Reversing the decline of threatened koala (Phascolarctos cinereus) populations in New South Wales: Using genomics to enhance conservation outcomes.

Genetic management is a critical component of threatened species conservation. Understanding spatial patterns of genetic diversity is essential for evaluating the resilience of fragmented populations to accelerating anthropogenic threats. Nowhere is this more relevant than on the Australian continent, which is experiencing an ongoing loss of biodiversity that exceeds any other developed nation. Using a proprietary genome complexity reduction-based method (DArTSeq), we generated a data set of 3239 high quality Single Nucleotide Polymorphisms (SNPs) to investigate spatial patterns and indices of genetic diversity in the koala (Phascolarctos cinereus), a highly specialised folivorous marsupial that is experiencing rapid and widespread population declines across much of its former range. Our findings demonstrate that current management divisions across the state of New South Wales (NSW) do not fully represent the distribution of genetic diversity among extant koala populations, and that care must be taken to ensure that translocation paradigms based on these frameworks do not inadvertently restrict gene flow between populations and regions that were historically interconnected. We also recommend that koala populations should be prioritised for conservation action based on the scale and severity of the threatening processes that they are currently faced with, rather than placing too much emphasis on their perceived value (e.g., as reservoirs of potentially adaptive alleles), as our data indicate that existing genetic variation in koalas is primarily partitioned among individual animals. As such, the extirpation of koalas from any part of their range represents a potentially critical reduction of genetic diversity for this iconic Australian species.

Evaluating the Acceptability of the Drink Less App and the National Health Service Alcohol Advice Web Page: Qualitative Interview Process Evaluation.

BACKGROUND: The extent to which interventions are perceived as acceptable to users impacts engagement and efficacy. OBJECTIVE: In this study, we evaluated the acceptability of (1) the smartphone app Drink Less (intervention) and (2) the National Health Service (NHS) alcohol advice web page (usual digital care and comparator) among adult drinkers in the United Kingdom participating in a randomized controlled trial evaluating the effectiveness of the Drink Less app. METHODS: A subsample of 26 increasing- and higher-risk drinkers (Alcohol Use Disorders Identification Test score≥8) assigned to the intervention group (Drink Less; n=14, 54%; female: n=10, 71%; age: 22-72 years; White: n=9, 64%) or usual digital care group (NHS alcohol advice web page; n=12, 46%; female: n=5, 42%; age: 23-68 years: White: n=9, 75%) took part in semistructured interviews. The interview questions were mapped on to the 7 facets of acceptability according to the Theoretical Framework of Acceptability: affective attitude, burden, perceived effectiveness, ethicality, intervention coherence, opportunity costs, and self-efficacy. Alongside these constructs, we also included a question on perceived personal relevance, which previous research has linked to acceptability and engagement. Framework and thematic analysis of data was undertaken. RESULTS: The Drink Less app was perceived as being ethical, easy, user-friendly, and effective for the period the app was used. Participants reported particularly liking the tracking and feedback sections of the app, which they reported increased personal relevance and which resulted in positive affect when achieving their goals. They reported no opportunity cost. Factors such as negative affect when not meeting goals and boredom led to disengagement in the longer term for some participants. The NHS alcohol advice web page was rated as being easy and user-friendly with no opportunity costs. However, the information presented was not perceived as being personally relevant or effective in changing drinking behavior. Most participants reported neutral or negative affect, most participants thought the alcohol advice web page was accessible, and some participants reported ethical concerns around the availability of suggested resources. Some participants reported that it had acted as a starting point or a signpost to other resources. Participants in both groups discussed motivation to change and contextual factors such as COVID-19 lockdowns, which influenced their perceived self-efficacy regardless of their assigned intervention. CONCLUSIONS: Drink Less appears to be an acceptable digital intervention among the recruited sample. The NHS alcohol advice web page was generally considered unacceptable as a stand-alone intervention among the recruited sample, although it may signpost and help people access other resources and interventions.

