Uncoupling neurogenic gene networks in the Drosophila embryo.

The EGF signaling pathway specifies neuronal identities in the Drosophila embryo by regulating developmental patterning genes such as intermediate neuroblasts defective (ind). EGFR is activated in the ventral midline and neurogenic ectoderm by the Spitz ligand, which is processed by the Rhomboid protease. CRISPR/Cas9 was used to delete defined rhomboid enhancers mediating expression at each site of Spitz processing. Surprisingly, the neurogenic ectoderm, not the ventral midline, was found to be the dominant source of EGF patterning activity. We suggest that Drosophila is undergoing an evolutionary transition in central nervous system (CNS)-organizing activity from the ventral midline to the neurogenic ectoderm.

Model-Informed Clinical Practice - Determining an Appropriate Ampicillin-Sulbactam Redosing Regimen in Surgical Patients by Utilizing Population Pharmacokinetics and Target Attainment Analysis.

In the current study, population pharmacokinetic (PK) of ampicillin-sulbactam was performed based on the clinical pharmacokinetics data collected from a prospective study conducted in 40 surgical patients undergoing prolonged surgery where antibiotic redosing was implemented. A population PK model was successfully developed to characterize the disposition of ampicillin and sulbactam. The final models were two-compartment models for both drugs, with creatinine clearance and heart failure affecting clearance and body surface area having an impact on the central volume of distribution of both ampicillin and sulbactam. Comprehensive Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of 24 different redosing scenarios. Simulation results indicated that the ampicillin-sulbactam 2-h redosing scheme recommended by ASHP guidelines is likely too conservative given that 3-g dose (2-g ampicillin/1-g sulbactam) with 4-h redosing interval can reach the breakpoint of 2 mg/L for ampicillin in all populations even with the aggressive pharmacokinetic/pharmacodynamic (PK/PD) target of 100% fT > MIC. With the target 50% fT > MIC, all redosing schemes evaluated, including the 8-h redosing scenario, are predicted to be able to reach the breakpoint of 64 mg/L in all patients. According to our findings, redosing of ampicillin-sulbactam should be every 4 h instead of the currently recommended 2-h redosing schedule. Our PTA results should inform future updates to existing general antibiotic redosing guidelines; and, when used in combination with the availability of institution- and/or unit-specific ampicillin susceptibility patterns, our PTA results may be used to customize SSI prophylaxis redosing recommendations for ampicillin-sulbactam at individual hospitals.

HOX and PBX gene dysregulation as a therapeutic target in glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common high-grade malignant brain tumour in adults and arises from the glial cells in the brain. The prognosis of treated GBM remains very poor with 5-year survival rates of 5%, a figure which has not improved over the last few decades. Currently, there is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. HOX gene dysregulation is now a widely recognised feature of many malignancies. METHODS: In this study we have focused on HOX gene dysregulation in GBM as a potential therapeutic target in a disease with high unmet need. RESULTS: We show significant dysregulation of these developmentally crucial genes and specifically that HOX genes A9, A10, C4 and D9 are strong candidates for biomarkers and treatment targets for GBM and GBM cancer stem cells. We evaluated a next generation therapeutic peptide, HTL-001, capable of targeting HOX gene over-expression in GBM by disrupting the interaction between HOX proteins and their co-factor, PBX. HTL-001 induced both caspase-dependent and -independent apoptosis in GBM cell lines. CONCLUSION: In vivo biodistribution studies confirmed that the peptide was able to cross the blood brain barrier. Systemic delivery of HTL-001 resulted in improved control of subcutaneous murine and human xenograft tumours and improved survival in a murine orthotopic model.

Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009-2011: a randomized controlled trial and brief review.

