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Background: Impaction in total hip arthroplasty has typically been conducted using a mallet. A surgical automated impactor has been developed with the goal of reducing surgeon variability, fatigue, and injury. There is also potential to reduce the variability of each impaction step in which automated impaction is used, through reproducible and consistent application of force. Methods: Patients were randomized into either the mallet control group, or the automated impaction study group (1:1 randomization). The primary endpoint analysis was conducted to demonstrate that femoral broaching time (in minutes) with an automated impactor is noninferior to femoral broaching time with manual instruments (mallet) under a noninferiority (NI) margin of 1.25 minutes, with a subsequent test of superiority. A total of 218 patients were randomized and treated (109 in each group). Results: Mean femoral broaching time was 5.8 minutes in the automated impaction study group (automated), and 8.1 minutes in the mallet control group (mallet), a 28.4% reduction (P = .0005). However, there was not a difference in surgery duration between the groups. Three fractures were reported in the mallet group and 1 in the automated group. Conclusions: In this randomized multicenter study, an automated impactor was shown to reduce femoral broaching time in primary total hip arthroplasty, with no increase in fractures, but no decrease in operating room time was noted.

Purpose: Brain metastases are common among adult patients with solid malignancies and are increasingly being treated with stereotactic radiosurgery (SRS). As more patients with brain metastases are becoming eligible for SRS, there is a need for practical review of patient selection and treatment considerations. Methods and Materials: Two patient cases were identified to use as the foundation for a discussion of a wide and representative range of management principles: (A) SRS alone for 5 to 15 lesions and (B) a large single metastasis to be treated with pre- or postoperative SRS. Patient selection, fractionation, prescription dose, treatment technique, and dose constraints are discussed. Literature relevant to these cases is summarized to provide a framework for treatment of similar patients. Results: Treatment of brain metastases with SRS requires many considerations including optimal patient selection, fractionation selection, and plan optimization. Conclusions: Case-based practice guidelines developed by the Radiosurgery Society provide a practical guide to the common scenarios noted above affecting patients with metastatic brain tumors.

A 77-year-old man with history of sacral chordoma and pulmonary embolism presented to the emergency room with a 1-day history of diffuse left flank and lower extremity swelling. The patient was found to have thrombus in the left common and external iliac veins. The patient was brought to Interventional Radiology for mechanical thrombectomy using the Inari ClotTriever and a sample of extracted thrombus was sent to pathology. Analysis on the sample was positive for sacral chordoma, consistent with tumor thrombus. The patient returned after 6 weeks with similar symptoms and repeat mechanical thrombectomy was performed with the Inari ClotTriever and stent placement through the left common and external iliac vein with an Ovation iX stent graft. The patient remained asymptomatic following the second procedure at repeat follow-up at 6 weeks.

Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive skin fibrosis. It has 2 main clinical subtypes—diffuse cutaneous scleroderma and limited cutaneous scleroderma. Non-cirrhotic portal hypertension (NCPH) is defined as presence of elevated portal vein pressures without cirrhosis. It is often a manifestation of an underlying systemic disease. On histopathology, NCPH may be found to be secondary to multiple abnormalities such as nodular regenerative hyperplasia (NRH) and obliterative portal venopathy. There have been reports of NCPH in patients with both subtypes of SSc secondary to NRH. However, simultaneous presence of obliterative portal venopathy has not been reported. We present a case of NCPH due to NRH and obliterative portal venopathy as a presenting sign of limited cutaneous scleroderma. The patient was initially found to have pancytopenia and splenomegaly and was erroneously labeled as cirrhosis. She underwent workup to rule out leukemia, which was negative. She was referred to our clinic and diagnosed with NCPH. Due to pancytopenia, she could not be started on immunosuppressive therapy for her SSc. Our case describes the presence of these unique pathological findings in the liver and highlights the importance of an aggressive search for an underlying condition in all patients diagnosed with NCPH.

Purpose: Recent randomized controlled trials evaluating stereotactic surgery (SRS) for resected brain metastases question the high rates of local control previously reported in retrospective studies. Tumor control probability (TCP) models were developed to quantify the relationship between radiation dose and local control after SRS for resected brain metastases. Methods and Materials: Patients with resected brain metastases treated with SRS were evaluated retrospectively. Melanoma, sarcoma, and renal cell carcinoma were considered radio-resistant histologies. The planning target volume (PTV) was the region of enhancement on T1 post-gadolinium magnetic resonance imaging plus a 2-mm uniform margin. The primary outcome was local recurrence, defined as tumor progression within the resection cavity. Cox regression evaluated predictors of local recurrence. Dose-volume histograms for the PTV were obtained from treatment plans and converted to 3-fraction equivalent doses (α/β = 12 Gy). TCP models evaluated local control at 1-year follow-up as a logistic function of dose-volume histogram data. Results: Among 150 cavities, 41 (27.3%) were radio-resistant. The median PTV volume was 14.6 mL (range, 1.3-65.3). The median prescription was 21 Gy (range, 15-25) in 3 fractions (range, 1-5). Local control rates at 12 and 24 months were 86% and 82%. On Cox regression, larger cavities (PTV > 12 cm3) predicted increased risk of local recurrence (P = .03). TCP modeling demonstrated relationships between improved 1-year local control and higher radiation doses delivered to radio-resistant cavities. Maximum PTV doses of 30, 35, and 40 Gy predicted 78%, 89%, and 94% local control among all radio-resistant cavities, versus 69%, 79%, and 86% among larger radio-resistant cavities. Conclusions: After SRS for resected brain metastases, larger cavities are at greater risk of local recurrence. TCP models suggests that higher radiation doses may improve local control among cavities of radio-resistant histology. Given maximum tolerated doses established for single-fraction SRS, fractionated regimens may be required to optimize local control in large radio-resistant cavities.

