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Abstract Cochlear implants (CI) are one of the most successful treatments available to enable individuals with severe to profound hearing loss to regain access to the world of sound. This is accomplished through the electrical stimulation of the auditory nerve using electrodes implanted inside the cochlea. The use of subjective user feedback makes the process of fitting these devices much more challenging in cases where users are not able to actively or accurately report their experience (e.g. pediatrics), making an objective measurement that reflects the accuracy or effectiveness of a program quite attractive. We recorded one objective measure, the electrically-stimulated cortical auditory evoked potential (eCAEP), non-invasively using the CI in response to a simulated speech sound in seven adult participants and compared it to their eCAEP recorded using a scalp EEG set-up. The eCAEPs recorded with CI electrodes were comparable to scalp recorded eCAEPs (grand mean cross-correlation of r = 0.83, individual mean cross-correlations ranged from 0.13 to 0.70). Evoked potential peaks P1, N1 and P2 showed no significant latency difference based on if the eCAEP was recorded on the scalp or using the CI. The eCAEP waveforms recorded via the CI appear to converge in a distinct P1-N1-P2 waveform by as early as 130 sweeps. In conclusion, in this study we show the feasibility of recording the eCAEP directly through the CI system, which could potentially be used to guide CI fitting and track auditory cortex development in response to CI use.

BackgroundThe increasing use of social media to share lived and living experiences of substance use presents a unique opportunity to obtain information on side effects, use patterns, and opinions on novel psychoactive substances. However, due to the large volume of data, obtaining useful insights through natural language processing technologies such as large language models is challenging. ObjectiveThis paper aims to develop a retrieval-augmented generation (RAG) architecture for medical question answering pertaining to clinicians’ queries on emerging issues associated with health-related topics, using user-generated medical information on social media. MethodsWe proposed a two-layer RAG framework for query-focused answer generation and evaluated a proof of concept for the framework in the context of query-focused summary generation from social media forums, focusing on emerging drug-related information. Our modular framework generates individual summaries followed by an aggregated summary to answer medical queries from large amounts of user-generated social media data in an efficient manner. We compared the performance of a quantized large language model (Nous-Hermes-2-7B-DPO), deployable in low-resource settings, with GPT-4. For this proof-of-concept study, we used user-generated data from Reddit to answer clinicians’ questions on the use of xylazine and ketamine. ResultsOur framework achieves comparable median scores in terms of relevance, length, hallucination, coverage, and coherence when evaluated using GPT-4 and Nous-Hermes-2-7B-DPO, evaluated for 20 queries with 76 samples. There was no statistically significant difference between GPT-4 and Nous-Hermes-2-7B-DPO for coverage (Mann-Whitney U=733.0; n1=37; n2=39; P=.89 two-tailed), coherence (U=670.0; n1=37; n2=39; P=.49 two-tailed), relevance (U=662.0; n1=37; n2=39; P=.15 two-tailed), length (U=672.0; n1=37; n2=39; P=.55 two-tailed), and hallucination (U=859.0; n1=37; n2=39; P=.01 two-tailed). A statistically significant difference was noted for the Coleman-Liau Index (U=307.5; n1=20; n2=16; P

A continuous infusion of flumazenil may be needed to mitigate prolonged sedation from benzodiazepines. Some benzodiazepines have extended durations of action. We describe a cirrhotic patient who was on an infusion of flumazenil for 37 days due to prolonged sedation from chlordiazepoxide. An 80-year-old man with alcohol use disorder and cirrhosis presented to the emergency department for abdominal distention and was admitted for management of ascites. On hospital day (HD) 2, he developed alcohol withdrawal, for which he received 350 mg of chlordiazepoxide over 48 h. Without receiving further sedatives, the patient remained deeply sedated. A bolus dose of flumazenil on HD 18 improved his mental status, allowing him to follow commands. A flumazenil infusion was started on HD 18. Serum chlordiazepoxide and nordiazepam concentrations were 230 ng/mL and 265 ng/mL, respectively, on hospital day 21, despite no additional doses since HD 4. The infusion was stopped 37 days after initiation (HD 55) and the patient was discharged on HD 76 to subacute rehabilitation. Patients with cirrhosis may develop prolonged sedation from chlordiazepoxide. This patient had detectable metabolites of chlordiazepoxide weeks after his last dose, which was associated with prolonged sedation managed with flumazenil infusion.

Purpose: This study assesses the efficacy and safety of self-expandable (SE) versus balloon-expandable (BE) stent grafts for managing visceral artery aneurysms (VAAs), focusing on procedural success and complication rates. Materials and Methods: We conducted a retrospective analysis of VAA patients treated at our institution from April 2006 to September 2021. The study reviewed patient demographics, aneurysm characteristics, treatment details, and outcomes, including endoleaks. Results: Among the 23 patients analyzed, splenic artery aneurysms represented 44% of cases. Fifteen patients were treated with balloon-expandable stent grafts (BE SGs), and eight patients were treated with self-expandable stent grafts (SE SGs). For saccular aneurysms, the average neck size was 10.10 ± 8.70 mm in the BE group versus 18.50 ± 3.40 mm in the SE group (p = 0.23), with an average sac size of 20.10 ± 18.9 mm in the BE group versus 15.60 ± 12.7 mm in the SE group (p = 0.16). The average sac-to-neck ratio was 1.69 ± 2.23 in the BE group versus 1.38 ± 0.33 in the SE group (p = 0.63). The BE group exhibited a significantly higher endoleak rate (60%) compared to the SE group (12.5%; p = 0.03). Conclusions: While further investigation is needed to fully assess the outcomes of stent graft treatment for VAAs, initial data show a significantly higher endoleak rate with BE SGs compared to SE SGs. The SE SGs may offer better outcomes due to their superior ability to conform to tortuous and mobile visceral arteries.

Abstract Background Expert consensus recommends prescription opioid safety counseling be provided when prescribing an opioid. This may be especially important for youth with preexistent alcohol and other drug (AOD) use who are at higher risk of developing opioid use disorder. This study examined the frequency that adolescent trauma patients prescribed opioids at hospital discharge received counseling and if this differed by adolescents’ AOD use. Method This study was embedded within a larger prospective stepped-wedge type III hybrid implementation study of AOD screening across a national cohort of pediatric trauma centers. Data were collected during 2018–2021 from admitted adolescent trauma patients (12–17 yo) at seven centers. Patient data were extracted from the electronic health record (EHR) on any prescribed discharged opioids, documentation of counseling delivered on prescribed opioid, who delivered counseling, and patients’ AOD screening results. Additionally, adolescents received an online survey within 30 days of hospital discharge that included asking about hospital discussions on safe use of prescription pain medication. Results Of the 247 adolescent trauma patients enrolled, 158 completed the 30-day survey. AOD screening results were documented in the EHR for 139 patients (88%), with 69 (44.1%) screening AOD-positive. Opioids at discharge were prescribed to 86 (54.4%) adolescent patients, with no significant difference between those screened AOD-positive and AOD-negative (42.4% vs. 46.3%, p = 0.89). Counseling was documented in the EHR for 30 (34.9%) of those prescribed an opioid and was not significantly different by sex, age, race, ethnicity or between adolescent patients with documentation of AOD use (29.3%) versus those who did not (33.3%, p = 0.71). According to the adolescent survey, among those prescribed an opioid, 61.2% reported someone had talked with them about safe use of newly prescribed pain medications with again no difference between AOD-positive and AOD-negative screening results (p = 0.34). Conclusions Although adolescent trauma patients recalled discussions on safe use of prescribed pain medication more often than was documented in the EHR, these discussions were not universal and did not differ if adolescents had screened positive or negative for AOD use as documented in the EHR. Trial Registry: clinicaltrials.gov NCT03297060.

