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Gaining awareness of psychosis (i.e., insight) is linked to depression, particularly in the post‐acute phase of psychosis. Informed by social rank theory, we examined whether the insight–depression relationship is explained by reduced social rank related to psychosis and whether self‐compassion (including uncompassionate self‐responding [UCS] and compassionate self‐responding [CSR]) and mindfulness buffered the relationship between social rank and depression in individuals with first episode psychosis during the post‐acute phase. Participants were 145 young people (Mage = 20.81; female = 66) with first episode psychosis approaching discharge from an early psychosis intervention centre. Questionnaires and interviews assessed insight, depressive symptoms, perceived social rank, self‐compassion, mindfulness and illness severity. Results showed that insight was not significantly associated to depression and thus no mediation analysis was conducted. However, lower perceived social rank was related to higher depression, and this relationship was moderated by self‐compassion and, more specifically, UCS. Mindfulness was related to depression but had no moderating effect on social rank and depression. Results supported previous findings that depressive symptoms are common during the post‐acute phase. The role of insight in depression for this sample is unclear and may be less important during the post‐acute phase than previously considered. Supporting social rank theory, the results suggest that low perceived social rank contributes to depression, and reducing UCS may ameliorate this effect. UCS, social rank and possibly mindfulness may be valuable intervention targets for depression intervention and prevention efforts in the recovery of psychosis. [ABSTRACT FROM AUTHOR]

Family members, who provide the majority of informal care during the recovery period from first-episode psychosis (FEP), experience high levels of psychological distress. However, there is a lack of effective and accessible interventions for FEP carers. To determine the effectiveness of an online intervention ("Altitudes") in relation to the primary outcome of FEP-carer stress at 6 months follow-up. We conducted a cluster randomized controlled trial in which FEP carers were randomized to Altitudes combined with specialized treatment as usual (STAU) or STAU alone. In addition to questionnaires, we included multiple waves of intensive ecological momentary assessment (EMA) to measure carer stress and family outcomes in 164 carers of young (15–27 years) FEP patients. Both groups improved over time on stress and a range of secondary outcomes, including mental health symptoms, self-efficacy, and expressed emotion with no group by time interactions. At 12 months there were significantly fewer visits to emergency departments by FEP patients in the Altitudes group (p = 0.022). Modelling of multiple EMA waves revealed that more time spent by carers with FEP patients predicted greater worry, expressed emotion, and adaptive coping. Engagement and usability findings for Altitudes were positive. Further refinements to our online carer interventions may be needed to engage carers in purposeful skill development for improved management of stress and communication with the young person compared with existing specialist family interventions. ACTRN12616000968471. [ABSTRACT FROM AUTHOR]

Although protein drugs are powerful biologic therapeutics, they cannot be delivered orally because their large size and hydrophilicity limit their absorption across the intestinal epithelium. One potential solution is the incorporation of permeation enhancers into oral protein formulations; however, few have advanced clinically due to toxicity concerns surrounding chronic use. To better understand these concerns, we conducted a 30-day longitudinal study of daily oral permeation enhancer use in mice and resultant effects on intestinal health. Specifically, we investigated three permeation enhancers: sodium caprate (C10), an industry standard, as well as 1-phenylpiperazine (PPZ) and sodium deoxycholate (SDC). Over 30 days of treatment, all mice gained weight, and none required removal from the study due to poor health. Furthermore, intestinal permeability did not increase following chronic use. We also quantified the gene expression of four tight junction proteins (claudin 2, claudin 3, ZO-1, and JAM-A). Significant differences in gene expression between untreated and permeation enhancer-treated mice were found, but these varied between treatment groups, with most differences resolving after a 1-week washout period. Immunofluorescence microscopy revealed no observable differences in protein localization or villus architecture between treated and untreated mice. Overall, PPZ and SDC performed comparably to C10, one of the most clinically advanced enhancers, and results suggest that the chronic use of some permeation enhancers may be therapeutically viable from a safety standpoint. [ABSTRACT FROM AUTHOR]

Isoleucine-Proline-Proline (IPP) and Leucine-Lysine-Proline (LKP) are food-derived tripeptides whose antihypertensive functions have been demonstrated in hypertensive rat models. However, peptides display low oral bioavailability due to poor intestinal epithelial permeability and instability. IPP and LKP were formulated into nanoparticles (NP) using chitosan (CL113) via ionotropic gelation and then coated with zein. Following addition of zein, a high encapsulation efficiency (EE) (>80%) was obtained for the NP. In simulated gastric fluid (SGF), 20% cumulative release of the peptides was achieved after 2 h, whereas in simulated intestinal fluid (SIF), ~90% cumulative release was observed after 6 h. Higher colloidal stability (39–41 mV) was observed for the coated NP compared to uncoated ones (30–35 mV). In vitro cytotoxicity studies showed no reduction in cellular viability of human intestinal epithelial Caco-2 and HepG2 liver cells upon exposure to NP and NP components. Administration of NP encapsulating IPP and LKP by oral gavage to spontaneously hypertensive rats (SHR) attenuated systolic blood pressure (SBP) for 8 h. This suggests that the NP provide appropriate release to achieve prolonged hypotensive effects in vivo. In conclusion, chitosan-zein nanoparticles (CZ NP) have potential as oral delivery system for the encapsulation of IPP and LKP. [ABSTRACT FROM AUTHOR]

Objective: Comorbid social anxiety is common in psychotic disorders and is associated with multiple negative consequences. However, the long‐term effects of persistent social anxiety versus fluctuating or no anxiety on social functioning and health‐related quality of life (HR‐QoL) have received scant attention. Therefore, we aimed to examine the prevalence of persistent social anxiety to determine its effect on social functioning and HR‐QoL in first‐episode psychosis (FEP). Methods: One hundred and eight individuals with remitted FEP were classified into three groups (persistent, fluctuating or no social anxiety) according to the Social Interaction Anxiety Scale over an 18‐month follow‐up period. The three groups were then compared at 18 months follow‐up to assess the influence of social anxiety on social functioning and HR‐QoL before and after controlling for confounders. Results: Of the 108 individuals with FEP, 25 (23.1%) had persistent social anxiety. This group presented lower social functioning and HR‐QoL levels compared to the groups with fluctuating or no anxiety symptoms. The effect on HR‐QoL remained significant after controlling for positive psychotic and depressive symptoms. Conclusions: In this study, nearly one‐quarter of young people with remitted FEP experienced persistent social anxiety symptoms, which had a negative impact on HR‐QoL. Thus, individuals with persistent social anxiety constitute a highly vulnerable group and may require targeted interventions to improve their social functioning and HR‐QoL. [ABSTRACT FROM AUTHOR]

The article presents a study which analyzed fresh maternal breast milk by flow cytommetry, quantitative real-time polymerase chain reaction and single-cell RNA-seq. Topics discussed include identification of epithelial lactocytes as the most abundant cell population in breast mil, unique lactocyte subtypes revealed by single-cell transcriptomic analysis, and breast milk sample collection and cell isolation.

