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Objective: To investigate perceived changes in academic self-efficacy associated with self-reported symptoms of COVID-19, changes in mental health, and trust in universities' management of the pandemic and transition to remote education during lockdown of Swedish universities in the spring of 2020. Methods: 4495 participated and 3638 responded to self-efficacy questions. Associations were investigated using multinomial regression. Results: Most students reported self-experienced effects on self-efficacy. Lowered self-efficacy was associated with symptoms of contagion, perceived worsening of mental health and low trust in universities' capacity to successfully manage the lockdown and transition to emergency remote education. Increased self-efficacy was associated with better perceived mental health and high trust in universities. Conclusion: The initial phase of the pandemic was associated with a larger proportion of students reporting self-experienced negative effects on academic self-efficacy. Since self-efficacy is a predictor of academic performance, it is likely that students' academic performance will be adversely affected. [ABSTRACT FROM AUTHOR]

Commensurate measures of alcohol-related consequences across countries and cultures are critical for addressing the global burden of hazardous alcohol use. The Rutgers Alcohol Problem Index (RAPI), developed and validated in the United States, is a popular measure of alcohol problems. This study examined measurement invariance of the RAPI across samples of U.S. and Swedish high school seniors. Latent mean differences in alcohol problems across countries and differences in associations between alcohol problems with alcohol use and protective behavioral strategies (PBS) were also examined. The RAPI was scalar invariant. Swedish students reported fewer problems than U.S. students (latent mean difference = −0.19, p =.047). In both samples, the RAPI was positively correlated with alcohol use frequency and quantity (ps <.001), and negatively correlated with PBS use (p s <.05). Overall, the RAPI demonstrated measurement invariance, and we found evidence for its validity across samples of U.S. and Swedish high school seniors. [ABSTRACT FROM AUTHOR]

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Background: It has become evident in the field of oncology that the outcome of medical treatment is influenced by the combined effect exerted on both cancer- and immune cells. Therefore, we evaluated potential immunological effects of 46 standard anticancer agents and 22 commonly administered concomitant non-cancer drugs. Methods: We utilized a miniaturized in vitro model system comprised of fluorescently labeled human colon and lung cancer cell lines grown as monocultures and co-cultured with activated peripheral blood mononuclear cells (PBMCs). The Bliss Independence Model was then applied to detect antagonism and synergy between the drugs and activated immune cells. Results: Among the standard anticancer agents, tyrosine kinase inhibitors (TKIs) stood out as the top inducers of both antagonism and synergy. Ruxolitinib and dasatinib emerged as the most notably antagonistic substances, exhibiting the lowest Bliss scores, whereas sorafenib was shown to synergize with activated PBMCs. Most concomitant drugs did not induce neither antagonism nor synergy. However, the statins mevastatin and simvastatin were uniquely shown to synergize with activated PBMC at all tested drug concentrations in the colon cancer model. Conclusion: We utilized a miniaturized tumor-immune model to enable time and cost-effective evaluation of a broad panel of drugs in an immuno-oncology setting in vitro. Using this approach, immunomodulatory effects exerted by TKIs and statins were identified. [ABSTRACT FROM AUTHOR]

Background: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components. Methods: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned. Discussion: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group. [ABSTRACT FROM AUTHOR]

It is widely believed that human culture originated in the appearance of Oldowan stone-tool production (circa 2.9 Mya) and a primitive but effective ability to copy detailed know-how. Cumulative cultural evolution is then believed to have led to modern humans and human culture via self-reinforcing gene-culture co-evolution. This outline evolutionary trajectory has come to be seen as all but self-evident, but dilemmas have appeared as it has been explored in increasing detail. Can we attribute even a minimally effective know-how copying capability to Oldowan hominins? Do Oldowan tools really demand know-how copying? Is there any other evidence that know-how copying was present? We here argue that this account, which we refer to as "Trajectory A", may be a red herring, and formulate an alternative "Trajectory B" that resolves these dilemmas. Trajectory B invokes an overlooked group-level channel of cultural inheritance (the Social Protocell) whereby networks of cultural traits can be faithfully inherited and potentially undergo cumulative evolution, also when the underpinning cultural traits are apelike in not being transmitted via know-how copying (Latent Solutions). Since most preconditions of Trajectory B are present in modern-day Pan, Trajectory B may even have its roots considerably before Oldowan toolmaking. The cumulative build-up of networks of non-cumulative cultural traits is then argued to have produced conditions that both called for and afforded a gradual appearance of the ability to copy know-how, but considerably later than the Oldowan. [ABSTRACT FROM AUTHOR]

Background and Objectives: Internet gaming disorder (IGD) is associated with health, social, and academic problems but whether these are consequences of the disorder rather than precursors or correlates is unclear. We aimed to evaluate whether IGD in the 1st year of university predicts health, academic and social problems 1 year later, controlling for baseline health, academic and social problems, demographics, and mental health symptoms. Methods: In a prospective cohort study, 1741 university students completed both a baseline online survey in their 1st year and a follow‐up survey 1 year later. Log‐binomial models examined the strength of prospective associations between baseline predictor variables (IGD, baseline health, academic and social problems, sex, age, and mental health symptoms) and occurrence of health, academic and social problems at follow‐up. Results: When extensively adjusted by the corresponding outcome at baseline, any mental disorder symptoms, sex, and age, baseline IGD was associated only with severe school impairment and poor social life (risk ratio [RR] = 1.77; 95% confidence interval [CI] = 1.14–2.75, p =.011; RR = 1.22; 95% CI = 1.07–1.38, p =.002, respectively). Conclusions and Scientific Significance: University authorities and counselors should consider that incoming 1st‐year students that meet criteria for IGD are likely to have increased academic and social impairments during their 1st year for which they may want to intervene. This study adds to the existing literature by longitudinally examining a greater array of negative outcomes of IGD than previously documented. [ABSTRACT FROM AUTHOR]

