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Individual differences in the quality of early experiences with primary caregivers have been reliably implicated in the development of socioemotional adjustment and, more recently, physical health. However, few studies have examined the development of such associations with physical health into the adult years. To that end, the current study used prospective, longitudinal data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (

An unsettled question in attachment theory and research is the extent to which children's attachment patterns with mothers and fathers jointly predict developmental outcomes. In this study, we used individual participant data (IPD) meta-analysis to assess whether early attachment networks with mothers and fathers are associated with children's internalizing and externalizing behavioral problems. Following a pre-registered protocol, data from 9 studies and 1,097 children (mean age: 28.67 months) with attachment classifications to both mothers and fathers were included in analyses. We used a linear mixed effects analysis to assess differences in children's internalizing and externalizing behavioral problems as assessed via the average of both maternal and paternal reports based on whether children had two, one, or no insecure (or disorganized) attachments. Results indicated that children with an insecure attachment relationship with one or both parents were at higher risk for elevated internalizing behavioral problems compared with children who were securely attached to both parents. Children whose attachment relationships with both parents were classified as disorganized had more externalizing behavioral problems compared to children with either one or no disorganized attachment relationship with their parents. Across attachment classification networks and behavioral problems, findings suggest (a) an increased vulnerability to behavioral problems when children have insecure or disorganized attachment to both parents, and (b) that mother-child and father-child attachment relationships may not differ in the roles they play in children's development of internalizing and externalizing behavioral problems.

Impacts of the COVID-19 pandemic in the United States have been exacerbated by pre-existing inequities in resources and opportunities, leaving the most vulnerable to face a multitude of hardships. The goal of the current study was to characterise COVID-19-related stressful life events in specific life domains and to identify the sociodemographic characteristics of individuals who are more likely to experience such events. Participants (n = 372, 57% female) in a follow-up study of the NICHD Study of Early Child Care and Youth Development completed the Epidemic-Pandemic Impacts Inventory (June-August 2020) to assess COVID-19-related stressors. Sociodemographic factors (gender, race/ethnicity, socioeconomic status and wealth) were examined simultaneously as predictors of the number of stressful life events in separate categories of work/finances, home life, social activity, health and healthcare, adjusted for covariates (household size, community COVID-19 transmission risk). In negative binomial regression analyses, being female (vs. male) predicted a 31%, 64%, 13% and 94% increase in the number of stressful life events in domains of work/finances, home life, social activity and healthcare, respectively, whereas each one standard deviation increase in wealth predicted a 17%, 16% and 21% reduction in the number of stressful life events in domains of work/finances, COVID-19 infection and healthcare, respectively. Findings highlight the pronounced and far-reaching impacts of the COVID-19 pandemic on women as well as the unique role wealth may play in lessening such impacts. This new knowledge may be leveraged to develop intervention and policy-related strategies to remediate impacts of COVID-19-related stressors on those most vulnerable.

Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V., ResMed Foundation European Respiratory Society, ERS European Respiratory Society, ERS European Respiratory Society, ERS, The ESADA network has received support from the European Union COST action B26 and the European Respiratory Society (ERS) funded Clinical Research Collaboration (CRC). Unrestricted seeding grants from the ResMed Foundation and the Philips Respironics Foundation for establishment of the database in 2007 and 2011 are gratefully acknowledged. The ESADA network has a scientific collaboration with Bayer AG., Nonfinancial support was provided by the European Sleep Research Society (ESRS) and the European Respiratory Society (ERS) in terms of logistics for communication, meetings and data presentations for the ESADA collaborators., Dr. Verbraecken reports grants and personal fees from ResMed, Bioprojet, Jazz Pharmaceutics; personal fees from Philips, Sanofi, Agfa-Gevaert, grants from AirLiquide; personal fees from Springer, Westfalen Medical, SomnoMed, Vivisol, Total Care, Medidis, Fisher & Paykel, Wave Medical, OSG, Mediq Tefa, NightBalance, Heinen & Löwenstein, AstraZen, Accuramed, Bekaert Deslee Academy and UCB Pharma, outside the submitted work. Dr. Hedner reports grants from ResMed, Philips Respironics, and the European Respiratory Society all related to maintenance of database on behalf of the ESADA group during the conduct of the study. Dr. Grote reports grants from Bayer, Resmed, Respironics/Philips, and from the European Respiratory Society during the conduct of the study; non-financial support and other from Itamar Medical, Resmed, Philips, and Astra Zeneca, outside the submitted work. In addition, Dr. Grote has a patent on sleep apnea therapy licensed. The remaining co-authors have no conflict of interest to declare.

International audience; Background and objective: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort.Methods: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2 ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency).Results: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP.Conclusion: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

WOS: 000482433800011, PubMed ID: 30467691, Purpose The aim of the current study was to further investigate the concept of previously reported high occurrence of comorbidities in obstructive sleep patients (OSA) with insomnia-like symptoms. We hypothesized that this finding at least partly is mediated by nocturnal hypoxia. Moreover, we speculated that the spectrum of the clinical OSA phenotypes differs between European geographical regions. Methods Cohort of the European Sleep Apnea Database (n = 17,325; 29.9% females) was divided into five subcohorts according to geographical region (North, East, South, West, Central) and further into four clinical presentation phenotypes based on daytime symptoms (EDS) and characteristics suggestive of insomnia. Results The insomnia phenotype (alone or together with EDS) dominated in all European regions. Isolated insomnia, however, was less common in the West. Insomnia phenotype was associated with the highest proportion of cardiovascular comorbidity (51.7% in the insomnia vs. 43.9% in the EDS type). Measures of nocturnal hypoxemia were independently associated with cardiovascular comorbidity in phenotypes with insomnia-like symptoms. The burden of comorbidities was high across all geographical regions and clinical phenotypes. Regional differences were clinically relevant for age (48 vs. 54 years), BMI (29 vs. 34 kg/m(2)), and ODI (15 vs. 32/h). Conclusion High prevalence of particularly cardiovascular comorbidity among patients with insomnia-like symptoms was linked to nocturnal hypoxemia. Considerable differences in clinical presentation were found among OSA patients across Europe. Our data underline that physicians should ask their patients with suspected OSA also for insomnia symptoms. It remains to be explored if a reduction of nocturnal hypoxemia predicts the improvement of insomnia symptoms., European Union COST action B26; European Respiratory Society (ERS); ResMed Inc.; Philips Respironics Inc., The ESADA network has received support from the European Union COST action B26. The European Respiratory Society (ERS) supports the ESADA for the second period as a Clinical Research Collaboration (CRC) (2015-2017 and 2018-2020). Unrestricted seeding grants from ResMed Inc. and Philips Respironics Inc. for establishment of the organization and the database are gratefully acknowledged.

