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Canopy-forming kelps are essential foundation species, supporting biodiversity and providing ecosystem services valued at more than USD$500 billion annually. The global decline of giant kelp forests due to climate-driven ecological stressors underscores the need for innovative restoration strategies. An emerging restoration technique known as 'green gravel' aims to seed young kelps over large areas without extensive underwater labor and represents a promising restoration tool due to cost-effectiveness and scalability. This video article illustrates a protocol and tools for culturing giant kelp, Macrocystis pyrifera. It also provides a resource for further studies to address the successes and limitations of this method in field settings. We outline field and laboratory-based methods for collecting reproductive tissue, sporulating, inoculating, rearing, maintaining, and monitoring substrates seeded with early life stages using the 'green gravel' technique. The protocol simplifies and centralizes current restoration practices in this field to support researchers, managers, and stakeholders in meeting kelp conservation objectives.

Introduction: Dementia is the fourth largest cause of death for individuals 70 years of age and older in the United States, and it is tremendously costly. Existing estimates of the indirect costs of dementia are dated and do not report on differences across the United States., Methods: We used data from multiple surveys to create cost estimates and projections for informal dementia caregiving at the U.S. state level from 2010 through 2050., Results: In 2019, the annual replacement cost of informal caregiving was $42,422 per prevalent case, and the forgone wage cost was $10,677 per prevalent case. In 2019, it would have cost $230 billion to hire home health aides to provide all this care. If past trends persist, this cost is expected to grow to $404 billion per year in 2050., Discussion: The cost of informal care varied substantially by state and is expected to grow through at least 2050., Highlights: In the United States in 2019, foregone wages due to informal dementia care was $58 billion. Replacing informal dementia care with health aides would have cost $230 billion. These costs vary dramatically by state, even when assessed per prevalent case. These costs are expected to nearly double by 2050., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had in interstate variation in COVID-19 outcomes; 2) whether states with greater health-care and public health capacity had better outcomes; 3) how politics influenced the results; 4) whether states that imposed more policy mandates and sustained them longer had better outcomes; and 5) whether there were trade-offs between a state having fewer cumulative SARS-CoV-2 infections and total COVID-19 deaths and its economic and educational outcomes., Methods: Data disaggregated by US state were extracted from public databases, including COVID-19 infection and mortality estimates from the Institute for Health Metrics and Evaluation's (IHME) COVID-19 database; Bureau of Economic Analysis data on state gross domestic product (GDP); Federal Reserve economic data on employment rates; National Center for Education Statistics data on student standardised test scores; and US Census Bureau data on race and ethnicity by state. We standardised infection rates for population density and death rates for age and the prevalence of major comorbidities to facilitate comparison of states' successes in mitigating the effects of COVID-19. We regressed these health outcomes on prepandemic state characteristics (such as educational attainment and health spending per capita), policies adopted by states during the pandemic (such as mask mandates and business closures), and population-level behavioural responses (such as vaccine coverage and mobility). We explored potential mechanisms connecting state-level factors to individual-level behaviours using linear regression. We quantified reductions in state GDP, employment, and student test scores during the pandemic to identify policy and behavioural responses associated with these outcomes and to assess trade-offs between these outcomes and COVID-19 outcomes. Significance was defined as p<0·05., Findings: Standardised cumulative COVID-19 death rates for the period from Jan 1, 2020, to July 31, 2022 varied across the USA (national rate 372 deaths per 100 000 population [95% uncertainty interval [UI] 364-379]), with the lowest standardised rates in Hawaii (147 deaths per 100 000 [127-196]) and New Hampshire (215 per 100 000 [183-271]) and the highest in Arizona (581 per 100 000 [509-672]) and Washington, DC (526 per 100 000 [425-631]). A lower poverty rate, higher mean number of years of education, and a greater proportion of people expressing interpersonal trust were statistically associated with lower infection and death rates, and states where larger percentages of the population identify as Black (non-Hispanic) or Hispanic were associated with higher cumulative death rates. Access to quality health care (measured by the IHME's Healthcare Access and Quality Index) was associated with fewer total COVID-19 deaths and SARS-CoV-2 infections, but higher public health spending and more public health personnel per capita were not, at the state level. The political affiliation of the state governor was not associated with lower SARS-CoV-2 infection or COVID-19 death rates, but worse COVID-19 outcomes were associated with the proportion of a state's voters who voted for the 2020 Republican presidential candidate. State governments' uses of protective mandates were associated with lower infection rates, as were mask use, lower mobility, and higher vaccination rate, while vaccination rates were associated with lower death rates. State GDP and student reading test scores were not associated with state COVD-19 policy responses, infection rates, or death rates. Employment, however, had a statistically significant relationship with restaurant closures and greater infections and deaths: on average, 1574 (95% UI 884-7107) additional infections per 10 000 population were associated in states with a one percentage point increase in employment rate. Several policy mandates and protective behaviours were associated with lower fourth-grade mathematics test scores, but our study results did not find a link to state-level estimates of school closures., Interpretation: COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises., Funding: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies., Competing Interests: Declaration of interests CA reports support for the current work from the Benificus Foundation. ADF reports other financial or non-financial support from Johnson & Johnson, Sanofi, and SwissRe outside of the submitted work. NF reports financial support from WHO and Gates Ventures outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Kelp forest ecosystems and their associated ecosystem services are declining around the world. In response, marine managers are working to restore and counteract these declines. Kelp restoration first started in the 1700s in Japan and since then has spread across the globe. Restoration efforts, however, have been largely disconnected, with varying methodologies trialled by different actors in different countries. Moreover, a small subset of these efforts are 'afforestation', which focuses on creating new kelp habitat, as opposed to restoring kelp where it previously existed. To distil lessons learned over the last 300 years of kelp restoration, we review the history of kelp restoration (including afforestation) around the world and synthesise the results of 259 documented restoration attempts spanning from 1957 to 2020, across 16 countries, five languages, and multiple user groups. Our results show that kelp restoration projects have increased in frequency, have employed 10 different methodologies and targeted 17 different kelp genera. Of these projects, the majority have been led by academics (62%), have been conducted at sizes of less than 1 ha (80%) and took place over time spans of less than 2 years. We show that projects are most successful when they are located near existing kelp forests. Further, disturbance events such as sea-urchin grazing are identified as regular causes of project failure. Costs for restoration are historically high, averaging hundreds of thousands of dollars per hectare, therefore we explore avenues to reduce these costs and suggest financial and legal pathways for scaling up future restoration efforts. One key suggestion is the creation of a living database which serves as a platform for recording restoration projects, showcasing and/or re-analysing existing data, and providing updated information. Our work establishes the groundwork to provide adaptive and relevant recommendations on best practices for kelp restoration projects today and into the future., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Theoretical ecological models, such as succession and facilitation, were defined in terrestrial habitats, and subsequently applied to marine and freshwater habitats in intertidal and then subtidal realms. One such model is the soil seed bank, defined as all viable seeds (or fruits) found near the soil surface that facilitate community restoration/recovery. "Banks of microscopic forms" have been hypothesized in aquatic habitats and recent work from aquaculture has highlighted dormancy in algal life cycle stages. To reinvigorate the discussions about these algal banks, we discuss differences in life cycles, dispersal, and summarize research on banks of macroalgal stages in aquatic ecosystems that may be easier to explore with modern advances in molecular technology. With focus on seminal work in global kelp forest ecosystems, we present a pilot study in northern California as proof of concept that Nereocystis luetkeana and Alaria marginata stages can be detected within kelp forests in the biofilm of rocks and bedrock using targeted primers long after zoospore release. Considering the increased interest in algae as an economic resource, [blue] carbon sink, and as ecosystem engineers, the potential for "banking" macroalgal forms could be a mechanism of resilience and recovery in aquatic populations that have complex life cycles and environmental cues for reproduction. Molecular barcoding is becoming an important tool for identifying banks of macroalgal forms in marine communities. Understanding banks of macroalgal stages, especially in deforested habitats with intense disturbance and grazer pressure, will allow researchers and marine resource managers to facilitate this natural process in recovery of the aquatic system., (© 2020 Phycological Society of America.)

