Ovarian function recovery in breast cancer patients receiving adjuvant anastrozole treatment: updated results from the phase 3 DATA trial.

PURPOSE: Patients with chemotherapy-induced ovarian function failure (CIOFF) may experience ovarian function recovery (OFR). Earlier, we showed that OFR during treatment with anastrozole impacted the prognosis of hormone receptor-positive (HR+) breast cancer (BC) patients with CIOFF. Here, we present the long-term follow-up results. METHODS: Postmenopausal women with HR+ BC who were 45-57 years of age and received chemotherapy were identified from the phase 3 DATA study (NCT00301457) on the extended use of anastrozole. Eligible patients were categorised into two groups: patients with CIOFF and definitely postmenopausal patients. Patients with CIOFF were monitored for OFR. Disease-free survival (DFS), distant recurrence-free survival (DRFS), and overall survival (OS) were compared between patients with OFR and patients without OFR using multivariable Cox regression analyses, including OFR as a time-dependent covariate. BC-specific mortality (BCSM) was compared between groups using the Fine and Gray method. RESULTS: This study included 656 patients: 395 patients with CIOFF and 261 definitely postmenopausal patients. OFR occurred in 39 (12%) of 329 patients with CIOFF who were monitored for OFR. The median follow-up time was 13.3 years. Patients with OFR experienced a deterioration in DFS (hazard ratio (HR) = 1.54; 95% confidence interval (CI) 0.85-2.81), DRFS (HR = 1.51; 95% CI 0.73-3.11), OS (HR = 1.64; 95% CI 0.75-3.55), and BCSM (subdistribution HR = 1.98; 95% CI 0.84-4.63) when compared with patients without OFR. CONCLUSION: In patients with CIOFF, OFR during treatment with anastrozole was associated with a deterioration in BC outcomes. These findings underscore the importance of adequate ovarian function suppression in this subgroup of patients.

Changes in adolescents' daily-life solitary experiences during the COVID-19 pandemic: an experience sampling study.

BACKGROUND: Adolescent solitude was drastically impacted by the COVID-19 pandemic. As solitude is crucial for adolescent development through its association with both positive and negative developmental outcomes, it is critical to understand how adolescents' daily-life solitary experiences changed as a result of the pandemic. METHODS: Using three waves of Experience Sampling Method data from a longitudinal study, we compared adolescents' daily-life solitary experiences in the early (nT1=100; MAge=16.1; SDAge=1.9; 93% girls) and mid-pandemic (nT2=204; MAge=16.5; SDAge=2.0; 79% girls) to their pre-pandemic experiences. RESULTS: We found that adolescents with lower levels of pre-pandemic social support and social skills reported wanting to be alone less and feeling like an outsider more at both time points during the pandemic. In the mid-pandemic wave, adolescents with higher levels of pre-pandemic social support and social skills reported decreases in positive affect compared to the pre-pandemic wave. CONCLUSION: This study shows that adolescents' daily-life solitary experiences worsened throughout the COVID-19 pandemic. There should be continued concern for the wellbeing of all adolescents, not only those already at risk, as effects of the pandemic on mental health might only manifest later.

Anticipating future threats: Evidence for association, but not interaction, of childhood adversity and identity development with threat anticipation in adolescence.

AIM: Childhood adversity may result in a negative expectation of future interactions with others, also referred to as 'threat anticipation'. It may also negatively impact on identity development, which subsequently may influence how individuals deal with their environment. Here, we examine the hypotheses that (1) identity synthesis is associated with reduced anticipation of threat, whereas the opposite would be true for identity confusion, and (2) that identity confusion exacerbates the association between childhood adversity and threat anticipation. METHODS: One thousand nine hundred and thirteen adolescents from the general population (mean age = 13.8 years, SD = 1.86, range = 11-20) completed self-report questionnaires assessing exposure to childhood adversity, identity development and threat anticipation. RESULTS AND DISCUSSION: Identity development was significantly associated with threat anticipation in the expected direction: identity synthesis was associated with reduced anticipation of threat (ß = -.0013, p < .001), whereas identity confusion was association with increased threat anticipation (ß = .0017, p < .001). Furthermore, childhood adversity was positively associated with threat anticipation (ß = .0018, p < .001). However, no evidence for an interaction effect of identity on the association between childhood adversity and threat anticipation was found, suggesting childhood adversity and identity development have an independent rather than synergistic effect on threat anticipation. CONCLUSION: The current study illustrates the importance of exposure to childhood adversity and identity development for threat anticipation in adolescence. Further research is needed to clarify how both factors influence each other within a developmental framework.