[Display omitted] The decades-long effort to deliver peptide drugs orally has resulted in several clinically successful formulations. These formulations are enabled by the inclusion of permeation enhancers that facilitate the intestinal absorption of peptides. Thus far, these oral peptide drugs have been limited to peptides less than 5 kDa, and it is unclear whether there is an upper bound of protein size that can be delivered with permeation enhancers. In this work, we examined two permeation enhancers, 1-phenylpiperazine (PPZ) and sodium deoxycholate (SDC), for their ability to increase intestinal transport of a model macromolecule (FITC-Dextran) as a function of its size. Specifically, the permeability of dextrans with molecular weights of 4, 10, 40, and 70 kDa was assessed in an in vitro and in vivo model of the intestine. In Caco-2 monolayers, both PPZ and SDC significantly increased the permeability of only FD4 and FD10. However, in mice, PPZ and SDC behaved differently. While SDC improved the absorption of all tested sizes of dextrans, PPZ was effective only for FD4 and FD10. This work is the first report of PPZ as a permeation enhancer in vivo , and it highlights the ability of permeation enhancers to improve the absorption of macromolecules across a broad range of sizes relevant for protein drugs. [ABSTRACT FROM AUTHOR]

Aim: We evaluated the acceptability, usability and safety of Kindred, a novel online intervention for carers of young people with borderline personality disorder (BPD) using a pre–post pilot trial design. The secondary aim explored whether Kindred use was associated with clinical improvements for caregivers on measures of burden of caregiving, stress, expressed emotion, family communication, disability, coping and knowledge of BPD and for patients on measures of severity of BPD symptoms and level of functional impairment. Methods: The trial site was the Helping Young People Early program for young people with BPD at Orygen in Melbourne, Australia. Informed consent was obtained from 20 adult carers (i.e., relatives or friends) and 10 young people aged 15–25 with BPD. Kindred, which was available for 3 months, incorporated online psychoeducation, carer‐to‐carer social networking and guidance from expert and peer moderators. Assessments were completed at baseline and 3 months follow‐up. Multiple indicators of acceptability, usability and safety were utilized. Results: Seventeen carers were enrolled in Kindred and eight young people completed baseline measures. A priori acceptability, usability and safety criteria were met. Carer burden, stress, expressed emotion, family communication, quality of life, functioning, coping and perceived knowledge of BPD improved at follow‐up. Sixty‐six percent of the young people (4/6) reported that they believed Kindred had improved their carers' understanding of BPD. Conclusion: Kindred was shown to be acceptable, usable and safe, with encouraging improvements in both carer and young person outcomes. Kindred warrants evaluation of its efficacy via an randomized controlled trial. [ABSTRACT FROM AUTHOR]

Background: First‐episode psychosis typically has its onset during adolescence. Prolonged deficits in social functioning are common in FEP and yet often variance in functioning remains unexplained. Developmental psychology frameworks may be useful for understanding these deficits. Eudaimonic well‐being (EWB), or positive self‐development, is a developmental psychology construct that has been shown to predict mental health outcomes across multiple populations but has not been systematically reviewed in FEP. Aim: Our aim was to systematically review the evidence for: the predictors of EWB, the effectiveness of EWB interventions and to examine the quality of this research in FEP. Methods: Selected studies measured either composite or components of EWB. A systematic search produced 2876 abstracts and 122 articles were identified for full screening which produced 17 final papers with 2459 participants. Results: Studies comprised six RCTs, eight prospective follow‐up studies and three case‐controlled studies. Self‐esteem and self‐efficacy were the most commonly measured components. A meta‐analysis of RCTs revealed no statistically significant effect of interventions on self‐esteem. The extant research indicates that character strengths may be associated with higher EWB. Self‐esteem may be lower in FEP compared with age matched controls but not different from ultra‐high risk patients. Self‐esteem appears to be associated with poorer insight and improved therapeutic alliance. Significant problems with both external and internal validity of reviewed studies were apparent. Conclusions: The hypotheses that lowered EWB is a risk factor for both onset of FEP and for poorer functional outcomes warrant further investigation. There is currently no evidence for effective interventions for EWB in FEP. [ABSTRACT FROM AUTHOR]

[Display omitted] The vast majority of drugs are not designed or developed for pediatric and infant populations. Peptide drugs, which have become increasingly relevant in the past several decades, are no exception. Unfortunately, nearly all of the 60+ approved peptide drugs are formulated for injection, a particularly unfriendly mode of administration for infants. Although three peptide drugs were recently approved for oral formulations, this major advance in peptide drug delivery is available only for adults. In this review, we consider the current challenges and opportunities for the oral formulation of peptide therapeutics, specifically for infant populations. We describe the strategies that enable oral protein delivery and the potential impact of infant physiology on those strategies. We also detail the limited but encouraging progress towards 1) adapting conventional drug development and delivery approaches to infants and 2) designing novel infant-centric formulations. Together, these efforts underscore the feasibility of oral peptide delivery in infants and provide motivation to increase attention paid to this underserved area of drug delivery and formulation. [ABSTRACT FROM AUTHOR]