Inspired concentration of carbon dioxide (FICO₂) in ophthalmic surgery performed under monitored anesthesia care (MAC) has been largely ignored in the recommended monitoring standards of professional anesthesia societies. Most ophthalmic procedures are performed using MAC with facial draping that has been shown to retain carbon dioxide in the ambient air surrounding the patient. The administration of supplemental oxygen has been shown to prevent hypoxia but not hypercapnia. Hypercapnia can lead to physiologic changes, including tachypnea, tachycardia, and increased intraocular pressure. Several closed-claim analyses have described adverse outcomes related to ventilation and oxygenation of patients during MAC. A literature search using the keywords of ophthalmic surgery, monitored anesthesia care, and inspired carbon dioxide was conducted, and relevant articles dealing with possible complications, methods of measurement, and abatement strategies were examined. No procedure has gained widespread acceptance, yet practitioners employ a variety of methods to decrease FICO₂, a parameter not mentioned in the anesthetic record although it is measured by current anesthesia workstations. The goal of this review is to encourage investigation of this underreported parameter., Competing Interests: The author has declared no financial relationships with any commercial entity related to the content of this article. The author did not discuss off-label use within the article. Disclosure statements are available for viewing upon request. The opinions expressed in this article are the author’s and do not represent the position of the Veterans Administration., (Copyright© by the American Association of Nurse Anesthetists.)

The distribution of organisms in an environment is neither uniform nor random but is instead spatially patterned. The factors that control this patterning are complex and the underlying mechanisms are poorly understood. Soil microbes are critical to ecosystem function but exhibit highly complex distributions and community dynamics due in large part to the scale-dependent effects of environmental heterogeneity. To better understand the impact of environmental heterogeneity on the distribution of soil microbes, we sequenced the 16S rRNA gene from bacterial communities in the microbe-dominated polar desert ecosystem of the McMurdo Dry Valleys (MDV), Antarctica. Significant differences in key edaphic variables and alpha diversity were observed among the three lake basins of the Taylor Valley (Kruskal-Wallis; pH: χ 2 = 68.89, P < 0.001, conductivity: χ 2 = 35.03, P < 0.001, observed species: χ 2 = 7.98, P = 0.019 and inverse Simpson: χ 2 = 18.52, P < 0.001) and each basin supported distinctive microbial communities (ANOSIM R = 0.466, P = 0.001, random forest ratio of 14.1). However, relationships between community structure and edaphic characteristics were highly variable and contextual, ranging in magnitude and direction across regional, basin, and local scales. Correlations among edaphic factors (pH and soil conductivity) and the relative abundance of specific phyla were most pronounced along local environmental gradients in the Lake Fryxell basin where Acidobacteria, Bacteroidetes, and Proteobacteria declined while Deinococcus-Thermus and Gemmatimonadetes increased with soil conductivity (all P < 0.1). Species richness was most strongly related to the soil conductivity gradient present within this study system. We suggest that the relative importance of pH versus soil conductivity in structuring microbial communities is related to the length of edaphic gradients and the spatial scale of sampling. These results highlight the importance of conducting studies over large ranges of key environmental gradients and across multiple spatial scales to assess the influence of environmental heterogeneity on the composition and diversity of microbial communities.