Heterogeneity in choice models of addiction: the role of context.

RATIONALE: Theories of addiction guide scientific progress, funding priorities, and policy development and ultimately shape how people experiencing or recovering from addiction are perceived and treated. Choice theories of addiction are heterogenous, and different models have divergent implications. This breeds confusion among laypeople, scientists, practitioners, and policymakers and reduces the utility of robust findings that have the potential to reduce the global burden of addiction-associated harms. OBJECTIVE: Here we differentiate classes of choice models and articulate a novel framing for a class of addiction models, called contextual models, which share as a first principle the influence of the environment and other contextual factors on behavior within discrete choice contexts. RESULTS: These models do not assume that all choice behaviors are voluntary, but instead that both proximal and distal characteristics of the choice environment-and particularly the benefits and costs of both drug use and non-drug alternatives-can influence behavior in ways that are outside of the awareness of the individual. From this perspective, addiction is neither the individual's moral failing nor an internal uncontrollable urge but rather is the result of environmental contingencies that reinforce the behavior. CONCLUSIONS: Contextual models have implications for guiding research, practice, and policy, including identification of novel target mechanisms while also improving existing interventions.

Chromosomal inversions harbour excess mutational load in the coral, Acropora kenti, on the Great Barrier Reef.

The future survival of coral reefs in the Anthropocene depends on the capacity of corals to adapt as oceans warm and extreme weather events become more frequent. Targeted interventions designed to assist evolutionary processes in corals require a comprehensive understanding of the distribution and structure of standing variation, however, efforts to map genomic variation in corals have so far focussed almost exclusively on SNPs, overlooking structural variants that have been shown to drive adaptive processes in other taxa. Here, we show that the reef-building coral, Acropora kenti, harbours at least five large, highly polymorphic structural variants, all of which exhibit signatures of strongly suppressed recombination in heterokaryotypes, a feature commonly associated with chromosomal inversions. Based on their high minor allele frequency, uniform distribution across habitats and elevated genetic load, we propose that these inversions in A. kenti are likely to be under balancing selection. An excess of SNPs with high impact on protein-coding genes within these loci elevates their importance both as potential targets for adaptive selection and as contributors to genetic decline if coral populations become fragmented or inbred in future.

A TNIP1-driven systemic autoimmune disorder with elevated IgG4.

Whole-exome sequencing of two unrelated kindreds with systemic autoimmune disease featuring antinuclear antibodies with IgG4 elevation uncovered an identical ultrarare heterozygous TNIP1Q333P variant segregating with disease. Mice with the orthologous Q346P variant developed antinuclear autoantibodies, salivary gland inflammation, elevated IgG2c, spontaneous germinal centers and expansion of age-associated B cells, plasma cells and follicular and extrafollicular helper T cells. B cell phenotypes were cell-autonomous and rescued by ablation of Toll-like receptor 7 (TLR7) or MyD88. The variant increased interferon-ß without altering nuclear factor kappa-light-chain-enhancer of activated B cells signaling, and impaired MyD88 and IRAK1 recruitment to autophagosomes. Additionally, the Q333P variant impaired TNIP1 localization to damaged mitochondria and mitophagosome formation. Damaged mitochondria were abundant in the salivary epithelial cells of Tnip1Q346P mice. These findings suggest that TNIP1-mediated autoimmunity may be a consequence of increased TLR7 signaling due to impaired recruitment of downstream signaling molecules and damaged mitochondria to autophagosomes and may thus respond to TLR7-targeted therapeutics.

Do engagement and behavioural mechanisms underpin the effectiveness of the Drink Less app?