Purpose: Loneliness has been identified as a significant challenge for people with psychosis. Interventions targeting loneliness are lacking but adopting a positive psychology approach may reduce loneliness, promote well-being, and support meaningful social interactions. Together with youth mental health consumers, we developed a digital smartphone application (app) called +Connect, which delivers positive psychology content daily for 6 weeks.Materials and Methods: Twelve participants diagnosed with a psychotic disorder were recruited from early psychosis services. Loneliness was assessed pre-intervention, post-intervention, and 3-month post-intervention. Acceptability, feasibility, and usability were measured post-intervention, including a semi-structured interview on the user's experience of +Connect.Results: We found evidence for the feasibility of +Connect. All but two participants completed the +Connect program, completing 95% (40.10 out of 42 days) of the program. Furthermore, 66.67% (8 out of the 12 participants) remained engaged with the program 3-months post-intervention. Our data indicates preliminary evidence that +Connect may reduce loneliness, with scores from pre-intervention (M = 50.00, SD = 8.47) to post-intervention (M = 48.10, SD = 10.38) and 3-months post-intervention (M = 42.89, SD = 7.04). We found that positive reinforcement of in-game rewards and evidence of positive mood changes added to the feasibility of the app. Regarding acceptability, while 10% (1/10 participants) reported not finding +Connect useful or enjoyable, 90% of participants agreed that +Connect helped them to increase their social confidence, enjoy life, look forward to being with other people, and feel more connected with others. Participant interviews supported these results, with participants highlighting the app's strengths in providing useful information, stimulating self-reflection, fostering positive affect, and encouraging transfer of skills into their social interactions.Discussion: While preliminary findings indicated that +Connect yielded high levels of acceptability and feasibility, it is important to consider that we recruited a small and selected sample of lonely young people. Further iterations of this proof of concept app, which can incorporate participant feedback such preferences for increased personalisation, in-app feedback, and gamification, may allow an opportunity to test an improved version in the future. [ABSTRACT FROM AUTHOR]

Background: Acceptance- and mindfulness-based approaches have gained popularity in recent years.Objective: A systematic review and meta-analysis of the efficacy and safety of acceptance- and mindfulness-based therapies for persons with a psychotic or schizophrenia spectrum disorder.Methods: Following PRISMA guidelines, relevant databases were searched for published randomized controlled trials (RCTs) up to October 2018. Outcomes were severity of overall symptomatology, hospitalization, positive and negative symptoms, depression, anxiety, social functioning, quality of life, acceptance, mindfulness skills and safety of the interventions.Results: Sixteen studies comprising 1268 people with a schizophrenia spectrum disorder were included in the meta-analyses. Moderate to large effect sizes were found for overall symptomatology and hospitalization at endpoint (SMD .80, 95% CI -1.31, -0.29 and MD 4.38, -5.58, -3.17 respectively) and follow-up (SMD 1.10, -2.09, -0.10 and MD 7.18, -8.67, - 5.68 respectively). There were significant small effects on negative symptoms (SMD .24; -0.44, -0.03), small to moderate effects for depression (SMD .47; -0.80, -0.14), social functioning (SMD .43; -0.75, - 0.12) and mindfulness (SMD .51; -0.97, -0.05), moderate to large effects for acceptance (SMD .78; -1.44, -0.12), while no significant effects for positive symptoms (SMD .27; -0.65, 0.00), anxiety (SMD 2.11; -4.64, 0.42) or quality of life (SMD .43; -0.88, 0.02). Majority of studies (75%) had low risk of bias and sensitivity analyses supported the findings.Conclusion: Acceptance- and mindfulness-based approaches appear to be effective and safe interventions for individuals with schizophrenia spectrum disorders and could be a useful extension of standard casemanagement and psychofarmacology. [ABSTRACT FROM AUTHOR]

Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. Aim: The primary aim of the study is, in a population of young people with first‐episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence‐based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24‐months follow‐up. Methods: Our single‐blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2‐year period in 180 remitted first‐episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow‐up. Results: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. Conclusion: This study will provide evidence as to whether an antipsychotic dose‐reduction recovery treatment leads to improved functioning and safer outcomes in first‐episode psychosis patients. In addition, it will be the first‐controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population. [ABSTRACT FROM AUTHOR]

Oral drug delivery systems have multiple goals, assessing and enabling intestinal absorption at efficacious doses being one of them. Here we highlight the in vitro advances in modeling drug absorption, which more faithfully reflect human intestinal physiology and reduce the reliance on animal models. [ABSTRACT FROM AUTHOR]

Third-wave behavioural interventions are increasingly popular for treating and preventing mental health conditions. Recently, researchers have begun testing whether these interventions can effectively targeting eating disorder risk factors (disordered eating, body image concerns). This meta-analysis examined whether third-wave behavioural interventions (acceptance and commitment therapy; dialectical behaviour therapy; mindfulness-based interventions; compassion-focused therapy) show potential for being effective eating disorder prevention programs, by testing their effects on eating disorder risk factors in samples without an eating disorder. Twenty-four studies (13 randomized trials) were included. Most studies delivered selective prevention programs (i.e. participants who reported elevated risk factor). Third-wave interventions led to significant pre-post (g = 0.59; 95% CI = 0.43, 0.75) and follow-up (g = 0.83; 95% CI = 0.38, 1.28) improvements in disordered eating, and significant pre-post improvements in body image (g = 0.35; 95% CI = 0.13, 0.56). DBT-based interventions were associated with the largest effects. Third-wave interventions were also significantly more efficacious than wait-lists (g = 0.39; 95% CI = 0.09, 0.69) in reducing disordered eating, but did not differ to other interventions (g = 0.25; 95% CI = -0.06, 0.57). Preliminary evidence suggests that third-wave interventions may have a beneficial effect in ameliorating eating disorder risk. [ABSTRACT FROM AUTHOR]

The tripeptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), inhibit angiotensin-converting enzyme (ACE) resulting in lowered blood pressure. Our hypothesis was that the medium chain fatty acid permeation enhancer, sodium caprate (C 10 ), may prevent the decrease in permeability of the tripeptides when PepT1 is inhibited by glycyl-sarcosine (Gly-Sar), a situation that may occur in the presence of food hydrolysates. Using Caco-2 monolayers and isolated rat jejunal tissue, the apparent permeability coefficients (P app ) of [ 3 H]-IPP and [ 3 H]-LKP were assessed in the presence of Gly-Sar with and without C 10 . Gly-Sar decreased the P app of both tripeptides across monolayers and isolated jejunal tissue, but C 10 restored it. C 10 likely increased the paracellular permeability of the tripeptides, as indicated by immunofluorescence changes in tight junction proteins in Caco-2 monolayers accompanied by a concentration-dependent decrease in transepithelial electrical resistance (TEER). [ 3 H]-IPP and [ 3 H]-LKP were orally-gavaged to normal rats with Gly-Sar, C 10 , or with a mixture. Plasma levels of both peptides were reduced by Gly-Sar to less than half that of the levels detected in its absence, but were restored when C 10 was co-administered. In spontaneously hypertensive rats (SHRs), unlabelled IPP and LKP lowered blood pressure when delivered either by i.v. or oral routes. Oral gavage of Gly-Sar reduced the hypotensive action of peptides in SHRs, but the effect was restored in the presence of C 10 . In conclusion, there was a reduction in the hypotensive effects of IPP and LKP in SHRs when intestinal PepT1 was inhibited by Gly-Sar, but C 10 may circumvent this by enhancing paracellular permeability. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the review is to understand the relationships between loneliness and related psychological and social factors in individuals with psychosis. Loneliness is poorly understood in people with psychosis. Given the myriad of social challenges facing individuals with psychosis, these findings can inform psychosocial interventions that specifically target loneliness in this vulnerable group.Methods: We adhered to the PRISMA guidelines and systematically reviewed empirical studies that measured loneliness either as a main outcome or as an associated variable in individuals with psychosis.Results: A total of ten studies examining loneliness in people diagnosed with a psychotic disorder were examined. Heterogeneity in the assessment of loneliness was found, and there were contradictory findings on the relationship between loneliness and psychotic symptomatology. In individuals with psychosis, loneliness may be influenced by psychological and social factors such as increased depression, psychosis, and anxiety, poor social support, poor quality of life, more severe internalised stigma and perceived discrimination, and low self-esteem.Conclusions: The relationship between loneliness and psychosis remains poorly understood due to a lack of rigorous studies. Although having strong social relationships is crucial to facilitate recovery from serious mental illness, psychosocial interventions that specifically target loneliness in individuals with psychosis are lacking and sorely needed. Interventions targeting loneliness in those with psychosis will also need to account for additional barriers associated with psychosis (e.g., social skill deficits, impoverished social networks, and negative symptoms). [ABSTRACT FROM AUTHOR]

Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP) are food-derived antihypertensive peptides which inhibit angiotensin-converting enzyme (ACE) and may have potential to attenuate hypertension. There is debate over their mechanism of uptake across small intestinal epithelia, but paracellular and PepT1 carrier-mediated uptake are thought to be important routes. The aim of this study was to determine their routes of intestinal permeability using in vitro , ex vivo and in vivo intestinal models. The presence of an apical side pH of 6.5 (mimicking the intestinal acidic microclimate) and of Gly-Sar (a high affinity competitive inhibitor and substrate for PepT1) were tested on the transepithelial apical to basolateral (A to B) transport of [ 3 H]-IPP and [ 3 H]-LKP across filter-grown Caco-2 monolayers in vitro and rat jejunal mucosae ex vivo . A buffer pH of 6.5 on the apical side enabled Gly-Sar to reduce the apparent permeability (P app ) of [ 3 H]-IPP and [ 3 H]-LKP, but this inhibition was not evident at an apical buffer pH of 7.4. Gly-Sar reduced the P app across isolated jejunal mucosae and the area under the curve (AUC) in intra-jejunal instillations when the apical/luminal buffer pH was either 7.4 or 6.5. However, the jejunal surface acidic pH was maintained in rat jejunal tissue even when the apical side buffer pH was 7.4 due to the presence of the microclimate which is not present in monolayers. PepT1 expression was confirmed by immunofluorescence on monolayers and brush border of rat jejunal tissue. This data suggest that IPP and LKP are highly permeable and cross small intestinal epithelia in part by the PepT1 transporter, with an additional contribution from the paracellular route. [ABSTRACT FROM AUTHOR]

Background: First-episode psychosis most often has its onset during late adolescence. In caring for the young person, families endure high levels of stress and depression. Meanwhile, the social networks of families often erode. Our group has previously shown that family cognitive behaviour therapy (CBT) leads to significantly improved perceived stress compared with specialist first-episode treatment as usual; however, there are well-known barriers to the dissemination of effective family interventions. To address this, we have developed a novel online intervention entitled 'Altitudes' that fully integrates purpose-built online social networking, expert and peer moderation, and evidence-based psychoeducation within a single application. The primary aim of this trial is to evaluate the effectiveness of Altitudes in reducing stress in carers over a 6-month period.Methods/design: We describe here a single-blinded cluster randomised controlled trial (cRCT) with permutated blocks. The clusters comprise individual families. The two treatment conditions include Altitudes plus Specialist Treatment as Usual (STAU) and STAU alone. Altitudes involves participation in our novel online programme whereas STAU comprises specialist family work at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. We aim to recruit 160 family members of young, 15-27 year-old, patients registered for treatment for first-episode psychosis (FEP) at EPPIC. The design includes two assessment time points, namely, baseline and 6-month follow-up. The study is due for completion within 2 years including an 18-month recruitment period and a 6-month treatment phase. The primary outcome is carers' perceived stress at 6 months. Secondary outcome measures include a biomarker of stress, depressive symptoms, worry, substance use, loneliness, social support, satisfaction with life, and a range of measures that tap into coping resources. We seek to gain a dynamic picture of carer stress through our Smartphone Ecological Momentary Assessment (SEMA) tool.Discussion: This is the first randomised controlled trial designed to evaluate an online intervention for carers of young people recovering from FEP. It has the potential to produce evidence in support of a highly novel, accessible, and cost-effective intervention to reduce stress in carers who are providing support to young people at a critical phase in their recovery from psychosis.Trial Registration: Australian New Zealand Clinical Trial Registry, identifier: ACTRN12616000968471 . Retrospectively registered on 22 July 2016. [ABSTRACT FROM AUTHOR]

