A Smartphone Serious Game for Adolescents (Grow It! App):Development, Feasibility, and Acceptance Study

BACKGROUND: Anxiety and mood problems in adolescents often go unnoticed and may therefore remain untreated. Identifying and preventing the development of emotional problems requires monitoring and effective tools to strengthen adolescents' resilience, for example, by enhancing coping skills. OBJECTIVE: This study describes the developmental process, feasibility, and acceptance of Grow It!, a multiplayer serious game app for adolescents aged 12-25 years. The app consists of the experience sampling method (ESM) to monitor thoughts, behaviors, and emotions in daily life to enhance self-insight and daily cognitive behavioral therapy–based challenges to promote adaptive coping. METHODS: Our approach entails an iterative game design process combined with an agile method to develop the smartphone app. The incorporated game features (ie, challenges, chat functionality, and visual representation) in the Grow It! app were co-designed with adolescent end users to increase participant engagement and adherence. RESULTS: The Grow It! app was delivered for Android and iOS in May 2020. Grow It! was offered to adolescents during the COVID-19 crisis between May and December 2020. Participants of the Grow It! COVID-19 study (sample 1: N=685; mean age 16.19, SD 3.11 years; 193/685, 28.2% boys; sample 2: N=1035; mean age 18.78, SD 3.51 years; 193/1035, 18.64% boys) completed 31.5% (13.2/42) to 49.5% (10.4/21) of challenges. Compliance of ESM was suboptimal (35.1/210, 16.7% to 32.5/105, 30.9%). Follow-up questionnaires indicated an overall score of the app of 7.1 out of 10. Moreover, 72.6% (278/383) to 75.6% (487/644) would recommend the app to friends. CONCLUSIONS: To our knowledge, Grow It! is the first gamified ESM app that both measures individual differences in emotional dynamics and offers an integrated cognitive behavioral therapy–based intervention. Our findings support the feasibility and acceptance, and therefore applicability, of the Grow It! app in adolescents. Further iterations of this serious game app will focus on the increase of compliance and on providing participants feedback through their personal mood profiles

A Genetic Population Isolate in The Netherlands Showing Extensive Haplotype Sharing and Long Regions of Homozygosity

Genetic isolated populations have features that may facilitate genetic analyses and can be leveraged to improve power of mapping genes to complex traits. Our aim was to test the extent to which a population with a former history of geographic isolation and religious endogamy, and currently with one of the highest fertility rates in The Netherlands, shows signs of genetic isolation. For this purpose, genome-wide genotype data was collected of 72 unrelated individuals from this population as well as in a sample of 104 random control subjects from The Netherlands. Additional reference data from different populations and population isolates was available through HapMap and the Human Genome Diversity Project. We performed a number of analyses to compare the genetic structure between these populations: we calculated the pairwise genetic distance between populations, examined the extent of identical-by-descent (IBD) sharing and estimated the effective population size. Genetic analysis of this population showed consistent patterns of a population isolate at all levels tested. We confirmed that this population is most closely related to the Dutch control subjects, and detected high levels of IBD sharing and runs of homozygosity at equal or even higher levels than observed in previously described population isolates. The effective population size of this population was estimated to be several orders of magnitude smaller than that of the Dutch control sample. We conclude that the geographic isolation of this population combined with rapid population growth has resulted in a genetic isolate with great potential value for future genetic studies

Causes and circumstances of maternal death:a secondary analysis of the Community-Level Interventions for (CLIP) trials cohort

