Real-world study of the multimorbidity and health service utilisation among individuals with non-diabetic hyperglycemia and type 2 diabetes mellitus in North West London.

INTRODUCTION: The prevalence of non-diabetic hyperglycemia (NDH) and type 2 diabetes mellitus (T2DM) is increasing. While T2DM is recognised to be associated with multimorbidity and early mortality, people with NDH are frequently thought to be devoid of such complications, potentially exposing individuals with NDH to suboptimal care. We therefore used the Discover London Secure Data Environment (SDE) dataset to appreciate the relationship of NDH/T2DM with multimorbidity, healthcare usage, and clinical outcomes. RESEARCH DESIGN AND METHODS: The dataset was retrospectively analysed between January 1, 2015 and December 31, 2020 to understand the relationship between NDH/T2DM and multimorbidity primary/secondary healthcare usage and clinical outcomes. This was compared with a cohort of individuals with thyroid disease but no NDH/T2DM. RESULTS: The dataset identified 152,384 and 124,190 adults with NDH and T2DM compared with 11,626 individuals with thyroid disease (control group). Individuals with NDH and individuals with T2DM had a high burden of disease, with only 13.1% of individuals with either NDH or T2DM not found to be suffering from at least one of the disease states of interest. The three most common comorbidities experienced by individuals with NDH were hypertension (41.4%), hypercholesterolemia (37.5%), and obesity (29.8%) compared with retinopathy (68.7%), hypertension (59.4%), and obesity (45.8%) in individuals with T2DM. Comparatively, the most common comorbidities in the control group were depression (30.8%), hypercholesterolemia (24.4%), and hypertension (17.1%). 28 (control group), 12 (NDH), and 16 (T2DM) primary care contacts per individual per year were identified, with 27,881, 282,371, and 314,880 inpatient admissions for the control, NDH, and T2DM cohorts, respectively. Prescription of drugs used to treat T2DM in individuals with NDH and T2DM was 27,772 (18.2%) and 109,361 (88.1%), respectively, accounting for approximately one in five individuals with NDH developing T2DM. CONCLUSION: Both NDH and T2DM were associated with significant multimorbidity alongside primary and secondary care utilisation. Given the morbidity highlighted with NDH, we highlight the need for earlier detection of NDH, recognition of multimorbidity associated with both NDH and T2DM, as well as the need for the further implementation of interventions to prevent progression to T2DM/multimorbidity.

Characteristics and outcomes of patients with COVID-19 at high risk of disease progression receiving sotrovimab, oral antivirals or no treatment in England: a retrospective cohort study.

OBJECTIVE: To describe characteristics and acute clinical outcomes for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated patients at highest risk per National Health Service (NHS) criteria. METHODS: Retrospective study of non-hospitalized patients between 1 December 2021 and 31 May 2022, using data from the Discover-NOW dataset (North-West London). Included patients were aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or untreated but expected to be eligible for early treatment per NHS highest-risk criteria. COVID-19-related and all-cause hospitalizations were reported for 28 days from COVID-19 diagnosis (index). Subgroup analyses were conducted in patients with advanced renal disease, those aged 18-64 and ≥65 years, and by period of Omicron BA.1, BA.2 and BA.5 (post-hoc exploratory) predominance. RESULTS: Overall, 1503 treated and 4044 eligible high-risk untreated patients were included. A high proportion of patients on sotrovimab had advanced renal disease (29.3%), ≥3 high-risk comorbidities (47.6%) and were aged ≥65 years (36.9%). Five of 696 (0.7%) patients on sotrovimab, <5/337 (0.3-1.2%) on nirmatrelvir/ritonavir, 10/470 (2.1%) on molnupiravir and 114/4044 (2.8%) untreated patients were hospitalized with COVID-19. Similar results were observed across all subgroups. The proportion of patients dying within 28 days of the index period was similarly low across all cohorts (<2%). CONCLUSION: Patients receiving sotrovimab appeared to show evidence of multiple high-risk comorbidities. Low hospitalization rates were observed for all treated cohorts across subgroups and periods of predominant variants of concern. These results require confirmation with comparative effectiveness analyses adjusting for differences in underlying patient characteristics.

Comparative effectiveness of sotrovimab versus no treatment in non-hospitalised high-risk COVID-19 patients in north west London: a retrospective cohort study.

