A recently evolved transcriptional network controls biofilm development in Candida albicans.

A biofilm is an organized, resilient group of microbes in which individual cells acquire properties, such as drug resistance, that are distinct from those observed in suspension cultures. Here, we describe and analyze the transcriptional network controlling biofilm formation in the pathogenic yeast Candida albicans, whose biofilms are a major source of medical device-associated infections. We have combined genetic screens, genome-wide approaches, and two in vivo animal models to describe a master circuit controlling biofilm formation, composed of six transcription regulators that form a tightly woven network with ∼1,000 target genes. Evolutionary analysis indicates that the biofilm network has rapidly evolved: genes in the biofilm circuit are significantly weighted toward genes that arose relatively recently with ancient genes being underrepresented. This circuit provides a framework for understanding many aspects of biofilm formation by C. albicans in a mammalian host. It also provides insights into how complex cell behaviors can arise from the evolution of transcription circuits.

A viral mutualist employs posthatch transmission for vertical and horizontal spread among parasitoid wasps.

Heritable symbionts display a wide variety of transmission strategies to travel from one insect generation to the next. Parasitoid wasps, one of the most diverse insect groups, maintain several heritable associations with viruses that are beneficial for wasp survival during their development as parasites of other insects. Most of these beneficial viral entities are strictly transmitted through the wasp germline as endogenous viral elements within wasp genomes. However, a beneficial poxvirus inherited by Diachasmimorpha longicaudata wasps, known as Diachasmimorpha longicaudata entomopoxvirus (DlEPV), is not integrated into the wasp genome and therefore may employ different tactics to infect future wasp generations. Here, we demonstrated that transmission of DlEPV is primarily dependent on parasitoid wasps, since viral transmission within fruit fly hosts of the wasps was limited to injection of the virus directly into the larval fly body cavity. Additionally, we uncovered a previously undocumented form of posthatch transmission for a mutualistic virus that entails external acquisition and localization of the virus within the adult wasp venom gland. We showed that this route is extremely effective for vertical and horizontal transmission of the virus within D. longicaudata wasps. Furthermore, the beneficial phenotype provided by DlEPV during parasitism was also transmitted with perfect efficiency, indicating an effective mode of symbiont spread to the advantage of infected wasps. These results provide insight into the transmission of beneficial viruses among insects and indicate that viruses can share features with cellular microbes during their evolutionary transitions into symbionts.

Large ecosystem-scale effects of restoration fail to mitigate impacts of land-use legacies in longleaf pine savannas.

Ecological restoration is a global priority, with potential to reverse biodiversity declines and promote ecosystem functioning. Yet, successful restoration is challenged by lingering legacies of past land-use activities, which are pervasive on lands available for restoration. Although legacies can persist for centuries following cessation of human land uses such as agriculture, we currently lack understanding of how land-use legacies affect entire ecosystems, how they influence restoration outcomes, or whether restoration can mitigate legacy effects. Using a large-scale experiment, we evaluated how restoration by tree thinning and land-use legacies from prior cultivation and subsequent conversion to pine plantations affect fire-suppressed longleaf pine savannas. We evaluated 45 ecological properties across four categories: 1) abiotic attributes, 2) organism abundances, 3) species diversity, and 4) species interactions. The effects of restoration and land-use legacies were pervasive, shaping all categories of properties, with restoration effects roughly twice the magnitude of legacy effects. Restoration effects were of comparable magnitude in savannas with and without a history of intensive human land use; however, restoration did not mitigate numerous legacy effects present prior to restoration. As a result, savannas with a history of intensive human land use supported altered properties, especially related to soils, even after restoration. The signature of past human land-use activities can be remarkably persistent in the face of intensive restoration, influencing the outcome of restoration across diverse ecological properties. Understanding and mitigating land-use legacies will maximize the potential to restore degraded ecosystems.

Plasticity and repeatability in spring migration and parturition dates with implications for annual reproductive success.

