation oncology, rehabilitation and specialist palliative care. Three supra-regional cancer centers are being established in the cities of Dublin, Cork and Galway and a National Cancer Forum, which has served as a multidisciplinary advisory board to the Government, has pushed the development and implementation of this plan. This has already resulted in a major expansion in the number of medical oncologists practicing in Ireland but further development is required to facilitate multidisciplinary care, to establish programs of education and training and to harness the scientific talent available to engage in the international effort against cancer. In Northern Ireland the Chief Medical Officer commissioned a report entitled "Cancer Services-Investing for the Future" whose key recommendations were that Northern Ireland should have one cancer center in Belfast and four smaller cancer units. This report also recommended the implementation of a multidisciplinary approach to cancer diagnosis, treatment and palliative care. As in the Republic, all the recommendations of the Report have been accepted and the planning and implementation of this plan are now well under way. Therefore, development of services for cancer patients is a top priority for both governments on the Island and, given the process of cancer service development, it is timely to bring international expertise such as the NCI on board as partners in this effort. The decision by the NCI to develop an agreement for cancer research and service development in Ireland is a major boost for those involved in cancer care and research and will, no doubt, help speed the process of redevelopment. There have already been several visits from senior NCI personnel to Ireland including Dr. Klausner, the Director of the NCI, to determine the potential impact of this agreement and to identify the most productive areas of interaction between the NCI and the Irish Cancer Community. As a result of these visits, the NCI has decided to focus on several areas of strategic importance whose objectives will be to enhance clinical services, improve patient care, promote North South collaboration and cement strategic Ireland-U.S. collaboration in cancer research and development. The agreement will build on existing informal links in U.S.-Irish scientific, medical education and training and also promote clinical trials and cancer epidemiology programs. Major components of the NCI Ireland Agreement will include some of the following: EDUCATION AND EXCHANGE OF SCHOLARS: Education will form one of the major platforms of this agreement through the support of educational programs for medical, nursing and scientific staff. These will include the exchange of scholars, including Ph.D., M.D. and nursing students. Particular emphasis will be given to the exchange of medical and nursing trainees focused on clinical research. This will have an immediate clinical impact and will naturally extend the support that has already been given to the training of medical and scientific trainees from the Island of Ireland. Further exchanges would include Ph.D. students, laboratory-based M.D.s in training, clinical visiting professors and investigators from the U.S. wishing to extend their studies in Ireland. CLINICAL TRIALS: Another major area for partnership will be the enhancement of a clinical trials infrastructure and clinical trial development. Modernization of cancer care requires that delivery of care should be in the context of evidence-based medicine. This requires a vigorous and contemporary clinical trials infrastructure which would center around the clinical trials infrastructure already established at the Northern Ireland Cancer Centre and the Irish Clinical Oncology Research Group (ICORG) in the Republic of Ireland. The NCI has already commissioned the development of a new Clinical Trials Information System (CTIS) which seeks as its goal to set international standards in the clinical trials process, and it has already committed significant resources to its implementation. The outcome of this element of partnership will be that clinical trials performed in Irish institutions will immediately be compatible for collation, analysis and presentation with studies performed in the U.S. Moreover, this system will allow participating centers to immediately conform to international standards. This proposal therefore permits participating institutions in Northern Ireland and the Republic of Ireland to quickly achieve data management standards of the highest quality. TELECONFERENCING: Teleconferencing capabilities are already established in both the NCI and in Ireland and indeed limited teleconferencing linkages have already been established between the partners. Further investment in this infrastructure will be vital to the success of major elements of this partnership. It will facilitate clinical trial development, education programs, patient services development and exchange of clinical and scientific ideas. Communication between sites will be essential to the success of this partnership. TUMOR REGISTRIES: Another area for major collaboration and partnership will be in the use of the Cancer Tumor Registries in both Northern Ireland and the Republic of Ireland. The monitoring of improvements in cancer care can only be undertaken with a reliable tumor registry that tracks population-based cancer incidence and mortality. These data are now available in both Northern Ireland and the Republic of Ireland, and both Governments recognize their importance. The NCI proposes to assist both Tumor Registries by developing a common database that can assist in consultation, informatic tools and quality control. Consolidation of the Registries, North and South, will improve the overall quality of data collection and provide information on a genetically stable population. This therefore will act as a major tool for epidemiological investigations and programs focused on screening and prevention. DEVELOPMENTS IN CANCER CLINICAL SERVICES: The NCI Ireland partnership also proposes to assist the further development of clinical service programs on the Island of Ireland. These will include the improvement and standardization of Radiation Oncology practice and the development of a consolidated Radiation Oncology program for research. There are a limited number of radiation facilities on the Island of Ireland and there are significant needs in terms of linking practice elements and the implementation of uniform standards of practice. Assistance in standardizing and driving the development of clinical services will also extend to elements of medical and surgical oncology practice as well as palliative care. The development of palliative care services is already at an advanced stage on the Island of Ireland and is one that the NCI will carefully evaluate in terms of its own developing programs. THE NCI ALL IRELAND CANCER CONFERENCE: An important event to highlight the commencement of this special relationship will be the NCI All Ireland Cancer Conference to be held in Belfast October 3-6, 1999. This Conference will address clinical, laboratory, epidemiological and political issues that are pertinent to the care of cancer patients. It will highlight important work by Irish, American and European scientists with further input from well-known international academic and biotechnology investigators from across the world. These international experts will not only be asked to speak on their areas of expertise but also to comment on clinical and scientific programs that may help improve North and South interaction and Transatlantic collaboration. Finally, it is hoped that the Conference will be a marker of a very special interaction on the Island of Ireland focused on the overall development of cancer services for patients. It will also signal the start of an important partnership between the NCI and those involved in cancer care and research in Ireland. This tripartite cooperative agreement is a most exciting venture and it will hopefully be an example of how an effort focused on a human problem common to all societies can generate a spirit of cooperation and help to eliminate strife.