Childhood Adversity and Emerging Psychotic Experiences: A Network Perspective.

BACKGROUND AND HYPOTHESIS: Childhood adversity is associated with a myriad of psychiatric symptoms, including psychotic experiences (PEs), and with multiple psychological processes that may all mediate these associations. STUDY DESIGN: Using a network approach, the present study examined the complex interactions between childhood adversity, PEs, other psychiatric symptoms, and multiple psychological mediators (ie, activity-related and social stress, negative affect, loneliness, threat anticipation, maladaptive cognitive emotion regulation, attachment insecurity) in a general population, adolescent sample (n = 865, age 12-20, 67% female). STUDY RESULTS: Centrality analyses revealed a pivotal role of depression, anxiety, negative affect, and loneliness within the network and a bridging role of threat anticipation between childhood adversity and maladaptive cognitive emotion regulation. By constructing shortest path networks, we found multiple existing paths between different categories of childhood adversity and PEs, with symptoms of general psychopathology (ie, anxiety, hostility, and somatization) as the main connective component. Sensitivity analyses confirmed the robustness and stability of the networks. Longitudinal analysis in a subsample with Wave 2 data (n = 161) further found that variables with higher centrality (ie, depression, negative affect, and loneliness) better predicted follow-up PEs. CONCLUSIONS: Pathways linking childhood adversity to PEs are complex, with multifaceted psychological and symptom-symptom interactions. They underscore the transdiagnostic, heterotypic nature of mental ill-health in young people experiencing PEs, in agreement with current clinical recommendations.

Risk factors for cancer of unknown primary: a literature review.

Cancer of Unknown Primary (CUP) is metastatic cancer with an unidentifiable primary tumour origin during life. It remains difficult to study the occurrence and aetiology of CUP. Hitherto, it is unclear whether risk factors are associated with CUP, yet identifying these factors could reveal whether CUP is a specific entity or a cluster of metastasised cancers from various primary tumour origins. Epidemiological studies on possible CUP risk factors were systematically searched in PubMed and Web of Science on February 1st, 2022. Studies, published before 2022, were included if they were observational human-based, provided relative risk estimates, and investigated possible CUP risk factors. A total of 5 case-control and 14 cohort studies were included. There appears to be an increased risk for smoking in relation to CUP. However, limited suggestive evidence was found to link alcohol consumption, diabetes mellitus, and family history of cancer as increased risks for CUP. No conclusive associations could be made for anthropometry, food intake (animal or plant-based), immunity disorders, lifestyle (overall), physical activity, or socioeconomic status and CUP risk. No other CUP risk factors have been studied. This review highlights smoking, alcohol consumption, diabetes mellitus and family history of cancer as CUP risk factors. Yet, there remains insufficient epidemiological evidence to conclude that CUP has its own specific risk factor profile.

The role of identity in the development of depressive, anxiety, and psychosis symptoms in adolescents exposed to childhood adversity.

