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Resource acquisition and growth yield are fundamental microbial traits that affect biogeochemical processes and have consequences for ecosystem functioning. However, there is a lack of empirical observations linking these traits. Using a landscape-scale survey of temperate near-neutral pH soils, we show tradeoffs in key community-level parameters linked to these traits. Increased investment into extracellular enzymes estimated using specific potential enzyme activity was associated with reduced growth yield obtained using carbon use efficiency measures from stable isotope tracing. Reduction in growth yield was linked more to carbon than nitrogen acquisition highlighting smaller stoichiometric than energetic constraints on community metabolism in examined soils.

Soil organic carbon (SOC) is a soil health indicator and understanding dynamics changing SOC stocks will help achieving net zero goals. Here we present four datasets featuring 11,750 data points covering co-located aboveground and below-ground metrics for exploring ecosystem SOC dynamics. Five sites across England with an established land use contrast, grassland and woodland next to each other, were rigorously sampled for aboveground (n = 109), surface (n = 33 soil water release curves), topsoil, and subsoil metrics. Commonly measured soil metrics were analysed in five soil increments for 0-1 metre (n = 4550). Less commonly measured soil metrics which were assumed to change across the soil profile were measured on a subset of samples only (n = 3762). Additionally, we developed a simple method for soil organic matter fractionation using density fractionation which is part of the less common metrics. Finally, soil metrics which may impact SOC dynamics, but with less confidence as to their importance across the soil profile were only measured on topsoil (~5-15 cm = mineral soil) and subsoil (below 50 cm) samples (n = 2567)., (© 2024. The Author(s).)

The seasonal coupling of plant and soil microbial nutrient demands is crucial for efficient ecosystem nutrient cycling and plant production, especially in strongly seasonal alpine ecosystems. Yet, how these seasonal nutrient cycling processes are modified by climate change and what the consequences are for nutrient loss and retention in alpine ecosystems remain unclear. Here, we explored how two pervasive climate change factors, reduced snow cover and shrub expansion, interactively modify the seasonal coupling of plant and soil microbial nitrogen (N) cycling in alpine grasslands, which are warming at double the rate of the global average. We found that the combination of reduced snow cover and shrub expansion disrupted the seasonal coupling of plant and soil N-cycling, with pronounced effects in spring (shortly after snow melt) and autumn (at the onset of plant senescence). In combination, both climate change factors decreased plant organic N-uptake by 70% and 82%, soil microbial biomass N by 19% and 38% and increased soil denitrifier abundances by 253% and 136% in spring and autumn, respectively. Shrub expansion also individually modified the seasonality of soil microbial community composition and stoichiometry towards more N-limited conditions and slower nutrient cycling in spring and autumn. In winter, snow removal markedly reduced the fungal:bacterial biomass ratio, soil N pools and shifted bacterial community composition. Taken together, our findings suggest that interactions between climate change factors can disrupt the temporal coupling of plant and soil microbial N-cycling processes in alpine grasslands. This could diminish the capacity of these globally widespread alpine ecosystems to retain N and support plant productivity under future climate change., (© 2024 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Palaeolimnological records provide valuable information about how phytoplankton respond to long-term drivers of environmental change. Traditional palaeolimnological tools such as microfossils and pigments are restricted to taxa that leave sub-fossil remains, and a method that can be applied to the wider community is required. Sedimentary DNA (sedDNA), extracted from lake sediment cores, shows promise in palaeolimnology, but validation against data from long-term monitoring of lake water is necessary to enable its development as a reliable record of past phytoplankton communities. To address this need, 18S rRNA gene amplicon sequencing was carried out on lake sediments from a core collected from Esthwaite Water (English Lake District) spanning ~105 years. This sedDNA record was compared with concurrent long-term microscopy-based monitoring of phytoplankton in the surface water. Broadly comparable trends were observed between the datasets, with respect to the diversity and relative abundance and occurrence of chlorophytes, dinoflagellates, ochrophytes and bacillariophytes. Up to 20% of genera were successfully captured using both methods, and sedDNA revealed a previously undetected community of phytoplankton. These results suggest that sedDNA can be used as an effective record of past phytoplankton communities, at least over timescales of <100 years. However, a substantial proportion of genera identified by microscopy were not detected using sedDNA, highlighting the current limitations of the technique that require further development such as reference database coverage. The taphonomic processes which may affect its reliability, such as the extent and rate of deposition and DNA degradation, also require further research., (© 2023 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.)