The role of early child care experiences on the development of the mother-child attachment relationship has been studied extensively. However, no prospective studies of early child care have addressed how these experiences might be reflected in the content of attachment representations during adolescence and beyond. The goal of this study was to estimate relatively precise associations between child care quality, child care quantity, and type of care in the first 54 months of life and the content of adolescents' attachment representations around age 18 years (N = 857; 51% female; 78% White, non-Hispanic; M income-to-needs ratio = 4.13), leveraging data from the longitudinal NICHD Study of Early Child Care and Youth Development (SECCYD). We identified a small positive association between the observed quality of early child care (but not quantity or type of care) and secure attachment states of mind as measured by the Adult Attachment Interview (but not the Attachment Script Assessment) at age 18 years that was robust to demographic covariates and observations of maternal and paternal sensitivity during childhood. We observed no significant interactions among child care variables. Associations between early child care experiences and indicators of adolescent attachment were likewise not moderated by maternal sensitivity from infancy to mid-adolescence or by maternal reports of child temperament in early childhood.

Gunduz C, Basoglu OK, Hedner J, et al; onbehalf of the European Sleep Apnoea Databasecollaborators (Biruni University; Ege University;Gothenburg University; Sahlgrenska UniversityHospital; University of Palermo; CNR Institute ofBiomedicine and Molecular Immunology; St. AdolfStift; Hospital de Santa Maria; University of Crete;Antoine-Beclere Hospital; G. PapanikolaouHospital; Institute of Tuberculosis and LungDiseases; University Hospital Brno; St. Ann’sUniversity Hospital; Universite ́ Grenoble Alpes)Hyperlipidaemia prevalence and cholesterolcontrol in obstructive sleep apnoea: Data from theEuropean sleep apnea database (ESADA).J InternMed2019;286: 676–688.Background and objective.Obstructive sleep apnoea(OSA) and hyperlipidaemia are independent riskfactors for cardiovascular disease. This studyinvestigates the association between OSA andprevalence of hyperlipidaemia in patients of theEuropean Sleep Apnea Database (ESADA) cohort.Methods.The cross-sectional analysis included11 892 patients (age 51.9 12.5 years, 70% male,body mass index (BMI) 31.3 6.6 kg/m2, meanoxygen desaturation index (ODI) 23.7 25.5events/h) investigated for OSA. The independentodds ratio (OR) for hyperlipidaemia in relation tomeasures of OSA (ODI, apnoea-hypopnoea index,mean and lowest oxygen saturation) was deter-mined by means of general linear model analysiswith adjustment for important confounders suchas age, BMI, comorbidities and study site.Results.Hyperlipidaemia prevalence increased from15.1% in subjects without OSA to 26.1% in thosewith severe OSA,P

Background and objective: Obstructive sleep apnoea (OSA) and dyslipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and plasma lipid concentrations in patients enrolled in the European Sleep Apnea Database (ESADA) cohort. Methods: The cross-sectional analysis included 8592 patients without physician-diagnosed hyperlipidaemia or reported intake of a lipid-lowering drug (age 50.1 ± 12.7 years, 69.1% male, BMI: 30.8 ± 6.6 kg/m2, mean apnoea–hypopnoea index (AHI): 25.7 ± 25.9 events/h). The independent relationship between measures of OSA (AHI, oxygen desaturation index (ODI), mean and lowest oxygen saturation) and lipid profile (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting triglycerides (TG)) was determined by means of general linear model analysis. Results: There was a dose response relationship between TC and ODI (mean ± SE (mg/dL): 180.33 ± 2.46, 184.59 ± 2.42, 185.44 ± 2.42 and 185.73 ± 2.44; P < 0.001 across ODI quartiles I–IV). TG and LDL concentrations were better predicted by AHI than by ODI. HDL-C was significantly reduced in the highest AHI quartile (mean ± SE (mg/dL): 48.8 ± 1.49 vs 46.50 ± 1.48; P = 0.002, AHI quartile I vs IV). Morbid obesity was associated with lower TC and higher HDL-C values. Lipid status was influenced by geographical location with the highest TC concentration recorded in Northern Europe. Conclusion: OSA severity was independently associated with cholesterol and TG concentrations.

The COVID-19 pandemic, caused by the SARS-CoV2 virus, has infected millions worldwide with cancer patients demonstrating a higher prevalence for severe disease and poorer outcomes. Recently, the BNT162b2 mRNA COVID-19 vaccine was released as the primary means to combat COVID-19. The currently reported incidence of local and systemic side effects was 27% in the general public. The safety of the BNT162b2 mRNA COVID-19 vaccine has not been studied in patients with an active cancer diagnosis who are either ongoing or plan to undergo oncologic therapy. This single center study reviewed the charts of 210 patients with active cancer diagnoses that received both doses of the BNT162b2 mRNA COVID-19 vaccine. The development of side effects from the vaccine, hospitalizations or exacerbations from various oncologic treatment were documented. Type of oncologic treatment (immunotherapy, chemotherapy, hormonal, biologic, radiation or mixed) was documented to identify if side effects were related to treatment type. The time at which the vaccine was administered in relation to treatment onset (on long term therapy, within 1 month of therapy or prior to therapy) was also documented to identify any relationships. Sixty five (31%) participants experienced side effects from the BNT162b2 mRNA COVID-19 vaccine, however most were mild to moderate. Treatment protocol was not linked to the development of vaccine related side effects (P = .202), nor was immunotherapy (P = .942). The timing of vaccine administered in relation to treatment onset was also not related to vaccine related side effects (P = .653). Six (2.9%) participants were hospitalized and 4 (2%) died. The incidence of side effects in cancer patients is similar to what has been reported for the general public (31% vs 27%). Therefore, we believe that the BNT162b2 mRNA COVID-19 vaccine is safe in oncologic patients undergoing numerous cancer treatments.

Although abuse and neglect in the early years of life have been reliably linked to poor mental health outcomes in childhood, only a few studies have examined whether the predictive significance of childhood abuse and neglect endures for symptoms of psychopathology into adulthood. Here we examined to what extent prospectively assessed child abuse and neglect is associated with self-reported symptoms of psychopathology measured from ages 23 through 39 years, controlling for early demographic covariates and self-reported symptoms of psychopathology measured at age 16 years. The sample included 140 participants from the Minnesota Longitudinal Study of Risk and Adaptation. Participants were 49% female and 69% White/non-Hispanic. At the time of their child's birth, 48% of the mothers were teenagers (M = 20.5 years, SD = 3.74), 65% were single, and 42% had completed less than a high school education. Results indicated that childhood abuse and neglect was robustly associated with symptoms of psychopathology in adulthood. Exploratory analyses focusing on specific parametrizations of abuse/neglect suggested that abuse perpetrated by maternal figures (rather than paternal or nonparental figures) was uniquely associated with high levels of self-reported symptoms of psychopathology in adulthood. We found no evidence that any subtype of abuse and/or neglect or abuse/neglect during any particular phase of development uniquely predicted symptoms of psychopathology after controlling for relevant covariates. These results highlight the long-lasting significance of childhood abuse and neglect for reports of mental health in adulthood. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The E4 allele of apolipoprotein (apoE4) is the primary genetic risk factor for late onset Alzheimer's disease (AD), yet the exact manner in which apoE4 leads to the development of AD is undetermined. Human and animal studies report that apoE4-related memory deficits appear earlier than the AD clinical manifestation, thus suggesting the existence of early, pre-pathological, apoE4 impairments that may later lead to AD onset. While current research regards the hippocampus as the initial and primary effected locus by apoE4, we presently investigate the possibility that apoE4 innately impairs any brain area that requires synaptic plasticity. To test this hypothesis, we trained young (3-4-month-old) target-replacement apoE3 and apoE4 mice in conditioned taste aversion (CTA) acquisition and extinction learnings- hippocampus-independent learnings that are easily performed at a young age. Synaptic vesicular markers analysis was conducted in the gustatory cortex (GC), basolateral amygdala (BLA), medial prefrontal cortex (mPFC), and hippocampal CA3 to reveal underlying apoE4-related impairments. We have found that young apoE4 mice are severely impaired in CTA acquisition and extinction learning. CTA acquisition impairments were correlated with reduced vGat and vGlut levels in the BLA and GC, but not in the CA3. CTA extinction was correlated with lower synaptophysin and vGlut levels in the mPFC, a central region in CTA extinction. Our results support apoE4-related early-life plasticity impairments that precede the AD clinical manifestations and affect any brain area that depends on extensive plasticity; early impairments that may promote the development of AD pathologies later in life.