Purpose: To inform development of procedures for using tumor-treating field arrays (TTFields) during glioblastoma radiation therapy by determining whether the placement and repositioning of arrays affects target volume coverage and cranial skin dose. Methods and Materials: Radiation plans from 10 consecutive patients treated for glioblastoma were copied to a cranial phantom and reoptimized for phantom anatomy. Dose distributions were then recalculated on 3 additional computed tomographic scans of the phantom with the TTFields electrode arrays placed over distinct locations on the phantom scalp to compare planning target volume (PTV) coverage and skin dose with and without TTFields in place in varying positions. Percent depth dose curves were also measured for radiation beams passing through the electrodes and compared with commonly used bolus material. Results: The presence of TTFields arrays decreased PTV V97% and D97% by as much as 1.7% and 2.7%, respectively, for a single array position, but this decrease was mitigated by array repositioning. On averaging the 3 array positions, there was no statistically significant difference in any dosimetric parameter of PTV coverage (V95-97%, D95-97%) across all cases compared with no array. Mean increases in skin D1cc and D20cc of 3.1% were calculated for the cohort. Surface dose for TTFields electrodes was less than that with a 5-mm superflab bolus. Conclusions: Our work demonstrates that placement of TTFields arrays does not significantly affect target volume coverage. We show that repositioning of TTFields arrays, as is required in clinical use, further minimizes any dosimetric changes and eliminates the need for replanning when arrays are moved. A slight, expected bolus effect is observed, but the calculated increases in skin dose are not clinically significant. These data support the development of clinical trials to assess the safety and efficacy of combining concurrent chemoradiotherapy with TTFields therapy for glioblastoma.

Purpose: Reirradiation for recurrent glioma remains controversial without knowledge of optimal patient selection, dose, fractionation, and normal tissue tolerances. We retrospectively evaluated outcomes and toxicity after conventionally fractionated reirradiation for recurrent high-grade glioma, along with the impact of concurrent chemotherapy. Methods and materials: We conducted a retrospective review of patients reirradiated for high-grade glioma recurrence between 2007 and 2016 (including patients with initial low-grade glioma). Outcome metrics included overall survival (OS), prognostic factors for survival, and treatment-related toxicity. Results: Patients (n = 118; median age 47 years; median Karnofsky performance status score: 80) were re-treated at a median of 28 months (range, 5-214 months) after initial radiation therapy. The median reirradiation dose was 41.4 Gy (range, 12.6-54.0 Gy) to a median lesion volume of 202 cm3 (range, 20-901 cm3). The median cumulative (initial radiation and reirradiation combined) potential maximum brainstem dose was 76.9 Gy (range, 5.0-108.3 Gy) and optic apparatus dose was 56.0 Gy (range, 4.5-90.9 Gy). Of the patients, 56% received concurrent temozolomide, 14%, bevacizumab, and 11%, temozolomide plus bevacizumab; 19% had no chemotherapy. The planned reirradiation was completed by 90% of patients. Median OS from the completion of reirradiation was 9.6 months (95% confidence interval [CI], 7.5-11.7 months) for all patients and 14.0, 11.5, and 6.7 months for patients with initial grade 2, 3, and 4 glioma, respectively. On multivariate analysis, better OS was observed with a >24-month interval between radiation treatments (hazard ratio [HR]: 0.3; 95% CI, 0.2-0.5; P < .001), reirradiation dose >41.4 Gy (HR: 0.6; 95% CI, 0.4-0.9; P = .03), and gross total resection before reirradiation (HR: 0.6, 95% CI, 0.3-0.9; P = .02). Radiation necrosis and grade ≥3 late neurotoxicity were both minimal (41.4 Gy in conventional fractionation, along with chemotherapy, was safe and well tolerated with meaningful survival duration. These data provide information that may be useful in implementing safe reirradiation treatments for appropriately selected patients and guiding future studies to define optimal reirradiation doses, maximal safe doses to critical structures, and the role of systemic therapy.