Aridisols are the dominant soil type in drylands, which occupy one-third of Earth's terrestrial surface. We examined controls on biogeographical patterns of Aridisol prokaryotic (bacterial and archaeal) communities at a regional scale by comparing communities from 100 Aridisols throughout the southwestern United States using high-throughput sequencing of the 16S rRNA gene. We found that microbial communities differed among global biomes and deserts of the Southwest. Differences among biomes were driven by differences in taxonomic identities, whereas differences among deserts of the Southwest were driven by differences in relative sequence abundance. Desert communities were dominated by Actinobacteria, Proteobacteria and Crenarchaeota, supporting the notion of a core set of abundant taxa in desert soils. Our findings contrast with studies showing little taxonomic overlap at the OTU level (97% sequence similarity) across large spatial scales, as we found ∼90% of taxa in at least two of the three deserts. Geographic distance structured prokaryotic communities indirectly through the influence of climate and soil properties. Structural equation modeling suggests that climate exerts a stronger influence than soil properties in shaping the composition of Aridisol microbial communities, with annual heat moisture index (an aridity metric) being the strongest climate driver. Annual heat moisture index was associated with decreased microbial diversity and richness. If the Desert Southwest becomes hotter and drier as predicted, these findings suggest that prokaryotic diversity and richness in Aridisols will decline., (© FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Microorganisms perform most decomposition on Earth, mediating carbon (C) loss from ecosystems, and thereby influencing climate. Yet, how variation in the identity and composition of microbial communities influences ecosystem C balance is far from clear. Using quantitative stable isotope probing of DNA, we show how individual bacterial taxa influence soil C cycling following the addition of labile C (glucose). Specifically, we show that increased decomposition of soil C in response to added glucose (positive priming) occurs as a phylogenetically diverse group of taxa, accounting for a large proportion of the bacterial community, shift toward additional soil C use for growth. Our findings suggest that many microbial taxa exhibit C use plasticity, as most taxa altered their use of glucose and soil organic matter depending upon environmental conditions. In contrast, bacteria that exhibit other responses to glucose (reduced growth or reliance on glucose for additional growth) clustered strongly by phylogeny. These results suggest that positive priming is likely the prototypical response of bacteria to sustained labile C addition, consistent with the widespread occurrence of the positive priming effect in nature.

Nitrogen (N) deposition affects myriad aspects of terrestrial ecosystem structure and function, and microbial communities may be particularly sensitive to anthropogenic N inputs. However, our understanding of N deposition effects on microbial communities is far from complete, especially for drylands where data are comparatively rare. To address the need for an improved understanding of dryland biological responses to N deposition, we conducted a two-year fertilization experiment in a semiarid grassland on the Colorado Plateau in the southwestern United States. We evaluated effects of varied levels of N inputs on archaeal, bacterial, fungal and chlorophyte community composition within three microhabitats: biological soil crusts (biocrusts), soil below biocrusts, and the plant rhizosphere. Surprisingly, N addition did not affect the community composition or diversity of any of these microbial groups; however, microbial community composition varied significantly among sampling microhabitats. Further, while plant richness, diversity, and cover showed no response to N addition, there were strong linkages between plant properties and microbial community structure. Overall, these findings highlight the potential for some dryland communities to have limited biotic ability to retain augmented N inputs, possibly leading to large N losses to the atmosphere and to aquatic systems., (© 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Growth and mortality of microorganisms have been characterized through DNA stable isotope probing (SIP) with 18 O-water in soils from a range of ecosystems. Conventional SIP has been improved by sequencing a marker gene in all fractions retrieved from an ultracentrifuge tube to produce taxon density curves, which allow estimating the atom percent isotope composition of each microbial taxon's genome. Very recent advances in SIP with 18 O-water include expansion of the technique to aquatic samples, investigations of microbial turnover in soil, and the first use of 18 O-water in RNA-SIP studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Phylogeny is an ecologically meaningful way to classify plants and animals, as closely related taxa frequently have similar ecological characteristics, functional traits and effects on ecosystem processes. For bacteria, however, phylogeny has been argued to be an unreliable indicator of an organism's ecology owing to evolutionary processes more common to microbes such as gene loss and lateral gene transfer, as well as convergent evolution. Here we use advanced stable isotope probing with (13)C and (18)O to show that evolutionary history has ecological significance for in situ bacterial activity. Phylogenetic organization in the activity of bacteria sets the stage for characterizing the functional attributes of bacterial taxonomic groups. Connecting identity with function in this way will allow scientists to begin building a mechanistic understanding of how bacterial community composition regulates critical ecosystem functions.

