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1.
Trials ; 25(1): 228, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38566197

ABSTRACT

BACKGROUND: Two million people in the UK are living with or beyond cancer and a third of them report poor quality of life (QoL) due to problems such as fatigue, fear of cancer recurrence, and concerns about returning to work. We aimed to develop and evaluate an intervention based on acceptance and commitment therapy (ACT), suited to address the concerns of cancer survivors and in improving their QoL. We also recognise the importance of exercise and vocational activity on QoL and therefore will integrate options for physical activity and return to work/vocational support, thus ACT Plus (+). METHODS: We will conduct a multi-centre, pragmatic, theory driven, randomised controlled trial. We will assess whether ACT+ including usual aftercare (intervention) is more effective and cost-effective than usual aftercare alone (control). The primary outcome is QoL of participants living with or beyond cancer measured using the Functional Assessment of Cancer Therapy: General scale (FACT-G) at 52 weeks. We will recruit 344 participants identified from secondary care sites who have completed hospital-based treatment for cancer with curative intent, with low QoL (determined by the FACT-G) and randomise with an allocation ratio of 1:1 to the intervention or control. The intervention (ACT+) will be delivered by NHS Talking Therapies, specialist services, and cancer charities. The intervention consists of up to eight sessions at weekly or fortnightly intervals using different modalities of delivery to suit individual needs, i.e. face-to-face sessions, over the phone or skype. DISCUSSION: To date, there have been no robust trials reporting both clinical and cost-effectiveness of an ACT based intervention for people with low QoL after curative cancer treatment in the UK. We will provide high quality evidence of the effectiveness and cost-effectiveness of adding ACT+ to usual aftercare provided by the NHS. If shown to be effective and cost-effective then commissioners, providers and cancer charities will know how to improve QoL in cancer survivors and their families. TRIAL REGISTRATION: ISRCTN: ISRCTN67900293 . Registered on 09 December 2019. All items from the World Health Organization Trial Registration Data Set for this protocol can be found in Additional file 2 Table S1.


Subject(s)
Acceptance and Commitment Therapy , Neoplasms , Humans , Quality of Life , Aftercare , Survivors , Cost-Benefit Analysis , Neoplasms/therapy , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
2.
World Psychiatry ; 23(1): 101-112, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38214639

ABSTRACT

Narratives describing first-hand experiences of recovery from mental health problems are widely available. Emerging evidence suggests that engaging with mental health recovery narratives can benefit people experiencing mental health problems, but no randomized controlled trial has been conducted as yet. We developed the Narrative Experiences Online (NEON) Intervention, a web application providing self-guided and recommender systems access to a collection of recorded mental health recovery narratives (n=659). We investigated whether NEON Intervention access benefited adults experiencing non-psychotic mental health problems by conducting a pragmatic parallel-group randomized trial, with usual care as control condition. The primary endpoint was quality of life at week 52 assessed by the Manchester Short Assessment (MANSA). Secondary outcomes were psychological distress, hope, self-efficacy, and meaning in life at week 52. Between March 9, 2020 and March 26, 2021, we recruited 1,023 participants from across England (the target based on power analysis was 994), of whom 827 (80.8%) identified as White British, 811 (79.3%) were female, 586 (57.3%) were employed, and 272 (26.6%) were unemployed. Their mean age was 38.4±13.6 years. Mood and/or anxiety disorders (N=626, 61.2%) and stress-related disorders (N=152, 14.9%) were the most common mental health problems. At week 52, our intention-to-treat analysis found a significant baseline-adjusted difference of 0.13 (95% CI: 0.01-0.26, p=0.041) in the MANSA score between the intervention and control groups, corresponding to a mean change of 1.56 scale points per participant, which indicates that the intervention increased quality of life. We also detected a significant baseline-adjusted difference of 0.22 (95% CI: 0.05-0.40, p=0.014) between the groups in the score on the "presence of meaning" subscale of the Meaning in Life Questionnaire, corresponding to a mean change of 1.1 scale points per participant. We found an incremental gain of 0.0142 quality-adjusted life years (QALYs) (95% credible interval: 0.0059 to 0.0226) and a £178 incremental increase in cost (95% credible interval: -£154 to £455) per participant, generating an incremental cost-effectiveness ratio of £12,526 per QALY compared with usual care. This was lower than the £20,000 per QALY threshold used by the National Health Service in England, indicating that the intervention would be a cost-effective use of health service resources. In the subgroup analysis including participants who had used specialist mental health services at baseline, the intervention both reduced cost (-£98, 95% credible interval: -£606 to £309) and improved QALYs (0.0165, 95% credible interval: 0.0057 to 0.0273) per participant as compared to usual care. We conclude that the NEON Intervention is an effective and cost-effective new intervention for people experiencing non-psychotic mental health problems.

