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Importance: Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP). Objective: To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement. Design, Setting, and Participants: The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016-April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018. Exposures: Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring. Main Outcomes and Measures: The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378). Results: Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33]). Conclusions and Relevance: Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.
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Fármacos Anti-VIH/uso terapéutico , Bisexualidad , Emtricitabina/uso terapéutico , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Profilaxis Pre-Exposición , Enfermedades de Transmisión Sexual/epidemiología , Tenofovir/uso terapéutico , Sexo Inseguro/estadística & datos numéricos , Adolescente , Adulto , Australia/epidemiología , Quimioterapia Combinada , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Vigilancia de la Población , Modelos de Riesgos Proporcionales , Adulto JovenRESUMEN
Background: Pre-exposure prophylaxis (PrEP) is the use of HIV anti-retroviral therapy to prevent HIV transmission in people at high risk of HIV acquisition. PrEP is highly efficacious when taken either daily, or in an on-demand schedule. In Australia co-formulated tenofovir-emtricitabine is registered for daily use for PrEP, however, this co-formulation is not listed yet on the national subsidized medicines list. We describe a study protocol that aims to demonstrate if the provision of PrEP to up to 3800 individuals at risk of HIV in Victoria, Australia reduces HIV incidence locally by 25% generally and 30% among GBM. Methods: PrEPX is a population level intervention study in Victoria, Australia in which generic PrEP will be delivered to 3800 individuals for up to 36 months. Study eligibility is consistent with the recently updated 2017 Australian PrEP guidelines. Participants will attend study clinics, shared care clinics, or outreach clinics for quarterly HIV/STI screening, biannual renal function tests and other clinical care as required. Study visits and STI diagnoses will be recorded electronically through the ACCESS surveillance system. At each study visit participants will be invited to complete behavioral surveys that collect demographics and sexual risk data. Diagnosis and behavioral data will be compared between PrEPX participants and other individuals testing within the ACCESS surveillance system. A subset of participants will complete in depth surveys and interviews to collect attitudes, beliefs and acceptability data. Participating clinics will provide clinic level data on implementation and management of PrEPX participants. The population level impact on HIV incidence will be assessed using Victorian HIV notification data. Discussion: This study will collect evidence on the real world impact of delivery of PrEP to 3800 individuals at risk of acquiring HIV in Victoria. This study will provide important information for the broader implementation of PrEP planning upon listing of the tenofovir-emtricitabine on the national subsidized list of medicines. The study is registered on the Australian New Zealand Clinical Trials Registry (ACTRN12616001215415).
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Lockie, RG, Moreno, MR, Lazar, A, Orjalo, AJ, Giuliano, DV, Risso, FG, Davis, DL, Crelling, JB, Lockwood, JR, and Jalilvand, F. The physical and athletic performance characteristics of Division I collegiate female soccer players by position. J Strength Cond Res 32(2): 334-343, 2018-Playing positions in soccer can exhibit different movement demands during a match, contributing to variations in physical and performance characteristics. National Collegiate Athletic Association (NCAA) soccer features different substitution rules when compared to FIFA-sanctioned matches, which could influence each players' characteristics. Therefore, this study determined the athletic performance characteristics of Division I female soccer players. Twenty-six players (3 goalkeepers; 8 defenders; 10 midfielders; 5 forwards) from the same squad completed assessments of: lower-body power (vertical and standing broad jump); linear (0-5, 0-10, 0-30 meter [m] sprint intervals) and change-of-direction (pro-agility shuttle; arrowhead change-of-direction speed test) speed; and soccer-specific fitness (Yo-Yo Intermittent Recovery Test [YYIRT] levels 1 and 2). Players were split into position groups, and a Kruskal-Wallis H test with post hoc pairwise analyses (p ≤ 0.05) calculated significant between-group differences. There were no differences in age, height, or body mass between the positions. Midfielders had a faster 0-5 m time compared with the defenders (p = 0.017) and the goalkeepers (p = 0.030). The defenders (p = 0.011) and midfielders (p = 0.013) covered a greater YYIRT2 distance compared with the goalkeepers. There were no other significant between-position differences. Overall, Division I collegiate female players from the same squad demonstrated similar characteristics as measured by soccer-specific performance tests, which could allow for flexibility in position assignments. However, a relatively homogenous squad could also indicate commonality in training prescription, particularly regarding acceleration and high-intensity running. Strength and conditioning coaches may have to consider the specific movement demands of individual positions when training these capacities.
