Formation of coastline features by large-scale instabilities induced by high-angle waves.

Along shore sediment transport that is driven by waves is generally assumed to smooth a coastline. This assumption is valid for small angles between the wave crest lines and the shore, as has been demonstrated in shoreline models. But when the angle between the waves and the shoreline is sufficiently large, small perturbations to a straight shoreline will grow. Here we use a numerical model to investigate the implications of this instability mechanism for large-scale morphology over long timescales. Our simulations show growth of coastline perturbations that interact with each other to produce large-scale features that resemble various kinds of natural landforms, including the capes and cuspate forelands observed along the Carolina coast of southeastern North America. Wind and wave data from this area support our hypothesis that such an instability mechanism could be responsible for the formation of shoreline features at spatial scales up to hundreds of kilometres and temporal scales up to millennia.

A large rubella outbreak with spread from the workplace to the community.

CONTEXT: Childhood vaccination has reduced rubella disease to low levels in the United States, but outbreaks continue to occur. The largest outbreak in the past 5 years occurred in Nebraska in 1999. OBJECTIVES: To examine risk factors for disease, susceptibility of the risk population, role of vaccine failure, and the need for new vaccination strategies in response to the Nebraska rubella outbreak. DESIGN, SETTING, AND PATIENTS: Investigation of 83 confirmed rubella cases occurring in Douglas County, Nebraska, between March 23 and August 24, 1999; serosurvey of 413 pregnant women in the outbreak locale between October 1998 and March 1999 (prior to outbreak) and April and November 1999 (during and after outbreak). MAIN OUTCOME MEASURES: Case characteristics, compared with that of the general county population; area childhood rubella vaccination rates; and susceptibility among pregnant women before vs during and after the outbreak. RESULTS: All 83 rubella cases were unvaccinated or had unknown vaccination status and fell into 3 groups: (1) 52 (63%) were young adults (median age, 26 years), 83% of whom were born in Latin American countries where rubella vaccination was not routine. They were either employed in meatpacking plants or were their household contacts. Attack rates in the plants were high (14.4 per 1000 vs 0. 19 per 1000 for general county population); (2) 16 (19%), including 14 children (9 of whom were aged <12 months) and 2 parents, were US-born and non-Hispanic, who acquired the disease through contacts at 2 day care facilities (attack rate, 88.1 per 1000); and (3) 15 (18%) were young adults (median age, 22 years) whose major disease risk was residence in population-dense census tracts where meatpacking-related cases resided (R(2) = 0.343; P<.001); 87% of these persons were born in Latin America. Among pregnant women, susceptibility rates were 13% before the outbreak and 11% during and after the outbreak. Six (25%) of 24 susceptible women tested were seropositive for rubella IgM. Rubella vaccination rates were 90.2% for preschool children and 99.8% for school-aged children. CONCLUSIONS: A large rubella outbreak occurred among unvaccinated persons in a community with high immunity levels. Crowded working and living conditions facilitated transmission, but vaccine failure did not. Workplace vaccination could be considered to prevent similar outbreaks. JAMA. 2000;284:2733-2739.

A reason why measures to avoid mite-induced asthma are more effective in children than in adults.

Mite-sensitive asthmatics seem to respond more markedly to a reduction in mite allergen in the bedding if they are children than if they are adults. In order to investigate this difference, 882 children who attended our allergy clinic were studied. The accompanying parents were asked standardized questions, and skin prick tests to Dermatophagoides pteronyssinus and D. farinae were performed on the children. The number of hours that the children spent in bed lessened progressively with increasing age, from a mean of 13.6 hrs. for 1 year olds to 9.5 hrs for 17 yr olds: the mean for the total population was 12.0 hrs. This was significantly longer than the mean for the parents, 8.4 hrs (p=.000). It is likely that a longer period of exposure to mite allergen in bed is an important reason why children respond more markedly to avoidance measures in the bedroom than adults do.

