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We appreciate Reierson’s thoughtful commentary on our 2019 paper, which described our experiences, ethical process, judgment calls, and lessons from a 2016-2017 data-sharing pilot between Crisis Text Line and academic researchers. The commentary raises important questions about the ethical conduct of health research in the digital age, particularly regarding informed consent, potential conflicts of interest, and the protection of vulnerable populations. Our article focused specifically on the noncommercial use of Crisis Text Line data for research purposes, so we restrict our reply to points relevant to such usage. While we acknowledge the limitations of Crisis Text Line’s Terms of Service as a means of informing users about data sharing for research, we maintain that our guidelines were ethically sound and aligned with well-established practices for institutional review board (IRB) review and researcher training. We emphasize the critical role of IRBs in ensuring that research involving vulnerable populations, including minors, is conducted ethically and with appropriate safeguards. Regarding potential conflicts of interest, we argue that unpaid, nonfiduciary advisory board service for a nonprofit organization does not constitute a conflict requiring disclosure. The transparent nature of our collaboration with Crisis Text Line, as evidenced by the authorship and acknowledgments in our paper, further underscores our commitment to ethical research practices. We recognize the complexity and evolving nature of the challenges surrounding data-sharing partnerships in digital health research. As the field progresses, we remain committed to ongoing, transparent engagement and to refining best practices in collaboration with colleagues, stakeholders, and the public. Our response aims to provide clarity and context for the concerns raised in the commentary while reaffirming the integrity and value of our original work. Ultimately, we maintain that our paper contributed meaningfully to the ongoing discourse on ethical data sharing and laid the groundwork for future improvements in this critical area of digital health research.

Neuroprotection is conceived as one of the potential tool to prevent or slow neuronal death and hence a therapeutic hope to treat neurodegenerative diseases, like Parkinson’s and Alzheimer’s diseases. Increase of oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation have been identified as main causes of neuronal death and adopted as targets to test experimentally the putative neuroprotective effects of various classes of drugs. Among these agents, antiepileptic drugs (AEDs), both the old and the newer generations, have shown to exert protective effects in different experimental models. Their mechanism of action is mediated mainly by modulating the activity of sodium, calcium and potassium channels as well as the glutamatergic and GABAergic (gamma-aminobutyric acid) synapses. Neurological pathologies in which a neuroprotective action of AEDs has been demonstrated in specific experimental models include: cerebral ischemia, Parkinson’s disease, and Alzheimer’s disease. Although the whole of experimental data indicating that neuroprotection can be achieved is remarkable and encouraging, no firm data have been produced in humans so far and, at the present time, neuroprotection still remains a challenge for the future.

Suicide is the third-leading cause of death among US adolescents aged 10-19 years, and about 10% attempt suicide each year. School-based universal prevention may reduce youth suicidal behavior. Sources of Strength uses a peer leader network diffusion model to promote healthy norms across a school population. A key challenge within schoolwide programs is reaching a large and diverse array of students, especially those less engaged with their peers. Motivated by this challenge, we developed and field-tested Text4Strength-a program of automated text messages targeting help-seeking attitudes and norms, social coping resources, and emotion regulation skills. This study conducted a pilot randomized controlled trial of Text4Strength in 1 high school as an extension of an ongoing schoolwide program (Sources of Strength), to test its impact on targets that have the potential to reduce suicidal behavior. Students at an upstate New York high school (N=223) received 1-2 text messages per week for 9 weeks, targeting strategies for coping with difficult feelings and experiences through clarifying emotions and focusing on positive affect concepts, awareness, and strengthening of youth-adult relationships; and positive help-seeking norms, skills, and resources. Surveys were administered at baseline, immediately post intervention and 3 months after texting ended. We measured proximal intervention targets (methods of coping during stressful events, ability to make sense of their own emotions, feelings of powerlessness during emotion management and recovery, relations with trusted adults at school, and help-seeking behaviors), symptoms and suicide ideation, and student replies to messages. No significant effects were observed for any outcome at either follow-up time point. Results showed that if there is a true (but undetected) intervention effect, it is small. Students with fewer friend nominations did not interact any more or less with the text messages. Exploratory moderation analyses observed no interaction between the intervention condition and the number of friends or baseline suicide ideation at any time point. In contrast to a promising previous field test, these results suggest that Text4Strength is unlikely to have impacted the outcomes of interest and that undetected moderate or large effects can be ruled out with high confidence. Although motivated by the need to reach more isolated students, students with fewer friends did not engage more or show a greater effect than other participants. This study was conducted in a single high school that was already implementing Sources of Strength, so the bar for showing a distinct effect from texting alone was high. Many further channels for reaching youth through private messaging remain unexplored. Alternative delivery systems should be investigated, such as embedding messaging in gaming chat systems and other media. More sophisticated systems drawing on chatbots may also achieve better outcomes. ClinicalTrials.gov NCT03145363; https://clinicaltrials.gov/study/NCT03145363.