3.
Sci Total Environ ; 905: 167225, 2023 Dec 20.
Article in English | MEDLINE | ID: mdl-37741411

ABSTRACT

Salinization of inland fresh surface waters in temperate climates is a growing concern due to increasing salt inputs from sources including chloride (Cl)-containing road salt de-icers, industrial waste, and landfill leachate. Groundwater pathways play an important role in the year-round delivery of Cl to streams, but quantifying this pathway, including spatiotemporal variability and amount of Cl mass stored in the subsurface, is challenging. The objective of this study was to demonstrate, evaluate, and compare the potential applications of the geoelectrical techniques - electromagnetics (EM) and direct current (DC) resistivity - for mapping salt contamination in shallow urban groundwater and characterizing the groundwater pathways delivering Cl to urban streams. EM and DC surveys were conducted (3D mapping and 2D time-lapse) across a 20 m salt-impacted stream section and surrounding riparian zone that is located near an arterial road and parking lot. Groundwater samples and soil cores were also collected to validate the geoelectrical results. Both the EM and DC surveys detected high salt concentrations in the shallow subsurface (up to 3 m depth) near the road, parking lot, and stream; however, DC more accurately represented groundwater Cl concentrations. DC results were used to calculate the total Cl mass in the subsurface, with the spatial mass distribution used to infer the temporal variability in the subsurface salt plume. Finally, time-lapse DC showed that the highest groundwater salt concentrations existed near the stream between June and October - this is expected to contribute to the elevated salt concentrations in the stream during summer months. This study has shown that EM and DC can be useful for identifying groundwater salt concentration, storage, and transport in a non-intrusive and efficient manner, making them valuable field tools for characterizing and quantifying groundwater salt pathways to urban streams.

4.
J Environ Manage ; 344: 118364, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37399619

ABSTRACT

Experimental (research-based) and non-research-based watershed monitoring programs often differ with respect to sampling frequency, monitored variables, and monitoring objectives. Isotopic variables, which are more commonly incorporated in research-based programs, can provide an indication of water sources and the transit time of water in a catchment. These variables may be a valuable complement to traditional water quality monitoring variables and have the potential to support improved hydrologic process-related insights from long term monitoring programs that typically have low resolution sampling. The purpose of this investigation is to explore the utility of incorporating isotopic variables (specifically δ18O, δ2H, and 222Rn) into routine monthly sampling regimes by comparing insights gained from these variables to monitoring only specific conductivity and chloride. A complete annual cycle of monthly groundwater and surface water monitoring data collected from the Upper Parkhill watershed in southwestern Ontario, Canada was used to characterize baseline watershed conditions, evaluate watershed resilience to climate change, and examine contamination vulnerability. Study results provide an improved understanding of appropriate tracer use in agricultural regions with isotopic variables able to provide important insights into the seasonality of hydrologic phenomena, such as the timing of groundwater recharge. A comparison of monitoring variables to present-day hydro-meteorological conditions suggests the importance of a winter dominated hydrologic regime and the potential influence of changes in precipitation on groundwater-surface water interactions. Estimated transit time dynamics indicate the likelihood for rapid contaminant transport through surface and shallow subsurface flow and highlight the possible effects of agricultural tile drainage. The sampling approach and data analysis methods adopted in this study provide the basis for improving routine watershed monitoring programs in agricultural regions.


Subject(s)
Groundwater , Water Pollutants, Chemical , Environmental Monitoring/methods , Water Quality , Agriculture , Ontario , Water Pollutants, Chemical/analysis
5.
J Med Internet Res ; 25: e44687, 2023 06 27.
Article in English | MEDLINE | ID: mdl-37368471