BACKGROUND: We assessed the effectiveness of sotrovimab vs no early COVID-19 treatment in highest-risk COVID-19 patients during Omicron predominance. METHODS: Retrospective cohort study using the Discover dataset in North West London. Included patients were non-hospitalised, aged ≥12 years and met ≥1 National Health Service highest-risk criterion for sotrovimab treatment. We used Cox proportional hazards models to compare HRs of 28-day COVID-19-related hospitalisation/death between highest-risk sotrovimab-treated and untreated patients. Age, renal disease and Omicron subvariant subgroup analyses were performed. RESULTS: We included 599 sotrovimab-treated patients and 5191 untreated patients. Compared with untreated patients, the risk of COVID-19 hospitalisation/death (HR 0.50, 95% CI 0.24, 1.06; p=0.07) and the risk of COVID-19 hospitalisation (HR 0.43, 95% CI 0.18, 1.00; p=0.051) were both lower in the sotrovimab-treated group; however, statistical significance was not reached. In the ≥65 years and renal disease subgroups, sotrovimab was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR 0.11, 95% CI 0.02, 0.82; p=0.03) and 82% (HR 0.18, 95% CI 0.05, 0.62; p=0.007), respectively. CONCLUSIONS: Risk of COVID-19 hospitalisation in sotrovimab-treated patients aged ≥65 years and with renal disease was significantly lower compared with untreated patients. Overall, risk of hospitalisation was also lower for sotrovimab-treated patients, but statistical significance was not reached.

A phase I COVID-19 vaccine trial among SARS-CoV-2 seronegative and seropositive individuals in Uganda utilizing a self-amplifying RNA vaccine platform: Screening and enrollment experiences.

We report the screening and enrollment process for a phase I vaccine trial in Masaka, Uganda that investigated the safety and immunogenicity of a self-amplifying SARS-CoV-2 RNA vaccine amongst individuals with and without antibodies to SARS-CoV-2. Participant screening and enrollment were conducted between December 2021 and April 2022. Individuals were eligible if they were aged between 18 and 45 years, healthy, and never vaccinated against COVID-19. SARS-CoV-2 antibody status was determined using two point-of-care rapid tests, i.e. Multi G (MGFT3) and Standard Q (Standard Q COVID-19 IgM/IgG Plus). Data were entered and managed in OpenClinica. Analyses were performed and presented descriptively. A total of 212 individuals were screened and 43(20.3%) enrolled. The most common reasons for exclusion were ≥ grade 1 laboratory abnormalities (39, 18.4%), followed by discordant SARS-CoV-2 antibody results (23, 10.9%). While the first 38 participants were quickly enrolled over a period of 9 weeks, it took another 9 weeks to enroll the remaining five, as antibody negative participants became scarce during the surge of the Omicron variant. The SARS-CoV-2 antibody positivity rate was determined to be 60.8% and 84.4% in each half of the 18 months of screening respectively. The mean age (±Standard Deviation, SD) of screened and enrolled participants was 27.7 (±8.1) and 30.2 (±8.3) years respectively. We demonstrated that it is feasible to successfully screen and enroll participants for COVID-19 vaccine trials in Uganda in the time of a pandemic. Our experiences may be useful for investigators planning to undertake similar work in Africa.

A quasi-experimental study examining the efficacy of multimodal bot screening tools and recommendations to preserve data integrity in online psychological research.

Bots are automated software programs that pose an ongoing threat to psychological research by invading online research studies and their increasing sophistication over time. Despite this growing concern, research in this area has been limited to bot detection in existing data sets following an unexpected encounter with bots. The present three-condition, quasi-experimental study aimed to address this gap in the literature by examining the efficacy of three types of bot screening tools across three incentive conditions ($0, $1, and $5). Data were collected from 444 respondents via Twitter advertisements between July and September 2021. The efficacy of five task-based (i.e., anagrams, visual search), question-based (i.e., attention checks, ReCAPTCHA), and data-based (i.e., consistency, metadata) tools was examined with Bonferroni-adjusted univariate and multivariate logistic regression analyses. In general, study results suggest that bot screening tools function similarly for participants recruited across incentive conditions. Moreover, the present analyses revealed heterogeneity in the efficacy of bot screening tool subtypes. Notably, the present results suggest that the least effective bot screening tools were among the most commonly used tools in existing literature (e.g., ReCAPTCHA). In sum, the study findings revealed highly effective and highly ineffective bot screening tools. Study design and data integrity recommendations for researchers are provided. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk and Prevention of Retinal Detachments in Patients with Stickler Syndrome.