Abstract Background Juvenile legal involved youth (JLIY) experience disproportionately high rates of suicidal and self-injurious thoughts and behaviors (SSITB). Many JLIY lack access to evidence-based treatment specifically designed to treat SSITB, thereby increasing the overall risk of suicide. The overwhelming majority of JLIY are not placed in secure facilities and almost all incarcerated youth are eventually released to the community. Consequently, SSITB are a major concern of JLIY residing in the community and it is critical that this population has access to evidence-based treatment for SSITB. Unfortunately, most community mental health providers who treat JLIY have not been trained in evidence-based interventions that are specifically designed to SSITB, which often leads to youth experiencing prolonged periods of SSITB. Training community mental health providers who serve JLIY in the detection and treatment of SSITB shows promise for decreasing the overall suicide risk for JLIY. Methods The current proposal aims to reduce SSITB among JLIY, and thus reduce mental health disparities in this vulnerable and underserved youth population, by increasing access to evidence-based treatment strategies specifically designed to treat SSITB behaviors. We will implement an agency-wide training among at least 9 distinct community mental health agencies that serve JLIY referred to treatment by a statewide court system in the Northeast. Agencies will be trained in an adapted version of the COping, Problem Solving, Enhancing life, Safety, and Parenting (COPES+) intervention. Training will be implemented via a cluster-randomized stepped wedge trial that proceeds through multiple phases. Discussion This research engages multiple systems (i.e., juvenile legal and mental health systems) serving JLIY and has the potential to directly inform treatment practices in juvenile legal and mental health systems. The current protocol has significant public health implications as the primary goals are to reduce SSITB among adolescents involved in the juvenile legal system. By implementing a training protocol with community-based providers to help them learn an evidence-based intervention, this proposal aims to reduce mental health disparities in a marginalized and underserved population. Trial registration osf.io/sq9zt

Abstract Background Emergency departments (EDs) are important venues for the distribution of naloxone to patients at high risk of opioid overdose, but less is known about patient perceptions on naloxone or best practices for patient education and communication. Our aim was to conduct an in-depth exploration of knowledge and attitudes toward ED naloxone distribution among patients who received a naloxone prescription. Methods We conducted semi-structured telephone interviews with 25 adult participants seen and discharged from three urban, academic EDs in Philadelphia, PA, with a naloxone prescription between November 2020 and February 2021. Interviews focused on awareness of naloxone as well as attitudes and experiences receiving naloxone in the ED. We used thematic content analysis to identify key themes reflecting patient attitudes and experiences. Results Of the 25 participants, 72% had previously witnessed an overdose and 48% had personally experienced a non-fatal overdose. Nineteen participants (76%) self-disclosed a history of substance use or overdose, and one reported receiving an opioid prescription during their ED visit and no history of substance use. In interviews, we identified wide variability in participant levels of knowledge about overdose risk, the role of naloxone in reducing risk, and naloxone access. A subset of participants was highly engaged with community harm reduction resources and well versed in naloxone access and use. A second subset was familiar with naloxone, but largely obtained it through healthcare settings such as the ED, while a final group was largely unfamiliar with naloxone. While most participants expressed positive attitudes about receiving naloxone from the ED, the quality of discussions with ED providers was variable, with some participants not even aware they were receiving a naloxone prescription until discharge. Conclusions Naloxone prescribing in the ED was acceptable and valued by most participants, but there are missed opportunities for communication and education. These findings underscore the critical role that EDs play in mitigating risks for patients who are not engaged with other healthcare or community health providers and can inform future work about the effective implementation of harm reduction strategies in ED settings.

Abstract Objectives Buprenorphine is a highly effective medication for the treatment of opioid use disorder, but it can cause precipitated withdrawal (PW) from opioids. Incidence, risk factors, and best approaches to management of PW are not well understood. Our objective was to describe adverse outcomes after buprenorphine administration among emergency department (ED) patients and assess whether they met the criteria for PW. Methods This study is a case series using retrospective chart review in a convenience sample of patients from 3 hospitals in an urban academic health system. This study included patients who were reported by clinicians as potential cases of PW. Relevant clinical data were abstracted from the electronic health record using a structured retrospective chart review instrument. Results A total of 13 cases were included and classified into the following 3 categories: (1) PW after buprenorphine administration consistent with guidelines (n = 5), (2) PW after deviating from guidelines (n = 4), and (3) protracted opioid withdrawal with no increase in Clinical Opiate Withdrawal Scale score (n = 4). A total of 11 patients had urine drug testing positive for fentanyl, and 11 patients received additional doses of buprenorphine for symptom management. Of the patients, 5 had self‐directed hospital discharges, and 6 were ultimately discharged with prescriptions for buprenorphine. Conclusions Cases of adverse outcomes after buprenorphine administration in the ED and hospital meet criteria for PW, although some cases may have represented protracted opioid withdrawal. Further investigation into the incidence, risk factors, management of PW as well as patient perspectives is needed to expand and sustain the use of buprenorphine in EDs and hospitals.

BackgroundSuicide and suicidal behavior during adolescence have been steadily increasing over the past two decades. The preponderance of interventions focuses on crisis intervention, underlying psychiatric disorders, regulating negative affect, and reducing cognitive distortions. However, low positive affectivity may be a mechanism that contributes to adolescent suicidal ideation and behaviors independent of other risk factors. Skills to Enhance Positivity (STEP) is an acceptance-based intervention, designed to increase attention to, and awareness of, positive affect and positive experiences. Results from a pilot RCT demonstrated engagement of the target (positive affect) and a decrease in clinical outcomes (suicidal events; i.e., either a suicide attempt or an emergency intervention for an acute suicidal crisis), providing support to test the clinical effectiveness of STEP in a larger clinical trial with clinical staff implementing the intervention.ObjectiveTo test the effectiveness of STEP, compared to Enhanced Treatment as Usual (ETAU), in reducing suicidal events and ideation in adolescents admitted to inpatient psychiatric care due to suicide risk. We hypothesize that those randomized to STEP, compared to ETAU, will have lower rates of suicide events, active suicidal ideation (SI), and depressed mood over the 6-month follow-up period. We hypothesize that those randomized to STEP, compared to ETAU, will demonstrate greater improvement in the hypothesized mechanisms of attention to positive affect stimuli and gratitude and satisfaction with life.MethodsParticipants will be randomized to either STEP or ETAU. STEP consists of four in-person sessions focused on psychoeducation regarding positive and negative affect, mindfulness meditation, gratitude, and savoring. Mood monitoring prompts and skill reminders will be sent via text messaging daily for the first month post-discharge and every other day for the following two months. The ETAU condition will receive text-delivered reminders to use a safety plan provided at discharge from the hospital and healthy habits messages, matched in frequency to the STEP group. This trial was registered on 6 August 2021 (ClinicalTrials.gov NCT04994873).ResultsThe STEP protocol was approved by the National Institute of Mental Health (NIMH) Data and Safety Monitoring Board on March 4, 2022. The RCT is currently in progress.DiscussionThe STEP protocol is an innovative, adjunctive treatment that has the potential to have positive effects on adolescent suicidal ideation and attempts beyond that found for standard treatment alone.