ABSTRACT

BACKGROUND: Digital health interventions (DHIs) are an established element of mental health service provision internationally. Regulators have positioned the best practice standard of evidence as an interventional study with a comparator reflective of standard care, often operationalized as a pragmatic trial. DHIs can extend health provision to those not currently using mental health services. Hence, for external validity, trials might openly recruit a mixture of people who have used mental health services and people who have not. Prior research has demonstrated phenomenological differences in mental health experience between these groups. Some differences between service users and nonservice users might influence the change created by DHIs; hence, research should systematically examine these differences to inform intervention development and evaluation work. This paper analyzes baseline data collected in the NEON (Narrative Experiences Online; ie, for people with experience of psychosis) and NEON-O (NEON for other [eg, nonpsychosis] mental health problems) trials. These were pragmatic trials of a DHI that openly recruited people who had used specialist mental health services and those who had not. All participants were experiencing mental health distress. NEON Trial participants had experienced psychosis in the previous 5 years. OBJECTIVE: This study aims to identify differences in baseline sociodemographic and clinical characteristics associated with specialist mental health service use for NEON Trial and NEON-O Trial participants. METHODS: For both trials, hypothesis testing was used to compare baseline sociodemographic and clinical characteristics of participants in the intention-to-treat sample who had used specialist mental health services and those who had not. Bonferroni correction was applied to significance thresholds to account for multiple testing. RESULTS: Significant differences in characteristics were identified in both trials. Compared with nonservice users (124/739, 16.8%), NEON Trial specialist service users (609/739, 82.4%) were more likely to be female (P<.001), older (P<.001), and White British (P<.001), with lower quality of life (P<.001) and lower health status (P=.002). There were differences in geographical distribution (P<.001), employment (P<.001; more unemployment), current mental health problems (P<.001; more psychosis and personality disorders), and recovery status (P<.001; more recovered). Current service users were more likely to be experiencing psychosis than prior service users. Compared with nonservice users (399/1023, 39%), NEON-O Trial specialist service users (614/1023, 60.02%) had differences in employment (P<.001; more unemployment) and current mental health problems (P<.001; more personality disorders), with lower quality of life (P<.001), more distress (P<.001), less hope (P<.001), less empowerment (P<.001), less meaning in life (P<.001), and lower health status (P<.001). CONCLUSIONS: Mental health service use history was associated with numerous differences in baseline characteristics. Investigators should account for service use in work to develop and evaluate interventions for populations with mixed service use histories. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-020-04428-6.


Subject(s)
Mental Health Services , Psychotic Disorders , Female , Humans , Male , Mental Health , Psychotic Disorders/therapy , Quality of Life
7.
Trials ; 24(1): 343, 2023 May 20.
Article in English | MEDLINE | ID: mdl-37210551

ABSTRACT

BACKGROUND: Mental health recovery narratives are a first-hand account of an individual's recovery from mental health distress, access to narratives can aid recovery. The NEON Intervention is a web-application providing access to a managed collection of narratives. We present the statistical analysis plan for assessing the effectiveness of the NEON Intervention in improving quality of life at 1-year post-randomisation. We pay particular focus on the statistical challenges encountered due to the online nature of this trial. METHODS AND DESIGN: The NEON Intervention is assessed in two trial populations, one for people with experience of psychosis in the last 5 years, and mental health distress in the last six months (NEON Trial) and one for people with experience of non-psychosis mental health problems (NEON-O Trial). Both NEON trials are two-arm randomised controlled superiority trials comparing the effectiveness of the NEON Intervention with usual care. The target sample size is 684 randomised participants for NEON and 994 for NEON-O. Participants were randomised centrally in a 1:1 ratio. RESULTS: The primary outcome is the mean score of subjective items on the Manchester Short Assessment of Quality-of-Life questionnaire (MANSA) at 52 weeks. Secondary outcomes are scores from the Herth Hope Index, Mental Health Confidence Scale, Meaning of Life questionnaire, CORE-10 questionnaire and Euroqol 5-Dimension 5-Level (EQ-5D-5L). CONCLUSION: This manuscript is the statistical analysis plan (SAP) for the NEON trials. Any post hoc analysis, such as those requested by journal reviewers will be clearly labelled as such in the final trial reporting. Trial registration Both trials were prospectively registered. NEON Trial: ISRCTN11152837, registered on 13 August 2018. NEON-O Trial: ISRCTN63197153, registered on 9 January 2020.