The fundamental trade-off between current and future reproduction has long been considered to result in a tendency for species that can grow large to begin reproduction at a larger size. Due to the prolonged time required to reach maturity, estimates of tree maturation size remain very rare and we lack a global view on the generality and the shape of this trade-off. Using seed production from five continents, we estimate tree maturation sizes for 486 tree species spanning tropical to boreal climates. Results show that a species' maturation size increases with maximum size, but in a non-proportional way: the largest species begin reproduction at smaller sizes than would be expected if maturation were simply proportional to maximum size. Furthermore, the decrease in relative maturation size is steepest in cold climates. These findings on maturation size drivers are key to accurately represent forests' responses to disturbance and climate change., (© 2024 John Wiley & Sons Ltd.)

Trees must allocate resources to core functions like growth, defense, and reproduction. These allocation patterns have profound effects on forest health, yet little is known about how core functions trade off over time, and even less is known about how a changing climate will impact tradeoffs. We conducted a 21-year survey of growth, defense, and reproduction in 80 ponderosa pine individuals spanning eight populations across environmental gradients along the Colorado Front Range, USA. We used linear mixed models to describe tradeoffs among these functions and to characterize variability among and within individuals over time. Growth and defense were lower in years of high cone production, and local drought conditions amplified year-to-year tradeoffs between reproduction and growth, where trees located at sites with hotter and drier climates showed stronger tradeoffs between reproduction and growth. Our results support the environmental stress hypothesis of masting, which predicts that greater interannual variation in tree functions will be associated with more marginal environments, such as those that are prone to drought. With warming temperatures and increased exposure to drought stress, trees will be faced with stronger interannual tradeoffs, which could lead to further decreases in growth and defensive efforts, ultimately increasing risks of mortality., (© 2023 The Authors. Ecology published by Wiley Periodicals LLC on behalf of The Ecological Society of America. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The benefits of masting (volatile, quasi-synchronous seed production at lagged intervals) include satiation of seed predators, but these benefits come with a cost to mutualist pollen and seed dispersers. If the evolution of masting represents a balance between these benefits and costs, we expect mast avoidance in species that are heavily reliant on mutualist dispersers. These effects play out in the context of variable climate and site fertility among species that vary widely in nutrient demand. Meta-analyses of published data have focused on variation at the population scale, thus omitting periodicity within trees and synchronicity between trees. From raw data on 12 million tree-years worldwide, we quantified three components of masting that have not previously been analysed together: (i) volatility, defined as the frequency-weighted year-to-year variation; (ii) periodicity, representing the lag between high-seed years; and (iii) synchronicity, indicating the tree-to-tree correlation. Results show that mast avoidance (low volatility and low synchronicity) by species dependent on mutualist dispersers explains more variation than any other effect. Nutrient-demanding species have low volatility, and species that are most common on nutrient-rich and warm/wet sites exhibit short periods. The prevalence of masting in cold/dry sites coincides with climatic conditions where dependence on vertebrate dispersers is less common than in the wet tropics. Mutualist dispersers neutralize the benefits of masting for predator satiation, further balancing the effects of climate, site fertility and nutrient demands., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The relationships that control seed production in trees are fundamental to understanding the evolution of forest species and their capacity to recover from increasing losses to drought, fire, and harvest. A synthesis of fecundity data from 714 species worldwide allowed us to examine hypotheses that are central to quantifying reproduction, a foundation for assessing fitness in forest trees. Four major findings emerged. First, seed production is not constrained by a strict trade-off between seed size and numbers. Instead, seed numbers vary over ten orders of magnitude, with species that invest in large seeds producing more seeds than expected from the 1:1 trade-off. Second, gymnosperms have lower seed production than angiosperms, potentially due to their extra investments in protective woody cones. Third, nutrient-demanding species, indicated by high foliar phosphorus concentrations, have low seed production. Finally, sensitivity of individual species to soil fertility varies widely, limiting the response of community seed production to fertility gradients. In combination, these findings can inform models of forest response that need to incorporate reproductive potential., (© 2022. The Author(s).)

Tree fecundity and recruitment have not yet been quantified at scales needed to anticipate biogeographic shifts in response to climate change. By separating their responses, this study shows coherence across species and communities, offering the strongest support to date that migration is in progress with regional limitations on rates. The southeastern continent emerges as a fecundity hotspot, but it is situated south of population centers where high seed production could contribute to poleward population spread. By contrast, seedling success is highest in the West and North, serving to partially offset limited seed production near poleward frontiers. The evidence of fecundity and recruitment control on tree migration can inform conservation planning for the expected long-term disequilibrium between climate and forest distribution., Competing Interests: Competing interest statement: M.B., W.D.K., and I.S.P. are collaborators on a 2020 review with T.W., (Copyright © 2021 the Author(s). Published by PNAS.)