Background Suicide is a national public health crisis and a critical patient safety issue. It is the 10th leading cause of death overall and the second leading cause of death among adolescents and young adults (15–34 years old). Research shows 80% of youth who died by suicide saw their primary care provider within the year of their death. It is imperative that primary care providers develop the knowledge and skills to talk with patients about distress and suicidal thoughts, and to assess and respond in the context of the ongoing patient - primary care provider relationship. Methods This study examines the effectiveness of simulation on suicide prevention training for providers-in-training by comparing two conditions: 1) a control group that receives online teaching on suicide prevention in primary care via brief online videos and 2) an experimental group that includes the same online teaching videos plus two standardized patient (SP) interactions (face-to-face and telehealth, presentation randomized). All SP interactions are video-recorded. The primary analysis is a comparison of the two groups’ suicide prevention skills using an SP “test case” at 6-month follow-up. Discussion The primary research question examines the impact of practice (through SP simulation) over and above online teaching alone on suicide prevention skills demonstrated at follow-up. We will assess moderators of outcomes, differences among SP simulations (i.e., face-to-face vs. telehealth modalities), and whether the experimental group’s suicide prevention skills improve over the three SP experiences. Trial registration The study was registered on Clinical Trials Registry ( clinicaltrials.gov ) on December 14, 2016. The Trial Registration Number is NCT02996344 .

Background Despite being preventable, suicide is a leading cause of death and a major global public health problem. For every death by suicide, many more suicide attempts are undertaken, and this presents as a critical risk factor for suicide. Currently, there are limited treatment options with limited underpinning research for those who present to emergency departments with suicidal behaviour. The aim of this study is to assess if adding one of two structured suicide-specific psychological interventions (Attempted Suicide Short Intervention Program [ASSIP] or Brief Cognitive Behavioural Therapy [CBT] for Suicide Prevention) to a standardised clinical care approach (Suicide Prevention Pathway [SPP]) improves the outcomes for consumers presenting to a Mental Health Service with a suicide attempt. Methods This is a randomised controlled trial with blinding of those assessing the outcomes. People who attempt suicide or experience suicidality after a suicide attempt, present to the Gold Coast Mental Health and Specialist Services, are placed on the Suicide Prevention Pathway (SPP), and meet the eligibility criteria, are offered the opportunity to participate. A total of 411 participants will be recruited for the study, with 137 allocated to each cohort (participants are randomised to SPP, ASSIP + SPP, or CBT + SPP). The primary outcomes of this study are re-presentation to hospitals with suicide attempts. Presentations with suicidal ideation will also be examined (in a descriptive analysis) to ascertain whether a rise in suicidal ideation is commensurate with a fall in suicide attempts (which might indicate an increase in help-seeking behaviours). Death by suicide rates will also be examined to ensure that representations with a suicide attempt are not due to participants dying, but due to a potential improvement in mental health. For participants without a subsequent suicide attempt, the total number of days from enrolment to the last assessment (24 months) will be calculated. Self-reported levels of suicidality, depression, anxiety, stress, resilience, problem-solving skills, and self- and therapist-reported level of therapeutic engagement are also being examined. Psychometric data are collected at baseline, end of interventions, and 6,12, and 24 months. Discussion This project will move both ASSIP and Brief CBT from efficacy to effectiveness research, with clear aims of assessing the addition of two structured psychological interventions to treatment as usual, providing a cost-benefit analysis of the interventions, thus delivering outcomes providing a clear pathway for rapid translation of successful interventions. Trials registration ClinicalTrials.gov NCT04072666 . Registered on 28 August 2019