In seasonal environments, animals should be adapted to match important life-history traits to when environmental conditions are optimal. Most animal populations therefore reproduce when resource abundance is highest to increase annual reproductive success. When facing variable, and changing, environments animals can display behavioural plasticity to acclimate to changing conditions. Behaviours can further be repeatable. For example, timing of behaviours and life history traits such as timing of reproduction may indicate phenotypic variation. Such variation may buffer animal populations against the consequences of variation and change. Our goal was to quantify plasticity and repeatability in migration and parturition timing in response to timing of snowmelt and green-up in a migratory herbivore (caribou, Rangifer tarandus, n = 132 ID-years) and their effect on reproductive success. We used behavioural reaction norms to quantify repeatability in timing of migration and timing of parturition in caribou and their plasticity to timing of spring events, while also quantifying phenotypic covariance between behavioural and life-history traits. Timing of migration for individual caribou was positively correlated with timing of snowmelt. The timing of parturition for individual caribou varied as a function of inter-annual variation in timing of snowmelt and green-up. Repeatability for migration timing was moderate, but low for timing of parturition. Plasticity did not affect reproductive success. We also did not detect any evidence of phenotypic covariance among any traits examined-timing of migration was not correlated with timing of parturition, and neither was there a correlation in the plasticity of these traits. Repeatability in migration timing suggests the possibility that the timing of migration in migratory herbivores could evolve if the repeatability detected in this study has a genetic or otherwise heritable basis, but observed plasticity may obviate the need for an evolutionary response. Our results also suggest that observed shifts in caribou parturition timing are due to plasticity as opposed to an evolutionary response to changing conditions. While this provides some evidence that populations may be buffered from the consequences of climate change via plasticity, a lack of repeatability in parturition timing could impede adaptation as warming increases.

Density-dependent plasticity in territoriality revealed using social network analysis.

Territories are typically defined as spatially exclusive areas that are defended against conspecifics. Given the spatial nature of territoriality, it is inherently density dependent, but the economics of territoriality also depend on the distribution and abundance of defended resources. Our objectives were to assess the effects of changing population density and food availability on individually based territorial phenotypes. We developed a novel analytical framework that bridges spatially explicit territories with social network analysis to model density-dependent territorial phenotypes. Using the outputs from our data pipeline, we modelled plasticity in territory size and territory intrusion rates in a long-term study population of North American red squirrels Tamiasciurus hudsonicus. Red squirrels defend year-round territories around a central hoard (midden) of white spruce Picea glauca cones. Importantly, white spruce is a masting species that produces large cone crops every 4-7 years (i.e. mast years) in our study area interspersed with non-mast years when few cones are produced. In the spring following mast years, populations are approximately double in size, but are lower in the spring of non-mast years. We predicted that territory size and intrusion rates would decrease as resource abundance, and consequently population density, increased. By contrast, as resource abundance decreased via depletion, and therefore density decreased, territories should increase in size and intrusions should also increase. As we expected, individual territory size and territorial intrusions were negatively density dependent, such that increased density after mast years resulted in smaller territories and fewer intrusions. When considering between-individual variation in plasticity across a density gradient, individuals responded differently to changes in population density within their lifetime. Our results show that territory size and intrusion rates display negative density dependence. When food becomes available in the autumn of a mast year and density in spring of the following year increases, territories shrink in size to effectively a small area around the midden. While our findings for red squirrels are unique compared to other systems, they serve as a reminder that the direction and strength of fundamental ecological relationships can depend on the nature of the system.

Bibliometric investigation of the integration of animal personality in conservation contexts.

