Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).

Global assessment of effective population sizes: Consistent taxonomic differences in meeting the 50/500 rule.

Effective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimum Ne of 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship between Ne and human activities. Through a quantitative review, we generated a dataset with 4610 georeferenced Ne estimates from 3829 populations, extracted from 723 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal and amphibian populations had a <54% probability of reaching N ̂ e = 50 and a <9% probability of reaching N ̂ e = 500. Populations listed as being of conservation concern according to the IUCN Red List had a smaller median N ̂ e than unlisted populations, and this was consistent across all taxonomic groups. N ̂ e was reduced in areas with a greater Global Human Footprint, especially for amphibians, birds and mammals, however relationships varied between taxa. We also highlight several considerations for future works, including the role that gene flow and subpopulation structure plays in the estimation of N ̂ e in wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based on Ne and help prioritise assessment of populations from taxa most at risk of failing to meet conservation thresholds.

Tropical Logistic Regression Model on Space of Phylogenetic Trees.

Classification of gene trees is an important task both in the analysis of multi-locus phylogenetic data, and assessment of the convergence of Markov Chain Monte Carlo (MCMC) analyses used in Bayesian phylogenetic tree reconstruction. The logistic regression model is one of the most popular classification models in statistical learning, thanks to its computational speed and interpretability. However, it is not appropriate to directly apply the standard logistic regression model to a set of phylogenetic trees, as the space of phylogenetic trees is non-Euclidean and thus contradicts the standard assumptions on covariates. It is well-known in tropical geometry and phylogenetics that the space of phylogenetic trees is a tropical linear space in terms of the max-plus algebra. Therefore, in this paper, we propose an analogue approach of the logistic regression model in the setting of tropical geometry. Our proposed method outperforms classical logistic regression in terms of Area under the ROC Curve in numerical examples, including with data generated by the multi-species coalescent model. Theoretical properties such as statistical consistency have been proved and generalization error rates have been derived. Finally, our classification algorithm is proposed as an MCMC convergence criterion for Mr Bayes. Unlike the convergence metric used by Mr Bayes which is only dependent on tree topologies, our method is sensitive to branch lengths and therefore provides a more robust metric for convergence. In a test case, it is illustrated that the tropical logistic regression can differentiate between two independently run MCMC chains, even when the standard metric cannot.

Recruitment dynamics of juvenile salmonids: Comparisons among populations and with classic case studies.

Understanding recruitment, the process by which individuals are added to a population or to a fishery, is critical for understanding population dynamics and facilitating sustainable fisheries management. Important variation in recruitment dynamics is observed among populations, wherein some populations exhibit asymptotic productivity and others exhibit overcompensation (i.e., compensatory density-dependence in recruitment). Our ability to understand this interpopulation variability in recruitment patterns is limited by a poor understanding of the underlying mechanisms, such as the complex interactions between density dependence, recruitment, and environment. Furthermore, most studies on recruitment are conducted using an observational design with long time series that are seldom replicated across populations in an experimentally controlled fashion. Without proper replication, extrapolations between populations are tenuous, and the underlying environmental trends are challenging to quantify. To address these issues, we conducted a field experiment manipulating stocking densities of juvenile brook trout Salvelinus fontinalis in three wild populations to show that these neighboring populations-which exhibit divergent patterns of density dependence due to environmental conditions-also have important differences in recruitment dynamics. Testing against four stock-recruitment models (density independent, linear, Beverton-Holt, and Ricker), populations exhibited ~twofold variation in asymptotic productivity, with no overcompensation following a Beverton-Holt model. Although environmental variables (e.g., temperature, pH, depth, substrate) correlated with population differences in recruitment, they did not improve the predictive power in individual populations. Comparing our patterns of recruitment with classic salmonid case studies revealed that despite differences in the shape and parameters of the curves (i.e., Ricker vs. Beverton-Holt), a maximum stocking density of about five YOY fish/m2 emerged. Higher densities resulted in very marginal increases in recruitment (Beverton-Holt) or reduced recruitment due to overcompensation (Ricker).

Morphological and Habitat Quality of Salmonid Streams and their Relationship with Fish-Based Indices in Aotearoa New Zealand and Ontario (Canada).

