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Increasingly, in vivo imaging holds a strategic position in bio-pharmaceutical innovation. We will present the implementation of an integrated multimodal imaging setup enabling the assessment of multiple, complementary parameters. The system allows the fusion of information provided by: Near infrared fluorescent biomarkers, bioluminescence (for tumor proliferation status), Photoacoustic and Ultrasound imaging. We will study representative applications to the development of a smart prodrug, delivering a highly cytotoxic chemotherapeutic agent to cancer tumors. The results realized the ability of this embedded, multimodality imaging platform to firstly detect bioluminescent and fluorescent signals, and secondly, record ultrasound and photoacoustic data from the same animal. This study demonstrated that the prodrug was effective in three different models of hypoxia in human cancers compared to the parental cytotoxic agent and the vehicle groups. Monitoring by photoacoustic imaging during the treatments revealed that the prodrug exhibits an intrinsic capability to prevent the progression of tumor hypoxia. It is essential for onco-pharmacology studies to precisely document the hypoxic status of tumors both before and during the time course of treatments. This approach opens new perspectives for exploitation of preclinical mouse models of cancer, especially when considering associations between hypoxia, neoangiogenesis and antitumor activity.

Background: Youth depression is highly prevalent and is related to impairments in academic, social and behavioural functioning. Evidence-based treatments are available, but many young people do not respond or sufficiently recover with first-line options, and a significant proportion experience relapse. Consequently, there is clear scope to enhance intervention in this critical period of early-onset depression. Memory specificity training (MeST) is a low-intensity intervention for depression that targets reduced specificity when recalling memories of the past, a common cognitive vulnerability in depression. This randomised controlled trial will assess the efficacy of adding a computerised version of MeST (c-MeST) to usual care for youth depression., Methods/design: Young people aged 15-25 years with a major depressive episode (MDE) will be recruited and randomised to have immediate access to the seven session online c-MeST program in addition to usual care, or to usual care and wait-list for c-MeST. The primary outcomes will be diagnostic status of an MDE and self-reported depressive symptoms assessed at baseline, 1-, 3- and 6-month intervals. Autobiographical memory specificity and other variables thought to contribute to the maintenance of reduced memory specificity and depression will be assessed as mediators of change., Discussion: Online provision of c-MeST provides a simple, low-intensity option for targeting a cognitive vulnerability that predicts the persistence of depressive symptoms. If found to be efficacious as an adjunct to usual care for depressed youth, it could be suitable for broader roll-out, as c-MeST is highly accessible and implementation requires only minimal resources due to the online and automated nature of intervention., Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12619000234112p. Registered on the 18 February 2019. All items from the WHO Trial Registration Data Set can be found within the protocol., Protocol Version: 1.0.

Background: Characteristic of the cardinal symptom of anhedonia, people with clinical depression report lower levels of anticipatory pleasure. However, the psychological mechanisms underlying these deficits are poorly understood. This is the first study to assess whether, and to what extent, phenomenological characteristics of episodic future thinking for positive future events are associated with anticipatory pleasure among depressed individuals., Methods: Individuals with a Major Depressive Episode (MDE; N = 117) and without (N = 47) completed ratings scales for depressive symptoms and trait anticipatory and consummatory pleasure. They then provided descriptions of personally-relevant positive future events and rated them for phenomenological characteristics and state anticipatory pleasure., Results: Between-groups analysis showed that those with MDE reported lower trait anticipatory and consummatory pleasure. They also simulated future events with less specificity, less detail/vividness, less use of mental imagery, less use of first-person perspective, less plausibility/perceived likelihood of occurring, and reported less associated state anticipatory pleasure. In regression analyses in the depressed group, lower scores for detail/vividness, mental imagery, and personal significance all uniquely predicted lower state anticipatory pleasure., Limitations: Cognitive functioning was not assessed, which may help clarify deficits that underpin these findings. History of previous depressive episodes in the comparison group were not assessed, which may mean the observed between-group effects are underestimated., Conclusions: This study provides further evidence of deficits in episodic future thinking and anticipatory pleasure in depressed individuals. It also establishes links between particular characteristics of episodic future thinking and state anticipatory pleasure, and indicates cognitive targets that may be amenable to intervention in order to reduce anhedonia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Reduced autobiographical memory specificity (rAMS) is a vulnerability factor found across unipolar depression (UD), posttraumatic stress disorder (PTSD), eating disorder, schizophrenia, and bipolar disorder (BD). A group delivered psychological therapy training called Memory Specificity Training (MeST) remediates rAMS in UD and PTSD, with additional downstream effects on related psychological processes and symptoms. Its impact in BD is unknown. In this case study, we examined the impact of a computerized version of MeST (c-MeST) on improving AMS and related symptoms and processes in participant with rapid cycling type I BD., Method: An experimental case study with an ABA design was used. During baseline (14 days, Phase A), the training phase (nine sessions across 17 days, Phase B), and a 1-month follow-up (Phase A), memory specificity, depressive symptoms, and related processes and symptoms were repeatedly measured., Results: Memory specificity increased significantly after the participant completed c-MeST. Session-to-session scores indicated that AMS improved most from the in-person baseline assessment to the first online session. All other measures of processes and symptoms deteriorated during the training phase but regressed to baseline during follow-up., Conclusion: Memory specificity was improved as indicated by increased AMS from pre-intervention measurement to 1-month follow-up. Other improvements in symptoms were not observed. Rather, some related maladaptive psychological processes and symptoms worsened during the training phase and regressed to baseline during follow-up., (© 2019 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: Adolescence is characterized by an increased vulnerability for internalizing psychopathologies such as depression and anxiety. A positive association between anxiety and depression has consistently been found in research. However, the specific direction of this association is less clear. In this study, we investigated the temporal associations between (social) anxiety and depressive symptoms. Furthermore, the role of dependent interpersonal stress as a potential mediating factor in these temporal associations was examined., Methods: Data were part of a larger longitudinal study on the emotional development of adolescents, which was initiated in February 2013. The total sample consisted of 2011 adolescents between the ages of 11 and 19. Data were analyzed using cross-lagged models., Results: Bidirectional positive associations were found between social anxiety symptoms and depressive symptoms. However, dependent interpersonal stress was not a mediator in the link between social anxiety and depression. Our results indicate that dependent interpersonal stress seems to be particularly related to depressive symptoms and not to social anxiety symptoms., Conclusions: Findings suggest that bidirectional associations between social anxiety and depressive symptoms exist. This implies that clinicians should be specifically vigilant for the development of depressive symptoms in socially anxious adolescents and the development of social anxiety symptoms in depressed adolescents. Our findings further highlight the importance of targeting dependent interpersonal stress in the context of depression., (© 2019 Wiley Periodicals, Inc.)

Exposure to negative life stress has been associated with difficulty retrieving memories for specific autobiographical events, with important consequences for the emergence of emotional disorders. We examined whether social support can protect against the effects of negative events on memory specificity. University students ( N  = 143) were assigned to groups based on whether or not they experienced a negative stressor, operationalised as whether or not their recent exam performance was in line with their expectations. After receiving their exam results (T1), and one month later (T2), participants completed measures of memory specificity, their attitudes towards themselves and the occurrence of other stress-related events. Participants also completed a general measure of perceived social support from friends, family, and significant others, and an equivalent measure for social support related to performance. For participants who experienced an exam-related stressor, reduced performance-specific social support from friends was associated with reduced memory specificity at T2, even when accounting for T1 memory specificity, individual differences in attitudes towards self, the experience of additional stressors, and gender. No such relation was present for participants who did not experience a stressor. These findings provide new understanding of the influence of social variables on autobiographical memory specificity.