The ability to regulate emotions is central to well-being, but healthy emotion regulation may not merely be about using the "right" strategies. According to the strategy-situation-fit hypothesis, emotion-regulation strategies are conducive to well-being only when used in appropriate contexts. This study is the first to test the strategy-situation-fit hypothesis using ecological momentary assessment of cognitive reappraisal--a putatively adaptive strategy. We expected people who used reappraisal more in uncontrollable situations and less in controllable situations to have greater well-being than people with the opposite pattern of reappraisal use. Healthy participants (n = 74) completed measures of wellbeing in the lab and used a smartphone app to report their use of reappraisal and perceived controllability of their environment 10 times a day for 1 week. Results supported the strategy-situation-fit hypothesis. Participants with relatively high well-being used reappraisal more in situations they perceived as lower in controllability and less in situations they perceived as higher in controllability. In contrast, we found little evidence for an association between greater well-being and greater mean use of reappraisal across situations. [ABSTRACT FROM AUTHOR]

Background Lifestyle issues contribute to the development of obesity, type 2 diabetes, and cardiovascular disease. Together with appropriate diet and exercise, nutraceuticals may contribute to managing prevention at an early stage prior to therapeutic intervention. However, many useful food-derived bioactive compounds will not sufficiently permeate the small intestine to yield efficacy without appropriate oral delivery technology. The pharmaceutical industry uses commercialised approaches for oral delivery including solubilizing technologies for small molecules, which could be applied to selected nutraceuticals with solubility issues. Systems currently being studied for labile and poorly permeable hydrophilic peptides and macromolecules include nanoparticles, intestinal permeation enhancers (PE) and mucolytics. These may also have potential for application to nutraceuticals with similar sub-optimal physicochemical characteristics. Scope and approach We introduce factors which effect oral delivery of four types of nutraceuticals, namely fatty acids, bioactive peptides, micronutrients, and phytochemicals. Factors preventing oral absorption can arise from molecule physicochemical characteristics, which influence solubility, stability, and epithelial permeability in the gastrointestinal tract (GIT). We highlight the potential of selected delivery strategies to improve oral bioavailability of different types of nutraceuticals. Key findings and conclusions There is an opportunity for the nutraceutical industry to leverage the pharmaceutical industry's progress in oral drug delivery. The use of delivery approaches using formulation with excipients or substances with a history of use in man has potential to improve solubility, stability, or permeability of nutraceuticals, leading to improved oral bioavailability. Leveraging oral delivery formulation approaches across nutraceutical and pharmaceutical molecules will lead to synergies for both fields. [ABSTRACT FROM AUTHOR]

Scaffolds which aim to provide an optimised environment to regenerate bone tissue require a balance between mechanical properties and architecture known to be conducive to enable tissue regeneration, such as a high porosity and a suitable pore size. Using freeze-dried collagen-based scaffolds as an analogue of native ECM, we sought to improve the mechanical properties by incorporating hydroxyapatite (HA) in different ways while maintaining a pore architecture sufficient to allow cell infiltration, vascularisation and effective bone regeneration. Specifically we sought to elucidate the effect of different hydroxyapatite incorporation methods on the mechanical, morphological, and cellular response of the resultant collagen-HA scaffolds. The results demonstrated that incorporating either micron-sized (CHA scaffolds) or nano-sized HA particles (CnHA scaffolds) prior to freeze-drying resulted in moderate increases in stiffness (2.2-fold and 6.2-fold, respectively, vs. collagen-glycosaminoglycan scaffolds, P < 0.05, a scaffold known to support osteogenesis), while enabling good cell attachment, and moderate mesenchymal stem cell (MSC)-mediated calcium production after 28 days' culture (2.1-fold, P < 0.05, and 1.3-fold, respectively, vs. CG scaffolds). However, coating of collagen scaffolds with a hydroxyapatite precipitate after freeze-drying (CpHA scaffolds) has been shown to be a highly effective method to increase the compressive modulus (26-fold vs. CG controls, P < 0.001) of scaffolds while maintaining a high porosity (~ 98%). The coating of the ligand-dense collagen structure results in a lower cell attachment level (P < 0.05), although it supported greater cell-mediated calcium production (P < 0.0001) compared with other scaffold variants after 28 days' culture. The comparatively good mechanical properties of these high porosity scaffolds is obtained partially through highly crosslinking the scaffolds with both a physical (DHT) and chemical (EDAC) crosslinking treatment. Control of scaffold microstructure was examined via alterations in freezing temperature. It was found that the addition of HA prior to freeze-drying generally reduced the pore size and so the CpHA scaffold fabrication method offered increased control over the resulting scaffolds microstructure. These findings will help guide future design considerations for composite biomaterials and demonstrate that the method of HA incorporation can have profound effects on the resulting scaffold structural and biological response. [ABSTRACT FROM AUTHOR]

Two food-derived ACE inhibitory peptides, Ile-Pro-Pro (IPP) and Leu-Lys-Pro (LKP), may have potential as alternative treatments for treatment of mild- or pre-hypertension. Lack of stability to secretory and intracellular peptidases and poor permeability across intestinal epithelia are typical limiting factors of oral delivery of peptides. The stability of IPP and LKP was confirmed in vitro in rat intestinal washes, and intestinal and liver homogenates over 60 min. A positive protein control for peptidases, insulin, was significantly digested in each format over the same period. Neither tripeptide showed cytotoxic activity on Caco-2 and Hep G2 cells using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, even after chronic exposure. The basal P app of fluorescein isothiocyanate (FITC)-labeled IPP and FITC-LKP across isolated rat jejunal and colonic mucosae were low, but were significantly increased in each tissue type by the medium chain fatty acids (MCFA) permeation enhancers, sodium caprate (C 10 ) and the sodium salt of 10-undecylenic acid (uC 11 ). IPP and LKP were therefore stable against intestinal and liver peptidases and were non-cytotoxic; their P app values across rat intestinal mucosae were low, but could be increased by MCFA. There is potential to make on oral dosage form once in vivo pharmacology is confirmed. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate trajectories of social functioning in young people with first-episode psychosis (FEP) with and without cannabis misuse using a secondary analysis of data from the Episode-II trial. Forty-two young people with FEP and comorbid cannabis use disorder were compared with 39 young people with FEP but without a cannabis use disorder. Social functioning was assessed every 6 months during a 30-month follow-up. Multilevel linear growth curve modeling was used to compare the social functioning trajectories over time for those with and without cannabis misuse. Cannabis misuse was not associated with social functioning at baseline assessment. Over a 30-month follow-up, FEP patients without cannabis disorder showed significant improvements in their social functioning, whereas patients with cannabis misuse at baseline displayed no such improvement. Patients with and without cannabis misuse differed significantly in their levels of social functioning after 24 months. Similar results were obtained after adjusting for potential confounders (i.e., age, gender, negative symptoms, premorbid functioning, DSM-IV diagnoses, baseline social functioning and other substance use). In the context of a specialized early intervention service, patients with cannabis misuse at baseline did not attain the improvements in social outcomes observed in their counterparts without cannabis misuse. There is a need to develop effective interventions to reduce cannabis misuse to ultimately improve social outcomes in young people with psychosis. [ABSTRACT FROM AUTHOR]