The origin of human cumulative culture is commonly envisioned as the appearance (some 2.0–2.5 million years ago) of a capacity to faithfully copy the knowhow that underpins socially learned traditions. While certainly plausible, this story faces a steep ‘startup problem’. For example, it presumes that ape-like early Homo possessed specialized cognitive capabilities for faithful know-how copying and that early toolmaking actually required such a capacity. The social protocell hypothesis provides a leaner story, where cumulative culture may have originated even earlier—as cumulative systems of non-cumulative traditions (’institutions’ and ‘cultural lifestyles’), via an emergent group-level channel of cultural inheritance. This channel emerges as a side-effect of a specific but in itself unremarkable suite of social group behaviours. It is independent of faithful know-how copying, and an ancestral version is argued to persist in Pan today. Hominin cultural lifestyles would thereby have gained in complexity and sophistication, eventually becoming independent units of selection (socionts) via a cultural evolutionary transition in individuality, abstractly similar to the origin of early cells. We here explore this hypothesis by simulating its basic premises. The model produces the expected behaviour and reveals several additional and non-trivial phenomena as fodder for future work. [ABSTRACT FROM AUTHOR]

Background: High-throughput screening (HTS) of small molecule drug libraries has greatly facilitated the discovery of new cancer drugs. However, most phenotypic screening platforms used in the field of oncology are based solely on cancer cell populations and do not allow for the identification of immunomodulatory agents. Methods: We developed a phenotypic screening platform based on a miniaturized co-culture system with human colorectal cancer- and immune cells, providing a model that recapitulates part of the tumor immune microenvironment (TIME) complexity while simultaneously being compatible with a simple image-based readout. Using this platform, we screened 1,280 small molecule drugs, all approved by the Food and Drug Administration (FDA), and identified statins as enhancers of immune cell-induced cancer cell death. Results: The lipophilic statin pitavastatin had the most potent anti-cancer effect. Further analysis demonstrated that pitavastatin treatment induced a pro-inflammatory cytokine profile as well as an overall pro-inflammatory gene expression profile in our tumor-immune model. Conclusion: Our study provides an in vitro phenotypic screening approach for the identification of immunomodulatory agents and thus addresses a critical gap in the field of immuno-oncology. Our pilot screen identified statins, a drug family gaining increasing interest as repurposing candidates for cancer treatment, as enhancers of immune cell-induced cancer cell death. We speculate that the clinical benefits described for cancer patients receiving statins are not simply caused by a direct effect on the cancer cells but rather are dependent on the combined effect exerted on both cancer and immune cells. [ABSTRACT FROM AUTHOR]

Understanding the immunological effects of chemotherapy is of great importance, especially now that we have entered an era where ever-increasing pre-clinical and clinical efforts are put into combining chemotherapy and immunotherapy to combat cancer. Single-cell RNA sequencing (scRNA-seq) has proved to be a powerful technique with a broad range of applications, studies evaluating drug effects in co-cultures of tumor and immune cells are however scarce. We treated a co-culture comprised of human colorectal cancer (CRC) cells and peripheral blood mononuclear cells (PBMCs) with the nucleoside analogue trifluridine (FTD) and used scRNA-seq to analyze posttreatment gene expression profiles in thousands of individual cancer and immune cells concurrently. ScRNA-seq recapitulated major mechanisms of action previously described for FTD and provided new insight into possible treatment-induced effects on T-cell mediated antitumor responses. [ABSTRACT FROM AUTHOR]

Quiescent cancer cells in malignant tumors can withstand cell-cycle active treatment and cause cancer spread and recurrence. Three-dimensional (3D) cancer cell models have led to the identification of oxidative phosphorylation (OXPHOS) as a context-dependent vulnerability. The limited treatment options for advanced hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) metastatic to the liver include the multikinase inhibitors sorafenib and regorafenib. Off-target effects of sorafenib and regorafenib are related to OXPHOS inhibition; however the importance of this feature to the effect on tumor cells has not been investigated in 3D models. We began by assessing global transcriptional responses in monolayer cell cultures, then moved on to multicellular tumor spheroids (MCTS) and tumoroids generated from a CRC patient. Cells were treated with chemotherapeutics, kinase inhibitors, and the OXPHOS inhibitors. Cells grown in 3D cultures were sensitive to the OXPHOS inhibitor nitazoxanide, sorafenib, and regorafenib and resistant to other multikinase inhibitors and chemotherapeutic drugs. Furthermore, nitazoxanide and sorafenib reduced viability, regrowth potential and inhibited mitochondrial membrane potential in an additive manner at clinically relevant concentrations. This study demonstrates that the OXPHOS inhibition caused by sorafenib and regorafenib parallels 3D activity and can be further investigated for new combination strategies. [ABSTRACT FROM AUTHOR]

Objective: The present study investigates if symptoms of COVID-19 contagion in different social contexts (cohabitants, family, acquaintances, and others) are associated with university students' own self-reported symptoms of COVID-19 contagion, mental health, and study capacity. This was investigated by a cross-sectional survey administrated in Sweden during the first wave of the COVID-19 pandemic, at the time when universities were locked down to limit viral spread and contagion. Results: Mild to moderate symptoms of COVID-19 in cohabitants and family members were associated with student's self-reported symptoms of contagion, while no associations could be seen in relation to mental health and study capacity. Symptoms of COVID-19 contagion in acquaintances and others were not associated with students' self-reported symptoms, nor with their mental health and study capacity. To conclude, during the initial lockdown of universities students' self-reported symptoms of contagion were mainly associated with cohabitants and family members, while symptoms of contagion in different social contexts were not associated with mental health and study capacity. Findings suggest that lockdown of universities may have contributed to limiting infection pathways, while still allowing students to focus on their studies despite significant contagion among others known to the student. [ABSTRACT FROM AUTHOR]