Background and Objectives: Depressed people hold positive beliefs about negative cognition (e.g., rumination is useful to find a solution), which may motivate those individuals to engage in sustained negative thinking. However, in reality, rumination often leads to unfavorable outcomes. Thus, such beliefs create a large discrepancy between one's expectations and the actual outcome. Therefore, we hypothesized that this prediction error would be associated with increased depressed mood., Methods: We observed how people update their positive beliefs about negative cognition within a volatile environment, in which negative cognition does not always result in a beneficial outcome. Forty-six participants were offered two response options (retrieving a negative or positive personal memory) and subsequently provided either an economic reward or punishment. Retrieving a negative (rather than positive) memory was initially reinforced, although this action-outcome contingency was reversed during the task. In the control condition, positive memory retrieval was initially reinforced, although a contingency reversal was employed to encourage negative memory retrieval., Results: Model-based computational modeling revealed that participants who showed a delay in switching from negative to positive (but not from positive to negative) responses experienced increased levels of depressed mood. This delay in switching was also found to be associated with depressive symptoms and trait rumination., Limitations: The non-clinical nature of the sample may limit the clinical implications of the results., Conclusions: Difficulty in updating positive beliefs (or outcome predictions) for negative cognition may play an important role in depressive symptomatology., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective/Background : Sleep can have an important influence on memory. However, it is unclear whether there is any relation between sleep quality and the specificity with which autobiographical memories are retrieved, a key factor associated with vulnerability for, and the presence of, depression and other psychiatric diagnoses. The present study provides the first investigation of the association between sleep quality and autobiographical memory specificity. Participants and Method : Fifty-four unselected community participants completed the Autobiographical Memory Test (AMT) to assess memory specificity, while subjective and objective measures of total sleep time and sleep onset latency were provided through a daily diary and an actigraphy wristwatch worn for a week. Participants also completed questionnaires that measure known correlates of AMT specificity: the Ruminative Response Scale (RRS) and Beck Depression Inventory (BDI-II). Results : Shorter sleep duration, measured using actigraphy, was associated with reduced autobiographical memory specificity. There was no evidence of an association between total sleep time recorded by self-report diaries, or of sleep onset latency recorded using actigraphy or diaries and memory specificity. The relation between actigraphy-assessed total sleep time and memory specificity was independent of the effects of rumination or depressive symptoms on these variables. Conclusions : Shorter sleep duration is associated with reduced memory specificity. Future research examining memory specificity and its association with psychopathology should consider the role of sleep quality around the time of memory recall in specificity.

Sharing specific autobiographical events is likely to influence the support people give us; a person who shares little detail of their lives may be unlikely to attract social support and this may in turn contribute towards anxious and depressive symptoms. Participants ( N  = 142) reported memories evoked by negative and positive cue words and these memories were coded for whether or not they referred to a specific event lasting less than 24 h. At this time (T1) and one year later (T2), participants also completed the UCLA Life Stress Interview (LSI), which includes a measure of social support, and measures of depression and anxiety comprising a general distress latent construct. The tendency to recall fewer specific memories was associated with lower social support given by friends and romantic partners and this was in turn associated with elevated general distress at T2, even when accounting for T1 social support and general distress. Our findings contribute to the literature regarding the social function of memory and suggest another route via which reduced specificity contributes to emotional disorders.

Background and Objectives: Memory Specificity Training (MeST), a group training protocol, is effective in improving autobiographical memory specificity (AMS), and in so doing, reducing emotional disorder symptoms amongst clinical groups. We examined MeST's effectiveness when the core component (memory specificity trials) is offered online and individually (c-MeST)., Methods: A multiple-baseline across-participants design with a randomization-to-baseline length (14 to 33 days) was used. Participants were twenty adults (16 female; M age  = 50, SD  = 12) experiencing reduced AMS, at least one lifetime depressive episode and who currently reported at least minimal depressive symptoms. During baseline, the training phase (nine sessions across 17 days) and a three-month follow-up assessment, AMS, depressive symptoms and related processes were measured., Results: AMS improved significantly by three months follow-up. Session-to-session scores indicated that AMS improved most from baseline to the first online session, with no further improvement thereafter. In contrast to studies with clinical participants, no significant change in symptoms or secondary processes such as rumination was found., Conclusions: Translating MeST into an online, individual version is a feasible, low-cost intervention for reduced AMS. Future research should examine c-MeST's potential for preventing increases in symptoms in at-risk samples with longer follow-ups as well as its potential for reducing symptoms in clinical groups., Competing Interests: Dr. Raes is one of the developers of the original in-group face-to-face MeST. Kris Martens en Drs Takano and Raes are the developers of the online, computerized MeST (c-MeST). Kris Martens and Dr. Raes additionally receive payments for training workshops and presentations related to MeST. We wish to confirm that there are no other known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (© 2019 The Authors.)

Objectives: Difficulties recalling specific events from one's autobiographical past have been associated with a range of emotional disorders. We present the first examination of whether diagnoses of depression or individual differences in depression severity explain the most variance in autobiographical memory specificity. We also examine the contribution of other key cognitive factors associated with reduced memory specificity - rumination and verbal fluency - to these effects., Methods: Participants with (n = 21) and without (n = 25) major depressive disorder completed self-report measures of depression severity (Beck Depression Inventory version II; BDI-II) and ruminative tendency (Ruminative Response Scale), a measure of verbal fluency, and the Autobiographical Memory Test (AMT) to assess memory specificity., Results: People diagnosed with depression recalled significantly fewer specific memories in the AMT relative to healthy controls. In a linear regression, diagnostic status explained a significant amount of unique variance in specificity whereas BDI-II scores did not. Diagnostic group differences in verbal fluency also explained a significant amount of variance in specificity., Conclusions: Our findings extend our understanding of the mechanisms involved in reduced memory specificity but future research must explore the causal contribution of weak executive functioning to reduced memory specificity., Practitioners Points: Diagnoses of depression were associated with problems recalling specific events from one's past. Problems with memory specificity amongst depressed people were associated with executive functioning difficulties. Problems with specificity were not associated with individual differences in depression severity or ruminative tendencies., (© 2018 The British Psychological Society.)

Background: The ability to retrieve specific autobiographical memories decreases with cognitive aging. This decline is clinically relevant due to its association with impairments in problem solving, daily functioning, and depression. A therapist-delivered group training protocol, Memory Specificity Training (MeST), has been shown to enhance the retrieval of specific memories while ameliorating the impairments and negative outcomes associated with reduced specificity. The therapist-delivered nature of this intervention means it is relatively expensive to deliver and difficult for people with mobility impairments, such as older people, to receive., Objective: The objective of this study was to test if a novel, Web-based computerized version of a group training protocol called Memory Specificity Training, has the potential to increase autobiographical memory specificity and impact associated secondary psychological processes., Methods: A total of 21 participants (13 female; mean age 67.05, SD 6.55) who experienced a deficit in retrieving specific autobiographical memory were trained with c-MeST. We assessed memory specificity at preintervention and postintervention, as well as secondary processes such as depressive symptoms, rumination, and problem-solving skills., Results: Memory specificity increased significantly after participants completed c-MeST (r=.57). Session-to-session scores indicated that autobiographical memory specificity improved most from the online baseline assessment to the first Web-based session. Symptoms or secondary processes such as problem-solving skills did not change significantly., Conclusions: A Web-based automated individual version of MeST is a feasible, low-cost intervention for reduced memory specificity in healthy older adults. Future studies should clarify the preventive impact of c-MeST in other at-risk sample populations with longer follow-up times., (©Kris Martens, Keisuke Takano, Tom J Barry, Jolien Goedleven, Louise Van den Meutter, Filip Raes. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.05.2019.)