BACKGROUND: Anti-malarial resistance remains an important public health challenge in Cambodia. The effectiveness of three therapies for uncomplicated falciparum malaria was evaluated in Oddar Meanchey province in Northern Cambodia from 2009 to 2011. METHODS: In this randomized, open-label, parallel group-controlled trial, 211 subjects at least 5 years old with uncomplicated falciparum malaria were treated with 3 days of directly observed therapy: 63 received artesunate-mefloquine (AS/MQ), 77 received dihydroartemisinin-piperaquine (DHA/PPQ), and 71 received atovaquone-proguanil (ATQ/PG). The subjects were followed for 42 days or until recurrent parasitaemia. Genotyping of msp1, msp2, and glurp among individual parasite isolates distinguished recrudescence from reinfection. Pfmdr1 copy number was measured by real-time PCR and half-maximal parasite inhibitory concentrations (IC50) were measured in vitro by 48-h isotopic hypoxanthine incorporation assay. RESULTS: The per-protocol PCR-adjusted efficacy (95% confidence interval) at 42 days was 80.6% (70.8-90.5%) for AS/MQ, 97.2% (93.3-100%) for DHA/PPQ, and 92.9% (86.1-99.6%) for ATQ/PG. On day 3, 57.9% remained parasitaemic in the AS/MQ and DHA/PPQ arms. At baseline, 46.9% had microscopic Plasmodium falciparum gametocytaemia. Both recurrences in the DHA/PPQ arm lost Pfmdr1 copy number amplification at recrudescence. All four recurrences in the ATQ/PG arm were wild-type for cytochrome bc1. One subject withdrew from the ATQ/PG arm due to drug allergy. CONCLUSIONS: This study was conducted at the epicentre of substantial multi-drug resistance that emerged soon thereafter. Occurring early in the national transition from AS/MQ to DHA/PPQ, both DHA/PPQ and ATQ/PG had acceptable efficacy against uncomplicated falciparum malaria. However, efficacy of AS/MQ was only 80% with apparent mefloquine resistance based on elevated Pfmdr1 copy number and IC50. By 2009, there was already significant evidence of artemisinin resistance not previously reported at the Northern Cambodia-Thai border. This study suggests the basis for early development of significant DHA/PPQ failures within 3 years of introduction. Artemisinin resistance likely occurred on the Northern border concurrently with that reported along the Western border in Pailin. Trial registration This legacy trial was conducted prior to International Committee of Medical Journal Editors' requirements for preregistration on ClinicalTrials.gov. The full protocol has been provided.

Soil Heating in Fire (SheFire): A model and measurement method for estimating soil heating and effects during wildland fires.

Fire has transformative effects on soil biological, chemical, and physical properties in terrestrial ecosystems around the world. While methods for estimating fire characteristics and associated effects aboveground have progressed in recent decades, there remain major challenges in characterizing soil heating and associated effects belowground. Overcoming these challenges is crucial for understanding how fire influences soil carbon storage, biogeochemical cycling, and ecosystem recovery. In this paper, we present a novel framework for characterizing belowground heating and effects. The framework includes (1) an open-source model to estimate fire-driven soil heating, cooling, and the biotic effects of heating across depths and over time (Soil Heating in Fire model; SheFire) and (2) a simple field method for recording soil temperatures at multiple depths using self-contained temperature sensor and data loggers (i.e., iButtons), installed along a wooden stake inserted into the soil (i.e., an iStake). The iStake overcomes many logistical challenges associated with obtaining temperature profiles using thermocouples. Heating measurements provide inputs to the SheFire model, and modeled soil heating can then be used to derive ecosystem response functions, such as heating effects on microorganisms and tissues. To validate SheFire estimates, we conducted a burn table experiment using iStakes to record temperatures that were in turn used to fit the SheFire model. We then compared SheFire predicted temperatures against measured temperatures at other soil depths. To benchmark iStake measurements against those recorded by thermocouples, we co-located both types of sensors in the burn table experiment. We found that SheFire demonstrated skill in interpolating and extrapolating soil temperatures, with the largest errors occurring at the shallowest depths. We also found that iButton sensors are comparable to thermocouples for recording soil temperatures during fires. Finally, we present a case study using iStakes and SheFire to estimate in situ soil heating during a prescribed fire and demonstrate how observed heating regimes would influence seed and tree root vascular cambium survival at different soil depths. This measurement-modeling framework provides a cutting-edge approach for describing soil temperature regimes (i.e., soil heating) through a soil profile and predicting biological responses.

