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A certified reference material of ricin (CRM-LS-1) was produced by the EuroBioTox consortium to standardise the analysis of this biotoxin. This study established the N-glycan structures and proportions including their loci and occupancy of ricin CRM-LS-1. The glycan profile was compared with ricin from different preparations and other cultivars and isoforms. A total of 15 different oligomannosidic or paucimannosidic structures were identified in CRM-LS-1. Paucimannose was mainly found within the A-chain and oligomannose constituted the major glycan type of the B-chain. Furthermore, the novel primary structure variants E138 and D138 and four different C-termini of the A-chain as well as two B-chain variants V250 and F250 were elucidated. While the glycan proportions and loci were similar among all variants in CRM-LS-1 and ricin isoforms D and E of all cultivars analysed, a different stoichiometry for isoforms D and E and the amino acid variants were found. This detailed physicochemical characterization of ricin regarding the glycan profile and amino acid sequence variations yields unprecedented insight into the molecular features of this protein toxin. The variable attributes discovered within different cultivars present signature motifs and may allow discrimination of the biotoxin's origin that are important in molecular forensic profiling. In conclusion, our data of in-depth CRM-LS-1 characterization combined with the analysis of other cultivars is representative for known ricin variants. [ABSTRACT FROM AUTHOR]

Background: Though Internet- and mobile-based interventions (IMIs) and mindfulness-based interventions (generally delivered in-situ) appear effective for people with substance use disorders, IMIs incorporating mindfulness are largely missing, including those targeting frequent cannabis use. Methods: This paper details the protocol for a three-arm randomized controlled trial comparing a mindfulness-based self-help IMI (arm 1) and cognitive-behavioral therapy (CBT)-based self-help IMI (arm 2) versus being on a waiting list (arm 3) in their effectiveness reducing cannabis use in frequent cannabis users. Predictors of retention, adherence and treatment outcomes will be identified and similarities between the two active intervention arms explored. Both active interventions last six weeks and consist of eight modules designed to reduce cannabis use and common mental health symptoms. With a targeted sample size of n = 210 per treatment arm, data will be collected at baseline immediately before program use is initiated; at six weeks, immediately after program completion; and at three and six months post baseline assessment to assess the retention of any gains achieved during treatment. The primary outcome will be number of days of cannabis use over the preceding 30 days. Secondary outcomes will include further measures of cannabis use and use of other substances, changes in mental health symptoms and mindfulness, client satisfaction, intervention retention and adherence, and adverse effects. Data analysis will follow ITT principles and primarily employ (generalized) linear mixed models. Discussion: This RCT will provide important insights into the effectiveness of an IMI integrating mindfulness to reduce cannabis use in frequent cannabis users. Trial registration: International Standard Randomized Controlled Trial Number Registry: ISRCTN14971662; date of registration: 09/09/2021. [ABSTRACT FROM AUTHOR]

Buying-shopping disorder and its transferability to the online sector is controversial. This study investigates in-store and online shopping patterns by comparing data-based modeling to a diagnostic cut-off approach. Further aims were to test model equivalence for gender and identify socio-demographic risk factors. In a representative survey, the Bergen Shopping Addiction Scale (BSAS) was applied, using both an online and in-store version. Latent class analyses were followed by multinomial logistic regression analyses to investigate socio-demographic variables. Measurement invariance across genders was tested with multi-group comparisons. With N = 1,012, 3-class solutions provided the best model fit for both in-store and online shopping. Most individuals (76, 86%) were grouped in non-addicted classes, followed by risky (21, 11%) and addicted classes (both 3%). Twenty-eight percent of individuals in the online addicted shopping class remained unidentified using the cut-off. For online shopping, only lower age and education differentiated classes significantly. Results indicate a close link between online and in-store shopping, albeit with distinguishing features. The cut-off yielded findings discrepant from class probabilities. That buying-shopping disorder mainly affects younger women of lower educational level must be questioned, given the limited associations identified. It is important not only to consider different settings of pathological shopping, but also to focus on groups that may not have appeared at risk in previous investigations (e.g., men, older age). The BSAS cut-off warrants further research. [ABSTRACT FROM AUTHOR]

