Stitching and registering highly multiplexed whole-slide images of tissues and tumors using ASHLAR.

MOTIVATION: Stitching microscope images into a mosaic is an essential step in the analysis and visualization of large biological specimens, particularly human and animal tissues. Recent approaches to highly multiplexed imaging generate high-plex data from sequential rounds of lower-plex imaging. These multiplexed imaging methods promise to yield precise molecular single-cell data and information on cellular neighborhoods and tissue architecture. However, attaining mosaic images with single-cell accuracy requires robust image stitching and image registration capabilities that are not met by existing methods. RESULTS: We describe the development and testing of ASHLAR, a Python tool for coordinated stitching and registration of 103 or more individual multiplexed images to generate accurate whole-slide mosaics. ASHLAR reads image formats from most commercial microscopes and slide scanners, and we show that it performs better than existing open-source and commercial software. ASHLAR outputs standard OME-TIFF images that are ready for analysis by other open-source tools and recently developed image analysis pipelines. AVAILABILITY AND IMPLEMENTATION: ASHLAR is written in Python and is available under the MIT license at https://github.com/labsyspharm/ashlar. The newly published data underlying this article are available in Sage Synapse at https://dx.doi.org/10.7303/syn25826362; the availability of other previously published data re-analyzed in this article is described in Supplementary Table S4. An informational website with user guides and test data is available at https://labsyspharm.github.io/ashlar/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

High Temperature Chemistry of Chlorinated Acenaphthylene. 3C Bay Acetylene Additions and Annealing by Five-Membered Ring Shifts.

Experimental and theoretical results concerning the growth and isomerization of chlorinated acenaphthylene, C12H8, during the pyrolysis of chlorohydrocarbons are presented here. A fullerene subunit, C12H8, is a useful system to investigate regarding C60 formation. However, direct experimental observation of isomerization and annealing processes in particular are difficult to confirm due to the high symmetry of the parent molecule. Chlorination lowers the symmetry, essentially labeling carbon atoms, allowing growth and isomerization to be followed directly. Pyrolysis of dichloro- and trichloroethylene, and their copyrolyses with trichlorobenzenes, provides an efficient and general source of chlorinated acenaphthylenes in a range of degrees of chlorination and over a number of unique congeners. Analysis of congener yields as a function of reagents employed, guided by DFT/B3LYP/6-311G(d,p) level calculations, strongly suggests that C2 addition across three-carbon bays in naphthalene is a major driver of growth. Additionally, extremely facile five-membered ring shifts are operative, with chlorine promoting isomerization. Theoretical study of C16H10- and C18H10-based congeners indicate that this is a general phenomenon, and with chlorine also favoring internal cyclopentafused rings in addition to increased isomerization rates, this suggests halogen moieties may be an important feature for efficient fullerene growth.

Effects of Cognitive Behavioral Stress Management on Negative Mood and Cardiac Autonomic Activity in ICD Recipients.

BACKGROUND: Behavioral intervention studies in patients with an implantable cardioverter-defibrillator (ICD) show promise in improving psychosocial outcomes but inconclusive effects on cardiovascular outcome. We assessed the effects of cognitive behavioral stress management (CBSM) on mood state and potentially arrhythmogenic cardiovascular responses to mental stress in ICD patients, in support of further larger scale arrhythmia trials. METHODS: A total of 103 ICD recipients were randomly assigned to 10-week programs of CBSM or "Patient Education" (ED). Of these, 83 patients continued to either CBSM (n = 44) or ED (n = 39) intervention. Study end points were mood change, heart rate variability (HRV), double product elevation (DP = heart rate × systolic blood pressure) by math and anger-recall stress, and arrhythmia up to 6 months follow-up. RESULTS: Adjusting for multiple testing, CBSM was associated with moderate effect size reductions in tension/anxiety (P = 0.010), anger/hostility (P = 0.020), perceived stress (P = 0.037), and total mood disturbance (P = 0.025), greatest immediately following intervention (P < 0.05), and partially attributable to increased negative mood following ED (P < 0.01). No significant intervention effects on high frequency or low frequency spectral power of HRV, DP responses, or cardiac arrhythmias were demonstrated. CONCLUSIONS: CBSM intervention in ICD recipients resulted in reduced anxiety, anger, and perceived stress, not sustained at 6 months follow-up, and without conclusive effect on cardiac autonomic or hemodynamic responses to mental stress, or arrhythmia. Findings support conduct of larger behavioral intervention arrhythmia trial, with consideration of reinforcement training and targeting of subgroup responders to therapy.

