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This study explores the sources and mechanisms of dissolved phosphorus (P) mobilization under base flow conditions in a headwater stream. We characterized the relevant chemical species and processes within the watershed to investigate connections between stream sediment, surface water, and groundwater with respect to P dynamics. Waters were monitored monthly during the 2017 snow-free period for temperature, pH, dissolved oxygen, conductivity, soluble reactive P (SRP), total P, strong acid anions, strong base cations, dissolved organic carbon (DOC), Al, Fe, and Mn. Phosphorus speciation within sediment samples was determined by sequential chemical extractions. The emerging groundwater was under-saturated by up to 40% with respect to O 2 , with pH = 7.24, T = 7.0 °C, and SRP = 3.0 μg L -1 . Groundwater P CO2 was up to ~35× the ambient P CO2 (410 ppm). Degassing of CO 2 from the emerging groundwater resulted in a significant increase in pH downstream, and an increase in the SRP concentration from 3.0 to a maximum of 40.6 μg L -1 . Laboratory experiments, using homogenized stream sediment, identified a reduction in the P adsorption capacity, and an increase in desorption of native P with increasing pH from ~7.25 (emerging groundwater) to ~8.50 (air-equilibrated surface water). These data allow us to identify the pH-dependent desorption from P-laden sediment as the most significant source of dissolved P in the headwater stream under base flow conditions., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hypertension (HTN) is a devastating disease with a higher incidence in African Americans than European Americans, inspiring searches for genetic variants that contribute to this difference. We report the results of a large-scale admixture scan for genes contributing HTN risk, in which we screened 1,670 African Americans with HTN and 387 control individuals for regions of the genome with elevated proportion of African or European ancestry. No loci were identified that were significantly associated with HTN. We also searched for evidence of an admixture signal at 40 candidate genes and eight previously reported linkage peaks, but none appears to contribute substantially to the differential HTN risk between African and European Americans. Finally, we observed nominal association at one of the loci detected in the admixture scan of Zhu et al. 2005 (p = 0.016 at 6q24.3 correcting for four hypotheses tested), although we caution that the significance is marginal and the estimated odds ratio of 1.19 per African allele is less than what would be expected from the original report; thus, further work is needed to follow up this locus., Competing Interests: Competing interests. The authors have declared that no competing interests exist.

Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America.

After the recent discovery that common genetic variation in 8q24 influences inherited risk of prostate cancer, we genotyped 2,973 SNPs in up to 7,518 men with and without prostate cancer from five populations. We identified seven risk variants, five of them previously undescribed, spanning 430 kb and each independently predicting risk for prostate cancer (P = 7.9 x 10(-19) for the strongest association, and P < 1.5 x 10(-4) for five of the variants, after controlling for each of the others). The variants define common genotypes that span a more than fivefold range of susceptibility to cancer in some populations. None of the prostate cancer risk variants aligns to a known gene or alters the coding sequence of an encoded protein.

Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P<<1.0x10-12) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P<3.4x10-5). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P<<1.0x10-12 for IL-6 SR, and P<2.0x10-9 for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant.

A whole-genome admixture scan in 1,597 African Americans identified a 3.8 Mb interval on chromosome 8q24 as significantly associated with susceptibility to prostate cancer [logarithm of odds (LOD) = 7.1]. The increased risk because of inheriting African ancestry is greater in men diagnosed before 72 years of age (P < 0.00032) and may contribute to the epidemiological observation that the higher risk for prostate cancer in African Americans is greatest in younger men (and attenuates with older age). The same region was recently identified through linkage analysis of prostate cancer, followed by fine-mapping. We strongly replicated this association (P < 4.2 x 10(-9)) but find that the previously described alleles do not explain more than a fraction of the admixture signal. Thus, admixture mapping indicates a major, still-unidentified risk gene for prostate cancer at 8q24, motivating intense work to find it.

Multiple sclerosis is a common disease with proven heritability, but, despite large-scale attempts, no underlying risk genes have been identified. Traditional linkage scans have so far identified only one risk haplotype for multiple sclerosis (at HLA on chromosome 6), which explains only a fraction of the increased risk to siblings. Association scans such as admixture mapping have much more power, in principle, to find the weak factors that must explain most of the disease risk. We describe here the first high-powered admixture scan, focusing on 605 African American cases and 1,043 African American controls, and report a locus on chromosome 1 that is significantly associated with multiple sclerosis.

