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Working memory (WM), a key determinant of many higher-order cognitive functions, declines in old age. Current research attempts to develop process-specific WM training procedures, which may lead to general cognitive improvement. Adaptivity of the training as well as the comparison of training gains to performance changes of an active control group are key factors in evaluating the effectiveness of a specific training program. In the present study, 55 younger adults (20-30 years of age) and 45 older adults (60-70 years of age) received 5 weeks of computerized training on various spatial and verbal WM tasks. Half of the sample received adaptive training (i.e., individually adjusted task difficulty), whereas the other half-worked on the same task material but on a low task difficulty level (active controls). Performance was assessed using criterion, near-transfer, and far-transfer tasks before training, after 5 weeks of intervention, as well as after a 3-month follow-up interval. Results indicate that (a) adaptive training generally led to larger training gains than low-level practice, (b) training and transfer gains were somewhat greater for younger than for older adults in some tasks, but comparable across age groups in other tasks, (c) far-transfer was observed to a test on sustained attention and for a self-rating scale on cognitive functioning in daily life for both young and old, and (d) training gains and transfer effects were maintained across the 3-month follow-up interval across age.

While there is a large body of evidence drawn from randomised controlled trials supporting the efficacy of SSGT in autistic adolescents, the control arms of these studies are almost exclusively treated either as usual or waitlist. Addressing this limitation, 90 verbal autistic adolescents (70% male) aged 12–17 years ( M  = 13.77, SD = 1.6) with IQ > 70 participated in this pragmatic two-armed randomised controlled trial design study evaluating the efficacy of sixteen 90-min sessions of SSGT KONTAKT® ( n  = 46) in comparison to a manualised interactive group cooking programme ( n  = 44) of equal dosage controlling for the potentially confounding effects of exposure to a social group context. The primary outcome was the adolescents’ progress towards achieving their personally meaningful social goals at follow-up. Secondary outcomes were changes in autistic traits, quality of life, facial emotion recognition skills, social anxiety, and loneliness. Assessments were conducted at baseline, post intervention and 12-week follow-up. The interaction between time point and group allocation was investigated through a random-effects regression model (linear mixed model) to examine changes in the dependent outcomes. While intention-to-treat analysis ( N  = 90) demonstrated that both SSGT (ES = 1.36, p  < .001) and active control (ES = 1.10, p  < .001) groups made progress towards their personally meaningful social goals at follow-up, KONTAKT® participants demonstrated greater progress in social goal attainment than their peers in the active control group (ES = 0.35, p  = .04). Findings suggest that KONTAKT® is efficacious in supporting autistic adolescents to achieve their personally meaningful social goals compared to other prosocial group activities. Trial registration : (1) Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12617001117303, registered 31 July 2017, anzctr.org.au; (2) ClinicalTrials.gov: NCT03294668 registered 22 September 2017, https://clinicaltrials.gov .

Neurofeedback techniques provide participants immediate feedback on neuronal signals, enabling them to modulate their brain activity. This technique holds promise to unveil brain–behavior relationship and offers opportunities for neuroenhancement. Establishing causal relationships between modulated brain activity and behavioral improvements requires rigorous experimental designs, including appropriate control groups and large samples. Our primary objective was to examine whether a single neurofeedback session, designed to enhance working memory through the modulation of theta or high-alpha frequencies, elicits specific changes in electrophysiological and cognitive outcomes. Additionally, we explored predictors of successful neuromodulation. A total of 101 healthy adults were assigned to groups trained to increase frontal theta, parietal high alpha, or random frequencies (active control group). We measured resting-state EEG, working memory performance, and self-reported psychological states before and after one neurofeedback session. Although our analyses revealed improvements in electrophysiological and behavioral outcomes, these gains were not specific to the experimental groups. An increase in the frequency targeted by the training has been observed for the theta and high alpha groups, but training designed to increase randomly selected frequencies appears to induce more generalized neuromodulation compared with targeting a specific frequency. Among all the predictors of neuromodulation examined, resting theta and high alpha amplitudes predicted specifically the increase of those frequencies during the training. These results highlight the challenge of integrating a control group based on enhancing randomly selected frequency bands and suggest potential avenues for optimizing interventions (e.g., by including a control group trained in both up- and down-regulation).