Subject(s)
Mental Health Recovery , Psychotic Disorders , Humans , Neon , Quality of Life , Mental Health , Psychotic Disorders/diagnosis , Psychotic Disorders/therapy , Cost-Benefit Analysis , Randomized Controlled Trials as Topic
8.
Sci Total Environ ; 876: 162781, 2023 Jun 10.
Article in English | MEDLINE | ID: mdl-36906011

ABSTRACT

Arbuscular mycorrhizal fungi were recovered from soil samples from the naturally radioactive soil at the long-abandoned South Terras uranium mine in Cornwall, UK. Species of Rhizophagus, Claroideoglomus, Paraglomus, Septoglomus, and Ambispora were recovered, and pot cultures from all except Ambispora were established. Cultures were identified to species level using morphological observation and rRNA gene sequencing combined with phylogenetic analysis. These cultures were used in pot experiments designed with a compartmentalised system to assess the contribution of fungal hyphae to the accumulation of essential elements, such as copper and zinc, and non-essential elements, such as lead, arsenic, thorium, and uranium into root and shoot tissues of Plantago lanceolata. The results indicated that none of the treatments had any positive or negative impact on shoot and root biomass. However, Rhizophagus irregularis treatments showed higher accumulation of copper and zinc in shoots, while R. irregularis and Septoglomus constrictum enhanced arsenic accumulation in roots. Moreover, R. irregularis increased uranium concentration in roots and shoots of the P. lanceolata plant. This study provides useful insight into fungal-plant interactions that determine metal and radionuclide transfer from soil into the biosphere at contaminated sites such as mine workings.


Subject(s)
Arsenic , Glomeromycota , Mycorrhizae , Soil Pollutants , Uranium , Mycorrhizae/chemistry , Uranium/analysis , Plant Roots/microbiology , Copper/analysis , Arsenic/analysis , Soil , Phylogeny , Soil Pollutants/analysis , Plants , Zinc/analysis
9.
Front Bioeng Biotechnol ; 10: 959441, 2022.
Article in English | MEDLINE | ID: mdl-36118573

ABSTRACT

The mammalian gut and its microbiome form a temporally dynamic and spatially heterogeneous environment. The inaccessibility of the gut and the spatially restricted nature of many gut diseases translate into difficulties in diagnosis and therapy for which novel tools are needed. Engineered bacterial whole-cell biosensors and therapeutics have shown early promise at addressing these challenges. Natural and engineered sensing systems can be repurposed in synthetic genetic circuits to detect spatially specific biomarkers during health and disease. Heat, light, and magnetic signals can also activate gene circuit function with externally directed spatial precision. The resulting engineered bacteria can report on conditions in situ within the complex gut environment or produce biotherapeutics that specifically target host or microbiome activity. Here, we review the current approaches to engineering spatial precision for in vivo bacterial diagnostics and therapeutics using synthetic circuits, and the challenges and opportunities this technology presents.

10.
Geochem Trans ; 23(1): 2, 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36167930

ABSTRACT

The Santa Elena Ophiolite is a well-studied ultramafic system in Costa Rica mainly comprised of peridotites. Here, tropical climatic conditions promote active laterite formation processes, but the biogeochemistry of the resulting serpentine soils is still poorly understood. The aim of this study was to characterize the soil geochemical composition and microbial community of contrasting landscapes in the area, as the foundation to start exploring the biogeochemistry of metals occurring there. The soils were confirmed as Ni-rich serpentine soils but differed depending on their geographical location within the ophiolite area, showing three serpentine soil types. Weathering processes resulted in mountain soils rich in trace metals such as cobalt, manganese and nickel. The lowlands showed geochemical variations despite sharing similar landscapes: the inner ophiolite lowland soils were more like the surrounding mountain soils rather than the north lowland soils at the border of the ophiolite area, and within the same riparian basin, concentrations of trace metals were higher downstream towards the mangrove area. Microbial community composition reflected the differences in geochemical composition of soils and revealed potential geomicrobiological inputs to local metal biogeochemistry: iron redox cycling bacteria were more abundant in the mountain soils, while more manganese-oxidizing bacteria were found in the lowlands, with the highest relative abundance in the mangrove areas. The fundamental ecological associations recorded in the serpentine soils of the Santa Elena Peninsula, and its potential as a serpentinization endemism hotspot, demonstrate that is a model site to study the biogeochemistry, geomicrobiology and ecology of tropical serpentine areas.