We compared fine-scale recombination rates at orthologous loci in humans and chimpanzees by analyzing polymorphism data in both species. Strong statistical evidence for hotspots of recombination was obtained in both species. Despite approximately 99% identity at the level of DNA sequence, however, recombination hotspots were found rarely (if at all) at the same positions in the two species, and no correlation was observed in estimates of fine-scale recombination rates. Thus, local patterns of recombination rate have evolved rapidly, in a manner disproportionate to the change in DNA sequence.

Admixture mapping (also known as "mapping by admixture linkage disequilibrium," or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with approximately 100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing approximately 450000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3011 as a MALD map (1.2 cM average spacing). We estimate that this map is approximately 70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.

Population stratification refers to differences in allele frequencies between cases and controls due to systematic differences in ancestry rather than association of genes with disease. It has been proposed that false positive associations due to stratification can be controlled by genotyping a few dozen unlinked genetic markers. To assess stratification empirically, we analyzed data from 11 case-control and case-cohort association studies. We did not detect statistically significant evidence for stratification but did observe that assessments based on a few dozen markers lack power to rule out moderate levels of stratification that could cause false positive associations in studies designed to detect modest genetic risk factors. After increasing the number of markers and samples in a case-cohort study (the design most immune to stratification), we found that stratification was in fact present. Our results suggest that modest amounts of stratification can exist even in well designed studies.

The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.

Ten microsatellite loci (Omy27DU,Omy325(A3)UoG, OmyFGT5TUF,OmyFGT14TUF, OmyFGT15TUF,OmyFGT23TUF, Omy77DU,Ssa20.19NUIG, Ots1BML, andOne18ASC) were amplified using the polymerase chain reaction to create genetic profiles for nine cell lines (RTG-2, RTH-149,RTL-W1,RTgill-W1, RTS-11, RTS-34st, RTP-2, RTP-91E and RTP-91F) from rainbow trout(Oncorhynchus mykiss) and one cell line (CHSE-214) from Chinook salmon (O. tschawytscha). A cell line (PHL) from anon-salmonid, the Pacific herring (Clupea harengus pallasi), was included as a control. The ten loci clearly revealed the uniqueness of each cell line, except for two cell lines (RTP-91E andRTP-91F) from the same fish. RTP-91E and RTP-91F were identical at all loci except Ssa20.19NUIG. The most useful locus for demonstrating uniqueness was Ots1BML. The information was used to demonstrate that an uncharacterized rainbow trout cell line (Clone 1A)was in fact CHSE-214, illustrating the usefulness of multiplexed microsatellites for the creation of genetic profiles for salmonid cell lines and for the testing of cell line cross-contamination.

Objective: To determine the long-term efficacy of percutaneous radiofrequency medial branch neurotomy in the treatment of chronic neck pain., Methods: Between 1991 and 1996, radiofrequency neurotomy was performed in 28 patients diagnosed as having cervical zygapophysial joint pain on the basis of controlled diagnostic blocks. The procedure was repeated in patients whose pain recurred. Outcome measures were the proportion of patients who responded to the initial procedure and the duration of relief subsequently obtained. Outcome was correlated with the operator performing the procedure, the type of electrode used, litigation status, and the type of diagnostic blocks used to establish the diagnosis., Results: Complete relief of pain was obtained in 71% of patients after an initial procedure. No patient who failed to respond to a first procedure responded to a repeat procedure, but if pain returned after a successful initial procedure, relief could be reinstated by a repeat procedure. The median duration of relief after a first procedure was 219 days when failures are included but 422 days when only successful cases are considered. The median duration of relief after repeat procedures was at least 219 days; several patients had ongoing relief at the time of follow-up. Outcome did not differ according to the operator, the type of electrode used, litigation status, or the type of diagnostic block used., Conclusion: Radiofrequency neurotomy provides clinically significant and satisfying periods of freedom from pain, and its effects can be reinstated if pain recurs.