Consistent individual differences in behavior, commonly termed animal personality, are a widespread phenomenon across taxa that have important consequences for fitness, natural selection, and trophic interactions. Animal personality research may prove useful in several conservation contexts, but which contexts remains to be determined. We conducted a structured literature review of 654 studies identified by combining search terms for animal personality and various conservation subfields. We scored the relevance of personality and conservation issues for each study to identify which studies meaningfully integrated the 2 fields as opposed to surface-level connections or vague allusions. We found a taxonomic bias toward mammals (29% of all studies). Very few amphibian or reptile studies applied personality research to conservation issues (6% each). Climate change (21%), invasive species (15%), and captive breeding and reintroduction (13%) were the most abundant conservation subfields that occurred in our search, though a substantial proportion of these papers weakly integrated conservation and animal personality (climate change 54%, invasive species 51%, captive breeding and reintroduction 40%). Based on our results, we recommend that researchers strive for consistent and broadly applicable terminology when describing consistent behavioral differences to minimize confusion and improve the searchability of research. We identify several gaps in the literature that appear to be promising and fruitful avenues for future research, such as disease transmission as a function of sociability or exploration as a driver of space use in protected areas. Practitioners can begin informing future conservation efforts with knowledge gained from animal personality research.

Investigación bibliométrica sobre la integración de la personalidad animal a los contextos de conservación Resumen Las diferencias individuales y constantes en el comportamiento, comúnmente llamadas personalidad animal, son un fenómeno generalizado en los taxones con consecuencias importantes para la aptitud, selección natural e interacciones tróficas. Las investigaciones sobre la personalidad animal pueden ser útiles en varios contextos de conservación, aunque falta determinar cuáles son estos contextos. Realizamos una revisión literaria estructurada de 654 estudios identificados mediante la combinación de los términos de búsqueda para la personalidad animal y varios subcampos de la conservación. Puntuamos la relevancia de la personalidad y los temas de conservación en cada estudio para identificar cuáles de estos integraron significativamente a ambos campos, contrario a las conexiones a nivel superficial o alusiones vagas. Descubrimos un sesgo taxonómico por los mamíferos (29% de todos los estudios). Pocos estudios enfocados en anfibios o reptiles aplicaron un estudio de personalidad a los temas de conservación (6% para cada uno). El cambio climático (21%), las especies invasoras (15%) y la reproducción en cautiverio y las reintroducciones (13%) fueron los subcampos de conservación más abundantes que aparecieron en nuestra búsqueda, aunque una proporción significativa de estos artículos integraron muy poco a la conservación y la personalidad animal (cambio climático 54%, especies invasoras 51%, reproducción en cautiverio y reintroducciones 40%). Con base en nuestros resultados, recomendamos que los investigadores procuren tener terminologías consistentes y de aplicación generalizada cuando describan las diferencias conductuales para así minimizar las confusiones y facilitar la búsqueda durante la investigación. Identificamos varios vacíos en la literatura que prometen ser vías fructíferas para las investigaciones en el futuro, como la transmisión de enfermedades como una función sociable o la exploración como un impulsor del uso del espacio en las áreas protegidas. Los practicantes pueden comenzar por guiar los siguientes esfuerzos de conservación con el conocimiento obtenido de las investigaciones sobre la personalidad animal.

Timing of Antiretroviral Therapy: Initiation and Birth Outcomes Among Pregnant Women With Human Immunodeficiency Virus in Tanzania

BACKGROUND: Combination antiretroviral therapy (cART) initiation during pregnancy reduces the risk of perinatal human immunodeficiency virus (HIV) transmission; however, studies have suggested that there may be unintended adverse consequences on birth outcomes for selected cART regimens. METHODS: We analyzed adverse birth outcomes among a prospective cohort of 1307 pregnant women with HIV in Dar es Salaam who initiated cART during the first or second trimester of a singleton pregnancy. Our primary analysis compared birth outcomes by gestational age at cART initiation among these women initiating cART in pregnancy. RESULTS: Among women who initiated cART in pregnancy, there was no relationship of gestational age at cART initiation with the risk of fetal death or stillbirth. However, women who initiated cART before 20 weeks of gestation compared with after 20 weeks had increased risk of preterm birth (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.03-1.67) but decreased risk of small-for-gestational age birth (RR, 0.71; 95% CI, .55-.93). CONCLUSIONS: With increasing use of cART preconception and early in pregnancy, clinicians should be aware of the benefits and potential risks of cART regimens to optimize birth outcomes.

Trends in opioid use following balloon kyphoplasty or vertebroplasty for the treatment of vertebral compression fractures.