In 2010 Russia and Norway signed a treaty that ended a 40-year dispute by dividing territory in the Barents Sea. Why did this case end in a cooperative agreement rather than continue an on-going dispute? This article examines a number of possible explanations at the international, bilateral, and domestic politics levels to answer this question. Ultimately, it concludes that the 2010 Norway-Russia boundary delimitation agreement succeeded because both sides had a strong economic interest in it, benefitted from the use of international law, had a history of working together at the bilateral level, and were able to manage adroitly the impact of business-state relations and identity politics on the issue. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the author discusses various articles featured in the journal's special section on construction and practices of security in regional organizations (ROs) and their role in global and national security governance.

A novel strategy to perform tomographic image reconstruction is presented, based on the integration of a priori information about the target image. Such information may come from a different imaging tool or a synthetic model. For a given image quality, providing a priori image information reduces the amount of image information to be reconstructed. According to the data processing inequality this requires less input data or physical measurements, therefore reducing exposure to ionising radiation. A prototype algorithm is described, consisting of a penalized ART where some a priori edge information is encoded in an inhomogeneous, anisotropic smoothing kernel. The algorithm is tested on a 2-dimensional set-up based on the Shepp-Logan phantom. [ABSTRACT FROM AUTHOR]

Switzerland only played a marginal role in the Cold War, even though the small country was situated very close to the central battleground of any potential armed conflict in Europe the 'special role' that Switzerland played in the East-West conflict was closely linked to its policy of strict neutrality. Swiss Cold War historians have focused on the reasons for the emergence of Switzerland's 'special case' in foreign and security policy and on the consequences of this policy for the political, economic, military, and social relations between Switzerland and its international environment. With the launching of the Parallel History Project (PHP) at ETH Zurich in 1998, Switzerland has become the home of one of the major Cold War History networks. As a result, the findings of a new generation of Swiss Cold War historians are increasingly integrated into an emerging international history of the East-West confrontation. [ABSTRACT FROM AUTHOR]

Neovascularization is a critical step in tissue engineering applications since implantation of voluminous grafts without sufficient vascularity results in hypoxic cell death of central tissues. We have developed a three-dimensional spheroidal coculture system consisting of human umbilical vein endothelial cells (HUVECs) and human primary fibroblasts (hFBs) to improve angiogenesis in tissue engineering applications. Morphological analysis of cryosections from HUVEC/hFB cospheroids revealed a characteristic temporal and spatial organization with HUVECs located in the center of the cospheroid and a peripheral localization of fibroblasts. In coculture spheroids, the level of apoptosis of endothelial cells was strongly decreased upon cocultivation with fibroblasts. Collagen-embedded HUVEC spheroids develop numerous lumenized capillary-like sprouts. This was also apparent for HUVEC/hFB cospheroids, albeit to a lesser extent. Quantification of cumulative sprout length revealed an approximately 35% reduction in endothelial cell sprouting upon cocultivation with fibroblasts in cospheroids. The slight reduction in endothelial cell sprouting was not mediated by a paracrine mechanism but is most likely due to the formation of heterogenic cell contacts between HUVECs and hFBs within the cospheroid. The model system introduced in this study is suitable for the development of a preformed lumenized capillary-like network ex vivo and may therefore be useful for improving angiogenesis in in vivo tissue engineering applications. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Multiple cell–cell interactions control bone morphogenesis and vascularization. We have employed a spheroidal coculture system of endothelial cells (EC) and osteoblasts (OB) to study cell contact-dependent gene regulation between these two cell types that may play a role in regulating OB differentiation and EC angiogenic properties. Coculture spheroids differentiate spontaneously to organize into a core of OB and a surface layer of endothelial cells. Individual spheroid culture of EC or OB leads to significant alterations in gene expression compared to standard monolayer culture (upregulation of Tie-2 in EC; upregulation of angiopoietin-2 in osteoblasts). More importantly, spheroidal coculture of endothelial cells and osteoblasts leads to significant changes of gene expression in both cell populations (upregulation of VEGFR-2 in EC; downregulation of VEGF, and upregulation of alkaline phosphatase in osteoblasts). These changes are dependent on cell–cell contact and are not seen in stimulation experiments with conditioned supernatants. Collectively, the data demonstrate complex bi-directional gene regulation mechanisms between EC and OB that are likely to play a critical role during OB differentiation and in controlling the properties of angiogenic EC. [Copyright &y& Elsevier]