Our overall objective is to synthesize mast-seeding data on North American Pinaceae to detect characteristic features of reproduction (i.e. development cycle length, serotiny, dispersal agents), and test for patterns in temporal variation based on weather variables. We use a large dataset ( n = 286 time series; mean length = 18.9 years) on crop sizes in four conifer genera ( Abies , Picea , Pinus , Tsuga ) collected between 1960 and 2014. Temporal variability in mast seeding (CVp) for 2 year genera ( Abies , Picea , Tsuga ) was higher than for Pinus (3 year), and serotinous species had lower CVp than non-serotinous species; there were no relationships of CVp with elevation or latitude. There was no difference in family-wide CVp across four tree regions of North America. Across all genera, July temperature differences between bud initiation and the prior year (Δ T ) was more strongly associated with reproduction than absolute temperature. Both CVp and Δ T remained steady over time, while absolute temperature increased by 0.09°C per decade. Our use of the Δ T model included a modification for Pinus , which initiates cone primordia 2 years before seedfall, as opposed to 1 year. These findings have implications for how mast-seeding patterns may change with future increases in temperature, and the adaptive benefits of mast seeding. This article is part of the theme issue 'The ecology and evolution of synchronized seed production in plants'.

We aimed to disentangle the patterns of synchronous and variable cone production (i.e. masting) and its relationship to climate in two conifer species native to dry forests of western North America. We used cone abscission scars to reconstruct ca 15 years of recent cone production in Pinus edulis and Pinus ponderosa , and used redundancy analysis to relate time series of annual cone production to climate indices describing the North American monsoon and the El Niño Southern Oscillation (ENSO). We show that the sensitivity to climate and resulting synchrony in cone production varies substantially between species. Cone production among populations of P. edulis was much more spatially synchronous and more closely related to large-scale modes of climate variability than among populations of P. ponderosa . Large-scale synchrony in P. edulis cone production was associated with the North American monsoon and we identified a dipole pattern of regional cone production associated with ENSO phase. In P. ponderosa , these climate indices were not strongly associated with cone production, resulting in asynchronous masting patterns among populations. This study helps frame our understanding of mast seeding as a life-history strategy and has implications for our ability to forecast mast years in these species. This article is part of the theme issue 'The ecology and evolution of synchronized seed production in plants'.

Despite its importance for forest regeneration, food webs, and human economies, changes in tree fecundity with tree size and age remain largely unknown. The allometric increase with tree diameter assumed in ecological models would substantially overestimate seed contributions from large trees if fecundity eventually declines with size. Current estimates are dominated by overrepresentation of small trees in regression models. We combined global fecundity data, including a substantial representation of large trees. We compared size-fecundity relationships against traditional allometric scaling with diameter and two models based on crown architecture. All allometric models fail to describe the declining rate of increase in fecundity with diameter found for 80% of 597 species in our analysis. The strong evidence of declining fecundity, beyond what can be explained by crown architectural change, is consistent with physiological decline. A downward revision of projected fecundity of large trees can improve the next generation of forest dynamic models., Competing Interests: Competing interest statement: C.J.C. and J.C. are coauthors on a 2020 article; S.J.W. and J.C. are coauthors on a 2019 article; J.R.P. and J.C. are coauthors on a 2020 article; M.U., J.K.Z., and J.C. are coauthors on two 2019 articles; and M. Silman, W.F.R., and J.C. are coauthors on 2018, 2019, and 2020 articles.

Indirect climate effects on tree fecundity that come through variation in size and growth (climate-condition interactions) are not currently part of models used to predict future forests. Trends in species abundances predicted from meta-analyses and species distribution models will be misleading if they depend on the conditions of individuals. Here we find from a synthesis of tree species in North America that climate-condition interactions dominate responses through two pathways, i) effects of growth that depend on climate, and ii) effects of climate that depend on tree size. Because tree fecundity first increases and then declines with size, climate change that stimulates growth promotes a shift of small trees to more fecund sizes, but the opposite can be true for large sizes. Change the depresses growth also affects fecundity. We find a biogeographic divide, with these interactions reducing fecundity in the West and increasing it in the East. Continental-scale responses of these forests are thus driven largely by indirect effects, recommending management for climate change that considers multiple demographic rates.