This is a process evaluation of a large UK-based randomised controlled trial (RCT) (n = 5602) evaluating the effectiveness of recommending an alcohol reduction app, Drink Less, compared with usual digital care in reducing alcohol consumption in increasing and higher risk drinkers. The aim was to understand whether participants' engagement ('self-reported adherence') and behavioural characteristics were mechanisms of action underpinning the effectiveness of Drink Less. Self-reported adherence with both digital tools was over 70% (Drink Less: 78.0%, 95% CI = 77.6-78.4; usual digital care: 71.5%, 95% CI = 71.0-71.9). Self-reported adherence to the intervention (average causal mediation effect [ACME] = -0.250, 95% CI = -0.42, -0.11) and self-monitoring behaviour (ACME = -0.235, 95% CI = -0.44, -0.03) both partially mediated the effect of the intervention (versus comparator) on alcohol reduction. Following the recommendation (self-reported adherence) and the tracking (self-monitoring behaviour) feature of the Drink Less app appear to be important mechanisms of action for alcohol reduction among increasing and higher risk drinkers.

Value-based decision-making in regular alcohol consumers following experimental manipulation of alcohol value.

BACKGROUND: Devaluation of alcohol leads to reductions in alcohol choice and consumption; however, the cognitive mechanisms that underpin this relationship are not well-understood. In this study we applied a computational model of value-based decision-making (VBDM) to decisions made about alcohol and alcohol-unrelated cues following experimental manipulation of alcohol value. METHOD: Using a pre-registered within-subject design, thirty-six regular alcohol consumers (≥14 UK units per week) completed a two-alternative forced choice task where they chose between two alcohol images (in one block) or two soft drink images (in a different block) after watching videos that emphasised the positive (alcohol value), and separately, the negative (alcohol devalue) consequences of alcohol. On each block, participants pressed a key to select the image depicting the drink they would rather consume. A drift-diffusion model (DDM) was fitted to reaction time and choice data to estimate evidence accumulation (EA) processes and response thresholds during the different blocks in each experimental condition. FINDINGS: In the alcohol devalue condition, soft drink EA rates were significantly higher compared to alcohol EA rates (p = 0.04, d = 0.31), and compared to soft drink EA rates in the alcohol value condition (p = 0.01, d = 0.38). However, EA rates for alcoholic drinks and response thresholds (for either drink type) were unaffected by the experimental manipulation. CONCLUSIONS: In line with behavioural economic models of addiction that emphasise the important role of alternative reinforcement, experimentally manipulating alcohol value is associated with changes in the internal cognitive processes that precede soft drink choice.

Effectiveness of a smartphone app (Drink Less) versus usual digital care for reducing alcohol consumption among increasing-and-higher-risk adult drinkers in the UK: a two-arm, parallel-group, double-blind, randomised controlled trial.

Background: Digital interventions, including apps and websites, can be effective for reducing alcohol consumption. However, many are not evidence- or theory-informed and have not been evaluated. We tested the effectiveness of the Drink Less app for reducing alcohol consumption compared with usual digital care in the UK. Methods: In this two-arm, parallel group, double-blind, randomised controlled trial, we enrolled increasing-and-higher-risk drinkers (AUDIT ≥ 8) in the UK, who were motivated to reduce their alcohol consumption and willing to use a digital intervention to do so, via online methods. Participants were randomly assigned (1:1), using an online algorithm, to receive a web link to download the Drink Less app (intervention) or to the NHS alcohol advice webpage (usual digital care). Researchers were masked to group allocation. Participants were followed up at one, three and six months. The primary outcome was self-reported weekly alcohol consumption at six months, adjusting for baseline consumption. The full analytic sample was used in most analyses, though missing data was treated in different ways. The primary, pre-registered intention-to-treat analysis assumed baseline-carried-forwards. Secondary pre-registered analyses also focused on the full analytic sample and used alternatives including multiple imputation and last observation carried forwards. This trial is registered with the ISRCTN registry, ISRCTN64052601. Findings: Between 07/13/2020 and 03/29/2022, 5602 people were randomly assigned to the Drink Less app (n = 2788) or comparator (n = 2814) groups. Six-month follow-up rates were 79% and 80%, respectively. The primary pre-registered conservative intention-to-treat approach assuming non-responders were drinking at baseline levels of consumption, found a non-significant greater reduction of 0.98 units in weekly alcohol consumption in the intervention group at 6-month follow-up (95% CI -2.67 to 0.70). The data were insensitive to detect the hypothesised effect (Bayes factor = 1.17). Data were not missing completely at random, with 6-month follow-up rates differing in terms of education, occupation, and income. We therefore conducted the pre-registered sensitivity analysis using multiple imputation, showing that the Drink Less app resulted in a 2.00-unit greater weekly reduction at 6-month follow-up compared with the NHS alcohol advice webpage (95% CI -3.76 to -0.24). Fewer than 0.1% of participants in both arms who responded to one, three or six-month follow-up reported adverse events linked to participation in the trial. Interpretation: The Drink Less app may be effective in reducing the alcohol consumption in increasing-and-higher-risk drinkers motivated to reduce their consumption. Funding: NIHR Public Health Research Programme.