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Atletas , Rendimiento Atlético/fisiología , Fútbol/fisiología , Aceleración , Estudios Transversales , Prueba de Esfuerzo , Femenino , Humanos , Movimiento , Carrera/fisiología , Universidades , Adulto JovenRESUMEN
This letter reports on an enhanced surveillance snapshot of hepatitis B and C at a men who have sex with men community testing site in inner Sydney. The finding show undiagnosed hepatitis B and C infection is rare in this population of gay and bisexual men. Evidence of immunity to hepatitis B through vaccination is high, however client knowledge of vaccination status is poor. Current targeted hepatitis screening practices were sufficient to detect all undiagnosed cases of hepatitis B and C in this population.
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Bisexualidad , Infecciones por VIH/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Homosexualidad Masculina , Humanos , Masculino , Tamizaje Masivo , Nueva Gales del Sur/epidemiología , Prevalencia , Factores de Riesgo , Población UrbanaRESUMEN
Obesity continues to be a global health problem, and thus it is imperative that new pathways regulating energy balance be identified. Recently, it was reported: (Hayashi K, Cao T, Passmore H, Jourdan-Le Saux C, Fogelgren B, Khan S, Hornstra I, Kim Y, Hayashi M, Csiszar K. J Invest Dermatol 123: 864-871, 2004) that mice carrying a missense mutation in myelin protein zero-like 3 (Mpzl3rc) have reduced body weight. To determine how Mpzl3 controls energy balance in vivo, we generated mice deficient in myelin protein zero-like 3 (Mpzl3-KO). Interestingly, KO mice were hyperphagic yet had reduced body weight and fat mass. Moreover, KO mice were highly resistant to body weight and fat mass gain after exposure to a high-fat, energy-dense diet. These effects on body weight and adiposity were driven, in part, by a pronounced increase in whole body energy expenditure levels in KO mice. KO mice also had reduced blood glucose levels during an intraperitoneal glucose challenge and significant reductions in circulating insulin levels suggesting an increase in insulin sensitivity. In addition, there was an overall increase in oxidative capacity and contractile force in skeletal muscle isolated from KO mice. Hepatic triglyceride levels were reduced by 92% in livers of KO mice, in part due to a reduction in de novo lipid synthesis. Interestingly, Mpzl3 mRNA expression in liver was increased in diet-induced obese mice. Moreover, KO mice exhibited an increase in insulin-stimulated Akt signaling in the liver, further demonstrating that Mpzl3 can regulate insulin sensitivity in this tissue. We have determined that Mpzl3 has a novel physiological role in controlling body weight regulation, energy expenditure, glycemic control, and hepatic triglyceride synthesis in mice.
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Glucemia/fisiología , Metabolismo Energético/fisiología , Lípidos/biosíntesis , Hígado/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/fisiología , Adiposidad/genética , Adiposidad/fisiología , Animales , Análisis Químico de la Sangre , Western Blotting , Temperatura Corporal/fisiología , Dieta , Dislipidemias/genética , Dislipidemias/metabolismo , Prueba de Tolerancia a la Glucosa , Hiperglucemia/genética , Hiperglucemia/metabolismo , Hígado/patología , Masculino , Ratones , Ratones Noqueados , Contracción Muscular/fisiología , Obesidad/genética , Obesidad/metabolismo , Obesidad/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Triglicéridos/metabolismo , Aumento de Peso/fisiologíaRESUMEN
Although approximately 35 million people in the US obtain drinking water from domestic wells, few studies have investigated the risk of arsenic exposure from this source. In this paper arsenic concentrations were modeled for public and domestic wells using a dataset from the US Geological Survey (USGS). Excess lifetime and annual risks for lung and bladder cancer were calculated based on the carcinogenic potency and average arsenic concentrations in public and domestic water supplies. Monte Carlo uncertainty analysis was used to estimate the degree of confidence in these estimations. Results indicated that domestic well users accounted for 12% of the US population, but 23% of overall arsenic exposure from drinking water. Assuming that the new and more restrictive arsenic maximum contaminant limit (MCL) is implemented for public water supplies, it is anticipated that the proportion of people experiencing excess annual fatalities from drinking water from domestic wells will increase to 29% unless corresponding efforts are made to reduce exposures among domestic well users. Differences between public and domestic wells were not consistent across the nation. Public wells tend to tap deeper aquifers than domestic wells, and as a result local arsenic-depth trends can contribute to differences between public and domestic wells. Domestic wells and public wells in the western US have the highest arsenic levels with excess fatality risks estimated to be in the range of 1 per 9300 to 1 per 6600 in these regions. Uncertainty distributions of excess fatalities were developed and resultant uncertainties were propagated in arsenic exposure and potency factor. Uncertainty in the carcinogenic potency of arsenic was the dominant source of uncertainty in most regions, but for domestic wells in the New England and Southeast regions uncertainty in arsenic exposure was dominant, indicating that additional data on arsenic concentrations in these areas would substantially improve regional risk estimates.