Background and Hypothesis: This systematic review and meta-analysis review the literature regarding the prevalence of visual hallucinations in patients with first-episode psychosis. Previous reviews have focused on the prevalence of visual hallucinations in a general psychosis population, highlighting a weighted prevalence of 27%. However, no reviews have focused specifically on the experiences of those with a first episode of psychosis. Understanding "first-episode" experiences is crucial, as intervention during this "critical period" is thought to define long-term outcome. Therefore, it is important that the prevalence of different symptoms during this period is accurately represented., Study Design: Systematic searches yielded 15 studies to be meta-analyzed. Information to calculate event rates was extracted. Studies were rated for their methodological quality using a risk of bias tool. The quality of included studies varied; generalizability bias was the domain with the most risk of bias., Study Results: Prevalence rates were synthesized from the 15 papers included in the final analysis, which generated a weighted prevalence estimate of 33% of people with first-episode psychosis experiencing visual hallucinations. Subgroup analyses were carried out and did not demonstrate significant associations., Conclusions: This meta-analysis provides a robust estimate of 33% for the prevalence of visual hallucinations in first-episode psychosis; highlighting that visual hallucinations are relatively common experiences., Competing Interests: The authors have declared that there are no conflicts of interest in relation to the subject of this study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Faecal indicator organisms (FIOs) are limited in their ability to protect public health from the microbial contamination of drinking water because of their transience and time required to deliver a result. We evaluated alternative rapid, and potentially more resilient, approaches against a benchmark FIO of thermotolerant coliforms (TTCs) to characterise faecal contamination over 14 months at 40 groundwater sources in a Ugandan town. Rapid approaches included: in-situ tryptophan-like fluorescence (TLF), humic-like fluorescence (HLF), turbidity; sanitary inspections; and total bacterial cells by flow cytometry. TTCs varied widely in six sampling visits: a third of sources tested both positive and negative, 50% of sources had a range of at least 720 cfu/100 mL, and a two-day heavy rainfall event increased median TTCs five-fold. Using source medians, TLF was the best predictor in logistic regression models of TTCs ≥10 cfu/100 mL (AUC 0.88) and best correlated to TTC enumeration (ρ s 0.81), with HLF performing similarly. Relationships between TLF or HLF and TTCs were stronger in the wet season than the dry season, when TLF and HLF were instead more associated with total bacterial cells. Source rank-order between sampling rounds was considerably more consistent, according to cross-correlations, using TLF or HLF (min ρ s 0.81) than TTCs (min ρ s 0.34). Furthermore, dry season TLF and HLF cross-correlated more strongly (ρ s 0.68) than dry season TTCs (ρ s 0.50) with wet season TTCs, when TTCs were elevated. In-situ TLF or HLF are more rapid and resilient indicators of faecal contamination risk than TTCs., (Copyright © 2021 British Geological Survey. Published by Elsevier Ltd.. All rights reserved.)

Soil microbial communities regulate global biogeochemical cycles and respond rapidly to changing environmental conditions. However, understanding how soil microbial communities respond to climate change, and how this influences biogeochemical cycles, remains a major challenge. This is especially pertinent in alpine regions where climate change is taking place at double the rate of the global average, with large reductions in snow cover and earlier spring snowmelt expected as a consequence. Here, we show that spring snowmelt triggers an abrupt transition in the composition of soil microbial communities of alpine grassland that is closely linked to shifts in soil microbial functioning and biogeochemical pools and fluxes. Further, by experimentally manipulating snow cover we show that this abrupt seasonal transition in wide-ranging microbial and biogeochemical soil properties is advanced by earlier snowmelt. Preceding winter conditions did not change the processes that take place during snowmelt. Our findings emphasise the importance of seasonal dynamics for soil microbial communities and the biogeochemical cycles that they regulate. Moreover, our findings suggest that earlier spring snowmelt due to climate change will have far reaching consequences for microbial communities and nutrient cycling in these globally widespread alpine ecosystems., (© 2021. The Author(s), under exclusive licence to International Society for Microbial Ecology.)

