Major issues regarding the efficiency of monitoring programs for nitrate contaminated groundwater.

Major issues regarding the efficiency of moni toring programs for nitrate contaminated groundwater are analyzed in this paper: (i) representativeness of monitoring networks; (ii) correct interpretation of the monitoring data and resulting time series and trends; and (iii) differentiation among the different sources of nitrates in groundwater. Following an overview of the nitrate contamination problem and possible solutions, as well as some of the difficulties found, a relatively straightforward method for assessing monitoring network representativity is presented, namely interpolation standard error assessment. It is shown how nitrate-concentration time series resulting from periodic observations can be corrected with a conservative tracer, in order to avoid misinterpretation and confirm or correct apparent trends. Finally, coupled ¹5N and ¹8O isotope signatures of nitrate (NO3⁻) in groundwater are used to differentiate among nitrogen (N) sources, to ensure correct targeting of restoration measures. The case study regards a Nitrate Vulnerable Zone in the south of Portugal, designated in compliance with the European Nitrates Directive, where coastal discharge of nutrient-rich groundwater threatens the good qualitative and ecological status of the Ria Formosa coastal lagoon. Results show that mineral fertilizer is the main source of N in groundwater, and that increases in N load can be masked by dilution phenomena.

Sexual assault of postmenopausal women: a retrospective review.

OBJECTIVE: To determine whether postmenopausal women have a greater susceptibility to genital and extragenital injuries as a result of sexual assault. DESIGN: Retrospective review of patient notes. SETTING: The Havens sexual assault referral centres, Camberwell and Paddington, London, UK. POPULATION: A total of 122 postmenopausal and 130 premenopausal women. METHODS: Eligible women were identified. Standardised Haven forms completed during forensic examination were retrieved for each participant, and relevant information was extrapolated to study forms. MAIN OUTCOME MEASURES: Demographic and assault-related characteristics, prevalence of genital and extragenital injury, type, size and location of injury, and logistic regression predicting study group. RESULTS: 37% of postmenopausal women and 17% of premenopausal women sustained genital injury (multivariate analysis OR 3.31, 95% CI 1.39-7.91), and 71% of postmenopausal women and 69% of premenopausal women were found to have extragenital injury (univariate analysis OR 1.35, 95% CI 0.79-2.32, not significant). Of those with extragenital injury, 41.4% of postmenopausal women and 20.9% of premenopausal women sustained large bruises (P < 0.01). CONCLUSIONS: When controlling for the effects of demographic and assault-related characteristics, postmenopausal women were more than three times more likely to sustain genital injury than premenopausal women following a sexual assault. No significant difference between the two groups was found for extragenital injuries; however, of those who sustained an extragenital injury, postmenopausal women were significantly more likely to have large bruises than premenopausal women.

Molecular cloning of LMO41, a new human LIM domain gene.

We have identified a new human LIM domain gene by isolating an autoantigenic cDNA clone from a human breast tumor cDNA library. The predicted amino acid sequence of the cDNA clone's 495 bp open reading frame contains two tandem LIM domain motifs, and within the LIM domain region there is 62% identity with the analogous region of the LIM-only gene LMO1. The homology to LMO1 is restricted to the 360 bp region encoding the tandemly repeated LIM domains, the rest of the open reading frame as well as the extensive, GC-rich 5' untranslated region, and 3' region of the 2 kb cDNA sequence are unrelated to any known genes. This gene has been designated LMO4.

Synergistic derepression of gibberellin signaling by removing RGA and GAI function in Arabidopsis thaliana.

RGA and GAI are negative regulators of the gibberellin (GA) signal transduction pathway in Arabidopsis thaliana. These genes may have partially redundant functions because they are highly homologous, and plants containing single null mutations at these loci are phenotypically similar to wild type. Previously, rga loss-of-function mutations were shown to partially suppress defects of the GA-deficient ga1-3 mutant. Phenotypes rescued include abaxial trichome initiation, rosette radius, flowering time, stem elongation, and apical dominance. Here we present work showing that the rga-24 and gai-t6 null mutations have a synergistic effect on plant growth. Although gai-t6 alone has little effect, when combined with rga-24, they completely rescued the above defects of ga1-3 to wild-type or GA-overdose phenotype. However, seed germination and flower development defects were not restored. Additionally, rga-24 and rga-24/gai-t6 but not gai-t6 alone caused increased feedback inhibition of expression of a GA biosynthetic gene in both the ga1-3 and wild-type backgrounds. These results demonstrate that RGA and GAI have partially redundant functions in maintaining the repressive state of the GA-signaling pathway, but RGA plays a more dominant role than GAI. Removing both RGA and GAI function allows for complete derepression of many aspects of GA signaling.