BACKGROUND AND OBJECTIVE: To report the impact of prophylactic laser retinopexy in the prevention of retinal detachments (RDs) in patients with Stickler syndrome. PATIENTS AND METHODS: This was a retrospective, comparative case series of patients with Stickler syndrome from the year 2000 to 2019. We compared the rate of RDs between individuals who did and did not receive prophylactic laser therapy. In patients with an RD, we compared the rate of RD in the fellow eye with and without prophylactic laser treatment. RESULTS: A total of 95 eyes were identified. Fifty-four percent of the overall population was female. The RD rate was 26.7% among eyes without previous prophylactic laser retinopexy and 4.6% among eyes with previous prophylactic laser retinopexy. A Cox proportional model revealed that laser prophylaxis treatment had a statistically significant effect on the risk of RD or retinal tear during the 25-year survival period from birth (P = .034). Eyes receiving treatment were 70% less likely to experience RD or retinal tear (hazard ratio, 0.297; 95% CI, 0.097 to 0.913). CONCLUSIONS: This study's results suggest a potential role for prophylactic laser retinopexy in the prevention of rhegmatogenous RD among patients with a clinical diagnosis of Stickler syndrome. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:7-11.].

Causal discovery replicates symptomatic and functional interrelations of posttraumatic stress across five patient populations.

Introduction: Approximately half of individuals with posttraumatic stress disorder (PTSD) may meet criteria for other psychiatric disorders, and PTSD symptoms are associated with diminished health and psychosocial functioning. However, few studies examine the longitudinal progression of PTSD symptoms concurrent with related symptom domains and functional outcomes, such that may neglect important longitudinal patterns of symptom progression beyond PTSD specifically. Methods: Therefore, we used longitudinal causal discovery analysis to examine the longitudinal interrelations among PTSD symptoms, depressive symptoms, substance abuse, and various other domains of functioning in five longitudinal cohorts representing veterans (n = 241), civilians seeking treatment for anxiety disorders (n = 79), civilian women seeking treatment for post-traumatic stress and substance abuse (n = 116), active duty military members assessed 0-90 days following TBI (n = 243), and civilians with a history of TBI (n = 43). Results: The analyses revealed consistent, directed associations from PTSD symptoms to depressive symptoms, independent longitudinal trajectories of substance use problems, and cascading indirect relations from PTSD symptoms to social functioning through depression as well as direct relations from PTSD symptoms to TBI outcomes. Discussion: Our findings suggest PTSD symptoms primarily drive depressive symptoms over time, tend to show independence from substance use symptoms, and may cascade into impairment in other domains. The results have implications for refining conceptualization of PTSD co-morbidity and can inform prognostic and treatment hypotheses about individuals experiencing PTSD symptoms along with co-occurring distress or impairment.

Longitudinal Measurement Invariance of the PHQ-9 and GAD-7.

Intraindividual change over time is commonly used to estimate treatment effectiveness. However, patients may not respond similarly to a scale after treatment, rendering pre-post change an unreliable metric. The current objective was to investigate longitudinal measurement invariance of the Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7 among 4,323 patients completing a partial hospital program. We used confirmatory factor analysis to determine (1) factor structure at pretreatment and posttreatment and (2) longitudinal invariance, accounting for dependent observations, using both classical and approximate measurement invariance approaches. Results indicated a two-factor solution for both scales. Longitudinal invariance was not established for either scale, thus, using raw score differences from the Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7 for measuring symptom change over time may be problematic. The most longitudinally consistent items captured somatic as opposed to affective/cognitive symptoms. We discuss the potential use of these measures for diagnostic screening and between-group comparisons and suggest alternative ways to monitor client progress over time. Limitations included a majority White sample and uniqueness of a partial hospital setting.

Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape.

Where 2020 saw the development and testing of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at an unprecedented pace, the first half of 2021 has seen vaccine rollout in many countries. In this Progress article, we provide a snapshot of ongoing vaccine efficacy studies, as well as real-world data on vaccine effectiveness and the impact of virus variants of concern. Where they have been deployed in a high proportion of the adult population, the currently approved vaccines have been extremely effective in preventing COVID-19, particularly severe disease. Nonetheless, there are still significant challenges in ensuring equitable vaccine access around the globe and lessons that can be learned for controlling this pandemic and for the next pandemic.

Knowledge, Attitudes, and Practices Regarding COVID-19 among Healthcare Workers in Uganda: A Cross-Sectional Survey.