This article discusses how the North Atlantic Treaty Organization (NATO) overcame the challenged posed by France in the mid- to late 1960s. French President Charles de Gaulle's decision to withdraw France's remaining forces from NATO's integrated military commands, and his visit to Moscow shortly thereafter, exposed the alliance to unprecedented tension. Yet as NATO moved toward a crisis, opportunities arose to define a new vision for the alliance in a time of détente. Trilateral talks among the United States, Britain, and the Federal Republic of Germany forged a consensus on strategy, force levels, burden sharing, and nuclear consultation - a consensus that was endorsed by the other member-states. The Harmel exercise in 1967 restored NATO's political purpose, expanding its political role as an instrument of peace. By 1968 NATO had evolved into a less hierarchical military alliance of fourteen and a more political and participatory alliance of fifteen (including France). This successful transformation of NATO moved the process of détente from the bilateral superpower accommodation of 1963 to the multilateral European rapprochement of the 1970s. [ABSTRACT FROM AUTHOR]

Discusses the interactions between diplomacy and social protest. Examination of the international political and military pressures that elicited the 'little d é tente' of 1963; Reforms within alliances and domestic institutions during the early 1960s; Long-term shortcomings of d é tente.

Introduction: The main objective of this study was to test the longer-term and differential efficacy of a mobile phone‒based life-skills training program designed to prevent substance use among adolescents.Study Design: A 2-arm, parallel-group, cluster RCT with assessments at baseline and follow-up after 6 and 18 months was conducted. The efficacy of the intervention was compared with that of an assessment-only control condition.Setting/participants: A total of 1,473 students with a mean age of 15.4 years were recruited in 2019/2020 within 89 Swiss secondary and upper secondary school classes.Intervention: The automated intervention program included online feedback and individually tailored text messages provided over 22 weeks. The contents were based on social cognitive theory and addressed self-management, social, and substance use resistance skills.Main Outcome Measures: Primary outcomes included 30-day prevalence rates for problem drinking and tobacco use.Results: The 18-month follow-up assessments were completed by 1,232 study (83.6%) participants. Those in the intervention group reported lower tobacco-smoking prevalence than the controls (OR=0.67; 95% CI=0.47, 0.96), but no significant difference in problem drinking (OR=0.84; 95% CI=0.61, 1.17) was observed. Among secondary outcomes, the intervention was effective at reducing cannabis-smoking prevalence (OR=0.55; 95% CI=0.39, 0.76) and cannabis use days (Cohen's d= -0.19; 95% CI= -0.29, -0.09), whereas no effects were observed for quantity of alcohol use, quantity of cigarettes smoked, well-being, or social skills. No significant moderators of the primary outcomes were observed.Conclusions: An automated mobile phone‒based life-skills training program produced longer-term effectiveness in preventing tobacco smoking and cannabis use, whereas no effects were observed for problem drinking. These results suggest that digitally delivered life-skills training programs are similarly effective and are an easy-to-implement alternative to training conducted within a school curriculum.Trial Registration: This study is registered at ISRCTN41347061 (registration date: 21/07/2018). [ABSTRACT FROM AUTHOR]