Forest vulnerability to drought is expected to increase under anthropogenic climate change, and drought-induced mortality and community dynamics following drought have major ecological and societal impacts. Here, we show that tree mortality concomitant with drought has led to short-term (mean 5 y, range 1 to 23 y after mortality) vegetation-type conversion in multiple biomes across the world (131 sites). Self-replacement of the dominant tree species was only prevalent in 21% of the examined cases and forests and woodlands shifted to nonwoody vegetation in 10% of them. The ultimate temporal persistence of such changes remains unknown but, given the key role of biological legacies in long-term ecological succession, this emerging picture of postdrought ecological trajectories highlights the potential for major ecosystem reorganization in the coming decades. Community changes were less pronounced under wetter postmortality conditions. Replacement was also influenced by management intensity, and postdrought shrub dominance was higher when pathogens acted as codrivers of tree mortality. Early change in community composition indicates that forests dominated by mesic species generally shifted toward more xeric communities, with replacing tree and shrub species exhibiting drier bioclimatic optima and distribution ranges. However, shifts toward more mesic communities also occurred and multiple pathways of forest replacement were observed for some species. Drought characteristics, species-specific environmental preferences, plant traits, and ecosystem legacies govern postdrought species turnover and subsequent ecological trajectories, with potential far-reaching implications for forest biodiversity and ecosystem services., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Climate warming is contributing to increases in wildfire activity throughout the western United States, leading to potentially long-lasting shifts in vegetation. The response of forest ecosystems to wildfire is thus a crucial indicator of future vegetation trajectories, and these responses are contingent upon factors such as seed availability, interannual climate variability, average climate, and other components of the physical environment. To better understand variation in resilience to wildfire across vulnerable dry forests, we surveyed conifer seedling densities in 15 recent (1988-2010) wildfires and characterized temporal variation in seed cone production and seedling establishment. We then predicted postfire seedling densities at a 30-m resolution within each fire perimeter using downscaled climate data, monthly water balance models, and maps of surviving forest cover. Widespread ponderosa pine (Pinus ponderosa) seed cone production occurred at least twice following each fire surveyed, and pulses of conifer seedling establishment coincided with years of above-average moisture availability. Ponderosa pine and Douglas-fir (Pseudotsuga menziesii) seedling densities were higher on more mesic sites and adjacent to surviving trees, though there were also important interspecific differences, likely attributable to drought and shade tolerance. We estimated that postfire seedling densities in 42% (for ponderosa pine) and 69% (for Douglas-fir) of the total burned area were below the lowest reported historical tree densities in these forests. Spatial models demonstrated that an absence of mature conifers (particularly in the interior of large, high-severity patches) limited seedling densities in many areas, but 30-yr average actual evapotranspiration and climatic water deficit limited densities on marginal sites. A better understanding of the limitations to postfire forest recovery will refine models of vegetation dynamics and will help to improve strategies of adaptation to a warming climate and shifting fire activity., (© 2019 by the Ecological Society of America.)

Recent droughts and increasing temperatures have resulted in extensive tree mortality across the globe. Understanding the environmental controls on tree regeneration following these drought events will allow for better predictions of how these ecosystems may shift under a warmer, drier climate. Within the widely distributed piñon-juniper woodlands of the southwestern USA, a multiyear drought in 2002-2004 resulted in extensive adult piñon mortality and shifted adult woodland composition to a juniper-dominated, more savannah-type ecosystem. Here, we used pre- (1998-2001) and 10-year post- (2014) drought stand structure data of individually mapped trees at 42 sites to assess the effects of this drought on tree regeneration across a gradient of environmental stress. We found declines in piñon juvenile densities since the multiyear drought due to limited new recruitment and high (>50%) juvenile mortality. This is in contrast to juniper juvenile densities, which increased over this time period. Across the landscape, piñon recruitment was positively associated with live adult piñon densities and soil available water capacity, likely due to their respective effects on seed and water availability. Juvenile piñon survival was strongly facilitated by certain types of nurse trees and shrubs. These nurse plants also moderated the effects of environmental stress on piñon survival: Survival of interspace piñon juveniles was positively associated with soil available water capacity, whereas survival of nursed piñon juveniles was negatively associated with perennial grass cover. Thus, nurse plants had a greater facilitative effect on survival at sites with higher soil available water capacity and perennial grass cover. Notably, mean annual climatic water deficit and elevation were not associated with piñon recruitment or survival across the landscape. Our findings reveal a clear shift in successional trajectories toward a more juniper-dominated woodland and highlight the importance of incorporating biotic interactions and soil properties into species distribution modeling approaches., (© 2015 John Wiley & Sons Ltd.)

National fuel-reduction programs aim to reduce the risk of wildland fires to human communities and to restore forest and rangeland ecosystems to resemble their historical structure, function, and diversity. There are a number of factors, such as seed bank dynamics, post-treatment climate, and herbivory, which determine whether this latter goal may be achieved. Here, we examine the short-term (2 years) vegetation response to fuel-reduction treatments (mechanical mastication, broadcast burn, and pile burn) and seeding of native grasses on understory vegetation in an upland piñon-juniper woodland in southeast Utah. We also examine how wildlife herbivory affects the success of fuel-reduction treatments. Herbaceous cover increased in response to fuel-reduction treatments in all seeded treatments, with the broadcast burn and mastication having greater increases (234 and 160 %, respectively) in herbaceous cover than the pile burn (32 %). In the absence of seeding, herbaceous cover only increased in the broadcast burn (32 %). Notably, fuel-reduction treatments, but not seeding, strongly affected herbaceous plant composition. All fuel-reduction treatments increased the relative density of invasive species, especially in the broadcast burn, which shifted the plant community composition from one dominated by perennial graminoids to one dominated by annual forbs. Herbivory by wildlife reduced understory plant cover by over 40 % and altered plant community composition. If the primary management goal is to enhance understory cover while promoting native species abundance, our study suggests that mastication may be the most effective treatment strategy in these upland piñon-juniper woodlands. Seed applications and wildlife exclosures further enhanced herbaceous cover following fuel-reduction treatments.