Methodological Insights on Recruitment and Retention From a Remote Randomized Controlled Trial Examining the Effectiveness of an Alcohol Reduction App: Descriptive Analysis Study.

BACKGROUND: Randomized controlled trials (RCTs) with no in-person contact (ie, remote) between researchers and participants offer savings in terms of cost and time but present unique challenges. OBJECTIVE: The goal of this study is to examine the differences between different forms of remote recruitment (eg, National Health Service [NHS] website, social media, and radio advertising) in the proportion of participants recruited, demographic diversity, follow-up rates, and cost. We also examine the cost per participant of sequential methods of follow-up (emails, phone calls, postal surveys, and postcards). Finally, our experience with broader issues around study advertising and participant deception is discussed. METHODS: We conducted a descriptive analysis of 5602 increasing-and-higher-risk drinkers (Alcohol Use Disorders Identification Test score ≥8), taking part in a 2-arm, parallel group, remote RCT with a 1:1 allocation, comparing the intervention (Drink Less app) with usual digital care (NHS alcohol advice web page). Participants were recruited between July 2020 and March 2022 and compensated with gift vouchers of up to £36 (a currency exchange rate of £1=US $1.26988 is applicable) for completing follow-up surveys, with 4 stages of follow-up: email reminders, phone calls, postal survey, and postcard. RESULTS: The three main recruitment methods were advertisements on (1) social media (2483/5602, 44.32%), (2) the NHS website (1961/5602, 35.01%), and (3) radio and newspapers (745/5602, 13.3%), with the remaining methods of recruitment accounting 7.37% (413/5602) of the sample. The overall recruitment cost per participant varied from £0 to £11.01. Costs were greater when recruiting participants who were men (£0-£28.85), from an ethnic minority group (£0-£303.81), and more disadvantaged (£0-£49.12). Targeted approaches were useful for recruiting more men but less useful in achieving diversity in ethnicity and socioeconomic status. Follow-up at 6 months was 79.58% (4458/5602). Of those who responded, 92.4% (4119/4458) responded by email. Each additional stage of follow-up resulted in an additional 2-3 percentage points of the overall sample being followed up, although phone calls, postal surveys, and postcards were more resource intensive than email reminders. CONCLUSIONS: For remote RCTs, researchers could benefit from using a range of recruitment methods and cost-targeted approaches to achieve demographic diversity. Automated emails with substantial financial incentives for prompt completion can achieve good follow-up rates, and sequential, offline follow-up options, such as phone calls and postal surveys, can further increase follow-up rates but are comparatively expensive. We also make broader recommendations focused on striking the right balance when designing remote RCTs. Careful planning, ongoing maintenance, and dynamic decision-making are required throughout a trial to balance the competing demands of participation among those eligible, deceptive participation among those who are not eligible, and ensuring no postrandomization bias is introduced by data-checking protocols.

Craving modulates attentional bias towards alcohol in severe alcohol use disorder: An eye-tracking study.