Healthcare workers (HCWs) are at high risk of COVID-19. However, data on HCWs' knowledge, attitudes, and practices (KAP) toward COVID-19 are limited. Between September and November 2020, we conducted a questionnaire-based COVID-19 KAP survey among HCWs at three hospitals in Uganda. We used Bloom's cut-off of ≥80% to determine sufficient knowledge, good attitude, and good practice, and multivariate Poisson regression with robust variance for statistical analysis. Of 717 HCWs invited to participate, 657 (91.6%) agreed and were enrolled. The mean age (standard deviation) of enrollees was 33.2 (10.2) years; most were clinical HCWs (64.7%) and had advanced secondary school/other higher-level education (57.8%). Overall, 83.9% had sufficient knowledge, 78.4% had a positive attitude, and 37.0% had good practices toward COVID-19. Factors associated with KAP were: Knowledge: being a clinical HCW (aRR: 1.12; 95% CI: 1.02-1.23) and previous participation in health research (aRR: 1.10; 95% CI: 1.04-1.17); Attitude: age > 35 years (aRR: 0.88; 95% CI: 0.79-0.98); Practice: being a clinical HCW (aRR: 1.91; 95% CI: 1.41-2.59). HCWs in Uganda have good knowledge and positive attitude but poor practices towards COVID-19. Differences in COVID-19 KAP between clinical and non-clinical HCWs could affect uptake of COVID-19 interventions including vaccination.

Willingness to participate in COVID-19 vaccine trials; a survey among a population of healthcare workers in Uganda.

BACKGROUND: Healthcare workers (HCWs) are at high risk of acquiring SARS-CoV-2 and COVID-19 and may therefore be a suitable population for COVID-19 vaccine trials. We conducted a survey to evaluate willingness-to-participate in COVID-19 vaccine trials in a population of HCWs at three hospitals in Uganda. METHODS: The survey was conducted between September and November 2020. Using a standardised questionnaire, data were collected on socio-demographics, previous participation in health research, COVID-19 information sources, underlying health conditions, and willingness-to-participate in COVID-19 vaccine trials. Data were analysed descriptively and a binomial generalised linear model with a log link function used to investigate factors associated with unwillingness to participate. RESULTS: 657 HCWs (female, 63%) were enrolled with a mean age of 33 years (Standard Deviation, 10). Overall willingness-to-participate was 70.2%. Key motivating factors for participation were: hope of being protected against COVID-19 (81.1%), altruism (73.3%), and the opportunity to get health care (26.0%). Selected hypothetical trial attributes reduced willingness-to-participate as follows: weekly-quarterly study visits over a 12-month period (70.2%-63.2%, P = 0.026); provision of approximately 50ml of blood at each study visit (70.2%-63.2%, P = 0.026); risk of mild-moderate local adverse reactions (70.2%-60.3%, P<0.001); chance of receiving candidate vaccine or placebo (70.2%-56.9%, P<0.001); and delay of pregnancy [Overall, 70.2%-57.1% P<0.001); Female, 62.8%-48.4% (P = 0.002); Male, 82.5%-71.5% (P = 0.003)]. Collectively, these attributes reduced willingness-to-participate from [70.2%-42.2% (P<0.001) overall; 82.5%-58.1% (P<0.001) in men; 62.8%-32.6% (P<0.001) in women]. Among individuals that were unwilling to participate, the commonest barriers were concerns over vaccine safety (54.6%) and fear of catching SARS-CoV-2 (31.6%). Unwillingness to participate was associated with being female (aRR 1.97, CI 1.46-2.67, P<0.001) and having university or other higher-level education (aRR 1.52, CI 1.05-2.2, P = 0.026). CONCLUSIONS: Willingness-to-participate in COVID-19 vaccine trials among HCWs in Uganda is high but may be affected by vaccine trial requirements and concerns about the safety of candidate vaccines.

A Multi-Modal Assessment of Clinical Predictors for Traumatic Brain Injury End-Points.