Experimental and theoretical studies into the formation of C4-C6 products in partially chlorinated hydrocarbon pyrolysis systems: a probabilistic approach to congener-specific yield predictions.

This work presents a study of the pyrolytic formation of vinylacetylene and benzene congeners formed from chlorinated hydrocarbon precursors, a complex, multipath polymerization system formed in a monomer-rich environment. (Co-)pyrolyses of dichloro- and trichloroethylene yield a rich array of products, and assuming a single dominant underlying growth mechanism, this (on comparing expected and observed products) allows a number of potentially competing channels to C4 and C6 products to be ruled out. Poor congener/isomer descriptions rule out even-carbon radical routes, and the absence of C3 and C5 products rule out odd-carbon processes. Vinylidenes appear unable to describe the increased reactivity of acetylenes with chlorination noted in our experiments, leaving molecular acetylene dimerization processes and, in C6 systems, the closely related Diels-Alder cyclization as the likely reaction mechanism. The feasibility of these routes is further supported by ab initio calculations. However, some of the most persuasive evidence is provided by congener-specific yield predictions enabled by the construction of a probability tree analogue of kinetic modeling. This approach is relatively quick to construct, provides surprisingly accurate predictions, and may be a very useful tool in screening for important reaction channels in poorly understood congener- or isomer-rich reaction systems.

Role of hydrogen abstraction acetylene addition mechanisms in the formation of chlorinated naphthalenes. 1. A quantum chemical investigation.

The addition of chloroacetylene or tetrachlorovinylacetylene to 2,4,5-trichlorophenyl radicals, leading to the formation of tetra-, penta-, and hexachloronaphthalene congeners, has been explored at the M06-2X/6-311+G(3df,3p)//B3LYP/6-31G(d) level of theory. The accuracy of this method was justified by comparing the barriers of several pertinent reactions against energies from single point calculations at the B3LYP/cc-pVDZ, CCSD(T)/6-31G(d), and G2MS levels. Bittner-Howard and Frenklach hydrogen abstraction acetylene addition mechanisms were developed, as was a channel based on acetylene additions to chlorinated [4.2.0]octa-1,3,5-trien-7-yl congeners. While the latter channel exhibits relatively high C2HCl addition barriers and may be a minor growth channel at best, both the Bittner-Howard and Frenklach sequences appear facile. In all mechanisms, the additions of C2HCl leading to a ß-chlorinated adduct is favored by ∼15 kJ mol(-1) relative to the α-chlorinated analogue, and the addition products typically access a variety of facile cyclization channels. The α-chlorinated product of C2HCl addition to 2,4,5-trichlorophenyl, however, undergoes a particularly rapid Cl-loss leading to 1-ethynyl-2,4,5-trichlorobenzene, effectively shutting down further growth. Generalization implies that α-chlorinated C6H5-CH═CH congeners do not participate in growth reactions. Addition of 2,4,5-trichlorophenyl to the C≡C bond of tetrachlorovinylacetylene and subsequent cyclization is found to be a facile route to hexachloronaphthalene formation and may be operative in fully chlorinated systems where the C6Cl5-CCl═CCl congeners cannot participate in the major growth processes.

Role of hydrogen abstraction acetylene addition mechanisms in the formation of chlorinated naphthalenes. 2. Kinetic modeling and the detailed mechanism of ring closure.

The dominant formation mechanisms of chlorinated phenylacetylenes, naphthalenes, and phenylvinylacetylenes in relatively low pressure and temperature (∼40 Torr and 1000 K) pyrolysis systems are explored. Mechanism elucidation is achieved through a combination of theoretical and experimental techniques, the former employing a novel simplification of kinetic modeling which utilizes rate constants in a probabilistic framework. Contemporary formation schemes of the compounds of interest generally require successive additions of acetylene to phenyl radicals. As such, infrared laser powered homogeneous pyrolyses of dichloro- or trichloroethylene were perturbed with 1,2,4- or 1,2,3-trichlorobenzene. The resulting changes in product identities were compared with the major products expected from conventional pathways, aided by the results of our previous computational work. This analysis suggests that a Bittner-Howard growth mechanism, with a novel amendment to the conventional scheme made just prior to ring closure, describes the major products well. Expected products from a number of other potentially operative channels are shown to be incongruent with experiment, further supporting the role of Bittner-Howard channels as the unique pathway to naphthalene growth. A simple quantitative analysis which performs very well is achieved by considering the reaction scheme as a probability tree, with relative rate constants being cast as branching probabilities. This analysis describes all chlorinated phenylacetylene, naphthalene, and phenylvinylacetylene congeners. The scheme is then tested in a more general system, i.e., not enforcing a hydrogen abstraction/acetylene addition mechanism, by pyrolyzing mixtures of di- and trichloroethylene without the addition of an aromatic precursor. The model indicates that these mechanisms are still likely to be operative.

