Super-Consistent Estimation of Points of Impact in Nonparametric Regression with Functional Predictors

Predicting scalar outcomes using functional predictors is a classic problem in functional data analysis. In many applications, however, only specific locations or time-points of the functional predictors have an impact on the outcome. Such ``points of impact'' are typically unknown and have to be estimated in addition to estimating the usual model components. We show that our points of impact estimator enjoys a super-consistent convergence rate and does not require knowledge or pre-estimates of the unknown model components. This remarkable result facilitates the subsequent estimation of the remaining model components as shown in the theoretical part, where we consider the case of nonparametric models and the practically relevant case of generalized linear models. The finite sample properties of our estimators are assessed by means of a simulation study. Our methodology is motivated by data from a psychological experiment in which the participants were asked to continuously rate their emotional state while watching an affective video eliciting a varying intensity of emotional reactions

Multivariate brain prediction of heart rate and skin conductance responses to social threat

Psychosocial stressors induce autonomic nervous system (ANS) responses in multiple body systems that are linked to health risks. Much work has focused on the common effects of stress, but ANS responses in different body systems are dissociable and may result from distinct patterns of cortical–subcortical interactions. Here, we used machine learning to develop multivariate patterns of fMRI activity predictive of heart rate (HR) and skin conductance level (SCL) responses during social threat in humans (N = 18). Overall, brain patterns predicted both HR and SCL in cross-validated analyses successfully (r(HR) = 0.54, r(SCL) = 0.58, both p < 0.0001). These patterns partly reflected central stress mechanisms common to both responses because each pattern predicted the other signal to some degree (r(HR→SCL) = 0.21 and r(SCL→HR) = 0.22, both p < 0.01), but they were largely physiological response specific. Both patterns included positive predictive weights in dorsal anterior cingulate and cerebellum and negative weights in ventromedial PFC and local pattern similarity analyses within these regions suggested that they encode common central stress mechanisms. However, the predictive maps and searchlight analysis suggested that the patterns predictive of HR and SCL were substantially different across most of the brain, including significant differences in ventromedial PFC, insula, lateral PFC, pre-SMA, and dmPFC. Overall, the results indicate that specific patterns of cerebral activity track threat-induced autonomic responses in specific body systems. Physiological measures of threat are not interchangeable, but rather reflect specific interactions among brain systems. SIGNIFICANCE STATEMENT We show that threat-induced increases in heart rate and skin conductance share some common representations in the brain, located mainly in the vmPFC, temporal and parahippocampal cortices, thalamus, and brainstem. However, despite these similarities, the brain patterns that predict these two autonomic responses are largely distinct. This evidence for largely output-measure-specific regulation of autonomic responses argues against a common system hypothesis and provides evidence that different autonomic measures reflect distinct, measurable patterns of cortical–subcortical interactions

Effectiveness of a Self-Management Intervention to Promote an Active Lifestyle in Persons With Long-Term Spinal Cord Injury: The HABITS Randomized Clinical Trial

Background. Most people with long-term spinal cord injury (SCI) have a very inactive lifestyle. Higher activity levels have been associated with health benefits and enhanced quality of life. Consequently, encouraging an active lifestyle is important and behavioral interventions are needed to establish durable lifestyle changes. Objective. The Healthy Active Behavioral Intervention in SCI (HABITS) study was aimed to evaluate the effectiveness of a structured self-management intervention to promote an active lifestyle in inactive persons with long-term SCI. Methods. This assessor-blinded randomized controlled trial was conducted at 4 specialized SCI units in the Netherlands. Sixty-four individuals with long-term SCI (>10 years), wheelchair-user and physically inactive, were included. Participants were randomized to either a 16-week self-management intervention consisting of group meetings and individual counseling and a book, or to a control group that only received information about active lifestyle by one group meeting and a book. Measurements were performed at baseline, 16 weeks, and 42 weeks. Primary outcome measures were self-reported physical activity and minutes per day spent in wheelchair driving. Secondary outcomes included perceived behavioral control (exercise self-efficacy, proactive coping), stages of change concerning exercise, and attitude toward exercise. Results. Mixed models analyses adjusted for age, sex, level of SCI, time since injury, baseline body mass index, and location did not show significant differences between the intervention and control groups on the primary and secondary outcomes (P ≥.05). Conclusions. A structured 16-week self-management intervention was not effective to change behavior toward a more active lifestyle and to improve perceived behavioral control, stages of change, and attitude

Not Taking no for an Answer: the Interactional Organization of Accepting and Refusing Childhood Vaccination in the Netherlands