The tendency to recall events from one's past in a non-specific and overgeneral way has been found to predict the onset and severity of a range of emotional disorders. Memory Specificity Training (MeST) was devised a decade ago in order to target and modify this tendency so as to reduce the symptoms of emotional disorder or to reduce the risk that such disorders might emerge over time. We present a meta-analytical review of research into the effects of MeST on autobiographical memory specificity in the context of emotional disorders (k = 13). MeST was associated with substantial improvement in memory specificity (d = -1.21) and depressive symptoms (d = 0.47) and MeST groups outperformed control groups at post-intervention in terms of specificity (d = 1.08) and depressive symptoms (d = -0.29). However, these effects were transitory and the benefit of MeST over control groups was mostly lost by follow-up assessment. There was mixed evidence in terms of MeST's effects on other processes associated with reduced specificity but MeST showed evidence of improving problem solving abilities and hopelessness. MeST holds promise as a novel intervention targeting reduced specificity but future studies are warranted with control groups that enable the investigation of MeST's mechanism of action and in studies with larger and more varied samples., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The Autobiographical Memory Test (AMT) has been central in psychopathological studies of memory dysfunctions, as reduced memory specificity or overgeneralised autobiographical memory has been recognised as a hallmark vulnerability for depression. In the AMT, participants are asked to generate specific memories in response to emotional cue words, and their responses are scored by human experts. Because the manual coding takes some time, particularly when analysing a large dataset, recent studies have proposed computerised scoring algorithms. These algorithms have been shown to reliably discriminate between specific and non-specific memories of English-speaking children and Dutch- and Japanese-speaking adults. The key limitation is that the algorithm is not developed for English-speaking adult memories, which may cover a wider range of vocabulary that the existing algorithm for English-speaking child memories cannot process correctly. In the present study, we trained a new support vector machine to score memories of English-speaking adults. In a performance test (predicting memory specificity against human expert coding), the adult-memory algorithm outperformed the child-memory variant. In another independent performance test, the adult-memory algorithm showed robust performances to score memories that were generated in response to a different set of cues. These results suggest that the adult-memory algorithm reliably scores memory specificity.

Introduction: Major depression is a prevalent and debilitating disorder, but many sufferers do not receive support or respond to current treatments. The development of easily accessible and low-intensity treatments that have clear cognitive mechanisms of change is indicated. Memory specificity training (MeST) is an intervention for depression that targets deficits in recalling detailed memories of past experiences through repeated practice of autobiographical memory retrieval. This randomised controlled trial will assess the efficacy of an online, computerised version of MeST (c-MeST)., Methods and Analysis: Adults aged 18 and over with a current major depressive episode (MDE) will be recruited and randomised to have access to the seven session, online c-MeST programme for 2 weeks, or to a wait-list control group. The primary outcomes will be diagnostic status of MDE and self-reported depressive symptoms at postintervention. One-month and three-month follow-ups will be collected. Increases in autobiographical memory specificity will be assessed as a mediator of change, as well as other variables thought to contribute to reduced memory specificity, such as rumination and cognitive avoidance., Ethics and Dissemination: Ethics approval has been granted by the Deakin University Human Research Ethics Committee to conduct the study (ID: 2017_168). The findings will be disseminated through scholarly publications and workshops and will inform future trials, such as with an active comparator or as an adjunct treatment., Trial Registration Number: ACTRN12618000257268; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Accumulating evidence shows that a cognitive factor associated with a worsening of depressive symptoms amongst people with and without diagnoses of depression - reduced Autobiographical Memory (rAMS) - can be ameliorated by a group cognitive training protocol referred to as Memory Specificity Training (MeST). When transporting interventions such as MeST from research to routine clinical practices (RCPs), modifications are inevitable, with potentially a decrease in effectiveness, so called voltage drop. We examined the transportability of MeST to RCPs as an add-on to treatment as usual with depressed in- and out- patients., Methods: We examined whether 1) MeST was adaptable to local needs of RCPs by implementing MeST in a joint decision-making process in seven Belgian RCPs 2) without losing its effect on rAMS. The effectiveness of MeST was measured by pre- and post- intervention measurements of memory specificity., Results: Adaptations were made to the MeST protocol to optimize the fit with RCPs. Local needs of RCPs were met by dismantling MeST into different subparts. By dismantling it in this way, we were able to address several challenges raised by clinicians. In particular, multidisciplinary teams could divide the workload across different team members and, for the open version of MeST, the intervention could be offered continuously with tailored dosing per patient. Both closed and open versions of MeST, with or without peripheral components, and delivered by health professionals with different backgrounds, resulted in a significant increase in memory specificity for depressed in- and out- patients in RCPs., Conclusions: MeST is shown to be a transportable and adaptable add-on intervention which effectively maintains its core mechanism when delivered in RCPs., Trial Registration: ISRCTN registry, IDISRCTN10144349 , registered on January 22, 2019. Retrospectively registered.

Research has shown that how well people can differentiate between different emotional states is an essential requirement for adaptive emotion regulation. People with low levels of emotion differentiation tend to be more vulnerable to develop emotional disorders. Although we know quite a lot about the correlates of emotion differentiation, research on factors or interventions which could improve emotion differentiation skills is scarce. Here, we hypothesize, and study empirically, whether a mindfulness-based intervention (MBI) may impact the differentiation of negative and positive emotions. A within-subjects pre-, post-, and follow-up design involving experience sampling was used. At each phase participants reported their current emotions and mindfulness skills up to 40 times across 4 consecutive days using smartphones. Multilevel modeling showed a significant improvement in negative emotion differentiation postintervention and at 4 months of follow-up, and a significant improvement in positive emotion differentiation at 4 months follow-up. The improvement in negative emotion differentiation, however, was no longer significant when controlling for levels of negative affect. A time-lagged mediation model showed that posttreatment changes in mindfulness skills mediated subsequent changes in negative emotion differentiation, also when controlling for levels of negative affect. These results suggest that MBI is a promising approach to improve people's emotion differentiation skills. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background. In the current scientific literature there are only few studies on the immediate functional loading of single implants. The aim of the present present study was to evaluate the 4-year survival rate, complication rate and peri-implant marginal bone loss (PIMBL) of immediately loaded single implants inserted in healed ridges and fresh post-extraction sites. Methods. Six centers were involved in this prospective study. The surgical and prosthetic protocol was defined in detail, before the start of recruiting patients. Recruitment of patients and performance of surgeries took place between February 2012 and February 2013. Criteria for inclusion were single-tooth gaps in healed ridges and fresh post-extraction sockets. All the fixtures (Anyridge®, Megagen Corporation, Gyeongbuk, South Korea) were functionally loaded immediately after insertion and followed for a period of 4 years. Outcome measures were implant survival, complications and PIMBL. Results. Forty-six patients (18‒73 years of age) were selected. In total, 57 fixtures were placed (10 in fresh post-extraction sockets). After 4 years of functional loading, only one fixture was lost; therefore, high survival rates (97.6% patient-based; 98.1% implant-based) were reported. In addition, a limited incidence of biologic (4.8% patient-based; 3.8% implant-based) and prosthetic (9.7% patient-based; 7.6% implant-based) complications was reported. The overall 4-year PIMBL amounted to 0.38±0.21 mm (healed ridges: 0.4±0.21 mm; fresh post-extraction sockets: 0.33±0.20 mm). Conclusion. Loading single implants immediately seems to be a highly successful treatment modality. However, long-term data are needed to confirm these positive outcomes.