This retrospective analysis of insurance claims evaluated real-world trends in prescription fills among patients treated with balloon kyphoplasty (N = 6,656) or vertebroplasty (N = 2,189) following diagnosis of vertebral compression fracture. Among those with evidence of opioid use, nearly half of patients discontinued or reduced prescription fills relative to pre-operative levels. INTRODUCTION: Vertebral compression fractures (VCF) are associated with debilitating pain, spinal misalignment, increased mortality, and increased healthcare-resource utilization in elderly patients. This study evaluated the effect of balloon kyphoplasty (BKP) or vertebroplasty (VP) on post-procedure opioid prescription fills and payer costs in patients with VCF. METHODS: This was a retrospective analysis of a large, nationally representative insurance-claims database. Clinical characteristics, opioid prescription patterns, and payer costs for subjects who underwent either BKP or VP to treat VCF were evaluated beginning 6 months prior to surgery through 7-month follow-up that included a 30-day, postoperative medication washout. Patient demographics, changes in opioid utilization, and payer costs were analyzed. RESULTS: A total of 8,845 patients met eligibility criteria (75.3% BKP and 24.7% VP) with a mean of age 77 and 74% female. Among the 75% of patients who used opioids, 48.7% of patients discontinued opioid medication and 8.4% reduced prescription fills versus preoperative baseline. Patients who reduced or discontinued prescriptions exhibited a decrease in all-cause payer costs relative to pre-intervention levels, which was a significantly greater change relative to patients with no change, increase, or new start of opioids. CONCLUSIONS: Interventional treatment for VCF was associated with decreased or discontinued opioid prescription fills and reduced payer costs in follow-up in a significant proportion of the study population. Reduction of opioid-based harms may represent a previously unrecognized benefit of vertebral augmentation for VCF, especially in this elderly and medically fragile population.

Social Effects on Annual Fitness in Red Squirrels.

When resources are limited, mean fitness is constrained and competition can cause genes and phenotypes to enhance an individual's own fitness while reducing the fitness of their competitors. Negative social effects on fitness have the potential to constrain adaptation, but the interplay between ecological opportunity and social constraints on adaptation remains poorly studied in nature. Here, we tested for evidence of phenotypic social effects on annual fitness (survival and reproductive success) in a long-term study of wild North American red squirrels (Tamiasciurus hudsonicus) under conditions of both resource limitation and super-abundant food resources. When resources were limited, populations remained stable or declined, and there were strong negative social effects on annual survival and reproductive success. That is, mean fitness was constrained and individuals had lower fitness when other nearby individuals had higher fitness. In contrast, when food resources were super-abundant, populations grew and social constraints on reproductive success were greatly reduced or eliminated. Unlike reproductive success, social constraints on survival were not significantly reduced when food resources were super-abundant. These findings suggest resource-dependent social constraints on a component of fitness, which have important potential implications for evolution and adaptation.

To mask or not to mask mosaicism? The impact of reporting embryo mosaicism on reproductive potential.

PURPOSE: To evaluate euploidy rates and probability of having at least one euploid embryo for transfer per cycle when mosaicism is reported compared to when it is masked. METHODS: Women age 18-46 years who underwent PGT-A with next generation sequencing of blastocyst biopsies were analyzed. When reported, mosaic embryos were classified as low-level, 20-40% mosaic, or high-level, 41-80% mosaic. When masked, low-level mosaics were categorized as euploid and high-level mosaics were considered aneuploid. Comparative analyses were performed with χ2 tests and t-tests. RESULTS: A total of 22,504 PGT-A biopsy cycles from 18,401 patients were included. These cycles were from 293 different clinics with a mean of 1.22 cycles per patient. The majority of cycles (94.8%) reported mosaicism, and only 5.2% cycles were masked. The euploidy rate was significantly lower when mosaicism was reported versus masked (38.7% v 47.4%, p < 0.0001), which remained significant for age 40 years old and younger. The mosaic reporting cohort was less likely to have at least one euploid embryo for transfer (68.8%) compared to the masked cohort (75.7%) (p < 0.0001); however, this was no longer significant after stratification by age. CONCLUSION: Mosaicism reporting shows an overall expected reduction in euploidy rate. In turn, the probability of having a euploid embryo to transfer depends on clinic transfer practices and patient preference. If mosaic embryos are not transferred, we observe a reduction in probability of having an embryo for transfer. Although the magnitude of these differences is small, our data show that mosaic reporting may contribute to embryo attrition rate.