The ethics of discharge planning for older adults: an ethnographic analysis.

This paper uses ethnographic data to examine ethical dilemmas in discharging elderly persons from the hospital. The focus is on two elements significantly influencing that process, the patient's decisional capacity and the involvement of family members in decision-making. Within the field of bioethics these issues have been discussed in terms of factors compromising the autonomy of the patient and the interdependency of family members. An ethnographic analysis demonstrates how several assumptions in bioethical approaches to these issues are problematic. First, bioethical discussions generally neglect social and structural factors that condition discharge decision-making. The rationality and mental capability of the individuals making decisions are presumed to exist independently of those persons' social contexts; they are also assumed to be concrete properties amenable to objective assessment. Bioethical models further assume that 'the family' is an identifiable ontological unit that exists independently of the setting in which decisions are made and that interdependency is a concrete attribute of familial relations. In contrast, this study shows how discharge planning is an event produced by the interplay among diverse interests. The structure of the discharge planner's role and processes of collective decision-making shape how medical staff perceive and define patients' decisional capacity and the involvement of families. This points to unintentional and unrecognized ways in which the patient's choices and control over decisions can be restricted. The analysis supports attempts to develop bioethical models based on socially grounded principles recognizing the importance of both autonomy and interdependence in long term care decisions.

Defining needs, defining systems: a critical analysis.

This article examines the model of need assessment commonly used in social service programs for older adults. Whereas this model defines need as an individual attribute, remediable through programmatic intervention, an alternative formulation suggests that organizational imperatives shape the definition of client need while obscuring their own role in the production of this information. A case study and historical analysis assess the roots of this process and its consequences for clients, staff, and aging programs.

Institutional environments and organizational responses to AIDS.

Drawing from theory on institutionalized organizational environments, this paper analyzes the actions of community-based service programs providing care for people with AIDS. The focus is on the interorganizational relations developed by the lead agencies in demonstration projects attempting to coordinate services in three communities. The paper identifies differential styles of organizational response to developmental and operational issues. These differences are related to the conceptual distinction between organizational responses to technical environments and those to normative, or "institutional," environmental features. Various factors are identified that appear to promote a higher degree of institutionalization in interorganizational relations. Coordination as a reform strategy is seen to have become, in itself, an institutionalized myth to which organizations must subscribe in order to gain legitimacy.

Multiple resolution skeletons.

This paper presents a new algorithm to compute skeletons of noisy images of objects which can be described as ``amorphous blobs.'' Such a requirement arose from our research to obtain a better understanding of the role of the pseudopod in leukocyte locomotion. It involves the modeling and detection of pseudopods which are by their nature nonrigid bodies appearing on the cell's surface membrane. By computing skeletons at different resolutions, a filtered version can be produced without violating the constraints imposed by the semantic knowledge of pseudopod morphology. The filtered version incorporates all the significant ``events'' that occur at the different resolutions. The resolution at which the shape is examined is related to the degree of smoothing, in that the lower the resolution gets, the higher the degree of smoothing. Skeleton branches that persist over several scales arise from convexities that are locally as well as globally significant. Their stability is related to their perceptual significance. Our approach is to combine an initial region centered description (skeleton) with a boundary analysis executed at different resolutions. Having computed the skeleton at different scales, we then use those computed at the lower resolutions as a measure of how global the underlying convexity is. Clearly the skeletons computed at higher resolutions represent the exact location and orientation of the underlying convexities.

A consecutive series of adults with brain injury treated with a washing and dressing retraining program.

OBJECTIVES: Single-case reports indicate that behavioral methods can assist persons with brain injury to redevelop self-care skills. However, the proportion of patients who could benefit from these interventions is unknown. The present study used a specific retraining protocol to treat all patients admitted to a single facility over a 3-year period who were unable to wash and dress independently. METHOD: Four patients out of 48 met the study criteria and were treated with the washing and dressing protocol. Three had traumatic brain injury, and one had brain injury after cerebral bleed. The training program involved behavioral observation, task analysis, consistent practice, and cue fading. The Adaptive Behavior Scale was used to measure behavior change. RESULTS: Three subjects achieved rapid independence in washing and dressing (20 days, 37 days, and 11 days of treatment), and one did not show significant clinical improvement. CONCLUSION: All patients admitted to the facility during a 3-year period who required washing and dressing retraining were treated with the same protocol. The consecutive series design prevented researchers from selecting patients who they believed were good treatment candidates; therefore, the findings support the general applicability of the training program.