Chronic obstructive pulmonary disease (COPD) affects over 16 million people in the United States and is a major cause of disability and death worldwide. Its prevalence and mortality are increasing disproportionately among the elderly, women, African-Americans, persons of lower socioeconomic status, and the populations of developing countries in which tobacco is aggressively marketed. In contrast to other major chronic diseases such as heart disease and cancer, medical treatments for COPD have not made decisive inroads into its morbidity or death rates over the last 20 years, resulting in continuing efforts to reduce disability in patients with established disease. Depression is a source of increased disability in COPD, and, as in other chronically ill patient populations, is often unrecognized and untreated in the primary and specialty care sectors. Nearly half of all patients experience some depressive symptoms and at least one-fifth have had one or more major depressive episodes, frequently of long duration. Evidence from randomized controlled trials supports the thesis that patients with mild depression improve with multidisciplinary rehabilitation, whereas patients with major depression may require specific pharmacotherapy to achieve significant improvement in mood disorder and day-to-day function. In addition to its impact on disability, depression may contribute indirectly to the etiology and progression of COPD through its relationship to addictive smoking. Mood disorder in adolescence and early adulthood contributes to early smoking and failure to quit, even after the onset of respiratory disease in later life. Patients with a history of major depression are more likely to fail in smoking cessation programs and to develop a major depressive episode when they do stop. This relationship calls for psychiatrically informed intervention models to improve long-term abstinence rates. The functional impairments associated with COPD are themselves potential promoters of depressive morbidity and chronicity, acting through complex causal pathways. Progressive hypoxia due to respiratory insufficiency leads to structural brain changes and neurocognitive deficits that impair day-to-day function and reduce adaptive potential; and oxygen therapy, as now practiced, offers minimal neurocognitive and mood benefits to most patients. Limited data from studies of experimental hypoxia in animals suggest that relatively mild lack of oxygen impairs the function and plasticity of critical neurotransmitter systems implicated in both cognition and mood, although current practice standards withhold oxygen therapy until late in the course of disease when the damaging effects of hypoxia on the brain have become well established. Neuropsychiatric approaches to the prevention, delay, and treatment of brain dysfunction should be a primary objective of research to improve patient outcomes. A comprehensive relational model that links pulmonary disease, hypoxia, neurocognitive impairment, and structural brain disease with depression provides a useful framework for the design of such studies. The near-term research agenda should include three components: (1) practical methods for improving physician and patient recognition of depression and neurocognitive impairment as targets for intervention; (2) additional trials of standard antidepressant treatment approaches for both major and minor depression; and (3) tests of the hypothesis that late-onset depression in patients with COPD is a marker for the presence of neurocognitive deficits and structural brain changes. The long-range research agenda must aim at preventive interventions designed to forestall brain deterioration. Controlled clinical trials of supplemental oxygen in patients with mild hypoxia and minimal cognitive deficits are needed to determine whether early treatment can reverse or moderate decline, reduce the incidence and chronicity of depression, and improve response to antidepressant treatment. Novel neuroprotective therapies such as antioxidant supplementation and modulation of monoaminergic neurotransmission, coupled with overall improvements in long-term respiratory disease management that minimize episodes of increased systemic oxidative stress, should be considered for multisite trials designed to define optimal treatment and prevention.

