Showing papers by "University of Dundee published in 2022"

The role of environmental technology for energy demand and energy efficiency: Evidence from OECD countries

Abstract: The present study aims to fill an important research gap by investigating the role of environmental-related technologies on energy demand and energy efficiency in a sample of 28 OECD economies. The current study utilizes annual data for the period of 1990–2014 and employs panel estimation techniques, which addresses the issues of cross-sectional dependence, fixed effect, and endogeneity. The results, across various estimates, confirm that environmental technology has a substantial negative influence on energy consumption and also plays an important role in improving energy efficiency by reducing energy intensity. These evidences suggest that environmental technology helps the OECD economies to reduce their overall energy consumption and improves overall energy efficiency in their respective countries. The comprehensive empirical outcomes document that financial development and income are the key determinants of energy demand. Given these results, the study proposes several fruitful implications regarding sustainable development goals of OECD countries.

The (in)justices of smart local energy systems: A systematic review, integrated framework, and future research agenda

Abstract: Smart technology alongside local energy systems are regularly considered critical for a low-carbon transition. More recently, a growing body of literature has started to examine the (in)justices that exist within energy systems and the impact this has on all people having equal access to safe, affordable, and sustainable energy. To date, little research has sought to synthesise the evidence base around whether smart local energy systems are an effective means of promoting energy justice. This paper presents a systematic literature review of 105 peer-reviewed articles, with a focus on understanding the antecedents of energy justice in local energy systems and the role smart technology can play in mitigating these (in)justices. We propose an integrated framework outlining our findings and discuss the implications for a future research agenda.

Identifying plant genes shaping microbiota composition in the barley rhizosphere

Abstract: Abstract A prerequisite to exploiting soil microbes for sustainable crop production is the identification of the plant genes shaping microbiota composition in the rhizosphere, the interface between roots and soil. Here, we use metagenomics information as an external quantitative phenotype to map the host genetic determinants of the rhizosphere microbiota in wild and domesticated genotypes of barley, the fourth most cultivated cereal globally. We identify a small number of loci with a major effect on the composition of rhizosphere communities. One of those, designated the QRMC-3HS , emerges as a major determinant of microbiota composition. We subject soil-grown sibling lines harbouring contrasting alleles at QRMC-3HS and hosting contrasting microbiotas to comparative root RNA-seq profiling. This allows us to identify three primary candidate genes, including a Nucleotide-Binding-Leucine-Rich-Repeat ( NLR ) gene in a region of structural variation of the barley genome. Our results provide insights into the footprint of crop improvement on the plant’s capacity of shaping rhizosphere microbes.

Discovery of G2019S-Selective Leucine Rich Repeat Protein Kinase 2 inhibitors with in vivo efficacy

Abstract: Mutations in the Leucine Rich Repeat Protein Kinase 2 gene (LRRK2) are the most common genetic causes of Parkinson's Disease (PD). The G2019S mutation is the most common inherited LRRK2 mutation, occurs in the kinase domain, and results in increased kinase activity. We report the discovery and development of compound 38, an indazole-based, G2019S-selective (>2000-fold vs. WT) LRRK2 inhibitor capable of entering rodent brain (Kp = 0.5) and selectively inhibiting G2019S-LRRK2. The compounds disclosed herein present a starting point for further development of brain penetrant G2019S selective inhibitors that hopefully reduce lung phenotype side-effects and pave the way to providing a precision medicine for people with PD who carry the G2019S mutation.

