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Despite recent advances in radiotherapeutic strategies, acquired resistance remains a major obstacle, leading to tumor recurrence for many patients. Once thought to be a strictly cancer cell intrinsic property, it is becoming increasingly clear that treatment-resistance is driven in part by complex interactions between cancer cells and non-transformed cells of the tumor microenvironment. Herein, we report that radiotherapy induces the production of extracellular vesicles by breast cancer cells capable of stimulating tumor-supporting fibroblast activity, facilitating tumor survival and promoting cancer stem-like cell expansion. This pro-tumor activity was associated with fibroblast production of the paracrine signaling factor IL-6 and was dependent on the expression of the heparan sulfate proteoglycan CD44v3 on the vesicle surface. Enzymatic removal or pharmaceutical inhibition of its heparan sulfate side chains disrupted this tumor-fibroblast crosstalk. Additionally, we show that the radiation-induced production of CD44v3+ vesicles is effectively silenced by blocking the ESCRT pathway using a soluble pharmacological inhibitor of MDA-9/Syntenin/SDCBP PDZ1 domain activity, PDZ1i. This population of vesicles was also detected in the sera of human patients undergoing radiotherapy, therefore representing a potential biomarker for radiation therapy and providing an opportunity for clinical intervention to improve treatment outcomes.

Imprime PGG (Imprime) is in late-stage clinical development as a combinatorial agent with several therapeutic modalities. Here we present pre-clinical mechanistic data supportive of Imprime, a soluble yeast β-1,3/1,6-glucan pathogen-associated molecular pattern able to prime innate immune cells in a Dectin-1dependent manner. In tumor-free mice, Imprime evoked broad innate immune responses (type I interferon signature, mobilization of myeloid cells, dendritic cell and monocyte/macrophage expression of co-stimulatory ligands like CD86, and activation of natural killer cells). Imprime-mediated activation of myeloid cells also resulted in functional priming of antigen-specific CD8 T cell response. In tumor-bearing mice, Imprime monotherapy further resulted in activation of systemic and tumor infiltrating macrophages and enhanced cytotoxic CD8 T cell trafficking. Imprime enhanced the anti-tumor activity of several combinatorial agents in mouse cancer models; anti-tyrosinase-related protein 1 antibody in B16F10 melanoma experimental lung metastasis model, anti-vascular endothelial growth factor receptor 2 antibody in H1299 and H441 lung cancer, and anti-programmed cell death protein 1 antibody in MC38 colon cancer models. Mechanistically, combining Imprime with these combinatorial therapeutic agents elicited enhanced innate immune activation, supporting immunological synergy. Finally, Imprime treatment induced similar in vitro phenotypic and functional activation of human innate immune cells. Collectively, these data demonstrate Imprime’s potential to orchestrate a broad, yet coordinated, anti-cancer immune response and complement existing cancer immunotherapies.

Did Frank Knight play a role in the formation of public choice theory? We argue that the dimensions of James Buchanan’s thought that form many of the core insights of public choice become clearer when seen against the work of his teacher, Frank Knight. Buchanan is demonstrative about his indebtedness to Knight; he terms him “my professor” and refers to his work frequently. Yet the upfront nature of this acknowledgement has perhaps served to short-circuit analysis as much as to stimulate it. Our analysis will center on Knight’s Intelligence and Democratic Action, a collection of lectures given in 1958 (published 1960), when he was invited by Buchanan to the University of Virginia. The lectures rehearse a number of ideas from other works, yet represent an intriguingly clear connection to ideas Buchanan would present over the coming two decades. In that sense, primarily through his influence on Buchanan, Knight can be seen as one of the largely unacknowledged forefathers of public choice theory.

BackgroundThe stigma of internet surfing is a relatively new area of study arising from the popularity of the internet. The Questionnaire on the Internal Stigma of Internet Surfing-9 (QISIS-9) was developed for the Chinese culture, so its suitability for use in other cultural contexts is uncertain. This paper examines the measurement invariance of the QISIS-9 among Sino-Australian undergraduates to verify the cross-cultural measurement invariance of QISIS-9 and promote cross-cultural (nationality) research regarding the internal stigma of internet surfing.MethodsThe Internal Stigma of Internet Surfing-9 (QISIS-9) was used to assess 200 Chinese undergraduates (50% female, Mage = 19.78) and 204 Australian undergraduates (76% female, Mage = 21.10), respectively.ResultsA confirmatory factor analysis (CFA) indicated that the single-factor model of QISIS-9 is acceptable with both Chinese and Australian undergraduates. However, the factor loading of Item 9, to which a reverse score is assigned, is not ideal for both samples. Thus, the item should be deleted. According to a multigroup confirmatory factor analysis (MCFA), QISIS-8, the revised version of QISIS-9, meets the strict measurement invariance among the Chinese and Australian participants. The QISIS-8 demonstrated appropriate internal consistency in the scores for both the Chinese and Australian undergraduates.ConclusionThe new QISIS-8 can effectively assess the internal stigma of internet surfing among Chinese and Australian undergraduates, and it provides a frame of reference for further cross-cultural (border) comparisons.