Contains fulltext : 214433.pdf (Publisher’s version ) (Closed access) Major life stress often produces a flat diurnal cortisol slope, an indicator of potential long-term health problems. Exposure to stress early in childhood or the accumulation of stress across the life span may be responsible for this pattern. However, the relative impact of life stress at different life stages on diurnal cortisol is unknown. Using a longitudinal sample of adults followed from birth, we examined three models of the effect of stress exposure on diurnal cortisol: the cumulative model, the biological-embedding model, and the sensitization model. As its name implies, the cumulative model focuses on cumulative life stress. In contrast, the biological-embedding model implicates early childhood stress, and the sensitization model posits that current life stress interacts with early life stress to produce flat diurnal cortisol slopes. Our analyses are consistent with the sensitization model, as they indicate that the combination of high stress exposure early in life and high current stress predict flat diurnal cortisol slopes. These novel findings advance understanding of diurnal cortisol patterns and point to avenues for intervention. 9 p.

Background The COVID-19 pandemic is a crisis unprecedented in its size and scope. Yet studies of resilience suggest most individuals will successfully negotiate this challenge and some may even experience growth and positive change. Some evidence suggests that the capacity to enact positive change in the face of adversity may be shaped by early life experiences. Methods In a subset of 374 participants (57% female, mean age = 29 years) in the Study of Early Child Care and Youth Development (SECCYD), a longitudinal, birth cohort, prospective models were tested to determine whether early life adversities in family and neighborhood contexts predict positive change events in response to the COVID-19 pandemic. Childhood family and neighborhood contexts were assessed using a combination of self-report questionnaires and US Census data. Adulthood positive change events (e.g., becoming more appreciative of things usually taken for granted) were assessed using the Epidemic-Pandemic Impacts Inventory (EPII). Results In regression analyses, neighborhood disadvantage in childhood, measured both by objective and subjective assessments, predicted a higher number of positive change events in response to the COVID-19 pandemic (β = .18, p = .004 and β = .15, p = .006, respectively). Examination of the positive change event subscales showed neighborhood disadvantage in childhood predicted increases in events related to ‘perspective taking and charitable giving’ (β = .20, p = .022 and β = .17, p = .002, respectively) and improved ‘social relationships’ (β = .18, p = .004 and β = .13, p = .020, respectively), but not to positive ‘health behaviors’ (ps > .05). All associations were independent of sociodemographic factors and childhood family dysfunction. Conclusions Findings suggest that neighborhood disadvantage in childhood may shape prosocial responses to stress in adulthood, potentially through early life adaptions to stress that are protective when facing adversity. There are several notable implications of the study findings. Although adversity in early life has clear negative impacts, it is possible that adversity experiences may also provide opportunities to develop adaptive strategies that foster resilience and growth when facing stress. Intervention efforts should consider leveraging such stress-adapted strengths to reduce the many negative impacts of early life adversity.

Retrospective self-report assessments of adults’ childhood experiences with their parents are widely employed in psychological science, but such assessments are rarely validated against actual parenting experiences measured during childhood. Here, we leveraged prospectively acquired data characterizing mother–child and father–child relationship quality using observations, parent reports, and child reports covering infancy through adolescence. At age 26 years, approximately 800 participants completed a retrospective measure of maternal and paternal emotional availability during childhood. Retrospective reports of childhood emotional availability demonstrated weak convergence with composites reflecting prospectively acquired observations ( R2s = .01–.05) and parent reports ( R2s = .02–.05) of parenting quality. Retrospective parental availability was more strongly associated with prospective assessments of child-reported parenting quality ( R2s = .24–.25). However, potential sources of bias (i.e., depressive symptoms and family closeness and cohesiveness at age 26 years) accounted for more variance in retrospective reports (39%–40%) than did prospective measures (26%), suggesting caution when using retrospective reports of childhood caregiving quality as a proxy for prospective data.

Obstructive sleep apnea (OSA) and asthma are often associated and several studies suggest a bidirectional relationship between asthma and OSA. This study analyzed the characteristics of patients with suspected OSA from the European Sleep Apnea Database according to presence/absence of physician-diagnosed asthma. Cross-sectional data in 16,236 patients (29.1% female) referred for suspected OSA were analyzed according to occurrence of physician-diagnosed asthma for anthropometrics, OSA severity and sleepiness. Sleep structure was assessed in patients studied by polysomnography (i.e. 48% of the sample). The prevalence of physician-diagnosed asthma in the entire cohort was 4.8% (7.9% in women, 3.7% in men, p&nbsp

Objective/Background: The Clinical Global Impression scale (CGI) reflects the clinician's assessment of the disease impact on patient's global functioning. We assessed predictors of CGI scale rating in patients with obstructive sleep apnea (OSA). Patients/Methods: Consecutive patients with suspected OSA (n = 7581) were identified in the European Sleep Apnea Database (ESADA). Anthropometrics, comorbidities, apnea severity obtained by polygraphy or polysomnography, and daytime sleepiness [Epworth Sleepiness Scale (ESS)] were assessed. The CGI 7-point scale was completed at the end of the diagnostic process (CGI-severity, ie, CGI-S) and, in a sub-population, at treatment follow-up (CGI-Improvement). Results: CGI-S was rated mild to moderate in 44% of patients. CGI rating at any given apnea intensity was worse in women than in men (p < 0.01). Patients undergoing polygraphy (n = 5075) were more frequently rated as severely ill compared to those studied with polysomnography (19.0% vs 13.0%, p < 0.001). In patients aged

Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. the FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1( + ) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. Methods: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. Results: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. the ALK( + ) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 +/- 1.6 months and median overall survival (mOS) was 89.1 +/- 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 +/- 2.5 months and mOS of 90.3 +/- 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. the most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. the observed mOS of 89 +/- 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 +/- 24 months is unprecedented for ROS1( + ) NSCLC., PfizerPfizer [IIS 53234545], We grateful to Pfizer for the funding of the grant IIS 53234545.