High-throughput sequencing 16S rRNA gene surveys have enabled new insights into the diversity of soil bacteria, and furthered understanding of the ecological drivers of abundances across landscapes. However, current analytical approaches are of limited use in formalizing syntheses of the ecological attributes of taxa discovered, because derived taxonomic units are typically unique to individual studies and sequence identification databases only characterize taxonomy. To address this, we used sequences obtained from a large nationwide soil survey (GB Countryside Survey, henceforth CS) to create a comprehensive soil specific 16S reference database, with coupled ecological information derived from survey metadata. Specifically, we modeled taxon responses to soil pH at the OTU level using hierarchical logistic regression (HOF) models, to provide information on both the shape of landscape scale pH-abundance responses, and pH optima (pH at which OTU abundance is maximal). We identify that most of the soil OTUs examined exhibited a non-flat relationship with soil pH. Further, the pH optima could not be generalized by broad taxonomy, highlighting the need for tools and databases synthesizing ecological traits at finer taxonomic resolution. We further demonstrate the utility of the database by testing against geographically dispersed query 16S datasets; evaluating efficacy by quantifying matches, and accuracy in predicting pH responses of query sequences from a separate large soil survey. We found that the CS database provided good coverage of dominant taxa; and that the taxa indicating soil pH in a query dataset corresponded with the pH classifications of top matches in the CS database. Furthermore we were able to predict query dataset community structure, using predicted abundances of dominant taxa based on query soil pH data and the HOF models of matched CS database taxa. The database with associated HOF model outputs is released as an online portal for querying single sequences of interest (https://shiny-apps.ceh.ac.uk/ID-TaxER/), and flat files are made available for use in bioinformatic pipelines. The further development of advanced informatics infrastructures incorporating modeled ecological attributes along with new functional genomic information will likely facilitate large scale exploration and prediction of soil microbial functional biodiversity under current and future environmental change scenarios., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jones, Goodall, George, Gweon, Puissant, Read, Emmett, Robinson, Jones and Griffiths.)

In Virtual Reality (VR), the requirements of much higher resolution and smooth viewing experiences under rapid and often real-time changes in viewing direction, leads to significant challenges in compression and communication. To reduce the stresses of very high bandwidth consumption, the concept of foveated video compression is being accorded renewed interest. By exploiting the space-variant property of retinal visual acuity, foveation has the potential to substantially reduce video resolution in the visual periphery, with hardly noticeable perceptual quality degradations. Accordingly, foveated image / video quality predictors are also becoming increasingly important, as a practical way to monitor and control future foveated compression algorithms. Towards advancing the development of foveated image / video quality assessment (FIQA / FVQA) algorithms, we have constructed 2D and (stereoscopic) 3D VR databases of foveated / compressed videos, and conducted a human study of perceptual quality on each database. Each database includes 10 reference videos and 180 foveated videos, which were processed by 3 levels of foveation on the reference videos. Foveation was applied by increasing compression with increased eccentricity. In the 2D study, each video was of resolution 7680×3840 and was viewed and quality-rated by 36 subjects, while in the 3D study, each video was of resolution 5376×5376 and rated by 34 subjects. Both studies were conducted on top of a foveated video player having low motion-to-photon latency (~50ms). We evaluated different objective image and video quality assessment algorithms, including both FIQA / FVQA algorithms and non-foveated algorithms, on our so called LIVE-Facebook Technologies Foveation-Compressed Virtual Reality (LIVE-FBT-FCVR) databases. We also present a statistical evaluation of the relative performances of these algorithms. The LIVE-FBT-FCVR databases have been made publicly available and can be accessed at https://live.ece.utexas.edu/research/LIVEFBTFCVR/index.html.