Self-specific CD8+T cells can escape clonal deletion, but the properties and capabilities of such cells in a physiological setting are unclear. We characterized polyclonal CD8+ T cells specific for the melanocyte antigen tyrosinase-related protein 2 (Trp2) in mice expressing or lacking this enzyme (due to deficiency in Dct, which encodes Trp2). Phenotypic and gene expression profiles of pre-immune Trp2/Kb-specific cells were similar; the size of this population was only slightly reduced in wild-type (WT) compared to Dct-deficient (Dct-/-) mice. Despite comparable initial responses to Trp2 immunization, WT Trp2/Kb-specific cells showed blunted expansion and less readily differentiated into a CD25+proliferative population. Functional self-tolerance clearly emerged when assessing immunopathology: adoptively transferred WT Trp2/Kb-specific cells mediated vitiligo much less efficiently. Hence, CD8+ T cell self-specificity is poorly predicted by precursor frequency, phenotype, or even initial responsiveness, while deficient activation-induced CD25 expression and other gene expression characteristics may help to identify functionally tolerant cells.

Simplification of stand structure of forests and woodlands through human-induced modification is a serious threat to biodiversity. Restoring lost habitat complexity and heterogeneity, such as woody debris, requires an understanding of the relationships between different elements that contribute to stand structure. In this study, we examine the structure and composition of a critically endangered box-gum grassy woodland in south-eastern Australia and relationships with woody debris loads. We found that: (1) despite modification by humans and differing susceptibility to dieback, the two dominant tree species, Blakeley's red gum, Eucalyptus blakelyi and yellow box, E. melliodora, occurred in similar proportions irrespective of vegetation density; (2) E. blakelyi had the largest number of stems and basal area, but while E. melliodora had fewer stems, it had a similar basal area to E. blakelyi. E. melliodora also showed fewer signs of dieback than E. blakelyi with between 40-50% trees in good condition compared to 2% for the latter species; (3) woody debris loads were low compared to other studies in woodland, but there were levels of heterogeneity indicating 'natural' accumulation was occurring; (4) tree basal area and woody debris loads had a 1:1 relationship across all sites and vegetation densities. Overall, our study indicated that ecosystem recovery was taking place (i.e. with many young trees), but there were fewer large trees that are known to supply most woody debris. Our findings highlight the slow accumulation of this critical resource because the volumes were lower than expected. Based on our results, we recommend: (1) aiming for approximately a 50:50 ratio of yellow box to Blakely's red gum basal area in woodland restoration projects; (2) to accelerate the recovery of woodland structure, addition of woody debris should be added at a minimum ratio of 1:1 to standing basal area (i.e. a basal area of 5.99 m2 requires a minimum volume of 3.11 m3) (3) managing for both volume and heterogeneity of woody debris loads; (4) preserving large diameter trees to harness proportionally higher woody debris and litter inputs.