A systematic review of methods used to conduct decentralised clinical trials

Abstract: Aims To evaluate, using quantitative and qualitative approaches, published data on the design and conduct of decentralised clinical trials (DCTs). Methods We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, ProQuest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and Google Scholar for publications reporting, discussing, or evaluating decentralised clinical research methods. Reports of randomised clinical trials using decentralised methods were included in a focused quantitative analysis with a primary outcome of number of randomised participants. All publications discussing or evaluating DCTs were included in a wider qualitative analysis to identify advantages, disadvantages, facilitators, barriers and stakeholder opinions of decentralised clinical trials. Quantitative data were summarised using descriptive statistics, and qualitative data analysed using a thematic approach. Results Initial searches identified 19 704 articles. After removal of duplicates, 18 553 were screened, resulting in 237 eligible for full-text assessment. Forty-five trials were included in the quantitative analysis; 117 documents were included in the qualitative analysis. Trials were widely heterogeneous in design and reporting, precluding meta-analysis of the effect of DCT methods on the primary recruitment outcome. Qualitative analysis formulated 4 broad themes: value, burden, safety and equity. Participant and stakeholder experiences of DCTs were incompletely represented. Conclusion DCTs are developing rapidly. However, there is insufficient evidence to confirm which methods are most effective in trial recruitment, retention, or overall cost. The identified advantages, disadvantages, facilitators and barriers should inform the development of DCT methods. We recommend further research on how DCTs are experienced and perceived by participants and stakeholders to maximise potential benefits.

Founder cell configuration drives competitive outcome within colony biofilms

Abstract: Abstract Bacteria can form dense communities called biofilms, where cells are embedded in a self-produced extracellular matrix. Exploiting competitive interactions between strains within the biofilm context can have potential applications in biological, medical, and industrial systems. By combining mathematical modelling with experimental assays, we reveal that spatial structure and competitive dynamics within biofilms are significantly affected by the location and density of the founder cells used to inoculate the biofilm. Using a species-independent theoretical framework describing colony biofilm formation, we show that the observed spatial structure and relative strain biomass in a mature biofilm comprising two isogenic strains can be mapped directly to the geographical distributions of founder cells. Moreover, we define a predictor of competitive outcome that accurately forecasts relative abundance of strains based solely on the founder cells’ potential for radial expansion. Consequently, we reveal that variability of competitive outcome in biofilms inoculated at low founder density is a natural consequence of the random positioning of founding cells in the inoculum. Extension of our study to non-isogenic strains that interact through local antagonisms, shows that even for strains with different competition strengths, a race for space remains the dominant mode of competition in low founder density biofilms. Our results, verified by experimental assays using Bacillus subtilis , highlight the importance of spatial dynamics on competitive interactions within biofilms and hence to related applications.

Visualisation of proteome-wide ordered protein abundances in Trypanosoma brucei

Abstract: Background: Trypanosoma brucei is a protozoan parasite and etiological agent of human and animal African trypanosomiasis. It has a complex life cycle, but the most studied cellular types are the in vitro cultivated bloodstream- and procyclic-forms. These correspond to the replicating, mammalian host bloodstream-dwelling, slender trypomastigotes and tsetse vector midgut-dwelling procyclic lifecycle stages, respectively. Several proteomics studies have reported the differential abundance of proteins between these in vitro cultivated cell types. However, there are no datasets providing protein abundance, from most to least abundant, within and between both cell types. Methods: We used MaxQuant software 1.6.10.4 to reprocess a recent large-scale proteomics experiment from our laboratory and extracted intensity-based quantifications of the bloodstream and procyclic form proteomes. Results: We created a web interface to visually explore protein abundances within and between the in vitro cultivated T. brucei bloodstream and procyclic form proteomes. Conclusions: The protein abundance visualization tool, searchable by protein name(s) and attribute(s), is likely to be useful to the trypanosome research community. It will allow users to contextualise their proteins of interest in terms of their abundances in the T. brucei bloodstream and procyclic form proteomes.

Psychosocial factors that distinguish between men and women who have suicidal thoughts and attempt suicide: findings from a national probability sample of adults