Immune Signature Against Plasmodium falciparum Antigens Predicts Clinical Immunity in Distinct Malaria Endemic Communities.

A large body of evidence supports the role of antibodies directed against the Plasmodium spp. parasite in the development of naturally acquired immunity to malaria, however an antigen signature capable of predicting protective immunity against Plasmodium remains to be identified. Key challenges for the identification of a predictive immune signature include the high dimensionality of data produced by high-throughput technologies and the limitation of standard statistical tests in accounting for synergetic interactions between immune responses to multiple targets. In this study, using samples collected from young children in Ghana at multiple time points during a longitudinal study, we adapted a predictive modeling framework which combines feature selection and machine learning techniques to identify an antigen signature of clinical immunity to malaria. Our results show that an individual's immune status can be accurately predicted by measuring antibody responses to a small defined set of 15 target antigens. We further demonstrate that the identified immune signature is highly versatile and capable of providing precise and accurate estimates of clinical protection from malaria in an independent geographic community. Our findings pave the way for the development of a robust point-of-care test to identify individuals at high risk of disease and which could be applied to monitor the impact of vaccinations and other interventions. This approach could be also translated to biomarker discovery for other infectious diseases.

Prosopis glandulosa persistence is facilitated by differential protection of buds during low- and high-energy fires.

Rangelands worldwide have experienced significant shifts from grass-dominated to woody-plant dominated states over the past century. In North America, these shifts are largely driven by overgrazing and landscape-scale fire suppression. Such shifts reduce productivity for livestock, can have broad-scale impacts to biodiversity, and are often difficult to reverse. Restoring grass dominance often involves restoring fire as an ecological process. However, many resprouting woody plants persist following disturbance, including fire, by resprouting from protected buds, rendering fire ineffective for reducing resprouting woody plant density. Recent research has shown that extreme fire (high-energy fires during periods of water stress) may reduce resprouting capacity. This previous research did not examine whether high-energy fires alone would be sufficient to cause mortality. We created an experimental framework for assessing the "buds-protection-resources" hypothesis of resprouting persistence under different fire energies. In July-August 2018 we exposed 48 individuals of a dominant resprouting woody plant in the region, honey mesquite (Prosopis glandulosa), to two levels of fire energy (high and low) and root crown exposure (exposed vs unexposed) and evaluated resprouting capacity. We censused basal and epicormic resprouts for two years following treatment. Water stress was moderate for several months leading up to fires but low in subsequent years. Epicormic and basal buds were somewhat protected from low- and high-energy fire. However, epicormic buds were protected in very few mesquites subjected to high-energy fires. High-energy fires decreased survival, caused loss of apical dominance, and left residual dead stems, which may increase chances of mortality from future fires. Basal resprout numbers were reduced by high-energy fires, which may have additional implications for long-term mesquite survival. While the buds, protection, and resources components of resprouter persistence all played a role in resprouting, high-energy fire decreased mesquite survival and reduced resprouting. This suggests that high-energy fires affect persistence mechanisms to different extents than low-energy fires. In addition, high-energy fires during normal rainfall can have negative impacts on resprouting capacity; water stress is not a necessary precursor to honey mesquite mortality from high-energy fire.

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus.

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called "heteroallelic". The donor's particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.

Even "WISE-R?"-an Update on the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation.

PURPOSE OF REVIEW: For over 20 years, the Women's Ischemia Syndrome Evaluation (WISE), a program sponsored by the National Heart, Lung, and Blood Institute, has explored diverse and important aspects of ischemic heart disease in women. RECENT FINDINGS: Women with symptoms and signs of ischemia but no significant epicardial obstructive coronary artery disease (INOCA) were documented to be at elevated risk for recurrent angina hospitalization, major adverse cardiac events, death, and health resource consumption rivaling those with obstructive coronary disease. WISE investigators have advanced our understanding of cardiovascular outcomes, systemic manifestations, psychological variables, socioeconomic factors, genetic contributions, hormonal status, advanced imaging, coronary functional findings, biomarkers, patient-reported outcomes, and treatments pertaining to women with this disease entity. This review delves into the WISE findings subsequent to a prior review1, postulates directions for future research, and asks are we "Even 'WISE-R?'".