11.
Trials ; 23(1): 90, 2022 Jan 29.
Article in English | MEDLINE | ID: mdl-35093141

ABSTRACT

BACKGROUND: Mental health recovery narratives are first-person lived experience accounts of recovery from mental health problems, which refer to events or actions over a period of time, and which include elements of adversity or struggle, and also self-defined or observable strengths, successes, or survival. Recorded recovery narratives are those presented in invariant form, including text, audio, or video. In a previous publication, we presented a protocol for three pragmatic trials of the Narrative Experiences Online (NEON) Intervention, a web application recommending recorded recovery narratives to participants. The aim of the definitive NEON Trial was to understand whether the NEON Intervention benefitted people with experience of psychosis. The aim of the smaller NEON-O and NEON-C trials was to evaluate the feasibility of conducting definitive trials of the NEON Intervention with people (1) experiencing non-psychosis mental health problems and (2) who informally care for others experiencing mental health problems. An open recruitment strategy with a 60-week recruitment period was developed. Recruitment for the NEON Trial and NEON-O Trial targeted mental health service users and people not using mental health services. The NEON Trial recruited to time and target. The NEON-O Trial achieved its target in 10 weeks. Analysis considered by a Programme Steering Committee after the target was achieved demonstrated a definitive result could be obtained if the trial was adapted for recruitment to continue. The UK Health Research Authority approved all needed amendments following ethical review. PURPOSE OF THIS ARTICLE: To describe the decision-making process for amending the NEON-O Trial and to describe amendments made to the NEON-O Trial to enable a definitive result. The article describes amendments to the aims, objectives, design, power calculation, recruitment rate, process evaluation design, and informed consent documents. The extended NEON-O Trial adopts analysis principles previously specified for the NEON Trial. The article provides a model for other studies adapting feasibility trials into definitive trials. TRIAL REGISTRATION: All trials prospectively registered. NEON Trial: ISRCTN11152837 . Registered on 13th August 2018. NEON-C Trial: ISRCTN76355273 . Registered on 9th January 2020. NEON-O Trial: ISRCTN63197153 . Registered on 9th January 2020. The NEON-O Trial ISRCTN was updated when amendments were approved. Amendment details: NOSA2, 30th October 2020.


Subject(s)
Mental Health Recovery , Psychotic Disorders , Humans , Mental Health , Neon , Quality of Life
12.
J Ment Health ; 31(2): 273-280, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34983300

ABSTRACT

BACKGROUND: Mental health recovery narratives are an active ingredient of recovery-oriented interventions such as peer support. Recovery narratives can create connection and hope, but there is limited evidence on the predictors of impact. AIMS: The aim of this study was to identify characteristics of the narrator, narrative content and participant which predict the short-term impact of recovery narratives on participants. METHOD: Independent studies were conducted in an experimental (n = 40) and a clinical setting (n = 13). In both studies, participants with mental health problems received recorded recovery narratives and rated impact on hopefulness and connection. Predictive characteristics were identified using multi-level modelling. RESULTS: The experimental study found that narratives portraying a narrator as living well with mental health problems that is intermediate between no and full recovery, generated higher self-rated levels of hopefulness. Participants from ethnic minority backgrounds had lower levels of connection with narrators compared to participants from a white background, potentially due to reduced visibility of a narrator's diversity characteristics. CONCLUSIONS: Narratives describing partial but not complete recovery and matching on ethnicity may lead to a higher impact. Having access to narratives portraying a range of narrator characteristics to maximise the possibility of a beneficial impact on connection and hopefulness.


Subject(s)
Mental Health Recovery , Ethnicity , Hope , Humans , Minority Groups , Narration
13.
Ecology ; 103(6): e3626, 2022 06.
Article in English | MEDLINE | ID: mdl-34967948

ABSTRACT

Plants are subject to trade-offs among growth strategies such that adaptations for optimal growth in one condition can preclude optimal growth in another. Thus, we predicted that a plant species that responds positively to one global change treatment would be less likely than average to respond positively to another treatment, particularly for pairs of treatments that favor distinct traits. We examined plant species' abundances in 39 global change experiments manipulating two or more of the following: CO2 , nitrogen, phosphorus, water, temperature, or disturbance. Overall, the directional response of a species to one treatment was 13% more likely than expected to oppose its response to a another single-factor treatment. This tendency was detectable across the global data set, but held little predictive power for individual treatment combinations or within individual experiments. Although trade-offs in the ability to respond to different global change treatments exert discernible global effects, other forces obscure their influence in local communities.