Introduction Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables noninvasive genomic analysis of NSCLC patients. Although plasma-detected genomic alterations (GAs) have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decisions. Methods This retrospective study of stage IIIB/IV NSCLC patients between the years 2014 and 2017 in Israel used cfDNA NGS (Guardant360; Guardant Health, Inc., Redwood City, California) to identify targetable GAs. Results We consecutively tested 116 NSCLC patients, 41.4% before first-line therapy (group A), 34.5% upon progression on chemotherapy or immunotherapy (group B1), and 24.1% upon progression on EGFR tyrosine kinase inhibitors (group B2). Targetable GAs were found in 31% of group A (15 of 48 patients), 32.5% in group B1 (13 of 40 patients) and 71% in group B2 (20 of 28 patients). Treatment decision was changed to targeted therapy in 23% (11 of 48 patients), 25% (10 of 40 patients) and 32% (9 of 28 patients), respectively (total cohort 26%; 30/116). Objective response rate (Response Evaluation Criteria in Solid Tumors) was 43% (12 of 28 patients) including one complete response, partial response in 39% (11 of 28 patients), stable disease in 32% (9 of 28 patients), and progressive disease in 25% (7 of 28 patients). Disease control rate was 75% for 5 months median treatment duration. Conclusions Comprehensive cfDNA testing impacted clinical decisions in one-quarter to one-third of initial and subsequent lines of treatment in advanced NSCLC patients. This retrospective study extends previous reports by showing that responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression.

This study examined the predictive significance of maternal sensitivity in early childhood for electrophysiological responding to and cognitive appraisals of infant crying at midlife in a sample of 73 adults (age = 39 years; 43 females; 58 parents) from the Minnesota Longitudinal Study of Risk and Adaptation. When listening to an infant crying, both parents and nonparents who had experienced higher levels of maternal sensitivity in early childhood (between 3 and 42 months of age) exhibited larger changes from rest toward greater relative left (vs. right) frontal EEG activation, reflecting an approach-oriented response to distress. Parents who had experienced greater maternal sensitivity in early childhood also made fewer negative causal attributions about the infant's crying; the association between sensitivity and attributions for infant crying was nonsignificant for nonparents. The current findings demonstrate that experiencing maternal sensitivity during the first 3½ years of life has long-term predictive significance for adults' processing of infant distress signals more than three decades later. (PsycINFO Database Record

The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.

Purpose Swept-source (SS) OCT angiography (OCTA) was used to determine the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with nonexudative age-related macular degeneration (AMD). Design Prospective, observational, consecutive case series. Participants Patients with intermediate AMD (iAMD) or geographic atrophy (GA) secondary to nonexudative AMD in 1 eye and exudative AMD in the fellow eye. Methods All patients were imaged using both the 3×3 mm and 6×6 mm SS OCTA fields of view (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). The en face slab used to detect the MNV extended from the outer retina to the choriocapillaris, and projection artifacts were removed using a proprietary algorithm. Main Outcome Measures Prevalence of subclinical MNV and time to exudation with Kaplan-Meier cumulative estimates of exudation at 1 year. Results From August 2014 through March 2017, 160 patients underwent SS OCTA (110 eyes with iAMD and 50 eyes with GA). Swept-source OCTA identified subclinical MNV at the time of first imaging in 23 of 160 eyes, for a prevalence of 14.4%. Six eyes demonstrated subclinical MNV during the follow-up. Of 134 eyes with follow-up visits, a total of 13 eyes demonstrated exudation, and of these 13 eyes, 10 eyes were found to have pre-existing subclinical MNV. By 12 months, the Kaplan-Meier cumulative incidence of exudation for all 134 eyes was 6.8%. For eyes with subclinical MNV at the time of first SS OCTA imaging, the incidence was 21.1%, and for eyes without subclinical MNV, the incidence was 3.6%. There was no difference in the cumulative incidence of exudation from pre-existing MNV in eyes with iAMD or GA ( P = 0.847, log-rank test). After the detection of subclinical MNV, the risk of exudation was 15.2 times (95% confidence interval, 4.2–55.4) greater compared with eyes without subclinical MNV. Conclusions By 12 months, the risk of exudation was greater for eyes with documented subclinical MNV compared with eyes without detectable MNV. For eyes with subclinical MNV, recommendations include more frequent follow-up and home monitoring. Intravitreal therapy is not recommended until prospective studies are performed.

The cross-sectional relationship of obstructive sleep apnea with moderate to severe chronic kidney disease, defined as an estimated glomerular filtration rate = 30) was found in 34% of subjects. The lowest nocturnal oxygen saturation was 81 +/- 10.2%. Chronic kidney disease prevalence in the whole sample was 8.7% or 6.1%, according to the Modification of Diet in Renal Disease or the Chronic Kidney Disease-Epidemiology Collaboration equations, respectively. Subjects with lower estimated glomerular filtration rate were older, more obese, more often female, had worse obstructive sleep apnea and more co-morbidities (P < 0.001, each). With both equations, independent predictors of estimated glomerular filtration rate < 60 were: chronic heart failure; female gender; systemic hypertension; older age; higher body mass index; and worse lowest nocturnal oxygen saturation. It was concluded that in obstructive sleep apnea, chronic kidney disease is largely predicted by co-morbidities and anthropometric characteristics. In addition, severe nocturnal hypoxaemia, even for only a small part of the night, may play an important role as a risk factor for kidney dysfunction.

Parents' attachment representations and child-parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta-analysis. Analyses on 4,396 parent-child dyads (58 studies, child age 11-96 months) revealed a combined effect size of r = .29. IPD meta-analyses revealed that effect sizes for the transmission of autonomous-secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent-child dyads, whereas transmission was stronger for older children. Findings support the ecological constraints hypothesis on attachment transmission. Implications for attachment theory and the use of IPD meta-analysis are discussed.