BACKGROUND: Incomplete vital registration systems mean that causes of death during pregnancy and childbirth are poorly understood in low-income and middle-income countries. To inform global efforts to reduce maternal mortality, we compared physician review and computerised analysis of verbal autopsies (interpreting verbal autopsies [InterVA] software), to understand their agreement on maternal cause of death and circumstances of mortality categories (COMCATs) in the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials. METHODS: The CLIP trials took place in India, Pakistan, and Mozambique, enrolling pregnant women aged 12–49 years between Nov 1, 2014, and Feb 28, 2017. 69 330 pregnant women were enrolled in 44 clusters (36 008 in the 22 intervention clusters and 33 322 in the 22 control clusters). In this secondary analysis of maternal deaths in CLIP, we included women who died in any of the 22 intervention clusters or 22 control clusters. Trained staff administered the WHO 2012 verbal autopsy after maternal deaths. Two physicians (and a third for consensus, if needed) reviewed trial surveillance data and verbal autopsies, and, in intervention clusters, community health worker-led visit data. They determined cause of death according to the WHO International Classification of Diseases-Maternal Mortality (ICD-MM). Verbal autopsies were also analysed by InterVA computer models (versions 4 and 5) to generate cause of death. COMCAT analysis was provided by InterVA-5 and, in India, by physician review of Maternal Newborn Health Registry data. Causes of death and COMCATs assigned by physician review, Inter-VA-4, and InterVA-5 were compared, with agreement assessed with Cohen's κ coefficient. FINDINGS: Of 61 988 pregnancies with successful follow-up in the CLIP trials, 143 maternal deaths were reported (16 deaths in India, 105 in Pakistan, and 22 in Mozambique). The maternal death rate was 231 (95% CI 193–268) per 100 000 identified pregnancies. Most deaths were attributed to direct maternal causes (rather than indirect or undetermined causes as per ICD-MM classification), with fair to good agreement between physician review and InterVA-4 (κ=0·56 [95% CI 0·43–0·66]) or InterVA-5 (κ=0·44 [0·30–0·57]), and InterVA-4 and InterVA-5 (κ=0·72 [0·60–0·84]). The top three causes of death were the same by physician review, InterVA-4, and InterVA-5 (ICD-MM categories obstetric haemorrhage, non-obstetric complications, and hypertensive disorders); however, attribution of individual patient deaths to obstetric haemorrhage varied more between methods (physician review, 38 [27%] deaths; InterVA-4, 69 [48%] deaths; and InterVA-5, 82 [57%] deaths), than did attribution to non-obstetric causes (physician review, 39 [27%] deaths; InterVA-4, 37 [26%] deaths; and InterVA-5, 28 [20%] deaths) or hypertensive disorders (physician review, 23 [16%] deaths; InterVA-4, 25 [17%] deaths; and InterVA-5, 24 [17%] deaths). Agreement for all nine ICD-MM categories was fair for physician review versus InterVA-4 (κ=0·48 [0·38–0·58]), poor for physician review versus InterVA-5 (κ=0·36 [0·27–0·46]), and good for InterVA-4 versus InterVA-5 (κ=0·69 [0·59–0·79]). The most commonly assigned COMCATs by InterVA-5 were emergencies (68 [48%] of 143 deaths) and health systems (62 [43%] deaths), and by physician review (India only) were health systems (seven [44%] of 16 deaths) and inevitability (five [31%] deaths); agreement between InterVA-5 and physician review (India data only) was poor (κ=0·04 [0·00–0·15]). INTERPRETATION: Our findings indicate that InterVA-5 is less accurate than InterVA-4 at ascertaining causes and circumstances of maternal death, when compared with physician review. Our results suggest a need to improve the next iteration of InterVA, and for researchers and clinicians to preferentially use InterVA-4 when recording maternal deaths. FUNDING: University of British Columbia (grantee of the Bill & Melinda Gates Foundation)

The Shine-Through Masking Paradigm Is a Potential Endophenotype of Schizophrenia

BACKGROUND: To understand the genetics of schizophrenia, a hunt for so-called intermediate phenotypes or endophenotypes is ongoing. Visual masking has been proposed to be such an endophenotype. However, no systematic study has been conducted yet to prove this claim. Here, we present the first study showing that masking meets the most important criteria for an endophenotype. METHODOLOGY/PRINCIPAL FINDINGS: We tested 62 schizophrenic patients, 39 non-affected first-degree relatives, and 38 healthy controls in the shine-through masking paradigm and, in addition, in the Continuous Performance Test (CPT) and the Wisconsin Card Sorting Test (WCST). Most importantly, masking performance of relatives was significantly in between the one of patients and controls in the shine-through paradigm. Moreover, deficits were stable throughout one year. Using receiver operating characteristics (ROC) methods, we show that the shine-through paradigm distinguishes with high sensitivity and specificity between schizophrenic patients, first-order relatives and healthy controls. CONCLUSIONS/SIGNIFICANCE: The shine-through paradigm is a potential endophenotype