INTRODUCTION: Childhood adversity is a major risk factor for psychiatric disorders and has especially been associated with an admixture of depressive, anxiety, and psychosis symptoms. Identity formation, a main developmental task during adolescence, may be impacted by these adverse experiences and act as an important process in the association between childhood adversity and psychopathology. METHODS: We investigated the association between childhood adversity, identity formation, and depressive, anxiety, and psychosis symptoms cross-sectionally in 1913 Flemish adolescents between 11 and 20 years old (mean = 13.76, SD = 1.86). Adolescents completed questionnaires during the first wave of the SIGMA study between January 2018 and May 2019. RESULTS: Childhood interpersonal adversity was associated with increased identity confusion and decreased identity synthesis. Additionally, identity confusion was associated with increased self-reported levels of psychopathology and potentially mediated the association between childhood adversity and psychopathology. CONCLUSION: This study highlights the importance of promoting healthy identity formation in adolescents with and without exposure to adverse childhood experiences.

Detecting anomalous experiences in the community: The Transpersonal Experiences Questionnaire (TEQ).

OBJECTIVES: There is growing recognition of the value of researching anomalous experiences in the general population to aid our understanding of the psychosis continuum. There are key differences in aims, foci and epistemologies of existing measures, with varying utility for specific research designs. This study addresses gaps in the literature by developing a measure of anomalous experiences with utility for longitudinal (time-sensitive) research, and with particular reliability for people towards the upper (high scoring) end of the continuum. METHODS: An online sample was recruited from the general population to provide questionnaire data for two study parts: (A) item selection and (B) psychometric evaluation. For Part A, both classical test theory and item response theory methods were used to select which items to be included from an initial pool of 57, generated from individuals with persistent anomalous experiences. For Part B, psychometric properties of the resulting measure were evaluated using exploratory and confirmatory factor analysis and tests of reliability and validity. RESULTS: Scores were provided by 532 participants, from which a 19-item scale, the Transpersonal Experiences Questionnaire (TEQ), was developed. The TEQ was found to be a unidimensional scale, with satisfactory internal consistency (0.85), good test-retest reliability and convergent validity. CONCLUSIONS: The TEQ can be used as a unidimensional scale to detect anomalous experiences in the general population, with particular reliability for people with higher incidence of these experiences.

Ecological and Convergent Validity of Experimentally and Dynamically Assessed Capacity for Social Contingency Detection Using the Perceptual Crossing Experiment in Adolescence.

The Perceptual Crossing Experiment (PCE) captures the capacity for social contingency detection using real-time social interaction dynamics but has not been externally validated. We tested ecological and convergent validity of the PCE in a sample of 208 adolescents from the general population, aged 11 to 19 years. We expected associations between PCE performance and (a) quantity and quality of social interaction in daily life, using Experience Sampling Methodology (ESM; ecological validity) and (b) self-reported social skills using a questionnaire (convergent validity). We also expected PCE performance to better explain variance in ESM social measures than self-reported social skills. Multilevel analyses showed that only self-reported social skills were positively associated with social experience of company in daily life. These initial results do not support ecological and convergent validity of the PCE. However, fueled by novel insights regarding the complexity of capturing social dynamics, we identified promising methodological advances for future validation efforts.

The role of threat anticipation in the development of psychopathology in adolescence: findings from the SIGMA Study.

Childhood adversity is associated with psychopathology. First evidence in adults suggests that threat anticipation, i.e., an enhanced anticipation of unpleasant events creating an enduring sense of threat, may be a putative mechanism linking childhood adversity to psychopathology. This study aimed to test the indirect effect of childhood adversity on psychopathology via threat anticipation in a large community sample of adolescents. We measured childhood trauma and bullying victimization (as indicators of childhood adversity), threat anticipation, general psychopathology and prodromal psychotic symptoms in adolescents aged 12-16 years (full sample size N = 1682; minimum sample size in the complete case sample N = 449) in wave I of the SIGMA study. We found strong evidence that childhood adversity (e.g. childhood trauma, adj. ß (aß) = 0.54, p < .001) and threat anticipation (e.g. aß = 0.36, p < .001) were associated with general psychopathology and prodromal psychotic symptoms. Moreover, there was evidence that the association between childhood adversity, general psychopathology and prodromal psychotic symptoms is mediated via pathways through threat anticipation (e.g. childhood trauma, aßindirect effect = 0.13, p < .001). Threat anticipation may be a potential mechanism linking childhood adversity and psychopathology in adolescents.