Widespread piñon (Pinus edulis) mortality occurred across the southwestern USA during 2002-2003 in response to drought and bark beetle infestations. Given the recent mortality and changes in regional climate over the past several decades, there is a keen interest in post-mortality regeneration dynamics in piñon-juniper woodlands. Here, we examined piñon and Utah juniper (Juniperus osteosperma) recruitment at 30 sites across southwestern Colorado, USA that spanned a gradient of adult piñon mortality levels (10-100%) to understand current regeneration dynamics. Piñon and juniper recruitment was greater at sites with more tree and shrub cover. Piñon recruitment was more strongly facilitated than juniper recruitment by trees and shrubs. New (post-mortality) piñon recruitment was negatively affected by recent mortality. However, mortality had no effect on piñon advanced regeneration (juveniles established pre-mortality) and did not shift juvenile piñon dominance. Our results highlight the importance of shrubs and juniper trees for the facilitation of piñon establishment and survival. Regardless of adult piñon mortality levels, areas with low tree and shrub cover may become increasingly juniper dominated as a result of the few suitable microsites for piñon establishment and survival. In areas with high piñon mortality and high tree and shrub cover, our results suggest that piñon is regenerating via advanced regeneration., (© 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.)

With growing interest in the effects of biodiversity on disease, there is a critical need for studies that empirically identify the mechanisms underlying the diversity-disease relationship. Here, we combined wetland surveys of host community structure with mechanistic experiments involving a multi-host parasite to evaluate competing explanations for the dilution effect. Sampling of 320 wetlands in California indicated that snail host communities were strongly nested, with competent hosts for the trematode Ribeiroia ondatrae predominating in low-richness assemblages and unsuitable hosts increasingly present in more diverse communities. Moreover, competent host density was negatively associated with increases in snail species richness. These patterns in host community assembly support a key prerequisite underlying the dilution effect. Results of multigenerational mesocosm experiments designed to mimic field-observed community assemblages allowed us to evaluate the relative importance of host density and diversity in influencing parasite infection success. Increases in snail species richness (from one to four species) had sharply negative effects on the density of infected hosts (-90% reduction). However, this effect was indirect; competition associated with non-host species led to a 95% reduction in host density (susceptible host regulation), owing primarily to a reduction in host reproduction. Among susceptible hosts, there were no differences in infection prevalence as a function of community structure, indicating a lack of support for a direct effect of diversity on infection (encounter reduction). In monospecific conditions, higher initial host densities increased infection among adult hosts; however, compensatory reproduction in the low-density treatments equalized the final number of infected hosts by the next generation, underscoring the relevance of multigenerational studies in understanding the dilution effect. These findings highlight the role of interspecific competition in mediating the relationship between species richness and parasite infection and emphasize the importance of field-informed experimental research in understanding mechanisms underlying the diversity-disease relationship.

Experimental infections provide an important foundation for understanding host responses to parasites. While infections with Ribeiroia ondatrae cause mortality and malformations in a wide range of amphibian second intermediate host species, little is known about how the parasite affects its snail first intermediate hosts or even what species can support infection. In this study, we experimentally exposed Helisoma trivolvis, a commonly reported host of R. ondatrae, and Biomphalaria glabrata, a confamilial snail known to host Ribeiroia marini, to increasing concentrations of embryonated eggs of R. ondatrae obtained from surrogate definitive hosts. Over the course of 8 wk, we examined the effect of parasite exposure on infection status, time-to-cercariae release, host size, and mortality of both snail species. Helisoma trivolvis was a highly competent host for R. ondatrae infection, with over 93% infection in all exposed snails, regardless of egg exposure level. However, no infections were detected among exposed B. glabrata, despite previous accounts of this snail hosting a congener parasite. Among exposed H. trivolvis, high parasite exposure reduced growth, decreased time-to-cercariae release, and caused marginally significant increases in mortality. Interestingly, while B. glabrata snails did not become infected with R. ondatrae, individuals exposed to 650 R. ondatrae eggs grew less rapidly than unexposed snails, suggesting a sub-lethal energetic cost associated with parasite exposure. Our results highlight the importance of using experimental infections to understand the effects of parasite exposure on host- and non-host species, each of which can be affected by exposure.