The effect of positive airway pressure treatment on weight and markers of central obesity in patients with obstructive sleep apnea remains unclear. We studied the change in body weight and anthropometric measures following positive airway pressure treatment in a large clinical cohort. Patients with obstructive sleep apnea with positive airway pressure treatment from the European Sleep Apnea Database registry (n = 1, 415, 77% male, age 54 ± 11 [mean ± SD] years, body mass index 31.7 ± 6.4 kg/m2, apnea–hypopnea index 37 ± 24 n per hr, Epworth Sleepiness Scale 10.2 ± 5.0) were selected. Changes in body mass index and neck/waist/hip circumferences at baseline and at follow-up visit were analysed. Overall, body mass index (0.0 [95% confidence interval, −0.1 to 0.2] kg/m2) and neck circumference (0.0 (95% confidence interval, −0.1 to 0.1] cm) were unchanged after positive airway pressure treatment compared with baseline (follow-up duration 1.1 ± 1.0 years and compliance 5.2 ± 2.1 hr per day). However, in non- obese (body mass index

Previous research suggests that the experience of abuse and neglect in childhood has negative implications for physical health in adulthood. Using data from the Minnesota Longitudinal Study of Risk and Adaptation (N = 115), the present research examined the predictive significance of childhood physical abuse, sexual abuse, and physical/cognitive neglect for multilevel assessments of physical health at midlife (age 37–39 years), including biomarkers of cardiometabolic risk, self-reports of quality of health, and a number of health problems. Analyses revealed that childhood physical/cognitive neglect, but not physical or sexual abuse, predicted all three health outcomes in middle adulthood, even when controlling for demographic risk factors and adult health maintenance behaviors. We discuss possible explanations for the unique significance of neglect in this study and suggest future research that could clarify previous findings regarding the differential impact of different types of abuse and neglect on adult health.

The present study used data from the Minnesota Longitudinal Study of Risk and Adaptation (MLSRA) to investigate how multiple dimensions of childhood abuse and neglect predict romantic relationship functioning in adulthood. Several dimensions of abuse and neglect (any experience, type, chronicity, co-occurrence, and perpetrator) were rated prospectively from birth through age 17.5 years. Multimethod assessments of relational competence and violence in romantic relationships were conducted repeatedly from ages 20 to 32 years. As expected, experiencing childhood abuse and neglect was associated with lower romantic competence and more relational violence in adulthood. Follow-up analyses indicated that lower romantic competence was specifically associated with physical abuse, maternal perpetration, chronicity, and co-occurrence, whereas more relational violence was uniquely associated with nonparental perpetration. We discuss these novel prospective findings in the context of theory and research on antecedents of romantic relationship functioning.

Objectives. To evaluate health impacts of drought during the most severe drought in California’s recorded history with a rapid assessment method. Methods. We conducted Community Assessments for Public Health Emergency Response during October through November 2015 in Tulare County and Mariposa County to evaluate household water access, acute stressors, exacerbations of chronic diseases and behavioral health issues, and financial impacts. We evaluated pairwise associations by logistic regression with pooled data. Results. By assessment area, households reported not having running water (3%–12%); impacts on finances (25%–39%), property (39%–54%), health (10%–20%), and peace of mind (33%–61%); worsening of a chronic disease (16%–46%); acute stress (8%–26%); and considering moving (14%–34%). Impacts on finances or property were each associated with impacts on health and peace of mind, and acute stress. Conclusions. Drought-impacted households might perceive physical and mental health effects and might experience financial or property impacts related to the drought. Public Health Implications. Local jurisdictions should consider implementing drought assistance programs, including behavioral health, and consider rapid assessments to inform public health action.

This paper reports the first large-sample investigation of the maltreatment-related correlates of low-income adolescents’ narratives about their childhood experiences with primary caregivers, as assessed with a modified version of the Adult Attachment Interview (AAI) and based on official reports of abuse and neglect (maltreatedn= 214, nonmaltreatedn= 140;Mage = 16.7 years). Drawing on factor-analytic and taxometric evidence indicating that AAI narratives vary along two state of mind (i.e., dismissing and preoccupied) and two inferred childhood experience (i.e., maternal and paternal) dimensions, here we demonstrate that the experience of maltreatment, particularly when chronic, is associated with increased risk for dismissing and preoccupied states of mind and more negative inferred childhood experiences. Although such maltreatment-related associations were generally not specific to any of the four AAI dimensions, the experience of physical and/or sexual abuse was uniquely associated with preoccupied states of mind and negative inferred paternal experiences even after controlling for the other AAI dimensions. More extensive paternal perpetration of maltreatment also was uniquely related to more negative inferred paternal experiences.

The present report used data from the Minnesota Longitudinal Study of Risk and Adaptation to investigate the factor structure and childhood abuse and/or neglect related antecedents of adults’ attachment states of mind in a high-risk sample. Adult Attachment Interviews (AAIs) were collected when participants were age 26 years (N= 164) and Current Relationship Interviews (CRIs) were collected from participants (N= 116) and their romantic partners when target participants were between ages 20 and 28 years (M= 25.3 years). For both the AAI and the CRI, exploratory factor analyses revealed that (a) attachment state of mind scales loaded on two weakly correlated dimensions reflecting dismissing and preoccupied states of mind and (b) ratings of unresolved discourse loaded on the same factor as indicators of preoccupied states of mind. Experiencing any subtype of abuse and/or neglect, especially during multiple developmental periods, and experiencing multiple subtypes of abuse and/or neglect during childhood were associated with risk for preoccupied (but not dismissing) AAI states of mind regarding childhood relationships with caregivers. Analyses focused on the particular subtypes, and perpetrators indicated that the predictive significance of childhood abuse/neglect for adult's AAI preoccupied states of mind was specific to experiences of abuse (but not neglect) perpetrated by primary caregivers. In addition, experiencing chronic or multiple subtypes of childhood abuse and/or neglect increased risk for dismissing (but not preoccupied) CRI states of mind regarding adult romantic partners.

Purpose To investigate the changes of the retinal microvascular network and microcirculation in high myopia. Design A cross-sectional, matched, comparative clinical study. Participants Twenty eyes of 20 subjects with nonpathological high myopia (28 ± 5 years of age) with a refractive error of −6.31 ± 1.23 D (mean ± SD) and 20 eyes of 20 age- and sex-matched control subjects (30 ± 6 years of age) with a refractive error of −1.40 ± 1.00 D were recruited. Methods Optical coherence tomography angiography (OCTA) was used to image the retinal microvascular network, which was later quantified by fractal analysis (box counting [D box ], representing vessel density) in both superficial and deep vascular plexuses. The Retinal Function Imager was used to image the retinal microvessel blood flow velocity (BFV). The BFV and microvascular density in the myopia group were corrected for ocular magnification using Bennett's formula. Results The density of both superficial and deep microvascular plexuses was significantly decreased in the myopia group in comparison to the controls ( P box , was 2.1% and 2.9% in the superficial and deep vascular plexuses, respectively. Microvessel density reached a plateau from 0.5 mm to 1.25 mm from the fovea in both groups, but that in the myopic group was about 3% lower than the control group. No significant differences were detected between the groups in retinal microvascular BFV in either arterioles or venules ( P > .05). Microvascular densities in both superficial (r = −0.45, P = .047) and deep (r = −0.54, P = .01) vascular plexuses were negatively correlated with the axial lengths in the myopic eye. No correlations were observed between BFV and vessel density ( P > .05). Conclusions Retinal microvascular decrease was observed in the high myopia subjects, whereas the retinal microvessel BFV remained unchanged. The retinal microvascular network alteration may be attributed to ocular elongation that occurs with the progression of myopia. The novel quantitative analyses of the retinal microvasculature may help to characterize the underlying pathophysiology of myopia and enable early detection and prevention of myopic retinopathy.