Habitat degradation is one of the major reasons for freshwater species decline. Hydrogeomorphological processes (such as sediment transport, bank erosion, and flooding) operate at the catchment scale and determine habitat features in river reaches. However, habitat quality indices and restoration for freshwater fish species are often implemented at small spatial scales of a few hundred metres. The Morphological Quality Index (MQI) considers fluvial processes at larger scales as well as channel forms, human impacts, and historical changes, but few studies have assessed its relevance for ecosystem health. We investigated relationships between the MQI, habitat quality (using the Qualitative Habitat Evaluation Index, QHEI), land cover, and fish metrics (number of fish species, index of biotic integrity (IBI), and trout biomass) in 26 salmonid streams in Aotearoa New Zealand and Southern Ontario, Canada. We found a significant correlation between the MQI and QHEI, and both metrics were correlated with urban and native forest proportion in the catchment. However, we found no relation between the MQI and the proportion of agricultural land in the catchment, while the QHEI was correlated with agricultural land in the riparian zone, highlighting the importance of vegetated riparian buffers in providing fish habitat. Establishing a strong correlation with fish metrics remains challenging. Nevertheless, a modified MQI targeting ecological health could be used as an effective management tool for aquatic conservation.

Rapid single-photon color imaging of moving objects.

This paper outlines an experimental demonstration of a Bayesian image reconstruction approach to achieve rapid single-photon color imaging of moving objects. The capacity to extract the color of objects is important in a variety of target identification and computer vision applications. Nonetheless, it remains challenging to achieve high-speed color imaging of moving objects in low-photon flux environments. The low-photon regime presents particular challenges for efficient spectral separation and identification, while unsupervised image reconstruction algorithms are often slow and computationally expensive. In this paper, we address both of these difficulties using a combination of hardware and computational solutions. We demonstrate color imaging using a Single-Photon Avalanche Diode (SPAD) detector array for rapid, low-light-level data acquisition, with an integrated color filter array (CFA) for efficient spectral unmixing. High-speed image reconstruction is achieved using a bespoke Bayesian algorithm to produce high-fidelity color videos. The analysis is conducted first on simulated data allowing different pixel formats and photon flux scenarios to be investigated. Experiments are then performed using a plasmonic metasurface-based CFA, integrated with a 64 × 64 pixel format SPAD array. Passive imaging is conducted using white-light illumination of multi-colored, moving targets. Intensity information is recorded in a series of 2D photon-counting SPAD frames, from which accurate color information is extracted using the fast Bayesian method introduced herein. The per-frame reconstruction rate proves to be hundreds of times faster than the previous computational method. Furthermore, this approach yields additional information in the form of uncertainty measures, which can be used to assist with imaging system optimization and decision-making in real-world applications. The techniques demonstrated point the way towards rapid video-rate single-photon color imaging. The developed Bayesian algorithm, along with more advanced SPAD technology and utilization of time-correlated single-photon counting (TCSPC) will permit live 3D, color videography in extremely low-photon flux environments.

Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein-Barr virus.

BACKGROUND AND PURPOSE: Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS) risk; evidence for other herpesviruses is inconsistent. Here, we test blood markers of infection with human herpesvirus 6 (HHV-6), varicella zoster virus (VZV), and cytomegalovirus (CMV) as risk factors for a first clinical diagnosis of central nervous system demyelination (FCD) in the context of markers of EBV infection. METHODS: In the Ausimmune case-control study, cases had an FCD, and population controls were matched on age, sex, and study region. We quantified HHV-6- and VZV-DNA load in whole blood and HHV-6, VZV, and CMV antibodies in serum. Conditional logistic regression tested associations with FCD risk, adjusting for Epstein-Barr nuclear antigen (EBNA) IgG, EBV-DNA load, and other covariates. RESULTS: In 204 FCD cases and 215 matched controls, only HHV-6-DNA load (positive vs. negative) was associated with FCD risk (adjusted odds ratio = 2.20, 95% confidence interval = 1.08-4.46, p = 0.03). Only EBNA IgG and HHV-6-DNA positivity were retained in a predictive model of FCD risk; the combination had a stronger association than either alone. CMV-specific IgG concentration modified the association between an MS risk-related human leucocyte antigen gene and FCD risk. Six cases and one control had very high HHV-6-DNA load (>1.0 × 106 copies/mL). CONCLUSIONS: HHV-6-DNA positivity and high load (possibly due to inherited HHV-6 chromosomal integration) were associated with increased FCD risk, particularly in association with markers of EBV infection. With growing interest in prevention/management of MS through EBV-related pathways, there should be additional consideration of the role of HHV-6 infection.