Objective: To assess factors that affect cisplatin nephrotoxicity., Methods: In 425 patients treated with cisplatin, we assessed the effect of pretreatment factors and treatment conditions on the rise in serum creatinine with the first course of cisplatin, on the maximum rise in serum creatinine over the entire course of the cisplatin therapy, and on residual nephrotoxicity after the last cisplatin treatment ended. (Because of the nature of the relationship between serum creatinine and creatinine clearance, rise in serum creatinine was divided by pretreatment creatinine squared.) Patients were dichotomized into the upper quartile versus the lower three quartiles of degree of nephrotoxicity. Multivariate analyses were based on logistic regression, controlling for cisplatin dose per course., Results: Controlling for cisplatin dose per course, factors most closely associated with nephrotoxicity during the first course of cisplatin were: serum albumin and potassium, body surface area, and administration of cisplatin over 2-5 days per course vs 1 day (negative associations). Controlling for cisplatin dose per course, the single factor most closely associated with maximum life-time cisplatin nephrotoxicity was concurrent use of a vinca alkaloid (negative association). Controlling for cisplatin dose per course, factors most closely associated with residual nephrotoxicity after the end of cisplatin therapy were cumulative dose of cisplatin, concurrent use of metoclopramide (positive associations), uric acid and concurrent use of phenytoin and a vinca alkaloid (negative associations). The association of nephrotoxicity with uric acid and with body surface area was felt to be an artifact resulting from its positive association with pretreatment serum creatinine. Nephrotoxicity during the first course of cisplatin also correlated significantly with autopsy kidney cortex platinum concentrations in 77 evaluable patients., Conclusions: (1) While several factors correlated with cisplatin nephrotoxicity, most of the observed nephrotoxicity was not explained by the variables identified. (2) While most patients received intravenous hydration, patients receiving high hydration volumes did not have significantly less nephrotoxicity than patients receiving lower hydration volumes: (3) Of the variables identified, serum albumin, metoclopramide and phenytoin may have affected nephrotoxicity by altering cisplatin uptake into or distribution within the kidney.

The objective of this study was to determine factors that affect cisplatin concentrations in human kidney cortex. We used flameless atomic absorption spectrophotometry to assay platinum in autopsy specimens of kidney cortex obtained from 83 cisplatin-treated patients. Concentrations were correlated with pretreatment factors and treatment conditions using univariate nonparametric statistics. Hierarchical stepwise multiple regression analyses of transformed (to normalize) data were then used to assess which factors were most important, controlling for other factors. Kidney-cortex platinum concentrations varied from 0 to 14.8 micrograms/g (median, 2.04 micrograms/g). The cumulative lifetime dose of cisplatin ranged from 10 to 1120 mg/m2 (median, 112 mg/m2). The time from the last cisplatin dose to death was < 1-609 days (median, 38 days). According to univariate statistics, factors that correlated (P < 0.05) with kidney-cortex platinum concentrations were the cisplatin dose per course, the pretreatment serum urea level, metoclopramide use (positive correlations), the time from the last cisplatin treatment to death, and the pretreatment serum albumin value (negative correlations). Factors that approached significance (0.05 < or = P < or = 0.10) were a history of hypertension, hyperbilirubinemia (positive), the serum calcium level, and phenytoin use (negative). In the multiple regression analysis, after controlling for the cisplatin dose per course and the time from the last treatment to death, only concurrent metoclopramide and phenytoin use entered the model. The hydration volume did not affect corrected kidney-cortex or kidney-medulla platinum concentrations. The following conclusions were reached: (1) it may be feasible to use lower hydration volumes than those used routinely, (2) any effect of hydration volume on cisplatin nephrotoxicity may not be mediated via a reduction in kidney-cortex platinum concentrations, (3) higher cisplatin doses might be tolerated with new 5-hydroxytryptamine-3 (5HT-3) antiemetics than were tolerated with metoclopramide, and (4) phenytoin should be tested for its ability to reduce cisplatin nephrotoxicity.

Purpose: Since doxorubicin causes cardiotoxicity, we wished to assess relative concentrations of doxorubicin and its metabolites in cardiac tissues of patients who had been treated antemortem. We also wished to determine factors that correlate with human cardiac doxorubicin and doxorubicinol concentrations., Patients and Methods: Autopsy tissues were collected from 35 patients who had received doxorubicin at any time antemortem, and were assayed by high pressure liquid chromatography., Results: The major species found in human autopsy cardiac tissues were doxorubicinol (median concentration 92 ng/g, range 0 to 484 ng/g), and doxorubicin (median 58 ng/g, range 0-1665 ng/g). Other doxorubicin metabolites were detected in cardiac tissues in < half the patients. Of ten organs studied, heart ranked fifth with respect to median doxorubicin concentration and ranked fourth with respect to median doxorubicinol concentration. By multiple stepwise regression analysis, factors most closely associated with cardiac doxorubicin concentrations were time from last treatment divided by dose intensity, serum total protein, albumin, and hemoglobin (negative correlations). Factors most closely associated with cardiac doxorubicinol concentrations were cumulative doxorubicin dose, total protein, hemoglobin, and uric acid (positive associations), and respiratory rate (negative association). The physiologic significance of these associations (if any) is uncertain. By paired t-tests, cardiac doxorubicin and doxorubicinol concentrations were significantly (p < 0.05) higher than concentrations in skeletal muscle and smooth muscle organs., Conclusions: Overall, the results suggest that the much greater tendency to develop doxorubicin toxicity in heart than in other types of muscle may be due to a propensity of cardiac muscle to accumulate doxorubicin. The results also suggest that doxorubicinol may play a role in doxorubicin cardiac toxicity, and that doxorubicin may be gradually converted to doxorubicinol in human tissues.