Bacteria grow and transform elements at different rates, and as yet, quantifying this variation in the environment is difficult. Determining isotope enrichment with fine taxonomic resolution after exposure to isotope tracers could help, but there are few suitable techniques. We propose a modification to stable isotope probing (SIP) that enables the isotopic composition of DNA from individual bacterial taxa after exposure to isotope tracers to be determined. In our modification, after isopycnic centrifugation, DNA is collected in multiple density fractions, and each fraction is sequenced separately. Taxon-specific density curves are produced for labeled and nonlabeled treatments, from which the shift in density for each individual taxon in response to isotope labeling is calculated. Expressing each taxon's density shift relative to that taxon's density measured without isotope enrichment accounts for the influence of nucleic acid composition on density and isolates the influence of isotope tracer assimilation. The shift in density translates quantitatively to isotopic enrichment. Because this revision to SIP allows quantitative measurements of isotope enrichment, we propose to call it quantitative stable isotope probing (qSIP). We demonstrated qSIP using soil incubations, in which soil bacteria exhibited strong taxonomic variations in (18)O and (13)C composition after exposure to [(18)O]water or [(13)C]glucose. The addition of glucose increased the assimilation of (18)O into DNA from [(18)O]water. However, the increase in (18)O assimilation was greater than expected based on utilization of glucose-derived carbon alone, because the addition of glucose indirectly stimulated bacteria to utilize other substrates for growth. This example illustrates the benefit of a quantitative approach to stable isotope probing., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Water drives the functioning of Earth's arid and semiarid lands. Drylands can obtain water from sources other than precipitation, yet little is known about how non-rainfall water inputs influence dryland communities and their activity. In particular, water vapor adsorption--movement of atmospheric water vapor into soil when soil air is drier than the overlying air--likely occurs often in drylands, yet its effects on ecosystem processes are not known. By adding (18)O-enriched water vapor to the atmosphere of a closed system, we documented the conversion of water vapor to soil liquid water across a temperature range typical of arid ecosystems. This phenomenon rapidly increased soil moisture and stimulated microbial carbon (C) cycling, and the flux of water vapor to soil had a stronger impact than temperature on microbial activity. In a semiarid grassland, we also observed that non-rainfall water inputs stimulated microbial activity and C cycling. Together these data suggest that, during rain-free periods, atmospheric moisture in drylands may significantly contribute to variation in soil water content, thereby influencing ecosystem processes. The simple physical process of adsorption of water vapor to soil particles, forming liquid water, represents an overlooked but potentially important contributor to C cycling in drylands.

Arizona and New Mexico receive half of their annual precipitation during the summer monsoon season, making this large-scale rain event critical for ecosystem productivity. We used the monsoon rains to explore the responses of soil bacterial and fungal communities to natural moisture pulses in a semiarid grassland. Through 454 pyrosequencing of the 16S rRNA gene and ITS region, we phylogenetically characterized these communities at 22 time points during a summer season. Relative humidity increased before the rains arrived, creating conditions in soil that allowed for the growth of microorganisms. During the course of the study, the relative abundances of most bacterial phyla showed little variation, though some bacterial populations responded immediately to an increase in soil moisture once the monsoon rains arrived. The Firmicutes phylum experienced over a sixfold increase in relative abundance with increasing water availability. Conversely, Actinobacteria, the dominant taxa at our site, were negatively affected by the increase in water availability. No relationship was found between bacterial diversity and soil water potential. Bacterial community structure was unrelated to all environmental variables that we measured, with the exception of a significant relationship with atmospheric relative humidity. Relative abundances of fungal phyla fluctuated more throughout the season than bacterial abundances did. Variation in fungal community structure was unrelated to soil water potential and to most environmental variables. However, ordination analysis showed a distinct fungal community structure late in the season, probably due to plant senescence.

Few studies have examined how below-ground interactions among plants affect the abundance and community composition of symbiotic mycorrhizal fungi. Here, we combined observations during drought with a removal experiment to examine the effects of below-ground interactions with arbuscular mycorrhizal (AM) shrubs on the growth of pinyon pines (Pinus edulis), and the abundance and community composition of their ectomycorrhizal (EM) fungi. Shrub density was negatively correlated with pinyon above- and below-ground growth and explained 75% of the variation in EM colonization. Consistent with competitive release, pinyon fine-root biomass, shoot length and needle length increased with shrub removal. EM colonization also doubled following shrub removal. EM communities did not respond to shrub removal, perhaps because of their strikingly low diversity. These results suggest that below-ground competition with AM shrubs negatively impacted both pinyons and EM fungi. Similar competitive effects may be observed in other ecosystems given that drought frequency and severity are predicted to increase for many land interiors.