Aims: The COVID-19 containment strategy in Sweden uses public health recommendations relying on personal responsibility for compliance. Universities were one of few public institutions subject to strict closure, meaning that students had to adapt overnight to online teaching. This study investigates the prevalence of self-reported recommendation compliance and associations with self-reported symptoms of contagion, self-experienced effects on mental health and academic self-efficacy among university students in Sweden in May–June 2020. Methods: This was a cross-sectional 23 question online survey in which data were analysed by multinomial regression, taking a Bayesian analysis approach complemented by null hypothesis testing. Results: A total of 4495 students consented to respond. Recommendation compliance ranged between 70% and 96%. Women and older students reported higher compliance than did men and younger students. Mild to moderate COVID-19 symptoms were reported by 30%, severe symptoms by fewer than 2%; 15% reported being uncertain and half of the participants reported no symptoms. Mental health effects were reported by over 80%, and changes in academic self-efficacy were reported by over 85%; in both these areas negative effects predominated. Self-reported symptoms and uncertainty about contagion were associated with non-compliance, negative mental health effects, and impaired academic self-efficacy. Conclusions: Students generally followed public health recommendations during strict closure of universities, but many reported considerable negative consequences related to mental health and academic self-efficacy. Digital interventions should be developed and evaluated to boost coping skills, build resilience and alleviate student suffering during the pandemic and future similar crises. [ABSTRACT FROM AUTHOR]

Evolutionary Transitions in Individuality (ETI) have been responsible for the major transitions in levels of selection and individuality in natural history, such as the origins of prokaryotic and eukaryotic cells, multicellular organisms, and eusocial insects. The integrated hierarchical organization of life thereby emerged as groups of individuals repeatedly evolved into new and more complex kinds of individuals. The Social Protocell Hypothesis (SPH) proposes that the integrated hierarchical organization of human culture can also be understood as the outcome of an ETI—one that produced a "cultural organism" (a "sociont") from a substrate of socially learned traditions that were contained in growing and dividing social communities. The SPH predicts that a threshold degree of evolutionary individuality would have been achieved by 2.0–2.5 Mya, followed by an increasing degree of evolutionary individuality as the ETI unfolded. We here assess the SPH by applying a battery of criteria—developed to assess evolutionary individuality in biological units—to cultural units across the evolutionary history of Homo. We find an increasing agreement with these criteria, which buttresses the claim that an ETI occurred in the cultural realm. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluates whether initiation rates, completion rates, response patterns and prevalence of psychiatric conditions differ by level of personal integrity information given to prospective participants in an online mental health self‐report survey. Methods: A three‐arm, parallel‐group, single‐blind experiment was conducted among students from two Swedish universities. Consenting participants following e‐mail invitation answered the World Health Organization (WHO) World Mental Health‐International College Student (WMH‐ICS) mental health self‐report survey, screening for eight psychiatric conditions. Random allocation meant consenting to respond (1) anonymously; (2) confidentially, or (3) confidentially, where the respondent also gave consent for collection of register data. Results: No evidence was found for overall between‐group differences with respect to (1) pressing a hyperlink to the survey in the invitation email; and (2) abandoning the questionnaire before completion. However, participation consent and self‐reported depression were in the direction of higher levels for the anonymous group compared to the two confidential groups. Conclusions: Consent to participate is marginally affected by different levels of personal integrity information. Current standard participant information procedures may not engage participants to read the information thoroughly, and online self‐report mental health surveys may reduce stigma and thus be less subject to social desirability bias. [ABSTRACT FROM AUTHOR]

Objective: During the COVID pandemic, government authorities worldwide have tried to limit the spread of the virus. Sweden's distinctive feature was the use of voluntary public health recommendations. Few studies have evaluated the effectiveness of this strategy. Based on data collected in the spring of 2020, this study explored associations between compliance with recommendations and observed symptoms of contagion in others, using self-report data from university students. Results: Compliance with recommendations ranged between 69.7 and 95.7 percent. Observations of moderate symptoms of contagion in "Someone else I have had contact with" and "Another person" were markedly associated with reported self-quarantine, which is the most restrictive recommendation, complied with by 81.2% of participants. Uncertainty regarding the incidence and severity of contagion in cohabitants was markedly associated with the recommendation to avoid public transportation, a recommendation being followed by 69.7%. It is concluded that students largely followed the voluntary recommendations implemented in Sweden, suggesting that coercive measures were not necessary. Compliance with recommendations were associated with the symptoms students saw in others, and with the perceived risk of contagion in the student's immediate vicinity. It is recommended that voluntary recommendations should stress personal relevance, and that close relatives are at risk. [ABSTRACT FROM AUTHOR]