Young adults in the United States are experiencing accelerating rates of suicidal thoughts and behaviors but have the lowest rates of formal mental health care. Digital suicide prevention interventions have the potential to increase access to suicide prevention care by circumventing attitudinal and structural barriers that prevent access to formal mental health care. These tools should be designed in collaboration with young adults who have lived experience of suicide-related thoughts and behaviors to optimize acceptability and use. This study aims to identify the needs, preferences, and features for an automated SMS text messaging-based safety planning service to support the self-management of suicide-related thoughts and behaviors among young adults. We enrolled 30 young adults (age 18-24 years) with recent suicide-related thoughts and behaviors to participate in asynchronous remote focus groups via an online private forum. Participants responded to researcher-posted prompts and were encouraged to reply to fellow participants-creating a threaded digital conversation. Researcher-posted prompts centered on participants' experiences with suicide-related thought and behavior-related coping, safety planning, and technologies for suicide-related thought and behavior self-management. Focus group transcripts were analyzed using thematic analysis to extract key needs, preferences, and feature considerations for an automated SMS text messaging-based safety planning tool. Young adult participants indicated that an automated digital SMS text message-based safety planning intervention must meet their needs in 2 ways. First, by empowering them to manage their symptoms on their own and support acquiring and using effective coping skills. Second, by leveraging young adults' existing social connections. Young adult participants also shared 3 key technological needs of an automated intervention: (1) transparency about how the intervention functions, the kinds of actions it does and does not take, the limits of confidentiality, and the role of human oversight within the program; (2) strong privacy practices-data security around how content within the intervention and how private data created by the intervention would be maintained and used was extremely important to young adult participants given the sensitive nature of suicide-related data; and (3) usability, convenience, and accessibility were particularly important to participants-this includes having an approachable and engaging message tone, customizable message delivery options (eg, length, number, content focus), and straightforward menu navigation. Young adult participants also highlighted specific features that could support core coping skill acquisition (eg, self-tracking, coping skill idea generation, reminders). Engaging young adults in the design process of a digital suicide prevention tool revealed critical considerations that must be addressed if the tool is to effectively expand access to evidence-based care to reach young people at risk for suicide-related thoughts and behaviors. Specifically, automated digital safety planning interventions must support building skillfulness to cope effectively with suicidal crises, deepening interpersonal connections, system transparency, and data privacy.

Psychiatrists-in-training typically learn that assessments of suicide risk should culminate in a probability judgment expressed as “low,” “moderate,” or “high.” This way of formulating risk has predominated in psychiatric education and practice, despite little evidence for its validity, reliability, or utility. We present a model for teaching and communicating suicide risk assessments without categorical predictions. Instead, we propose risk formulations which synthesize data into four distinct judgments to directly inform intervention plans: (1) risk status (the patient’s risk relative to a specified subpopulation), (2) risk state (the patient’s risk compared to baseline or other specified time points), (3) available resources from which the patient can draw in crisis, and (4) foreseeable changes that may exacerbate risk. An example case illustrates the conceptual shift from a predictive to a preventive formulation, and we outline steps taken to implement the model in an academic psychiatry setting. Our goal is to inform educational leaders, as well as individual educators, who can together cast a prevention-oriented vision in their academic programs.