[Smoking behavior of family physicians, specialists and students in Rotterdam, 1989]. / Rookgedrag van huisartsen, specialisten en studenten in Rotterdam, 1989.

In a survey of smoking habits and attitudes among general practitioners of the Rotterdam area, consultants at the University Hospital of Rotterdam, medical students and students of the Department of Health Policy and Management (HPM) at the Erasmus University of Rotterdam, it was found that 30 percent of this population smoked. Among the male general practitioners and the male HPM students more smokers were found than in the general male population. Smoking prevalence among female doctors and students is lower than among their male counterparts and also lower than that among the general female population. Amongst doctors the knowledge of smoking cessation methods and the relationship between smoking and diseases was found to be suboptimal. Students of medicine are not inclined to start smoking. This will reinforce the present downward trend in the proportion of physicians who smoke.

Compositional studies of human RPE lipofuscin: mechanisms of molecular modifications.

The accumulation of lipofuscin has previously been implicated in several retinal diseases including Best's macular dystrophy, Stargardt's disease and age-related macular degeneration (AMD). Previously one of the major fluorophores of lipofuscin was identified as a bis-retinoid pyridinium salt called A2E, which is known to photochemically cause damage. In addition to A2E, there are numerous components in RPE lipofuscin that are unidentified. These compounds were determined to be structurally related to A2E by their fragmentation pattern with losses of 106, 190, 174 and/or 150 amu from the parent ion and the formation of fragments of ca 592 amu. The vast majority consists of relatively hydrophobic components corresponding to derivatized A2E with molecular weights in discrete groups of 800-900, 970-1080 and > 1200 m/z regions. In order to determine the mechanism of these modifications, A2E was chemically modified by; (1) the formation of specific esters, (2) reaction with specific aldehydes and (3) spontaneous auto-oxidation. The contribution of ester formation to the naturally occurring components of lipofuscin was discounted since their fragmentation patterns were different to those found in vivo. Alternatively, reactions with specific aldehydes result in nearly identical products as those found in vivo. Artificial aging of RPE lipofuscin gives a complex mixture of structurally related components. This results from the auto- and/or photooxidation of A2E to form aldehydes, which then back react with A2E giving a series of higher molecular weight products. The majority of these modifications result in compounds that are much more hydrophobic than A2E. These higher molecular weight materials have increased values of log P compared to A2E. This increase in hydrophobicity most likely aids in the sequestering of A2E into granules with the concomitant diminution of its reactivity. Therefore, these processes may serve as protective mechanisms for the RPE.

Compositional studies of human RPE lipofuscin.

Age-related macular degeneration (AMD) is an ocular disease that causes visual loss and legal blindness in the elderly population. The etiology of AMD is complex and may include genetic predispositions, accumulation of lipofuscin and drusen, local inflammation and neovascularization. The accumulation of lipofuscin has been shown to precede the death of photoreceptor cells and the deterioration of the RPE. As a result, the determination of the photosensitive components of lipofuscin has been of major interest. One of these components, previously identified as a bis-retinoid pyridinium compound, is referred to as A2E. A2E has been characterized by mass spectrometry and is known to have a mass of 592 Da. Most remaining chromophores in RPE lipofuscin are structurally related to A2E as determined by their fragmentation pattern with losses of M ± 190, 174 and/or 150 Da. Analysis of lipofuscin from various donors indicated that the extracts consist of as many as 15 of these hydrophobic components, which are also observed to form spontaneously in vitro over extended periods of time. These consist of ca 90% of the A2E-like components in RPE lipofuscin and correspond to derivatized A2E with discrete molecular weights of 800-900 m/z, 970-1080 m/z and above 1200 m/z regions. It was determined that these species are formed from self-reaction of A2E oxidation products or their reaction with A2E itself to form higher molecular weight products. The majority of modifications are much more hydrophobic than A2E and exhibit increasingly higher values of log P. This acts as a driving force for the sequestering of A2E into granules resulting in a concomitant diminution of its reactivity in vivo.