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Arsénico/análisis , Ingestión de Líquidos , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Químicos del Agua/análisis , Abastecimiento de Agua/estadística & datos numéricos , Arsénico/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Neoplasias/epidemiología , Neoplasias/etiología , Medición de Riesgo , Estados Unidos , United States Environmental Protection Agency , Contaminantes Químicos del Agua/toxicidad , Abastecimiento de Agua/normasRESUMEN
General opioid receptor antagonists reduce food intake and body weight in rodents, but the contributions of specific receptor subtypes are unknown. We examined whether genetic deletion of the kappa-opioid receptor (KOR) in mice alters metabolic physiology. KOR-knockout (KO) and wild-type (WT) mice were fed a high-energy diet (HED) for 16 wk. KO mice had 28% lower body weight and 45% lower fat mass when compared to WT mice fed an HED. No differences in caloric intake were found. An HED reduced energy expenditure in WT mice, but not in KO mice. KOR deficiency led to an attenuation of triglyceride synthesis in the liver. Malonyl CoA levels were also reduced in response to an HED, thereby promoting hepatic beta-oxidation. Glycemic control was also found to be improved in KO mice. These data suggest a key role for KORs in the central nervous system regulation of the metabolic adaptation to an HED, as we were unable to detect expression of KOR in liver, white adipose tissue, or skeletal muscle in WT mice. This study provides the first evidence that KORs play an essential physiological role in the control of hepatic lipid metabolism, and KOR activation is a permissive signal toward fat storage.-Czyzyk, T. A., Nogueiras, R., Lockwood, J. F., McKinzie, J. H., Coskun, T., Pintar, J. E., Hammond, C., Tschöp, M. H., Statnick, M. A. kappa-Opioid receptors control the metabolic response to a high-energy diet in mice.
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Ingestión de Energía , Hígado/metabolismo , Receptores Opioides kappa/metabolismo , Triglicéridos/biosíntesis , Tejido Adiposo Blanco/metabolismo , Animales , Peso Corporal/genética , Regulación de la Expresión Génica/genética , Ratones , Ratones Noqueados , Músculo Esquelético/metabolismo , Especificidad de Órganos/genética , Oxidación-Reducción , Receptores Opioides kappa/genéticaRESUMEN
Cardiolipin is a major membrane polyglycerophospholipid that is required for the reconstituted activity of a number of key mitochondrial enzymes involved in energy metabolism. Cardiolipin is subjected to remodeling subsequent to its de novo biosynthesis to attain appropriate acyl composition for its biological functions. Yet, the enzyme(s) involved in the remodeling process have not been identified. We report here the identification and characterization of a murine gene that encodes an acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1). Expression of the ALCAT1 cDNA in either insect or mammalian cells led to a significant increase in acyl-CoA:monolysocardiolipin acyltransferase and acyl-CoA: dilysocardiolipin acyltransferase activities that exhibited a dependence upon ALCAT1 enzyme levels. The recombinant ALCAT1 enzyme recognizes both monolysocardiolipin and dilysocardiolipin as substrates with a preference for linoleoyl-CoA and oleoyl-CoA as acyl donors. In contrast, no significant increases in acyltransferase activities by the recombinant ALCAT1 were detected against either glycerol-3-phosphate or a variety of other lysophospholipids as substrates, including lysophosphatidylcholine, lysophosphatidylethanolamine, and lysophosphatidylserine. Immunocytohistochemical analysis showed that the ALCAT1 enzyme is localized in the endoplasmic reticulum, which is supported by a significant ALCAT activity in isolated liver and heart microsomes. Northern blot analysis indicates that the mouse ALCAT1 is widely distributed, with the highest expression in heart and liver. In support of a role for ALCAT1 in maintaining heart function, the ALCAT1 gene is conserved among different species of vertebrates, but not in non-atrium organisms. ALCAT1 represents the first identified cardiolipin-remodeling enzyme from any living organism; its identification implies a novel role for the endoplasmic reticulum in cardiolipin metabolism.