Objectives We sought to review empirical studies of psychological factors accounting for distress in caregivers of young people with early psychosis. Method Following the PRISMA guidelines, we included studies that empirically tested psychological models of caregiver distress in early psychosis by searching the following databases up until March 2014: PsycINFO, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL). This was followed by additional manual searches of reference lists and relevant journals. Results The search identified 15 papers describing 13 studies together comprising 1056 caregivers of persons with early psychosis. The mean age of caregivers was 47.2 years (SD = 9.8), of whom 71.5% were female and 74.4% were parents. Nine different psychological variables were examined in the included studies, which were categorised in the following non-mutually exclusive groups: coping, appraisal/attribution and interpersonal response. There was considerable data to support the link between distress and psychological factors such as avoidant coping, appraisal and emotional over-involvement. However, the possibilities of drawing conclusions were limited by a number of methodological issues, including cross-sectional data, small sample sizes, confounding variables not being accounted for, and a wide variation in outcome measures. Discussion The strengths of the review were the systematic approach, the exclusion of non-empirical papers and the rating of methodological quality by two independent raters. Limitations were that we excluded studies published in languages other than English, that data extraction forms were developed for this study and hence not tested for validity, and that there was a potential publication bias in favour of significant findings. Conclusion and implications A better grasp of the psychological factors accounting for caregiver distress early in the course of illness may help us understand the trajectory of distress. This is an important step in preventing long-term distress in caregivers and supporting recovery in the whole family. [ABSTRACT FROM AUTHOR]

Facebook is an environment in which adolescents can experiment with self-presentation. Unfortunately, Facebook can also be an environment in which cyberbullying occurs. The aim of the current study was to investigate whether specific self-presentation behaviours in Facebook were associated with cyberbullying victimisation for adolescents. The contents of 147 adolescent (15–24 years) Facebook profile pages were recorded and used to predict cyberbullying victimisation. Coded contents included the presence or absence of Facebook profile features (e.g., relationship status) and the specific content of certain features (e.g., type and valence of wall posts). Participants completed measures of cyberbullying victimisation and traditional bullying victimisation and perpetration. More than three out of four participants reported experiencing at least one victimisation experience on Facebook in the preceding 6 months. A series of Facebook features and experiences of traditional bullying victimisation/perpetration were found to be associated with an increased risk of cyberbullying victimisation. Number of Facebook friends and traditional bullying victimisation were also significant predictors of cyberbullying victimisation. These results support the hypothesis that self-presentation on Facebook can increase the likelihood of eliciting negative attention from potential perpetrators. This has important implications for the development of cyberbullying prevention and education programs that teach adolescents about measures they may take to decrease their risk for cyberbullying victimisation within social networking sites like Facebook. [ABSTRACT FROM AUTHOR]

Highlights: [•] We provide the views of adolescent victims of cyberbullying in social networking sites. [•] Victims’ definition of cyberbullying is different and more complex than presented in previous research. [•] Victim impact was the most important criterion. No participant referenced power imbalance. [•] Emotional, social and behavioural impacts were the most reported by victims. [Copyright &y& Elsevier]

Cyberbullying victimization is associated with a range of emotional and behavioral outcomes for adolescents. However, previous research has shown that this type of victimization does not affect all individuals negatively. The factors that account for individual differences in reactions to the same online experiences are not well understood. Using a qualitative inductive approach, a set of strong themes relating to factors that either increased the severity of impact of cyberbullying victimization or buffered victims against the impact emerged from interviews with 25 adolescents aged 15-24 years. Themes related to publicity, anonymity of perpetrators, features of the medium, presence of bystanders, and individual level factors were identified as potential influences upon impact severity. The implications of these results for further research and for school/university cyberbullying prevention programs for victims, perpetrators, and bystanders are discussed. [ABSTRACT FROM AUTHOR]

Background: Treatment of segmental bone loss remains a major challenge in orthopaedic surgery. Traditional techniques (eg, autograft) and newer techniques (eg, recombinant human bone morphogenetic protein-2 [rhBMP-2]) have well-established performance limitations and safety concerns respectively. Consequently there is an unmet need for osteoinductive bone graft substitutes that may eliminate or reduce the use of rhBMP-2. Questions/purposes: Using an established rabbit radius osteotomy defect model with positive (autogenous bone graft) and negative (empty sham) control groups, we asked: (1) whether a collagen-glycosaminoglycan scaffold alone can heal the defect, (2) whether the addition of hydroxyapatite particles to the collagen scaffold promote faster healing, and (3) whether the collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds are able to promote faster healing (by carrying a low dose rhBMP-2). Methods: A 15-mm transosseous radius defect in 4-month-old skeletally mature New Zealand White rabbits were treated with either collagen-hydroxyapatite or collagen-glycosaminoglycan scaffolds with and without rhBMP-2. Autogenous bone graft served as a positive control. Time-series radiographs at four intervals and postmortem micro-CT and histological analysis at 16 weeks were performed. Qualitative histological analysis of postmortem explants, and qualitative and volumetric 3-D analysis of standard radiographs and micro-CT scans enabled direct comparison of healing between test groups. Results: Six weeks after implantation the collagen-glycosaminoglycan group had callus occupying greater than ½ the defect, whereas the sham (empty) control defect was still empty and the autogenous bone graft defect was completely filled with unremodeled bone. At 6 weeks, the collagen-hydroxyapatite scaffold groups showed greater defect filling with dense callus compared with the collagen-glycosaminoglycan controls. At 16 weeks, the autogenous bone graft groups showed evidence of early-stage medullary canal formation beginning at the proximal and distal defect borders. The collagen-glycosaminoglycan and collagen-glycosaminoglycan-rhBMP-2 groups had nearly complete medullary canal formation and anatomic healing at 16 weeks. However, collagen-hydroxyapatite-rhBMP-2 scaffolds showed the best levels of healing, exhibiting a dense callus which completely filled the defect. Conclusions: The collagen-hydroxyapatite scaffold showed comparable healing to the current gold standard of autogenous bone graft. It also performed comparably to collagen-glycosaminoglycan-rhBMP-2, a representative commercial device in current clinical use, but without the cost and safety concerns. Clinical Relevance: The collagen-glycosaminoglycan scaffold may be suitable for a low load-bearing defect. The collagen-hydroxyapatite scaffold may be suitable for a load-bearing defect. The rhBMP-2 containing collagen-glycosaminoglycan and collagen-hydroxyapatite scaffolds may be suitable for established nonunion defects. [ABSTRACT FROM AUTHOR]