Traumatic brain injury (TBI) is a complex injury that has a multi-faceted recovery process. The current "gold standard" for classifying severity of TBI symptoms is the Glasgow Outcome Scale (GOSE), a crude measure of overall dysfunction after TBI. Exploratory factor analysis performed on TRACK-TBI Pilot (N = 297) identified candidate multi-variate outcome measures of neuropsychological impairment and cognitive speed and flexibility at 6 months post-TBI that were confirmed in data from the COBRIT study (N = 645) using confirmatory factor analysis. These new outcome measures were used as the dependent variables in an ordinal logistic regression model, using common data elements (CDE) collected in the emergency department as independent variables, including basic demographics, socioeconomic status, medical history, and measures of blood alcohol and blood pressure. We directly compared these prediction models with the GOSE as the 6-month outcome variable and found that in both the TRACK-TBI pilot and COBRIT studies, both neuropsychiatric complications (approx. 36.0% and 22.3% variance explained) and cognitive speed and flexibility (approx. 33.9% and 24.5% variance explained) were better explained by the prediction model, compared with GOSE (approx. 19.9% and 14.4% variance explained), respectively. While differences in overall distributions of impairment between TRACK-TBI pilot and COBRIT exist and should be explored further for applications of these prediction models, we think these multi-variate end-points more accurately characterize patients' functioning at six-months post-TBI. A multi-variate assessment of end-points seems especially important for characterizing TBI outcomes in cases where gross impairment, such as those measured by the GOSE, may be less evident.

A randomized dismantling trial of the open and engaged components of acceptance and commitment therapy in an online intervention for distressed college students.

This dismantling trial compared the effects of a full online Acceptance and Commitment Therapy (ACT) intervention to the isolated effects of the Open (i.e., acceptance, cognitive defusion) and Engaged (i.e., values, committed action) components of ACT. A sample of 181 distressed college students were randomized to one of four conditions: a 12-session full ACT website (Full), a version targeting the Open components (Open), a version targeting the Engaged components (Engaged), or waitlist. Participants in active conditions were also randomized to receive phone coaching or just email prompts to increase program adherence. All three ACT conditions significantly improved over time relative to the waitlist condition on the primary outcome of mental health symptoms. The Engaged and Full conditions had greater rates of reliable change on the primary outcome relative to waitlist, but not the Open condition. Similarly, only Engaged and Full conditions improved on positive mental health relative to waitlist. The Full condition had greater improvements on a few ACT process measures relative to Engaged and Open conditions, particularly cognitive fusion. Overall, results indicate targeting only the Open components of ACT was somewhat less effective, and that including both the Open and Engaged components led to greater decreases in cognitive fusion.

Experiential avoidance and negative affect as predictors of daily drinking.

People who drink alcohol to cope with negative affect tend to drink more and experience more frequent negative alcohol-related consequences. Experiential avoidance-the tendency to avoid, suppress, or otherwise attempt to control unwanted inner experiences-is a largely pathological process that may help account for how negative affect is linked to increased alcohol consumption. However, research to-date has typically used global, trait-like measures, which limit our understanding of the conditions under which experiential avoidance is problematic. The current study tested both between-person (trait) and within-person (daily) variation in experiential avoidance and negative affect as predictors of solitary and social drinking in a sample of 206 adult drinkers who completed daily diaries for 21 days. Participants higher in trait experiential avoidance drank alone more often, whereas those higher in trait negative affect consumed greater quantities when drinking alone. Although daily fluctuations in experiential avoidance did not predict solitary drinking, there was a significant interaction between daily experiential avoidance and trait negative affect. For participants high in trait negative affect, greater experiential avoidance on a given day predicted consuming more when drinking alone. For participants low in trait negative affect, greater experiential avoidance on a given day predicted drinking alone more often, but consuming fewer drinks on these occasions. Experiential avoidance did not predict social drinking in any model. Overall, results suggest that a broader tendency to experience negative affect sets the context for experiential avoidance to be linked to more harmful patterns of drinking. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

When is experiential avoidance harmful in the moment? Examining global experiential avoidance as a moderator.

BACKGROUND AND OBJECTIVES: Although experiential avoidance has been shown to predict a wide range of mental health problems, there has been minimal research to-date on the more immediate effects of engaging in experiential avoidance in the moment or the moderators that predict when it is more or less harmful. METHODS: An ecological momentary assessment (EMA) study was conducted with 70 undergraduate students who completed assessments three times a day, over 7 day as well as a baseline assessment of global questionnaires. RESULTS: Both greater global experiential avoidance and momentary experiential avoidance independently predicted greater momentary negative affect, lower positive affect, and lower valued action. Global experiential avoidance was also a significant moderator of momentary experiential avoidance such that experiential avoidance in the moment was more strongly related to negative effects among those high in global experiential avoidance. LIMITATIONS: Study limitations include a non-clinical student sample and use of unvalidated EMA items. CONCLUSIONS: Overall, these results suggest engaging in experiential avoidance in the moment has more negative, immediate effects particularly among those who engage in global, inflexible patterns of experiential avoidance.