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Aciltransferasas/genética , Aciltransferasas/metabolismo , Cardiolipinas/metabolismo , Retículo Endoplásmico/enzimología , Aciltransferasas/química , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células COS , Línea Celular , Clonación Molecular , ADN Complementario/genética , Regulación Enzimológica de la Expresión Génica , Masculino , Ratones , Datos de Secuencia Molecular , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Spodoptera , Distribución Tisular , TransfecciónRESUMEN
Acyl CoA-monoacylglycerol acyltransferase (MGAT) catalyzes the first step in triacyglycerol resynthesis involved in dietary absorption in enterocytes. Despite its potentially important role in dietary fat absorption, a gene encoding a human intestinal MGAT has not been identified. In this study, we report the identification and functional characterization of a human intestinal MGAT (hMGAT2) and its splice variant (hMGAT2V). The hMGAT2 gene encodes a peptide of 334 amino acids with a molecular mass of 38.2 kDa that shares 81 and 47% amino acid identities with the mouse MGAT2 and the human diacylglycerol acyltransferase (DGAT2) enzymes, respectively. The hMGAT2 gene is localized on chromosome 11q13.5, adjacent to the DGAT2 gene, suggesting gene duplication. Transient expression of hMGAT2, but not an alternatively spliced variant, hMGAT2V, in COS-7 cells led to a ninefold increase in the synthesis of DAG. The human and mouse differ significantly in tissue distribution of MGAT2. In addition to a predominant expression in the small intestine in both species, distinct levels were also found in the human liver, contrasting with higher levels in the mouse kidney. In comparison with a single 1.8-kb transcript in mouse, the hMGAT2 gene expressed two transcripts of 3.0 and 6.0 kb in size that encode MGAT2 and an inactive peptide with unknown functions, respectively. Despite a significant level of hMGAT2 mRNA in the human liver, little MGAT activity was detected in liver microsomes when tested against monoacyglcerols with different unsaturated side chains, suggesting possible posttranscriptional regulation.
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Aciltransferasas/genética , Aciltransferasas/metabolismo , Intestino Delgado/enzimología , Aciltransferasas/química , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Células COS , Cromosomas Humanos Par 11 , Diglicéridos/biosíntesis , Estabilidad de Enzimas , Humanos , Hígado/enzimología , Ratones , Microsomas Hepáticos/enzimología , Datos de Secuencia Molecular , Señales de Clasificación de Proteína , ARN Mensajero/análisis , Especificidad de la Especie , Especificidad por Sustrato , Distribución Tisular , TransfecciónRESUMEN
Acyl-CoA:monoacylglycerol transferase (MGAT) plays a predominant role in dietary fat absorption in the small intestine, where it catalyzes the first step of triacylglycerol resynthesis in enterocytes for chylomicron formation and secretion. Although the mouse small intestine exhibits the highest MGAT enzyme activity among all of the tissues studied, the gene encoding the enzyme has not been identified so far. In the present studies, we report the identification and characterization of a mouse intestinal MGAT, MGAT2. Transient expression of MGAT2 in AV-12, COS-7, and Caco-2 cells led to a more than 70-, 30-, and 35-fold increase in the synthesis of diacylglycerol, respectively. MGAT2 expressed in mammalian cells can catalyze the acylation of rac-1-, sn-2-, and sn-3-monoacylglycerols, and the enzyme prefers monoacylglycerols containing unsaturated fatty acyls as substrates. MGAT2 also demonstrates weak DGAT activity, which can be distinguished from its MGAT activity by detergent treatment that abolishes DGAT but not MGAT activity. We also analyzed the biochemical features of MGAT2 and demonstrated homogenate protein-, time-, and substrate concentration-dependent MGAT enzyme activity in transiently transfected COS-7 cells. Northern blot analysis indicates that the mouse MGAT2 is most abundantly expressed in the small intestine, suggesting that MGAT2 may play an important role in dietary fat absorption.