There has been a recent growth in investigations into the neural mechanisms underlying the problems recalling specific autobiographical events that are a core feature of emotional disorders. In this review we provide the first synthesis of this literature, taking into account brain as well as cognitive mechanisms. We suggest that these problems are driven by idiosyncratic activation in areas of the brain associated with assigning salience and self-relevance to emotional memories. Other areas associated with inhibiting distraction and constructing vivid memory representations are also important. Each of these mechanisms may work independently or in concert with one another. Importantly, this interaction between mechanisms may differ between diagnostic and demographic groups such that similar problems in specificity may be characterised by different mechanisms. Given this challenge, neuroimaging may prove useful in identifying patient-specific biomarkers for interventions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The CaRFAX model, proposed by Williams J. M. G. (2006. Capture and rumination, functional avoidance, and executive control (CaRFAX): Three processes that underlie overgeneral memory. Cognition and Emotion, 20, 548-568. doi: 10.1080/02699930500450465 ; Williams, J. M. G., Barnhofer, T., Crane, C., Herman, D., Raes, F., Watkins, E., & Dalgleish, T. (2007). Autobiographical memory specificity and emotional disorder. Psychological Bulletin, 133(1), 122-148. doi: 10.1037/0033-2909.133.1.122 ) posits that reduced autobiographical memory specificity, a key factor associated with the emergence and maintenance of emotional disorders, may result from heightened rumination. We provide the first meta-analysis of the relation between autobiographical memory specificity and trait rumination. PsycINFO, PsycARTICLES and MEDLINE databases were searched and the following were extracted: the correlation between the number of specific memories recalled in the Autobiographical Memory Test and self-reported trait rumination scores, and its sub-factors - brooding and reflection. The pooled effect size for the correlation between memory specificity and trait rumination was small (d = -.05) and did not differ significantly from zero (p = .09). The effect sizes for the correlation with brooding and reflection were not significantly different from zero. There is limited support for the association between trait rumination and memory specificity suggested in CaRFAX.

Background and Objectives: Cognitive bias to sleep-related information is thought to be a core feature of sleep disturbances. The bias may enhance pre-sleep arousal, such as excessive worry about sleeplessness, which prevents people from initiating normal sleep onset. The present study focused on (a) attention bias toward sleep-related stimuli and (b) difficulty in updating working memory for sleep-related stimuli as two possible mechanisms underlying pre-sleep cognitive arousal., Method: Participants (n = 61, a community sample) completed a dot-probe task (with sleep-related and matched control word stimuli) and a 1-back and 2-back task (with sleep-related and non-sleep-related pictorial stimuli)., Results: For the dot-probe task, the results showed no significant association between pre-sleep cognitive arousal and sleep-related attention bias. However, the results of the 2-back task suggest that pre-sleep arousal is associated with decreased interference by sleep-related stimuli in maintaining non-sleep-related information. That is, individuals with higher levels of pre-sleep arousal are more efficient at processing sleep-related materials., Limitations: The non-clinical nature of the sample may limit the clinical implications of the findings., Conclusions: Although the current results cannot be explained by the extant cognitive theories of insomnia, we offer an alternative explanation based on the idea of worry as mental habit: mental processes that occur frequently (e.g., repetitive thoughts about sleep) require less cognitive resource. Therefore, sleep-related information may be processed easily without consuming much cognitive effort., (Copyright © 2018. Published by Elsevier Ltd.)

Repetitive negative thinking (RNT) is considered a transdiagnostic variable underlying common symptoms (e.g., depressed mood) across various mood disorders. Depressive rumination is one typical and frequent manifestation of RNT and is a well-known vulnerability factor of depression onset, maintenance and recurrence. Due to the time-related constraints in assessment settings and the association of rumination on sadness with diagnosis of depression, the rapid identification of individuals scoring high on this construct may become a useful screening tool in non-clinical samples. The main aim of the present study was to test the psychometric properties of the Spanish version of the Short Depressive Rumination Scale (SDRS) in a large sample (N = 649). Confirmatory Factor Analysis supported a one-factor model accounting for 75% of variance with an excellent internal consistency (α = .93) in spite of the reduced number of items (4 items). Criterion validity results based on associations with other well-established rumination (sub)scales, age, scores in depression and gender differences, were congruent. The results suggest that the SDRS, the shortest existing scale assessing depressive rumination to our knowledge, can be a useful instrument for a rapid assessment of depressive rumination in community samples.

Background: Although many studies have been published on single implants, long-term data remain scarce., Purpose: To evaluate immediately restored single implants after at least 8 years of follow-up in terms of buccal bone, soft tissue alterations, aesthetic ratings, and patient-reported outcomes., Materials and Methods: This prospective cohort study included patients who were consecutively treated with an immediately restored single implant installed in an extraction socket (IIT) or a healed ridge (CIT) in the anterior maxilla. Biomaterials were never used. CBCTs were taken at study termination, soft tissue alterations, and Pink Esthetic Score were evaluated between 1 year and study termination using standardized clinical images. Patient satisfaction was also registered., Results: About 11/16 initially treated patients in the IIT cohort (10 men, 6 women; mean age 45) and 18/23 initially treated patients in the CIT cohort (12 men, 11 women; mean age 40) could be evaluated after more than 8 years. A buccal bone wall less than 2 mm was found at all implant sites. A thin buccal bone wall less than 1 mm was found at 42% of the implant sites. In the CIT cohort, 8 patients had a missing buccal bone in the crestal area, although bone was present at the time of surgery. Alveolar process deficiency significantly deteriorated (P ≤ .046), whereas vertical soft tissue levels and PES remained stable over time in both cohorts. Patients expressed high overall satisfaction., Conclusions: Substantial dimensional changes may be expected at the buccal aspect of single implants inserted in the premaxilla. As a result, contour augmentation procedures at the time of implant placement should be considered to counteract these bone alterations, even when implants are fully embedded in bone upon insertion., (© 2018 Wiley Periodicals, Inc.)

Longitudinal studies examining the role of response styles to positive affect (i.e., dampening and enhancing) for depressive symptoms have yielded inconsistent results. We examined concurrent and prospective relations of dampening and enhancing with depressive and anhedonic symptoms, and whether these relations depend on the frequency of uplifts. Early adolescents (N = 674, 51.6% girls, M age  = 12.7 years, range 11.3-14.9) completed questionnaires three times (one-year intervals). Dampening interacted with daily uplifts predicting concurrent depressive symptoms. Dampening was unrelated to depressive and anhedonic symptoms one year later. High dampening and low enhancing predicted relative increases in anhedonia over two years. Relationships did not differ for girls and boys. Therapeutic interventions designed to promote adaptive responding to positive affect may, thus, reduce anhedonia in adolescence.

Overgeneral memory (OGM) refers to the failure to recall memories of specific personally experienced events, which occurs in various psychiatric disorders. One pathway through which OGM is theorized to develop is the avoidance of thinking of negative experiences, whereby cumulative avoidance may maladaptively generalize to autobiographical memory (AM) more broadly. We tested this, predicting that negative experiences would interact with avoidance to predict AM specificity. In Study 1 (N = 281), negative life events (over six months) and daily hassles (over one month) were not related to AM specificity, nor was avoidance, and no interaction was found. In Study 2 (N = 318), we revised our measurements and used an increased timeframe of 12 months for both negative life events and daily hassles. The results showed no interaction effect for negative life events, but they did show an interaction for daily hassles, whereby increased hassles and higher avoidance of thinking about them were associated with reduced AM specificity, independent of general cognitive avoidance and depressive symptoms. No evidence was found that cognitive avoidance or AM specificity moderated the effect of negative experiences on depressive symptoms. Our findings suggest that life events over 6-12 months are not associated with AM specificity, but chronic daily hassles over 12 months predict reduced AM specificity when individuals avoid thinking about them. The findings provide evidence for the functional-avoidance hypothesis of OGM development and future directions for longitudinal studies.