Purpose: In a previous study, individuals who followed a particular new religious movement (NRM) reported significantly less distress even though they reported similar levels of delusional ideation when compared with individuals diagnosed with psychotic disorders. Protective factors such as social relationship quality and quality of life (QOL) were hypothesized to explain attenuated distress associated with delusional ideation. Methods: NRM individuals ( n = 29), individuals diagnosed with psychotic disorders ( n = 25), and control individuals ( n = 63) were recruited. Psychotic symptoms, delusion-proneness, and facets of social relationships quality and QOL were examined across group. Potential moderators of the relationship between group membership and distress were further examined in multiple regression models. Results: NRM participants reported more social relationships that were of higher quality (as demonstrated by more crisis supports, unique and overlap supports, more helpful supports and more reciprocated supports) than individuals with psychotic disorders. NRM participants also reported significantly higher QOL than individuals with psychotic disorders. Furthermore, NRM participants reported more distinct and less reciprocated supports, and significantly higher psychological, environmental, and total QOL, when compared with control participants. The relationship between group membership, delusional ideation, and distress was moderated by relationship reciprocity as well as by total QOL. Conclusions: Findings highlight the importance of establishing healthy reciprocal social relationships and improving QOL in people diagnosed with psychotic disorders, as these factors may act as a buffer against distress associated with delusional beliefs. [ABSTRACT FROM AUTHOR]

This essay discusses the ways in which the 1920 and 1933 obscenity cases involving Ulysses—the first banning the novel in America and the second liberating it—provide a window into the world of lawyers and judges that remains useful today. My perspective on the two cases as a former prosecutor and sitting judge is followed first by my lament that too many members of my profession are insufficiently comfortable in our lawyers' skin, causing them to act like something they are not, with results ranging from the pathetic to the outright dangerous. Second, I explain how the Ulysses cases illustrate a troubling fact about judges in America: when they are equipped with indeterminate rules of decision that allow them to change the direction of the law, as a general matter, judges cannot be counted on to lead the way toward needed changes. Rather, their decisions tend to track and ratify public opinion at the time they are made. In other words, judges are more likely to follow than lead. As a result, when needed change eventually arrives, as it did with respect to government censorship of the written word, it usually arrives too late. [ABSTRACT FROM AUTHOR]

Aim: First-episode psychosis and borderline personality disorder are severe mental disorders that have their onset in youth. Their co-occurrence is clinically well recognized, is associated with significant risks and is complex to treat. Yet, there is no published specific intervention for this problem. This study reports a pilot randomized controlled trial comparing combined specialist first-episode treatment plus specialist early intervention for borderline personality, entitled Helping Young People Early, with specialist first-episode treatment alone. We aimed to evaluate the safety and feasibility of adding early intervention for borderline personality. Methods: The study investigated the safety of specialist first-episode treatment plus specialist early intervention for borderline personality in relation to deterioration in psychosis, aggression, self-harm and suicidality, and feasibility in relation to the completion of therapy phases. Sixteen patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision (DSM-IV-TR) criteria for first-episode psychosis and borderline personality (four or more DSM-IV criteria) were randomized either to specialist first-episode treatment alone or specialist first-episode treatment plus specialist early intervention for borderline personality and were followed up at the end of treatment and 6 months later. Results: The results showed that it was feasible to recruit and assess a high risk and complex group of patients who were agreeable to study participation. Specialist first-episode treatment plus specialist early intervention for borderline personality was an acceptable and safe treatment. Conclusion: A larger-scale randomized controlled trial of early intervention for borderline personality for young first-episode psychosis patients with co-occurring full or subsyndromal borderline personality is warranted. [ABSTRACT FROM AUTHOR]

Abstract: The prevention of relapse is an important treatment goal in first-episode psychosis. Randomized controlled trials (RCTs) provide the gold standard methodology for evaluating interventions for relapse prevention. Properly designed RCTs which include relapse as a treatment outcome should rigorously operationalize psychotic relapse. The aim of this systematic literature review was to evaluate according to six criteria the operationalization of relapse in RCTs of clinical innovations for the prevention of relapse in first-episode psychosis. Through a systematic literature search of relevant RCTs in first-episode psychosis patients, eight pharmacological and eight non-pharmacological trials, published between 1982 and 2009, were indentified. Readmission to a psychiatric hospital was the most common definition of psychotic relapse. Five studies did not measure relapse using any standardized or validated observer-rated instruments. The majority of the studies did not specify a duration criterion for relapse. Only three studies satisfied six criteria for the adequate operationalization of relapse. These results raise concerns regarding the internal and external validity of these research findings. There is an urgent need for a standardized, universally adopted set of criteria for psychotic relapse with appropriate specification of measurement instruments for use in future RCTs. [Copyright &y& Elsevier]

Objective: To investigate predictors of adherence with a cognitive-behavioural intervention in first-episode psychosis (FEP) patients. Method: Predictors of adherence to cognitive-behavioural therapy (CBT) were longitudinally investigated in the experimental arm of a randomized controlled trial designed to evaluate the effectiveness of a CBT intervention for relapse prevention early in the course of psychosis when compared with treatment as usual within 2 high quality, youth oriented, specialist FEP programs (the EPISODE II trial). Results: Longer duration of untreated psychosis (DUP) and poorer level of insight predicted poor adherence to CBT. This association remained significant after controlling for potential confounders. Conclusions: Treatment delay may decrease adherence with CBT in FEP patients. Reducing DUP and promoting insight early in the course of psychosis are likely to enhance adherence with CBT. [ABSTRACT FROM AUTHOR]