Location of Artinite (Mg2CO3(OH)2·3H2O) within the MgO-CO2-H2O system using ab initio thermodynamics.

The MgO-CO2-H2O system have a variety of important industrial applications including in catalysis, immobilisation of radionuclides and heavy metals, construction, and mineralisation and permanent storage of anthropogenic CO2. Here, we develop a computational approach to generate phase stability plots for the MgO-CO2-H2O system that do not rely on traditional experimental corrections for the solid phases. We compare the predictions made by several dispersion-corrected density-functional theory schemes, and we include the temperature-dependent Gibbs free energy through the quasi-harmonic approximation. We locate the Artinite phase (Mg2CO3(OH)2·3H2O) within the MgO-CO2-H2O phase stability plot, and we demonstrate that this widely-overlooked hydrated and carbonated phase is metastable and can be stabilised by inhibiting the formation of fully-carbonated stable phases. Similar considerations may apply more broadly to other lesser known phases. These findings provide new insight to explain conflicting results from experimental studies, and demonstrate how this phase can potentially be stabilised by optimising the synthesis conditions.

Comparison of Modified Manual Acid-Phenol Chloroform Method and Commercial RNA Extraction Kits for Resource Limited Laboratories.

Method: In a comparative experimental cross-sectional study, RNA was extracted from oral swabs and blood samples from 25 healthy individuals at the Department of Molecular Medicine, KNUST. RNA was extracted by the manual AGPC extraction method and commercial RNA extraction kits. The quantity (ng/µl) and purities (260/280 nm) of the extracted RNA were measured spectrophotometrically using the IMPLEN NanoPhotometer® N60. The presence of RNA in the extracts was confirmed using 2% agarose gel electrophoresis. Statistical analyses were conducted using R language. Results: The yield of RNA extracted from blood and oral swab samples using modified AGPC was significantly higher compared to the commercial methods (p < 0.0001). However, the purity of RNA extracted by the manual AGPC method from blood was significantly lower than the commercial methods (p < 0.0001). Moreover, the purity from oral swabs using the manual AGPC method was significantly lower compared to QIAamp (p < 0.0001) and the OxGEn kits method (p < 0.001). Conclusion: The modified manual AGPC method has a very high yield of RNA extracts using blood samples, which could serve as an alternate cost-effective method for RNA extraction in resource-limited laboratories; however, its purity may not be suitable for downstream processes. Moreover, the manual AGPC method may not be suitable for extracting RNA from oral swab samples. Future investigation is needed to improve the purity of the manual AGPC RNA extraction method and also confirmation of the obtained results by PCR amplification and RNA purity verification by sequencing.

PrAna: an R package to calculate and visualize England NHS primary care prescribing data.

BACKGROUND: The objective of this work to calculate prescribed quantity of an active pharmaceutical ingredient (API) in prescription medications for human use, to facilitate research on the prediction of amount of API released to the environment and create an open-data tool to facilitate spatiotemporal and long-term prescription trends for wider usage. DESIGN: We have developed an R package, PrAna to calculate the prescribed quantity (in kg) of an APIs by postcode using England's national level prescription data provided by National Health Service, for the years 2015-2018. Datasets generated using PrAna can be visualized in a real-time interactive web-based tool, PrAnaViz to explore spatiotemporal and long-term trends. The visualisations can be customised by selecting month, year, API, and region. RESULTS: PrAnaViz's targeted API approach is demonstrated with the visualisation of prescribed quantities of 14 APIs in the Bath and North East Somerset (BANES) region during 2018. Once the APIs list is loaded, the back end retrieves relevant data and populates the graphs based on user-defined data features in real-time. These plots include the prescribed quantity of APIs over a year, by month, and individual API by month, general practice, postcode, and medicinal form. The non-targeted API approach is demonstrated with the visualisation of clarithromycin prescribed quantities at different postcodes in the BANES region. CONCLUSION: PrAna and PrAnaViz enables the analysis of spatio-temporal and long-term trends with prescribed quantities of different APIs by postcode. This can be used as a support tool for policymakers, academics and researchers in public healthcare, and environmental scientist to monitor different group of pharmaceuticals emitted to the environment and for prospective risk assessment of pharmaceuticals in the environment.