A Rapid Evidence Assessment on The Effectiveness of Interventions for Autistic Adolescents with Harmful Sexual Behaviors.

The management and treatment of harmful sexual behaviors (HSBs) in autistic adolescents is a complex area of research and clinical practice. Autistic adolescents face unique challenges in understanding social and sexual interactions, putting them at a higher risk of engaging in HSBs. Existing research on interventions for HSBs among autistic adults is growing, but evidence for adolescents is not well understood. Thus, understanding the effectiveness of interventions targeting HSBs in autistic adolescents is crucial. We conducted a rapid evidence assessment to review peer-reviewed research on the effectiveness of interventions for autistic adolescents at risk of or engaging in HSBs. In all, 12 studies met the criteria for review. Inclusion criteria required articles to be published in a peer-reviewed journal, be related to HSB prevention and intervention in adolescents aged 12 to 18 with autism spectrum disorder, be written in English, and include original data. Six databases were used, and we screened the titles and abstracts of 34 studies. The reviewed studies described cognitive-behavioral therapy, pharmacological interventions, family involvement, and multidisciplinary team approaches in addressing HSBs. However, the literature has significant limitations and we suggest that the literature is not robust enough to indicate a promising evidence-based approach for interventions for autistic adolescents who are at risk of or who display and engage in HSBs, and the findings are not transferable to practice. Additional research is required to better prepare healthcare professionals for addressing HSBs in autistic adolescents.

The safeguarding capability of adults in Catholic Church ministries: A global perspective.

BACKGROUND: In the wake of historical sexual abuse across the Catholic Church globally, the Church continues to develop policies and processes to prevent and respond to child sexual abuse, including supporting the skills, knowledge, and confidence of members of the Church. OBJECTIVE: We investigated the safeguarding capabilities of a range of people with different roles within Catholic Church ministries in various countries. PARTICIPANTS AND SETTING: Our 184 participants included lay people, religious men and women, school staff, safeguarding officers and tertiary students associated with the Catholic Church. Data were collected across seven different countries. METHODS: We measured the awareness, confidence, attitudes, and knowledge of participants and examined differences between participants in different roles within the Church and different countries through General Linear Models. RESULTS: We found varying levels of awareness, confidence, attitudes, and knowledge regarding sexual abuse prevention and safeguarding. We pinpointed the significant differences in three of these domains (confidence, attitudes, and knowledge) both between people with different roles in the church worldwide, but also between the countries from which participants came from. CONCLUSIONS: We found that people in various countries and roles within the Church are at different stages of their safeguarding journey. Some are still understanding their roles (attitudes), some are still learning about how it is operationalised (awareness), and others are acquiring skills that will prepare them for enacting safeguarding policies and practices (confidence).

Engaging Parents in Child-Focused Child Sexual Abuse Prevention Education Strategies: A Systematic Review.

Parents are their children's first teachers and there are long-standing calls for their involvement in child sexual abuse prevention. In this rapid systematic review, we asked the following questions: what rationales are used to justify parental involvement in child-focused child sexual abuse (CSA) prevention programs? what approaches are used for parental engagement in child-focused CSA prevention programs? and what are the facilitators and barriers to parental involvement in child-focused CSA prevention programs? We searched CINAHL, Cochrane, ERIC, Medline, PsycInfo, Scopus, and SocINDEX in May 2021. A total of 57 papers met our inclusion criteria, comprised of 50 empirical studies, and 7 program descriptions. Rationales for parental involvement included monitoring and shaping parental attitudes toward CSA program delivery in schools; reinforcing children's learning at home; promoting parent-child communication about CSA prevention; building parent capacity to respond to child disclosures; and supporting program delivery for preschoolers. Types of parental involvement included the following: communication, learning at home, volunteering, decision-making, and collaboration with the community. Barriers to parent involvement included ineffective program engagement modalities, and parental fears and misconceptions.