Abstract: Abstract Background Previous research has highlighted the importance of understanding which psychosocial factors distinguish between those with suicide thoughts compared to those who attempt suicide. This study aims to investigate these distinguishing factors further within an ideation-to-action framework and to explore sex differences in suicide risk. Methods Participants ( n = 7546, aged 16+) were from the cross-sectional Adult Psychiatric Morbidity Survey (APMS; 2014) of England. Face-to-face and self-completion questionnaires assessed lifetime suicidal ideation, lifetime suicide attempts, demographic characteristics, life experiences, social support, health and mental illness. Multinomial logistic regression examined factors differentiating between those with suicidal ideation only and suicide attempt histories (with or without suicidal ideation) in men and women. Results Overall men were less likely to report suicidal thoughts and attempts, compared to females. More factors differentiated between suicidal thoughts and attempts in women compared to in men; these included hospital admission for mental illness, below degree level qualifications, being single and childhood adversity. In men, factors which significantly differentiated between suicidal thoughts and attempts included self-report of professional diagnosis of mental illness and childhood adversity. Higher levels of social support were associated with being in the suicidal thoughts group v. in the attempts group in men. Conclusion This study identified some key differences between men and women in factors associated with suicide attempts compared to suicidal thoughts. The findings support the use of the ideation-to-action framework to investigate sex differences in suicidal behaviour. Future research should examine the extent to which these factors are associated with suicide risk over time.

Fine tuning of a PID controller with inlet derivative filter using Pareto solution for gantry crane systems

Abstract: Gantry cranes are widely used in transporting heavy loads in construction projects and critical industries such as petrochemical industry and nuclear power stations. Their mission should be accomplished with as high accuracy for the trolley positioning, and minimum values of sway oscillation angles as possible. So, the control strategies aim to achieve high productivity (through transporting the trolley with good precision) while considering safety precautions (through eliminating sway oscillations). One of the linear closed loop control methods is using PD and PID controllers. This research provides a non-linear mathematical model for single-pendulum gantry crane with two stable control schemes that depend on PID and PD controllers equipped with inlet derivative filter for every scheme. The two control schemes utilize a PID controller for positioning the trolley and a PD controller for eliminating undesired sway angles of the payload. In the second scheme, the input voltage control signal is always saturated to be positive to preserve the direction of rotation of the driving DC motor. The controllers include up to five gains and two inlet derivative filter coefficients which are tuned using Multi-Objective Genetic Algorithm (NSGA-II) with four different fitness functions and one weighted function to choose a suitable solution from other Pareto solutions. The simulation results are presented to show the superiority of the second scheme precision in trolley transporting with minimum payload sway oscillations.

Prediction of Major Adverse Cardiovascular Events From Retinal, Clinical, and Genomic Data in Individuals With Type 2 Diabetes: A Population Cohort Study

Abstract: Improved identification of individuals with type 2 diabetes at high cardiovascular (CV) risk could help in selection of newer CV risk-reducing therapies. The aim of this study was to determine whether retinal vascular parameters, derived from retinal screening photographs, alone and in combination with a genome-wide polygenic risk score for coronary heart disease (CHD PRS) would have independent prognostic value over traditional CV risk assessment in patients without prior CV disease.Patients in the Genetics of Diabetes Audit and Research Tayside Scotland (GoDARTS) study were linked to retinal photographs, prescriptions, and outcomes. Retinal photographs were analyzed using VAMPIRE (Vascular Assessment and Measurement Platform for Images of the Retina) software, a semiautomated artificial intelligence platform, to compute arterial and venous fractal dimension, tortuosity, and diameter. CHD PRS was derived from previously published data. Multivariable Cox regression was used to evaluate the association between retinal vascular parameters and major adverse CV events (MACE) at 10 years compared with the pooled cohort equations (PCE) risk score.Among 5,152 individuals included in the study, a MACE occurred in 1,017 individuals. Reduced arterial fractal dimension and diameter and increased venous tortuosity each independently predicted MACE. A risk score combining these parameters significantly predicted MACE after adjustment for age, sex, PCE, and the CHD PRS (hazard ratio 1.11 per SD increase, 95% CI 1.04-1.18, P = 0.002) with similar accuracy to PCE (area under the curve [AUC] 0.663 vs. 0.658, P = 0.33). A model incorporating retinal parameters and PRS improved MACE prediction compared with PCE (AUC 0.686 vs. 0.658, P < 0.001).Retinal parameters alone and in combination with genome-wide CHD PRS have independent and incremental prognostic value compared with traditional CV risk assessment in type 2 diabetes.