Increased atherosclerosis in mice reconstituted with apolipoprotein E null macrophages.

Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by the macrophage in atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for the apoE gene. After 13 weeks on an atherogenic diet, C57BL/6 mice reconstituted with apoE null marrow developed 10-fold more atherosclerosis than controls in the absence of significant differences in serum cholesterol levels or lipoprotein profiles. ApoE expression was absent in the macrophage-derived foam cells of C57BL/6 mice reconstituted with apoE null marrow. Thus, lack of apoE expression by the macrophage promotes foam cell formation. These data support a protective role for apoE expression by the macrophage in early atherogenesis.

Leukocyte low density lipoprotein receptor (LDL-R) does not contribute to LDL clearance in vivo: bone marrow transplantation studies in the mouse.

The targeted disruption of the low density lipoprotein (LDL) receptor gene in mice results in accumulation of plasma LDL cholesterol and in predisposition to diet-induced aortic atherosclerosis. Although the liver is the central organ for receptor mediated clearance of LDL, the in vivo role of other organs and tissues in LDL catabolism has not been directly studied. Since bone marrow-derived cells such as blood leukocytes and tissue macrophages express LDL receptors and contribute a large mass to the body, we designed bone marrow transplantation (BMT) experiments to reconstitute LDL receptor null mice [LDL-R(-/-)] with marrow obtained from LDL-R wild-type mice [LDL-R(+/+)] and evaluate the effects on parameters of plasma lipid metabolism. Although reconstitution of the transplanted mice with donor bone marrow cells was complete, no differences in plasma lipid levels and lipoprotein distribution were found between groups, irrespective of the diet used, and turnover studies using 125I-labeled LDL showed that LDL receptor expression by leukocytes and macrophages does not significantly contribute to plasma LDL clearance. The complementary experiment of transplanting LDL-R(-/-) marrow into C57BL/6 recipients [LDL-R(-/-)-->LDL(+/+)], performed to evaluate the role of leukocyte LDL-R in normocholesterolemic condition, also produced no effects on plasma lipid parameters. LDL binding studies using macrophages isolated from transplanted mice showed a lack of LDL-R expression. Thus, despite their large number and wide distribution, bone marrow-derived cells do not significantly influence receptor-mediated clearance of plasma LDL.

Are combinations of questions better than individual questions for detecting sensitization to mite allergen?

Previous studies have found that questions are considerably less sensitive for predicting sensitization to dust mites than to pollens or to household pets. We studied 1160 children with respiratory symptoms to find whether the sensitivity for predicting mite allergy could be increased by asking several rather than single questions. Parents accompanying the children were asked standardized validated questions. Of the four individual questions relevant to mites, the one with the highest sensitivity for predicting a positive skin prick test to this allergen was whether the symptoms were worse when the house was being swept, vacuumed or dusted (29.8%). If an affirmative answer to that question, or to any of the other three questions, was taken as predictive of sensitization, the sensitivity increased to 54.2%. However, requiring only a single affirmative answer to this combination of questions decreased the specificity. The sensitivity of the combination of questions was comparable to that of questions for predicting positive tests to tree pollens (56.4%), cats (56.4%), grass pollens (52.5%) and dogs (51.4%). We conclude that asking a combination of questions is an useful for indicating possible sensitization to dust mite as are questions for detecting sensitization to other common inhalant allergens.

The accuracy of features in the clinical history for predicting atopic sensitization to airborne allergens in children.