Objectives The primary objective of this study was to examine opioid prescription frequency and identify differences across a national cohort of pediatric trauma centers in rates of prescribing opioids to injured adolescents at discharge.Methods This was a retrospective observational study using electronic health records of injured adolescents (12–17 years) admitted to one of 10 pediatric trauma centers.Results Of the 1345 electronic health records abstracted, 720 (53.5%, 95% CI 50.8 to 56.2) patients received opioid prescriptions at discharge with variability across sites (28.6%–72%). There was no association between patient factors and frequency of prescribing opioids. Center’s trauma volume was significantly positively correlated with a higher rate of opioid prescribing at discharge (r=0.92, p=0.001). There was no significant difference between the frequency of opioid prescriptions at discharge among alcohol and other drugs (AOD)-positive patients (53.8%) compared with AOD-negative patients (53.5%).Conclusions Across a sample of 10 pediatric trauma centers, just over half of adolescent trauma patients received an opioid prescription at discharge. Prescribing rates were similar for adolescent patients screening positive for AOD use and those screening negative. The only factor associated with a higher frequency of prescribing was trauma center volume. Consensus and dissemination of outpatient pain management best practices for adolescent trauma patients is warranted.Level of evidence III—prognostic.Trial registration number NCT03297060.

Objectives The present research examines genomics and in vivo dynamics of family context and experienced affect following discharge from psychiatric hospitalisation for suicidal thoughts and behaviours (STBs). The purpose of this paper is to provide an overview of a new model, description of model-guided integration of multiple methods, documentation of feasibility of recruitment and retention and a description of baseline sample characteristics.Design The research involved a longitudinal, multimethod observational investigation.Setting Participants were recruited from an inpatient child and adolescent psychiatric hospital. 194 participants ages 13–18 were recruited following hospitalisation for STB.Primary and secondary outcome measures Participants underwent a battery of clinical interviews, self-report assessments and venipuncture. On discharge, participants were provided with a phone with (1) the electronically activated recorder (EAR), permitting acoustic capture later coded for social context, and (2) ecological momentary assessment, permitting assessment of in vivo experienced affect and STB. Participants agreed to follow-ups at 3 weeks and 6 months.Results A total of 71.1% of approached patients consented to participation. Participants reported diversity in gender identity (11.6% reported transgender or other gender identity) and sexual orientation (47.6% reported heterosexual or straight sexual orientation). Clinical interviews supported a range of diagnoses with the largest proportion of participants meeting criteria for major depressive disorder (76.9%). History of trauma/maltreatment was prevalent. Enrolment rates and participant characteristics were similar to other observational studies.Conclusions The research protocol characterises in vivo, real-world experienced affect and observed family context as associated with STB in adolescents during the high-risk weeks post discharge, merging multiple fields of study.

Progress monitoring is a process of collecting ongoing samples of student work and tracking performance of individual students over time. Progress monitoring involves administering parallel sets of items to the same student on a regular basis (at least monthly) that are sensitive to changes in the student’s understanding based on instruction. The sets of items administered over time should be parallel in difficulty so that differences in performance can be attributed to differences in the student’s understanding as opposed to variability in item difficulty across sets. In this manuscript, we describe an approach to designing items that controls item-level variability by constraining the item features that may elicit different cognitive processing. This approach adapts the principles of Automated Item Generation (AIG) and includes carefully designing test specifications, isolating specific components of the content that will be assessed, creating item models to serve as templates, duplicating the templates to create parallel item clones, and verifying that the duplicated item clones align with the original item model. An example from an operational progress monitoring system for mathematics in Kindergarten through Grade 6 is used to illustrate the process. We also propose future studies to empirically evaluate the assertion of parallel form difficulty.

OBJECTIVES:. To describe the prevalence, associated risk factors, and outcomes of serious neurologic manifestations (encephalopathy, stroke, seizure, and meningitis/encephalitis) among patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN:. Prospective observational study. SETTING:. One hundred seventy-nine hospitals in 24 countries within the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 Registry. PATIENTS:. Hospitalized adults with laboratory-confirmed SARS-CoV-2 infection. INTERVENTIONS:. None. RESULTS:. Of 16,225 patients enrolled in the registry with hospital discharge status available, 2,092 (12.9%) developed serious neurologic manifestations including 1,656 (10.2%) with encephalopathy at admission, 331 (2.0%) with stroke, 243 (1.5%) with seizure, and 73 (0.5%) with meningitis/encephalitis at admission or during hospitalization. Patients with serious neurologic manifestations of COVID-19 were older with median (interquartile range) age 72 years (61.0–81.0 yr) versus 61 years (48.0–72.0 yr) and had higher prevalence of chronic medical conditions, including vascular risk factors. Adjusting for age, sex, and time since the onset of the pandemic, serious neurologic manifestations were associated with more severe disease (odds ratio [OR], 1.49; p < 0.001) as defined by the World Health Organization ordinal disease severity scale for COVID-19 infection. Patients with neurologic manifestations were more likely to be admitted to the ICU (OR, 1.45; p < 0.001) and require critical care interventions (extracorporeal membrane oxygenation: OR, 1.78; p = 0.009 and renal replacement therapy: OR, 1.99; p < 0.001). Hospital, ICU, and 28-day mortality for patients with neurologic manifestations was higher (OR, 1.51, 1.37, and 1.58; p < 0.001), and patients had fewer ICU-free, hospital-free, and ventilator-free days (estimated difference in days, –0.84, –1.34, and –0.84; p < 0.001). CONCLUSIONS:. Encephalopathy at admission is common in hospitalized patients with SARS-CoV-2 infection and is associated with worse outcomes. While serious neurologic manifestations including stroke, seizure, and meningitis/encephalitis were less common, all were associated with increased ICU support utilization, more severe disease, and worse outcomes.

BackgroundAdolescents involved in the juvenile justice system who use cannabis are at an increased risk of future substance use disorders and rearrest. Many court-involved, nonincarcerated (CINI) youth are referred for services in the community and often encounter multiple barriers to care, highlighting the need for minimally burdensome services that can be delivered in justice settings. Digital health interventions are accessible, easy to implement, and can provide ongoing support but have not been developed to address the unique needs of CINI youth who use cannabis. ObjectiveThis multiphase study will aim to develop, implement, and pilot test a novel smartphone app, Teen Empowerment through Computerized Health (TECH), to reduce cannabis and other substance use among CINI youth. TECH is conceptualized as a digital adjunct to a brief computerized intervention delivered by our family court partner. MethodsFollowing the principles of user-centered design, phase I interviews with CINI youth aged 14-18 years (n=14-18), their caregivers (n=6-8), and behavioral health app developers (n=6-8) will guide the TECH design decisions. Next, in phase II, CINI youth (n=10) will beta test the TECH app prototype for 1 month; their feedback regarding feasibility and acceptability will directly inform the app refinement process. Finally, in phase III, CINI youth (n=60) will participate in a pilot randomized controlled trial for 6 months, comparing the preliminary effectiveness of the adjunctive TECH app on cannabis use outcomes. ResultsPhase I data collection began in September 2020 and was completed in December 2021; 14 CINI youth, 8 caregivers, and 11 behavioral health app developers participated in the study. Phases II and III will occur in 2022 and 2023 and 2023 and 2025, respectively. ConclusionsThis body of work will provide insight into the feasibility and acceptability of a smartphone-based adjunctive intervention designed for CINI youth. Phase III results will offer a preliminary indication of the effectiveness of the TECH app in reducing cannabis use among CINI youth. International Registered Report Identifier (IRRID)DERR1-10.2196/35402