The Critical Appraisal Tool for Anatomical Meta-analysis: A framework for critically appraising anatomical meta-analyses.

The hallmark of evidence-based medicine is the meta-analysis (MA). For much of its rich history, the field of anatomy has been dominated by descriptive, cadaveric studies. In the last two decades, quantitative measurements and statistical analyses have frequently accompanied such studies. These studies have directly led to the publication of anatomical MAs, which have ushered in the exciting field of evidence-based anatomy. Although critical appraisal tools exist for clinical MAs, none of them are specifically tailored for anatomical MAs. Therefore, the purpose of this article is to provide a framework by which clinical anatomists and others can critically appraise anatomical MAs using the Critical Appraisal Tool for Anatomical Meta-analysis (CATAM). Using a running example from a recently published MA, we show how to use the CATAM rubric in a step-by-step fashion. Each scored section of the CATAM rubric is summated into a total score (maximum 50 points). This score is then referenced to a conversion chart, which assigns a qualitative value to the MA in a range from "very good" to "poor." Future studies can investigate the interrater reliability of the instrument, and possibly subject the CATAM rubric to a Delphi panel. As anatomical MAs become more commonplace at surgical grand rounds and journal clubs in academic medical centers throughout the world, we hope that the CATAM rubric can help facilitate meaningful discussions about the quality and clinical relevance of anatomical MAs.

Mistletoes and their eucalypt hosts differ in the response of leaf functional traits to climatic moisture supply.

Trade-offs between photosynthesis and the costs of resource capture inform economic strategies of plants across environmental gradients and result in predictable variation in leaf traits. However, understudied functional groups like hemiparasites that involve dramatically different strategies for resource capture may have traits that deviate from expectations. We measured leaf traits related to gas exchange in mistletoes and their eucalypt hosts along a climatic gradient in relative moisture supply, measured as the ratio of precipitation to pan evaporation (P/Ep), in Victoria, Australia. We compared traits for mistletoes vs. hosts as functions of relative moisture supply and examined trait-trait correlations in both groups. Eucalypt leaf traits responded strongly to decreasing P/Ep, consistent with economic theory. Leaf area and specific leaf area (SLA) decreased along the P/Ep gradient, while C:N ratio, leaf thickness, N per area, and δ13C all increased. Mistletoes responded overall less strongly to P/Ep based on multivariate analyses; individual traits sometimes shifted in parallel with those of hosts, but SLA, leaf thickness, and N per area showed no significant change across the gradient. For mistletoes, leaf thickness was inversely related to leaf dry matter content (LDMC), with no relationship between SLA and mass-based N. In mistletoes, reduced costs of transpiration (reflecting their lack of roots) and abundant succulent leaf tissue help account for observed differences from their eucalypt hosts. Trait-based analysis of atypical functional types such as mistletoes help refine hypotheses based on plant economics and specialized adaptations to resource limitation.

Daily variation in sleep characteristics in individuals with and without post traumatic stress disorder.