Background: A large proportion of apprentices shows addictive behaviours like cigarette smoking, alcohol, cannabis, or compulsive Internet use, others do not show such behaviours at all. ready4life is a smartphone application-based coaching program for apprentices, which takes into account the heterogeneity of adolescent addictive behaviour by promoting life skills and reducing risk behaviours. The main objective of the planned study is to test the efficacy of ready4life for addiction prevention among apprentices in Switzerland within a controlled trial.Methods/design: The efficacy of the ready4life coaching program will be tested in comparison to an assessment only control group, within a cluster-randomised controlled trial with one follow-up assessment after 6 months. At the beginning of the program, participants of the intervention group will receive an individual profile, showing areas in which they have sufficient resources and in which there is a need for coaching. Based on this feedback, they can select two out of the following six program modules: stress, social skills, Internet use, tobacco/e-cigarettes, cannabis, and alcohol. Participants of the intervention group will receive individualised coaching by a conversational agent (chatbot) for a period of four months. The coaching relies on motivational and social-cognitive principles of behaviour change. Within weekly dialogues, the coach provides individually tailored information in different formats, such as videoclips, texts, or pictures. Study participants will be 1318 apprentices with a minimum age of 15, recruited in approximately 100 vocational school classes in Switzerland. Primary outcome will be a composite measure for addictive behaviours including (1) at risk-drinking, (2) tobacco/e-cigarette smoking, (3) cannabis use, and (4) problematic Internet use.Discussion: The study will reveal whether this universally implementable but individually tailored intervention approach is effective in preventing the onset and escalation of addictive behaviors among apprentices.Trial Registration: ISRCTN59908406 (registration date: 21/10/2020). [ABSTRACT FROM AUTHOR]

Background and Aims: Problem gambling constitutes a public health concern associated with psychopathological comorbidity, substance use, and financial difficulties. Most individuals with gambling problems avoid counseling services due to perceived stigma and their preference for self-reliance. Treatment accessibility could be improved through web-based interventions. Methods: We recruited 360 individuals with gambling problems and randomized them to a web-based intervention (n 5 185) or an active control group consisting of a self-help manual for problem gambling (n 5 175). The primary outcome was the number of days of gambling in the last 30 days. Secondary outcomes included money spent in the last 30 days, time gambling in the last 7 days, gambling-related problems, consumption of alcohol and cigarettes, and psychopathological comorbidity measured at posttreatment and 6-month follow-up. Results: The primary outcome decreased significantly for both groups, with no significant difference between the groups. There were significant group 3time interactions according to the Gambling Symptom Assessment Scale (F 5 8.83, p <0 .001), the Problem Gambling Severity Index (F 5 3.54, p 5 0.030), for cigarettes smoked in the last 7 days (F 5 26.68, p < 0.001), the Patient Health Questionnaire-9 (F 5 19.41, p <0 .001), and the Generalized Anxiety Disorder-7 (F 5 41.09, p <0 .001) favoring the intervention group. We experienced an overall high dropout rate (76%). Conclusions: Win Back Control seems to be an effective low-threshold treatment option for individuals with gambling problems that might otherwise be unapproachable for outpatient treatment services. Nevertheless, the high dropout rate should be considered when interpreting the study results, as they may have introduced a degree of variability. [ABSTRACT FROM AUTHOR]

Background: Web-based self-help interventions that aim to reduce problematic substance use are able to reach "hidden" consumer groups in the general population who often fear stigmatization and thus avoid institutional addiction treatment. In Western European countries, including Switzerland, cocaine is the most widely used psychoactive substance after alcohol, tobacco, and cannabis. Although approximately one in six users develop serious problems of dependency, only a minority seeks help from psychiatrists or in outpatient counseling centers or psychiatric hospitals. Offering web-based therapy treatment may potentially reach users who hesitate to approach institutional treatment services and help them reduce their cocaine use before they get into more serious trouble. Methods/design: The study will use a three-arm randomized controlled trial (RCT) design to test the efficacy of a web-based self-help intervention with or without guided chat counseling compared with that of a waiting list control condition in reducing or stopping cocaine use. The primary outcome measure will be the weekly quantity of cocaine used. Secondary outcome measures will include the number of cocaine use days in the past 30 days, the severity of cocaine dependence, the use of alcohol, tobacco, and/or other illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of eight modules that are designed to reduce cocaine use and depression symptoms. These modules are based on the principles of Motivational Enhancement Therapy and Cognitive Behavioral Therapy, such as Behavioral Self-Management. The three individual chat therapy sessions will be based on the same therapy approaches and will be tailored to participants' self-help data and aim to assist the reinstatement of social rewards and the improvement of social support and relationships. Discussion: This study will be the first RCT to test the effectiveness of a web-based self-help intervention in combination with or without chat counseling in reducing cocaine use. The expected findings will contribute substantial knowledge that may help design effective guided and unguided web-based treatment for cocaine users. Moreover, the study will elucidate to what extent a therapeutic alliance with cocaine users can be established in a guided Internetdelivered setting. Additionally, the present study will investigate changes in social support with specific guided therapy interventions that aim to ameliorate social support and social perceptions and compare these changes with those in an unguided self-help intervention. [ABSTRACT FROM AUTHOR]