Suicide has been a leading manner of death for US Air Force personnel in recent years. Universal prevention programs that reduce suicidal thoughts and behaviors in military populations have not been identified. To determine whether the Wingman-Connect program for Airmen-in-training reduces suicidal ideation, depression, and occupational problems compared with a stress management program and to test the underlying network health model positing that cohesive, healthy units are protective against suicidal ideation. This cluster randomized clinical trial was conducted from October 2017 to October 2019 and compared classes of personnel followed up for 6 months. The setting was a US Air Force technical training school, with participants studied to their first base assignment, whether US or international. Participants in 216 classes were randomized, with an 84% retention rate. Data analysis was performed from November 2019 to May 2020. The Wingman-Connect program used group skill building for cohesion, shared purpose, and managing career and personal stressors (3 blocks of 2 hours each). Stress management training covered cognitive and behavioral strategies (2 hours). Both conditions had a 1-hour booster session, plus text messages. The primary outcomes were scores on the suicidal ideation and depression scales of the Computerized Adaptive Test for Mental Health and self-reports of military occupational impairment. Class network protective factors hypothesized to mediate the effect of Wingman-Connect were assessed with 4 measures: cohesion assessed perceptions that classmates cooperate, work well together, and support each other; morale was measured with a single item used in other studies with military samples; healthy class norms assessed perceptions of behaviors supported by classmates; and bonds to classmates were assessed by asking each participant to name classmates whom they respect and would choose to spend time with. A total of 215 classes including 1485 individuals (1222 men [82.3%]; mean [SD] age, 20.9 [3.1] years) participated; 748 individuals were enrolled in the Wingman-Connect program and 737 individuals were enrolled in the stress management program. At 1 month, the Wingman-Connect group reported lower suicidal ideation severity (effect size [ES], -0.23; 95% CI, -0.39 to -0.09; P = .001) and depression symptoms (ES, -0.24; 95% CI, -0.41 to -0.08; P = .002) and fewer occupational problems (ES, -0.14; 95% CI, -0.31 to -0.02; P = .02). At 6 months, the Wingman-Connect group reported lower depression symptoms (ES, -0.16; 95% CI, -0.34 to -0.02; P = .03), whereas the difference in suicidal ideation severity was not significant (ES, -0.13; 95% CI, -0.29 to 0.01; P = .06). The number needed to treat to produce 1 fewer participant with elevated depression at either follow-up point was 21. The benefits of the training on occupational problems did not extend past 1 month. The Wingman-Connect program strengthened cohesive, healthy class units, which helped reduce suicidal ideation severity (estimate, -0.035; 95% CI, -0.07 to -0.01; P = .02) and depression symptom scores (estimate, -0.039; 95% CI, -0.07 to -0.01; P = .02) at 1 month. Wingman-Connect is the first universal prevention program to reduce suicidal ideation and depression symptoms in a general Air Force population. Group training that builds cohesive, healthy military units is promising for upstream suicide prevention and may be essential for ecological validity. Extension of the program to the operational Air Force is recommended for maintaining continuity and testing the prevention impact on suicidal behavior. ClinicalTrials.gov Identifier: NCT04067401.

To develop and refine interventions to prevent youth suicide, knowledge is needed about specific processes that reduce risk at a population level. Using a cross-sectional design, the present study tested hypotheses regarding associations between self-reported suicide attempts, emotion regulation difficulties, and positive youth–adult relationships among 7,978 high-school students (48.6 % male, 49.9 % female) in 30 high schools from predominantly rural, low-income communities. 683 students (8.6 %) reported a past-year suicide attempt. Emotion regulation difficulties and a lack of trusted adults at home and school were associated with increased risk for making a past-year suicide attempt, above and beyond the effects of depressive symptoms and demographic factors. The association between emotion regulation difficulties and suicide attempts was modestly lower among students who perceived themselves as having higher levels of trusted adults in the family, consistent with a protective effect. Having a trusted adult in the community (outside of school and family) was associated with fewer suicide attempts in models that controlled only for demographic covariates, but not when taking symptoms of depression into account. These findings point to adolescent emotion regulation and relationships with trusted adults as complementary targets for suicide prevention that merit further intervention studies. Reaching these targets in a broad population of adolescents will require new delivery systems and “option rich” (OR) intervention designs.

The permeability of metallic and ceramic open-cell foams prepared by the gelcasting technique was assessed by fitting of Forchheimer’s equation to experimental pressure drop curves. The ceramic composition was based on pure hydroxyapatite, while the metallic composition was based on titanium metal. Experimental Darcian ( k 1 ) and non-Darcian ( k 2 ) permeability constants displayed values in the range 0.40–3.24 × 10 −9 m 2 and 3.11–175.8 × 10 −6 m respectively. Tortuosity was evaluated by gas diffusion experiments and ranged from 1.67 to 3.60, with porosity between 72 and 81% and average hydraulic pore size between 325 and 473 μm. Such features were compared to data reported in the literature for cancellous bones and synthetic scaffolds for bone graft. A detailed discussion concerning the limitations of Darcy’s law for fitting laboratory data and for predicting fluid flow through scaffolds in real biomedical applications is also performed. Pore size was obtained by image analysis and was also derived from permeation-absorption-diffusion experiments. In both cases, values were within the range expected for porous scaffolds applications.