BACKGROUND AND AIMS: Competing models disagree on three theoretical questions regarding alcohol-related attentional bias (AB), a key process in severe alcohol use disorder (SAUD): (1) is AB more of a trait (fixed, associated with alcohol use severity) or state (fluid, associated with momentary craving states) characteristic of SAUD; (2) does AB purely reflect the over-activation of the reflexive/reward system or is it also influenced by the activity of the reflective/control system and (3) does AB rely upon early or later processing stages? We addressed these issues by investigating the time-course of AB and its modulation by subjective craving and cognitive load in SAUD. DESIGN: A free-viewing eye-tracking task, presenting pictures of alcoholic and non-alcoholic beverages, combined with a concurrent cognitive task with three difficulty levels. SETTING: A laboratory setting in the detoxification units of three Belgian hospitals. PARTICIPANTS: We included 30 patients with SAUD self-reporting craving at testing time, 30 patients with SAUD reporting a total absence of craving and 30 controls matched on sex and age. All participants from SAUD groups met the DSM-5 criteria for SAUD. MEASUREMENTS: We assessed AB through early and late eye-tracking indices. We evaluated the modulation of AB by craving (comparison between patients with/without craving) and cognitive load (variation of AB with the difficulty level of the concurrent task). FINDINGS: Dwell time measure indicated that SAUD patients with craving allocated more attention towards alcohol-related stimuli than patients without craving (P < 0.001, d = 1.093), resulting in opposite approach/avoidance AB according to craving presence/absence. SAUD patients without craving showed a stronger avoidance AB than controls (P = 0.003, d = 0.806). AB did not vary according to cognitive load (P = 0.962, η2 p = 0.004). CONCLUSIONS: The direction of alcohol-related attentional bias (approach/avoidance) appears to be determined by patients' subjective craving at testing time and does not function as a stable trait of severe alcohol use disorder. Alcohol-related attentional bias appears to rely on later/controlled attentional stages but is not modulated by the saturation of the reflective/control system.

Investigating the impact of 'dark nudges' on drinking intentions: A between groups, randomized and online experimental study.

OBJECTIVES: This study explored how 'dark nudges' (tactics used in alcohol industry-funded responsible drinking campaigns) affect drinking intentions, perceived source credibility and whether individual differences in perceptions of prototypical drinkers moderated these effects. DESIGN: Two 2 × 2 between-groups online experimental studies. METHODS: Study 1 (N = 164) presented three alcohol health messages per condition, comprising social norm (healthy/unhealthy ("dark nudge")) by frame (loss/gain). Study 2 (N = 229) presented one message per condition, comprising cancer causality (single cause/multiple causes (dark nudge)) by funding disclosure (disclosure/non-disclosure (dark nudge)). Outcomes were drinking intentions and perceived source credibility. Exploratory analyses considered prototype perceptions as a between-subjects moderator. RESULTS: No significant effects of message frame, social norm, fundi or multiple cancer causality arguments on drinking intentions were found. In Study 2, in the dark nudge multiple cancer causality conditions, perceived source credibility was high when funding was undisclosed, but significantly lower when it was disclosed. Exploratory analyses suggested effects were moderated by prototype similarity. In Study 1, higher perceived similarity to a heavy drinker and lower perceived similarity to a responsible drinker were associated with higher drinking intentions in the unhealthy norm/gain frame condition, but lower drinking intentions in the other conditions. CONCLUSIONS: Framing, social norm, funding disclosure and multiple causality manipulations as tested in this study did not exert a dark nudge effect on drinking intentions. However, the exploratory analyses suggest it could be hypothesised that the types of messages used in alcohol industry-funded responsible drinking campaigns may result in greater drinking intentions among those who identify more as heavy drinkers and less as responsible drinkers. Perceived prototype similarity may be an important moderator of the impact of alcohol health messages that warrants further research. Study 2 suggests disclosure of industry funding guides judgements of the credibility of sources of misleading messages about alcohol and cancer.