Autopsy tissues were collected from ten patients who had received etoposide, 150-3480 mg, from 1 to 412 days antemortem and from five patients who had received teniposide, 234-1577 mg, from 3 to 52 days antemortem. Tissues were assayed for etoposide and teniposide using high-pressure liquid chromatography with electrochemical detection. Etoposide was detectable in tissues of three of four patients dying < 5 days after their last etoposide treatments to cumulative doses of 150-432 (median, 280) mg but was detectable in tissues of only one of six patients dying 7-412 (median, 37) days after their last etoposide treatment to a cumulative dose of 607-3600 (median, 1553) mg. The highest tissue concentrations were in the small bowel, prostate, thyroid, bladder, spleen, and testicle. Intermediate concentrations were found in the lymph node, skeletal muscle, adrenal gland, stomach, tumor, liver, lung, pancreas, and kidney, and the lowest concentrations were found in the heart, brain, diaphragm, vagina, and esophagus. Teniposide was detectable in one patient dying 3 days after a cumulative teniposide dose of 576 mg (spleen, prostate, heart > large bowel, liver, pancreas > thyroid, adrenal, stomach, small bowel, bladder, testicle, and skeletal muscle) but was not detectable in any tissue from four patients dying 5-52 (median, 8) days after their last treatment to a cumulative teniposide dose of 234-1577 (median, 520) mg. The very short tissue half-life contrasts with our previous observations for human autopsy tissue concentrations of mitoxantrone, doxorubicin, menogaril metabolites, diaziquone, and amsacrine. The short tissue half-life may help explain the schedule dependency of epipodophyllotoxin efficacy and may also help explain the lack of visceral toxicity of these compounds.

The radial motor nerve fibers were studied in 30 subjects using a technique of surface stimulation in the axilla and the antecubital fossa. Surface recording over the extensor digitorum communis 8cm from the distal stimulation site was done. Mean distal latency was 2.6msec (SD = 0.44), amplitude 11.24mV (SD = 3.5), and conduction velocity 68m/sec (SD = 7.0). Side-to-side comparison using the t-test demonstrated no significant differences. Five subjects were tested 75 more times on two successive days and showed a variation in latency of 0.2msec or less in 74 of 75 trials. Amplitude was consistent during each day's trial, but it varied slightly from one day to the next. Three case reports show the usefulness of the procedure.

Because of its location in the antecubital fossa, the lateral cutaneous nerve of the forearm is at risk of injury when a person is carrying objects with the forearm flexed or during venipuncture. Injury to this nerve, however, is rarely reported. A case report of traumatic injury to the lateral cutaneous nerve, the use of appropriate nerve conduction studies for diagnosis, and a discussion of the available literature is presented.

Of 50 normal subjects, 23 (46%) had at least one false positive electrodiagnostic test for carpal tunnel syndrome (CTS). There were 30% of the subjects who exhibited an abnormal median to ulnar sensory amplitude ratio of less than 1.1. In 7 subjects 8 extremities (14%) revealed prolonged residual latencies, and 4 extremities in 4 subjects (8%) had a difference of 0.4 msec between the median and ulnar palmar sensory latencies. The results of this study indicate that certain reported criteria for CTS are abnormal in a high percentage of normal subjects, thereby making them of limited value in the diagnosis of CTS. Of all the criteria studied, it appears that the comparison of the median to ulnar sensory latency across the carpal tunnel is of greatest potential value. However, even here a more conservative difference of 0.5 msec between median and ulnar nerves must be used to avoid false positive tests for CTS.

A nerve conduction method is demonstrated for cranial nerve XII, the hypoglossal nerve. Submandibular surface stimulation is performed while recording over the anterior surface of the tongue. There were 30 normal adult subjects and 60 hypoglossal nerves studied. Evoked response parameters are reported as follows: mean latency 2.2 +/- 0.4 msec, mean amplitude 3.8 +/- 1.6 mV (baseline to peak, best of 5 responses). This nerve conduction method is reliable and should expand the electrophysiological assessment of XII cranial nerve motor function.