BACKGROUND: Sleep disturbances are common in individuals with post traumatic stress disorder (PTSD). However, little is known about how daily variation in sleep characteristics is related to PTSD. This study examined the night-to-night and weekday versus weekend variation in sleep duration, sleep quality, trouble falling asleep, and difficulty staying asleep in individuals with and without PTSD. METHODS: Participants (N = 157; 80 with PTSD, 77 without PTSD) completed daily self-reports of their nighttime sleep characteristics for 15 consecutive days. Linear mixed models were used to examine the associations between the 7 days of the week and weekday versus weekend variation in sleep characteristics and PTSD. RESULTS: Individuals with PTSD reported shorter sleep duration, lower sleep quality, more trouble falling asleep, and more difficulty staying asleep than individuals without PTSD. The pattern of change across the week and between weekdays and weekends was different between those with and without PTSD for sleep quality and trouble falling asleep. Among those with PTSD, sleep duration, sleep quality, and trouble falling asleep differed across the 7 days of the week and showed differences between weekdays and weekends. For those without PTSD, only sleep duration differed across the 7 days of the week and showed differences between weekdays and weekends. Neither group showed 7 days of the week nor weekday versus weekend differences in difficulty staying asleep. CONCLUSIONS: On average those with PTSD had shorter sleep duration, poorer sleep quality, and greater trouble falling and staying asleep. In particular, the day of week variation in sleep quality and trouble falling asleep specifically distinguishes those with PTSD from those without PTSD. Our findings suggest that clinical care might be improved by assessments of sleep patterns and disturbances across at least a week, including weekdays and weekends. Future studies should explore the mechanisms related to the patterns of sleep disturbance among those with PTSD.

Crayfish (Cherax quadricarinatus) susceptibility to acute hepatopancreatic necrosis disease (AHPND).

Acute hepatopancreatic necrosis disease (AHPND) is an OIE-listed enteric disease that has continued to plague the shrimp aquaculture industry since its first discovery in 2009. AHPND is one of the biggest disease threats to the shrimp aquaculture industry along with white spot disease (WSD) which has severely impacted both crayfish and shrimp aquaculture. AHPND is caused by specific marine Vibrio spp. which carry plasmid-borne binary toxins PirAVp and PirBVp. This research investigated if crayfish are susceptible to AHPND-causing Vibrio parahaemolyticus (VpAHPND) to discern the potential risk that AHPND may pose to the crayfish aquaculture industry. Susceptibility was investigated by challenging Cherax quadricarinatus (Australian red claw crayfish) and Penaeus vannamei (Pacific white shrimp) with VpAHPND in a cohabitation immersion bioassay. Upon termination of the bioassay, crayfish survival was significantly higher than shrimp survival (87% vs. 33%). Hepatopancreas dissected from experimentally challenged animals were screened for the binary toxin genes pirAVp and pirBVp by real-time and duplex conventional PCR assays, and also were examined by H&E histology for the detection of characteristic AHPND pathology. Although AHPND toxin genes pirAVp and pirBVp were detected in a subset of crayfish samples, histopathology did not reveal any pathognomonic lesions that are characteristic of AHPND in any crayfish samples examined. These findings suggest that crayfish are likely resistant to AHPND.

Assessment of home care aides' respiratory exposure to total volatile organic compounds and chlorine during simulated bathroom cleaning: An experimental design with conventional and "green" products.

Home care (HC) aide visits to clients' homes often involve cleaning and disinfecting (C&D) bathrooms. Some ingredients in C&D household products are associated with respiratory illness, including sodium hypochlorite (bleach) and quaternary ammonium compounds (quats). "Green" products may be safer for the environment, however there are limited quantitative evaluations of their respiratory risks. This study assessed airborne concentrations and time profiles of total volatile organic compounds (TVOC) and chlorine generated during typical bathroom cleaning performed by aides using conventional and green products. Aides performed cleaning tasks in a simulated residential bathroom constructed in an environmental air sampling laboratory. A balanced experimental design involved each aide coming to the lab for four visits during which she performed two 20-min cleaning sessions using one of three C&D products (bleach-based, 1-5% sodium hypochlorite by weight; quats-based, 0.1-1% by weight quaternary ammonium compounds; and "green," 0.05% by weight thymol, a component of botanical thyme oil) or distilled water as a control. TVOC and chlorine direct reading instruments were attached to aides with sample inlets located in the breathing zone. Ten-second averages of TVOC and chlorine gas concentrations and instantaneous peak concentrations were recorded for the sessions' duration. TVOC concentrations by methods of C&D application (spraying, streaming, wiping) also were evaluated. The study completed 169 air sampling sessions with 22 aides. The quats-based product generated more than twice the average TVOC concentrations (mean = 1,210 ppb) than the bleach-based (mean = 593 ppb) or green (mean = 498 ppb) products. Each product generated TVOC concentrations that rose rapidly within the first few minutes of application. Spraying produced the highest TVOC exposures, wiping the lowest. Thirteen aides (65%) experienced peak chlorine exposures above the OSHA PEL ceiling limit (1 ppm) when using the bleach-based product. HC aides may experience respiratory hazards from use of conventional or green C&D products formulated with bleach or other respiratory irritants and sprayed in small, poorly ventilated spaces typical of bathrooms. Spraying should be avoided.