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N-Acetilglucosaminiltransferasas/química , N-Acetilglucosaminiltransferasas/genética , Aciltransferasas/genética , Aciltransferasas/metabolismo , Secuencia de Aminoácidos , Animales , Northern Blotting , Células COS , Células CACO-2 , Cromatografía en Capa Delgada , Clonación Molecular , ADN Complementario/metabolismo , Detergentes/farmacología , Diacilglicerol O-Acetiltransferasa , Relación Dosis-Respuesta a Droga , Glicéridos/metabolismo , Humanos , Intestinos/enzimología , Cinética , Ratones , Datos de Secuencia Molecular , N-Acetilglucosaminiltransferasas/metabolismo , Homología de Secuencia de Aminoácido , Distribución Tisular , TransfecciónRESUMEN
PURPOSE: To examine graduating medical students' perceptions of the adequacy of instruction in managed care and in 11 curricular content areas identified by experts as a necessary part of managed care education. This study sought to determine whether medical students perceived these content areas as relevant to managed care and to evaluate the extent to which students' perceptions of the adequacy of instruction varied as a function of managed care penetration in the locations of their respective medical schools. METHOD: Data from the Association of American Medical Colleges' 1999 Medical School Graduation Questionnaire (GQ) were analyzed. Students' ratings of adequacy of instruction were summarized. Correlations between ratings of instruction in managed care and 11 related content areas were calculated, as well as correlations between managed care penetration in the locations of the students' schools and the proportion of students rating instruction as inadequate. RESULTS: A majority of 1999 medical school graduates (60%) rated instruction in managed care as inadequate; other content areas to which majorities of graduates gave inadequate ratings were practice management (72%), quality assurance (57%), medical care cost control (57%), and cost-effective medical practice (56%). Ratings in these four content areas were highly correlated with ratings of instruction in managed care. The correlation between managed care penetration and rating of instruction in managed care was statistically significant (r = -.37); correlations between managed care penetration and instruction in the other content areas were not. CONCLUSIONS: On the 1999 GQ, a majority of medical students responded that they felt they had not received adequate instruction in managed care. Further, the responses suggest that these medical students defined managed care in terms of managing costs, rather than managing health care, or developing population-based approaches to the delivery of health care.
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Actitud del Personal de Salud , Educación de Pregrado en Medicina , Programas Controlados de Atención en Salud/organización & administración , Estudiantes de Medicina/psicología , Humanos , Encuestas y CuestionariosRESUMEN
Until recently, the construction of polarizers for operation below approximately 260 nm were limited to materials such as magnesium fluoride and crystalline quartz. These materials have a much smaller birefringence than calcite, but unlike calcite they have good transmission below 200 nm. These materials are, however, not well suited for Glan-Taylor-type polarizer designs, as they do not produce a large angular separation of the polarized components. A new material, a-barium borate, has recently become available, which transmits to just below 200 nm and has a birefringence that approaches that of calcite. We analyze the performance of various polarizer designs that use this material. Results are presented that compare theory with experimental investigation of a manufactured device.
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Erupciones Volcánicas , 34661 , Sistemas de Información , Comunicaciones por Satélite , Equipos y Suministros , Medición de RiesgoRESUMEN
The accumulation of total carbon, nitrogen, and phosphorus in soils, available soil nutrients, and foliar nutrients in the native dominant Metrosideros polymorpha were determined across a wide elevational range on 9 lava flows on Mauna Loa, Hawai'i. The flows included a young (<140 y) and an old (>2800 y) áá (rough surface texture) and pahoehoe (smooth) flow on the wet east and dry northwest side of the mountain. Soil element pools and nutrient availability increased with flow age independent of climate. The dry sites accumulated organic matter and nutrients more slowly than comparable wet sites, but relative nutrient availability to plants (as indicated by soil assays and foliar nutrients) was greater in the dry sites. Accumulation of soil organic matter and nutrients occurred most rapidly in lowerelevation sites on the young flows, but the largest accumulations occurred at higher elevations on old flows. The range of sites sampled represents a complete and largely independent matrix of major factors governing ecosystem structure and function.