BACKGROUND: The clinical history is given considerable weight when one decides which allergens are responsible for a patient's symptoms, and in research studies the clinical history has been used as the "gold standard" with which different tests for allergy are compared. OBJECTIVES: To determine whether standardized questions accurately predict replies to detailed questions asked by an experienced allergist, and to assess the utility of certain standardized questions for predicting sensitization to individual allergen groups. METHODS: Trained interviewers put standardized questions to parents of 1160 children, aged 1 to 17 years, who had respiratory symptoms and had been newly referred to the allergy clinic of a children's hospital. For the first 151 of the subjects the answers were compared with those elicited by questions asked by a pediatric allergist. Skin prick tests and pollen counts were performed by a technologist. RESULTS: The standardized questions had an accuracy for predicting the allergist's history of 93% to 97% for all questions except one. The standardized questions with the highest accuracy for predicting the skin test results to the appropriate allergens were the following: for mite, improvement in symptoms when outdoors (66.8%) and when in dry areas 69.4%), and aggravation during house cleaning (65.9%) and when bed making (70.6%); for dog, symptoms when with dogs (80.6%); for cat, symptoms when with cats (77.3%); for tree pollen, symptoms worse in April (70.8%) and when among trees in March and April (80.8%); and for grass pollen, exacerbation in June (69.2l%) and during lawn mowing (71.2%). Although specificity was generally above 80%, sensitivity was variable, ranging from 11% to 56%. CONCLUSIONS: The standardized questions accurately predicted a detailed history obtained by an experienced allergist. Because standardized questions are reproducible they are the preferred method of history taking for research projects. Because several of the standardized questions have a high specificity they are useful for excluding sensitization to individual allergen groups, but because they have only a modest sensitivity, they are less helpful for detecting those who are sensitized to individual allergen groups.

Infections during severe primary undernutrition and subsequent refeeding: paradoxical findings.

BACKGROUND: Our earlier uncontrolled observations during primary famine and subsequent refeeding did not suggest that severe undernutrition inevitably increases vulnerability to infection. Some infections appeared suppressed by famine but reactivated by refeeding. AIMS: To examine prospectively the occurrence of infections in a large cohort of primary famine victims before and during refeeding. METHODS: From 1973 to 1993, 4382 famine victims aged 14 or more with an estimated weight loss greater than 25% were weighed and examined for infection before and after one, two, three and four weeks of refeeding. In 137, serum C-reactive protein was measured in an effort to detect latent asymptomatic infections before and after two weeks of refeeding. Refeeding diets included wheat, sorghum, millet, ghee and milk powder. RESULTS: Mean weight loss +/- SD was 28.7 +/- 2.3%. Before refeeding overt infections were found in 4.9%, an incidence rising to 29.1% at two weeks of refeeding and declining after four. Those developing infections gained more weight at two weeks, 4.6 3 +/- 0.81 kg, than those never infected, 3.94 +/- 0.76 (p = < 0.001 t test). C-reactive protein levels confirmed the presence of latent infections before refeeding. CONCLUSIONS: Severe undernutrition can suppress certain infections, mostly those due to intracellular pathogens and especially P. falciparum. Refeeding reactivates suppressed infection and can increase vulnerability to certain new infections especially of viral origin. Those gaining weight the most rapidly may be at greatest risk. Refeeding with foods alien to local culture could play a role in reactivating latent infections. Our findings may be limited to severe undernutrition and not apply to lesser forms or secondary undernutrition in hospital patients. These studies were done during charitable provision of medical care to famine victims.

Allergic rhinitis and recurrent epistaxis in children.

BACKGROUND: Many allergists, but few otolaryngologists, consider allergic rhinitis to be a common cause of nosebleeds in childhood. OBJECTIVE: To determine whether the two conditions are related, and whether epistaxis could be due solely to the local effects of nasal symptoms. METHODS: We studied 557 children who were referred consecutively to an allergy clinic of a children's hospital. Standardized questions were put to their accompanying parents, and skin prick tests were performed on the children, using common local inhalant allergens. RESULTS: On univariate analysis children who had both nasal symptoms and a positive skin test were found to have recurrent nosebleeds more frequently (20.2%) than had those with nasal symptoms on their own (9.9%), a positive skin test alone (3.4%), or neither (2.1%). Similarly, on logistic regression the odds ratio (OR) of nosebleeds was 3.3, 1.3, 1.65, and 1, respectively. Nosebleeds were more common in those who owned a dog or a cat and had a positive skin test to that species than in the remainder of the children (27.8% vs 10.8%). CONCLUSIONS: Allergic rhinitis is commonly associated with recurrent epistaxis. In many children it appears that nosebleeds are due to nasal symptoms plus some abnormality that is found in the atopic state: a disorder of hemostasis is suspected as the contributing factor.