Although teacher-student relationships are assumed to in part reflect early caregiving quality, their social provisions also undergo notable normative change over the course of primary school, shifting from a secure base for social exploration to an instrumental relationship centered on achieving academic goals. This report leveraged prospective, longitudinal data from the Study of Early Child Care and Youth Development (N = 1,306, 52% male, 77% White/non-Hispanic) to investigate whether the association between early caregiving and subsequent teacher-student relationship quality remains stable or diminishes in magnitude over time. Associations between early maternal sensitivity and teacher-student closeness faded from Kindergarten to Grade 6. In contrast, associations between early caregiving and teacher-student conflict endured and were partially accounted for by child externalizing problems.

Background Longitudinal investigations of relatively large typical-risk (e.g., Booth-LaForce & Roisman, 2014) and higher-risk samples (e.g., Raby et al., 2017; Roisman et al., 2017) have produced evidence consistent with the claim that attachment states of mind in adolescence and young adulthood, as measured by the Adult Attachment Interview (AAI), are associated with the quality of caregiving experienced during childhood. None of these studies, however, has examined whether such associations are consistent across sex and/or race, as would be expected in light of the sensitivity hypothesis of attachment theory. Methods We examine whether sex or race moderates previously reported links between caregiving and AAI states of mind in two longitudinal studies (pooled N = 1,058) in which caregiving was measured either within (i.e., observed [in]sensitive care) or outside (i.e., childhood maltreatment) of the normative range of caregiving experiences. Results Hierarchical moderated regression analyses in both longitudinal cohorts provided evidence that maternal insensitivity and experiences of maltreatment were prospectively associated with dismissing and preoccupied states of mind in adolescence, as hypothesized. Moreover, these associations were generally comparable in magnitude for African American and White/non-Hispanic participants and were not conditional on participants' biological sex. Conclusions Both maternal insensitivity and the experience of maltreatment increased risk for insecure attachment states of mind in adolescence. Moreover, our analyses provided little evidence that either participant race or participant sex assigned at birth moderated these nontrivial associations between measures of the quality of experienced caregiving and insecure attachment states of mind in adolescence. These findings provide support for the sensitivity hypothesis of attachment theory and inform the cultural universality hypothesis of attachment processes.

Lung cancer (LC) is the leading cause of cancer mortality worldwide. Despite advances in the treatment strategy, including surgery, chemotherapy, radiotherapy, immunotherapy, and targeted therapy, 5-year survival is estimated as 9% to 20%.1,2 During the past decade, LC incidence has been increasing and age at the time of diagnosis continues to decrease.3,4 Median age at diagnosis is 70 years, and approximately 13% of all patients with LC are younger than age 50 years. Numerous studies have suggested that LC in young patients constitutes an entity with unique characteristics, such as a higher percentage of female patients, a lower rate of smoking history, a higher percentage of family history of LC, a higher rate of adenocarcinoma histology, and more advanced stage at diagnosis.5-13 However, it is still controversial whether youthful patients with LC have better or worse outcomes.14-16 In addition, most of the literature regarding young patients is associated with Asian cohorts, whereas less data about white communities are available. Currently, a considerable percentage of patients with non–small-cell lung cancer (NSCLC) benefit from personalized therapy protocols that are based on the genomic profile of tumors.17,18 Mutations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes affect the prognosis of patients. Recent studies have shown that young patients with NSCLC harbor more driver mutations than older patients. The rate of mutations documented in the young white population varies between articles and is approximately 20% to 30% for EGFR mutation and 10% to 20% for ALK rearrangement.17-19 There are conflicting data on whether younger patients with NSCLC achieve better or worse outcomes compared with the older population, yet most studies show that younger patients have better survival rates.7-10 Identifying the clinicopathologic characteristics and making appropriate proactive molecular profiling of the youthful population can guide treatment strategy in the clinical setting. Therefore, in the current study, we carried out a comprehensive analysis of patient clinicopathologic features and clinical outcomes in both young (age ≤ 50 years) and older (age > 60 years) patients with NSCLC.

Research suggests intergenerational links between childhood abuse and neglect and subsequent parenting quality, but little is known about the potential mechanisms underlying intergenerational continuities in parenting. Adult romantic functioning may be one plausible mechanism, given its documented associations with both adverse caregiving in childhood and parenting quality in adulthood. The present study used data from the Minnesota Longitudinal Study of Risk and Adaptation to (a) investigate prospective associations between childhood experiences of abuse and neglect and multiple parenting outcomes in adulthood, and (b) evaluate the degree to which adult romantic functioning mediates those associations. Information regarding childhood abuse and neglect was gathered prospectively from birth through age 17.5 years. Multimethod assessments of romantic functioning were collected repeatedly through early adulthood (ages 20 to 32 years), and parenting quality was assessed as participants assumed a parenting role (ages 21 to 38 years). As expected, childhood abuse and neglect experiences predicted less supportive parenting (observed and interview rated) and higher likelihood of self-reported Child Protective Services involvement. The association with interview-rated supportive parenting was partially mediated by lower romantic competence, whereas the association with Child Protective Services involvement was partially mediated by more relational violence in adult romantic relationships. Implications of these novel prospective findings for research and clinical intervention are discussed.

Long non‐coding RNA s (lncRNA s) comprise a family of non‐coding transcripts that are emerging as relevant gene expression regulators of different processes, including tumour development. To determine the possible contribution of lncRNA to the pathogenesis of follicular lymphoma (FL ) we performed RNA ‐sequencing at high depth sequencing in primary FL samples ranging from grade 1‐3A to aggressive grade 3B variants using unpurified (n = 16) and purified (n = 12) tumour cell suspensions from nodal samples. FL grade 3B had a significantly higher number of differentially expressed lncRNA s (dif‐lncRNA s) with potential target coding genes related to cell cycle regulation. Nine out of the 18 selected dif‐lncRNA s were validated by quantitative real time polymerase chain reaction in an independent series (n = 43) of FL . RP 4‐694A7.2 was identified as the top deregulated lncRNA potentially involved in cell proliferation. RP 4‐694A7.2 silencing in the WSU ‐FSCCL FL cell line reduced cell proliferation due to a block in the G1/S phase. The relationship between RP 4‐694A7.2 and proliferation was confirmed in primary samples as its expression levels positively related to the Ki‐67 proliferation index. In summary, lncRNA s are differentially expressed across the clinico‐biological spectrum of FL and a subset of them, related to cell cycle, may participate in cell proliferation regulation in these tumours. Fil: Roisman, Alejandro. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Castellano, Giancarlo. Universidad de Barcelona; España Fil: Navarro, Alba. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Gonzalez Farre, Blanca. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Universidad de Barcelona; España Fil: Pérez Galan, Patricia. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Esteve Codina, Anna. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; España Fil: Dabad, Marc. Barcelona Institute Of Science And Technology.; España. Universitat Pompeu Fabra; España Fil: Heath, Simon. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; España Fil: Gut, Marta. Universitat Pompeu Fabra; España. Barcelona Institute Of Science And Technology.; España Fil: Bosio, Mattia. Barcelona Supercomputing Center - Centro Nacional de Supercomputacion; España Fil: Bellot, Pau. Barcelona Institute Of Science And Technology. Institut Català D'investigació Química.; España Fil: Salembier, Philippe. Universidad Politécnica de Catalunya; España Fil: Oliveras, Albert. Universidad Politécnica de Catalunya; España Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Magnano, Andrea Laura. Hospital Clínico de Barcelona; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Horn, Heike. Eberhard Karls Universität Tübingen.; Alemania Fil: Rosenwald, Andreas. University of Würzburg; Alemania Fil: Ott, German. Department of Clinical Pathology; Alemania Fil: Aymerich, Marta. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: López Guillermo, Armando. Hospital Clínico de Barcelona; España Fil: Jares, Pedro. Universidad de Barcelona; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Martín Subero, José I.. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España Fil: Campo, Elías. Centro de Investigación Biomédica en Red de Cáncer; España. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Hospital Clínico de Barcelona; España Fil: Hernández, Luis. Lymphoid Neoplasm Programme, Institut d'Investigacions Biomèdiques August Pi i Sunyer; España. Centro de Investigación Biomédica en Red de Cáncer; España