Background: In European countries, including Switzerland, as well as in many states worldwide, cannabis is the most widely used psychoactive substance after alcohol and tobacco. Although approximately one in ten users develop serious problems of dependency, only a minority attends outpatient addiction counseling centers. The offer of a combined web-based self-help and chat counseling treatment could potentially also reach those users who hesitate to approach such treatment centers and help them to reduce their cannabis use. Methods/design: This paper presents the protocol for a three-armed randomized controlled trial that will test the effectiveness of a web-based self-help intervention in combination with, or independent of, tailored chat counseling compared to a waiting list in reducing or enabling the abstention from cannabis use in problematic users. The primary outcome will be the weekly quantity of cannabis used. Secondary outcome measures will include the number of days per week on which cannabis is used, the severity of cannabis use disorder, the severity of cannabis dependence, cannabis withdrawal symptoms, cannabis craving, the use of alcohol, tobacco, and other non-cannabis illicit drugs, changes in mental health symptoms, and treatment retention. The self-help intervention will consist of 8 modules designed to reduce cannabis use based on the principles of motivational interviewing, self-control practices, and methods of cognitive behavioral therapy. The two additional individual chat-counseling sessions in the additional chat condition will be based on the same therapy approaches and tailored to participants' self-help information data and personal problems. The predictive validity of participants' baseline characteristics on treatment retention and outcomes will be explored. Discussion: To the best of our knowledge, this will be the first randomized controlled trial to test the effectiveness of online self-help therapy in combination or without chat counseling in reducing or enabling the abstention from cannabis use. It will also investigate predictors of outcome and retention for these interventions. [ABSTRACT FROM AUTHOR]

This article explores what political science literature has to say about the promises and perils of expanding democratic governance. International relations literature and comparative politics literature both deal with the claim that stable democracies do not fight each other. However, these two strands of literature only to a minor extent exchange research findings on the causes of war. International relations scholars are well aware of the fact that the early stages of democratization in particular may trigger conflict, and they explain that they are referring to the size of a country's power and the distribution of capabilities among the major powers, among other factors. In contrast, comparativists focus on the opening of domestic political space. In a transitional state, open political space fosters elite competition, which cannot be regulated by weak political institutions and therefore may cause civil war. They are less aware of the fact that these internal dynamics may even enhance the risk of political violence beyond territorial borders. Both of these approaches must be used to focus on the consequences of democratization on a regional scale. In 'bad neighbourhoods', including the Balkans, the Caucasus, the Middle East and the Great Lakes in Africa, democratization can trigger conflict beyond state frontiers by altering the incentives and opportunities of political actors. [ABSTRACT FROM AUTHOR]

Abstract: Survival of tissue transplants generated in vitro is strongly limited by the slow process of graft vascularization in vivo. A method to enhance graft vascularization is to establish a primitive vascular plexus within the graft prior to transplantation. Endothelial cells (EC) cultured as multicellular spheroids within a collagen matrix form sprouts resembling angiogenesis in vitro. However, osteoblasts integrated into the graft suppress EC sprouting. This inhibition depends on direct cell–cell-interactions and is characteristic of mature ECs isolated from preexisting vessels. In contrast, sprouting of human blood endothelial progenitor cells is not inhibited by osteoblasts, making these cells suitable for tissue engineering of pre-vascularized bone grafts. [Copyright &y& Elsevier]