Gut Feelings as a Third Track in General Practitioners’ Diagnostic Reasoning

BACKGROUND: General practitioners (GPs) are often faced with complicated, vague problems in situations of uncertainty that they have to solve at short notice. In such situations, gut feelings seem to play a substantial role in their diagnostic process. Qualitative research distinguished a sense of alarm and a sense of reassurance. However, not every GP trusted their gut feelings, since a scientific explanation is lacking. OBJECTIVE: This paper explains how gut feelings arise and function in GPs' diagnostic reasoning. APPROACH: The paper reviews literature from medical, psychological and neuroscientific perspectives. CONCLUSIONS: Gut feelings in general practice are based on the interaction between patient information and a GP's knowledge and experience. This is visualized in a knowledge-based model of GPs' diagnostic reasoning emphasizing that this complex task combines analytical and non-analytical cognitive processes. The model integrates the two well-known diagnostic reasoning tracks of medical decision-making and medical problem-solving, and adds gut feelings as a third track. Analytical and non-analytical diagnostic reasoning interacts continuously, and GPs use elements of all three tracks, depending on the task and the situation. In this dual process theory, gut feelings emerge as a consequence of non-analytical processing of the available information and knowledge, either reassuring GPs or alerting them that something is wrong and action is required. The role of affect as a heuristic within the physician's knowledge network explains how gut feelings may help GPs to navigate in a mostly efficient way in the often complex and uncertain diagnostic situations of general practice. Emotion research and neuroscientific data support the unmistakable role of affect in the process of making decisions and explain the bodily sensation of gut feelings.The implications for health care practice and medical education are discussed

Global landscape review of serotype-specific invasive pneumococcal disease surveillance among countries using PCV10/13: The pneumococcal serotype replacement and distribution estimation (PSERENADE) project

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon

Temporal Information Processing in Short- and Long-Term Memory of Patients with Schizophrenia

Cognitive deficits of patients with schizophrenia have been largely recognized as core symptoms of the disorder. One neglected factor that contributes to these deficits is the comprehension of time. In the present study, we assessed temporal information processing and manipulation from short- and long-term memory in 34 patients with chronic schizophrenia and 34 matched healthy controls. On the short-term memory temporal-order reconstruction task, an incidental or intentional learning strategy was deployed. Patients showed worse overall performance than healthy controls. The intentional learning strategy led to dissociable performance improvement in both groups. Whereas healthy controls improved on a performance measure (serial organization), patients improved on an error measure (inappropriate semantic clustering) when using the intentional instead of the incidental learning strategy. On the long-term memory script-generation task, routine and non-routine events of everyday activities (e.g., buying groceries) had to be generated in either chronological or inverted temporal order. Patients were slower than controls at generating events in the chronological routine condition only. They also committed more sequencing and boundary errors in the inverted conditions. The number of irrelevant events was higher in patients in the chronological, non-routine condition. These results suggest that patients with schizophrenia imprecisely access temporal information from short- and long-term memory. In short-term memory, processing of temporal information led to a reduction in errors rather than, as was the case in healthy controls, to an improvement in temporal-order recall. When accessing temporal information from long-term memory, patients were slower and committed more sequencing, boundary, and intrusion errors. Together, these results suggest that time information can be accessed and processed only imprecisely by patients who provide evidence for impaired time comprehension. This could contribute to symptomatic cognitive deficits and strategic inefficiency in schizophrenia

Psychophysiological Markers of Vulnerability to Psychopathology in Men with an Extra X Chromosome (XXY)

Studying genetically defined syndromes associated with increased risk for psychopathology may help in understanding neurodevelopmental mechanisms related to risk for psychopathology. Klinefelter syndrome (47,XXY) is one of the most common sex chromosomal aneuploidies (1 in 650 male births) and associated with increased vulnerability for psychopathology, including psychotic symptoms. Yet, it remains unknown whether this increased risk is associated with underlying psychophysiological mechanisms that are typically deficient in individuals with psychotic disorders. The present study assessed three “classic” psychophysiological markers of psychosis in Klinefelter syndrome (KS): smooth pursuit eye movements (SPEM), prepulse inhibition (PPI) and P50 suppression. Fourteen adults with KS and 15 non-clinical adults participated in the study. Data on SPEM (reflecting visuo-motor control) as well as PPI and P50 suppression (reflecting sensory gating) were collected. Dysfunctions in SPEM were observed in individuals with KS, with less smooth pursuit as expressed in lower position gain. Also, reduced sensory gating in individuals with KS was suggested by significantly reduced prepulse inhibition of the startle response (PPI) (effect size 1.6). No abnormalities were found in suppression of the P50 (effect size 0.6). We speculate that impairments in these psychophysiological mechanisms may reflect core brain dysfunctions that may also mediate the described increased vulnerability for psychotic symptoms in KS. Although speculative, such deficit specific, rather than disorder specific, psychophysiological dysfunctions in KS might convey vulnerability to other types of psychopathology as well. As KS already can be diagnosed prenatally, the predictive value of childhood impairments in prepulse inhibition and smooth pursuit for development of psychopathology later in life could be assessed. In sum, studying individuals with KS may prove to be an avenue of research leading to new hypotheses and insights into “at risk” pathways to psychopathology