Communication-intervention strategies for reducing vaccine hesitancy have been primarily based on survey and interview data. Virtually absent is an understanding of how vaccine hesitancy is organized interactionally in its primary, natural environment of medical consultations between parents and healthcare providers. This article uses conversation analysis to describe the sequence organization of the action of providers soliciting parents’ vaccination intent. We demonstrate that parents’ acceptance is “preferred” and sequence-closure relevant and that refusal is “dispreferred” and sequence-expansion relevant. Regarding vaccine refusal, we describe three different sequence-expansive actions, including soliciting an account, cautioning about the consequences of vaccine refusal, and “keeping the door open” to future vaccination. Data are 62 videotaped interactions between providers and parents of newborns in the Netherlands. Findings have implications for the design of communication-intervention strategies involving understanding parents’ perspectives and providing them with information toward the goal of reducing their vaccine hesitancy

Hepatic Cyst Infection During Use of the Somatostatin Analog Lanreotide in Autosomal Dominant Polycystic Kidney Disease: An Interim Analysis of the Randomized Open-Label Multicenter DIPAK-1 Study

Introduction and Aims: The DIPAK-1 Study investigates the reno- and hepatoprotective efficacy of the somatostatin analog lanreotide compared with standard care in patients with later stage autosomal dominant polycystic kidney disease (ADPKD). During this trial, we witnessed several episodes of hepatic cyst infection, all during lanreotide treatment. We describe these events and provide a review of the literature. Methods: The DIPAK-1 Study is an ongoing investigator-driven, randomized, controlled, open-label multicenter trial. Patients (ADPKD, ages 18–60 years, estimated glomerular filtration rate 30–60 mL/min/1.73 m2) were randomized 1:1 to receive lanreotide 120 mg subcutaneously every 28 days or standard care during 120 weeks. Hepatic cyst infection was diagnosed by local physicians. Results: We included 309 ADPKD patients of which seven (median age 53 years [interquartile range: 48–55], 71% female, median estimated glomerular filtration rate 42 mL/min/1.73 m2 [interquartile range: 41–58]) developed eight episodes of hepatic cyst infection during 342 patient-years of lanreotide use (0.23 cases per 10 patient-years). These events were limited to patients receiving lanreotide (p < 0.001 vs. standard care). Baseline characteristics were similar between subjects who did or did not develop a hepatic cyst infection during lanreotide use, except for a history of hepatic cyst infection (29 vs. 0.7%, p < 0.001). Previous studies with somatostatin analogs reported cyst infections, but did not identify a causal relationship. Conclusions: These data suggest an increased risk for hepatic cyst infection during use of somatostatin analogs, especially in ADPKD patients with a history of hepatic cyst infection. The main results are still awaited to fully appreciate the risk–benefit ratio. ClinicalTrials.gov identifier: NCT 01616927

RNA-binding proteins to assess gene expression states of co-cultivated cells in response to tumor cells

BACKGROUND: Tumors and complex tissues consist of mixtures of communicating cells that differ significantly in their gene expression status. In order to understand how different cell types influence one another's gene expression, it will be necessary to monitor the mRNA profiles of each cell type independently and to dissect the mechanisms that regulate their gene expression outcomes. RESULTS: In order to approach these questions, we have used RNA-binding proteins such as ELAV/Hu, poly (A) binding protein (PABP) and cap-binding protein (eIF-4E) as reporters of gene expression. Here we demonstrate that the epitope-tagged RNA binding protein, PABP, expressed separately in tumor cells and endothelial cells can be used to discriminate their respective mRNA targets from mixtures of these cells without significant mRNA reassortment or exchange. Moreover, using this approach we identify a set of endothelial genes that respond to the presence of co-cultured breast tumor cells. CONCLUSION: RNA-binding proteins can be used as reporters to elucidate components of operational mRNA networks and operons involved in regulating cell-type specific gene expression in tissues and tumors

The risk and protective factors of heightened prenatal anxiety and depression during the COVID-19 lockdown

While pregnant women are already at-risk for developing symptoms of anxiety and depression, this is heightened during the COVID-19 pandemic. We compared anxiety and depression symptoms, as indicators of psychological distress, before and during COVID-19, and investigated the role of partner, social network and healthcare support on COVID-19-related worries and consequently on psychological distress. A national survey, conducted during the first lockdown in The Netherlands, assessed COVID-19 experiences and psychological distress (N = 1421), whereas a comparison sample (N = 1439) was screened for psychological distress in 2017–2018. During COVID-19, the percentage of mothers scoring above the questionnaires’ clinical cut-offs doubled for depression (6% and 12%) and anxiety (24% and 52%). Women reported increased partner support during COVID-19, compared to pre-pandemic, but decreased social and healthcare support. Higher support resulted in lower COVID-19-related worries, which in turn contributed to less psychological distress. Results suggest that a global pandemic exerts a heavy toll on pregnant women’s mental health. Psychological distress was substantially higher during the pandemic than the pre-pandemic years. We identified a protective role of partner, social, and healthcare support, with important implications for the current and future crisis management. Whether increased psychological distress is transient or persistent, and whether and how it affects the future generation remains to be determined