Objective: To determine the clinical outcomes at one year of Stages T2-T3 prostate cancer by cryosurgery utilizing pretreatment with total androgen ablation therapy and temperature monitoring to control the freezing process. Study Group To date, 347 patients have had 356 cryosurgical procedures, 280 have reached one year post treatment. Of these 131 had re-evaluation with prostatic biopsy and serum PSA., Methods: Transrectal ultrasound (TRUS) measurement of tumor size and biopsy of extraprostatic space was used to stage patients into two main groups: confined (66.6%) versus nonconfined (19.3%). Radiation failures (14.1%) formed a separate group. Failure rates for the 131 men include all cancer diagnosed during the one year period following cryosurgery., Results: The one year failure rate for the study group was 19.8% (26/131). For stages T2a, T2h C, T3 and radiation failures, the rates of positive biopsies were 13.9%, 12.9%, 33.3% and 35%, respectively. For those with local control of cancer (negative biopsy), 80% had prostate specific antigen (PSA) levels of < 0.5 ng/ml. The statistical variables for persistent cancer with prostate specific antigen > 0.5 ng/ml were: sensitivity of 66.7%, PPV of 16.7%, NPV of 98% and specificity of 83.7%. A statistically significant difference exist between stages T2 vs T3 and radiation failures (p = < 0.5). Major complications of rectal fistula and total incontinence for previously non-treated cancer versus radiation failures were 0.33% and 8.7% respectively, a 26 times greater risk., Conclusion: Results of cryosurgery for all stages of prostate cancer at one year are encouraging, being 80% free of disease (biopsy and prostate specific antigen). The morbidity of the previously non-treated cancers from this procedure for us was minimal with high patient acceptance. For radiation failures a local control rate of 65% was achieved. However, early in our experience significant morbidity did occur and our enthusiasm for attempted salvage was initially tempered.

Pulmonary responses in rats were compared after short-term inhalation exposure to polymorphs of silica dust. Groups of CD rats were exposed 6 h a day for 3 d to crystalline silica or amorphous silica. Another group was exposed to Ludox colloidal silica for 6 h a day, 5 d a week for two or four weeks. Thereafter the groups were killed, and the lungs washed at several postexposure times. The crystalline silica produced persistent pulmonary inflammatory responses characterized by neutrophil recruitment and consistently elevated biomarkers of cytotoxicity in bronchoalveolar lavage fluids, and progressive histopathological lesions were observed within one month of the exposure. Amorphous silica produced a transient pulmonary inflammatory response, and Ludox elicited transient pulmonary inflammatory responses at 50 or 150 mg center dot m-3 but not at 10 mg center dot m-3. After three months most of the biochemical values of the Ludox-exposed animals had returned to the control level. These results demonstrate that crystalline silica dust is more potent in producing pulmonary toxicity when compared with amorphous or colloidal silica particles.

Fiber dimension and durability are recognized as important features in influencing the development of pulmonary carcinogenic and fibrogenic effects. Using a short-term inhalation bioassay, we have studied pulmonary deposition and clearance patterns and evaluated and compared the pulmonary toxicity of two previously tested reference materials, an inhaled organic fiber, Kevlar para-aramid fibrils, and an inorganic fiber, wollastonite. Rats were exposed for 5 days to aerosols of Kevlar fibrils (900-1344 f/cc; 9-11 mg/m3) or wollastonite fibers (800 f/cc; 115 mg/m3). The lungs of exposed rats were digested to quantify dose, fiber dimensional changes over time, and clearance kinetics. The results showed that inhaled wollastonite fibers were cleared rapidly with a retention half-time of < 1 week. Mean fiber lengths decreased from 11 microns to 6 microns over a 1-month period, and fiber diameters increased from 0.5 micron to 1.0 micron in the same time. Fiber clearance studies with Kevlar showed a transient increase in the numbers of retained fibrils at 1 week postexposure, with rapid clearance of fibers thereafter, and retention half-time of 30 days. A progressive decrease in the mean lengths from 12.5 microns to 7.5 microns and mean diameters from 0.33 micron to 0.23 micron was recorded 6 months after exposure to inhaled Kevlar fibrils. The percentages of fibers > 15 microns in length decreased from 30% immediately after exposure to 5% after 6 months; the percentages of fibers in the 4 to 7 microns range increased from 25 to 55% in the same period.(ABSTRACT TRUNCATED AT 250 WORDS)

A tailored approach to cryosurgery of prostate cancer is presented. The authors have performed 214 cryoprocedures to date with use of this protocol. The technique requires pretreatment with androgen ablation therapy, preoperative diagnosis and staging with ultrasound (US)-guided biopsies, and detailed knowledge of prostate and rectal anatomy. Five cryoprobes are placed in the prostate under US guidance in a configuration that depends on tumor location, sites of extracapsular extension, the size of the tumor, and gland geometry. Freezing starts anteriorly to keep from obstructing the ultrasound beam. Two freezes are performed at the known cancer site, and additional freezes are performed, if necessary, to include the remainder of the gland. Thermosensors enable monitoring of the cryosurgical ice ball and determination of the number of freezes. Cryosurgery is always performed by a urologist and a radiologist working together.

Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex). The positive margins decreased from 35.3% in the group undergoing prostatectomy alone to 11.5% in the group of men who received combination therapy before radical prostatectomy. In 41 apical tumors, the incidence of positive margins decreased from 50% in the control group to 18.6% in the combination therapy group. In stage C disease, the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5% after 3 months and 16.7% after 6 months. Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients. However, the initial results obtained in the present study are very encouraging.