Environmental pollution can disrupt the interactions between animals and their symbiotic bacteria, which can lead to adverse effects on the host even in the absence of direct chemical toxicity. It is therefore crucial to understand how environmental pollutants affect animal microbiomes, especially for those chemicals that are designed to target microbes. Here, we study the effects of two biocidal nanoparticles (NPs) (Ag and CuO) on the soil bacterial community and the resident gut microbiome of the earthworm Eisenia fetida over a 28-day period using metabarcoding techniques. Exposures to NPs were conducted following OECD test guidelines and effects on earthworm reproduction and juvenile biomass were additionally recorded in order to compare effects on the host to effects on microbiomes. By employing a full concentration series, we were able to link pollutants to microbiome effects in high resolution. Multivariate analysis, differential abundance analysis and species sensitivity distribution analysis showed that Ag-NPs are more toxic to soil bacteria than CuO-NPs. In contrast to the strong effects of CuO-NPs and Ag-NPs on the soil bacterial community, the earthworm gut microbiome is largely resilient to exposure to biocidal NPs. Despite this buffering effect, CuO-NPs did negatively affect the relative abundance of some earthworm symbionts, including 'Candidatus Lumbricincola'. Changes in the soil bacterial community and the earthworm microbiome occur at total copper concentrations often found or modelled to occur in agricultural fields, demonstrating that soil bacterial communities and individual taxa in the earthworm microbiome may be at risk from environmental copper exposure including in nanomaterial form., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We explore in-situ fluorescence spectroscopy as an instantaneous indicator of total bacterial abundance and faecal contamination in drinking water. Eighty-four samples were collected outside of the recharge season from groundwater-derived water sources in Dakar, Senegal. Samples were analysed for tryptophan-like (TLF) and humic-like (HLF) fluorescence in-situ, total bacterial cells by flow cytometry, and potential indicators of faecal contamination such as thermotolerant coliforms (TTCs), nitrate, and in a subset of 22 samples, dissolved organic carbon (DOC). Significant single-predictor linear regression models demonstrated that total bacterial cells were the most effective predictor of TLF, followed by on-site sanitation density; TTCs were not a significant predictor. An optimum multiple-predictor model of TLF incorporated total bacterial cells, nitrate, nitrite, on-site sanitation density, and sulphate (r 2 0.68). HLF was similarly related to the same parameters as TLF, with total bacterial cells being the best correlated (ρ s 0.64). In the subset of 22 sources, DOC clustered with TLF, HLF, and total bacterial cells, and a linear regression model demonstrated HLF was the best predictor of DOC (r 2 0.84). The intergranular nature of the aquifer, timing of the study, and/or non-uniqueness of the signal to TTCs can explain the significant associations between TLF/HLF and indicators of faecal contamination such as on-site sanitation density and nutrients but not TTCs. The bacterial population that relates to TLF/HLF is likely to be a subsurface community that develops in-situ based on the availability of organic matter originating from faecal sources. In-situ fluorescence spectroscopy instantly indicates a drinking water source is impacted by faecal contamination but it remains unclear how that relates specifically to microbial risk in this setting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 United Kingdom Research and Innovation, as represented by its component body, the British Geological Survey. Published by Elsevier B.V. All rights reserved.)

Fluorescent natural organic matter at tryptophan-like (TLF) and humic-like fluorescence (HLF) peaks is associated with the presence and enumeration of faecal indicator bacteria in groundwater. We hypothesise, however, that it is predominantly extracellular material that fluoresces at these wavelengths, not bacterial cells. We quantified total (unfiltered) and extracellular (filtered at < 0.22 µm) TLF and HLF in 140 groundwater sources across a range of urban population densities in Kenya, Malawi, Senegal, and Uganda. Where changes in fluorescence occurred following filtration they were correlated with potential controlling variables. A significant reduction in TLF following filtration (ΔTLF) was observed across the entire dataset, although the majority of the signal remained and thus considered extracellular (median 96.9%). ΔTLF was only significant in more urbanised study areas where TLF was greatest. Beneath Dakar, Senegal, ΔTLF was significantly correlated to total bacterial cells (ρ s  0.51). No significant change in HLF following filtration across all data indicates these fluorophores are extracellular. Our results suggest that TLF and HLF are more mobile than faecal indicator bacteria and larger pathogens in groundwater, as the predominantly extracellular fluorophores are less prone to straining. Consequently, TLF/HLF are more precautionary indicators of microbial risks than faecal indicator bacteria in groundwater-derived drinking water.