Background and Aims: Estonia has one of the highest alcohol‐attributable mortality rates within the European Union. The aim of this study was to estimate the efficacy of an on‐line self‐help intervention to reduce problem drinking at the population level. Design On‐line open randomized controlled trial with an 8‐week intervention and an active control group (intervention n = 303, control n = 286). Assessments took place at baseline and at 6 months follow‐up. Setting: On‐ and offline channels were used for population‐based recruitment within a nation‐wide prevention campaign in Estonia. Participants: Inclusion criteria were age ≥ 18 years, heavy drinking [Alcohol Use Disorders Identification (AUDIT) test score ≥ 8], literacy in Estonian and at least weekly access to the internet; n = 589 participants were randomized (50% male, 1% other; mean age 37.86 years; 45% with higher level of education). Intervention and comparator: The intervention consisted of 10 modules based on principles of cognitive–behavioral therapy and motivational interviewing. The active control group received access to a website with a self‐test including personalized normative feedback and information for standard alcohol treatment. Measurements The primary outcome was AUDIT scores at 6 months follow‐up adjusted for baseline scores. Findings Intention‐to‐treat analyses were applied. Missing data were addressed by using baseline observation carried forward (BOCF) and multiple imputation by chained equations (MI); 175 completed follow‐up in the intervention group and 209 in the control group. AUDIT score at follow‐up was significantly smaller in the intervention [BOCF mean = 13.91, standard deviation (SD) = 7.61, MI mean = 11.03, SD = 6.55] than control group (BOCF mean = 15.30, SD = 7.31; MI mean = 14.30, SD = 7.21), with a group difference of −1.38 [95% confidence interval (CI) = –2.58, –0.18], P = 0.02 for BOCF and −3.26 (95% CI = –2.01, –4.51), P < 0.001 for MI. Conclusions: A randomized controlled trial has found that an on‐line self‐help intervention with minimal guidance was effective at reducing problem drinking in Estonia. [ABSTRACT FROM AUTHOR]

Background: Depression and harmful alcohol use are two of the top five leading causes of years of life lost to disability in high-income countries. Integrated treatment targeting both at the same time is often considered more complicated and difficult and, therefore, more expensive. Consequently, integrated internet-based interventions could be a valuable addition to traditional care.Methods: A three-arm randomized controlled trial was conducted comparing the effectiveness of (1) an integrated, minimal-guidance, adherence-focused self-help intervention designed to reduce both alcohol use and depression symptoms (AFGE-AD); (2) a similar intervention designed to reduce alcohol use only (AFGE-AO), and (3) internet access as usual (IAU) as a control condition, in at least moderately depressed alcohol misusers from February 2016-March 2020. We recruited 689 alcohol misusers (51.6 % males, mean age = 42.8 years) with at least moderate depression symptoms not otherwise in treatment from the general population. Six months after baseline, 288 subjects (41.8 %) were reachable for the final assessment.Results: All interventions yielded reduced alcohol-use after six months (AFGE-AD: -16.6; AFGE-AO: -19.8; IAU: -13.2). Those who undertook active-interventions reported significantly fewer standard drinks than controls (AFGE-AD: p = .048, d=0.10; AFGE-AO: p = .004, d=0.20). The two active-intervention groups also reported significantly less severe depression symptoms than controls (AFGE-AD: p = .006, d=0.41; AFGE-AO: p = .008, d=0.43). Testing revealed noninferiority between the two interventions.Conclusions: This study documented sustained effectiveness of the first integrated, fully internet-based self-help intervention developed for the reduction of both alcohol use and depression symptoms in at least moderately depressed adult alcohol misusers recruited from the general population. [ABSTRACT FROM AUTHOR]