Rising political polarization in recent decades has hampered and gridlocked policymaking, as well as weakened trust in democratic institutions. These developments have been linked to the idea that new media technology fosters extreme views and political conflict by facilitating self-segregation into "echo chambers" where opinions are isolated and reinforced. This opinion-centered picture has recently been challenged by an emerging political science literature on "affective polarization", which suggests that current polarization is better understood as driven by partisanship emerging as a strong social identity. Through this lens, politics has become a question of competing social groups rather than differences in policy position. Contrary to the opinion-centered view, this identity-centered perspective has not been subject to dynamical formal modeling, which generally permits hypotheses about micro-level explanations for macro-level phenomena to be systematically tested and explored. We here propose a formal model that links new information technology to affective polarization via social psychological mechanisms of social identity. Our results suggest that new information technology catalyzes affective polarization by lowering search and interaction costs, which shifts the balance between centrifugal and centripetal forces of social identity. We find that the macro-dynamics of social identity is characterized by two stable regimes on the societal level: one fluid regime, in which identities are weak and social connections heterogeneous, and one solid regime in which identities are strong and groups homogeneous. We also find evidence of hysteresis, meaning that a transition into a fragmented state is not readily reversed by again increasing those costs. This suggests that, due to systemic feedback effects, if polarization passes certain tipping points, we may experience run-away political polarization that is highly difficult to reverse. [ABSTRACT FROM AUTHOR]

Young adult drinkers engage in a range of drinking patterns from abstaining to heavy drinking in both the United States and Sweden. Heavy drinking during young adulthood in both countries is associated with a variety of negative consequences. Personalized feedback interventions have been identified as effective prevention strategies to prevent or reduce heavy drinking in the United States. This study examined transitions in drinking profiles and compared the efficacy of a personalized feedback intervention for 3965 young adults in the United States (1,735) and Sweden (2230) during their transition out of high school. Using goodness-of-fit criteria, results indicated that three drinking profiles exist among young adults transitioning out of high school: very low drinkers/abstainers, moderate to heavy drinkers, and very heavy drinkers. Latent Markov models revealed a moderating effect of country on personalized feedback intervention such that intervention condition participants in the United States were more likely to belong to the light drinker/abstainer or moderate to heavy profile relative to the very heavy drinking profile at 6-month follow-up. There was no significant effect of personalized feedback intervention in Sweden. Future research could investigate the impact of when personalized feedback interventions are administered and could examine if personalized feedback interventions should be more intentionally culturally adapted in order to be more effective. [ABSTRACT FROM AUTHOR]

Cluster point processes comprise a class of models that have been used for a wide range of applications. While several models have been studied for the probability density function of the offspring displacements and the parent point process, there are few examples of non-Poisson distributed cluster sizes. In this paper, we introduce a generalization of the Thomas process, which allows for the cluster sizes to have a variance that is greater or less than the expected value. We refer to this as the cluster sizes being over- and under-dispersed, respectively. To fit the model, we introduce minimum contrast methods and a Bayesian MCMC algorithm. These are evaluated in a simulation study. It is found that using the Bayesian MCMC method, we are in most cases able to detect over- and under-dispersion in the cluster sizes. We use the MCMC method to fit the model to nerve fiber data, and contrast the results to those of a fitted Thomas process. [ABSTRACT FROM AUTHOR]

We review issues stemming from current models regarding the drivers of cultural complexity and cultural evolution. We disagree with the implication of the treadmill model, based on dual-inheritance theory, that population size is the driver of cultural complexity. The treadmill model reduces the evolution of artifact complexity, measured by the number of parts, to the statistical fact that individuals with high skills are more likely to be found in a larger population than in a smaller population. However, for the treadmill model to operate as claimed, implausibly high skill levels must be assumed. Contrary to the treadmill model, the risk hypothesis for the complexity of artifacts relates the number of parts to increased functional efficiency of implements. Empirically, all data on hunter-gatherer artifact complexity support the risk hypothesis and reject the treadmill model. Still, there are conditions under which increased technological complexity relates to increased population size, but the dependency does not occur in the manner expressed in the treadmill model. Instead, it relates to population size when the support system for the technology requires a large population size. If anything, anthropology and ecology suggest that cultural complexity generates high population density rather than the other way around. [ABSTRACT FROM AUTHOR]

This study investigates the incremental validity of changes in ten stress-related acute dynamic risk factors, collected through automated telephony over 30 consecutive days following parole, for predicting time to recidivism during the following year. Before release, the participants completed self-report assessment of some stable risk factors – impulsiveness and history of problematic substance use – as well as an assessment of symptoms of anxiety experienced during the weeks prior to release. Analysis of the baseline assessments showed that impulsiveness and a history of problematic substance use, but not pre-release symptoms of anxiety, were associated with recidivism during the parole year. Growth modelling using a linear mixed model was used to assess whether inmates on parole showed changes in acute dynamic risk factors during the first month following release. Individual growth model slopes and intercept were then extracted and used as covariates in a series of Cox regression analyses to test whether changes in acute dynamic risk factors could provide incremental predictive validity beyond baseline stable risk factors. Changes in five dynamic risk factors were associated with an increased risk of recidivism, of which daily drug use and daily summary score showed incremental predictive improvement beyond impulsiveness and history of problematic drug use. [ABSTRACT FROM AUTHOR]

This randomized trial evaluates whether automated telephony could be used to perform daily assessments in paroled offenders (N = 108) during their first 30 days after leaving prison. All subjects were called daily and answered assessment questions. Based on the content of their daily assessments, subjects in the intervention group received immediate feedback and a recommendation by automated telephony, and their probation officers also received a daily report by email. The outcome variables were analyzed using linear mixed models. The intervention group showed greater improvement than the control group in the summary scores (M = 9.6, 95% confidence interval [CI] = [0.5, 18.7], p = .038), in mental symptoms (M = 4.6, CI = [0.2, 9.0], p = .042), in alcohol drinking (M = 0.8, CI = [0.1, 1.4], p = .031), in drug use (M = 1.0, CI = [0.5, 1.6], p = .000), and in most stressful daily event (M = 1.9, CI = [1.1, 2.7], p = .000). In conclusion, automated telephony may be used to follow up and to give interventions, resulting in reduced stress and drug use, in paroled offenders. [ABSTRACT FROM AUTHOR]