Item does not contain fulltext Children who experience high-quality early parenting tend to have better physical health, but limited research has tested whether this association extends into adulthood using prospective, observational assessments. Likewise, mechanisms that may explain such links have not yet been illuminated. In this study, we test whether the quality of early maternal sensitivity experienced during the first 3½ years of life predicts cardiometabolic risk at midlife (ages 37 and 39 years) via attachment representations measured in young adulthood (ages 19 and 26 years). We do so by comparing the predictive significance of two different forms of attachment representations coded from the Adult Attachment Interview (AAI): (a) secure base script knowledge and (b) coherence of mind. Using data from the Minnesota Longitudinal Study of Risk and Adaptation, we find that early maternal sensitivity is negatively associated with cardiometabolic risk at midlife. Secure base script knowledge (but not coherence of mind) partially mediated this link. These findings are consistent with the possibility that early parenting has lasting significance for physical health in part by promoting higher levels of secure base script knowledge. 17 p.

PubMed ID: 27701416, Background Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. Methods A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of ?5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness ("EDS") and nocturnal sleep problems other than OSA (labelled as "insomnia"): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/noninsomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. Results The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/ insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p

Background: Glutathione S-transferases (GSTs) are drug-metabolising enzymes involved in biotransformation of carcinogens, drugs, xenobiotics and oxygen free radicals. Polymorphisms of GST genes contribute to inter-individual and population variability in the susceptibility to environmental risk factors, cancer predisposition and pharmacotherapy responses. However, data about GST variability in Argentina are lacking. Aim: The purpose was to determine the prevalence of GSTM1, GSTT1 and GSTP1 polymorphisms in the general population from a central region of Argentina and to perform inter-population comparisons. Subjects and methods:GSTM1 and GSTT1 gene deletions and GSTP1 c.313A > G were genotyped by PCR assays in 609 healthy and unrelated Argentinians. Results: The frequencies of variant genotypes in Argentinians were GSTM1-null (45%), GSTT1-null (17%) and GSTP1-GG (11%). GSTM1-present genotype was significantly associated with GSTP1-AG or GSTP1-GG variants (p = 0.037; p = 0.034, respectively). Comparison with worldwide populations demonstrated that the GST distributions in Argentina are similar to those reported for Italy and Spain, whereas significant differences were observed regarding Asian and African populations (p < 0.001). Conclusion: This study has determined, for the first time, the normative profile of three pharmacogenetically relevant polymorphisms (GSTM1, GSTT1 and GSTP1) in the largest Argentinian cohort described to date, providing the basis for further epidemiological and pharmacogenetic studies in this country. Fil: Weich, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Roisman, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Cerliani, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Aráoz, Hilda V.. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina Fil: Chertkoff, Lilien Patricia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Richard, Silvina Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina Fil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina

Mycosis fungoides is the most common type of primary cutaneous T cell lymphoma. We have evaluated CDKN2A losses and MYC gains/amplifications by FISH analysis, as well as expression of miR-155 and members of the oncogenic cluster miR-17-92 (miR17, miR18a, miR19b, and miR92a) in MF patients with advanced disease. Formalin-fixed paraffin-embedded skin biopsies from 36 patients at diagnosis, 16 with tumoral MF (T-MF), 13 in histological transformation to a large T cell lymphoma (TR-MF), and 7 cases with folliculotropic variant (F-MF), were studied. Twenty cases showed genomic alterations (GAs): 8 (40 %) had CDKN2A deletion, 7 (35 %) showed MYC gain, and 5 (25 %) exhibited both alterations. GAs were more frequently observed in F-MF (p = 0.004) and TR-MF (p = 0.0001) than T-MF. GAs were significantly higher in cases presenting lesions in head, neck, and lower extremities compared to those observed in trunk and upper extremities (p = 0.03), when ≥25 % neoplastic cells were CD30 positive (p = 0.016) as well as in cases with higher Ki-67 proliferation index (p = 0.003). Patients with GAs showed bad response to treatment (p = 0.02) and short survival (p = 0.04). Furthermore, MF patients showed higher miRNA expression compared to controls (p ≤ 0.0223). T-MF showed higher miR17 and miR-18a expression compared to F-MF and TR-MF (p ≤ 0.0387) while miR19b, miR92a, and miR-155 showed increased levels in F-MF and TR-MF with respect to T-MF (p ≤ 0.0360). Increased expression of miR17 and miR19b in GA group compared to cases without alterations (p ≥ 0.0307) was also detected. Our results add new information about genomic imbalances in MF patients, particularly in F-MF, and extend the present view of miRNA deregulation in this disease.

Increasing evidence suggests that attachment representations take at least two forms: a secure base script and an autobiographical narrative of childhood caregiving experiences. This study presents data from the first 26 years of the Minnesota Longitudinal Study of Risk and Adaptation (N = 169), examining the developmental origins of secure base script knowledge in a high-risk sample and testing alternative models of the developmental sequencing of the construction of attachment representations. Results demonstrated that secure base script knowledge was predicted by observations of maternal sensitivity across childhood and adolescence. Furthermore, findings suggest that the construction of a secure base script supports the development of a coherent autobiographical representation of childhood attachment experiences with primary caregivers by early adulthood.