BackgroundNew York City (NYC) bore the greatest burden of COVID-19 in the United States early in the pandemic. In this case series, we describe characteristics and outcomes of racially and ethnically diverse patients tested for and hospitalized with COVID-19 in New York City's public hospital system.MethodsWe reviewed the electronic health records of all patients who received a SARS-CoV-2 test between March 5 and April 9, 2020, with follow up through April 16, 2020. The primary outcomes were a positive test, hospitalization, and death. Demographics and comorbidities were also assessed.Results22254 patients were tested for SARS-CoV-2. 13442 (61%) were positive; among those, the median age was 52.7 years (interquartile range [IQR] 39.5-64.5), 7481 (56%) were male, 3518 (26%) were Black, and 4593 (34%) were Hispanic. Nearly half (4669, 46%) had at least one chronic disease (27% diabetes, 30% hypertension, and 21% cardiovascular disease). Of those testing positive, 6248 (46%) were hospitalized. The median age was 61.6 years (IQR 49.7-72.9); 3851 (62%) were male, 1950 (31%) were Black, and 2102 (34%) were Hispanic. More than half (3269, 53%) had at least one chronic disease (33% diabetes, 37% hypertension, 24% cardiovascular disease, 11% chronic kidney disease). 1724 (28%) hospitalized patients died. The median age was 71.0 years (IQR 60.0, 80.9); 1087 (63%) were male, 506 (29%) were Black, and 528 (31%) were Hispanic. Chronic diseases were common (35% diabetes, 37% hypertension, 28% cardiovascular disease, 15% chronic kidney disease). Male sex, older age, diabetes, cardiac history, and chronic kidney disease were significantly associated with testing positive, hospitalization, and death. Racial/ethnic disparities were observed across all outcomes.Conclusions and relevanceThis is the largest and most racially/ethnically diverse case series of patients tested and hospitalized for COVID-19 in New York City to date. Our findings highlight disparities in outcomes that can inform prevention and testing recommendations.

The eastern bettong (Bettongia gaimardi), a medium-sized digging marsupial, was reintroduced to a predator-free reserve after 100 years of absence from the Australian mainland. The bettong may have the potential to restore temperate woodlands degraded by a history of livestock grazing, by creating numerous small disturbances by digging. We investigated the digging capacity of the bettong and compared this to extant fauna, to answer the first key question of whether this species could be considered an ecosystem engineer, and ultimately if it has the capacity to restore lost ecological processes. We found that eastern bettongs were frequent diggers and, at a density of 0.3–0.4 animals ha−1, accounted for over half the total foraging pits observed (55%), with echidnas (Tachyglossus aculeatus), birds and feral rabbits (Oryctolagus cuniculus) accounting for the rest. We estimated that the population of bettongs present dug 985 kg of soil per ha per year in our study area. Bettongs dug more where available phosphorus was higher, where there was greater basal area of Acacia spp. and where kangaroo grazing was less. There was no effect on digging of eucalypt stem density or volume of logs on the ground. While bettong digging activity was more frequent under trees, digging also occurred in open grassland, and bettongs were the only species observed to dig in scalds (areas where topsoil has eroded to the B Horizon). These results highlight the potential for bettongs to enhance soil processes in a way not demonstrated by the existing fauna (native birds and echidna), and introduced rabbit.

Rajesh K Rajpal, Bryan Ross, Sachin D Rajpal, Khoa HoangSee Clearly Vision Group, McLean, VA, USAAbstract: Ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by clinicians to manage ocular inflammation and pain following cataract surgery. Over the past decade, the US Food and Drug Administration has approved multiple topical NSAIDs for these purposes, including several reformulated products. One of these medications, bromfenac ophthalmic solution, has a long and extensive history, with proven efficacy and safety in patients following cataract surgery. The evolution of bromfenac ophthalmic solution over the years has involved either lowering the concentration of the active ingredient or extending the dosing interval to improve patient adherence/compliance. This review will focus on the history and progression of bromfenac ophthalmic solution and report the available patient preference and adherence data regarding this ocular NSAID throughout its evolution.Keywords: cataract surgery, nonsteroidal anti-inflammatory drugs, COX inhibitors

Napapon Sailasuta, Kent Harris, Thao Tran, Brian RossClinical MR Unit, Huntington Medical Research Institutes, Pasadena, CA, USAAbstract: We applied 13C magnetic resonance spectroscopy (MRS), a nonradioactive, noninvasive brain imaging technique, to quantify the oxidation of [1-13C] acetate in a conventional clinical magnetic resonance imaging (MRI) scanner in five consecutive elderly subjects at various clinical stages of Alzheimer's disease (AD) progression. [1-13C] acetate entered the brain and was metabolized to [5-13C] glutamate and glutamine, as well as [1-13C] glutamate and glutamine, and the final glial oxidation product, 13C bicarbonate, at a linear rate. Calculation of the initial slope was similar in a single subject, examined twice, 1 month apart (test-re-test 8%). Mean rate of cerebral bicarbonate production in this elderly group was 0.040 ± 0.01 (n = 5). Assuming that the rate of conversion of acetate to bicarbonate is a reflection of glial metabolic rate and that glial metabolic rate is a surrogate marker for 'neuroinflammation', our preliminary results suggest that [1-13C] MRS may provide biomarkers for diseases, believed to involve microglia and other cells of the astrocyte series. Among these is AD, for which novel drugs which ameliorate the damaging effects of neuroinflammation before symptoms of dementia appear, are in advanced development. The value of 13C MRS as an early, noninvasive biomarker may lie in the conduct of cost-effective clinical trials.Keywords: Alzheimer's disease, noninvasive biomarker, glial activation