BackgroundAdolescents in residential substance use treatment are at extremely high risk for relapse following discharge to the community. Parenting practices, including parental monitoring and parent-adolescent communication, have been established as key predictors of adolescent substance use outcomes and relapse. However, traditional office-based therapy may not be feasible for parents who face structural and systemic barriers. There is a clear need for effective, accessible, and scalable interventions for parents of adolescents receiving residential substance use treatment. In a prior pilot randomized controlled trial, we tested Parent SMART (Substance Misuse among Adolescents in Residential Treatment)—a technology-assisted parenting intervention informed by extensive formative research—as an adjunct to residential treatment as usual (TAU). Parent SMART demonstrated high feasibility and acceptability, as well as evidence of effectiveness in improving parental monitoring and communication. ObjectiveThis protocol paper describes a fully-powered randomized controlled pragmatic effectiveness trial of Parent SMART as an adjunct to residential TAU. We hypothesize that families who receive Parent SMART will demonstrate greater improvements in parenting skills, reductions in adolescent substance use, and reductions in adolescent problem behaviors relative to families that receive residential TAU. We will test the exploratory hypothesis that reductions in adolescent substance use will be partially mediated by improvements in parenting skills. MethodsAdolescent-parent dyads (n = 220 dyads; 440 total) will be randomized to either residential TAU only or Parent SMART+TAU. Parents randomized to Parent SMART will receive access to a networking forum, an off-the-shelf computer program called Parenting Wisely, and up to four telehealth coaching calls. Multimethod follow-up assessments consisting of self-reported parent and adolescent measures, a parent-adolescent in vivo interaction task, and 8-panel urine screens will be conducted 6, 12, and 24 weeks postdischarge from residential care. Measures will assess parenting skills, adolescent substance use, and adolescent problem behaviors. Analyses will be conducted using latent change score structural equation modeling. ResultsThe trial was funded in August 2021; ethics approval was obtained in August 2020, prior to funding. Due to concerns with the administrative interface in the pilot trial, the Parent SMART networking forum is currently being rebuilt by a different vendor. The programming is scheduled to be completed by December 2021, with recruitment beginning in February 2022. ConclusionsThe proposed research has the potential to advance the field by serving a high-need, underserved population during a vital treatment juncture; targeting parenting practices (putative mediators) that have been shown to predict adolescent substance use outcomes; addressing barriers to accessing continuing care; and testing a highly scalable intervention model. Trial RegistrationClinicalTrials.gov NCT05169385; https://clinicaltrials.gov/ct2/show/NCT05169385 International Registered Report Identifier (IRRID)PRR1-10.2196/35934

Learning from others provides the foundation for culture and the advancement of knowledge. Learning a new visuospatial skill from others represents a specific challenge-overcoming differences in perspective so that we understand what someone is doing and why they are doing it. The "what" of visuospatial learning is thought to be easiest from a shared 0° first-person perspective and most difficult from a 180° third-person perspective. However, the visual disparity at 180° promotes face-to-face interaction, which may enhance learning by scaffolding social perspective taking, the "why" of visuospatial learning. We tested these potentially conflicting hypotheses in child and young adult learners. Thirty-six children (4-6 years) and 57 young adults (18-27 years) observed a live model open a puzzle box from a first-person (0°) or third-person (90° or 180°) perspective. The puzzle box had multiple solutions, only one of which was modelled, which allowed for the assessment of imitation and goal emulation. Participants had three attempts to open the puzzle box from the model's perspective. While first-person (0°) observation increased imitation relative to a 180° third-person perspective, the 180° observers opened the puzzle box most readily (i.e., fastest). Although both age groups were excellent imitators and able to take the model's perspective, adults were more faithful imitators, and children were more likely to innovate a new solution. A shared visual perspective increased imitation, but a shared mental perspective promoted goal achievement and the social transmission of innovation. "Perfection of means and confusion of goals-in my opinion-seem to characterize our age" Einstein (1973) pg 337, Ideas and Opinions.

BackgroundSubstance use among adolescents in the U.S. is associated with adverse physical and mental health outcomes in the long-term. Universal youth-focused substance use prevention programs have demonstrated effectiveness but are often not sustainable due to the significant amount of time, effort, and resources required. We describe a trial protocol for a brief, low-participant-burden intervention to improve substance use-specific parent-child communication through the promotion of family meals and increased parental engagement.MethodsThis study is a parallel-group randomized controlled trial designed to assess the efficacy of a 13-week intervention. A total of 500 dyads of parents and their 5th-7th grade children are recruited from across Massachusetts. Dyads are randomized to the intervention or attention-control condition using block urn randomization, based on child grade, gender, and school. Parents/guardians in the substance use preventive intervention arm receive a short handbook, attend two meetings with an interventionist, and receive two SMS messages per week. Parents/guardians in the control arm receive the same dose but with content focused on nutrition, physical activity, and weight stigma. Participant dyads submit videos of family meals, audio recordings of prompted conversations, and quantitative surveys over an 18-month period (baseline, 3, 6, 12, 18 months post-intervention). The primary outcomes measure the quantity and quality of parent-child substance use conversations and proximal child indicators (i.e., substance use attitudes and expectancies, affiliation with substance-using peers, and intentions and willingness to use substances). The secondary outcome is child substance use initiation.DiscussionThis is a novel, brief, communication-focused intervention for parents/guardians that was designed to reduce participant burden. The intervention has the potential to improve parent-child engagement and communication and conversations about substance use specifically and decrease child substance use risk factors and substance use initiation.Trial registrationClinicalTrials.gov NCT03925220. Registered on 24 April 2019.

IMPORTANCE:. Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES:. To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS:. A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES:. Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS:. Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS:. Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

Abstract Background The American College of Surgeons mandates universal screening for alcohol misuse and delivery of an intervention for those screening positive as a requirement for certification as a level 1 trauma center. Though this requirement has been mandated for over a decade, its implementation has been challenging. Our research team completed an implementation study supporting seven pediatric trauma centers’ compliance with the requirement by developing and implementing an institutional alcohol Screening, Brief Intervention and Referral to Treatment (SBIRT) policy for adolescent trauma patients. A mixed-methods approach indicated that SBIRT adoption rates increased at all sites; however, providers’ fidelity to the SBIRT intervention was variable, and providers reported a number of barriers to SBIRT implementation. The goal of this study is to conduct a fully powered type III hybrid effectiveness-implementation trial to test the effectiveness of a comprehensive implementation strategy in increasing the implementation of SBIRT for alcohol and other drug use (AOD) in pediatric trauma centers. Methods Our implementation strategy is based on the Science to Service Laboratory (SSL), an approach developed by the SAMHSA-funded Addiction Technology Transfer Centers that consists of three core elements (i.e., didactic training + performance feedback + leadership coaching). Utilizing a stepped wedge design, a national cohort of 10 pediatric trauma centers will receive the SSL implementation strategy. At six distinct time points, each of the 10 sites will provide data from 30 electronic medical records (n = 1800 in total). A subset of adolescents will also report on fidelity of intervention delivery and linkage to care (i.e., continued AOD discussion and/or treatment with a primary care provider) 1 month after hospital discharge. In addition, nurses, social workers, and leaders will report on organizational readiness for implementation at four distinct time points. Discussion This protocol proposes a unique opportunity to examine whether a comprehensive implementation strategy can improve the fidelity of SBIRT delivery across a national cohort of pediatric trauma centers. With injured adolescents, this could optimize the detection and intervention of AOD use and improve adolescent health. Trial registration Clinicaltrials.gov NCT03297060.