Population variation in density-dependent growth, mortality and their trade-off in a stream fish.

Important variation in the shape and strength of density-dependent growth and mortality is observed across animal populations. Understanding this population variation is critical for predicting density-dependent relationships in natural populations, but comparisons amongst studies are challenging as studies differ in methodologies and in local environmental conditions. Consequently, it is unclear whether: (a) the shape and strength of density-dependent growth and mortality are population-specific; (b) the potential trade-off between density-dependent growth and mortality differs amongst populations; and (c) environmental characteristics can be related to population differences in density-dependent relationships. To elucidate these uncertainties, we manipulated the density (0.3-7 fish/ m2 ) of young-of-the-year brook trout (Salvelinus fontinalis) simultaneously in three neighbouring populations in a field experiment in Newfoundland, Canada. Within each population, our experiment included both spatial (three sites per stream) and temporal (three consecutive summers) replication. We detected temporally consistent population variation in the shape of density-dependent growth (negative linear and negative logarithmic), but not for mortality (positive logarithmic). The strength of density-dependent growth across populations was reduced in sections with a high percentage of boulder substrate, whereas density-dependent mortality increased with increasing flow, water temperature and more acidic pH. Neighbouring populations exhibited different mortality-growth trade-offs: the ratio of mortality-to-growth increased linearly with increasing density at different rates across populations (up to 4-fold differences), but also increased with increasing temperature. Our results are some of the first to demonstrate temporally consistent, population-specific density-dependent relationships and trade-offs at small spatial scales that match the magnitude of interspecific variation observed across the globe. Furthermore, key environmental characteristics explain some of these differences in predictable ways. Such population differences merit further attention in models of density dependence and in science-based management of animal populations.

Aortic Root Dilation and Testosterone Use: Are They Associated?

Aortic root dilation and thoracic aortic aneurysms are relatively rare in young and healthy patient populations. However, a number of observed incidental cases regarding young males and testosterone use raises suspicion of a potential risk factor for aortic root dilation. The authors' patient, a healthy 40-year-old man with a significant history of testosterone use who developed a massively dilated aortic root, is sufficiently alarming to report. Notwithstanding anecdotal cases, there exists a well-known association between elite strength athletes and aortic root dilation. Nevertheless, very little clinical research exists on the relationship between testosterone use and aortic root dilation and/or thoracic aortic aneurysms. Furthermore, a small number of animal studies showed a relationship between testosterone and vascular dilation, particularly the aorta. Although testosterone may play a role in the development of aortic pathologies, further research is necessary to clarify the possible relationship if cases such as these are to be prevented.

The future is not always open.

We demonstrate the breakdown of several fundamentals of Lorentzian causality theory in low regularity. Most notably, chronological futures (defined naturally using locally Lipschitz curves) may be non-open and may differ from the corresponding sets defined via piecewise C 1 -curves. By refining the notion of a causal bubble from Chrusciel and Grant (Class Quantum Gravity 29(14):145001, 2012), we characterize spacetimes for which such phenomena can occur, and also relate these to the possibility of deforming causal curves of positive length into timelike curves (push-up). The phenomena described here are, in particular, relevant for recent synthetic approaches to low-regularity Lorentzian geometry where, in the absence of a differentiable structure, causality has to be based on locally Lipschitz curves.

Alignment-insensitive bilayer THz metasurface absorbers exceeding 100% bandwidth.