Nanomaterials (NMs) can interact with the innate immunity of organisms. It remains, however, unclear whether these interactions can compromise the immune functioning of the host when faced with a disease threat. Co-exposure with pathogens is thus a powerful approach to assess the immuno-safety of NMs. In this paper, we studied the impacts of in vivo exposure to a biocidal NM on the gut microbiome, host immune responses, and susceptibility of the host to a bacterial challenge in an earthworm. Eisenia fetida were exposed to CuO-nanoparticles in soil for 28 days, after which the earthworms were challenged with the soil bacterium Bacillus subtilis . Immune responses were monitored by measuring mRNA levels of known earthworm immune genes. Effects of treatments on the gut microbiome were also assessed to link microbiome changes to immune responses. Treatments caused a shift in the earthworm gut microbiome. Despite these effects, no impacts of treatment on the expression of earthworm immune markers were recorded. The methodological approach applied in this paper provides a useful framework for improved assessment of immuno-safety of NMs. In addition, we highlight the need to investigate time as a factor in earthworm immune responses to NM exposure.

Purpose: Section 136 (S136) of the Mental Health Act (1983, 2007) provides legislative powers for police officers to detain those suspected of being 'mentally disordered' for a mental health assessment. Despite its increasing use, there is currently little qualitative research exploring detainee's experiences. Methodology: Participants recruited from NHS places of safety participated in a semi-structured interview. The novel application of Critical Incident Technique (CIT) within this study enabled the specific identification of critical incidents which mental health service users thought had either helped with, or worsened the S136 detention experience. A wish list of absent factors was also gathered. Findings: Six categories of helpful critical incidents, seven categories of unhelpful critical incidents and five categories of wish-list items were identified. The importance of authentic relationships underpinned many categories, as well as challenging stigma, considering previous detentions; and receiving practical support. Originality/value: The outlined study is the first of its kind to utilise CIT methodology to specifically identify critical incidents related to the process of S136 detention. These findings provide specific ways to improve the experience of detention informed directly by those who have been directly subjected to S136. Key points Take time to invest in meaningful relationships with those who are detained; asking about the individual's life experience and their perception of its relationship to their current presenting difficulties. Identify the service user's values -what's important to them, and what gives meaning to their life - and discuss this in relation to what their worries, concerns or wishes may be for treatment. Discuss previous experiences of involuntary admission- this can support all parties involved to consider the impact of detention upon the individual, and services. Use problem-free discussions to normalise and help de-stigmatise mental health difficulties and support rapport building. Provide practical support, such as food, drink and routinely allow those who are detained to gather personal belongings such as a change of clothes or a book. Ensure advocacy services are always available and accessible for those who are detained under S136. Where possible, avoid the use of restrictive or stigmatising practices in front of the public where possible ( e.g. use of handcuffs, police vehicles as transport) to minimise risk of increasing mental health stigma.

Soil microorganisms act as gatekeepers for soil-atmosphere carbon exchange by balancing the accumulation and release of soil organic matter. However, poor understanding of the mechanisms responsible hinders the development of effective land management strategies to enhance soil carbon storage. Here we empirically test the link between microbial ecophysiological traits and topsoil carbon content across geographically distributed soils and land use contrasts. We discovered distinct pH controls on microbial mechanisms of carbon accumulation. Land use intensification in low-pH soils that increased the pH above a threshold (~6.2) leads to carbon loss through increased decomposition, following alleviation of acid retardation of microbial growth. However, loss of carbon with intensification in near-neutral pH soils was linked to decreased microbial biomass and reduced growth efficiency that was, in turn, related to trade-offs with stress alleviation and resource acquisition. Thus, less-intensive management practices in near-neutral pH soils have more potential for carbon storage through increased microbial growth efficiency, whereas in acidic soils, microbial growth is a bigger constraint on decomposition rates.

Significant prolonged aryl hydrocarbon receptor (AHR) activation, classically exhibited following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin, can cause a variety of undesirable toxicological effects. Novel pharmaceutical chemistries also have the potential to cause activation of AHR and consequent toxicities in pre-clinical species and man. Previous methods either employed relatively expensive and low-throughput primary hepatocyte dosing with PCR endpoint, or low resolution overexpressing reporter gene assays. We have developed, validated and applied an in vitro microtitre plate imaging-based medium throughput screening assay for the assessment of endogenous species-specific AHR activation potential via detection of induction of the surrogate transcriptional target Cytochrome P450 CYP1A1. Routine testing of pharmaceutical drug development candidate chemistries using this assay can influence the chemical design process and highlight AHR liabilities. This assay should be introduced such that human AHR activation liability is flagged early for confirmatory testing., (© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Productivity and predation are thought to be crucial drivers of bacterial diversity. We tested how the productivity-diversity of a natural bacterial community is modified by the presence of protist predators with different feeding preferences. In the absence of predators, there was a unimodal relationship between bacterial diversity and productivity. We found that three protist species (Bodo, Spumella and Cyclidium) had widely divergent effects on bacterial diversity across the productivity gradient. Bodo and Cyclidium had little effect on the shape of the productivity-diversity gradient, while Spumella flattened the relationship. We explain these results in terms of the feeding preferences of these predators.