A molecular marker of artemisinin-resistant Plasmodium falciparum malaria.

Plasmodium falciparum resistance to artemisinin derivatives in southeast Asia threatens malaria control and elimination activities worldwide. To monitor the spread of artemisinin resistance, a molecular marker is urgently needed. Here, using whole-genome sequencing of an artemisinin-resistant parasite line from Africa and clinical parasite isolates from Cambodia, we associate mutations in the PF3D7_1343700 kelch propeller domain ('K13-propeller') with artemisinin resistance in vitro and in vivo. Mutant K13-propeller alleles cluster in Cambodian provinces where resistance is prevalent, and the increasing frequency of a dominant mutant K13-propeller allele correlates with the recent spread of resistance in western Cambodia. Strong correlations between the presence of a mutant allele, in vitro parasite survival rates and in vivo parasite clearance rates indicate that K13-propeller mutations are important determinants of artemisinin resistance. K13-propeller polymorphism constitutes a useful molecular marker for large-scale surveillance efforts to contain artemisinin resistance in the Greater Mekong Subregion and prevent its global spread.

The Emerging Role of Radiomics in COPD and Lung Cancer.

Medical imaging plays a key role in evaluating and monitoring lung diseases such as chronic obstructive pulmonary disease (COPD) and lung cancer. The application of artificial intelligence in medical imaging has transformed medical images into mineable data, by extracting and correlating quantitative imaging features with patients' outcomes and tumor phenotype - a process termed radiomics. While this process has already been widely researched in lung oncology, the evaluation of COPD in this fashion remains in its infancy. Here we outline the main applications of radiomics in lung cancer and briefly review the workflow from image acquisition to the evaluation of model performance. Finally, we discuss the current assessments of COPD and the potential application of radiomics in COPD.

Haplotype block analysis of an Argentinean hexaploid wheat collection and GWAS for yield components and adaptation.

BACKGROUND: Increasing wheat (Triticum aestivum L.) production is required to feed a growing human population. In order to accomplish this task a deeper understanding of the genetic structure of cultivated wheats and the detection of genomic regions significantly associated with the regulation of important agronomic traits are necessary steps. To better understand the genetic basis and relationships of adaptation and yield related traits, we used a collection of 102 Argentinean hexaploid wheat cultivars genotyped with the 35k SNPs array, grown from two to six years in three different locations. Based on SNPs data and gene-related molecular markers, we performed a haplotype block characterization of the germplasm and a genome-wide association study (GWAS). RESULTS: The genetic structure of the collection revealed four subpopulations, reflecting the origin of the germplasm used by the main breeding programs in Argentina. The haplotype block characterization showed 1268 blocks of different sizes spread along the genome, including highly conserved regions like the 1BS chromosome arm where the 1BL/1RS wheat/rye translocation is located. Based on GWAS we identified ninety-seven chromosome regions associated with heading date, plant height, thousand grain weight, grain number per spike and fruiting efficiency at harvest (FEh). In particular FEh stands out as a promising trait to raise yield potential in Argentinean wheats; we detected fifteen haplotypes/markers associated with increased FEh values, eleven of which showed significant effects in all three evaluated locations. In the case of adaptation, the Ppd-D1 gene is consolidated as the main determinant of the life cycle of Argentinean wheat cultivars. CONCLUSION: This work reveals the genetic structure of the Argentinean hexaploid wheat germplasm using a wide set of molecular markers anchored to the Ref Seq v1.0. Additionally GWAS detects chromosomal regions (haplotypes) associated with important yield and adaptation components that will allow improvement of these traits through marker-assisted selection.