Alcohol is one of the leading risk factors for global disease burden and overconsumption leads to a wide variety of negative consequences in everyday life. Digital interventions have shown small positive effects in contributing to reductions in problematic use. Specific research on smartphone apps is sparse and the few studies published indicate effects ranging from negative or null to small or moderate. TeleCoach™, a web-based skills training smartphone app, has shown positive effects in non-treatment-seeking university students with excessive drinking. This pilot trial aimed to evaluate app effects in a sample of internet help-seekers from the general population in Sweden. A total of 89 participants were recruited via online advertisement. Following baseline assessment for hazardous use, they were randomized to TeleCoach or a web-based control app offering brief information and advice regarding problematic alcohol use. The primary outcome was number of standard drinks per week; secondary outcomes included drinking quantity and frequency, binge drinking and blood alcohol count measures as well as app user data and comorbidity related to depression, anxiety, and drug use. Analysis of baseline and 6-week follow-up outcomes showed significant within-group effects on alcohol consumption but no significant between-group differences. Effect sizes for the within-group changes in the primary outcome over time were significant [ F (1, 55)=43.98; p < 0.001], with a Cohen's d of 1.37 for the intervention group and 0.92 for the control group. This difference in effect sizes indicated that continuation of the study as a large randomized, controlled trial with up to 1,000 participants could be worthwhile. Clinical Trial Registration: www.ClinicalTrials.gov , identifier NCT03696888. [ABSTRACT FROM AUTHOR]

Despite remarkable empirical and methodological advances, our theoretical understanding of the evolutionary processes that made us human remains fragmented and contentious. Here, we make the radical proposition that the cultural communities within which Homo emerged may be understood as a novel exotic form of organism. The argument begins from a deep congruence between robust features of Pan community life cycles and protocell models of the origins of life. We argue that if a cultural tradition, meeting certain requirements, arises in the context of such a "social protocell," the outcome will be an evolutionary transition in individuality whereby traditions and hominins coalesce into a macroscopic bio-socio-technical system, with an organismal organization that is culturally inherited through irreversible fission events on the community level. We refer to the resulting hypothetical evolutionary individual as a "sociont." The social protocell provides a preadapted source of alignment of fitness interests that addresses a number of open questions about the origins of shared adaptive cultural organization, and the derived genetic (and highly unusual) adaptations that support them. Also, social cooperation between hominins is no longer in exclusive focus since cooperation among traditions becomes salient in this model. This provides novel avenues for explanation. We go on to hypothesize that the fate of the hominin in such a setting would be mutualistic coadaptation into a part-whole relation with the sociont, and we propose that the unusual suite of derived features in Homo is consistent with this hypothesis. [ABSTRACT FROM AUTHOR]

Problem: Emergency care in child and adolescent psychiatry often lacks a coherent treatment model. This study reports on the development and implementation of a salutogenic treatment model at the Child & Adolescent Psychiatric Emergency Unit in Malmö, Sweden. Methods: The development and implementation involved all staff categories and was guided by a recognized authority on salutogenesis. Generalized resistance resources (GRR) were identified that could be implemented at the unit to improve patients' sense of coherence. Findings: Eight GRR were developed and implemented at the unit. During the 6‐month period following the implementation, patients (n = 41) and parents reported satisfaction with the treatment, while mental health improved between admission and discharge, and both treatment length and readmission rates were reduced. Conclusion: A salutogenic treatment model involving GRR seems to be a promising approach in child and adolescent psychiatric emergency treatment. [ABSTRACT FROM AUTHOR]

Objectives Hazardous drinking could negatively affect health and lead to alcohol use disorders, but it is unclear how hazardous drinking affects treatment outcomes of depression and anxiety and stressrelated mental health problems. The aim of this study was to examine whether hazardous drinking, measured by Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), influences the outcomes of repeated assessments of psychological functioning (Outcome Questionnaire-45), stress (Perceived Stress Scale) and sleep (Karolinska Sleep Questionnaire), during and after treatment in patients with mental ill health. Methods The study was conducted within REGASSA, a randomised controlled trial aimed at comparing Internet-based cognitive-behaviour therapy and physical exercise with treatment as usual on primary care patients with mental ill health. The study involved 871 participants who completed the AUDIT at baseline and who were assessed repeatedly during and after treatment on psychological functioning, stress and sleep by interactive voice response, a computerised, automated telephone technology. Results At baseline, hazardous drinkers were more depressed and had lower scores on psychological functioning than non-hazardous drinkers, while there were no differences on stress and sleep. During the follow-ups, hazardous drinking negatively influenced perceived stress, that is, hazardous drinkers seemed to have less treatment effect on stress, and the results remained after controlling for depression. There were no differences during the follow-ups regarding psychological functioning and sleep. Conclusions Hazardous drinking negatively influenced perceived stress. The findings of the study emphasise the importance of screening for alcohol habits in mental ill-health patients, since risky drinking may affect the outcomes of treatment. [ABSTRACT FROM AUTHOR]

While epidermal nerve fiber (ENF) data have been used to study the effects of small fiber neuropathies through the density and the spatial patterns of the ENFs, little research has been focused on the effects on the individual nerve fibers. Studying the individual nerve fibers might give a better understanding of the effects of the neuropathy on the growth process of the individual ENFs. In this study, data from 32 healthy volunteers and 20 diabetic subjects, obtained from suction induced skin blister biopsies, are analyzed by comparing statistics for the nerve fibers as a whole and for the segments that a nerve fiber is composed of. Moreover, it is evaluated whether this type of data can be used to detect diabetic neuropathy, by using hierarchical models to perform unsupervised classification of the subjects. It is found that using the information about the individual nerve fibers in combination with the ENF counts yields a considerable improvement as compared to using the ENF counts only. [ABSTRACT FROM AUTHOR]