Journal Article↗

Parasite adaptation to extreme conditions in a desert environment.

Deserts represent universally recognized extreme environments for animal life. This paper documents the highly specialized adaptations of Pseudodiplorchis americanus, a monogenean parasite of the desert toad, Scaphiopus couchii. Building on a long-term record of parasite population ecology (continuing since the early 1980s), field studies focus on the effects of severe drought in the Sonoran Desert, Arizona, in the mid 1990s. This provides a test of the ability of the host-parasite system to tolerate exceptional perturbation. The analysis provides new insight into parasite infection dynamics in a natural wildlife system through integration of host and parasite population age structure. The environmental check interrupted host recruitment in 1993-95 and parasite recruitment in 1995-97. This produced an imprint in age structure and infection levels recognizable over several years: parasite recruitment failure reduced transmission 2-3 years later. The host (maximum life span 17 years) tolerated the disruption but the impact was more serious for the parasite (life span 3 years) leading to extinction of some previously stable populations. Despite this demonstration of a rare event exacerbating external environmental constraints, experimental studies suggest that the internal (host) environment normally creates the most severe conditions affecting P. americanus. Only about 3% of parasites survive from invasion until first reproduction. Post-invasion factors including host immunity, characteristic of most parasite life cycles, constitute a greater constraint upon survival than external conditions, even in a desert environment.

Adaptation, Physiological↗

The reliability of magnitude estimation for dyspnea measurement.

The reliability of magnitude estimation with an open scale was evaluated in a physiologically stable population of adults with chronic respiratory disease who experienced chronic dyspnea. Magnitude estimation was used to measure one dimension of dyspnea, perceptual sensitivity. The relationship between external inspiratory resistive loads (stimuli) and numbers that reflected the perceived intensity of the breathing effort (response) as expressed by a power function was measured on three visits 3 to 5 days apart. The correlations of the exponent of the power function between visits were high and stable.

Adult↗

Blunt renal trauma. Changes in aetiology, Diagnostic procedure, treatment and complications over thirty years.

In a rural area with a relatively stable population, 216 persons were hospitalized for blunt renal trauma over a 30-year period (1946-75). In the final 10 years the frequency of such trauma increased, as also did the proportions of females and younger patients (11-30 years old). In the final 5 years the overall incidence was 6.2 cases per 100 000 inhabitants and year. Motor traffic accidents were increasingly the cause of blunt renal trauma. Injuries from compression showed a stable frequency. Renal trauma attributed to blows varied with the incidence of accidents involving horses and sports. Treatment was mainly conservative, except in major injuries. Emergency excretory urography was rarely used during the first 10 years of the study, but thereafter with increasing frequency. Early complications were seen only during the first 20 years of the study.

Adolescent↗

Toxoplasma gondii: stable complementation of sag1 (p30) mutants using SAG1 transfection and fluorescence-activated cell sorting.