Metamaterial absorbers have been a topic of considerable interest in recent years, with a particular focus on Terahertz (THz) frequencies due to many natural materials having a weak interaction with THz light. Great efforts have aimed to expand such THz absorbers to cover a wide bandwidth whilst also being highly efficient. However, many of these require cascaded or stacked multilayer resonant elements, where even a small deviation in the alignment between layers is extremely detrimental to the performance. Here, we propose a bilayer metasurface absorber (thickness ∼ λ/6) that is immune to such layer misalignments capable of exceeding a fractional bandwidth (FWHM) of 100% of the central frequency. The design works due to a novel absorption mechanism based on Salisbury Screen and anti-reflection absorption mechanisms, using fractal cross absorbers to expand the bandwidth. Our work is of particular benefit to developing devices which require ultra-wide bandwidth, such as bolometric sensing and planar blackbody absorbers, with the extremely robust absorption responses being unaffected by any misalignments between layers - a limiting factor of previous absorbers.

Towards Portable Nanophotonic Sensors.

A range of nanophotonic sensors composed of different materials and device configurations have been developed over the past two decades. These sensors have achieved high performance in terms of sensitivity and detection limit. The size of onchip nanophotonic sensors is also small and they are regarded as a strong candidate to provide the next generation sensors for a range of applications including chemical and biosensing for point-of-care diagnostics. However, the apparatus used to perform measurements of nanophotonic sensor chips is bulky, expensive and requires experts to operate them. Thus, although integrated nanophotonic sensors have shown high performance and are compact themselves their practical applications are limited by the lack of a compact readout system required for their measurements. To achieve the aim of using nanophotonic sensors in daily life it is important to develop nanophotonic sensors which are not only themselves small, but their readout system is also portable, compact and easy to operate. Recognizing the need to develop compact readout systems for onchip nanophotonic sensors, different groups around the globe have started to put efforts in this direction. This review article discusses different works carried out to develop integrated nanophotonic sensors with compact readout systems, which are divided into two categories; onchip nanophotonic sensors with monolithically integrated readout and onchip nanophotonic sensors with separate but compact readout systems.

Inextendibility of spacetimes and Lorentzian length spaces.

We study the low-regularity (in-)extendibility of spacetimes within the synthetic-geometric framework of Lorentzian length spaces developed in Kunzinger and Sämann (Ann Glob Anal Geom 54(3):399-447, 2018). To this end, we introduce appropriate notions of geodesics and timelike geodesic completeness and prove a general inextendibility result. Our results shed new light on recent analytic work in this direction and, for the first time, relate low-regularity inextendibility to (synthetic) curvature blow-up.

CMOS compatible metamaterial absorbers for hyperspectral medium wave infrared imaging and sensing applications.

We experimentally demonstrate a CMOS compatible medium wave infrared metal-insulator-metal (MIM) metamaterial absorber structure where for a single dielectric spacer thickness at least 93% absorption is attained for 10 separate bands centred at 3.08, 3.30, 3.53, 3.78, 4.14, 4.40, 4.72, 4.94, 5.33, 5.60 µm. Previous hyperspectral MIM metamaterial absorber designs required that the thickness of the dielectric spacer layer be adjusted in order to attain selective unity absorption across the band of interest thereby increasing complexity and cost. We show that the absorption characteristics of the hyperspectral metamaterial structures are polarization insensitive and invariant for oblique incident angles up to 25° making them suitable for practical implementation in an imaging system. Finally, we also reveal that under TM illumination and at certain oblique incident angles there is an extremely narrowband Fano resonance (Q > 50) between the MIM absorber mode and the surface plasmon polariton mode that could have applications in hazardous/toxic gas identification and biosensing.

Evaluation of a pilot police-led suicide early alert surveillance strategy in the UK.

INTRODUCTION: Those bereaved by suicide are at increased risk of psychological harm, which can be reduced with the provision of timely support. This paper outlines an evaluation of a pilot police-led suicide strategy, in comparison to a coroner-led suicide strategy looking at the number, and length of time it takes for deaths to be recorded for each strategy. Additionally, the police-led strategy offers timely contact from support services for bereaved individuals. We examined what impact this offer of support had on the capacity of support services. METHODS: A mixed methods evaluation compared how long it took for suspected suicides to be recorded using both strategies. The number of referrals received by support services during the pilot strategy were compared with those from previous years. A feedback focus group, and interviews, were held with key stakeholders. RESULTS: The coroner strategy was more consistent at identifying suspected suicides; however, reports were filed quicker by the police. Bereaved individuals were willing to share contact details with police officers and consent for referral to support services which lead to increased referrals. The focus group and interviews revealed that the pilot police strategy needs better integration into routine police practice. CONCLUSIONS: This strategy has the potential to deliver a real benefit to those bereaved by suicide; however, there are still aspects which could be improved.