Radical prostatectomy is the most common therapy for localized prostate cancer. Unfortunately, resection is associated with positive surgical margins in 35-50% of cases. We report the use of ultrasound-guided staging biopsies to stage tumors preoperatively with greater accuracy. We also report the use of androgen ablation therapy (AAT) as an adjunct to radical prostatectomy in an attempt to downstage tumors preoperatively and decrease the incidence of positive margins. Between 1 June 1991 and 31 July 1992, 131 patients underwent radical prostatectomies, 119 of whom underwent AAT before surgery and 12 of whom did not. Specimens were examined for the presence of positive surgical margins, extracapsular extension, and perineural invasion. Cases pretreated with AAT had a 9.2% positive surgical margin rate compared with 33% in untreated subjects. Extracapsular extension was seen in 22 of 119 (18.5%) of AAT, and 5 of 12 (41.7%) of non-AAT, cases. Perineural invasion was nearly 3 times less likely in AAT patients. Moreover, perineural invasion was significantly less marked in AAT patients. We present a subset of 11 patients who were definitively proven as pathologic stage C cancer by transrectal ultrasound (TRUS)-guided needle biopsy. These cases had prostate cancer intermixed with fatty tissue and pigmented seminal vesicle epithelium, elements not found in the prostate. In this selected stage C subset, gland shrinkage, evidence of downstaging, and tumor obliteration were seen after AAT. We conclude that TRUS-guided staging biopsy can definitively stage prostate cancer as stage C when tumor is intermixed with extraprostatic elements, and AAT appears to decrease the incidence of positive surgical margins by tumoral necrosis and selective perineural kill. We believe that these findings demonstrate the antitumor effects of AAT and deserve further scrutiny in a large randomized clinical trial.

Chronic alcohol intake is often associated with alterations to iron homeostasis and an increase in the serum levels of carbohydrate-deficient transferrin. As the liver is a major iron storage site and also synthesizes transferrin, the normal serum iron transport protein, the aim of this study was to test the hypothesis that these disturbances in iron homeostasis were caused by altered hepatocyte iron uptake from the abnormal transferrin. To achieve this, we have investigated iron uptake from both transferrin and asialotransferrin by hepatocytes from male Sprague-Dawley rats fed the De Carli and Lieber alcohol diet. Iron uptake from transferrin by hepatocytes from alcoholic rats was less than 60% that of control values, and in the presence of 50 mM ethanol decreased still further to 35% of the uptake by the corresponding control cells. Iron uptake from rat asialotransferrin was reduced in both groups when compared to that observed from normal transferrin; 13% by control cells and 39% by hepatocytes from alcohol-fed rats. Alcohol, however, had no further effect on asialotransferrin uptake by either hepatocytes from alcohol-fed rats, or their pair-fed controls. Transferrin binding to hepatocytes was also influenced by the alcohol diet. Although there was no difference in binding at 37 degrees C, cells from alcohol-fed rats bound 85% of this total at 4 degrees C, compared to 44% by control hepatocytes. Similar values were also obtained for hepatocyte binding of asialotransferrin; alcohol feeding resulted in an increase in binding at 4 degrees C to 73% from 58% with control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Methods: The diagnostic performance of transrectal ultrasound (TRUS) gland volume and prostate specific antigen (PSA) results were evaluated in 204 men consecutively scheduled to undergo transurethral prostatic resection (TUR)., Results: Nonpalpable prostate cancer was detected by TRUS alone in 18% (29 of 161) and by TUR alone in 9% (14/161), for an overall cancer incidence of 27%. A predicted PSA value (TRUS gland volume x 0.20 ng/ml/g = polyclonal PSA) was used for comparison with serum PSA for each patient. TRUS positive predictive value improved from 52% to 86% when serum PSA exceeded the predicted value. The specificity and positive predictive value of PSA at 2.5 ng/ml were 23% and 37%, respectively, which increased to 88% and 72%, respectively, when serum PSA exceeded the predicted value., Conclusions: Predicted PSA values produce decision levels near the 95th percentile for each patient and assist individual biopsy decisions better than grouped gland volume ranges. Wider application of TRUS and PSA in any clinical setting or early detection program is now possible.

This study assessed the role of social support in the outcome of child management training (CMT) for single parents of conduct problem children and assessed the impact of adjunctive ally support training (AST) on treatment outcome. Single parents (N = 22) with a child diagnosed as oppositional or conduct-disordered received CMT or CMT plus AST. Each group received the same 6-week parent training program and the AST group received an extra social support intervention. Measures of parent behavior, child deviance, social support (SS), and parental depression were obtained at pre- and posttreatment and at 6-month follow-up. Both groups improved, and changes maintained at follow-up. AST produced no extra gains. Responders from either group were more likely than nonresponders to report high levels of SS from friends. Results emphasize the importance of SS and the difficulty of incorporating changes in SS into treatment programs.

A study was conducted to compare results of transrectal ultrasound with pathologic findings on 116 patients who underwent radical prostatectomy for treatment of prostate cancer. In 96% (111 of 116), transrectal ultrasound guided biopsies of a hypoechoic lesion proved cancer; seven patients had known Stage A cancer; one patient had cancer detected by palpation and not detected by ultrasound. Cancers in the outer gland (peripheral and central zones) were compared with cancers in the inner gland (transition zone) by both ultrasound and pathology. Forty-eight percent (52 of 108) of cancers originating in the outer gland showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the outer gland were the prostatic capsule (38%), anterior fibromuscular stroma (5%), seminal vesicle (18%), the base of the gland at the neurovascular bundle (21%), and the apex (31%). Twenty-two percent (17 of 54) of cancers originating in the inner gland (transition zone) showed extraprostatic extension (Stage C disease). The primary sites of tumor escape from the inner gland were the anterior fibromuscular stroma (6%) and apex (11%). Both histologic and biologic differences between outer and inner gland cancers were found when tumor size was controlled. Gleason scores were significantly different for inner and outer gland cancers, with mean scores of 6.2 +/- 1.6 and 7.4 +/- 0.9, respectively. An odds ratio of 8.6 confirmed the increased risk of extraprostatic extension for outer gland cancer. Outer gland cancers showed increased aggressive behavior of both histologic and biologic nature. The difference in biologic aggressiveness of outer and inner gland cancers has definite implications for treatment options. Use of other diagnostic parameters, such as DNA ploidy, may help to determine which cancers to treat and when to treat them; this may have more relevance for cancers originating in the inner gland. Strategic transrectal ultrasound guided biopsy affords accurate tumor mapping and staging when modes of internal spread and escape of cancer from both outer and inner gland are known. Thus, transrectal ultrasound may be our "window of observation" through which additional research may explain the histologic and biologic discrepancies between outer and inner gland cancers.