This study attempted to disentangle the effects of peer selection and socialization on heavy drinking and marijuana use among adolescents whose parents received 2 distinct brief interventions (BIs). It also examined whether the two BI models—Family Check-Up and Psychoeducation—had differential effects on peer processes. Parents were randomized to BI conditions and their adolescents (61% male, age 12-19 years) completed self-report measures of days of heavy drinking, days of marijuana use, and perceived peer substance involvement at baseline, 6 months, and 12 months. Separate cross-lagged panel models revealed evidence of selection and socialization for both heavy drinking and marijuana over the first 6 months and evidence of only selection over the subsequent 6 months. Consistent with prior studies, a less robust pattern of peer processes was found when simultaneously controlling for both heavy drinking and marijuana. Results highlight the need to examine multiple substances simultaneously and suggest that the BIs may have had protective effects on peer influences over time.

This paper discusses two methods of altering the harmonic content of the spatial air-gap flux density waveform in synchronous machines (generators and motors). First, fractional-conductor windings are analysed for adoption as a replacement for a conventional distributed winding arrangement, their advantages and disadvantages briefly discussed and an example design scenario presented. Second, analysis and discussion regarding the use of semi-magnetic slot wedges as a replacement for glass-fibre type wedges is presented to complement the choice of winding in synchronous machines. Both methods are shown to benefit machine performance under certain circumstances.

The racing greyhound industry in Australia has come under scrutiny in recent years due to animal welfare concerns, including wastage where physically sound greyhounds fail to enter or are removed from the racing industry because of poor performance. The reasons why some greyhounds perform poorly in racing are not well understood, but may include insufficient reinforcement for racing or negative affective states in response to the race meet environment. The current study investigated ways to measure affective states of greyhounds (n = 525) at race meets across three racetracks and the factors influencing performance by collecting behavioural and demographic data, and infrared thermographic images of greyhounds’ eyes at race meets. Increasing Eye Temp After had a negative association with performance (n = 290, Effect = −0.173, s.e. = 0.074, p-value = 0.027), as did increasing age (n = 290, Effect = −0.395, s.e. = 0.136, p-value = 0.004). The start box number also had a significant association, with boxes 4, 5 and 7 having an inverse relationship with performance. There was a significant effect of racetrack on mean eye temperatures before and after the race (n = 442, Effect = 1.910, s.e. = 0.274, p-value < 0.001; Effect = 1.595, s.e. = 0.1221, p-value < 0.001 for Gosford and Wentworth respectively), suggesting that some tracks may be inherently more stressful for greyhounds than others. Mean eye temperature before the race increased as the race meet progressed (n = 442, Effect = 0.103, s.e. = 0.002, p-value < 0.001). Behaviours that may indicate frustration in the catching pen were extremely common at two of the tracks but much less common at the third, where toys attached to bungees were used to draw greyhounds into the catching pen.

Background: Survival of patients with locally advanced, unresectable (stage III), non-small-cell lung cancer treated with radiotherapy is poor. Trials of the addition of chemotherapy to radiotherapy have produced conflicting results.Objective: To compare chemotherapy plus radiotherapy with radiotherapy alone in patients with stage III, non-small-cell lung cancer.Data Sources: English-language journal articles published between 1987 and 1995 identified in a MEDLINE search.Study Selection: Randomized trials that reported survival after previously untreated patients received chemotherapy plus radiotherapy or radiotherapy alone were reviewed.Data Extraction: For all eligible articles, reported survival curves were used to determine the relative risk for death in each of 3 years. These data were combined to determine a pooled estimate of the relative risk for death at 1, 2, and 3 years.Data Synthesis: Fourteen articles reporting on a total of 2589 patients were reviewed. Compared with radiotherapy, the combination of chemotherapy and radiotherapy reduced the risk for death at 1 year (relative risk, 0.88 [95% Cl, 0.80 to 0.96]), 2 years (relative risk, 0.87 [Cl, 0.81 to 0.94]), and 3 years (relative risk, 0.83 [Cl, 0.77 to 0.90]). This corresponded to a mean gain in life expectancy of about 2 months. The magnitude of the treatment effect was similar when trials of concurrently and sequentially administered chemotherapy were considered separately.Conclusion: The addition of chemotherapy to radiotherapy improves survival in patients with locally advanced, unresectable, non-small-cell lung cancer. The absolute benefit is relatively small, however, and should be balanced against the increased toxicity associated with the addition of chemotherapy. [ABSTRACT FROM AUTHOR]

Mental health issues are a significant concern after technological disasters such as the 2010 Gulf Oil Spill; however, there is limited knowledge about the long-term effects of oil spills. The study was part of a larger research effort to improve understanding of the mental and behavioral health effects of the Deepwater Horizon Gulf Oil Spill. Data were collected immediately following the spill and the same individuals were resampled again after the second anniversary (n = 314). The results show that mental health symptoms of depression, serious mental illness and posttraumatic stress have not statistically decreased, and anxiety symptoms were statistically equivalent to immediate symptoms. Results also showed that the greatest effect on anxiety is related to the extent of disruption to participants’ lives, work, family, and social engagement. This study supports lessons learned following the Exxon Valdez spill suggesting that mental health effects are long term and recovery is slow. Elevated symptoms indicate the continued need for mental health services, especially for individuals with high levels of disruption resulting in increased anxiety. Findings also suggest that the longer-term recovery trajectories following the Deepwater Horizon Gulf Oil Spill do not fall within traditional disaster recovery timelines.

Concerns about nanotechnology have prompted studies on how the release of these engineered nanoparticles impact our environment. Herein, the impact of 20 nm silver nanoparticles (AgNPs) on the life history traits of Arabidopsis thaliana was studied in both above- and below-ground parts, at macroscopic and microscopic scales. Both gross phenotypes (in contrast to microscopic phenotypes) and routes of transport and accumulation were investigated from roots to shoots. Wild type Arabidopsis growing in soil, regularly irrigated with 75 μg/L of AgNPs, did not show any obvious morphological change. However, their vegetative development was prolonged by two to three days and their reproductive growth shortened by three to four days. In addition, the germination rates of offspring decreased drastically over three generations. These findings confirmed that AgNPs induce abiotic stress and cause reproductive toxicity in Arabidopsis. To trace transport of AgNPs, this study also included an Arabidopsis reporter line genetically transformed with a green fluorescent protein and grown in an optical transparent medium with 75 μg/L AgNPs. AgNPs followed three routes: (1) At seven days after planting (DAP) at S1.0 (stages defined by Boyes et al. 2001 [41]), AgNPs attached to the surface of primary roots and then entered their root tips; (2) At 14 DAP at S1.04, as primary roots grew longer, AgNPs gradually moved into roots and entered new lateral root primordia and root hairs; (3) At 17 DAP at S1.06 when the Arabidopsis root system had developed multiple lateral roots, AgNPs were present in vascular tissue and throughout the whole plant from root to shoot. In some cases, if cotyledons of the Arabidopsis seedlings were immersed in melted transparent medium, then AgNPs were taken up by and accumulated in stomatal guard cells. These findings in Arabidopsis are the first to document specific routes and rates of AgNP uptake in vivo and in situ.

The rise of large developing countries has led to considerable discussions of re-balancing global relations and giving greater priority to understanding South-South relations. This paper, in exploring the central ideas of Chinese and Brazilian foreign policy and the behavior of these two rising Southern countries toward Sub-Saharan Africa, argues that the English School of International Relations is well suited to understanding the intentions and actions that characterize South-South relations.

Cancer of Cowper's gland is a very rare cancer. This case represents the 9th case in the medical literature. As such, there are no phase II or phase III trials to guide treatment. In this article, we report the successful treatment of a patient over a 7-year period guided solely by molecular profiling. Through multiple cycles to treatment, the cancer was controlled using drugs targeting c-kit, as the cancer steadily increased the expression of c-kit. This report also documents the use of a novel drug combination based on sunitinib that was well tolerated and may warrant testing in other c-kit-dependent cancers.