We present the first characterization of the spectral properties of superradiant light emitted from the ultranarrow, 1-mHz-linewidth optical clock transition in an ensemble of cold ^{87}Sr atoms. Such a light source has been proposed as a next-generation active atomic frequency reference, with the potential to enable high-precision optical frequency references to be used outside laboratory environments. By comparing the frequency of our superradiant source to that of a state-of-the-art cavity-stabilized laser and optical lattice clock, we observe a fractional Allan deviation of 6.7(1)×10^{-16} at 1 s of averaging, establish absolute accuracy at the 2-Hz (4×10^{-15} fractional frequency) level, and demonstrate insensitivity to key environmental perturbations.

The old Japanese Proverb states,” None of us are as smart as all of us.” In recent years, the educational system in the United States has been evolving from a largely centralized decision-making structure to a more decentralized one. This shift to school-based management requires fundamental changes to the organizational structure of the district as well as the roles within the organization. From administrators to parents, school based management demands a change in the "status quo" (Cotton, 1991). It involves shifting decision making from the central office administrators to that of local schools (Henkin, Cistone and Dee, 1999).

Ecogeographical rules help explain spatial and temporal patterns in intraspecific body size. However, many of these rules, when applied to ectothermic organisms such as reptiles, are controversial and require further investigation. To explore factors that influence body size in reptiles, we performed a heuristic study to examine body size variation in an Australian lizard, Boulenger's Skink Morethia boulengeri from agricultural landscapes in southern New South Wales, south-eastern Australia. We collected tissue and morphological data on 337 adult lizards across a broad elevation and climate gradient. We used a model-selection procedure to determine if environmental or ecological variables best explained body size variation. We explored the relationship between morphology and phylogenetic structure before modeling candidate variables from four broad domains: (1) geography (latitude, longitude and elevation), (2) climate (temperature and rainfall), (3) habitat (vegetation type, number of logs and ground cover attributes), and (4) management (land use and grazing history). Broad phylogenetic structure was evident, but on a scale larger than our study area. Lizards were sexually dimorphic, whereby females had longer snout-vent length than males, providing support for the fecundity selection hypothesis. Body size variation in M. boulengeri was correlated with temperature and rainfall, a pattern consistent with larger individuals occupying cooler and more productive parts of the landscape. Climate change forecasts, which predict warmer temperature and increased aridity, may result in reduced lizard biomass and decoupling of trophic interactions with potential implications for community organization and ecosystem function.

It is widely postulated that nutritional factors drive bottom-up, resource-based patterns in herbivore ecology and distribution. There is, however, much controversy over the roles of different plant constituents and how these influence individual herbivores and herbivore populations. The density of koala (Phascolarctos cinereus) populations varies widely and many attribute population trends to variation in the nutritional quality of the eucalypt leaves of their diet, but there is little evidence to support this hypothesis. We used a nested design that involved sampling of trees at two spatial scales to investigate how leaf chemistry influences free-living koalas from a low-density population in south east New South Wales, Australia. Using koala faecal pellets as a proxy for koala visitation to trees, we found an interaction between toxins and nutrients in leaves at a small spatial scale, whereby koalas preferred trees with leaves of higher concentrations of available nitrogen but lower concentrations of sideroxylonals (secondary metabolites found exclusively in eucalypts) compared to neighbouring trees of the same species. We argue that taxonomic and phenotypic diversity is likely to be important when foraging in habitats of low nutritional quality in providing diet choice to tradeoff nutrients and toxins and minimise movement costs. Our findings suggest that immediate nutritional concerns are an important priority of folivores in low-quality habitats and imply that nutritional limitations play an important role in constraining folivore populations. We show that, with a careful experimental design, it is possible to make inferences about populations of herbivores that exist at extremely low densities and thus achieve a better understanding about how plant composition influences herbivore ecology and persistence.