Subject(s)
Nitrogen , Plants , Acclimatization , Temperature , Water
14.
Sci Total Environ ; 807(Pt 3): 151054, 2022 Feb 10.
Article in English | MEDLINE | ID: mdl-34699817

ABSTRACT

Quantifying the contribution of septic systems to contaminant, including nutrient, loading to streams is needed in many watersheds to inform water quality management programs. However, this quantification is challenging due to the distributed locations of septic systems and uncertainties regarding the pathways delivering effluent from septic systems (functioning and failing) to a stream. The objectives of this study were firstly to evaluate how septic effluent inputs to streams vary with stream discharge conditions for multiple subwatersheds with different characteristics (i.e., geology, septic system density, and typical age), and secondly to examine new approaches for distinguishing the pathways and the contributing areas delivering septic effluent to streams. These approaches use the artificial sweetener acesulfame as a conservative tracer for septic effluent in applications of: (i) stream concentration-discharge (C-Q) relationships using low frequency sampling data, (ii) hysteresis behavior in event-based C-Q relationships, and (iii) longitudinal stream sampling. For all nine subwatersheds studied, the amount of septic effluent reaching the subwatershed outlets was considerably higher during high stream discharge (event) conditions compared to low discharge (baseflow) conditions, suggesting pathways other than groundwater may also be important. Generally, the percentage of septic effluent reaching the outlets was less for subwatersheds with newer households compared to those with older households. The combined interpretation of low frequency and event-based C-Q relationships indicate that complex pathways control the delivery of septic effluent to the subwatershed outlets. The interpretations suggest that groundwater pathways may dominate in some subwatersheds, while more rapid pathways associated with failing septic systems (e.g., overland runoff) may be important in others. Finally, longitudinal stream sampling illustrate the potential of acesulfame data to identify key areas contributing septic effluent to the stream. The novel approaches used here can be applied to guide future investigations aiming to quantify and manage water quality impairment from septic systems.


Subject(s)
Groundwater , Rivers , Sewage , Water Pollution , Geology , Nutrients , Uncertainty , Water Quality
15.
Synth Syst Biotechnol ; 6(3): 231-241, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34541345

ABSTRACT

The development of Drug Delivery Systems (DDS) has led to increasingly efficient therapies for the treatment and detection of various diseases. DDS use a range of nanoscale delivery platforms produced from polymeric of inorganic materials, such as micelles, and metal and polymeric nanoparticles, but their variant chemical composition make alterations to their size, shape, or structures inherently complex. Genetically encoded protein nanocages are highly promising DDS candidates because of their modular composition, ease of recombinant production in a range of hosts, control over assembly and loading of cargo molecules and biodegradability. One example of naturally occurring nanocompartments are encapsulins, recently discovered bacterial organelles that have been shown to be reprogrammable as nanobioreactors and vaccine candidates. Here we report the design and application of a targeted DDS platform based on the Thermotoga maritima encapsulin reprogrammed to display an antibody mimic protein called Designed Ankyrin repeat protein (DARPin) on the outer surface and to encapsulate a cytotoxic payload. The DARPin9.29 chosen in this study specifically binds to human epidermal growth factor receptor 2 (HER2) on breast cancer cells, as demonstrated in an in vitro cell culture model. The encapsulin-based DDS is assembled in one step in vivo by co-expressing the encapsulin-DARPin9.29 fusion protein with an engineered flavin-binding protein mini-singlet oxygen generator (MiniSOG), from a single plasmid in Escherichia coli. Purified encapsulin-DARPin_miniSOG nanocompartments bind specifically to HER2 positive breast cancer cells and trigger apoptosis, indicating that the system is functional and specific. The DDS is modular and has the potential to form the basis of a multi-receptor targeted system by utilising the DARPin screening libraries, allowing use of new DARPins of known specificities, and through the proven flexibility of the encapsulin cargo loading mechanism, allowing selection of cargo proteins of choice.