After Taxotere fails, treatment options for metastatic prostate cancer are limited. The three drugs with FDA approval in this setting, Jevtana, Provenge and Zytiga, are associated with median survivals of less than 2 years. In part, the impact on survival is the result of low response rates, indicating a significant proportion of patients exhibiting de novo resistance to these agents. An alternate approach is to let treatment selection be governed by gene expression profiling so that the treatment is tailored to the specific patient. Here, we report a case of metastatic prostate cancer with a dramatic response to treatment selected based on molecular profiling. This patient had failed LHRH agonist, bicalutamide, Taxotere, and doxorubicin. Molecular profiling showed overexpression of the androgen receptor and he had a dramatic response of measurable disease to second-line hormonal therapy with ketoconazole, estrogen and Leukine.

El objetivo de este artículo es responder una pregunta básica que no sólo se hacen los brasileros, sino también personas en otros países en desarrollo en los cuales se sobrevaluaron las agendas de reforma liberales, la pregunta es: ¿por qué China ha crecido tan rápidamente y Brasil no? En la primera sección se establecen las bases para comparar Brasil y China contextualizando estos países dentro del concepto del BRIC. La segunda sección tiene como objetivo una explicación parcial, midiendo los resultados de crecimiento de una generación hija del Consenso de Washington. Dado el agnosticismo sobre los paquetes totalmente liberales y el enigma de por qué los reformadores incompletos crecieron más, el artículo se sumerge en un análisis comparativo de las reformas brasileras y chinas enfocándose únicamente en el tema de política macroeconómica, especialmente los regímenes monetario y cambiarlo, y sus efectos en el crecimiento en la tercera sección. Es decir, la experiencia brasilera con los regímenes de inflación objetivo y tipo de cambio flexible, desde 1999 ha contribuido a un crecimiento lento de pare y siga además de una inflación relativamente alta, mientras que el enfoque favorecido por China, más controlado, ha producido lo contrario. Finalmente, el artículo concluye ofreciendo consejos de política económica a otros países en desarrollo, los del BRIC, el N-11, u otros.

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax-naïve and -resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax-responsive and -relapsed CLL.

The photophysical properties of conformationally flexible (TPA-C) and partially rigidified (Cz-C) triarylamine acids were explored in solid as well as solution state and correlated with the structure. TPA-C and Cz-C exhibited moderate solid-state fluorescence (Φ f  = 6.2 % (TPA-C) and 5.6 % (Cz-C)) and self-reversible mechanofluorochromism. TPA-C produced fluorescent polymorphs (TPA-C-1 and TPA-C-2) with tunable fluorescence. TPA-C-1 showed unusual carboxylic acid intermolecular interactions whereas TPA-C-2 and Cz-C showed usual carboxylic acid dimer. TPA-C exhibited strong solvent polarity dependent tunable fluorescence (Φ f  = 0.01 to 0.11 compared to quinine sulphate standard) but Cz-C was non-emissive in the solution state. The dual emissive TPA-C showed highly sensitive fluorescence changes in organic solvents (CH 3 CN, THF, DMF, EtOH) when trace amount of water was added. In CH 3 CN, TPA-C showed weak fluorescence at 474 nm and addition of water (1 %) exhibited significant blue shift (λ max  = 416 nm). The fluorescence intensity was gradually decreased with blue shifting in DMF, THF and EtOH with water addition. Importantly, TPA-C showed drastically different fluorescence in n-propanol (n-PA) and iso-propanol (IPA). TPA-C in n-PA showed fluorescence at 408 nm that was clearly red shifted to 438 nm with 0.1 % addition of IPA. The limit of detection (LOD) of water in CH 3 CN, DMF, THF and EtOH by TPA-C revealed 0.02, 0.7, 0.08 and 0.77 %, respectively. The LOD of IPA sensing in n-PA is 0.05 % and indicated the very efficient sensing and distinguishing propanol isomers. Thus, simple triphenylamine acid showed excellent water sensing and propanol isomers discrimination that could be attributed to the twisted intramolecular charge transfer (TICT) formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new deep blue emissive organic fluorophore (N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(diphenylamino)benzamide (NCDPB)) was designed and synthesized, which showed strong fluorescence both in solution and solid-state. Solid-state structural analysis of NCDPB revealed non-planar twisted molecular conformation with extended hydrogen bonding between the amide functionalities. The propeller shaped triphenylamine (TPA) and non-planar cyclohexyl unit prevented close π…π stacking and produced strong deep blue emission in the solid state (λ max  = 400 nm, quantum yield (Φ f ) = 12.6 %). NCDPB also exhibited strong solvent polarity dependent tunable emission in solution (λ max  = 402-462 nm, Φ f  = 1.15 (compared to quinine sulphate)). NCDPB showed reversible fluorescence switching between two fluorescence states upon mechanical crushing and heating/solvent exposure. Mechanical crushing caused red shifting of fluorescence from 400 to 447 nm and heating/solvent exposure reversed the fluorescence. Further, NCDPB also displayed off-on reversible/self-reversible fluorescence switching upon exposure to trifluoracetic acid (TFA) and NH 3 . The repeated fluorescence switching cycles indicated high reversibility without any significant change of fluorescence intensity. The drastically different fluorescence of NCDPB in CH 3 OH and EtOH was utilized to distinguish them and monitor CH 3 OH contamination in ethanol and benzene. It showed limit of detection (LOD) of methanol up to 0.25 % and 7 % in benzene and ethanol, respectively. The water sensitive fluorescence modulation of NCDPB in organic solvents was used to sensing water contamination in common organic solvents. Thus, integration of twisted TPA with H-bonding urea produced dual state emitting organic fluorophore with multi-responsive fluorescence switching and solvent sensing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Organic fluorescence sensor for selectively detecting and quantifying toxic heavy metal ions has received significant interest due to their environmental hazards. Herein, we have designed and synthesized a simple tripodal Schiff base ligand (1) based on hydroxy-naphthaldehyde and tris(2-aminoethyl)amine (TREN) and demonstrated highly selective turn-on fluorescence sensing of Cd 2+ ions. The free ligand did not show any fluorescence in DMF. In contrast, Cd 2+ (10 - 4  M) addition exhibited a strong enhancement of fluorescence at 450 nm. Interestingly, other metal ions including Zn 2+ , which exhibit similar chemistry, did not show any turn-on fluorescence. The concentration-dependent studies of 1 with Cd 2+ showed the detection limit of 6.78 × 10 - 8  M. NMR spectra of 1 with Cd 2+ and computational studies were performed to understand the mechanism of sense., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Relapsed T-acute lymphoblastic leukemia (T-ALL) has limited treatment options. We investigated mechanisms of resistance to BH3 mimetics in T-ALL to develop rational combination strategies. We also looked at the preclinical efficacy of NWP-0476, a novel BCL-2/BCL-xL inhibitor, as single agent and combination therapy in T-ALL., Experimental Design: We used BH3 profiling as a predictive tool for BH3 mimetic response in T-ALL. Using isogenic control, venetoclax-resistant (ven-R) and NWP-0476-resistant (NWP-R) cells, phosphokinase array was performed to identify differentially regulated signaling pathways., Results: Typical T-ALL cells had increased dependence on BCL-xL, whereas early T-precursor (ETP)-ALL cells had higher BCL-2 dependence for survival. BCL-2/BCL-xL dual inhibitors were effective against both subtypes of T-lineage ALL. A 71-protein human phosphokinase array showed increased LCK activity in ven-R cells, and increased ACK1 activity in ven-R and NWP-R cells. We hypothesized that pre-TCR and ACK1 signaling pathways are drivers of resistance to BCL-2 and BCL-xL inhibition, respectively. First, we silenced LCK gene in T-ALL cell lines, which resulted in increased sensitivity to BCL-2 inhibition. Mechanistically, LCK activated NF-κB pathway and the expression of BCL-xL. Silencing ACK1 gene resulted in increased sensitivity to both BCL-2 and BCL-xL inhibitors. ACK1 signaling upregulated AKT pathway, which inhibited the pro-apoptotic function of BAD. In a T-ALL patient-derived xenograft model, combination of NWP-0476 and dasatinib demonstrated synergy without major organ toxicity., Conclusions: LCK and ACK1 signaling pathways are critical regulators of BH3 mimetic resistance in T-ALL. Combination of BH3 mimetics with tyrosine kinase inhibitors might be effective against relapsed T-ALL., (©2023 The Authors; Published by the American Association for Cancer Research.)