Toxoplasma gondii and the related Apicomplexan protozoan pathogens, Plasmodium, Cryptosporidium, and Eimeria, are obligate intracellular parasites which cause severe disease in their hosts. The recent development of transient transfection of Toxoplasma permits the development of strategies utilizing "reverse genetics" to identify molecules critical to parasite survival within the host. We have utilized transfection of Toxoplasma tachyzoites to stably complement a sag1 (or p30) mutant that does not make detectable SAG1. Transfection of mutants with the wild-type SAG1 gene resulted in transient expression of SAG1 in approximately 15-20% of the transfected population. Stable transformants were enriched by repeated sorting of live parasites using a fluorescein-labeled monoclonal antibody specific for SAG1. Cloned recombinant parasites expressed SAG1 at wild-type levels and maintained expression for over 5 months after transfection (approximately 300 divisions). Cloned transformants (which proved to be siblings) carried both the mutated gene and one copy of the transfected gene which had inserted randomly into the Toxoplasma genome.

Animals↗

The buffer effect and large-scale population regulation in migratory birds.

Buffer effects occur when sites vary in quality and fluctuations in population size are mirrored by large changes in animal numbers in poor-quality sites but only small changes in good-quality sites. Hence, the poor sites 'buffer' the good sites, a mechanism that can potentially drive population regulation if there are demographic costs of inhabiting poor sites. Here we show that for a migratory bird this process can apply on a country-wide scale with consequences for both survival and timing of arrival on the breeding grounds (an indicator of reproductive success). The Icelandic population of the black-tailed godwit, Limosa limosa islandica, wintering in Britain has increased fourfold since the 1970s (ref. 5) but rates of change within individual estuaries have varied from zero to sixfold increases. In accordance with the buffer effect, rates of increase are greater on estuaries with low initial numbers, and godwits on these sites have lower prey-intake rates, lower survival rates and arrive later in Iceland than godwits on sites with stable populations. The buffer effect can therefore be a major process influencing large-scale population regulation of migratory species.

Animals↗

Effective size and F-statistics of subdivided populations for sex-linked loci.

For a population subdivided into an arbitrary number (s) of subpopulations, each consisting of different numbers of separate sexes, with arbitrary distributions of family size and variable migration rates by males (dm) and females (df), the recurrence equations for inbreeding coefficient and coancestry between individuals within and among subpopulations for a sex-linked locus are derived and the corresponding expressions for asymptotic effective size are obtained by solving the recurrence equations. The usual assumptions are made which are stable population size and structure, discrete generations, the island migration model, and without mutation and selection. The results show that population structure has an important effect on the inbreeding coefficients in any generation, asymptotic effective size, and F-statistics. Gene exchange among subpopulations inhibits inbreeding in initial generations but increases inbreeding in later generations. The larger the migration rate, the greater the final inbreeding coefficients and the smaller the effective size. Thus if the inbreeding coefficient is to be restricted to a specific value within a given number of generations, the appropriate population structure (the values of s, dm, and df) can be obtained by using the recurrence equations. It is shown that the greater the extent of subdivision (large s, small dm and df), the larger the effective size. For a given subdivided population, the effective size for a sex-linked locus may be larger or smaller than that for an autosomal locus, depending on the sex ratio, variance and covariance of family size, and the extend of subdivision. For the special case of a single unsubdivided population, our recurrence equations for inbreeding coefficient and coancestry and formulas for effective size reduce to the simple expressions derived by previous authors.

Animals↗

A close look at the demography of Afghanistan.

The first survey designed to allow estimates of the demographic characteristics of Afghanistan's sedentary population was conducted during the period 1972-1974. Our analysis of these data, based on recently developed techniques for handling imcomplete or inaccurate data, suggests that this population lives under conditions that are extreme when judged by modern standards. Marriage is early, especially for females, and universal. Marital fertility conforms to a pattern of natural fertility and total fertility is high. The birth rate is among the highest in the world today, and the expectation of life at birth is among the very lowest. Mortality is lower in urban areas than in rural areas, whereas total fertility is approximately the same in both. Our estimates of fertility and mortality imply stable populations which match closely the observed age distributions for both the rural and urban areas.

Afghanistan↗

A high prevalence of HLA-H 845A mutations in hemochromatosis patients and the normal population in eastern England.