Alloyed AuFeZnSe quantum dots@gold nanorod nanocomposite as an ultrasensitive and selective plasmon-amplified fluorescence OFF-ON aptasensor for arsenic (III)

Abstract: According to documented reports, more than 200 million people across the globe are exposed to arsenic (As) contamination at levels above the World Health Organization (WHO) guideline limit of 10 μg/L. In this work, a novel fluorescence OFF-ON ultrasensitive aptasensor was developed for As (III). To construct the fluorescence aptasensor, AuFeZnSe alloyed quantum dots (QDs) were newly synthesized and surface-coated with amphiphilic polymers (Amp-P) to render the QDs biocompatible and stable. Thereafter, cationic gold nanorods (AuNRs) were electrostatically bonded to the Amp-P-QDs to form an Amp-P-QDs-AuNR nanocomposite which switched OFF the fluorescence of the bound QDs. Thiolated anti-As (III) DNA aptamer (Apt) was thereafter assembled on the Amp-P-QDs-AuNR surface to form a Amp-P-Apt-QDs-AuNR probe. The affinity binding interaction between the targeted As (III) concentration and the Apt, triggered localized surface plasmon resonance (LSPR) from AuNRs to amplify the fluorescence intensity signal, thereby switching ON the fluorescence of the bound Amp-P-QDs. Comparison of the Amp-P-Apt-QDs and the Amp-P-Apt-QDs-AuNR probes, showed that the presence of AuNR enhanced the fluorescence of the bound Amp-P-QDs for As (III) by as much as 230%, representing an ∼20-fold increase over the Amp-P-Apt-QDs probe without AuNRs. Under optimum conditions, As (III) was selectively and quantitatively detected with ultra-high sensitivity. The linear range was 0.01–100 μg/L, while the obtained detection limit of 0.01 μg/L (69.12 pM) was 1000 times lower than the WHO recommended limit. We successfully applied the Amp-P-Apt-QDs-AuNR probe to detect As (III) in environmental and biological samples with analytical recoveries from ∼93 to 105%.

Photodynamic versus white-light-guided resection of first-diagnosis non-muscle-invasive bladder cancer: PHOTO RCT