Cloning of a novel nucleolar guanosine 5'-triphosphate binding protein autoantigen from a breast tumor.

A cDNA clone encoding an immunoreactive autoantigen (Ngp-1) was isolated by screening lambda gt11 human ductal breast tumor expression libraries with autologous patient serum. The complete 2.3-kb nucleotide sequence of the cDNA was found to contain an open reading frame that could encode a protein of 731 amino acids. The predicted amino acid sequence contains a high concentration of charged amino acids in the carboxy terminal quarter of the molecule, three guanosine 5'-triphosphate (GTP)-binding protein motifs, and a consensus nuclear localization signal. The arrangement and spacing of the GTP-binding protein motifs indicate that Ngp-1 belongs to a newly described subfamily of GTPases. Except for the consensus motifs, neither nucleotide sequence, nor the predicted amino acid sequence of the Ngp-1 cDNA showed the slightest homology to any vertebrate gene product sequence listed in the databases. Northern blot analysis showed the 2.3-kb transcript to be ubiquitously expressed at relatively low levels in all human tissues tested, with the highest level of expression in the testes. Immunohistochemical analysis of tissue sections with affinity-purified antiserum raised against a recombinant Ngp-1 protein revealed that the antigen was exclusively localized to the nucleolus and nucleolar organizer regions in all cell types analyzed.

A comparison of hospital and community case management programs for persons with AIDS.

To determine whether locus of AIDS case management affects the content of this service, a survey of case managers in 42 major American cities was conducted. One hundred seventy-one case managers working in both public hospitals and community-based organizations (CBOs) responded. Hospital case managers were substantially more likely to report clinical training than CBO case managers. Hospital case managers' case loads were more likely to include drug users and patients with more urgent needs such as housing and drug abuse treatment. While CBO case managers were more likely to work to develop services in the community, hospital case managers reported working more closely with medical staff and discharge planning committees. CBO case managers reported greater difficulty obtaining a number of key services for their clients including home health care, housekeeping, and entitlements; hospital case managers reported greater difficulty obtaining emotional support volunteers. These results indicate that locus of case management strongly affects the structure and content of this service. The importance of these findings for future program planning is discussed.

The DELLA motif is essential for gibberellin-induced degradation of RGA.

RGA and GAI are homologous genes that encode putative transcriptional regulators that repress gibberellin (GA) signaling in Arabidopsis. Previously we showed that the green fluorescent protein (GFP)-RGA fusion protein is localized to the nucleus in transgenic Arabidopsis, and expression of this fusion protein rescues the rga null mutation. The GA signal seems to derepress the GA response pathway by degrading the repressor protein RGA. The GA-insensitive, semidominant, semidwarf gai-1 mutant encodes a mutant protein with a 17-amino acid deletion within the DELLA domain of GAI. It was hypothesized that this mutation turns the gai protein into a constitutive repressor of GA signaling. Because the sequences missing in gai-1 are identical between GAI and RGA, we tested whether an identical mutation (rga-Delta 17) in the RGA gene would confer a phenotype similar to gai-1. We demonstrated that expression of rga-Delta 17 or GFP-(rga-Delta 17) under the control of the RGA promoter caused a GA-unresponsive severe dwarf phenotype in transgenic Arabidopsis. Analysis of the mRNA levels of a GA biosynthetic gene, GA4, showed that the feedback control of GA biosynthesis in these transgenic plants was less responsive to GA than that in wild type. Immunoblot and confocal microscopy analyses indicated that rga-Delta17 and GFP-(rga-Delta 17) proteins were resistant to degradation after GA application. Our results illustrate that the DELLA domain in RGA plays a regulatory role in GA-induced degradation of RGA. Deletion of this region stabilizes the rga-Delta 17 mutant protein, and regardless of the endogenous GA status rga-Delta 17 becomes a constitutively active repressor of GA signaling.

11beta-hydroxysteroid dehydrogenase type 1: a new regulator of fetal lung maturation.