Metal-organic frameworks (MOFs) with their tunable topology, functionality and coordination environment have been considered as potential materials for various applications including electrocatalysis. Herein, we have synthesised a water coordinated nickel based 2D metal-organic framework (Ni-MOF) and a coordination complex (Ni-C) and investigated their electrocatalytic OER activity. The Ni-MOF showed a 2D sheet structure with one water coordination whereas a four water molecule coordinated charged complex was formed in the Ni-C. Thermogravimetric analysis (TGA) confirmed their water coordination and good thermal stability. Interestingly, electrocatalytic OER studies showed strongly enhanced activity for the Ni-MOF and that it required a low overpotential (194 mV) to produce a geometric current density of 10 mA cm -2 . The Ni-C required 225 mV to produce 10 mA cm -2 . The post-catalytic analysis suggested that the Ni-MOF and Ni-C are converted to nickel hydroxides/oxyhydroxides during electrocatalysis and acted as the catalytic centre. The low Tafel slope and charge transfer resistance further supported the higher activity of Ni-MOF based nickel hydroxides/oxyhydroxides. Chronoamperometric studies revealed the excellent stability of the Ni-MOF based catalyst over 72 h. The present study revealed the potential of developing highly active electrocatalysts based on Ni-MOFs by optimizing the topology and coordination environment.

Carbazole-based, π-conjugated donor-acceptor fluorophores were synthesized by integrating imidazole/thiazole units. Then, we investigated the impact of subtle structural changes on fluorescence properties. Carbazole integrated with imidazole (Cz-I) and carbazole integrated with thiazole (Cz-T) showed strong fluorescence in solution (quantum yield ( Φ f ) = 0.18 (Cz-I) and 0.14 (Cz-T) compared with the standard quinine sulfate) and solid-state ( Φ f = 8.0% (Cz-I) and 14.6% (Cz-T)). Cz-I showed relatively more blue-shifted emission in solution compared with the solid-state ( λ max = 417 nm (CH 3 CN) and 460 nm (solid)). Cz-T exhibited deep-blue emission in the solid-state compared with solution ( λ max = 455 nm (CH 3 CN) and 418 nm (solid)). Interestingly, Cz-T exhibited a drastic change in fluorescence in organic solvents (CH 3 CN, THF, CH 3 OH, DMSO) with a low percentage (1%) of water. Cz-I showed reversible fluorescence switching between two fluorescence states upon exposure to trifluoracetic acid (TFA)/ammonia (NH 3 ). In contrast, Cz-T displayed reversible/self-reversible off-on fluorescence switching upon exposure to TFA or NH 3 . Mechanofluorochromic studies of Cz-I showed a slight reduction in fluorescence intensity upon crushing and reversal to the initial state upon heating. Cz-T exhibited off-on reversible/self-reversible fluorescence switching upon crushing/heating. Computational studies indicated that thiazole integration improved the electron-withdrawing characteristics compared with imidazole and contributed to contrasting fluorescence responses. Thus, a simple change of nitrogen with sulfur produced contrasting self-assembly in the solid-state that led to different functional properties and stimuli-induced fluorescence switching., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The use of metal-organic compounds as electrocatalysts for water splitting reactions has gained increased attention; however, a fundamental understanding of the structural requirement for effective catalytic activity is still limited. Herein, we synthesized water-coordinated mono and bimetallic copper complexes (CuPz-H 2 O·H 2 O, CuPz-H 2 O, CuBipy-H 2 O·H 2 O, and CuMorph-H 2 O) with varied intermetallic spacing (pyrazine/4,4'-bipyridine) and explored the structure-dependent oxygen evolution reaction (OER) activity in alkaline medium. Single crystal structural studies revealed water-coordinated monometallic complexes (CuMorph-H 2 O) and bimetallic complexes (CuPz-H 2 O·H 2 O, CuPz-H 2 O, CuBipy-H 2 O·H 2 O). Further, CuPz-H 2 O·H 2 O and CuBipy-H 2 O·H 2 O contained lattice water along with coordinated water. Interestingly, the bimetallic copper complex with lattice water and shorter interspacing between the metal centres (CuPz-H 2 O·H 2 O) showed strong OER activity and required an overpotential of 228 mV to produce a benchmark current density of 10 mA cm -2 . Bimetallic copper complex (CuPz-H 2 O) without lattice water but the same intermetallic spacing and bimetallic complex with increased interspacing but with lattice water (CuBipy-H 2 O·H 2 O) exhibited relatively lower OER activity. CuPz-H 2 O and CuBipy-H 2 O·H 2 O required an overpotential of 236 and 256 mA cm -2 , respectively. Monometallic CuMorph-H 2 O showed the lowest OER activity (overpotential 271 mV) compared to bimetallic complexes. The low Tafel slope and charge transfer resistance of CuPz-H 2 O·H 2 O facilitated faster charge transfer kinetics at the electrode surface and supported the enhanced OER activity. The chronoamperometric studies indicated good stability of the catalyst. Overall, the present structure-electrocatalytic activity studies of copper complexes might provide structural insight for designing new efficient electrocatalysts based on metal coordination compounds., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Highly efficient and stable Earth abundant transition metal electrocatalysts are in great demand for the oxygen evolution reaction (OER), a bottleneck process involved in the water splitting reaction and metal-air batteries. Herein, we have demonstrated a single step direct fabrication of cobalt hydroxide (Co(OH) 2 ) nanowires doped with vanadium(V) in a less stable +4 oxidation state and fluoride (F) ions (V-Co(OH) 2 ) on a carbon cloth electrode that showed highly enhanced OER activity under alkaline conditions. V-Co(OH) 2 nanowires synthesized under the optimized conditions produced excellent OER activity with an ultralow overpotential of 136 mV at 10 mA cm -2 (scan rate 1 mV s -1 ), a small Tafel slope (51.6 mV dec -1 ) and good stability over 72 h. To the best of our knowledge, this is the lowest overpotential reported for cobalt-based electrocatalysts to achieve a geometric current density of 10 mA cm -2 . The controlled synthesis and HR-TEM studies revealed the formation of hybrid nanostructures (nanowires along with spherical assembly of nanoparticles) and codoping of V and F ions played an important role in enhancing the OER activity. The detailed chemical composition and oxidation state analysis by X-ray photoelectron spectroscopy (XPS) confirmed the doping of V 4+ and ionic F in V-Co(OH) 2 with mixed valence states of Co 2+ /Co 3+ and a higher Co 2+ ratio. The outstanding OER activity of V-Co(OH) 2 is attributed to the formation of a spherical assembly of nanoparticles with nanowires, which provided a high number of catalytically active sites with enhanced charge transport, and doping of higher valence V 4+ and strongly electronegative F in V-Co(OH) 2 with a higher ratio of Co 2+ /Co 3+ promoted OOH* intermediate generation and significantly boosted the OER activity. Overall, the present work highlights the possibility of achieving highly active Earth abundant OER electrocatalysts by controlling the mixed oxidation state of Co with a judicious choice of dopants along with maintaining optimal nanostructure morphologies.