Geometry of the ideal free distribution: individual behavioural variation and annual reproductive success in aggregations of a social ungulate.

Variation in social environment can mitigate risks and rewards associated with occupying a particular patch. We aim to integrate Ideal Free Distribution (IFD) and Geometry of the Selfish Herd (GSH) to address an apparent conflict in their predictions of equal mean fitness between patches (IFD) and declining fitness benefits within a patch (GSH). We tested these hypotheses in a socio-spatial context using individual caribou that were aggregated or disaggregated during calving and varied in their annual reproductive success (ARS). We then tested individual consistency of these spatial tactics. We reveal that two socio-spatial tactics accorded similar mean ARS (IFD); however, ARS for aggregated individuals declined near the periphery (GSH). Individuals near the aggregation periphery exhibited flexibility, whereas others were consistent. The integration of classical theories through a contemporary lens of consistent individual differences provides evidence for an integrated GSH and IFD strategy that may represent an evolutionary stable state.

The Ecology of Individual Differences Empirically Applied to Space-Use and Movement Tactics.

Movement provides a link between individual behavioral ecology and the spatial and temporal variation in an individual's landscape. Individual variation in movement traits is an important axis of animal personality, particularly in the context of foraging ecology. We tested whether individual caribou (Rangifer tarandus) displayed plasticity in movement and space-use behavior across a gradient of resource aggregation. We quantified first-passage time and range-use ratio as proxies for movement-related foraging behavior and examined how these traits varied at the individual level across a foraging resource gradient. Our results suggest that individuals adjusted first-passage time but not range-use ratio to maximize access to high-quality foraging resources. First-passage time was repeatable, and intercepts for first-passage time and range-use ratio were negatively correlated. Individuals matched first-passage time but not range-use ratio to the expectations of our patch-use model that maximized access to foraging resources, a result that suggests that individuals acclimated their movement patterns to accommodate both intra- and interannual variation in foraging resources on the landscape. Collectively, we highlight repeatable movement and space-use tactics and provide insight into how individual plasticity in movement interacts with landscape processes to affect the distribution of behavioral phenotypes and potentially fitness and population dynamics.

Cost-effectiveness of balloon kyphoplasty and vertebroplasty versus conservative medical management in the USA.

The cost-effectiveness of surgical versus conservative medical management of vertebral compression fractures in the US was analyzed in the context of inpatient versus outpatient treatment. Surgical intervention (balloon kyphoplasty and vertebroplasty) was found to be cost-effective relative to conservative medical management at a US willingness-to-pay threshold. INTRODUCTION: To date, only one published study has evaluated the cost-effectiveness (C/E) of balloon kyphoplasty (BKP) or vertebroplasty (VP) in US Medicare patients with osteoporotic vertebral compression fractures. This study further evaluates the C/E of surgical treatment vs. conservative medical management (CMM), expanding on prior modeling by accounting for quality-adjusted life-years gained. METHODS: A Markov microsimulation model of 1000 patients was constructed. Cost data were based on an analysis of Medicare claims payments, with propensity-score matching performed for BKP and VP vs. controls (CMM). Mortality inputs were based on US life tables, modified to account for age at initial fracture, presence of subsequent fracture(s), and relative risk of mortality by treatment. Separate incremental cost-effectiveness ratios (ICERs) were calculated for BKP and VP in inpatient and outpatient surgical treatment locations to account for individual clinical profiles presenting to each. RESULTS: The discounted ICER for inpatient BKP vs. CMM was $43,455 per QALY gained; for outpatient BKP vs. CMM, $10,922; for inpatient VP vs. CMM, $39,774; and for outpatient VP vs. CMM, $12,293. Probabilistic sensitivity analysis confirmed that both BKP and VP would be considered C/E vs. CMM at a US willingness-to-pay (WTP) threshold of $50,000/QALY in 80% and 100% of 500 model simulations, respectively. The most sensitive parameters included quality of life estimates and hazard ratios for mortality. CONCLUSION: While VP and BKP are more expensive treatment options than CMM in the short term, model results suggest interventional treatment is cost-effective, among patients eligible for surgery, at a US WTP threshold. This conclusion supports those from economic analyses conducted in EU-member countries.