Morphologic effects of a sulfur(IV) aerosol on the nasal cavity of beagle dogs.

Morphologic changes were observed in nasal cavities of beagle dogs after long-term exposure to a respirable sulfur(IV) aerosol at a concentration equivalent to a sulfur dioxide (SO2) concentration of 0.6 mg/m3. The changes were characterized by a thickened epithelial layer resulting from epithelial proliferation, by a loss of secretory material, and by moderate mononuclear cell infiltration.

In situ hybridization of cytospin preparations: a rapid nonisotopic screening method for isolated cells.

A simple and rapid method for light microscopic in situ hybridization on cytospin preparations is described and demonstrated for detection of viral nucleic acid in a virus-infected cell line. Cells were fixed by acetone followed by chloroform, denatured by heat, hybridized at 37 C, and hybridized sites detected with a multiple step procedure (primary anti-biotin antibody, biotinylated second antibody, streptavidin-peroxidase). This method can be used for screening studies at the light microscope level, and offers a useful and simple way to determine optimum hybridization conditions for subsequent electron microscopic investigations.

The decrease in severity of asthma in children of parents who smoke since the parents have been exposing them to less cigarette smoke.

BACKGROUND: In 1985 we became aware that the smoking of parents aggravates their children's asthma. Since then we have advised all referring doctors to urge parents not to expose their asthmatic children to smoke. METHODS: We investigated 807 nonsmoking asthmatic children, from 1 through 17 years of age, who were consecutively referred between 1983 and 1990. We compared the children who were seen before July 1986 with those seen after that date. RESULTS: Those seen in the later period had intimate exposure to a far smaller number of cigarettes smoked per day, both by mothers (7 vs 3, p = 0.005) and by fathers (5 2, p = 0.001). A concurrent improvement was observed in adjusted measures of asthma severity in their children (asthma score 7.5 vs 6.5, p = 0.047; forced expiratory volume in 1 second as a percent of predicted [FEV1%] 79.2 vs 93.7, p = 0.000; and forced expiratory flow rate during middle half of forced vital capacity [FEF25%-75%] 67.3 vs 82.0, p = 0.009), and for every cigarette less smoked in the room with the child the FEV1 increased by 3%. When parents of those seen in the later period were asked whether they had been told that smoke would aggravate their child's asthma, 80% affirmed that they had. The difference in asthma severity between the two time periods was much less in children of nonsmokers than in children of smokers. CONCLUSION: It appears that if parents are aware that smoke will aggravate their child's asthma, the child will be exposed to fewer cigarettes, and the asthma will be less severe.

Sexual dimorphism of the kidney in the NMRI mouse as shown by Dolichos biflorus agglutinin labelling.

The histological affinity pattern of Dolichos biflorus agglutinin (DBA) in kidneys from mice (NMRI, Balb/c, CBA) and rats (Wistar) fixed by perfusion with formalin, Bouin, or HgCl2 was investigated with a horseradish peroxidase conjugate. The animals were examined from fetal stage to adulthood. Adult female NMRI mice exhibited constant DBA labelling, with DBA binding to cells of the proximal and collecting tubules. Moreover the vascular endothelium of the renal papilla was found to be DBA-positive in 50% of adult female animals. In contrast, there was only very little DBA binding in the kidneys of male adult NMRI mice. There was no sexual dimorphism in lectin labelling in kidneys from other strains of mice or from rats.

Retrovirus-like particles from the human T47D cell line are related to mouse mammary tumour virus and are of human endogenous origin.