Fluorine and nitrogen codoped cobalt hydroxide-graphene oxide nanocomposites (N,F-Co(OH) 2 /GO) were synthesized by a simple hydrothermal method and demonstrated highly enhanced oxygen evolution activity in an alkaline medium. N,F-Co(OH) 2 /GO synthesized under optimized reaction conditions required an overpotential of 228 mV to produce the benchmark current density of 10 mA cm -2 (scan rate 1 mV s -1 ). In contrast, N,F-Co(OH) 2 without GO and Co(OH) 2 /GO without fluorine required higher overpotentials (370 (N,F-Co(OH) 2 ) and 325 mV (Co(OH) 2 /GO)) for producing the current density of 10 mA cm -2 . The low Tafel slope (52.6 mV dec -1 ) and charge transfer resistance, and high electrochemical double layer capacitance of N,F-Co(OH) 2 /GO compared to N,F-Co(OH) 2 indicate faster kinetics at the electrode-catalyst interface. The N,F-Co(OH) 2 /GO catalyst showed good stability over 30 h. High-resolution transmission electron microscope (HR-TEM) images showed good dispersion of polycrystalline Co(OH) 2 nanoparticles in the GO matrix. X-ray photoelectron spectroscopic (XPS) analysis revealed the coexistence of Co 2+ /Co 3+ and the doping of nitrogen and fluorine in N,F-Co(OH) 2 /GO. XPS further revealed the presence of F in its ionic state and being covalently attached to GO. The integration of highly electronegative F with GO stabilizes the Co 2+ active centre along with improving the charge transfer and adsorption process that contributes to improved OER. Thus, the present work reports a facile method for preparing F-doped GO-Co(OH) 2 electrocatalysts with enhanced OER activity under alkaline conditions.

Introducing methoxy substituent into triphenylamine-acetophenone based donor-π-acceptor fluorophore, 3-(4-(diphenylamino)phenyl)-1-phenylprop-2-en-1-one (1), produced strong solvatofluorochromism including white light emission, fluorescent polymorphs and mechano-responsive fluorescence switching. The unsubstituted and methoxy substituted compounds displayed strong solvent polarity mediated tunable emission in the solution. Interestingly, 3-(4-(diphenylamino)phenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (2) and 3-(4-(diphenylamino)-2-methoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one (3) showed single molecule white light emission in DMSO and ethanol, respectively. 1-3 exhibited strong green/yellow fluorescence in the solid-state (Quantum yield (Φ f ) = 10 to 23%). 2 produced fluorescent polymorphs (green (2-G) and yellow (2-Y). Single crystal structural analysis revealed that donor and acceptor phenyl units adopted coplanar conformation in 2-G and 3 whereas twisted molecular conformation in 1 and 2-Y. Further, 2-G exhibited π…π interactions facilitated isolated dimers whereas 2-Y showed well separated molecules in the crystal lattice. Aggregation induced emission (AIE) studies showed morphological transformation induced fluorescence tuning for 2. The intramolecular charge transfer (ICT) from TPA to acetophenone was confirmed by computational studies. Mechanofluorochromic (MFC) studies of 1 showed only slight reduction of intensity without modulating fluorescence wavelength significantly but 2 and 3 exhibited visible emissive colour change from yellow to green and vice versa by crushing and heating. Both 2 and 3 also exhibited self-reversible fluorescence switching that was confirmed by PXRD pattern. Thus, methoxy group introduction resulted in obtaining white light emitting fluorescence molecules in the solution state and self-reversible fluorescence switching materials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: Monitoring treatment of tenosynovial giant cell tumor (TGCT) is complicated by the irregular shape and asymmetrical growth of the tumor. We compared responses to pexidartinib by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with those by tumor volume score (TVS) and modified RECIST (m-RECIST). Materials & methods: MRIs acquired every two cycles were assessed centrally using RECIST 1.1, m-RECIST and TVS and tissue damage score (TDS). Results: Thirty-one evaluable TGCT patients were treated with pexidartinib. From baseline to last visit, 94% of patients (29/31) showed a decrease in tumor size (median change: -60% [RECIST], -66% [m-RECIST], -79% [TVS]). All methods showed 100% disease control rate. For TDS, improvements were seen in bone erosion (32%), bone marrow edema (58%) and knee effusion (46%). Conclusion: TVS and m-RECIST offer potentially superior alternatives to conventional RECIST for monitoring disease progression and treatment response in TGCT. TDS adds important information about joint damage associated with TGCT.

Water pollution by organic dyes poses great challenge to the environment and living organism. Hence effective removal of organic dyes by cost effective methods have received significant attention in recent years. Herein, we report the complete removal of organic dyes (rhodamine B), methylene blue) and eosin yellow) from water via effective adsorption by MoO 3 catalyst. Hydrothermally synthesised MoO 2 (1) and amorphous MoS x (2) using ammonium molybdate without and with thiourea exhibited low dye adsorption. In contrast, crystalline micro/nanoplates of MoO 3 (3 and 4) obtained from calcination of 1 and 2 showed highly enhanced dye adsorption. Particularly 4 showed higher dye adsorption compared to 3. UV-Visible absorption studies confirmed complete removal of organic dyes upon stirring with MoO 3 catalyst. Dye removal studies further revealed that cationic dyes are adsorbed faster than anionic dye that could be attributed to the surface charge of MoO 3 . Interestingly, the adsorbed dyes were not released from MoO 3 for more than 50 days. The exhausted MoO 3 catalyst can be recovered by annealing at 400 °C. MoO 3 catalyst has also been used as packing materials in dropper column and demonstrated effective removal of dyes by passing through dyes separately as well as mixture., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To assess the response to pexidartinib treatment in six cohorts of adult patients with advanced, incurable solid tumors associated with colony-stimulating factor 1 receptor (CSF1R) and/or KIT proto-oncogene receptor tyrosine kinase activity., Patients and Methods: From this two-part phase I, multicenter study, pexidartinib, a small-molecule tyrosine kinase inhibitor that targets CSF1R, KIT, and FMS-like tyrosine kinase 3 (FLT3), was evaluated in six adult patient cohorts (part 2, extension) with advanced solid tumors associated with dysregulated CSF1R. Adverse events, pharmacokinetics, and tumor responses were assessed for all patients; patients with tenosynovial giant cell tumor (TGCT) were also evaluated for tumor volume score (TVS) and patient-reported outcomes (PRO). CSF1 transcripts and gene expression were explored in TGCT biopsies., Results: Ninety-one patients were treated: TGCT patients ( n = 39) had a median treatment duration of 511 days, while other solid tumor patients ( n = 52) had a median treatment duration of 56 days. TGCT patients had response rates of 62% (RECIST 1.1) and 56% (TVS) for the full analysis set. PRO assessments for pain showed improvement in patient symptoms, and 76% (19/25) of TGCT tissue biopsy specimens showed evidence of abnormal CSF1 transcripts. Pexidartinib treatment of TGCT resulted in tumor regression and symptomatic benefit in most patients. Pexidartinib toxicity was manageable over the entire study., Conclusions: These results offer insight into outcome patterns in cancers whose biology suggests use of a CSF1R inhibitor. Pexidartinib results in tumor regression in TGCT patients, providing prolonged control with an acceptable safety profile., (©2021 The Authors; Published by the American Association for Cancer Research.)