Lifetime and Current Self-Harm Thoughts and Behaviors and Their Relationship to Parent and Peer Attachment.

Background: Previous research suggests attachment is a vulnerability factor for self-harm thoughts and behaviors in adults. Yet, few studies have investigated this relationship during adolescence, although adolescence is a critical period for changes in attachment relationships and self-harm onset. Whether and how attachment relates to self-harm thoughts and behaviors as measured in daily life is also unknown. Aims: To investigate whether and how paternal, maternal, and peer attachment are associated with lifetime and current adolescent self-harm thoughts and behaviors. Additionally, to examine how different attachment bonds interact in relation to lifetime and current adolescent self-harm thoughts and behaviors. Method: Pre-existing data from N = 1,913 adolescents of the SIGMA study were used. Attachment and lifetime history of self-harm thoughts and behaviors were measured via retrospective questionnaires. Current self-harm thoughts and behaviors were assessed 10 times per day for 6 days using the experience sampling method (ESM). Results: Paternal and maternal attachments were associated with lifetime self-harm thoughts and behaviors and current self-harm thoughts. No significant associations were found between peer attachment and self-harm outcomes. Limitations: Some analyses were underpowered. Conclusion: Our results highlight the importance of parent-child attachment relationships, which may be intervention targets for prevention and treatment of adolescent self-harm.

General psychopathology and its social correlates in the daily lives of youth.

BACKGROUND: Adolescence is a period of both great social change, and of vulnerability to psychiatric distress. However, little is known about the associations between early psychopathology and social interactions at the fundamental level of daily life. To better understand the social correlates of subclinical psychopathology in adolescence, we assessed associations between general psychopathology and the quantity and quality of daily-life social interactions. METHODS: During a six-day experience sampling period, adolescent and young adult participants in Study 1 (n = 663) and Study 2 (n = 1027) reported the quantity and quality of their everyday social interactions. General psychopathology was assessed using the Symptom Checklist-90 and Brief Symptom Inventory-53. The relationship between psychopathology and each outcome variable was tested in separate multilevel linear and logistic regression models. RESULTS: General psychopathology was associated with social interaction quality. Associations between psychopathology and the number of social interactions were less apparent: In Study 1, participants with more psychopathology were not more alone, whereas Study 2 participants with higher levels of psychopathology were alone more. LIMITATIONS: Limitations include no separate investigation of distinct types of psychopathology, and relatively low compliance to the experience sampling in Study 2. CONCLUSIONS: Consistent associations between subclinical psychopathology and the quality of social interactions support the fundamentally social nature of early psychopathology. Moreover, negative experiences of social interactions may be more valuable markers of early psychopathology than a reduced quantity of social behaviors. Conceptualizations of daily-life social functioning, and prevention/intervention efforts would benefit from a greater consideration of the quality of everyday social experiences.

Vegetable and fruit consumption and cancer of unknown primary risk: results from the Netherlands cohort study on diet and cancer.

BACKGROUND: Cancer of Unknown Primary (CUP) is a metastatic cancer for which the primary lesion remains unidentifiable during life and little is also known about the modifiable risk factors that contribute to its development. This study investigates whether vegetables and fruits are associated with CUP risk. METHODS: We used data from the prospective Netherlands Cohort Study on Diet and Cancer which includes 120,852 participants aged between 55 and 69 years in 1986. All participants completed a self-administered questionnaire on cancer risk factors at baseline. Cancer follow-up was established through record linkage to the Netherlands Cancer Registry and the Dutch Pathology Registry. As a result, 867 incident CUP cases and 4005 subcohort members were available for case-cohort analyses after 20.3 years of follow-up. Multivariable adjusted hazard ratios were calculated using proportional hazards models. RESULTS: We observed no associations between total vegetable and fruit consumption (combined or as separate groups) and CUP risk. However, there appeared to be an inverse association between the consumption of raw leafy vegetables and CUP. With respect to individual vegetable and fruit items, we found neither vegetable nor fruit items to be associated with CUP risk. CONCLUSIONS: Overall, vegetable and fruit intake were not associated with CUP incidence within this cohort.