Coerced resilience in fire management.

Mechanisms underlying the loss of ecological resilience and a shift to an alternate regime with lower ecosystem service provisioning continues to be a leading debate in ecology, particularly in cases where evidence points to human actions and decision-making as the primary drivers of resilience loss and regime change. In this paper, we introduce the concept of coerced resilience as a way to explore the interplay among social power, ecological resilience, and fire management, and to better understand the unintended and undesired regime changes that often surprise ecosystem managers and governing officials. Philosophically, coercion is the opposite of freedom, and uses influence or force to gain compliance among local actors. The coercive force imposed by societal laws and policies can either enhance or reduce the potential to manage for essential structures and functions of ecological systems and, therefore, can greatly alter resilience. Using a classical fire-dependent regime shift from North America (tallgrass prairie to juniper woodland), and given that coercion is widespread in fire management today, we quantify relative differences in resilience that emerge in a policy-coerced fire system compared to a theoretical, policy-free fire system. Social coercion caused large departures in the fire conditions associated with alternative grassland and juniper woodland states, and the potential for a grassland state to emerge to dominance became increasingly untenable with fire as juniper cover increased. In contrast, both a treeless, grassland regime and a co-dominated grass-tree regime emerged across a wide range of fire conditions in the absence of policy controls. The severe coercive forcing present in fire management in the Great Plains, and corresponding erosion of grassland resilience, points to the need for transformative environmental governance and the rethinking of social power structures in modern fire policies.

Effects of Minimal Versus Intensive Intervention to Enhance Motivational Interviewing in HIV Care.

We conducted a randomized trial comparing the effect of two different levels of motivational interviewing training on clinician communication behaviors and patient experiences. We enrolled 12 HIV clinicians who attended a one-day MI workshop focusing on behavior change counseling skills. We then randomized clinicians to receive (or not) 3-5 rounds of personalized feedback from the MI trainer. We compared outcomes before and after the interventions and between the intervention groups. We tested time-by-study arm interactions to determine if one group improved more than the other. For all analyses, we used generalized estimating equations to account for clustering of patients within clinicians, with Gaussian or negative binomial distributions as appropriate. Patients of clinicians in both intervention groups rated their visits as more MI consistent (6.86 vs. 6.65, p = 0.005) and audio-recording analysis revealed that visits were more patient-centered (1.34 vs. 0.96, p = 0.003) with a more positive patient affect (22.36 vs. 20.84, p < 0.001) after versus before the intervention, without differences between intervention arms. Several specific clinician behaviors such as empathic statements, asking patient opinions and open-ended questions improved more in the workshop+feedback versus the workshop-only intervention arm. A few specific communication behaviors increased (total and complex reflections) after versus before the intervention, without differences between intervention arms. The workshop alone was as effective as the workshop plus feedback in improving patient experiences and overall communication measures. Certain communication behaviors improved more with the more intensive intervention, but these additional benefits may not warrant the extra financial and logistical resources required.

Health Literacy and Demographic Disparities in HIV Care Continuum Outcomes.

Studies evaluating the association between human immunodeficiency virus (HIV) infection continuum of care outcomes [antiretroviral (ART) adherence, retention in care, viral suppression] and health literacy have yielded conflicting results. Moreover, studies from the southern United States, a region of the country disproportionately affected by the HIV epidemic and low health literacy, are lacking. We conducted an observational cohort study among 575 people living with HIV (PLWH) at the Vanderbilt Comprehensive Care Clinic (Nashville, Tennessee). Health literacy was measured using the brief health literacy screen, a short tool which can be administered verbally by trained clinical personnel. Low health literacy was associated with a lack of viral suppression, but not with poor ART adherence or poor retention. Age and racial disparities in continuum of care outcomes persisted after accounting for health literacy, suggesting that factors in addition to health literacy must be addressed in order to improve outcomes for PLWH.

The relationship between adverse neighborhood socioeconomic context and HIV continuum of care outcomes in a diverse HIV clinic cohort in the Southern United States.