Background: Despite an initial steep decrease in alcohol misuse among Estonians through structural intervention means and the scaling up of alcohol counselling in the mid-2000's, most of the country's alcohol misuse indicators remain clearly higher than European averages. Consequently, an online self-help program was launched as part of an initial behavioral intervention initiative to foster progress in alcohol prevention on a population level.Methods: A two-arm randomized controlled trial (RCT) has been designed to compare the efficacy of a culturally-adapted minimal-guidance online self-help program, the 8-week "Selge" online program against a control condition that consists of a self-administered test of alcohol use and advice regarding usual treatment in Estonia. A target sample of 600 individuals will be recruited and randomly assigned to either condition. The program will contain 10 modules based on principles of cognitive behavioural therapy (CBT) and motivational interviewing (MI). Participants in the control group will have access to the full treatment after they complete their final follow-up assessment. The primary outcome will be change in the Alcohol Use Disorders Identification Test (AUDIT) score between the 6-month follow-up and baseline assessments. Secondary outcomes will include the number of standard drinks consumed and alcohol-free days, drinking motives and motivation for change, as well as changes in mental health. Assessments will be completed at baseline, at the end of treatment, and at 6 months follow-up. Data analysis will follow the intention-to-treat principle and employ (generalised) linear mixed models.Discussion: The "Selge" program is the first and only internet program for the intervention of alcohol misuse in Estonia. If proven effective, it will foster progress in the intervention of alcohol misuse in the Estonian population and be implemented as a standard program amidst the continuum of intervention and care.Trial Registration: Current Controlled Trials ISRCTN48753339 registered 04/06/2019 retrospectively. [ABSTRACT FROM AUTHOR]

Background: Life-skills trainings conducted within the school curriculum are effective in preventing the onset and escalation of substance use among adolescents. However, their dissemination is impeded due to their large resource requirements. Life-skills training provided via mobile phones might represent a more economic and scalable approach. The main objective of the planned study is to test the efficacy of a mobile phone-based life-skills training to prevent substance use among adolescents within a controlled trial.Methods/design: The efficacy of a mobile phone-based life-skills training to prevent substance use among adolescents will be tested in comparison to an assessment only control group, within a cluster-randomised controlled trial with two follow-up assessments after 6 and 18 months. The fully automated program is based on social cognitive theory and addresses self-management skills, social skills, and substance use resistance skills. Participants of the intervention group will receive up to 4 weekly text messages over 6 months in order to stimulate (1) positive outcome expectations, e.g., on using self-management skills to cope with stress, (2) self-efficacy, e.g., to resist social pressure, (3) observational learning, e.g. of interpersonal competences, (4) facilitation, e.g., of strategies to cope with negative emotions, and (5) self-regulation, e.g., by self-monitoring of stress and emotions. Active program engagement will be stimulated by interactive features such as quiz questions, message- and picture-contests, and integration of a friendly competition with prizes in which program users collect credits with each interaction. Study participants will be 1312 students between the ages of 14 and 16 years from approximately 100 secondary school classes. Primary outcome criteria will be problem drinking according to the short form of the Alcohol Use Disorders Identification Test and cigarette smoking within the last 30 days preceding the follow-up assessment at month 18.Discussion: This is the first study testing the efficacy of a mobile phone-based life-skills training for substance use prevention among adolescents within a controlled trial. Given that this intervention approach proves to be effective, it could be easily implemented in various settings and would reach large numbers of young people in a cost-effective way.Trial Registration: ISRCTN41347061 (registration date: 21/07/2018). [ABSTRACT FROM AUTHOR]