Abstract: Around 7500 people are diagnosed with non-muscle-invasive bladder cancer in the UK annually. Recurrence following transurethral resection of bladder tumour is common, and the intensive monitoring schedule required after initial treatment has associated costs for patients and the NHS. In photodynamic diagnosis, before transurethral resection of bladder tumour, a photosensitiser that is preferentially absorbed by tumour cells is instilled intravesically. Transurethral resection of bladder tumour is then conducted under blue light, causing the photosensitiser to fluoresce. Photodynamic diagnosis-guided transurethral resection of bladder tumour offers better diagnostic accuracy than standard white-light-guided transurethral resection of bladder tumour, potentially reducing the chance of subsequent recurrence.The objective was to assess the clinical effectiveness and cost-effectiveness of photodynamic diagnosis-guided transurethral resection of bladder tumour.This was a multicentre, pragmatic, open-label, parallel-group, non-masked, superiority randomised controlled trial. Allocation was by remote web-based service, using a 1 : 1 ratio and a minimisation algorithm balanced by centre and sex.The setting was 22 NHS hospitals.Patients aged ≥ 16 years with a suspected first diagnosis of high-risk non-muscle-invasive bladder cancer, no contraindications to photodynamic diagnosis and written informed consent were eligible.Photodynamic diagnosis-guided transurethral resection of bladder tumour and standard white-light cystoscopy transurethral resection of bladder tumour.The primary clinical outcome measure was the time to recurrence from the date of randomisation to the date of pathologically proven first recurrence (or intercurrent bladder cancer death). The primary health economic outcome was the incremental cost per quality-adjusted life-year gained at 3 years.We enrolled 538 participants from 22 UK hospitals between 11 November 2014 and 6 February 2018. Of these, 269 were allocated to photodynamic diagnosis and 269 were allocated to white light. A total of 112 participants were excluded from the analysis because of ineligibility (n = 5), lack of non-muscle-invasive bladder cancer diagnosis following transurethral resection of bladder tumour (n = 89) or early cystectomy (n = 18). In total, 209 photodynamic diagnosis and 217 white-light participants were included in the clinical end-point analysis population. All randomised participants were included in the cost-effectiveness analysis. Over a median follow-up period of 21 months for the photodynamic diagnosis group and 22 months for the white-light group, there were 86 recurrences (3-year recurrence-free survival rate 57.8%, 95% confidence interval 50.7% to 64.2%) in the photodynamic diagnosis group and 84 recurrences (3-year recurrence-free survival rate 61.6%, 95% confidence interval 54.7% to 67.8%) in the white-light group (hazard ratio 0.94, 95% confidence interval 0.69 to 1.28; p = 0.70). Adverse event frequency was low and similar in both groups [12 (5.7%) in the photodynamic diagnosis group vs. 12 (5.5%) in the white-light group]. At 3 years, the total cost was £12,881 for photodynamic diagnosis-guided transurethral resection of bladder tumour and £12,005 for white light. There was no evidence of differences in the use of health services or total cost at 3 years. At 3 years, the quality-adjusted life-years gain was 2.094 in the photodynamic diagnosis transurethral resection of bladder tumour group and 2.087 in the white light group. The probability that photodynamic diagnosis-guided transurethral resection of bladder tumour was cost-effective was never > 30% over the range of society's cost-effectiveness thresholds.Fewer patients than anticipated were correctly diagnosed with intermediate- to high-risk non-muscle-invasive bladder cancer before transurethral resection of bladder tumour and the ratio of intermediate- to high-risk non-muscle-invasive bladder cancer was higher than expected, reducing the number of observed recurrences and the statistical power.Photodynamic diagnosis-guided transurethral resection of bladder tumour did not reduce recurrences, nor was it likely to be cost-effective compared with white light at 3 years. Photodynamic diagnosis-guided transurethral resection of bladder tumour is not supported in the management of primary intermediate- to high-risk non-muscle-invasive bladder cancer.Further work should include the modelling of appropriate surveillance schedules and exploring predictive and prognostic biomarkers.This trial is registered as ISRCTN84013636.This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 40. See the NIHR Journals Library website for further project information.Around 7500 people are diagnosed with early-stage bladder cancer in the UK each year. Early bladder cancer is contained within the bladder and has not yet invaded the bladder’s muscle wall or spread elsewhere in the body. The cancer will return (recur) in around half of people after initial treatment and they have to attend hospital for regular check-ups, with costs to both them and the NHS. The first step in treating early bladder cancer is surgery to remove the tumour. This surgery is normally performed under white light. Photodynamic diagnosis is a new technique in which a liquid is put into the patient’s bladder before surgery and a blue light is used during the operation. This causes the bladder cancer to fluoresce so that it can be seen more easily by the surgeon. The Photodynamic versus white-light-guided resection of first diagnosis non-muscle-invasive bladder cancer ( PHOTO ) trial aimed to find out whether or not using photodynamic diagnosis at initial surgery would reduce how often the cancer recurred and whether or not this could reduce the cost of treating early bladder cancer. A total of 538 people with early bladder cancer who had a medium to high chance of their cancer returning after treatment were enrolled in the PHOTO trial. They were included in one of two treatment groups, at random: 269 had photodynamic surgery and 269 had standard white-light surgery. People in both groups were monitored regularly for any recurrences, with further treatment as appropriate. After 3 years, 4 out of 10 people in each group had a recurrence of their bladder cancer. We found no difference between the treatment groups in the number of people with recurrences. We found no evidence of a benefit to patients, and the total costs of photodynamic surgery were higher than those of standard white light. We therefore recommend that it is no longer used in the treatment of this group of patients.