Perspectives from Young South African and Zimbabwean Women on Attributes of Four (Placebo) Vaginal Microbicide Delivery Forms.

INTRODUCTION: Incorporating end-user input into the design of new vaginal microbicides for women is key to optimizing their uptake, consistent use, and, ultimately, success in combatting the heterosexual HIV epidemic. METHODS: The Quatro Study assessed four placebo forms of vaginally inserted HIV-microbicides among young microbicide-naïve African women: on-demand film, insert and gel, and monthly ring. Participants randomly used each product for 1 month and provided product satisfaction ratings (1-5 scale), and opinions on product attributes and potential alternative designs. Qualitative data were collected through focus group discussions at study exit. Multivariable associations between attribute opinions and overall product rating were examined using Poisson regression models with robust standard errors to assess the attributes most influential to satisfaction. RESULTS: Overall opinions of products and their individual attributes were generally positive; all products were rated either 4 or a 5 by ≥ 50% of participants. Attributes related to ease of use and interference with normal activities were the most salient predictors of satisfaction. Preferences for duration of use tended toward relatively shorter use periods for the ring (i.e., 1-3 months vs. 12 months) and for coitally independent dosing for the on-demand products. CONCLUSIONS: How well a product fit in with participants' lifestyles was important to their overall satisfaction. For on-demand products, greater flexibility around timing of use was desired, to avoid coital dependency of the dosing.

Is neoadjuvant chemoradiotherapy sufficient in patients with advanced rectal malignancy and positive extra-mesorectal lateral lymph nodes?

AIM: There is current debate about the optimal management of lateral pelvic lymph nodes (LPLNs) in rectal cancer between Western and Eastern centres. This paper aims to report the rate of histologically proven positive LPLNs in a group of patients undergoing the conventional Western approach to primary and recurrent rectal cancer. METHOD: A retrospective cohort review of all patients who underwent LPLN dissection at Royal Prince Alfred Hospital in Sydney, Australia. This included patients who underwent pelvic exenteration who had LPLNs excised either en bloc for laterally invasive or recurrent tumours or as part of selective node dissection for suspicious lymph nodes on preoperative imaging. Histopathological results for these patients were compared with node status at preoperative imaging. RESULTS: Seventy-one patients satisfied the inclusion criteria. Of those patients with positive nodes on histology, 27% (9/33) with radiologically positive LPLNs were treated with preoperative radiotherapy and 75% (9/12) with radiologically positive LPLNs were not treated with preoperative radiotherapy (P = 0.004). None of the 12 patients with radiologically negative nodes treated with radiotherapy had positive nodes; 25% (3/12) of the patients with radiologically negative nodes who were not treated with radiotherapy had positive nodes. Fifty-three per cent of patients developed postoperative complications. CONCLUSION: Our study suggests that in patients with radiologically positive LPLNs chemoradiotherapy may not be enough to sterilize these extra-mesorectal lymph nodes as a large proportion (27%) will have residual viable adenocarcinoma cells. In patients with radiologically negative LPLNs, however, the addition of chemoradiotherapy may serve to adequately sterilize these lymph nodes without the need for prophylactic LPLN dissection.