Poor nutritional status in patients with cystic fibrosis (CF) is associated with increased mortality. Patients with CF often have a decreased sensation of smell secondary to recurrent sinus infections or sinus surgery; in other CF populations, a decreased sensation of smell has been associated with poor nutritional status. We hypothesized that a decreased sensation of smell would be associated with worse nutritional status in patients with CF. We studied 50 (26 F and 24 M) of 58 consecutive patients with CF (86%) aged 14-53 years (28 +/- 8; mean +/- SD) who attended the University of Washington Medical Center from June 1994 to March 1995 and who agreed to participate. Demographic information was obtained, and nutritional status was assessed by ideal body weight, arm muscle area, arm fat area, pancreatic sufficiency, insulin-requiring diabetes, vitamins A and E levels, albumin, iron, iron binding capacity, ferritin, cholesterol, and zinc levels. Objective sensation of small was examined (Sensonics, Philadelphia, PA), a sinus compacted tomogram (CT) was performed, and a questionnaire for prior sinus symptoms, sinus surgery, medications, and subjective sensation of smell was administered. Twenty-seven of 49 subjects (55%) had an objective decrease in sensation of smell, 23/50 (46%) had had prior sinus surgery. 46/50 (92%) were pancreatic insufficient, and 8/50 (16%) were insulin-requiring diabetics. Weight for height ranged from the 38th to 157th percentile (100 +/- 18; mean +/- SD). Arm muscle area ranged from the < 5th to the 75th percentile (25 +/- 23; mean +/- SD). Arm fat area ranged from the < 5th to the 95th percentile (45 +/- 39; mean +/- SD). Sinus CT scans were abnormal in all patients (100%). Patients with anosmia were more likely to have had sinus surgery, but their nutritional status was no different from that of patients with a normal sensation of smell. We conclude that decreased sensation of smell is common in patients with CF, especially those with prior sinus surgery. Subjective sensation of smell and sinus CT scans were unreliable indicators of a decreased objective sensation of smell. In this pilot study, no association was found between sensation of smell and nutritional status.

Background: Chronic pain in the cervical zygapohyseal joints is a common problem after whiplash injury, but treatment is difficult. Percutaneous radiofrequency neurotomy can relieve the pain by denaturing the nerves innervating the painful joint, but the efficacy of this treatment has not been established., Methods: In a randomized, double-blind trial, we compared percutaneous radio-frequency neurotomy in which multiple lesions were made and the temperature of the electrode making the lesions was raised to 80 degrees C with a control treatment using an identical procedure except that the radio-frequency current was not turned on. We studied 24 patients (9 men and 15 women; mean age, 43 years) who had pain in one or more cervical zygapophyseal joints after an automobile accident (median duration of pain, 34 months). The source of their pain had been identified with the use of double-blind, placebo-controlled local anesthesia. Twelve patients received each treatment. The patients were followed by telephone interviews and clinic visits until they reported that their pain had returned to 50 percent of the preoperative level., Results: The median time that elapsed before the pain returned to at least 50 percent of the preoperative level was 263 days in the active-treatment group and 8 days in the control group (P=0.04). At 27 weeks, seven patients in the active-treatment group and one patient in the control group were free of pain. Five patients in the active-treatment group had numbness in the territory of the treated nerves, but none considered it troubling., Conclusions: In patients with chronic cervical zygapophyseal-joint pain confirmed with double-blind, placebo-controlled local anesthesia, percutaneous radio-frequency neurotomy with multiple lesions of target nerves can provide lasting relief.

Through a leak in the steam heating system, the anticorrosive agent 2-diethylaminoethanol was released into the air of a large office building. Irritative symptoms were experienced by most of the 2500 employees, and 14 workers developed asthma within 3 months of exposure. This study was undertaken to review clinical characteristics of these asthmatics. Environmental exposure monitoring data and medical records were reviewed. Seven of 14 cases were defined as "confirmed" and 7 of 14 as "suspect," using the National Institute for Occupational Safety and Health surveillance case definition of occupational asthma. Spirometry was positive in 4 of 14 of the cases and peak flow testing in 10 of 14. Three cases were diagnosed on the basis of work-related symptoms and physical examination alone. The study suggests that acute exposure to the irritating steam additive 2-diethylaminoethanol was a contributing factor in the development of clinical asthma in this population.

Although recent epidemiologic studies have established that patients with chronic medical illness and depressed mood are more disabled than euthymic patients, detailed data on the benefits and risks of antidepressant treatment in medically high-risk patients have been slow to accumulate. The authors have examined multiple outcome indicators in patients with disabling chronic obstructive pulmonary disease and comorbid depression. Thirty patients completed a 12-week, randomized controlled trial of nortriptyline. Nortriptyline was clearly superior to placebo for treatment of depression. Nortriptyline treatment was accompanied by marked improvements in anxiety, certain respiratory symptoms, overall physical comfort, and day-to-day function; placebo effects were negligible. Physiological measures reflecting pulmonary insufficiency were generally unaffected by treatment. These data provide impetus for renewed efforts to improve recognition and treatment of mood disorders in even severely disabled medical patients.