Three hundred and ninety eight self-referred men with no histories of prostate problems were followed once each year for up to four years to determine the feasibility of early prostate cancer detection by digital rectal examination, transrectal ultrasound, and prostate-specific antigen. Evaluation of prostate-specific antigen was based on a polyclonal level of normal of 2.6 nanograms per milliliter by the Yang assay. Biopsies were performed when indicated by either transrectal ultrasound or digital rectal examination. The overall cancer detection rate for the four year period was 6.3 percent. A 3:1 cancer detection advantage of transrectal ultrasound over digital rectal examination was shown. Transrectal ultrasound and prostate-specific antigen each detected 92 percent of the proven cancers, and were complementary when either test was normal, together detecting 100 percent of the cancers. Thirty two percent (8/25) of all cancers were detected by digital examination, with digital exam having no predictive power after two study years. Prostate-specific antigen as an initial screening test for early prostate cancer may identify a suspicious group, whom may further be evaluated by transrectal ultrasound and digital exam. Results of this study lend credibility to the large scale randomized screening study proposed by the U.S. National Institutes of Health in which prostate-specific antigen and digital rectal examination are to be used as initial tests for prostate cancer detection.

Palpable cancer of the prostate is widely believed to be clinically significant. The authors compared the clinical significance of palpable prostate cancer with nonpalpable prostate cancer discovered with transrectal ultrasound (US). A strong association between lesion volume measured with preoperative transrectal US and volumetric measurements in 60 radical prostatectomy specimens permitted the use of tumor size measured with transrectal US as a reasonable estimation of gross tumor volume. In a subsequent clinical series, 147 biopsy-proved cancers were grouped according to size measured at US, the findings at digital rectal examination (DRE), and the Gleason score. For the 147 patients with known prostate cancer, a statistically significant difference between Gleason scores of palpable and nonpalpable cancers could not be demonstrated when the size of the tumor and its location within the prostate were held constant. Assuming that the Gleason score is a reliable indication of malignant potential and clinical significance, the authors conclude that nonpalpable prostatic cancer detected with transrectal US alone may be just as clinically significant as prostatic cancer discovered with DRE.

The authors examined 784 self-referred men over age 60 years to compare clinical usefulness of transrectal ultrasound (US) and digital rectal examination in a screening program for prostate cancer. Biopsy was performed in 77 cases, 83% (64 of 77) for abnormalities detected with transrectal US and 38% (29 of 77) because of findings at digital examination. Twenty-two cancers were detected, 20 with transrectal US and ten at digital examination. Overall detection rate for prostate cancer with transrectal US was two times higher than that with digital examination (2.6% vs 1.3%). Sensitivity, specificity, and negative predictive value for transrectal US and digital examination were calculated for a range of prevalences (0.028-0.1543). Sensitivity was two times higher for transrectal US than for digital examination. Transrectal US demonstrated 100% (17 of 17) of tumors with the most favorable prognosis (less than or equal to 1.5 cm in diameter) compared with 41% (seven of 17) for digital examination. The authors conclude that transrectal US is more sensitive than digital examination in the detection of prostate cancer, and they advocate broader implementation and evaluation of transrectal US as a tool for early detection.

Administration of endotoxins is often followed within 12-24 h by marked hypoferremia. Because the hepatocyte is the major site of both iron storage and transferrin synthesis, we have investigated the effects of an Escherichia coli endotoxin (lipopolysaccharide, LPS) on these parameters on isolated hepatocytes from normal Wistar rats (ND), rats previously treated intraperitoneally with 2.5 mg/kg (LD) or 25 mg/kg (HD) LPS, and control rats injected intraperitoneally with sterile saline (CD). No effects were observed on iron uptake from transferrin by ND cells incubated in vitro with up to 350 micrograms LPS/10(7) hepatocytes. There was also no significant difference in iron uptake between CD, HD, and LD hepatocytes 1 h after LPS injection. However, hepatocytes isolated 24 h after LPS administration took up iron significantly faster than controls. The uptake of non-transferrin-bound iron was also increased in HD and LD hepatocytes at 24 h but only in HD cells at 1 h. Transferrin binding was not altered in LPS-treated cells from ND rats but was depressed in cells from LPS-treated rats both at 1 h and at 24 h after injection. Transferrin receptor recycling was significantly increased at 24 h in cells from both LD and HD rats. Transferrin and total protein synthesis were also depressed at 1 h in LPS-treated rats, returning to normal values at 24 h. Direct preincubation of ND cells, however, failed to increase synthesis except at the highest concentrations of LPS. We conclude that LPS has an immediate (although indirect) effect on protein synthesis by the hepatocyte but not on iron uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Biplanar, transrectal ultrasound (US) guidance of needles was used in the transperineal biopsy of possibly malignant prostatic lesions in 80 patients (83 biopsies). A 22-gauge cytologic needle was used to locate and fixate the lesion, and aspiration specimens for cytologic and histologic evaluation were obtained (with 22- and 14-gauge needles, respectively). Twenty-one 19-gauge needle core biopsies were also performed. Forty-nine patients (61%) had histologically prove adenocarcinoma. The rate of cancer diagnosis was 53% with cytologic evaluation and 54% with histologic evaluation (combined yield, 61%). This included 34% of cancers less than 1.0 cm in diameter and 56% of those 1.0-1.5 cm. Thirteen of 23 (57%) of these lesions were nonpalpable or equivocal on digital rectal examination. These results suggest that transrectal US guidance of thin-needle biopsies is useful in diagnosing early prostate cancer.