Purpose: To establish methodology for the culture of human choroidal melanocytes to compare their responsiveness to melanocyte stimulating hormone (MSH) with that of their transformed melanoma counterparts and with that of the retinal epithelial cell., Methods: Choroidal melanocytes from the choroid of eyes enucleated for the presence of malignant melanoma were cultured in MCDB 153 medium supplemented with insulin, transferrin, hydrocortisone, glutamine, nystatin, vitamin E, phorbol myristate acetate, bovine hypothalamic extract, cholera toxin, and chelexed fetal calf serum., Results: High yields of pure spindle-shaped bipolar melanocytes were obtained with a doubling time of 3 to 4 days in nine consecutive eyes. Cells continued to divide after 4 months in culture. In contrast, uveal malignant melanoma cells grew rapidly in a relatively simple medium of Ham's F12:DMEM (1:1) supplemented with fetal calf serum, insulin, transferrin and glutamine. This medium was unable to support choroidal melanocytes. Choroidal melanocytes were DOPA-positive with appreciable tyrosinase activity that significantly increased with treatment with MSH. MSH also significantly altered the size, local density, and distribution of primary and mature melanosomes of ocular melanocytes. In contrast, uveal melanoma cells had a low level of tyrosinase activity and failed to respond to MSH with either an increase in enzyme activity or melanosome size. Retinal epithelial cells failed to show significant tyrosinase activity under the conditions studied or any increase in melanosome size in response to MSH., Conclusion: Ocular melanocytes show evidence of regulation by MSH and a range of mitogenic stimuli unlike the transformed melanoma cells, implying a loss of regulatory control in the latter.

Following our recent finding that calmodulin antagonists can reduce cancer cell attachment to extracellular matrix proteins, we investigated the calmodulin antagonistic and anti-attachment properties of the non-steroidal anti-oestrogens tamoxifen and droloxifene. These drugs and four of their active metabolites were found to have calmodulin antagonist activity with IC50 values of 2-4 microM and to be capable of inhibiting attachment of murine B16 melanoma to extracellular matrix proteins in vitro. IC50 values for inhibition of attachment were 11 microM for tamoxifen and ranged from 5 to 40 microM for the other five compounds tested. (Poor reproducibility in drug potency between attachment experiments was almost certainly due to the low aqueous solubility of these drugs.) The effects of tamoxifen on cell/matrix adhesion were most evident between 15 min and 3 h of cell attachment. No effects of tamoxifen were evident in cells which had been allowed to attach for 6 h or more. Tamoxifen at concentrations between 0.1 and 30 microM was without effect on intracellular free calcium concentration. Tamoxifen also inhibited attachment of human ocular melanoma cells and human breast cancer (MCF7) cells to type I collagen. The concentration at which tamoxifen and its metabolites affect cell attachment in vitro (2-14 microM) is of the same order as the tissue concentrations of these drugs achieved clinically. The possibility exists that reduction of cell/matrix interactions may contribute to the clinical anti-metastatic efficacy of tamoxifen and some of its active metabolites.

Diabetes has no known cure and is a leading source of morbidity and mortality. Clinical management involves patients managing a complex and variable regimen. This article reviews the determinants of effective self-management and the methods of promoting better self-management. Trait variables (e.g., personality and demographics) have been presumed to affect self-management, but evidence suggests they have little impact. The important determinants of self-management are transient situational factors such as psychological stress and social pressure to eat. Interventions to promote better self-management have reported initial improvements in blood glucose control, but the long-term effects are unclear. We conclude that self-management has been inadequately assessed and that attempts to improve self-management have relied excessively on providing information. More research is needed to clarify determinants of self-management, and interventions to improve self-management will need to change these determinants.