Position paper: the science of deep specification.

We introduce our efforts within the project 'The science of deep specification' to work out the key formal underpinnings of industrial-scale formal specifications of software and hardware components, anticipating a world where large verified systems are routinely built out of smaller verified components that are also used by many other projects. We identify an important class of specification that has already been used in a few experiments that connect strong component-correctness theorems across the work of different teams. To help popularize the unique advantages of that style, we dub it deep specification, and we say that it encompasses specifications that are rich, two-sided, formal and live (terms that we define in the article). Our core team is developing a proof-of-concept system (based on the Coq proof assistant) whose specification and verification work is divided across largely decoupled subteams at our four institutions, encompassing hardware microarchitecture, compilers, operating systems and applications, along with cross-cutting principles and tools for effective specification. We also aim to catalyse interest in the approach, not just by basic researchers but also by users in industry.This article is part of the themed issue 'Verified trustworthy software systems'.

Evaluating an Adjunctive Mobile App to Enhance Psychological Flexibility in Acceptance and Commitment Therapy.

The primary aims of this study were to evaluate the feasibility and potential efficacy of a novel adjunctive mobile app designed to enhance the acquisition, strengthening, and generalization of acceptance and commitment therapy (ACT) skills being taught in therapy. A sample of 14 depressed/anxious clients receiving ACT used the ACT Daily app for 2 weeks in a pre-post, open trial design. Participants reported a high degree of program satisfaction. Clients significantly improved over the 2-week period on depression and anxiety symptoms as well as a range of psychological inflexibility measures. Analyses of mobile app data indicated effects of ACT Daily skill coaching on in-the-moment measures of inflexibility and symptoms, with unique effects found for acceptance and mindfulness. Adjunctive ACT mobile apps appear promising in enhancing therapy effects on psychological inflexibility and outcomes. A tailored skill coaching approach like ACT Daily based on randomly prompted assessments may be especially promising.

Eye problems in a woman with Churg-Strauss syndrome.

Churg-Strauss syndrome is a rare, systemic vasculitis of unknown cause. Ocular involvement is a rare but established complication and can lead to vision damage or blindness if not treated promptly. Treatment of ocular manifestations corresponds with systemic treatment of the disease and consists primarily of corticosteroids.

Web-Based Acceptance and Commitment Therapy for Mental Health Problems in College Students: A Randomized Controlled Trial.

There are significant challenges in addressing the mental health needs of college students. The current study tested an acceptance and commitment therapy (ACT), web-based self-help program to treat a broad range of psychological problems students struggle with. A sample of 79 college students was randomized to web-based ACT or a waitlist condition, with assessments at baseline and posttreatment. Results indicated adequate acceptability and program engagement for the ACT website. Relative to waitlist, participants receiving ACT improved on overall distress, general anxiety, social anxiety, depression, academic concerns, and positive mental health. There were no between-group effects on eating concerns, alcohol use, or hostility, or on some key ACT process of change measures. ACT participants improved more on mindful acceptance and obstruction to valued living, both of which mediated treatment outcomes. Results are discussed in the context of lessons learned with the website prototype, and areas for further research are presented.

Conditional Ultrasound Sensitivity of Poly[(N-isopropylacrylamide)-co-(vinyl imidazole)] Microgels for Controlled Lipase Release.

Triggering the release of cargo from a polymer network by ultrasonication as an external, noninvasive stimulus can be an interesting concept for on-demand release. Here, it is shown that, in pH- and thermosensitive microgels, the ultrasound sensitivity of the polymer network depends on the external conditions. Crosslinked poly[(N-isopropylacrylamide)-co-(vinyl imidazole)] microgels showed a volume phase transition temperature (VPTT) of 25-50 °C, which increases with decreasing pH. Above the VPTT the polymer chains are collapsed, while below VPTT they are extended. Only in the case of maximum observed swelling, where the polymer chains are expanded, the microgels are mechanically fragmented through ultrasonication. In contrast, when the polymer chains are partially collapsed it is not possible to manipulate the microgels by ultrasound. Additionally, the ultrasound-induced on-demand release of wheat germ lipase from the microgels could be demonstrated successfully. The principle of conditional ultrasound sensitivity is likely to be general and can be used for selection of matrix-cargo combinations.