Two hundred fifty-six patients with hypoechoic lesions of the prostate found at transrectal ultrasound (US) were evaluated with prostate-specific antigen (PSA) study, digital rectal examination (DRE), and US-guided transrectal biopsy. Positive predictive values for cancer were calculated for transrectal US alone and in combination with DRE, PSA study, or both. Results were correlated with lesion size. The positive predictive value for transrectal US alone was 41%; this value increased to 61% if the patient had positive results from DRE, 52% if the PSA level was elevated, and 71% if both the DRE results and PSA level were abnormal. The positive predictive value for transrectal US fell to 24% if results of the DRE were normal, 12% if the PSA level was normal, and 5% if both DRE results and PSA level were normal. No cancers were detected in lesions 1.0 cm or smaller if DRE results and PSA level were normal. DRE and PSA study are valuable complements to abnormal transrectal US examinations. Biopsy of small suspicious lesions may not be indicated if results of both of the studies are normal.

The clinical and morphologic features of 18 patients with paratesticular rhabdomyosarcoma are reviewed. Although medical attention was sought frequently within 2 months the lesion was mistaken initially for other more common scrotal conditions in more than a third of the patients, delaying a correct diagnosis for 3 weeks to 4 months. Half of the patients had retroperitoneal lymph node metastases. However, with multimodal therapy 61 per cent remain free of disease at a median of 6 years from diagnosis.

Over a 7-month period, from a total of 417 transrectal ultrasound (US) studies, 45 transperineal biopsies of the prostate were performed in the radiology department. Transrectal US guidance and local anesthesia were used. Twenty-two of 32 hypoechoic lesions, located within the peripheral zone tissue of the gland, were proved by histologic study to be cancerous. Hyperechoic lesions were all histologically benign hyperplasias. The patients experienced no major complications necessitating hospitalization or increased length of hospital stay as a result of the procedure.

Adenocarcinoma of the prostate produces specific ultrasonic findings that can be used in diagnosis. We have examined 211 patients using transrectal ultrasound in both the sagittal and axial planes. Thirty-three carcinomas were detected, and 31 histologically confirmed; 24 by needle biopsy, six by transurethral resection, one by total prostatectomy, and two by the demonstration of distant metastases. On ultrasound, all of the carcinomas were less echogenic than normal prostate. All appeared to originate in the peripheral zone of the prostate and produced asymmetry of the gland. The majority of carcinomas in this series showed capsular involvement and ten penetrated and extended beyond the prostatic capsule. The results of this series indicate that transrectal ultrasound can be used to detect cancer of the prostate gland. Ultrasound demonstrated the extent of tumor involvement and enabled accurate staging of these cancers.

To determine which individual parameters contribute to the increased bilirubin clearance which follows phenobarbital administration in the rat, dose response studies are being conducted relating changes in various aspects of bilirubin transport to the dose of phenobarbital administered. The relationships between phenobarbital dose, immunoreactive ligandin concentrations, and cytosolic glutathione-S-transferase (GSHT) enzymatic activities were determined in the 100,000g liver cytosol obtained from non-fasted male Sprague-Dawley rats, treated for 6 days (ip) with either phenobarbital at various doses ranging from 1 to 125 mg/kg/day or distilled water. Ligandin levels were measured by radioimmunoassay employing an antiserum which reacts with both GSHT-1 (Ya) and -2 (Yc) subunits. Ligandin concentration increased in a dose-dependent fashion, achieving a maximal observed value of 278% of control at the highest administered phenobarbital dose. Values were significantly elevated compared to controls at doses as low as 3 mg/kg/day. GSH-dependent delta 5-3-ketosteroid isomerase (KSI) activity, which reflects predominantly GSH transferase subunit 1, and GSHT activity against 1-chloro-2,4-dinitrobenzene (CDNB) also increased over the entire range of phenobarbital doses administered. Both of these enzymatic activities were highly correlated with immunoreactive ligandin levels (KSI: r = 0.89, p less than 0.005; GSHT (CDNB): r = 0.92, p less than 0.001). By contrast, GSHT activity against 1,2-dichloro-4-nitrobenzene (DCNB), which resides principally on GSHT subunits not present in ligandin, did not correlate significantly with measured ligandin concentrations. These studies indicate that phenobarbital is capable of inducing immunoreactive ligandin concentrations and related enzymatic activities at doses as small as 5% of those commonly employed to demonstrate this effect.