This manuscript is part of a special issue to commemorate professor Paul Eelen, who passed away on August 21, 2016. Paul was a clinically oriented scientist, for whom learning principles (Pavlovian or operant) were more than salivary responses and lever presses. His expertise in learning psychology and his enthusiasm to translate this knowledge to clinical practice inspired many inside and outside academia. Several of his original writings were in the Dutch language. Instead of editing a special issue with contributions of colleagues and friends, we decided to translate a selection of his manuscripts to English to allow wide access to his original insights and opinions. Even though the manuscripts were written more than two decades ago, their content is surprisingly contemporary. This introductory article presents a reflection on Paul's career and legacy and introduces the selected manuscripts that are part of this special issue.

Impaired ability to recall specific autobiographical memories is characteristic of depression, which when reversed, may have therapeutic benefits. This cluster-randomized controlled pilot trial investigated efficacy and aspects of acceptability, and feasibility of MEmory Specificity Training (MEST) relative to Psychoeducation and Supportive Counselling (PSC) for Major Depressive Disorder (N = 62). A key aim of this study was to determine a range of effect size estimates to inform a later phase trial. Assessments were completed at baseline, post-treatment and 3-month follow-up. The cognitive process outcome was memory specificity. The primary clinical outcome was symptoms on the Beck Depression Inventory-II at 3-month follow-up. The MEST group demonstrated greater improvement in memory specificity relative to PSC at post-intervention (d = 0.88) and follow-up (d = 0.74), relative to PSC. Both groups experienced a reduction in depressive symptoms at 3-month follow-up (d = 0.67). However, there was no support for a greater improvement in depressive symptoms at 3 months following MEST relative to PSC (d = -0.04). Although MEST generated changes on memory specificity and improved depressive symptoms, results provide no indication that MEST is superior to PSC in the resolution of self-reported depressive symptoms. Implications for later-phase definitive trials of MEST are discussed., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Co-rumination has been shown advantageous for friendship quality, but disadvantageous for mental health. Recently, two components have been distinguished, with co-brooding predicting increases in depressive symptoms and co-reflection decreases. The current study aimed to replicate these findings and investigated whether both components also show differential relations with friendship quality. Gender was investigated as a moderator. Path analyses were used on data of 313 adolescents aged 9-17 (50.5% girls). Co-brooding was related to more concurrent and prospective depressive symptoms in girls. Co-reflection predicted less concurrent and prospective depressive symptoms in girls and higher concurrent positive friendship quality for boys and girls. This study underscores the value of studying co-rumination components and suggests that boys and girls in this context differ in their pathways towards depression.

The underlying mechanisms of the effectiveness of mindfulness-based interventions for emotional well-being remain poorly understood. Here, we examined the potential mediating effects of cognitive reactivity and self-compassion on symptoms of depression, anxiety and stress using data from an earlier randomised controlled school trial. A moderated time-lagged mediation model based on multilevel modelling was used to analyse the data. The findings showed that post-treatment changes in cognitive reactivity and self-coldness, an aspect of self-compassion, mediated subsequent changes in symptoms of depression, anxiety and stress. These results suggest that cognitive reactivity and self-coldness may be considered as transdiagnostic mechanisms of change of a mindfulness-based intervention programme for youth.

Recent systematic reviews point to the scarcity of single implants followed up longer than 5 years, and the incidence of biologic/technical complications is underreported. This prospective follow-up study documents 8- to 10-year clinical outcomes of immediately restored single implants in extraction sockets (immediate implant treatment [IIT]) and healed bone (conventional implant treatment [CIT]). Patients received a single, chemically modified, moderately rough titanium implant and a provisional crown on the day of surgery in the anterior maxilla (second premolar to second premolar). Provisional crowns were replaced by permanent crowns after 10 weeks. Implant survival, complications, crestal bone changes, plaque score, probing depth, and bleeding on probing were regularly recorded up to 10 years of follow-up. Of 16 patients who underwent IIT, 11 could be evaluated after 8 years. Of the 23 patients who received an implant in healed bone, 18 were finally evaluated. One implant failed in the IIT group at 12 weeks; all implants survived in the CIT group; 38% of the patients experienced at least one complication; 10% had one or more biologic complications, whereas 31% experienced one or more technical complications. There were no significant changes in crestal bone level from 1 to ≥ 8 years of follow-up for either group or between IIT and CIT at any time point (P ≥ .129). Only 6.9% (2 of 29) implants demonstrated progressive bone loss > 2 mm combined with pockets ≥ 6 mm. Immediately restored single implants in extraction sockets and healed ridges demonstrate good long-term outcomes in terms of implant survival, crestal bone loss, and peri-implant health. However, biologic and especially technical complications are common.

Episodic future thinking (EFT) refers to the mental simulation of future events that might be personally-experienced; a crucial mental process in adaptation. Psychiatric disorders are associated with deficits in recalling episodic memory, however, no study has reviewed the empirical literature to assess for similar deficits in EFT. A systematic review comparing psychiatric groups with control groups on the specificity and episodic detail of EFT returned 19 eligible studies. An overall effect of g = -0.84 (95%CI = -1.06, - 0.62, p < .001) indicated individuals with a psychiatric diagnosis have significantly less specific and detailed EFT. Publication bias was not detected, but heterogeneity was. No methodological characteristics were significant moderators. Subgroup analyses showed significant effects for depression (g = -0.79, p < .001, k = 7), bipolar disorder (g = -1.00, p < .001, k = 2), and schizophrenia (g = -1.06, p < .001, k = 6), but not posttraumatic stress disorder (g = -1.04, p = .260, k = 2) or complicated grief (g = -0.41, p = .08, k = 2). Deficits in EFT are apparent in some psychiatric disorders. However, many clinical groups are understudied, and the causal mechanisms and remediation of these deficits require further research attention., (Copyright © 2018. Published by Elsevier Ltd.)

Cognitive models of emotional disorders suggest that reduced autobiographical memory specificity that results from exposure to traumatic events may play an important role in the aetiology and maintenance of these disorders. However, there has yet to be a comprehensive meta-analysis of the association between trauma exposure and memory specificity, and the role of posttraumatic stress symptoms on this association. We searched PsycINFO and MEDLINE databases and extracted data from studies regarding the mean number or proportion of specific memories that participants with and without trauma exposure recalled on the Autobiographical Memory Test. We also extracted data on differences between groups in terms of posttraumatic stress and depressive symptoms, along with data on trauma timing and participants' ages at the time of assessment. The effect size of memory specificity between participants with and without exposure to trauma was large, d = 0.77, and differed significantly from zero, p < .001. In metaregression, trauma timing was a significant predictor of the heterogeneity in trauma-exposure specificity effect sizes, but posttraumatic stress and depressive symptoms were not. Compromised memory specificity represents an important cognitive consequence of trauma exposure that might have an important influence on risk for, and maintenance of, subsequent emotional pathologies., (Copyright © 2018 International Society for Traumatic Stress Studies.)