Abstract: Background and aims: Given the scarcity of alcohol prevention and alcohol use disorder treatments in many low and middle‐income countries, the World Health Organization launched an e‐health portal on alcohol and health that includes a Web‐based self‐help program. This paper presents the protocol for a multicentre randomized controlled trial (RCT) to test the efficacy of the internet‐based self‐help intervention to reduce alcohol use. Design: Two‐arm randomized controlled trial (RCT) with follow‐up 6 months after randomization. Setting: Community samples in middle‐income countries. Participants: People aged 18+, with Alcohol Use Disorders Identification Test (AUDIT) scores of 8+ indicating hazardous alcohol consumption. Intervention and comparator: Offer of an internet‐based self‐help intervention, ‘Alcohol e‐Health’, compared with a ‘waiting list’ control group. The intervention, adapted from a previous program with evidence of effectiveness in a high‐income country, consists of modules to reduce or entirely stop drinking. Measurements: The primary outcome measure is change in the Alcohol Use Disorders Identification Test (AUDIT) score assessed at 6‐month follow‐up. Secondary outcomes include self‐reported the numbers of standard drinks and alcohol‐free days in a typical week during the past 6 months, and cessation of harmful or hazardous drinking (AUDIT < 8). Analysis: Data analysis will be by intention‐to‐treat, using analysis of covariance to test if program participants will experience a greater reduction in their AUDIT score than controls at follow‐up. Secondary outcomes will be analysed by (generalized) linear mixed models. Complier average causal effect and baseline observations carried forward will be used in sensitivity analyses. Comments: If the Alcohol e‐Health program is found to be effective, the potential public health impact of its expansion into countries with underdeveloped alcohol prevention and alcohol use disorder treatment systems world‐wide is considerable. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Aim of the study was to analyze the mold filling capacity and the dimensional accuracy of a spinel-based investment for titanium castings. Methods: Expansion of the investment in dependence of the preheating temperature was measured in a dilatometer. The degree of transformation of MgO and Al2O3 to spinel (MgAl2O4) was evaluated by means of X-ray powder diffraction. Mold filling capacity was assessed by casting a grid and calculating the percentage of completed segments. Dimensional accuracy was analyzed by casting a hollow cylinder and measuring the difference between the inner diameter of the resin pattern and the resulting titanium casting. Results: Spinel formation starts at 819°C. Diffraction patterns prove the formation of spinel from MgO and Al2O3. The amount of spinel increases with increasing preheating temperature. The final expansion of the investment at the end of the preheating cycle at 450°C shows a linear correlation to the maximum preheating temperature. The degree of mold filling is reciprocal to the preheating temperature. The dimensional accuracy shows a linear correlation to the amount of spinel. Best dimensional accuracy was obtained at about 900°C. After a preheating temperature of 884°C, as recommended by the manufacturer, the cast specimens showed a slightly lower inner diameter as compared to the resin patterns. Significance: The results suggest that with the spinel investment analyzed an excellent accuracy of titanium castings may be obtained. [Copyright &y& Elsevier]

It has been recognized that the rate of cutaneous wound healing declines with age, yet the molecular processes that affect this decline remain poorly understood. The purpose of this study was to compare reepithelialization and contraction rates, and growth factor profiles in full-thickness wounds in swine of various ages. Multiple full-thickness excisional wounds were created on the dorsum of 24-month-old (n=2), 4-month-old (n=2), and 2-month-old (n=2) Yucatan Minipigs. The extent of reepithelialization was shown to decrease with increasing age in a manner that was statistically significant among the 2-month-old (79%), 4-month-old (48%), and 24-month-old pigs (22%). Enzyme-linked immunosorbent assay results showed that endogenous vascular endothelial growth factor concentrations in the 2- and 4-month-old animals peaked on day 4, reaching levels of 482 pg/ml and 420 pg/ml, respectively. In the 24-month-old pigs the vascular endothelial growth factor concentration peaked later (day 6), and was present at a lower level (229 pg/ml). On day 4 the vascular endothelial growth factor levels in the older pigs reached only 120 pg/ml, representing a four-fold decrease in concentration compared to the younger pigs. A comparison of platelet-derived growth factor-BB concentrations across the age groups showed similar patterns in the 2- and 4-month-old pigs (peaks of 77 and 91 pg/ml on days 2 and 3, respectively), and levels in the 24-month-old were below the sensitivity level (31.5 pg/ml) of the assay. Transforming growth factor-β1 levels across the age groups did not differ in a manner that was statistically significant, and all age groups peaked on day 9. Wound contraction showed no statistical differences among the age groups from days 3 to 9. On day 11, however, wound contraction in 2-month-old pigs was about 10% faster than in 24-month-old pigs (p < 0.05). These data suggest a possible new algorithm for treating wounds in aged skin, by which exogenous growth factors... [ABSTRACT FROM AUTHOR]