Molecular mechanisms in the pyrolysis of unsaturated chlorinated hydrocarbons: formation of benzene rings. 1. Quantum chemical studies.

Analogues of important aromatic growth mechanisms in hydrocarbon pyrolysis and combustion systems are extended to chlorinated systems. We consider the addition of C2Cl2 to both C4Cl3 and C4Cl5 radicals at the M06-2X/6-311+G(3df,3p)//B3LYP/6-31G(d) level of theory, and we demonstrate that these reaction systems have much in common with those of nonchlorinated species. In particular, we find that these radicals appear to lead preferentially to fulvenes, and not to the observed aromatic products, as is found in nonchlorinated systems. We have therefore also considered nonradical C4/C2 channels by way of Diels-Alder cyclization of C4Cl4/C2Cl2 and C4H2Cl2/C2HCl pairs to describe aromatic formation. While the latter pair readily leads to the formation of partially chlorinated benzenes, the fully chlorinated congeners are sterically prohibited from ring closing directly; this leads to a series of novel rearrangement processes which predict the formation of hexachloro-1,5-diene-3-yne, in addition to hexachlorobenzene, in good agreement with experiment. This suggests, for the first time, that facile nonradical routes to aromatic formation are operative in partially and fully chlorinated pyrolysis and combustion systems.

Molecular mechanisms in the pyrolysis of unsaturated chlorinated hydrocarbons: formation of benzene rings. 2. Experimental and kinetic modeling studies.

The mechanism of formation of benzene rings during the pyrolysis of dichloro- and trichloroethylenes has been investigated by the method of laser powered homogeneous pyrolysis coupled with product analysis by gas chromatography. Additionally, selected (co)pyrolyses between the chlorinated ethylenes, CH2Cl2, C4Cl4, C4Cl6, and C2H2 have been performed to explicitly probe the roles of 2C3 and C4/C2 reaction pairs in aromatic growth. The presence of odd-carbon products in neat C4Cl6 pyrolyses indicates that 2C3 processes are operative in these systems; however, comparison with product yields from C2HCl3 suggests that C4/C2 processes dominate most other systems. This is further evidenced by an absence of C3 and other odd-carbon species in (co)pyrolyses with dichloromethane which should seed C3-based growth. The reactions of perchlorinated C4 species C4Cl5, C4Cl3, and C4Cl4 with C2Cl2 were subsequently explored through extensive kinetic simulations of the possible reaction pathways based on previous kinetic models and the exhaustive quantum chemical investigations of our preceding work. The experimental and theoretical results strongly suggest that, at moderate temperatures, aromatic ring formation from chlorinated ethylenes normally follows a Diels-Alder coupling of C4 and C2 molecular units followed by internal shifts; the one exception is the C4Cl4 + C2Cl2 system, where steric factors lead to the formation of nonaromatic products. There is little evidence for radical-based routes in these systems.

A simple epidural simulator: a blinded study assessing the 'feel' of loss of resistance in four fruits.

CONTEXT: Complex epidural simulators are now available, but these are expensive and not widely available. Simple simulators using fruit have been described before. OBJECTIVE: To ascertain which easily available fruit would best simulate the 'feel' of loss of resistance experienced in epidural insertion and be used as a teaching tool. DESIGN: A single blinded study using four different fruits housed in a purpose-built box to conceal the identities of the fruits. The fruits were labelled A, B, C and D. SETTING: Two teaching hospitals in Glasgow, Scotland between 2006 and 2007. PARTICIPANTS: Fifty participants consisting of consultant anaesthetists, specialist registrars and senior house officers all with previous epidural experience. INTERVENTION: Insertion of a Tuohy needle into the four concealed fruits (orange, banana, kiwi and honeydew melon). Each participant then completed a questionnaire that included recording of the realism of the 'feel' of loss of resistance of each fruit. MAIN OUTCOME MEASURES: The 'feel' of loss of resistance for each fruit was scored on a 100-mm Visual Analogue Scale. A '0  mm' represented 'completely unrealistic feel' and '100  mm' represented 'indistinguishable feel from a real patient'. RESULTS: A total of 62.6% of participants recorded the banana as their first choice. This result was statistically significant after taking into account the grades of the participants, their years of experience, the needle gauge used and the participants' chosen technique. CONCLUSION: The banana is a cheap and easily available training tool to introduce novice anaesthetists to the feel of loss of resistance, which is best experienced before the first insertion of an epidural in a patient.