Dampening and enhancing responses to positive affect have been linked to depressive symptoms. The main aim of the present study was to examine such responses in an interpersonal peer context and to examine their relation with depressive symptoms. A community sample of 665 seventh-graders (52.0% girls, Mage = 12.7 years) took part in the study. Using a newly developed questionnaire, the Co-Dampening and Co-Enhancing Questionnaire (CoDEQ), a two-factor model distinguishing co-dampening and co-enhancing was validated. Relations with general depressive symptoms, anhedonic symptoms, and friendship quality were investigated. The direction of relations was examined over a 1-year interval using cross-lagged analyses. Cross-sectional results revealed that higher levels of co-dampening and lower levels of co-enhancing were associated with more depressive and anhedonic symptoms, while controlling for co-rumination levels. For anhedonic symptoms, this pattern also held over and above intrapersonal dampening and enhancing. Friendship quality was related to higher concurrent levels of co-enhancing and lower levels of co-dampening. The longitudinal results pointed towards a scar model, in that both depressive and anhedonic symptoms predicted relative increases in co-dampening over time; however, this did not hold in a model in which dampening and enhancing were included as control variables.

Objective: Clinical assessment and diagnostic processes heavily rely on memory-based symptom reports. The current study investigated memory for symptoms and the peak-end effect for dyspnea in patients with medically unexplained symptoms and healthy participants., Methods: Female patients with medically unexplained dyspnea (MUD) (n=22) and matched healthy controls (n=22) participated in two dyspnea induction trials (short, long). Dyspnea ratings were collected: (1) continuously during symptom induction (concurrent with respiratory measures), (2) immediately after the experiment, and (3) after 2weeks. Symptoms, negative affect, and anxiety were assessed at baseline and after every trial. The mediating role of state anxiety in symptom reporting was assessed. The peak-end effect was tested with forced-choice questions measuring relative preference for the trials., Results: Compared to controls, dyspnea induction resulted in higher levels of symptoms, anxiety, concurrent dyspnea ratings, and minute ventilation in the patient group. In both groups, immediate retrospective ratings were higher than averaged concurrent ratings. No further increase in dyspnea ratings was observed at 2-week recall. Retrospective dyspnea ratings were mediated by both state anxiety and concurrent dyspnea ratings. Patients did not show a peak-end effect, whereas controls did., Conclusion: The findings show that patients' experience of a dyspneic episode is subject to immediate memory bias, but does not change over a longer time period. The results also highlight the importance of affective state during symptom experience for both symptom perception and memory., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Reduced specificity of autobiographical memories is a hallmark of depressive cognition. Autobiographical memory (AM) specificity is typically measured by the Autobiographical Memory Test (AMT), in which respondents are asked to describe personal memories in response to emotional cue words. Due to this free descriptive responding format, the AMT relies on experts' hand scoring for subsequent statistical analyses. This manual coding potentially impedes research activities in big data analytics such as large epidemiological studies. Here, we propose computerized algorithms to automatically score AM specificity for the Dutch (adult participants) and English (youth participants) versions of the AMT by using natural language processing and machine learning techniques. The algorithms showed reliable performances in discriminating specific and nonspecific (e.g., overgeneralized) autobiographical memories in independent testing data sets (area under the receiver operating characteristic curve > .90). Furthermore, outcome values of the algorithms (i.e., decision values of support vector machines) showed a gradient across similar (e.g., specific and extended memories) and different (e.g., specific memory and semantic associates) categories of AMT responses, suggesting that, for both adults and youth, the algorithms well capture the extent to which a memory has features of specific memories. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Biased information processing has been highlighted as a possible vulnerability factor for sleep problems. A theory states that perceived sleeplessness triggers a strong approach motivation (or craving) for sleep, and then activates persistent preoccupation with sleep. However, there is no clear evidence that perceived sleeplessness is associated with such a motivation toward sleep-related information. Thus, we examined the untested idea that people with subjective sleep disturbances would prefer sleep-related topics, using a modified version of the pay-per-view task. In this task, 58 participants were offered two question-type options: the "sleep" option, where participants were asked to answer a question about their sleep, and the "eat" option, where participants needed to answer a question about their eating habits and beliefs. Each option is associated with a variable amount of economic reward and therefore participants sometimes face a conflict between the economic reward and their intrinsic preference for a specific question type. Results showed that people with higher levels of subjective sleep disturbances forgo greater amounts of reward to have an opportunity to answer sleep-related (as opposed to than eating-related) questions. These findings suggest that people who perceive themselves as lacking sleep are highly motivated to engage in sleep-related information processing., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Due to its abundant chondrogenic matrix and hypoxic tissue, chondrosarcoma is chemo- and radio-resistant. Our group has developed a proteoglycan targeting strategy by using a quaternary ammonium (QA) function as a carrier of DNA alkylating agents to chondrosarcoma environment. Here, we assessed the relevance of this strategy applied to hypoxia-activated prodrugs, by conjugating a QA to 2-nitroimidazole phosphoramidate. This derivative, named as 8-QA , was evaluated respectively to its non-QA equivalent and to a QA-conjugated but non-hypoxia activated. Firstly binding to aggrecan was confirmed from dissociation constant determined by Surface Plasmon Resonance. In vitro , in HEMC-SS chondrosarcoma cells cultured in monolayer and in spheroids, 8-QA showed higher cytotoxic activity in hypoxia versus normoxia, and led to a strong accumulation of cells in S phase and apoptosis. In vivo , a HEMC-SS xenograft model was implanted on SCID mice and characterized for hypoxia by photoacoustic imaging as well as proteoglycan content. When HEMC-SS bearing mice were given 8-QA at 47 μmol/kg according to a q4d x 6 schedule, a significant 62.1% inhibition of tumor growth was observed, without associated hematological side effects. Mechanistic studies of treated tumors highlighted decrease in mitotic index associated to increase in both p21 and p53S15 markers. Interestingly, 8-QA treatment induced an increase of DNA damages as measured by γH2AX predominantly found in pimonidazole-positive hypoxic areas. These preclinical results are the first to demonstrate the interest of addressing hypoxia-activated prodrugs selectively to proteoglycan of chondrogenic tumor tissue, as a promising therapeutic strategy., Competing Interests: CONFLICTS OF INTEREST All authors declare no conflicts of interest.

Learning theories of depression have proposed that depressive cognitions, such as negative thoughts with reference to oneself, can develop through a reinforcement learning mechanism. This negative self-reference is considered to be positively reinforced by rewarding experiences such as genuine support from others after negative self-disclosure, and negatively reinforced by avoidance of potential aversive situations. The learning account additionally predicts that negative self-reference would be maintained by an inability to adjust one's behavior when negative self-reference no longer leads to such reward. To test this prediction, we designed an adapted version of the reversal-learning task. In this task, participants were reinforced to choose and engage in either negative or positive self-reference by probabilistic economic reward and punishment. Although participants were initially trained to choose negative self-reference, the stimulus-reward contingencies were reversed to prompt a shift toward positive self-reference (Study 1) and a further shift toward negative self-reference (Study 2). Model-based computational analyses showed that depressive symptoms were associated with a low learning rate of negative self-reference, indicating a high level of reward expectancy for negative self-reference even after the contingency reversal. Furthermore, the difficulty in updating outcome predictions of negative self-reference was significantly associated with the extent to which one possesses negative self-images. These results suggest that difficulty in adjusting action-outcome estimates for negative self-reference increases the chance to be faced with negative aspects of self, which may result in depressive symptoms.