A case-control comparison of acute-phase peripheral blood gene expression in participants diagnosed with minor ischaemic stroke or stroke mimics.

BACKGROUND: Past studies suggest that there are changes in peripheral blood cell gene expression in response to ischaemic stroke; however, the specific changes which occur during the acute phase are poorly characterised. The current study aimed to identify peripheral blood cell genes specifically associated with the early response to ischaemic stroke using whole blood samples collected from participants diagnosed with ischaemic stroke (n = 29) or stroke mimics (n = 27) following emergency presentation to hospital. Long non-coding RNA (lncRNA), mRNA and micro-RNA (miRNA) abundance was measured by RNA-seq, and the consensusDE package was used to identify genes which were differentially expressed between groups. A sensitivity analysis excluding two participants with metastatic disease was also conducted. RESULTS: The mean time from symptom onset to blood collection was 2.6 h. Most strokes were mild (median NIH stroke scale score 2.0). Ten mRNAs (all down-regulated in samples provided by patients experiencing ischaemic stroke) and 30 miRNAs (14 over-expressed and 16 under-expressed in participants with ischaemic stroke) were significantly different between groups in the whole cohort and sensitivity analyses. No significant over-representation of gene ontology categories by the differentially expressed genes was observed. Random forest analysis suggested a panel of differentially expressed genes (ADGRG7 and miRNAs 96, 532, 6766, 6798 and 6804) as potential ischaemic stroke biomarkers, although modelling analyses demonstrated that these genes had poor diagnostic performance. CONCLUSIONS: This study provides evidence suggesting that the early response to minor ischaemic stroke is predominantly reflected by changes in the expression of miRNAs in peripheral blood cells. Further work in independent cohorts particularly in patients with more severe stroke is needed to validate these findings and investigate their clinical relevance.

Identifying cancer driver genes in individual tumours.

Cancer is a heterogeneous disease with a strong genetic component making it suitable for precision medicine approaches aimed at identifying the underlying molecular drivers within a tumour. Large scale population-level cancer sequencing consortia have identified many actionable mutations common across both cancer types and sub-types, resulting in an increasing number of successful precision medicine programs. Nonetheless, such approaches fail to consider the effects of mutations unique to an individual patient and may miss rare driver mutations, necessitating personalised approaches to driver-gene prioritisation. One approach is to quantify the functional importance of individual mutations in a single tumour based on how they affect the expression of genes in a gene interaction network (GIN). These GIN-based approaches can be broadly divided into those that utilise an existing reference GIN and those that construct de novo patient-specific GINs. These single-tumour approaches have several limitations that likely influence their results, such as use of reference cohort data, network choice, and approaches to mathematical approximation, and more research is required to evaluate the in vitro and in vivo applicability of their predictions. This review examines the current state of the art methods that identify driver genes in single tumours with a focus on GIN-based driver prioritisation.

Bot or Not? Detecting and Managing Participant Deception When Conducting Digital Research Remotely: Case Study of a Randomized Controlled Trial.

BACKGROUND: Evaluating digital interventions using remote methods enables the recruitment of large numbers of participants relatively conveniently and cheaply compared with in-person methods. However, conducting research remotely based on participant self-report with little verification is open to automated "bots" and participant deception. OBJECTIVE: This paper uses a case study of a remotely conducted trial of an alcohol reduction app to highlight and discuss (1) the issues with participant deception affecting remote research trials with financial compensation; and (2) the importance of rigorous data management to detect and address these issues. METHODS: We recruited participants on the internet from July 2020 to March 2022 for a randomized controlled trial (n=5602) evaluating the effectiveness of an alcohol reduction app, Drink Less. Follow-up occurred at 3 time points, with financial compensation offered (up to £36 [US $39.23]). Address authentication and telephone verification were used to detect 2 kinds of deception: "bots," that is, automated responses generated in clusters; and manual participant deception, that is, participants providing false information. RESULTS: Of the 1142 participants who enrolled in the first 2 months of recruitment, 75.6% (n=863) of them were identified as bots during data screening. As a result, a CAPTCHA (Completely Automated Public Turing Test to Tell Computers and Humans Apart) was added, and after this, no more bots were identified. Manual participant deception occurred throughout the study. Of the 5956 participants (excluding bots) who enrolled in the study, 298 (5%) were identified as false participants. The extent of this decreased from 110 in November 2020, to a negligible level by February 2022 including a number of months with 0. The decline occurred after we added further screening questions such as attention checks, removed the prominence of financial compensation from social media advertising, and added an additional requirement to provide a mobile phone number for identity verification. CONCLUSIONS: Data management protocols are necessary to detect automated bots and manual participant deception in remotely conducted trials. Bots and manual deception can be minimized by adding a CAPTCHA, attention checks, a requirement to provide a phone number for identity verification, and not prominently advertising financial compensation on social media. TRIAL REGISTRATION: ISRCTN Number ISRCTN64052601; https://doi.org/10.1186/ISRCTN64052601.