[No abstract available], ResMed Foundation; Philips; European Respiratory Society, ERS; Fondation Air Liquide, Conflict of interest: A. Pataka has nothing to disclose. M.R. Bonsignore has nothing to disclose. S. Ryan has nothing to disclose. R.L. Riha has nothing to disclose. J-L. Pepin reports grants and research funds from Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire, personal fees from Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz Pharmaceutical, Night Balance, Philips, Resmed and Sefam. S. Schiza has nothing to disclose. O.K. Basoglu has nothing to disclose. P. Sliwinski has nothing to disclose. O. Ludka has nothing to disclose. P. Steiropoulos has nothing to disclose. U. Anttalainen has nothing to disclose. W.T. McNicholas has nothing to disclose. J. Hedner reports grants from ResMed Foundation, Philips Respironics and the European Respiratory Society, for start-up and conduct of the study. L. Grote reports grants from Resmed Foundation and Respironics Foundation, during the conduct of the study; personal fees for lecturing from Resmed, Philips and Itamar, grants from Resmed, other (equipment) from Itamar, outside the submitted work; in addition, L. Grote has a patent for sleep apnoea treatment pending., Support statement: The ESADA network has received support from the European Union COST action B26 and is currently a Clinical Research Collaboration funded by the European Respiratory Society. Additionally, the ESADA study group has received unrestricted seeding grants from the ResMed and the Philips Respironics Foundation for the establishment of the database in 2007 and 2011. The ESADA has an ongoing collaboration with Bayer AG. Non-financial support was provided by the European Sleep Research Society and the European Respiratory Society for communication, meetings and data presentations for the ESADA collaborators.

Background Real-life comparative data on BRAF inhibitors (BRAFi) and BRAFi + MEK inhibitors (MEKi) combination in BRAF-mutant (BRAFm) non–small-cell lung cancer (NSCLC) is lacking. Patients and Methods Consecutive BRAFm advanced NSCLC patients (n = 58) treated in 9 Israeli centers in 2009-2018 were identified. These were divided according to mutation subtype and treatment into groups A1 (V600E, BRAFi; n = 5), A2 (V600E, BRAFi + MEKi; n = 15), A3 (V600E, no BRAFi; n = 7), B1 (non-V600E, BRAFi ± MEKi; n = 7), and B2 (non-V600E, no BRAFi; n = 23); one patient received both BRAFi and BRAFi + MEKi. Safety, objective response rate, progression-free survival with BRAFi ± MEKi, and overall survival were assessed. Results Objective response rate was 40%, 67%, and 33% in groups A1, A2, and B1, respectively (P = .5 for comparison between groups A1 and A2). In group B1, G469A and L597R mutations were associated with response to BRAFi + MEKi. Median progression-free survival was 1.2 months (95% confidence interval [CI], 0.5-5.3), 5.5 months (95% CI, 0.7-9.3), and 3.6 months (95% CI, 1.5-6.7) for groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .04). Median overall survival with BRAFi ± MEKi was 1.7 months (95% CI, 0.5-NR), 9.5 months (95% CI, 0.2-14.9), and 7.1 months (95% CI, 1.8-NR) in groups A1, A2, and B1, respectively (log-rank for comparison between groups A1 and A2, P = .6). Safety profiles differed slightly, and similar treatment discontinuation rates were observed with BRAFi and BRAFi + MEKi. Conclusion In the real-life setting, activity and safety of BRAFi + MEKi in V600E BRAFm NSCLC are comparable to those observed in prospective clinical trials; the combination of BRAFi + MEKi is superior to monotherapy with a BRAFi. Further research should be done to explore the impact of BRAFi + MEKi treatment on the natural history of BRAFm NSCLC.

Attachment theory suggests that early experiences with caregivers are carried forward across development in the form of mental representations of attachment experiences. Researchers have investigated at least two representation-based constructs when studying attachment and successful adaptation in adulthood: (a) coherence of autobiographical discourse/memories and (b) knowledge of the secure base script. Here, we present data examining the unique contributions of coherent discourse regarding childhood caregiving experience and secure base script knowledge in a prospective high-risk longitudinal study, the Minnesota Longitudinal Study of Risk and Adaptation. The current study included three indicators of the quality of romantic relationships: (a) observed quality of interaction with romantic partners, (b) self-reported relationship satisfaction, and (c) interview-rated effectiveness of romantic engagement. Parent-child relationship quality was also assessed across three key outcomes: (a) infant attachment security, (b) observations of supportive parenting, and (c) interview-rated supportive parenting. When examining both attachment representations simultaneously, each representation-based construct was uniquely associated with different relationship quality indices. Specifically, secure base script knowledge was uniquely associated with infant attachment security in the next generation, and coherence of discourse was uniquely associated with observations of romantic relationships quality and interview-rated supportive parenting. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Efficacy of immune check-point inhibitors (ICPi) in NSCLC with rare targetable drivers (RTDs) is largely unknown.Consecutive patients with NSCLC and RTDs (non-EGFR/ALK, n-82) were selected from the Davidoff Cancer Center database. ORR, PFS, OS with ICPi, OS since advanced disease diagnosis, TMB, MSI, and PD-L1 expression were analyzed; uni- and multivariate PFS and OS analyses were done. OS with ICPi was compared between the RTD cohort and the non-selected NSCLC cohort (n-278).Of 50 tumors tested, 32%, 38%, and 30% were associated with ≥50%, 1-49% and1% PD-L1 expression, respectively. Median TMB (n-48) comprised 4 muts/Mb (0-57); TMB ≥ 10 muts/Mb was seen in 19% of tumors. Both TMB and PD-L1 expression varied across different RTDs. All the 47 tumors were MSI stable. ORR with ICPi (n-44) was 16%, median PFS was 3.2 months (95% CI, 2.6-5.0), median OS was 16.2 months (95% CI, 8.4-NR). No correlation was seen between OS with ICPi and PD-L1 expression (p 0.4), TMB (p 0.8), or RTD type (p 0.3). In the multivariate analysis, ECOG PS (p-0.005), targeted agents exposure (p-0.005), and ICPi exposure (p-0.04) were the only variables which correlated with OS since advanced disease diagnosis. Median OS since advanced disease diagnosis comprised 32 months (95% CI, 19.9-44.9) and 13 months (95% CI, 6.6-15.9) for patients who were and were not exposed to ICPi, respectively (log-rank test-6.3; p-0.01). In the inter-cohort comparison, for patients matched for ECOG PS (0/1), median OS with ICPi comprised 17.5 months (95% CI, 8.1-NR) and 8.6 months (95% CI, 6.7-NR) for RTD and non-selected patients, respectively (log-rank test-2.4, p-0.1).In NSCLC with RTD, ICPi have favorable efficacy and independent impact on OS. NSCLC with RTD is associated with MSI stable status and variable levels of PD-L1 expression and TMB; their predictive value remains to be determined.

This study used data from the Minnesota Longitudinal Study of Risk and Adaptation (N = 267) to investigate whether abuse and neglect experiences during the first 5 years of life have fading or enduring consequences for social and academic competence over the next 3 decades of life. Experiencing early abuse and neglect was consistently associated with more interpersonal problems and lower academic achievement from childhood through adulthood (32-34 years). The predictive significance of early abuse and neglect was not attributable to the stability of developmental competence over time, nor to abuse and neglect occurring later in childhood. Early abuse and neglect had enduring associations with social (but not academic) competence after controlling for potential demographic confounds and early sensitive caregiving. [ABSTRACT FROM AUTHOR]