Upregulated expression of DDX5 predicts recurrence and poor prognosis in breast cancer

Abstract: DEAD-box helicase 5 (DDX5) has been shown to promote tumorigenesis and cancer progression. However, the relationship between DDX5 and recurrence in breast cancer (BC) patients remains unknown. The objective of the present study was to evaluate the correlation of DDX5 with recurrence-free survival (RFS) and breast cancer-specific survival (BCSS) in patients with BC. The expression of DDX5 was examined by immunohistochemical analysis. RFS was calculated by Kaplan-Meier survival analysis. Univariate and multivariable associations were assessed by Cox proportional hazards models. In the present study, a total of 868 BC patients were analysed, and we found that DDX5 protein was significantly overexpressed in BC tissues compared to adjacent normal tissues. Elevated DDX5 was associated with an aggressive phenotype in BC patients. Moreover, DDX5 protein was upregulated in recurrent patients compared with nonrecurrent patients, and DDX5 protein levels were positively associated with worse RFS and BCSS in BC patients. High DDX5 expressing BC patients with age more than 50 year, advanced clinical stage or histological grade had a significantly increased risk of recurrence and shorter survival. Our findings highlight the significance of DDX5 in the recurrence and clinical outcome of BC patients and suggest that DDX5 may be a potential predictive biomarker for patients with BC.

Bore Impact on Decks of Coastal Structures

Abstract: Bore impact on horizontal fixed decks of coastal structures is studied by use of the Level I Green–Naghdi (GN) equations and the Navier–Stokes (NS) equations. The bore is generated by the ...

Bore Impact on Decks of Coastal Structures

Abstract: Bore impact on horizontal fixed decks of coastal structures is studied by use of the Level I Green–Naghdi (GN) equations and the Navier–Stokes (NS) equations. The bore is generated by the breaking of a water reservoir, and may represent the propagation of a tsunami on land or broken storm waves. The bore-induced horizontal and vertical forces are determined and their variation with the bore and deck conditions is studied in this work. Various conditions of deck location with respect to the water level are considered, including cases with the deck under or above the still-water level. Two types of bore are considered, namely (i) a bore generated by a dam break, where the reservoir water depth is substantially larger than the downstream depth, and (ii) a bore generated by an initial mound of water, where the reservoir water depth is comparable to the downstream depth. It is shown that these mechanisms result in the formation of significantly different bore shapes. It is also shown that the relative height of the reservoir and the downstream water depth play a significant role in the bore generation and its impact on coastal structures. It is also found that the bore-induced forces vary almost linearly with the change in amplitude of the reservoir, while a change in the length of the reservoir has little effect on the loads. The horizontal force on submerged decks is shown to be independent of the submergence depth of the deck; this is due to the uniform velocity distribution over the water column of the bore. Results of the GN and NS models are compared with each other for submerged cases and the limitations, accuracy, and efficiency of these models in studying this problem are discussed. Results of the GN equations are in close agreement with the NS equations, making them a computationally efficient alternative for the study of this problem.

Developing Scotland’s First Green Health Prescription Pathway: A One-Stop Shop for Nature-Based Intervention Referrals

Abstract: Lifestyle modifications are part of comprehensive treatment plans to help manage the symptoms of pre-existing chronic conditions. However, behavior change is notoriously difficult as patients often lack the necessary support. The present manuscript outlines the development of a Green Health Prescription pathway that was designed to link patients with appropriate lifestyle interventions (i.e., nature-based interventions) and to support attendance. Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was undertaken in three focus groups (i.e., National Health Service healthcare professionals, service-users, and nature-based intervention delivery partners) to highlight areas of strength and weakness within the proposed pathway prior to delivery. The SWOT analyses revealed that the pathway was supported by all three focus groups. Weaknesses and threats were identified including sustainability of nature-based interventions in terms of funding, the need to connect patients with appropriate interventions based on their physical and mental health needs, and the requirement to have a "one-stop shop" for information to ensure that the pathway was accessible for all service-users and healthcare professionals. Results were addressed and considered throughout the development of the pathway.The Green Health Prescription pathway was launched in 2019 and gave patients the ability to receive a prescription from a healthcare professional, community service, or to self-refer. The pathway allows patients to contact a consultant, via a telephone service, who is trained to match them with a programme that the patient believes will be enjoyable and that fits their treatment needs. Data collection to assess the efficacy of the pathway is ongoing.