Background: High rates of remission are associated with effective treatments for first-episode psychosis (FEP). However, the goal of relapse prevention remains elusive for many remitted FEP patients. Aims: This paper describes the clinical and functional status of remitted FEP patients at a specialist service, and outlines the rationale and methodology of a randomized controlled trial of a multimodal relapse prevention therapy for these patients. Method: Eighty one remitted FEP patients and 63 of their family members attending the Early Psychosis Prevention and Intervention Centre (EPPIC) were randomized to treatment as usual (TAU) or to a relapse prevention therapy (RPT). Baseline data included demographics, Axis I and II diagnoses, psychiatric symptoms, functional status, and family distress, burden, and communication styles. Results: The findings indicated high rates of depressive and negative symptoms and substance abuse problems. Less than half of the patients had returned to employment. A high rate of depressive and anxiety symptoms was evident amongst family members, and burden was comparable to results from other FEP studies. Conclusions: FEP patients who reach remission have wide-ranging clinical and psychosocial needs. Relapse risk remains high, and relapse prevention is a critical priority. Family members also need specific interventions. Declaration of interest: This study described in this paper has been funded by an independent research grant from Eli Lilly via the Lilly Melbourne Academic Psychiatry Consortium. [ABSTRACT FROM AUTHOR]

Objective: This paper provides a selective review of forensic research with the aim of making recommendations for the development and evaluation of psychosocial interventions for the mainstream community mental health setting to address the needs of patients with a history of offending. Conclusion: Mainstream community mental health services can be guided by existing findings in the design of psychosocial intervention and prevention programmes. There is growing need to develop and evaluate such interventions. [ABSTRACT FROM AUTHOR]

Objective: This paper outlines a rationale for expanding research and clinical innovations focused upon relapse prevention following a first episode of psychosis. Some general principles for further progress are extracted from an overview of the first-episode psychosis (FEP) relapse literature. A cognitive behaviour therapy intervention for relapse prevention for FEP, that has been developed at the Early Psychosis Prevention and Intervention Centre, is described to illustrate these principles. Conclusions: Further progress is needed in refining interventions specific to the prevention of relapse following FEP. Future progress is dependent upon improved understanding of the interaction of biological, interpersonal and psychological processes underpinning relapse. [ABSTRACT FROM AUTHOR]

Abstract: Research in schizophrenia has provided empirical support for the use of self-report inventories for early warning signs of relapse, but to date no published studies have reported on the predictive validity of self-reported early warning signs of relapse in a first-episode cohort. Sixty patients, who had remitted following their first episode of psychosis, participated in a 9–12 month prospective follow-up study. Outcome data on putative prodromal symptoms was available on 46 participants. The Early Signs Scale (ESS) achieved adequate sensitivity but poor specificity and positive predictive validity (PPV) in predicting relapse or symptom exacerbations, although a post hoc increase in the established cut-off significantly improved the outcome. The findings provide qualified support for the use of the ESS in relapse prevention with first-episode patients who are in remission. Further prospective studies with larger numbers of first-episode patients will enable sample sizes enable the comparison of the effectiveness of several prodromal scales using ROC analysis, or a combination of risk factors using regression models. [Copyright &y& Elsevier]

The article focuses on the difference between U.S. attorneys and the U.S. Attorney General on the issue of supervising federal capital punishment. It discusses reasons why a U.S. Attorney General should defer when U.S. attorneys recommend against the death penalty. The author of this article feels that the attorney general should overrule U.S. attorneys to require them to seek the death penalty only in exceptional circumstances, to vindicate specific and narrow federal interests that are not present in the kind of murder cases in which the attorney general has recently acted.

Presents a tribute for judge Eugene H. Nickerson in the U.S. Argument over an act of Congress that required the deportation of aliens upon conviction of certain crimes; Love for his work in the courthouse; Genuine interest on people.

Aim: Major depressive disorder (MDD) has far reaching impacts for young people, their families and society. Cognitive behavioural therapy (CBT) is one of the first‐line treatments for young people experiencing MDD; however, there is limited research examining how young people with MDD experience CBT. The aim of this study was to explore their experience and their views of this intervention. Methods: We employed a qualitative research design, with semi‐structured interviews and thematic analysis. Eight participants aged between 17 and 24 years who received CBT for MDD in a randomized controlled trial were recruited. Results: Five themes were identified: the importance of relationship with clinician; the range of useful components within CBT; the ability for CBT to accommodate different techniques and presenting issues; the importance of checking in with clients during the process of therapy; and the impacts of MDD on therapy. Conclusions: The findings highlight the importance of clinicians having a youth friendly and collaborative approach that allows a modular delivery of a range of CBT techniques to suit the client's presenting issue and formulation. There is a need to continually check how young people are responding to interventions, and to be aware of potential cognitive deficits and adjust therapy accordingly. This is a small study that provides insight into how young people with MDD experience CBT and avenues to explore for tailoring provision of CBT to enhance the therapeutic experience for this population. [ABSTRACT FROM AUTHOR]

Traditionally, behavioral, social, and health science researchers have relied on global/retrospective survey methods administered cross-sectionally (i.e., on a single occasion) or longitudinally (i.e., on several occasions separated by weeks, months, or years). More recently, social and health scientists have added daily life survey methods (also known as intensive longitudinal methods or ambulatory assessment) to their toolkit. These methods (e.g., daily diaries, experience sampling, ecological momentary assessment) involve dense repeated assessments in everyday settings. To facilitate research using daily life survey methods, we present SEMA3 (http://www.SEMA3.com), a platform for designing and administering intensive longitudinal daily life surveys via Android and iOS smartphones. SEMA3 fills an important gap by providing researchers with a free, intuitive, and flexible platform with basic and advanced functionality. In this article, we describe SEMA3's development history and system architecture, provide an overview of how to design a study using SEMA3 and outline its key features, and discuss the platform's limitations and propose directions for future development of SEMA3. [ABSTRACT FROM AUTHOR]