Small extracellular vesicles but not microvesicles from Opisthorchis viverrini promote cell proliferation in human cholangiocytes.

Chronic infection with O. viverrini has been linked to the development of cholangiocarcinoma (CCA), which is a major public health burden in the Lower Mekong River Basin countries, including Thailand, Lao PDR, Vietnam and Cambodia. Despite its importance, the exact mechanisms by which O. viverrini promotes CCA are largely unknown. In this study, we characterized different extracellular vesicle populations released by O. viverrini (OvEVs) using proteomic and transcriptomic analyses and investigated their potential role in host-parasite interactions. While 120k OvEVs promoted cell proliferation in H69 cells at different concentrations, 15k OvEVs did not produce any effect compared to controls. The proteomic analysis of both populations showed differences in their composition that could contribute to this differential effect. Furthermore, the miRNAs present in 120k EVs were analysed and their potential interactions with human host genes was explored by computational target prediction. Different pathways involved in inflammation, immune response and apoptosis were identified as potentially targeted by the miRNAs present in this population of EVs. This is the first study showing specific roles for different EV populations in the pathogenesis of a parasitic helminth, and more importantly, an important advance towards deciphering the mechanisms used in establishment of opisthorchiasis and liver fluke infection-associated malignancy.

Modeling the value-based decision to consume alcohol in response to emotional experiences.

Evidence for negative reinforcement of alcohol use is mixed; one possible explanation for this is that people make value-based decisions whether to regulate their emotions via alcohol or an alternative, and only drink-to-cope when alcohol's reinforcing value is larger than that of available alternatives. If this is the case, immediately following a negative emotional event, the value for alcohol should increase primarily in heavy drinkers, whereas in light drinkers, alternative ways of coping should be valued. We conducted a preregistered online experiment (N = 200) with a mixed design (between: heavy vs. light drinker; within: negative/neutral/positive mood induction). In each of three experimental sessions, participants first provided value ratings for a set of alcohol and food stimuli. Second, they were subjected to a mood induction. Third, they made forced choices between either two alcohol or food stimuli. We then applied a drift-diffusion model to these data and tested whether alcohol- and food-related decision-making parameters are differentially affected following the mood inductions in heavy and light drinkers. In preregistered analyses, we found that heavy drinkers did not value alcohol more but valued food less after the negative mood induction. Exploratory analyses uncovered that both heavy- and light-drinking participants valued alcohol more following the negative mood induction if they reported high alcohol craving at the start of the session. Collectively, these results provide some evidence for the idea that drinking-to-cope might be a value-based decision-making process. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Australasian dingo archetype: de novo chromosome-length genome assembly, DNA methylome, and cranial morphology.

BACKGROUND: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long-read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed. FINDINGS: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on chromosomes 11, 16, 25, and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and 9 previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mitochondrial DNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified 2 differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphologic data, comprising geometric morphometric assessment of cranial morphology, place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue shows she had a larger cranial capacity than a similar-sized domestic dog. CONCLUSIONS: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphologic characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney.