Type 2 diabetes mellitus and cancer of unknown primary risk: results from the Netherlands Cohort Study.

OBJECTIVE: Cancer of unknown primary (CUP) is a metastatic malignancy with an unidentifiable primary tumour origin. Previous studies suggest that type 2 diabetes mellitus (T2DM) and CUP risk are associated. This study examines the association in greater depth by investigating T2DM status, T2DM duration, T2DM age at diagnosis, and medication that was being used in relation to CUP. METHODS: Data were utilized from the Netherlands Cohort Study, a prospective cohort that includes 120 852 participants aged 55-69 years at baseline in 1986. All participants completed a self-administered questionnaire on cancer risk factors. CUP cases were identified through record linkage with the Netherlands Cancer Registry and Dutch Pathology Registry. After 20.3 years of follow-up, 963 incident CUP cases and 4288 subcohort members were available for case-cohort analyses. Proportional hazards models were employed to estimate multivariable-adjusted hazard ratios (HRs). RESULTS: Overall, we observed a nonsignificant positive association between T2DM status and CUP risk [HR, 1.35; 95% confidence interval (CI), 0.92-1.99], which increased in women after stratification for sex (HR, 1.55; 95% CI, 0.90-2.64). For participants who were aged less than 50 years at diagnosis of T2DM, a statistically significant positive association was found in relation to CUP (HR, 2.42; 95% CI, 1.26-4.65), compared with participants without T2DM. CONCLUSION: Our findings indicate that there is a nonsignificant positive association between T2DM and CUP risk and that the association became stronger in women in stratified analyses.

Identifying Clusters of Adolescents Based on Their Daily-Life Social Withdrawal Experience.

Social withdrawal is often presented as overall negative, with a focus on loneliness and peer exclusion. However, social withdrawal is also a part of normative adolescent development, which indicates that groups of adolescents potentially experience social withdrawal differently from one another. This study investigated whether different groups of adolescents experienced social withdrawal in daily life as positive versus negative, using experience sampling data from a large-scale study on mental health in general population adolescents aged 11 to 20 (n = 1913, MAge = 13.8, SDAge = 1.9, 63% female) from the Flemish region in Belgium. Two social withdrawal clusters were identified using model-based cluster analysis: one cluster characterized by high levels of positive affect and one cluster characterized by high levels of negative affect, loneliness and exclusion. Logistic regression showed that boys had 66% decreased odds of belonging to the negative cluster. These results show that daily-life social withdrawal experiences are heterogeneous in adolescence, which strengthens the view that, both in research and clinical practice, social withdrawal should not be seen as necessarily maladaptive.

Adherence to the World Cancer Research Fund and the American Institute for Cancer Research lifestyle recommendations for cancer prevention and Cancer of Unknown Primary risk.

BACKGROUND & AIMS: The World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) updated their cancer prevention recommendations in 2018. Adherence to these recommendations has been associated with lower cancer risk and mortality. However, adherence in relation to Cancer of Unknown Primary (CUP) risk has not been studied. This study investigates whether adherence to the WCRF/AICR recommendations is associated with CUP risk. METHODS: Data from the prospective Netherlands Cohort Study on diet and cancer was used to measure adherence to the recommendations in relation to CUP risk. The cohort includes 120 852 participants (aged 55-69 years), who completed a self-administered questionnaire on cancer risk factors at baseline. Adherence was investigated with respect to body fatness, physical activity, plant foods, meat consumption and alcohol. Incident CUP cases were identified through record linkage to the Netherlands Cancer Registry and Dutch Pathology Registry. A follow-up of 20.3 years, resulted in 856 incident CUP cases and 3911 subcohort members with complete information available for case-cohort analyses. Multivariable adjusted hazard ratios were estimated using proportional hazards models and were adjusted for age at baseline, sex, cigarette smoking (status, frequency, and duration) and total energy intake. RESULTS: Highest adherence appeared to be associated with decreased CUP risk in the age-sex adjusted model (HR: 0.76, 95% CI: 0.62-0.92). After additional adjustment for cigarette smoking (status, frequency, and duration), the association attenuated and was no longer statistically significant. No multiplicative interactions were observed between sex nor smoking status and overall adherence in relation to CUP. CONCLUSION: Within this cohort, highest adherence to the WCRF/AICR recommendations is not statistically significantly associated with decreased CUP risk after multivariable adjustment.