Internet-based cognitive behavioral therapy for insomnia (iCBT-I) provides flexibility but requires significant time and includes potentially challenging components such as sleep restriction therapy. This raises questions about its incremental effectiveness compared to less demanding minimal interventions such as sleep hygiene psychoeducation. This study aimed to assess the incremental efficacy of self-guided iCBT-I with optional on-demand feedback for university students with insomnia compared to a single session of digital psychoeducation on sleep hygiene. In a randomized controlled trial, 90 students with insomnia (Insomnia Severity Index ≥10) were randomly allocated to self-help-based iCBT-I (45/90, 50%) or one session of digital sleep hygiene psychoeducation with stimulus control instructions (active control group [aCG]: 45/90, 50%). The self-help-based iCBT-I consisted of 6 sessions on psychoeducation, sleep restriction, and stimulus control, including written feedback on demand from an eCoach. Assessments occurred at baseline (T1), 8 weeks after treatment (T2), and at a 6-month follow-up (T3) via web-based self-assessment and diagnostic telephone interviews. The primary outcome was insomnia severity at T2. Analyses of covariance were conducted in an intention-to-treat sample. Secondary outcomes included diagnoses of insomnia and major depression, sleep quality, sleep efficiency, worrying, recovery experiences, recovery activities, presenteeism, procrastination, cognitive irritation, and recuperation in sleep. There was no difference in insomnia severity at T2 between the iCBT-I group (mean 11.27, SD 5.21) and aCG group (mean 12.36, SD 4.16; F =1.12; P=.29; d=-0.26; 95% CI 0.68 to 0.17). A significant difference emerged at T3 (iCBT-I: mean 9.43, SD 5.36; aCG: mean 12.44, SD 5.39; F =4.72; P=.03), favoring iCBT-I with a medium effect (d=-0.57; 95% CI 1.07 to -0.06). Most secondary outcomes revealed no significant differences between the groups. In total, 51% (23/45) of participants in the iCBT-I group completed all 6 sessions, and 69% (31/45) completed the 4 core sessions. In the short term, students might benefit from low-intensity, easily accessible digital sleep hygiene psychoeducation or iCBT-I. However, it appears that iCBT-I offers superiority over sleep hygiene psychoeducation in the long term. German Clinical Trials Register DRKS00017737; https://drks.de/search/de/trial/DRKS00017737.

Many popular activities are thought by the general public to improve cognitive function. Such expectations can influence how often people engage in these activities, as well as the scientific evaluation of their putative cognitive benefits, e.g., placebo effects. Here, we gathered survey data about the public's perceptions of nine different activities commonly thought to be cognitively stimulating, including \"brain-training\" games. Information was collected about the degree to which participants thought each activity was beneficial for improving cognitive function and how often they engaged in each activity. The patterns of correlation between ratings reveal details about the perception of cognitive benefits and its relation to engagement. They suggest that participants varied with respect to an overarching perception of the entire set of activities, which were perceived also as divided into three clusters. Frequency of engagement and perceived cognitive benefits were positively correlated across participants for each activity considered individually. But, when the activities were compared, the magnitude of their perceived benefits was not a good predictor of their frequency of engagement (and vice versa). Though small, there were systematic demographic differences. Women were more optimistic than men about cognitive benefits. Individual participants differed in the range of their ratings of benefit across activities, and these ranges were greater for younger than older participants, suggesting that perceptions of benefit are more differentiated among the young. Besides contributing to a better understanding of public expectations of cognitive benefits, the findings of this study are relevant to the critical evaluation of such benefits. Our survey can be viewed as providing an interface between expectations held by the general public and the design of studies examining the efficacy of cognitive training. The type of information it provides could be used in the selection of activities performed by an active control group, so that control activities match the treatment intervention as closely as possible with respect to such expectations.

Neural correlates of working memory training remain a matter of debate, especially in older adults. We used functional magnetic resonance imaging (fMRI) together with an n-back task to measure brain plasticity in healthy middle-aged adults following an 8-week adaptive online verbal working memory training. Participants performed 32 sessions of this training on their personal computers. In addition, we assessed direct effects of the training by applying a verbal working memory task before and after the training. Participants (mean age 55.85 ± 4.24 years) were pseudo-randomly assigned to the experimental group (n=30) or an active control group (n=27). Training resulted in an activity decrease in regions known to be involved in verbal working memory (i.e., fronto-parieto-cerebellar circuitry and subcortical regions), indicating that the brain became potentially more efficient after the training. These activation decreases were associated with a significant performance improvement in the n-back task inside the scanner reflecting considerable practice effects. In addition, there were training-associated direct effects in the additional, external verbal working memory task (i.e., HAWIE-R digit span forward task), indicating that the training generally improved performance in this cognitive domain. These results led us to conclude that even at advanced age cognitive training can improve working memory capacity and increase neural efficiency in specific regions or networks.