Retention in care and viral suppression are critical to delaying HIV progression and reducing transmission. Neighborhood socioeconomic context (NSEC) may affect HIV care receipt. We therefore assessed NSEC's impact on retention and viral suppression in a diverse HIV clinical cohort. HIV-positive adults with ≥1 visit at the Vanderbilt Comprehensive Care Clinic and 5-digit ZIP code tabulation area (ZCTA) information between 2008 and 2012 contributed. NSEC z-score indices used neighborhood-level socioeconomic indicators for poverty, education, labor-force participation, proportion of males, median age, and proportion of residents of black race by ZCTA. Retention was defined as ≥2 HIV care visits per calendar year, >90 days apart. Viral suppression was defined as an HIV-1 RNA <200 copies/mL at last measurement per calendar year. Modified Poisson regression was used to estimate risk ratios (RR) and 95% confidence intervals (CI). Among 2272 and 2541 adults included for retention and viral suppression analyses, respectively, median age and CD4 count at enrollment were approximately 38 (1st and 3rd quartile: 30, 44) years and 351 (176, 540) cells/µL, respectively, while 24% were female, and 39% were black. Across 243 ZCTAs, median NSEC z-score was 0.09 (-0.66, 0.48). Overall, 79% of person-time contributed was retained and 74% was virally suppressed. In adjusted models, NSEC was not associated with retention, though being in the 4th vs. 1st NSEC quartile was associated with lack of viral suppression (RR = 0.88; 95% CI: 0.80-0.97). Residing in the most adverse NSEC was associated with lack of viral suppression. Future studies are needed to confirm this finding.

A new algorithm to build bridges between two patient-reported health outcome instruments: the MOS SF-36® and the VR-12 Health Survey.

PURPOSE: To develop bridging algorithms to score the Veterans Rand-12 (VR-12) scales for comparability to those of the SF-36® for facilitating multi-cohort studies using data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) linked to Medicare Health Outcomes Survey (MHOS), and to provide a model for minimizing non-statistical error in pooled analyses stemming from changes to survey instruments over time. METHODS: Observational study of MHOS cohorts 1-12 (1998-2011). We modeled 2-year follow-up SF-36 scale scores from cohorts 1-6 based on baseline SF-36 scores, age, and gender, yielding 100 clusters using Classification and Regression Trees. Within each cluster, we averaged follow-up SF-36 scores. Using the same cluster specifications, expected follow-up SF-36 scores, based on cohorts 1-6, were computed for cohorts 7-8 (where the VR-12 was the follow-up survey). We created a new criterion validity measure, termed "extensibility," calculated from the square root of the mean square difference between expected SF-36 scale averages and observed VR-12 item score from cohorts 7-8, weighted by cluster size. VR-12 items were rescored to minimize this quantity. RESULTS: Extensibility of rescored VR-12 items and scales was considerably improved from the "simple" scoring method for comparability to the SF-36 scales. CONCLUSIONS: The algorithms are appropriate across a wide range of potential subsamples within the MHOS and provide robust application for future studies that span the SF-36 and VR-12 eras. It is possible that these surveys in a different setting outside the MHOS, especially in younger age groups, could produce somewhat different results.

Shrubland resilience varies across soil types: implications for operationalizing resilience in ecological restoration.