Complementary and Integrative Treatments for Attention-Deficit/Hyperactivity Disorder in Youth.

First-line psychopharmacologic and psychosocial treatments for attention-deficit/hyperactivity disorder in children are effective but limited by tolerability and accessibility problems. Many complementary and integrative strategies have been investigated as alternative or adjunctive treatments for the disorder, and the literature has progressed to meta-analyses for several. Although heterogeneity of study methods and risk of bias pervades the literature, we conclude that Omega-3 supplementation, dietary restriction of artificial food colorings, and physical activity can be considered evidence-based. Additionally, meditation, yoga, and sleep hygiene are safe, partially effective, cost effective and sensible adjunctive treatment strategies.

Safeguarding in Church: Children and Young People's Perceptions of Safety in Religious and Other Faith-Based Settings.

Organizations that interact with children and young people have a duty of care to ensure the safety of those children and young people from any manner of abuse, particularly from child sexual abuse. Faith-based ("religious") organizations are of particular interest due to the number of victims/survivors speaking out about their experiences of grooming, child sexual abuse, and other forms of harm in religious organizations. Focusing on addressing the risks and improving safeguarding efforts, prevention activities benefit from giving children agency and a voice. We conducted a study using two focus groups with children and young people involved with two different Christian denominations. We conducted activities and led discussions regarding their views about safety in the context of the faith-based organization with which they engage. Children and young people described different potentially unsafe situations, their likely frequency, and the level of impact such situations would have from their own point of view. They also described how they thought adults in their faith-based organization would see them. Thematic analysis of the data supported four themes related to young people's sense of safety: concerning behavior of adults and other young people, fear of judgment by others (adults and peers), sense of or lack of empowerment due to power dynamics, and the importance of a sense of "familiarity." Visual comparisons of the data on scatterplots suggested differences not only in the level of impact and frequency of potentially unsafe situations between young people and adults but also between the two denominations. Children and young people can provide a wealth of information regarding their safety concerns when involved in programs and services at faith-based organizations. Clergy and other faith-based organizational leaders should consider how the context in which young people are involved (including interdenominational and interfaith difference, as well as the diverse types of activities young people are involved with) can affect their safety concerns.

Systematic Review and Meta-Analyses: Safety and Efficacy of Complementary and Alternative Treatments for Pediatric Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: Complementary and alternative treatments (CATs) for ADHD have proliferated over the past decade; however, their safety and efficacy remain uncertain. We completed a systematic review and meta-analyses across CAT domains. METHODS: Systematic search and data extraction identified randomized controlled trials for pediatric ADHD (ages 3-19 years) that included probably blind ADHD symptom outcome measures. We evaluated basic (RCT of a CAT compared with sham/placebo, attention/active control, treatment as usual, and waitlist control), complementary (RCTs comparing an evidence-based treatment with a CAT and the same evidence-based treatment), and alternative (evidence-based treatment to CAT) efficacy. Random-effect meta-analyses were conducted when at least 3 blinded studies were identified for a specific CAT domain. RESULTS: Eighty-seven of 2253 nonduplicate screened manuscripts met inclusion criteria. No study reported significantly greater adverse effects for CATs than controls; naturopathy reported fewer adverse effects than evidence-based treatments but did not demonstrate basic efficacy. In the systematic review of basic efficacy, evidence of effectiveness was mixed but replicated previous evidence for the possible efficacy of cognitive training, neurofeedback, and essential fatty acid supplementation for certain patients. With respect to alternative and complementary efficacy, no CAT outperformed or enhanced evidence-based treatments (stimulant medications and behavioral therapy) when replication was required. Individual meta-analyses indicated that cognitive training was the only CAT that demonstrated overall basic efficacy ( SMD = 0.216; p = 0.032). CONCLUSION: Clinicians may cautiously recommend (but monitor) cognitive training when evidence-based treatments are not feasible or effective for a patient. Additional studies are needed to further understand the potential of CAT domains.

Vulnerable yet forgotten? A systematic review identifying the lack of evidence for effective suicide interventions for young people in contact with child protection systems.