16.
Sci Total Environ ; 799: 149443, 2021 Dec 10.
Article in English | MEDLINE | ID: mdl-34371419

ABSTRACT

Internal P stores in offshore lakebed sediments play an important role in lake nutrient dynamics. While P stores in nearshore aquifer sediments may also be important for nutrient dynamics, it is unclear whether P accumulates in these sediments, and if so, what factors control P accumulation and its potential later release from the sediments to nearshore waters. This knowledge gap was addressed by conducting field investigations at seven nearshore sites located along the shores of Lake Erie, Lake Huron and Lake Ontario, Canada, with more detailed dissolved and sediment phase characterization completed for two nearshore sites. PO4 concentrations were observed to be higher (>50 µg/L) in the more reducing nearshore aquifers compared to more oxidizing nearshore aquifers (<20 µg/L), despite similar total solid phase P concentrations at the sites. PO4 mobility in the nearshore aquifers was found to be closely linked to redox-driven Fe cycling. In the more reducing aquifers, dissolved PO4 was highest near the redox boundary present in the shallow sediments where oxic infiltrating surface water mixes with reducing groundwater. In the more oxidizing aquifers, solid phase characterization indicated that PO4 is sequestered to Fe oxide mineral phases throughout the nearshore aquifer which explains the low dissolved PO4. While pH was not found to be important for PO4 mobility at the study sites, batch laboratory experiments indicate that increased infiltration of more alkaline surface water into nearshore aquifers may promote PO4 release from the sediments. The study findings demonstrate that while internal P storage mechanisms in nearshore aquifer sediments may currently be limiting P loads to lakes, it is possible that P stores that build up over time may result in increased P loads to lakes in the future.


Subject(s)
Groundwater , Water Pollutants, Chemical , Environmental Monitoring , Geologic Sediments , Lakes , Ontario , Phosphorus/analysis , Water Pollutants, Chemical/analysis
17.
Int J Eat Disord ; 54(7): 1224-1237, 2021 07.
Article in English | MEDLINE | ID: mdl-33998020

ABSTRACT

OBJECTIVE: Increasing the availability and accessibility of evidence-based treatments for eating disorders is an important goal. This study investigated the effectiveness and cost-effectiveness of guided self-help via face-to-face meetings (fGSH) and a more scalable method, providing support via email (eGSH). METHOD: A pragmatic, randomized controlled trial was conducted at three sites. Adults with binge-eating disorders were randomized to fGSH, eGSH, or a waiting list condition, each lasting 12 weeks. The primary outcome variable for clinical effectiveness was overall severity of eating psychopathology and, for cost-effectiveness, binge-free days, with explorative analyses using symptom abstinence. Costs were estimated from both a partial societal and healthcare provider perspective. RESULTS: Sixty participants were included in each condition. Both forms of GSH were superior to the control condition in reducing eating psychopathology (IRR = -1.32 [95% CI -1.77, -0.87], p < .0001; IRR = -1.62 [95% CI -2.25, -1.00], p < .0001) and binge eating. Attrition was higher in eGSH. Probabilities that fGSH and eGSH were cost-effective compared with WL were 93% (99%) and 51% (79%), respectively, for a willingness to pay of £100 (£150) per additional binge-free day. DISCUSSION: Both forms of GSH were associated with clinical improvement and were likely to be cost-effective compared with a waiting list condition. Provision of support via email is likely to be more convenient for many patients although the risk of non-completion is greater.


Subject(s)
Binge-Eating Disorder , Cognitive Behavioral Therapy , Adult , Cost-Benefit Analysis , Health Behavior , Humans , Treatment Outcome
18.
JMIR Form Res ; 5(5): e24417, 2021 May 27.
Article in English | MEDLINE | ID: mdl-34042595

ABSTRACT

BACKGROUND: The internet enables sharing of narratives about health concerns on a substantial scale, and some digital health narratives have been integrated into digital health interventions. Narratives describing recovery from health problems are a focus of research, including those presented in recorded (eg, invariant) form. No clinical trial has been conducted on a web-based intervention providing access to a collection of Recorded Recovery Narratives (RRNs). OBJECTIVE: This study presents knowledge produced through the development of the Narrative Experiences Online (NEON) Intervention, a web-based intervention incorporating the algorithmic recommendation of RRNs. METHODS: Knowledge was gathered through knowledge integration (KI) activities. KI1 synthesized previous studies to produce the NEON Impact Model describing how accessing RRNs produces health-related outcomes. KI2 developed curation principles for the NEON Collection of RRNs through consultation with the NEON Lived Experience Advisory Panel and the curation of a preliminary collection. KI3 identified harm minimization strategies for the NEON Intervention through consultation with the NEON International Advisory Board and Lived Experience Advisory Panel. The NEON Intervention was finalized through 2 research studies (RS). In RS1, mental health service users (N=40) rated the immediate impact of randomly presented narratives to validate narrative feedback questions used to inform the recommendation algorithm. In RS2, mental health service users (n=25) were interviewed about their immediate response to a prototype of the NEON Intervention and trial procedures and then were interviewed again after 1 month of use. The usability and acceptability of the prototype and trial procedures were evaluated and refinements were made. RESULTS: KI1 produced the NEON Impact Model, which identifies moderators (recipient and context), mechanisms of connection (reflection, comparison, learning, and empathy), processes (identification of change from narrative structure or content and internalization of observed change), and outcomes (helpful and unhelpful). KI2 identified 22 curation principles, including a mission to build a large, heterogeneous collection to maximize opportunities for connection. KI3 identified seven harm minimization strategies, including content warnings, proactive and reactive blocking of narratives, and providing resources for the self-management of emotional distress. RS1 found variation in the impact of narratives on different participants, indicating that participant-level feedback on individual narratives is needed to inform a recommender system. The order of presentation did not predict narrative feedback. RS2 identified amendments to web-based trial procedures and the NEON Intervention. Participants accessed some narratives multiple times, use reduced over the 4-week period, and narrative feedback was provided for 31.8% (105/330) of narrative accesses. CONCLUSIONS: RRNs can be integrated into web-based interventions. Evaluating the NEON Intervention in a clinical trial is feasible. The mixed methods design for developing the NEON Intervention can guide its extension to other clinical populations, the design of other web-based mental health interventions, and the development of narrative-based interventions in mental health.