In ecosystems with alternative stable states, restoration success can be thought of as overcoming the resilience of an undesirable state to promote an alternative state that yields greater ecosystem services. Since greater resilience of undesirable states translates into reduced restoration potential, quantifying differences in resilience can enhance restoration planning. In the context of shrub-encroached rangeland restoration, shrubland resilience is the capacity of a woody vegetated state to absorb management interventions designed to produce a more desirable grass-dominated state, and remain within its current regime. Therefore, differences in the resilience of a state can be quantified in a relative sense by measuring whether a state switches to an alternate state following perturbation or remains in its current stability domain. Here we designed an experimental manipulation to assess the contribution of soils to differences in the relative resilience of a shrub-invaded state. In this large-scale experiment, we repeated perturbations across a gradient of soil textures to inform restoration practitioners of differences in the relative resilience of shrubland occurring on different soil types to common rangeland restoration practices. On each soil type, we compared the relative ability of the shrubland state to withstand chemical and mechanical brush control treatments, commonly employed in this study region, to untreated controls. While the shrubland community composition did not differ prior to the study, its capacity to absorb and recover from brush removal treatments depended on soil type. Shrubland resilience to chemical and mechanical brush removal was highest on coarse soils. On these soils, brush removal temporarily restored grassland dominance, but woody plants quickly regained pretreatment levels of dominance. However, shrublands on fine soils did not recover following treatments, continuing to be grass-dominated for the duration of the study. This study highlights a simple approach for prioritizing restoration actions by mapping the locations of different soil attributes that support shrub-dominated states with differing levels of resilience to brush control. This experimental approach provides a basis for operationalizing resilience in restoration and prioritizing management actions across a range of environmental conditions, which is critical given the economic constraints associated with broad-scale mechanical and chemical interventions for rangeland restoration.

Validation of a New Three-Item Self-Report Measure for Medication Adherence.

Few self-report measures of medication adherence have been rigorously developed and validated against electronic drug monitoring (EDM). Assess the validity of the 3-item self-report scale by comparing it with a contemporaneous EDM measure. We conducted an observational study in which adherence assessments were done monthly for up to 4 months for 81 patients with HIV who were taking antiretroviral medications. We report results for both HIV antiretroviral medications, and also for other, non-HIV-related medications. Raw and calibrated self-report adherence measures, electronic drug monitoring adherence measures, and sociodemographic variables. The mean age of patients was 46 years, 37 % were female, 49 % had some education beyond high school, 22 % were Black, and 22 % were Hispanic. Cronbach's alphas for the 3-item scale for HIV and non-HIV medications were 0.83 and 0.87, respectively. The mean differences (raw/uncalibrated self-report scale minus EDM) for HIV and non-HIV medications were 7.5 and 5.2 points on a 100-point scale (p < 0.05 for both). Pearson correlation coefficients between the calibrated 3-item scale and the EDM for HIV and non-HIV medications were 0.47 and 0.59, respectively. The c-statistics for the ROC curves for the calibrated scale, using cut-offs of 0.8 and 0.9 for the EDM gold standard measure to define non-adherence, were between 0.74 and 0.76 for HIV and non-HIV medications. This 3-item adherence self-report scale showed good psychometric characteristics and good construct validity when compared with an EDM standard, for both HIV and non-HIV medications. In clinical care it can be a useful first-stage screener for non-adherence. In clinical research and quality improvement settings it can be a useful tool when more complex and expensive methods such as EDM or pharmacy claims are impractical or unavailable.

Pore Water Collection, Analysis and Evolution: The Need for Standardization.

Investigating the ecological impacts of contaminants released into the environment requires integration of multiple lines of evidence. Collection and analysis of interstitial water is an often-used line of evidence for developing benthic exposure estimates in aquatic ecosystems. It is a well-established principle that chemical and toxicity data on interstitial water samples should represent in-situ conditions; i.e., sample integrity must be maintained throughout the sample collection process to avoid alteration of the in-situ geochemical conditions. Unfortunately, collection and processing of pore water is not standardized to address possible geochemical transformations introduced by atmospheric exposure. Furthermore, there are no suitable benchmarks (ecological or human health) against which to evaluate adverse effects from chemicals in pore water; i.e., empirical data is lacking on the toxicity of inorganic contaminants in sediment interstitial water. It is clear that pore water data is best evaluated by considering the bioavailability of trace elements and the partitioning of contaminants between the aqueous and solid phases. It is also evident that there is a need for sediment researchers and regulatory agencies to collaborate in developing a standardized approach for sediment/pore water collection and data evaluation. Without such guidelines, the number of different pore water collection and extraction techniques will continue to expand, and investigators will continue to evaluate potentially questionable data by comparison to inappropriate criteria.