Charting functional E3 ligase hotspots and resistance mechanisms to small-molecule degraders

Abstract: Abstract Targeted protein degradation is a new pharmacologic paradigm established by drugs that recruit target proteins to E3 ubiquitin ligases via a ternary ligase-degrader-target complex. Based on the structure of the degrader and the neosubstrate, different E3 ligase interfaces are critically involved in this process, thus forming defined “functional hotspots”. Understanding disruptive mutations in functional hotspots informs on the architecture of the underlying assembly, and highlights residues prone to cause drug resistance. Until now, their identification was driven by structural methods with limited scalability. Here, we employ haploid genetics to show that hotspot mutations cluster in the substrate receptors of the hijacked ligases and find that type and frequency of mutations are shaped by the essentiality of the harnessed ligase. Intersection with deep mutational scanning data revealed hotspots that are either conserved, or specific for chemically distinct degraders or recruited neosubstrates. Biophysical and structural validation suggest that hotspot mutations frequently converge on altered ternary complex assembly. Moreover, we identified and validated hotspots mutated in patients that relapse from degrader treatment. In sum, we present a fast and experimentally widely accessible methodology that empowers the characterization of small-molecule degraders and informs on associated resistance mechanisms.

Seeing the forest for the trees: A social-ecological systems approach to managing outdoor recreation visitation in parks and protected areas

Abstract: Parks and protected areas visitation in the United States has increased substantially over the past several decades, and dramatically within the past few years. This expansion in visitation raises concerns regarding the influence of social, situational, and ecological factors upon visitor behaviors, decision-making, and overall experiences. This study investigated the relationship between three influencing factors and visitors’ coping behaviors and overall satisfaction on the White Mountain National Forest (WMNF) of New Hampshire. A mail-back and online survey method was used to collect data from WMNF visitors from June to September of 2020 (n = 642). Structural equation modeling and binary logistic regression analyses suggest social factors (e.g., crowding and conflict), situational factors (e.g., litter and access), and ecological factors (e.g., weather and seasonality) were significant predictors of visitor decision-making and overall satisfaction on the WMNF. Moreover, a majority of the sample consistently employed behavioral adaptations such as resource and temporal substitution, and in some instances, permanently abandoned their recreation experiences altogether, all in an effort to maintain satisfaction. This study demonstrates that in addition to social factors, situational and ecological factors should also be integrated when assessing the broader human-nature relationship. This research advances the social-ecological systems framework and suggests the importance of considering the interconnectivity between recreation visitor experiences and natural resources when sustainably managing parks and protected areas. This study found that social, situational, and ecological factors are driving the need for visitor substitution behaviors on the WMNF. Resource and temporal substitution were most common, with an approximate 95% probability of visitor engagement. Results indicate visitors are able to effectively cope with situational and ecological impacts, partially cope with crowding impacts, and unable to cope with conflict related impacts. These findings suggest visitor conflict, followed by crowding, should be prioritized by resource managers. Additionally, resource managers should work with adjacent communities and stakeholders on communication and engagement strategies, especially in areas proximate to recreation sites prone to crowding and conflict.

Fraying at the Edges: A Subsystems/Normative Power Analysis of the EU's “One China Policy/Policies”

Abstract: Abstract The European Union's position on “one China” has stood since the establishment of diplomatic relations with the People's Republic of China (PRC) in 1975. As a union of distinct member states, the nature of the European Union's (EU) foreign policymaking complicates efforts to maintain coherent common positions. Its effective “one China policy” (and those of its member states) is no exception. In recent years, the edges of the bloc's long-standing policy have started to fray as the EU–PRC relationship has become more fraught and many member states have sought to deepen their effective, if “unofficial,” engagement with Taiwan. I explore these changes to the EU's effective “one China policy” by employing a subsystems framework, starting from the position that the EU has foreign policies (rather than a singular policy ) created through three subsystems. Through the Normative Power Europe lens, I explore the extent to which the actors pulling at these “threads” at the edges of the EU's policy are motivated by normative concerns. I argue that the “fraying” of the EU's “one China policy” is not the result of a conscious decision by the EU as a collective normative actor but stems from shifting preferences within the national and supranational subsystems.

Peace Processes and the Integration of Pro-Government Militias: The Case of Village Guards in Turkey:

Abstract: Militia groups have only recently started to attract scholarly attention in the literature on internal conflicts. This attention is mostly focused on either the causes of their emergence or their f...