Recovery From Nicotine Addiction: A Diffusion Model Decomposition of Value-Based Decision-Making in Current Smokers and Ex-smokers.

INTRODUCTION: A considerable number of people successfully give up tobacco smoking. In nicotine-dependent individuals, tobacco choice is determined by greater expected drug value; however, less is known about the underlying mechanisms through which people quit smoking. AIMS AND METHODS: This study aimed to explore whether computational parameters of value-based decision-making (VBDM) characterize recovery from nicotine addiction. Using a preregistered, between-subject design, current daily smokers (n = 51) and ex-smokers who used to smoke daily (n = 51) were recruited from the local community. Participants completed a two-alternative forced choice task in which they chose between either two tobacco-related images (in one block) or tobacco-unrelated images (in a different block). During each trial, participants pressed a computer key to select the image they rated most positively during a previous task block. To estimate evidence accumulation (EA) processes and response thresholds during the different blocks, a drift-diffusion model was fitted to the reaction time and error data. RESULTS: Ex-smokers had significantly higher response thresholds when making tobacco-related decisions (p = .01, d = 0.45) compared to current smokers, although there were no significant group differences during tobacco-unrelated decisions. Furthermore, there were no significant group differences in EA rates when making tobacco or tobacco-unrelated decisions. CONCLUSIONS: Greater cautiousness when making value-based decisions about tobacco-related cues characterized recovery from nicotine addiction. IMPLICATIONS: The number of people dependent on nicotine has decreased steadily during the past decade; however, the mechanisms that underlie recovery are currently less well understood. The present study applied advances in the measurement of value-based choice. The aim was to explore whether the internal processes that underpin VBDM discriminate current daily tobacco smokers from ex-tobacco smokers who used to smoke daily. Findings revealed that recovery from nicotine addiction was characterized by higher response thresholds when making value-based decisions about tobacco-related cues; this may serve as a novel target for treatment interventions that focus on helping people to stop smoking.

The Australasian dingo archetype: De novo chromosome-length genome assembly, DNA methylome, and cranial morphology.

Background: One difficulty in testing the hypothesis that the Australasian dingo is a functional intermediate between wild wolves and domesticated breed dogs is that there is no reference specimen. Here we link a high-quality de novo long read chromosomal assembly with epigenetic footprints and morphology to describe the Alpine dingo female named Cooinda. It was critical to establish an Alpine dingo reference because this ecotype occurs throughout coastal eastern Australia where the first drawings and descriptions were completed. Findings: We generated a high-quality chromosome-level reference genome assembly (Canfam_ADS) using a combination of Pacific Bioscience, Oxford Nanopore, 10X Genomics, Bionano, and Hi-C technologies. Compared to the previously published Desert dingo assembly, there are large structural rearrangements on Chromosomes 11, 16, 25 and 26. Phylogenetic analyses of chromosomal data from Cooinda the Alpine dingo and nine previously published de novo canine assemblies show dingoes are monophyletic and basal to domestic dogs. Network analyses show that the mtDNA genome clusters within the southeastern lineage, as expected for an Alpine dingo. Comparison of regulatory regions identified two differentially methylated regions within glucagon receptor GCGR and histone deacetylase HDAC4 genes that are unmethylated in the Alpine dingo genome but hypermethylated in the Desert dingo. Morphological data, comprising geometric morphometric assessment of cranial morphology place dingo Cooinda within population-level variation for Alpine dingoes. Magnetic resonance imaging of brain tissue show she had a larger cranial capacity than a similar-sized domestic dog. Conclusions: These combined data support the hypothesis that the dingo Cooinda fits the spectrum of genetic and morphological characteristics typical of the Alpine ecotype. We propose that she be considered the archetype specimen for future research investigating the evolutionary history, morphology, physiology, and ecology of dingoes. The female has been taxidermically prepared and is now at the Australian Museum, Sydney.