Momentary Manifestations of Negative Symptoms as Predictors of Clinical Outcomes in People at High Risk for Psychosis: Experience Sampling Study.

BACKGROUND: Negative symptoms occur in individuals at ultrahigh risk (UHR) for psychosis. Although there is evidence that observer ratings of negative symptoms are associated with level of functioning, the predictive value of subjective experience in daily life for individuals at UHR has not been studied yet. OBJECTIVE: This study therefore aims to investigate the predictive value of momentary manifestations of negative symptoms for clinical outcomes in individuals at UHR. METHODS: Experience sampling methodology was used to measure momentary manifestations of negative symptoms (blunted affective experience, lack of social drive, anhedonia, and social anhedonia) in the daily lives of 79 individuals at UHR. Clinical outcomes (level of functioning, illness severity, UHR status, and transition status) were assessed at baseline and at 1- and 2-year follow-ups. RESULTS: Lack of social drive, operationalized as greater experienced pleasantness of being alone, was associated with poorer functioning at the 2-year follow-up (b=-4.62, P=.01). Higher levels of anhedonia were associated with poorer functioning at the 1-year follow-up (b=5.61, P=.02). Higher levels of social anhedonia were associated with poorer functioning (eg, disability subscale: b=6.36, P=.006) and greater illness severity (b=-0.38, P=.045) at the 1-year follow-up. In exploratory analyses, there was evidence that individuals with greater variability of positive affect (used as a measure of blunted affective experience) experienced a shorter time to remission from UHR status at follow-up (hazard ratio=4.93, P=.005). CONCLUSIONS: Targeting negative symptoms in individuals at UHR may help to predict clinical outcomes and may be a promising target for interventions in the early stages of psychosis.

Pleiotropic Effects of Atorvastatin Result in a Downregulation of the Carboxypeptidase U System (CPU, TAFIa, CPB2) in a Mouse Model of Advanced Atherosclerosis.

Statins (hydroxymethyl-glutaryl-CoA-reductase inhibitors) lower procarboxypeptidase U (proCPU, TAFI, proCPB2). However, it is challenging to prove whether this is a lipid or non-lipid-related pleiotropic effect, since statin treatment decreases cholesterol levels in humans. In apolipoprotein E-deficient mice with a heterozygous mutation in the fibrillin-1 gene (ApoE-/-Fbn1C1039G+/-), a model of advanced atherosclerosis, statins do not lower cholesterol. Consequently, studying cholesterol-independent effects of statins can be achieved more straightforwardly in these mice. Female ApoE -/-Fbn1C1039G+/- mice were fed a Western diet (WD). At week 10 of WD, mice were divided into a WD group (receiving WD only) and a WD + atorvastatin group (receiving 10 mg/kg/day atorvastatin +WD) group. After 15 weeks, blood was collected from the retro-orbital plexus, and the mice were sacrificed. Total plasma cholesterol and C-reactive protein (CRP) were measured with commercially available kits. Plasma proCPU levels were determined with an activity-based assay. Total plasma cholesterol levels were not significantly different between both groups, while proCPU levels were significantly lower in the WD + atorvastatin group. Interestingly proCPU levels correlated with CRP and circulating monocytes. In conclusion, our results confirm that atorvastatin downregulates proCPU levels in ApoE-/-Fbn1C1039G+/- mice on a WD, and evidence was provided that this downregulation is a pleiotropic effect of atorvastatin treatment.