Human activities, particularly agriculture, have transformed much of the world's terrestrial environment. Within these anthropogenic landscapes, a variety of relictual and semi-natural habitats exist, which we term countryside elements. The habitat value of countryside elements (hereafter termed 'elements') is increasingly recognised. We quantify the relative value of four kinds of such 'elements' (linear roadside remnants, native vegetation patches, scattered trees and tree plantings) used by a threatened Australian arboreal marsupial, the squirrel glider (Petaurus norfolcensis). We examined relationships between home range size and the availability of each 'element' and whether the usage was relative to predicted levels of use. The use of 'elements' by gliders was largely explained by their availability, but there was a preference for native vegetation patches and scattered trees. We found home range size was significantly smaller with increasing area of scattered trees and a contrasting effect with increasing area of linear roadside remnants or native vegetation patches. Our work showed that each 'element' was used and as such had a role in the conservation of the squirrel glider, but their relative value varied. We illustrate the need to assess the conservation value of countryside elements so they can be incorporated into the holistic management of agricultural landscapes. This work demonstrates the disproportional value of scattered trees, underscoring the need to specifically incorporate and/or enhance the protection and recruitment of scattered trees in biodiversity conservation policy and management.

Background and objectivesElevated blood lipids during childhood are predictive of dyslipidemia in adults. Although obese and inactive children have elevated values, any potentially protective role of elementary school physical education is unknown. Our objective was to determine the effect of a modern elementary school physical education (PE) program on the blood lipid concentrations in community-based children.MethodsIn this cluster-randomized controlled trial, 708 healthy children (8.1±0.3 years, 367 boys) in 29 schools were allocated to either a 4-year intervention program of specialist-taught PE (13 schools) or to a control group of the currently practiced PE conducted by generalist classroom teachers. Fasting blood lipids were measured at ages 8, 10, and 12 years and intervention and control class activities were recorded.ResultsIntervention classes included more fitness work and more moderate and vigorous physical activity than control classes (both p3.36mmol.L(-1),130 mg/dL) was lower in the intervention than control group (14% vs. 23%, p = 0.02). There was also an intervention effect on mean LDL-C across all boys (reduction of 9.6% for intervention v 2.8% control, p = 0.02), but not girls (p = 0.2). The intervention effect on total cholesterol mirrored LDL-C, but there were no detectable 4-year intervention effects on high-density lipoprotein cholesterol or triglycerides.ConclusionsThe PE program delivered by specialist teachers over four years in elementary school reduced the incidence of elevated LDL-C in boys and girls, and provides a means by which early preventative practices can be offered to all children.Trial registrationAustralia New Zealand Clinical Trial Registry ANZRN12612000027819 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347799.

Increasing physical activity and decreasing sedentary behavior are associated with a higher quality of life and lower mortality rates for cancer survivors, a growing population group. Studies detailing the behavior of cancer survivors are limited. Therefore, we investigated physical activity and sedentary behavior of cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Participants were those who provided physical activity and sedentary behavior data. Those who were pregnant,

To contribute to the current debate as to the relative influences of dietary intake and physical activity on the development of adiposity in community-based children.Participants were 734 boys and girls measured at age 8, 10 and 12 years for percent body fat (dual emission x-ray absorptiometry), physical activity (pedometers, accelerometers); and dietary intake (1 and 2-day records), with assessments of pubertal development and socioeconomic status.Cross-sectional relationships revealed that boys and girls with higher percent body fat were less physically active, both in terms of steps per day and moderate and vigorous physical activity (both sexes p

BACKGROUND: In a previous longitudinal analysis of our cohort as 8 to 10 year-olds, insulin resistance (IR) increased with age, but was not modified by changes in percent body fat (%BF), and was only responsive to changes in physical activity (PA) in boys. We aimed to determine whether these responses persisted as the children approached adolescence. METHODS: In this prospective cohort study, 256 boys and 278 girls were assessed at ages 8, 10 and 12 years for fasting blood glucose and insulin, %BF (dual energy X-ray absorptiometry); PA (7-day pedometers), fitness (multistage run); and pubertal development (Tanner stage). RESULTS: From age 8 to 12 years, the median homeostatic model of IR (HOMA-IR) doubled in boys and increased 250% in girls. By age 12, 23% of boys and 31% of girls had elevated IR, as indicated by HOMA-IR greater than 3. Longitudinal relationships, with important adjustments for covariates body weight, PA, %BF, Tanner score and socioeconomic status showed that, on average, for every 1 unit reduction of %BF, HOMA-IR was lowered by 2.2% (95% CI 0.04-4) in girls and 1.6% (95% CI 0-3.2) in boys. Furthermore, in boys but not girls, HOMA-IR was decreased by 3.5% (95%CI 0.5-6.5) if PA was increased by 2100 steps/day. CONCLUSION: Evidence that a quarter of our apparently healthy 12 year-old Australians possessed elevated IR suggests that community-based education and prevention strategies may be warranted. Responsiveness of IR to changes in %BF in both sexes during late preadolescence and to changes in PA in the boys provides a specific basis for targeting elevated IR. That body weight was a strong covariate of IR, independent of %BF, points to the importance of adjusting for weight in correctly assessing these relationships in growing children.