Retrovirus-like particles were secreted in a steroid-dependent manner by the human mammary carcinoma cell line T47D. The particles exhibited typical retroviral properties such as their electron microscopic appearance (95 nm in diameter) and occasional budding, sedimentation at 1.14 g/ml, reverse transcriptase activity and genomic RNA. The T47D particles were related to mouse mammary tumour virus (MMTV) as shown by their ultrastructural appearance (B type-like eccentric dense cores and budding), Mg2+ dependence of the reverse transcriptase activity; immunological reactivity with MMTV-directed antibodies (revealing proteins of 63K, 52K, 26K and 18K), and hybridization of particle RNA with MMTV DNA under stringent conditions. Purified particles were able to incorporate deoxynucleoside triphosphates in the absence of an exogenous primer and template, thus indicating the existence of a complete and biochemically functional reverse transcription apparatus (reverse transcriptase, RNA and primer) and the ability to direct endogenous cDNA synthesis. Labelled particle cDNA hybridized strongly to human genomic DNA but not to mouse and cat DNA, thus indicating the human origin of the T47D particles. Furthermore all human DNAs, hybridized with the labelled particle cDNA, showed a uniform hybridization pattern of restriction fragments, indicating the endogenous origin and distribution of the proviral particle DNA in the human genome.

Effect of passive smoking on asthmatic children who have and who have not had atopic dermatitis.

We studied 240 children with asthma who were themselves nonsmokers and had been referred consecutively to our clinic. They were aged 6 to 17 years. The severity of asthma was assessed by symptom score, by spirometry, and, in those who could perform the test reliably, by histamine bronchial challenge test. Those who reported having had a chronic or chronically relapsing itchy rash in characteristic locations were recorded as having had atopic dermatitis. Multiple analysis of variance revealed that children whose mothers smoked had significantly more severe asthma (p less than 0.001) but that atopic dermatitis had no apparent effect on the severity of asthma, either in its main effect (p = 0.71) or in its interaction with maternal smoking (p = 0.66). Although our previous study indicates that smoking mothers' children are more likely to develop asthma if they have had atopic dermatitis than if they have not, the severity of asthma does not appear to be associated with a history of atopic dermatitis. In smoking mothers' children the asthma was just as severe in those who had not had atopic dermatitis as in those who had.

Intradermal vaccination against hepatitis B in a group of medical students.

A prospective study of a low-dose (one-tenth) intradermal regimen using recombinant hepatitis B vaccine was undertaken during two consecutive years in 4th-year medical students. Eighty-one per cent of the vaccinees (123/152) sero-converted with anti-HBs levels of greater than 10 IU/l. The lower titre of hepatitis B surface antibodies compared with published studies on intramuscular immunisation, together with a sero-conversion rate of only 81%, makes the intradermal method, in our opinion, a suboptimal form of hepatitis B immunisation.

Bone tumor induction after incorporation of short-lived radionuclides.

Temporally-limited internal irradiation after incorporation of short-lived bone-seeking radionuclides is a useful experimental tool for the investigation of extrinsic and intrinsic factors which modify the dose dependence of bone tumor risk. Here we describe some of the results obtained in experiments with female mice (mainly NMRI). The future aim of such experiments should be the prediction of risk of late effects using early molecular-biological changes. Molecular-biological descriptions in our model are at present very limited.

In situ embedding of cell monolayers cultured on plastic surfaces for electron microscopy.

Various procedures suitable for routine in situ embedding of cell monolayers were tested including: (1) the use of different Epon substitutes, (2) the use of different types of plasticware obtained from different sources, and (3) different methods of preparing capsules for sectioning. Different resins reacted differently with different plastics and type of preparation. Merck Epon substitute bound to most of the plastics tested. Ladd Epon substitute released cleanly from all plastics tested when a suitable method of preparation was used. The results show that for routine embedding of cell monolayers it is necessary to select an appropriate Epon substitute and method of preparation of capsules for the type of plasticware used. A routine method is described, with various alternative steps which can be applied when particular difficulties are encountered.