Effects of supplemental vibrational force on space closure, treatment duration, and occlusal outcome: A multicenter randomized clinical trial.

INTRODUCTION: A multicenter parallel 3-arm randomized clinical trial was carried out in 3 university hospitals in the United Kingdom to investigate the effect of supplemental vibratory force on space closure and treatment outcome with fixed appliances. METHODS: Eighty-one subjects less than 20 years of age with mandibular incisor irregularity undergoing extraction-based fixed appliance treatment were randomly allocated to supplementary (20 minutes/day) use of an intraoral vibrational device (AcceleDent; OrthoAccel Technologies, Houston, Tex) (n = 29), an identical nonfunctional (sham) device (n = 25), or fixed-appliance only (n = 27). Space closure in the mandibular arch was measured from dental study casts taken at the start of space closure, at the next appointment, and at completion of space closure. Final records were taken at completion of treatment. Data were analyzed blindly on a per-protocol basis with descriptive statistics, 1-way analysis of variance, and linear regression modeling with 95% confidence intervals. RESULTS: Sixty-one subjects remained in the trial at start of space closure, with all 3 groups comparable for baseline characteristics. The overall median rate of initial mandibular arch space closure (primary outcome) was 0.89 mm per month with no difference for either the AcceleDent group (difference, -0.09 mm/month; 95% CI, -0.39 to 0.22 mm/month; P = 0.57) or the sham group (difference, -0.02 mm/month; 95% CI, -0.32 to 0.29 mm/month; P = 0.91) compared with the fixed only group. Similarly, no significant differences were identified between groups for secondary outcomes, including overall treatment duration (median, 18.6 months; P >0.05), number of visits (median, 12; P >0.05), and percentage of improvement in the Peer Assessment Rating (median, 90.0%; P >0.05). CONCLUSIONS: Supplemental vibratory force during orthodontic treatment with fixed appliances does not affect space closure, treatment duration, total number of visits, or final occlusal outcome. REGISTRATION: NCT02314975. PROTOCOL: The protocol was not published before trial commencement. FUNDING: AcceleDent units were donated by OrthoAccel Technologies; no contribution to the conduct or the writing of this study was made by the manufacturer.

Territory size decreases minimally with increasing food abundance in stream salmonids: Implications for population regulation.

How the local density of territorial animals responds to changes in food abundance will depend on the flexibility of territory size. Quantitative estimates of territory size over a broad range of food abundance are relatively rare because of the difficulty of measuring food abundance in the wild. Stream salmonids are an ideal model system for investigating flexibility in territory size, because food abundance can be quantified in the field and manipulated in the laboratory. We conducted a meta-analysis to test whether territory size decreases with increasing food abundance, and a mixed model analysis to test among three competing predictions: with increasing food abundance, territory size will be (1) fixed-the slope of a regression of log territory size vs. log food abundance = 0; (2) flexible and decreasing, as if individuals are defending a fixed amount of food-a slope = -1; and (3) initially compressible, but with an asymptotic minimum size-a slope between 0 and -1. We collected data from 16 studies that manipulated or measured food abundance while monitoring changes in territory size of young-of-the-year salmonids; 10 were experimental laboratory studies, whereas six were observational field studies. Overall, territory size decreased significantly with increasing food abundance; the weighted average correlation coefficient was -0.31. However, the estimated slope of the relationship between log territory size and log food abundance was only -0.23, significantly different from 0, and also significantly shallower than -1. Our estimated slope suggests that attempts to increase the density of territorial salmonids by increasing food abundance and reducing territory size will be inefficient; a 20-fold increase in food abundance would be required to double population density. Our analysis may also have implications for other species with a territorial mosaic social system-i.e. contiguous territories. In these social systems, social inertia will dampen any effects of changes in food abundance on the local density of settlers, compared to non-territorial species or those with non-contiguous territories.