Prison release planning is rarely based on adequate assessment using evidence-based instruments. This study uses well-established self-reports for screening of problem severity and for predicting recidivism, measured as reconvictions during one-year following release, in prisoners about to be conditionally released on probation in Sweden between 2009 and 2010. One Hundred and six prisoners completed the following measures: Karolinska Scales of Personality, Hopkins Symptom Checklist-25, Alcohol Use Disorders Identification Test, Drug Use Disorders Identification Test. Results show frequent mental health and substance use problems and high scores on the KSP psychopathy factor. Anxiety and problematic drug use were the two most important factors associated with one-year recidivism. Prior to release, self-reports could be useful for screening of problem severity, and for predicting recidivism. [ABSTRACT FROM AUTHOR]

Objective: The primary objective was to evaluate 6-month outcomes for brief and extensive automated telephony interventions targeting problematic alcohol use, in comparison to an assessment-only control group. The secondary objective was to compare levels of problematic alcohol use (hazardous, harmful or probable dependence), gender and age among study participants from clinical psychiatric and addiction outpatient settings and from populationbased telephone helpline users and Internet help-seeker samples. Results: The Alcohol Use Disorders Identification Test (AUDIT) was used for screening of problematic alcohol use and 6-month follow-up assessment. A total of 248 of help-seekers with at least hazardous use (AUDIT scores of ≥ 6/≥ 8 for women/men) were recruited from clinical and general population settings. Minor recruitment group differences were identified with respect to AUDIT scores and age at baseline. One hundred and sixty persons (64.5%) did not complete the follow-up assessment. The attrition group had a higher proportion of probable dependence (71% vs. 56%; p = 0.025), and higher scores on the total AUDIT, and its subscales for alcohol consumption and alcohol problems. At follow up, within-group problem levels had declined across all three groups, but there were no significant betweengroup differences. [ABSTRACT FROM AUTHOR]

Purpose: Substance use disorders and problematic substance use are common problems in adolescence and young adulthood. Brief personalized feedback has been suggested for treatment of alcohol and drug problems and poor mental health. This repeated measurement randomized controlled trial examines the effect of an interactive voice response (IVR) system for assessing stress, depression, anxiety and substance use. Methods: The IVR system was used twice weekly over 3 months after treatment initiation, with or without addition of a personalized feedback intervention on stress and mental health symptoms. Both IVR assessment only (control group) and IVR assessment including feedback (intervention group) were provided as an add-on to treatment-as-usual procedures (TAU) in outpatient treatment of substance use problems in adolescents and young adults ( N = 73). Results: By using a mixed models approach, differences in change scores were analyzed over the three-month assessment period. Compared to the control group, the intervention group demonstrated significantly greater improvement in the Arnetz and Hasson stress score (AHSS, p = 0.019), the total Symptoms Checklist 8 score (SCL-8D, p = 0.037), the SCL-8D anxiety sub-score ( p = 0.017), and on a summarized feedback score ( p = 0.026), but not on the depression subscale. There were no differences in global substance use scores between the intervention group (feedback on mental health symptoms) and the control group. Conclusion: In conclusion, IVR may be useful for follow-up and repeated interventions as an add-on to regular treatment, and personalized feedback could potentially improve mental health in adolescents and young adults with problematic substance use. [ABSTRACT FROM AUTHOR]

Purpose: University students in a study on estimated blood alcohol concentration (eBAC) feedback apps were offered participation in a second study, if reporting continued excessive consumption at 6-week follow-up. This study evaluated the effects on excessive alcohol consumption of offering access to an additional skills training app. Method: A total of 186 students with excessive alcohol consumption were randomized to an intervention group or a wait list group. Both groups completed online follow-ups regarding alcohol consumption after 6 and 12 weeks. Wait list participants were given access to the intervention at 6-week follow-up. Assessment-only controls ( n = 144) with excessive alcohol consumption from the ongoing study were used for comparison. Results: The proportion of participants with excessive alcohol consumption declined in both intervention and wait list groups compared to controls at first ( p < 0.001) and second follow-ups ( p = 0.054). Secondary analyses showed reductions for the intervention group in quantity of drinking at first follow-up (−4.76, 95% CI [−6.67, −2.85], Z = −2.09, p = 0.037) and in frequency of drinking at both follow-ups (−0.83, 95% CI [−1.14, −0.52], Z = −2.04, p = 0.041; −0.89, 95% CI [−1.16, −0.62], Z = −2.12, p = 0.034). The odds ratio for not having excessive alcohol consumption among men in the intervention group compared to male controls was 2.68, 95% CI [1.37, 5.25] ( Z = 2.88, p = 0.004); the figure for women was 1.71, 95% CI [1.11, 2.64] ( Z = 2.41, p = 0.016). Conclusion: Skills training apps have potential for reducing excessive alcohol use among university students. Future research is still needed to disentangle effects of app use from emailed feedback on excessive alcohol consumption and study participation. Trial Registration: NCT02064998 [ABSTRACT FROM AUTHOR]

Few studies have assessed acute dynamic risk repeatedly among paroled offenders to investigate the relationship between changes in acute dynamic risk and recidivism in crime. The present study investigates whether one-month changes in ten stress-related acute dynamic risk factors, collected through automated telephony while the participants were still in prison and over 30 consecutive days following parole, predict one-year criminal recidivism, including its predictive accuracy. The study also investigates whether a brief feedback intervention in conjunction with the daily assessments reduces recidivism compared to an assessment-only control group. Changes in five risk factors were found to be associated with increased risk of criminal recidivism after controlling for the results in prison, the initial value after parole, and the intervention. The predictive accuracy is marginally accurate: Summary score (AUC) D .666; Level of stress (AHSS) D .644; Psychiatric symptoms (SCL-8D) D .641; Anxiety symptoms D .673; Severity of most stressful daily event D .690. No differences in one-year recidivism rates were established between the intervention group and the control group. The study shows that daily assessments can usefully be made of dynamic risk factors in paroled offenders. [ABSTRACT FROM AUTHOR]