Studies on autobiographical memory retrieval highlight the prominence of rapid and direct access to a specific event memory. Because it has been believed that autobiographical memory retrieval mostly relies on an effortful generative process, there is little empirical evidence on the early stage of information processing that contributes to autobiographical memory specificity (AMS). Therefore, we investigated the associations between AMS and automatic activation of information stimulated by rapid presentation of emotional words. Study 1 involved a visual search task to assess activation of various distractors in working memory. Participants with reduced AMS showed a tendency to activate distractors that were not semantically associated with preceding cues. In Study 2, we manipulated the levels of AMS by using a computerized version of Memory Specificity Training (c-MeST) to observe the changes in the activation of distractors. Results showed that increases in AMS were associated with decreases in activation of cue-unassociated distractors. These findings suggest that reduced AMS can be characterized by dispersed activation spreading over semantically unassociated distractors in automatic information selection of working memory. Because we also found an association between depressive symptoms and AMS, the role of automatic information processing in the relation between reduced AMS and depression is discussed., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In the present study, we explored the linguistic nature of specific memories generated with the Autobiographical Memory Test (AMT) by developing a computerized classifier that distinguishes between specific and nonspecific memories. The AMT is regarded as one of the most important assessment tools to study memory dysfunctions (e.g., difficulty recalling the specific details of memories) in psychopathology. In Study 1, we utilized the Japanese corpus data of 12,400 cue-recalled memories tagged with observer-rated specificity. We extracted linguistic features of particular relevance to memory specificity, such as past tense, negation, and adverbial words and phrases pertaining to time and location. On the basis of these features, a support vector machine (SVM) was trained to classify the memories into specific and nonspecific categories, which achieved an area under the curve (AUC) of .92 in a performance test. In Study 2, the trained SVM was tested in terms of its robustness in classifying novel memories (n = 8,478) that were retrieved in response to cue words that were different from those used in Study 1. The SVM showed an AUC of .89 in classifying the new memories. In Study 3, we extended the binary SVM to a five-class classification of the AMT, which achieved 64%-65% classification accuracy, against the chance level (20%) in the performance tests. Our data suggest that memory specificity can be identified with a relatively small number of words, capturing the universal linguistic features of memory specificity across memories in diverse contents.

Objectives: The impact of single implants on oral health-related quality of life (OHRQoL) is scarcely investigated, especially when combined with immediate placement and loading in extraction sockets. The aim was to describe prospectively the changes of OHRQoL with single implants placed in the esthetic zone in healed ridges or in extraction sockets after 5 years., Material and Methods: Ninety-six patients, enrolled at three clinical centers, received 102 single implants placed in a healed ridge (n = 54 implants/50 patients) or in extraction sockets (n = 48 implants/46 patients). Implants were immediately provisionalized, and permanent crowns were cemented after 12 weeks. Oral health impact profile questionnaires (OHIP-14) were completed before surgery, after 1 (provisional crown), 6 (permanent crown), 12 and 60 months, respectively. The overall OHIP-14 score pertains to seven domains with two items each and was assessed on a Likert scale of 0-4 (0 = never and 4 = very often). The evolution of the total OHIP-14 score and changes within all OHIP domains over time and between groups were assessed with a linear mixed-effect model analysis., Results: After 5 years, overall implant survival was 98%. The total OHIP-14 score for both groups combined decreased from 0.50 at baseline to 0.17 at 6 months (P < 0.001), indicative of improvement. For both groups, this remained stable up to 5 years (P = 0.41). However, after 5 years, the total OHIP-14 score revealed a statistically significantly higher improvement in the healed group compared with the extraction group (P = 0.027)., Conclusion: Missing a single tooth in the maxillary esthetic zone leads to limited OHRQoL problems as reflected by a low overall OHIP score. However, OHRQoL improves less in the extraction group, reflecting that replacing a missing tooth is perceived as more beneficial than replacing a present tooth., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: Adolescent and young adult cancer (AYAC) survivors show an elevated risk of distress. Targeted psychosocial interventions for this distinct population are needed. This study examined the potential efficacy of a mindfulness-based intervention (MBI) to alleviate emotional distress and improve quality of life (QoL) in AYAC survivors., Methods: Participants were 16 AYAC survivors, aged 14-24, who had completed acute medical treatment. A two-baseline (8 and 1 week before the intervention), post- (1 week after the intervention) and 3 months follow-up within-subjects design was used. Each participant completed two baseline assessments, followed by an 8-week MBI. The primary outcome variables were emotional distress and QoL. Secondary outcomes were cognitive vulnerability factors and mindfulness skills., Results: Multilevel modeling showed (1) a significant reduction in emotional distress and improvement in QoL at 3 months of follow-up, (2) a significant reduction in negative attitudes toward self (i.e., a cognitive vulnerability factor), and (3) a significant improvement in mindfulness skills., Conclusion: MBI is a promising approach that is used to treat emotional distress and to improve QoL in AYAC survivors. Further research using randomized controlled trials is needed to generalize these findings. Trial registration information: www.trialregister.nl ; NTR4358.

Objectives: Retrospective symptom reports tend to overestimate actual symptom intensity. This study explored how focusing on sensory-perceptual or on affective-motivational aspects of a somatic experience influenced retrospective symptom reports in high and low habitual symptom reporters (HSR). We hypothesized that a focus on affective-motivational aspects of somatic episodes contributes to retrospective overestimation compared to a focus on sensory-perceptual aspects., Design: Dyspnoea (rebreathing) and pain (cold pain) were induced during two experimental sessions in healthy women: 21 high and 24 low HSR, selected using cut-off scores on a symptom checklist. Within-subject manipulation of sensory and affective processing focus (PF) took place at the encoding phase before symptom induction., Methods: Dyspnoea and pain ratings were collected immediately after the symptom inductions and after 2 weeks. Breathing behaviour was recorded during dyspnoea trials, while affective state and symptom measures were collected after each trial., Results: Compared to pain, dyspnoea induction was perceived as more unpleasant, arousing, and threatening (ps < .001). Affective PF led to higher arousal (p < .01) and threat ratings (p = .01) than sensory PF. Affective PF also led to an increase in retrospective dyspnoea ratings over the course of 2 weeks (p = .039), which was not observed for pain, nor for dyspnoea after sensory PF. The effects of PF on symptom ratings were independent of the HSR levels., Conclusions: The PF during symptom encoding may explain previously observed bias in retrospective symptom reporting. The results are relevant to understand the mechanisms underlying symptom overreporting. Statement of contribution What is already known on this subject? Retrospective symptom ratings are often biased when compared to the momentary assessments. Attending to either sensory or affective aspects of the somatic experience is one of the factors affecting self-reported symptoms. What does this study add? Focusing on affective aspects elicited by the somatic experience led to an increase in retrospective symptom ratings over time. This is particularly so for more aversive somatic experiences. Directing the processing focus to sensory aspects during symptom encoding can attenuate bias in retrospective symptom reporting., (© 2017 The British Psychological Society.)

The development of novel therapeutic strategies allowing the destruction of tumour cells while sparing healthy tissues is one of the main challenges of cancer chemotherapy. Here, we report on the design and antitumour activity of a low-molecular-weight drug delivery system programmed for the selective release of the potent monomethylauristatin E in the tumour microenvironment of solid tumours. After intravenous administration, this compound binds covalently to plasmatic albumin through Michael addition, thereby enabling its passive accumulation in tumours where extracellular β-glucuronidase initiates the selective release of the drug. This targeting device produces outstanding therapeutic efficacy on orthotopic triple-negative mammary and pancreatic tumours in mice (50% and 33% of mice with the respective tumours cured), leading to impressive reduction or even disappearance of tumours without inducing side effects.