Glucocorticoids (GCs) induce surfactant synthesis in the late fetal lung. Deficient GC action causes respiratory distress syndrome. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. We investigated 11beta-HSD1 in the late fetal lung using the licorice-derived inhibitor, glycyrrhetinic acid (GE), in pregnant rats (day 13 of gestation until term). Control fetal mice and rats showed high 11beta-HSD activity in the late fetal lung; levels of plasma 11-dehydrocorticosterone were also high. Reduction/loss of pulmonary 11beta-HSD1 activity in GE-treated rats substantially impaired fetal lung maturation. Lungs from GE-exposed rats had lower surfactant protein-A (mRNA and protein) levels and reduced amniotic fluid lecithin/sphingomyelin ratios. There was a marked depletion of lung surfactant before and after birth, as detected by both light and electron microscopy. The data emphasize the importance of 11beta-HSD1 in amplifying key GC-dependent maturational processes in the late fetal lung.

Foetal lung maturation in 11beta-hydroxysteroid dehydrogenase type 1 knockout mice.

Glucocorticoids (GCs) induce surfactant synthesis in the late foetal lung. Deficient GC action causes respiratory distress syndrome (RDS). 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. Reduction or loss of pulmonary 11beta-HSD1 activity in glycyrrhetinic acid-treated rats substantially impaired foetal lung maturation (Hundertmark et al., Horm Metab Res, this issue). To test these data, we investigated 11beta-HSD1 activity and lung maturity in the late foetal lung using 11beta-HSD1 knockout mice. Control foetal mice showed high 11beta-HSD activity in the late foetal lung and levels of plasma 11-dehydrocorticosterone were high. Lungs from 11beta-HSD1 -/- mice had lower surfactant protein-A (mRNA and protein) levels and significant depletion of lung surfactant according to both light and electron microscopy, and also had reduced amniotic fluid lecithin/sphingomyelin ratios. These results support the previous experiments with glycyrrhetinic acid and emphasize the importance of 11beta-HSD1 in foetal lung maturation.

Repressing a repressor: gibberellin-induced rapid reduction of the RGA protein in Arabidopsis.

RGA (for repressor of ga1-3) and SPINDLY (SPY) are likely repressors of gibberellin (GA) signaling in Arabidopsis because the recessive rga and spy mutations partially suppressed the phenotype of the GA-deficient mutant ga1-3. We found that neither rga nor spy altered the GA levels in the wild-type or the ga1-3 background. However, expression of the GA biosynthetic gene GA4 was reduced 26% by the rga mutation, suggesting that partial derepression of the GA response pathway by rga resulted in the feedback inhibition of GA4 expression. The green fluorescent protein (GFP)-RGA fusion protein was localized to nuclei in transgenic Arabidopsis. This result supports the predicted function of RGA as a transcriptional regulator based on sequence analysis. Confocal microscopy and immunoblot analyses demonstrated that the levels of both the GFP-RGA fusion protein and endogenous RGA were reduced rapidly by GA treatment. Therefore, the GA signal appears to derepress the GA signaling pathway by degrading the repressor protein RGA. The effect of rga on GA4 gene expression and the effect of GA on RGA protein level allow us to identify part of the mechanism by which GA homeostasis is achieved.

Innovative working schedule: introducing one short nap during the night shift.

In order to test the possible long-term effects of the implementation of a short nap during night shifts, an experiment was conducted over a period of 1 year with 12 volunteer shiftworkers operating in an industrial plant. They were authorized, under certain conditions, to use individual sleeping areas, for a maximum of 1 hour, between 23h30 and 3h30. The participants were asked to fill in a short questionnaire every day during the entire study. The questions concerned the schedule of the main sleep period, the afternoon nap and the night-time nap, if any, as well as the evaluation of mood and the quality of work. This daily questionnaire was supplemented by an extensive questionnaire applied every 2 months in order to assess the main changes introduced in the life of the participants by this new working schedule. Results showed that this new organization introduced a general satisfaction about the quality and the easiness of the work at night. The vigilance level was considered to be higher during the hours following the nap. The efficacy of the nap time progressively increased for most subjects. The general quality of life improved for most subjects. While a few of them considered that falling asleep was less easy on the following morning at home, the statistical analysis did not show any detrimental effect of the short rest period on the length of the immediately consecutive main sleep period. However, different statistical analyses allow us to reveal significant differences between the main sleep durations following the night shift compared with those following both the afternoon shift and the resting period. The main sleep duration following the night shift was not statistically different from that of the morning shift. These results are very encouraging. A short nap during the night shift can be considered as a positive way to counteract the low level of vigilance that normally occurs during the late part of the night.