Children and young people in out-of-home care are at a higher risk of suicide than young people not involved with child protection systems. Despite this, there is a lack of evidence of effective suicide prevention interventions for this vulnerable population. We reviewed the types of suicide prevention interventions that have been used and evaluated with children and young people and staff and carers in out-of-home care/child protection systems. We conducted a systematic review of existing literature using PRISMA guidelines. Only five studies met the inclusion criteria. Two evaluated youth-focused interventions: emotional intelligence therapy; and multidimensional treatment foster care, while three evaluated adult-focused "gatekeeper training." Youth-focused interventions led to reductions in suicidal thoughts (suicidal ideation), and adult-focused interventions led to increased knowledge, skills, and behaviors such as referring youth to supports. Only one study, one of the youth-focused ones, evaluated the impact of the intervention in terms of suicide attempts but found no reduction. Large numbers of children enter into care with a high risk of suicide. With the considerable overlap between the trauma characteristics and mental health needs of young people in out-of-home care and suicide risk factors in the general population of young people, we recommend developing (and evaluating) new or adapted existing suicide prevention interventions designed specifically for the out-of-home care context. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Second-Opinion Program for the Care of Youths Prescribed Five or More Psychotropics in Washington State.

This retrospective study describes a second-opinion review program for the care of children in Washington State who received Medicaid coverage and who were prescribed five or more psychotropic medications, primarily by mental health specialists. In total, 136 second-opinion reviews from 2013 and 169 from 2018 were included in this study. Attention-deficit hyperactivity disorder (ADHD), behavioral difficulties, anxiety, and trauma were prevalent among these children, and participants were commonly prescribed ADHD medications, selective serotonin reuptake inhibitors, and second-generation antipsychotics. The incidence of reviews remained stable over the two periods, but psychosocial treatment increased significantly over this time. This study sheds light on the initiation, maintenance, and identification of polypharmacy psychotropic regimens and highlights psychosocial treatment as an intervention that increases best practice care for at-risk patients.

Role of arachidonic acid, lipoxygenase, and mitochondrial depolarization in reperfusion arrhythmias.

We have sought evidence that arachidonic acid (AA) induces mitochondrial depolarization in isolated myocytes by a lipoxygenase (LOX)-dependent mechanism and that such depolarization might contribute to arrhythmogenesis following ischemia-reperfusion injury. A method was developed for measuring mitochondrial depolarization in isolated adult rat myocytes in suspension, using tetramethylrhodamine ethyl ester. The addition of AA to myocytes resulted in mitochondrial depolarization that was inhibited by the LOX inhibitor baicalein, by the reactive oxygen species (ROS) scavenger mercaptoproprionylglycine, and by the anion channel inhibitor diisothiocyanatostilbene-disulfonic acid (DIDS). AA induced mitochondrial uncoupling and mitochondrial ATPase activity in myocytes, but both were insensitive to baicalein. We conclude that the metabolic effect of AA in myocytes puts mitochondria into an energetically compromised state where membrane potential is easily changed by the DIDS-sensitive LOX/ROS-mediated opening of an inner membrane anion channel. In an in vivo anesthetized rat model of coronary artery occlusion, baicalein was found to strongly inhibit arrhythmias induced by ischemia-reperfusion injury. Arrhythmias following ischemia-reperfusion injury have been previously associated with DIDS-sensitive ROS-mediated mitochondrial depolarization, and free fatty acids including AA were previously found to accumulate during such injury. We therefore conclude that arrhythmias following ischemia-reperfusion injury might originate from mitochondrial depolarization mediated by LOX and AA.

Safeguarding Capabilities in Preventing Child Sexual Abuse: Exploratory Factor Analysis of a Scale Measuring Safeguarding Capabilities in Youth-Serving Organizations Workers.

Media reports and government enquiries have shone a spotlight on institutional child sexual abuse (CSA) globally. With youth-serving organizations seeking to identify how to improve policies and procedures developed to protect children, a gap exists in research and organizational quality assurance procedures. A new tool is needed to measure the capability of workers to implement and support effective child-safeguarding policies and practices. To address this, our aim was to develop the Safeguarding Capabilities in Preventing Child Sexual Abuse Scale. Participants (n = 345) from a range of youth-serving sectors in Australia answered 128 questions. Using exploratory factor analysis to assess the underlying factor structure and refine the item pool, items loaded onto four factors. Reliability coefficients ranged from .68 to .95. Results showed that knowledge, attitudes, self-efficacy to take action, and awareness are all key capabilities related to creating conditions of safety for children and young people and preventing CSA in youth-serving organizations.