Objectives Mental ill-health has become a large health problem and it is important for caregivers to provide effective treatment alternatives. REGASSA is a randomized controlled study performed in primary care to study the effects of 12 weeks of Internet-based cognitive behaviour therapy ( ICBT) and physical exercise ( PE) compared with treatment as usual ( TAU) in patients with mild-to-moderate mental ill-health. The present study aimed to examine the results of these treatment alternatives on psychological functioning, stress, and sleep disturbances. Methods The study comprised 879 patients with mental ill-health taking part in the REGASSA study. Data were collected by Interactive Voice Response ( IVR), a computerized, automated telephone technique. The treatments were compared at baseline, twice during treatment, at the end of treatment and at three follow-ups after treatment. Measures used were the Outcome Questionnaire-45, the short versions of the Perceived Stress Scale, and the Karolinska Sleep Questionnaire. Results Linear mixed models showed that the patients in ICBT and PE had better results than in TAU on psychological functioning and sleep disturbances, p < .001 , with weak-to-moderate effect sizes. On stress there were no differences; all groups made improvements. Women had stronger effects than men. More patients recovered on psychological functioning ( OQ-45) in ICBT and PE than in TAU. Conclusions Internet-based cognitive behaviour therapy and PE proved to be effective treatment alternatives for patients with mild-to-moderate mental ill-health in improving psychological functioning, stress, and sleep disturbances and could be useful alternatives in primary care. Practitioner points Internet-based cognitive behaviour therapy and physical exercise proved to be effective treatment alternatives for mental ill-health patients in primary care., Automated techniques (Interactive Voice Response) could be useful for following treatment course in large groups of patients in the health care., It is important to use measures that capture different aspects of patients' health problems., The recruitment of participants was based on patients' interest and inclusion criteria which may have affect the generalizability. [ABSTRACT FROM AUTHOR]

Epidermal nerve fibre (ENF) density and morphology are used to study small fibre involvement in diabetic, HIV, chemotherapy induced and other neuropathies. ENF density and summed length of ENFs per epidermal surface area are reduced, and ENFs may appear more clustered within the epidermis in subjects with small fibre neuropathy than in healthy subjects. Therefore, it is important to understand the spatial structure of ENFs. In this paper, we compare the ENF patterns between healthy subjects and subjects suffering from mild diabetic neuropathy. The study is based on suction skin blister specimens from the right foot of 32 healthy subjects and eight subjects with mild diabetic neuropathy. We regard the ENF entry point (location where the trunks of a nerve enters the epidermis) and ENF end point (termination of the nerve fibres) patterns as realizations of spatial point processes, and develop tools that can be used in the analysis and modelling of ENF patterns. We use spatial summary statistics and shift plots and define a new tool, reactive territory, to study the spatial patterns and to compare the patterns of the two groups. We will also introduce a simple model for these data in order to understand the growth process of the nerve fibres. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The increasing size of datasets in drug discovery makes it challenging to build robust and accurate predictive models within a reasonable amount of time. In order to investigate the effect of dataset sizes on predictive performance and modelling time, ligand-based regression models were trained on open datasets of varying sizes of up to 1.2 million chemical structures. For modelling, two implementations of support vector machines (SVM) were used. Chemical structures were described by the signatures molecular descriptor. Results showed that for the larger datasets, the LIBLINEAR SVM implementation performed on par with the well-established libsvm with a radial basis function kernel, but with dramatically less time for model building even on modest computer resources. Using a non-linear kernel proved to be infeasible for large data sizes, even with substantial computational resources on a computer cluster. To deploy the resulting models, we extended the Bioclipse decision support framework to support models from LIBLIN-EAR and made our models of logD and solubility available from within Bioclipse. [ABSTRACT FROM AUTHOR]

A response by Dwight Read and Claes Andersson to the letters to the editor about their article "The Evolution of Cultural Complexity: Not by the treadmill alone" in the June 2016 issue is presented.

Among the drivers and constraints on the evolution of complex hominin culture that have been proposed throughout the years, demographic factors have been particularly persistent, and they have recently again come to gain traction in the literature in the shape of the so-called treadmill model. The treadmill model connects cultural complexity to group size via a need to constantly "outrun a treadmill of cultural loss," whose backward motion is caused by errors in culture transmission. The entrenchment of the treadmill explanation of cultural complexity, however, takes place against a background of critiques of the model and the presence of other explanatory propositions. This creates a need for deentrenchment: wider integration, elaboration, and critique of the premises of the treadmill model and the evidence advanced to validate it. We begin by reviewing the treadmill model, making an assessment of its current status, and then moving on to a more synthetic proposition by placing the model into the context of other models addressing the elaboration of cultural complexity.We end by considering the broader implications for the study of the evolution of culture and of human behavior to be gained from more integrated modeling of the various factors affecting cultural complexity. [ABSTRACT FROM AUTHOR]

Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar enediyne (1), the helical stiff stilbene (2), or the semi-rigid glycoluril motif fused to the porphyrins (3), are compared. Binding constants Ka = 104-106 M-1 reveal subtle differences between these tweezers, that are discussed in terms of porphyrin dislocation modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis. [ABSTRACT FROM AUTHOR]