Daily-Life Social Experiences as a Potential Mediator of the Relationship Between Parenting and Psychopathology in Adolescence.

Adolescence is a vulnerable period for psychopathology development, and certain parenting styles are consistent and robust predictors of a broad range of mental health outcomes. The mechanisms through which maladaptive parenting styles affect the development of psychopathology are assumed to be largely social in nature. Yet, the social mechanisms linking parenting to psychopathology are unexplored at arguably the most important level of functioning: daily life. This study aims to identify the associations between three parenting styles, and the experience of daily-life social interactions. Furthermore, we aim to explore the extent to which these parenting styles and altered daily-life social experiences are associated with psychopathology. In this study, we recruited a sample of N = 1,913 adolescents (63.3% girls; mean age = 13.7, age range = 11 to 20) as part of the first wave of the longitudinal cohort study "SIGMA". Parenting styles (psychological control, responsiveness, and autonomy support) and psychopathology symptoms were assessed using a retrospective questionnaire battery. The experienced quality of social interactions in different types of company was assessed using the experience sampling method, ten times per day for 6 days. Direct associations between parenting styles and general quality of daily-life social experiences were tested using a three-level linear model, revealing significant associations between social experiences and different parenting styles. When interaction effects were added to this model, we found that maternal responsiveness and paternal psychological control mainly related to altered qualities of social interactions with parents, while paternal autonomy support was associated with better experiences of non-family social interactions. Finally, an exploratory path analysis highlighted how both paternal autonomy support and altered quality of non-family interactions are uniquely associated with psychopathology levels. These findings demonstrate the general and pervasive effects of maladaptive parenting styles, as parenting seems to broadly affect adolescents' interactions with different types of social partners in everyday life. Moreover, they illustrate a potential mediated relationship in which altered daily-life social interactions could drive the development of psychopathology. A stronger focus may be required on the role of altered day-to-day social experiences in the prevention and potentially, the treatment, of adolescent psychopathology.

The Impact of COVID-19 on Adolescents' Daily Lives: The Role of Parent-Child Relationship Quality.

COVID-19 lockdown measures have profoundly impacted adolescent' daily life, with research suggesting an increase in irritability, stress, loneliness, and family conflict. A potential protective factor is parent-child relationship quality; however, no studies have investigated this. We used data from SIGMA, a longitudinal, experience sampling cohort study, in which N = 173 adolescents aged 11 to 20 were tested before and during COVID-19. Multilevel analyses showed decreased daily-life irritability and increased loneliness from pre- to mid-pandemic. Daily-life stress levels were unchanged. Relationship quality was negatively associated with irritability and loneliness and buffered against the increase in loneliness. Effect sizes were small and do not support a strong effect of the first lockdown on irritability, stress, loneliness, and family conflict in adolescents.

Family history of cancer in first degree relatives and risk of cancer of unknown primary.

OBJECTIVE: Cancer of Unknown Primary (CUP) refers to the presence of metastatic lesions, with no identifiable primary site during the patient's lifetime. Poor survival and lack of available treatment highlight the need to identify potential CUP risk factors. We investigated whether a family history of cancer is associated with increased CUP risk. METHODS: We performed a case cohort analysis using data from the Netherlands Cohort Study, which included a total of 963 CUP cases and 4,288 subcohort members. A Cox Proportional Hazards Regression was used to compare CUP risk in participants who reported to have a family member with cancer to those who did not, whilst adjusting for confounders. RESULTS: In general, we observed no increased CUP risk in those who reported a family history of cancer. CUP risk appeared slightly increased in those who reported cancer in a sibling (HR: 1.16, 95% CI: 0.97-1.38), especially in those with a sister with cancer compared with those without (HR: 1.23, 95% CI: 0.99-1.53), although these findings are not statistically significant. CONCLUSION: Having a family history of cancer is not an independent risk factor of CUP.