19.
Environ Sci Technol ; 55(12): 8079-8089, 2021 06 15.
Article in English | MEDLINE | ID: mdl-34043335

ABSTRACT

Metal oxides that form near sediment-water interfaces in marine and riverine settings are known to act as a sediment trap for pollutants of environmental concern (e.g., arsenic and mercury). The occurrence of these pollutant traps near sediment-water interfaces in nearshore lake environments is unclear yet important to understand because they may accumulate pollutants that may be later released as environmental conditions change. This study evaluates the prevalence of pollutant sediment traps in nearshore aquifers adjacent to large lakes and the factors that affect the accumulation and release of pollutants, specifically arsenic. Field data from six sites along the Laurentian Great Lakes indicate widespread enrichment of arsenic in nearshore aquifers with arsenic sequestered to iron oxide phases. Arsenic enrichment at all sites (solid-phase arsenic >2 µg/g) suggests that this is a naturally occurring phenomenon. Arsenic was more mobile in reducing aquifers with elevated dissolved arsenic (up to 60 µg/L) observed, where reducing groundwater mixes with infiltrating oxic lake water. Dissolved arsenic was low (<3 µg/L) in all oxic nearshore aquifers studied despite high solid-phase arsenic concentrations. The findings have broad implications for understanding the widespread accumulation of reactive pollutants in nearshore aquifers and factors that affect their release to large lakes.


Subject(s)
Arsenic , Groundwater , Water Pollutants, Chemical , Arsenic/analysis , Environmental Monitoring , Geologic Sediments , Lakes , Water Pollutants, Chemical/analysis
20.
Sci Total Environ ; 778: 146069, 2021 Jul 15.
Article in English | MEDLINE | ID: mdl-33714832

ABSTRACT

Bioretention systems are popular low impact development stormwater management features designed to remove pollutants, including phosphorus (P), from urban stormwater runoff. While the performance of bioretention systems in retaining P has been well studied, seasonal variability of P retention in field-scale systems installed in cold climates, including the influence of high road de-icing salt (sodium chloride) inputs, remains unclear. Two large field-scale bioretention systems installed in London, Ontario, Canada were monitored over their initial operational period to evaluate the seasonal trends in the retention of different forms of P in bioretention systems and the impact of high salt loading. Over the 12-month monitoring period, a net retention of total P and dissolved organic P, and a net release of soluble reactive P and total dissolved P mass were observed. Reduced hydrological performance and increased effluent P concentrations resulted in high P release from the bioretention systems in early to mid-spring (March and April), with most release occurring during a few individual large precipitation events. Laboratory-scale column experiments were performed using the engineered soil media installed in the field-scale bioretention systems to isolate the effect of high salt loading on P release. Column experiments combined with field data indicate that prolonged high salt loads through winter and spring may have contributed to elevated spring P release, mostly in the form of soluble reactive P, from the field-scale bioretention systems. Findings from this study are needed to better understand the performance of bioretention systems with respect to P retention as required to improve urban stormwater management in cold climates. Results have implications for further investigations of the impact of road salt on P mobility in bioretention systems and more broadly in roadside soils and groundwater systems.


Subject(s)
Phosphorus , Rain , Cold Climate , London , Ontario , Phosphorus/analysis , Seasons , Sodium Chloride , Soil
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