The lysosomal storage disease alpha-mannosidosis is caused by the deficiency of the lysosomal acid hydrolase alpha-mannosidase (LAMAN) leading to lysosomal accumulation of neutral mannose-linked oligosaccharides throughout the body, including the brain. Clinical findings in alpha-mannosidosis include skeletal malformations, intellectual disabilities and hearing impairment. To date, no curative treatment is available. We previously developed a beneficial enzyme replacement therapy (ERT) regimen for alpha-mannosidase knockout mice, a valid mouse model for the human disease. However, humoral immune responses against the injected recombinant human alpha-mannosidase (rhLAMAN) precluded long-term studies and chronic treatment. Methods: Here, we describe the generation of an immune-tolerant alpha-mannosidosis mouse model that allowed chronic injection of rhLAMAN by transgenic expression of a catalytically inactive variant of human LAMAN in the knockout background. Results: Chronic ERT of rhLAMAN revealed pronounced effects on primary substrate storage throughout the brain, normalization of lysosomal enzyme activities and morphology as well as a decrease in microglia activation. The positive effect of long-term ERT on neuronal lysosomal function was reflected by an improvement of cognitive deficits and exploratory activity. in vivo and in vitro uptake measurements indicate rapid clearance of rhLAMAN from circulation and a broad uptake into different cell types of the nervous system. Interpretation: Our data contribute to the understanding of neurological disorders treatment by demonstrating that lysosomal enzymes such as rhLAMAN can penetrate into the brain and is able to ameliorate neuropathology. [ABSTRACT FROM AUTHOR]

Unlabelled: This study evaluated automated techniques including personalized normative feedback and protective behavioral strategies, for brief interventions intended to reduce peak alcohol concentrations in university students. After completing baseline assessment, a total of 1,678 hazardous-drinking consumers were randomized to a single or a repeated Internet (WEB) or Interactive Voice Response (IVR) intervention, or to a control group (Single WEB: 323; Single IVR: 329; Repeated WEB: 318; Repeated IVR: 334;Control Group: 374). At follow-up, six weeks after baseline, questionnaires were returned by 1,422 participants (Single WEB: 277; Single IVR: 286; Repeated WEB: 259; Repeated IVR: 279;Control Group: 321). It was found that peak estimated BAC was reduced in the total group (b -0.14, 95% confidence interval (CI) -0.023; -0.005), in the total (b -0.17, 95% CI -0.027; -0.007) and single (b -0.021, 95% CI -0.032; -0.011) WEB group, and in the total (b -0.011, 95% CI -0.021; -0.015) and repeated (b -0.012, 95% CI -0.023; -0.000) IVR groups, compared to controls. The reduction in peak estimated BAC was greater in the single WEB group compared to the single IVR group (b -0.011, 95% CI -0.022; -0.000). This study concluded that both WEB and IVR interventions have a small but significant effect in reducing heavy episodic drinking, which may be due to the relatively large sample size. Repeated intervention may be needed if delivered by IVR. [ABSTRACT FROM AUTHOR]

This study evaluated automated techniques including personalized normative feedback and protective behavioral strategies, for brief interventions intended to reduce peak alcohol concentrations in university students. After completing baseline assessment, a total of 1,678 hazardous-drinking consumers were randomized to a single or a repeated Internet (WEB) or Interactive Voice Response (IVR) intervention, or to a control group (Single WEB: 323; Single IVR: 329; Repeated WEB: 318; Repeated IVR: 334; Control group: 374). At follow-up, six weeks after baseline, questionnaires were returned by 1,422 participants (Single WEB: 277; Single IVR: 286; Repeated WEB: 259; Repeated IVR: 279; Control group: 321). It was found that peak estimated BAC was reduced in the total group (b -0.14, 95% confidence interval (CI) -0.023; -0.005), in the total (b -0.17, 95% CI -0.027; -0.007) and single (b -0.021, 95% CI -0.032; -0.011) WEB group, and in the total (b -0.011, 95% CI -0.021; -0.015) and repeated (b -0.012, 95% CI -0.023; -0.000) IVR groups, compared to controls. The reduction in peak estimated BAC was greater in the single WEB group compared to the single IVR group (b -0.011, 95% CI -0.022; -0.000). This study concluded that both WEB and IVR interventions have a small but significant effect in reducing heavy episodic drinking, which may be due to the relatively large sample size. Repeated intervention may be needed if delivered by IVR. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Patients’ problematic substance use prevalence and effects were explored in relation to internet-based cognitive behavioral therapy (ICBT) outcomes for depression, panic disorder and social anxiety disorder. Methods: At baseline and treatment conclusion, 1601 ICBT patients were assessed with self-rated measures for alcohol and drug use (AUDIT/DUDIT), depressive symptoms (MADRS-S), panic disorder symptoms (PDSS-SR) and social anxiety symptoms (LSAS-SR). Results: Problematic substance use (AUDIT ≥8 for men, ≥6 for women; DUDIT ≥1) occurred among 32.4% of the patients; 24.1% only alcohol, 4.6% only drugs, and 3.7% combined alcohol and drug use. Hazardous alcohol use and probable alcohol dependence negatively affected panic disorder outcomes, and hazardous drug use led to worse social anxiety outcomes. Depression outcomes were not affected by substance use. Treatment adherence was negatively affected by problematic drug use among men and 25–34 year olds; combined substance use negatively affected adherence for women and 35–64 year olds. Conclusion: Problematic substance use does not preclude ICBT treatment but can worsen outcomes, particularly problematic alcohol use for panic disorder patients and hazardous drug use for social anxiety patients. ICBT clinicians should exercise particular caution when treating men and younger patients with problematic drug use, and women or older patients with combined substance use. [ABSTRACT FROM AUTHOR]