Three major systems are currently available in most urban settings for the delivery of long-term oxygen therapy. These are compressed oxygen in tanks, liquid oxygen, and oxygen concentrators. Each system has advantages and disadvantages. The choice of system for any individual patient must be based on relative cost, the need for portability, and safety features. The cost of oxygen and regulations governing its reimbursement vary widely throughout the country. Oxygen should be supplied by reputable vendors who meet specific criteria for assuring quality service. In many instances referral to a home care agency for teaching and supervision of the patient is essential. Patient compliance with long-term oxygen therapy is often poor due to factors such as lack of significant subjective improvement, unrealistic fears or embarrassment concerning use of oxygen, and feelings of depression or hopelessness that the patient may experience when told he needs oxygen.

One hundred ninety-nine self-defined homosexual males were asked about the ages at which milestone events occurred in the coming out process (i.e., initial awareness of same-sex attractions, same-sex acts, self-designation as homosexual, initial involvement in a long-term relationship, self-disclosures to significant others, and acquiring a positive gay identity). Overall findings indicated that an orderly developmental sequence underlies the coming out process; however, not all subjects progressed in a predictable fashion from an awareness of same-sex feelings through behavior to eventual self-labelling, self-disclosure, and final stabilization of a positive gay identity. A number of individual differences emerged: 18% of the sample labelled themselves "homosexual" in the absence of any overt same-sex sexual experience; 22% arrived at homosexual self-definitions while participating in a long-term relationship with another man; 23% adopted homosexual self-definitions only after involvement in such a relationship. Fifteen percent of the respondents indicated that they had not acquired a positive gay identity (i.e., were not glad to be gay). These individuals differed from the remainder of the sample on a number of significant measures reflective of psychological health. Significant differences were also found among three cohort groups with respect to age at occurrence of particular milestone events. Findings from the present investigation were explored in relation to both the theoretical conceptions and available empirical data concerned with homosexual identity formation.

A randomized controlled trial was conducted to assess efficacy and cost of sustained home nursing care for patients with chronic lung disease. Three hundred one patients were randomly assigned to a respiratory home care group (RHC) that received care from respiratory home care nurses, a standard home care group (SHC) that received care from regular home care nurses, or an office care group (OC) that received whatever care they needed except for home care. Patients were followed for 1 year. At the end of the study year, there was no difference in survival, pulmonary function, or everyday functioning among the three groups. Average annual cost of care for all study patients was $7,647 (1981-82 dollars). The average annual health care costs for patients in the RHC group was $9,768; for those in the SHC group, $8,058; and for those in the OC group, $5,051 (F = 6.45, df = 2/298, P = 0.02). These results suggest that the current policy of limited coverage of home nursing services by Medicare and other third-party payers may be appropriate.

A nonclinical sample of 88 homosexual males responded to a questionnaire that assessed their sex-role self-concept and their attitudes toward both women and male homosexuality. Results indicated that in terms of socially valued masculine and feminine characteristics, the majority of homosexual males viewed themselves as predominantly androgynous. These respondents also favored equality between the sexes, reflecting positive attitudes toward women. Similarly, those homosexual men who supported equality between the sexes also held more positive attitudes toward male homosexuality.

Homosexual identity is conceptualized as a life-spanning developmental process that eventually leads to personal acceptance of a positive gay self-image and a coherent personal identity. Habermas' theory of ego development is utilized to provide a synthesis and understanding of the literature on the construction and maintenance of the homosexual identity. It is concluded that the homosexual identity generally emerges in a three-stage process in which the person progresses from: (1) an egocentric interpretation of homoerotic feelings to (2) an internalization of the normative, conventional assumptions about homosexuality to (3) a post-conventional phase in which societal norms are critically evaluated and the positive gay identity is achieved and managed. Developmental tasks associated with each stage are outlined in terms of their ego-integrative functions. Although the stages in the process of homosexual identity formation are theoretically the same for females and males, because of the paucity of research on the homosexual identity in females, this paper deals chiefly with males.