We have examined normal individuals and all the patients currently being treated for hemochromatosis at the Norfolk and Norwich hospital for mutations in the HLA-H gene. We found a gene frequency in 200 normal subjects for teh 845A (C282Y) allele of 0.085, corresponding to a carrier frequency of 17% which is among the highest reported anywhere in the world. The frequency for the less penetrant 187G (H63D) allele was 0.16 among 58 of the normal subjects, which corresponds to a carrier frequency of 32%. All 18 hemochromatosis patients were homozygous for the 845A allele which is not significantly different from other reports in our subset of 12 unrelated patients. These findings present a snapshot of a relatively stable population containing a predicted 3,500 individuals homozygous for the 845A allele but not diagnosed with hemochromatosis. This population will be an excellent model for studies on the penetrance of the 845A homozygous genotype and population screening.

Alleles↗

Cancer mortality in migrant populations within Italy.

Italian death certification rates from all causes of death, all diseases of the circulatory system, all neoplasms, and cancers of the upper digestive and respiratory tract, stomach, intestines, lung and breast in middle age (45-64 years) were analyzed according to selected geographic areas of birth and residence at death. For total cancer mortality and most neoplasms considered, the rates in middle age were closer to those of place of birth than to those of area of residence, although this pattern was more evident for some sites (e.g., mouth or pharynx, esophagus, larynx, stomach or bladder) than for others (e.g., intestines or breast). In most cases, migration had an adverse effect on cancer rates, and the lowest mortality was reported among stable populations (i.e., those with the same area of birth and death). These findings are discussed in relation to the major migration fluxes within Italy during the current century. Moreover, these analyses give information on the quality of Italian cancer death certification, since the observation that area of birth is often a more important determinant of cancer rates than area of residence provides indirect evidence that cancer death certification in various Italian geographic areas is satisfactorily reliable and consistent.

Adult↗

Increasing incidence of multiple sclerosis in the province of Sassari, northern Sardinia.

Sardinia is a high-risk area for multiple sclerosis (MS), with prevalence rates of 150 per 100,000 population. The study included 689 MS patients (female-male ratio 2.6) with disease onset between 1965 and 1999 in the province of Sassari. The mean annual incidence rate increased significantly from 1.1 per 100,000 population in 1965-1969 to 5.8 in 1995-1999, with no significant difference for gender and province sub-areas. The mean age at onset increased significantly during the same period from 25.7 to 30.6 years, while the proportion of patients with progressive initial course declined over time. The marked increase of MS incidence and the change of MS clinical phenotype over time cannot be explained by ascertainment bias only, thus pointing to a corresponding change in the distribution of exogenous risk factors in this highly genetically stable population.

Adult↗

In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain.

Recent studies suggest that neurons born in the developing basal forebrain migrate long distances perpendicularly to radial glia and that many of these cells reach the developing neocortex. This form of tangential migration, however, has not been demonstrated in vivo, and the sites of origin, pathways of migration and final destinations of these neurons in the postnatal brain are not fully understood. Using ultrasound-guided transplantation in utero, we have mapped the migratory pathways and fates of cells born in the lateral and medial ganglionic eminences (LGE and MGE) in 13.5-day-old mouse embryos. We demonstrate that LGE and MGE cells migrate along different routes to populate distinct regions in the developing brain. We show that LGE cells migrate ventrally and anteriorly, and give rise to the projecting medium spiny neurons in the striatum, nucleus accumbens and olfactory tubercle, and to granule and periglomerular cells in the olfactory bulb. By contrast, we show that the MGE is a major source of neurons migrating dorsally and invading the developing neocortex. MGE cells migrate into the neocortex via the neocortical subventricular zone and differentiate into the transient subpial granule neurons in the marginal zone and into a stable population of GABA-, parvalbumin- or somatostatin-expressing interneurons throughout the cortical plate.

Animals↗

The grandmultipara: is she still a risk?

Grandmultiparity is reported to increase both maternal and perinatal mortality and morbidity. Unique religious and demographic factors in Jerusalem allowed us to analyze a population wherein parity could be dissociated from socioeconomic status. A total of 7785 mothers was studied, 889 (11.5%) of whom were grandmultiparas. Comparison of grandmultiparous mothers with all others revealed no increase in the incidence of hypertension, diabetes, uterine atonia, antenatal or postnatal hemorrhage, cesarean sections, stillbirth rate, or congenital malformations. The grandmultipara had significantly lower neonatal mortality and low birth weight rates and a significantly higher incidence of multiple births and trisomy 21 (p less than 0.01). These results strongly suggest that grandmultiparity in and of itself in a healthy, economically stable population afforded modern medical care is not a major risk factor and that previous reports primarily reflected social class factors and not parity per se.

Female↗