Microneedle patches (MNPs) have been ranked as the highest global priority innovation for overcoming immunisation barriers in low-income and middle-income countries. This trial aimed to provide the first data on the tolerability, safety, and immunogenicity of a measles and rubella vaccine (MRV)-MNP in children. This single-centre, phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial was conducted in The Gambia. To be eligible, all participants had to be healthy according to prespecified criteria, aged 18–40 years for the adult cohort, 15–18 months for toddlers, or 9–10 months for infants, and to be available for visits throughout the follow-up period. The three age cohorts were randomly assigned in a 2:1 ratio (adults) or 1:1 ratio (toddlers and infants) to receive either an MRV-MNP (Micron Biomedical, Atlanta, GA, USA) and a placebo (0·9% sodium chloride) subcutaneous injection, or a placebo-MNP and an MRV subcutaneous injection (MRV-SC; Serum Institute of India, Pune, India). Unmasked staff ransomly assigned the participants using an online application, and they prepared visually identical preparations of the MRV-MNP or placebo-MNP and MRV-SC or placebo-SC, but were not involved in collecting endpoint data. Staff administering the study interventions, participants, parents, and study staff assessing trial endpoints were masked to treatment allocation. The safety population consists of all vaccinated participants, and analysis was conducted according to route of MRV administration, irrespective of subsequent protocol deviations. The immunogenicity population consisted of all vaccinated participants who had a baseline and day 42 visit result available, and who had no protocol deviations considered to substantially affect the immunogenicity endpoints. Solicited local and systemic adverse events were collected for 14 days following vaccination. Unsolicited adverse events were collected to day 180. Age de-escalation between cohorts was based on the review of the safety data to day 14 by an independent data monitoring committee. Serum neutralising antibodies to measles and rubella were measured at baseline, day 42, and day 180. Analysis was descriptive and included safety events, seroprotection and seroconversion rates, and geometric mean antibody concentrations. The trial was registered with the Pan African Clinical Trials Registry PACTR202008836432905, and is complete. Recruitment took place between May 18, 2021, and May 27, 2022. 45 adults, 120 toddlers, and 120 infants were randomly allocated and vaccinated. There were no safety concerns in the first 14 days following vaccination in either adults or toddlers, and age de-escalation proceeded accordingly. In infants, 93% (52/56; 95% CI 83·0–97·2) seroconverted to measles and 100% (58/58; 93·8–100) seroconverted to rubella following MRV-MNP administration, while 90% (52/58; 79·2–95·2) and 100% (59/59; 93·9–100) seroconverted to measles and rubella respectively, following MRV-SC. Induration at the MRV-MNP application site was the most frequent local reaction occurring in 46 (77%) of 60 toddlers and 39 (65%) of 60 infants. Related unsolicited adverse events, most commonly discolouration at the application site, were reported in 35 (58%) of 60 toddlers and 57 (95%) of 60 infants that had received the MRV-MNP. All local reactions were mild. There were no related severe or serious adverse events. The safety and immunogenicity data support the accelerated development of the MRV-MNP. Bill & Melinda Gates Foundation.

In December 2020, UNAIDS released a new set of ambitious targets calling for 95% of all people living with HIV to know their HIV status, 95% of all people with diagnosed HIV infection to receive sustained antiretroviral therapy, and 95% of all people receiving antiretroviral therapy to have viral suppression by 2025. Adopted by United Nations Member states in June 2021 as part of the new Political Declaration on HIV and AIDS, these targets, combined with ambitious primary prevention targets and focused attention to supporting enablers, aim to bridge inequalities in treatment coverage and outcomes and accelerate HIV incidence reductions by focusing on progress in all sub-populations, age groups and geographic settings. Here we summarise the evidence and decisions underpinning the new global targets.

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

We present results from a large (n = 3,016) field experiment at a global organization testing whether a brief science-based online diversity training can change attitudes and behaviors toward women in the workplace. Our preregistered field experiment included an active placebo control and measured participants’ attitudes and real workplace decisions up to 20 weeks postintervention. Among groups whose average untreated attitudes—whereas still supportive of women—were relatively less supportive of women than other groups, our diversity training successfully produced attitude change but not behavior change. On the other hand, our diversity training successfully generated some behavior change among groups whose average untreated attitudes were already strongly supportive of women before training. This paper extends our knowledge about the pathways to attitude and behavior change in the context of bias reduction. However, the results suggest that the one-off diversity trainings that are commonplace in organizations are unlikely to be stand-alone solutions for promoting equality in the workplace, particularly given their limited efficacy among those groups whose behaviors policymakers are most eager to influence.