The autobiographical memory test (AMT) is a widely used measure to assess the specificity of autobiographical memories. Reduced Autobiographical Memory Specificity (AMS) or increased overgeneralization of memories is considered as a cognitive hallmark of depression. Therefore, reduced AMS is the subject of much psychopathological research, and is a promising target for psychological interventions. Although considerable evidence has been gathered on the clinical relevance of reduced AMS over the past decades, studies on AMS have been mainly conducted in Western populations, and few have been conducted in Asian populations. This could be because of the unknown psychometric properties of the AMT given cultural and language differences. Therefore, the present study examined the psychometric properties of the AMT in a Japanese community sample (N=1240). Our data replicated that (a) the AMT has a uni-factorial structure; (b) AMS has a small but statistically significant negative correlation with depressive symptoms; (c) AMS shows a significant declining trend as a function of age, which influences the magnitude of the association between AMS and depressive symptoms in older adults. These findings suggest that the AMT has robust psychometric properties across different languages and cultural backgrounds., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: This preclinical study aimed to evaluate placental oxygenation in pregnant rats by real-time photoacoustic (PA) imaging on different days of gestation and to specify variations in placental oxygen saturation under conditions of maternal hypoxia and hyperoxygenation., Material and Methods: Placentas of fifteen Sprague-Dawley rats were examined on days 14, 17, and 20 of pregnancy with a PA imaging system coupled to high-resolution ultrasound imaging. Pregnant rats were successively exposed to hyperoxygenated and hypoxic conditions by changing the oxygen concentration in inhaled gas. Tissue oxygen saturation was quantitatively analyzed by real-time PA imaging in the skin and 3 regions of the placenta. All procedures were performed in accordance with applicable ethical guidelines and approved by the animal care committee., Results: Maternal hypoxia was associated with significantly greater decrease in blood oxygen saturation (ΔO2 Saturation) in the skin (70.74% ±7.65) than in the mesometrial triangle (32.66% ±5.75) or other placental areas (labyrinth: 18.58% ± 6.61; basal zone: 13.13% ±5.72) on different days of pregnancy (P<0.001). ΔO2 Saturation did not differ significantly between the labyrinth, the basal zone, and the decidua. After the period of hypoxia, maternal hyperoxygenation led to a significant rise in oxygen saturation, which returned to its initial values in the different placental regions (P<0.001)., Conclusions: PA imaging enables the variation of blood oxygen saturation to be monitored in the placenta during maternal hypoxia or hyperoxygenation. This first preclinical study suggests that the placenta plays an important role in protecting the fetus against maternal hypoxia., Competing Interests: The authors have declared that no competing interests exist.

The aim of this prospective multicenter study was to evaluate the outcomes of single implants subjected to immediate functional loading. Inclusion criteria were single-tooth placement in postextraction sockets or fully healed sites, and sufficient bone height and width to place an implant of at least 3.5 × 10.0 mm. All implants were functionally loaded immediately after placement and followed for 2 years. Outcome measures were implant survival, complications, and peri-implant marginal bone loss (MBL). A total of 57 implants (38 maxilla, 19 mandible) were placed in 46 patients (23 men, 23 women, aged 18-73 years). Of these, 10 implants were placed in postextraction sockets. One implant failed, in a healed site, giving a patient-based overall 2-year survival rate of 97.6%. The incidence of biologic complications was 1.8%; prosthetic complications amounted to 7.5%. The peri-implant MBL was 0.37 ± 0.22 mm (healed sites: 0.4 mm ± 0.22; postextraction sockets: 0.3 mm ± 0.22). The immediate functional loading of single implants seems to represent a safe and successful procedure. Long-term follow-up studies on a larger sample of patients are needed to confirm these results.

Background: Research has shown that depressed patients suffer from reduced autobiographical memory specificity (rAMS). This cognitive phenomenon is associated with the maintenance and recurrence of depressive symptoms., Objectives: This pilot study aims to investigate the feasibility and effectiveness of a relatively new group-based intervention (Memory Specificity Training; MeST) that aims to reduce rAMS in an outpatient setting., Methods: Twenty-six depressed outpatients received MeST during the waiting period prior to psychotherapy. The Client Satisfaction Questionnaire (CSQ-8) was used to measure client satisfaction after the training. The Autobiographical Memory Test (AMT) was used to measure memory specificity before and after the training. Depressive symptoms were measured using the Beck Depression Inventory (BDI-II) and the Montgomery Asberg Depression Rating Scale (MADRS), before and after the training, and at a 3-month follow-up., Results: Participants as well as trainers were positive about the use of MeST. Participants also showed an increase in memory specificity and a decrease in depressive symptoms., Conclusions: This study suggests that MeST is feasible in an outpatient setting, that it increases autobiographical memory specificity and that it may decrease depressive symptoms. A randomized controlled trial is recommended to examine MeST and its effects on autobiographical memory specificity, depressive symptoms and depressive relapse more extensively. Copyright © 2015 John Wiley & Sons, Ltd. Key Practitioner Message: Research suggests that modification of rAMS can advance recovery and reduce the chance of developing a depression relapse. However, most existing psychotherapies for depression do not include these specific interventions. This is the first study to show that MeST in an outpatient setting is feasible and can lead to an increase in autobiographical memory specificity and that it may decrease depressive symptoms. A larger scale randomized controlled trial is required to examine whether the addition of MeST to care as usual decreases depressive symptoms more effectively than care as usual without MeST, and to examine whether subgroups of patients benefit specifically from this intervention (e.g. patients with more severely decreased memory specificity)., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: Patients with somatic symptom disorder (SSD) have persistent distressing somatic symptoms that are associated with excessive thoughts, feelings, and behaviors. Reduced autobiographical memory specificity (rAMS) is related to a range of emotional disorders and is considered a vulnerability factor for an unfavorable course of pathology. The present study investigated whether the specificity of health-related autobiographical memories is reduced in patients with SSD with medically unexplained dyspnea complaints, compared with healthy controls., Methods: Female patients with SSD (n = 30) and matched healthy controls (n = 24) completed a health-related Autobiographical Memory Test, the Beck Depression Inventory, the Ruminative Response Scale, and rumination scales concerning bodily reactions. Depressive symptoms and rumination were assessed because both variables previously showed associations with rAMS., Results: Patients with SSD recalled fewer specific (F(1,52) = 13.63, p = .001) and more categoric (F(1,52) = 7.62, p = .008) autobiographical memories to health-related cue words than healthy controls. Patients also reported higher levels of depressive symptoms and rumination (all t > 3.00, p < .01). Importantly, the differences in memory specificity were independent of depressive symptoms and trait rumination., Conclusions: The present study extends findings on rAMS to a previously unstudied sample of patients with SSD. Importantly, the presence of rAMS could not be explained by increased levels of depressive symptoms and rumination. We submit that rAMS in this group reflects how health-related episodes and associated symptoms are encoded in memory.

The self-positivity bias, which is inherent to healthy people, is known to be blunted in depression. The lack of positive or excessive negative self-reference is considered to be a potential mechanism underlying depressive rumination. However, the motivational factors that drive people to approach and avoid emotional self-related materials are still unclear. Therefore, we measured intrinsic motivation that is associated with emotional self-references by using a reward-based decision-making task (pay-per-view paradigm). Forty-nine undergraduates completed two tasks in which they were asked to choose between negative vs. positive references (Task 1) and self vs. other references (Task 2) for variable monetary rewards. Participants with lower levels of depressive symptoms showed a self-positivity bias, sacrificing rewards for the opportunity to engage in positive self-reference, whereas those with higher levels of depressive symptoms had no specific preference for either negative or positive self-reference (Task 1). However, all participants sacrificed monetary rewards for the opportunity for self-reference versus other reference, regardless of the symptom level or the primed valence (Task 2). Together, these findings suggest that depressive cognition could be characterised by the lack of intrinsic motivation for positive self-reference, which is attributable to the biased valence selection, but not to self-other preferences.