Iron is an essential element in the metabolism of all cells. Elevated levels of the metal have been found in the brains of patients of numerous neurodegenerative disorders, including Parkinson's disease (PD). The pathogenesis of PD is largely unknown, although it is thought through studies with experimental models that oxidative stress and dysfunction of brain iron homeostasis, usually a tightly regulated process, play significant roles in the death of dopaminergic neurons. Accumulation of iron is present at affected neurons and associated microglia in the substantia nigra of PD patients. This additional free-iron has the capacity to generate reactive oxygen species, promote the aggregation of α-synuclein protein, and exacerbate or even cause neurodegeneration. There are various treatments aimed at reversing this pathologic increase in iron content, comprising both synthetic and natural iron chelators. These include established drugs, which have been used to treat other disorders related to iron accumulation. This paper will discuss how iron dysregulation occurs and the link between increased iron and oxidative stress in PD, including the mechanism by which these processes lead to cell death, before assessing the current pharmacotherapies aimed at restoring normal iron redox and new chelation strategies undergoing research.

This study tests whether the nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine (L-NNA), combines favorably with ionizing radiation (IR) in controlling squamous carcinoma tumor growth. Animals bearing FaDu and A431 xenografts were treated with L-NNA in the drinking water. IR exposure was 10 Gy for tumor growth and survival studies and 4 Gy for ex vivo clonogenic assays. Cryosections were examined immunohistochemically for markers of apoptosis and hypoxia. Blood flow was assayed by fluorescent microscopy of tissue cryosections after i.v. injection of fluorospheres. Orally administered L-NNA for 24 hrs reduces tumor blood flow by 80% (p

Mitochondria are vitally important organelles involved in an array of functions. The most notable is their prominent role in energy metabolism, where they generate over 90% of our cellular energy in the form of ATP through oxidative phosphorylation. Mitochondria are involved in various other processes including the regulation of calcium homeostasis and stress response. Mitochondrial complex I impairment and subsequent oxidative stress have been identified as modulators of cell death in experimental models of Parkinson's disease (PD). Identification of specific genes which are involved in the rare familial forms of PD has further augmented the understanding and elevated the role mitochondrial dysfunction is thought to have in disease pathogenesis. This paper provides a review of the role mitochondria may play in idiopathic PD through the study of experimental models and how genetic mutations influence mitochondrial activity. Recent attempts at providing neuroprotection by targeting mitochondria are described and their progress assessed.

Sailasuta N, Harris K, Tran T, Ross BMinimally invasive biomarker confirms glial activation present in Alzheimer’s disease: a preliminary study. Neuropsychiatr Dis Treat. 2011;7:495–499.Original article

Abstract Background and aims Quantitative tests of liver function (QTLF) which are based on the hepatic metabolism or clearance of test substances have been successfully used to predict prognosis of a variety of different liver diseases. Still sufficient data in HIV-patients under anti-retroviral therapy (ART) are lacking. Therefore, the aim of this prospective study was to investigate if and to what extent ART influences a broad panel of quantitative tests of liver function in patients with HIV-infection. Patients and methods Nineteen patients (14 males, 5 females, mean age 40 years) with HIV-infection underwent QTLF including lidocaine half-life test (LHT), galactose elimination capacity (GEC), and indocyanine green clearance (IGC). These tests were performed before and 3 to 6 months after initiation of anti-retroviral therapy. Twenty age-matched healthy, medication-and virus-free adults served as controls. Results Lidocaine half-life was significantly lower in HIV-patients without ART. Combining anti-retroviral therapies shifted cytochrome p450 activity back into standard ranges. Galactose elimination capacity as a parameter of cytosolic liver function and indocyanine green clearance as a parameter of liver perfusion were not affected by ART. Conclusions QTLF may be a tool to predict prognosis or hepatic complications in HIV-infected patients with liver disease. Early determination of lidocaine half-life seems to be useful - this should be considered during the treatment of HIV-positive individuals.