Complete genomic characterization in patients with cancer of unknown primary origin in routine diagnostics.

BACKGROUND: In ∼3%-5% of patients with metastatic disease, tumor origin remains unknown despite modern imaging techniques and extensive pathology work-up. With long diagnostic delays and limited and ineffective therapy options, the clinical outcome of patients with cancer of unknown primary (CUP) remains poor. Large-scale genome sequencing studies have revealed that tumor types can be predicted based on distinct patterns of somatic variants and other genomic characteristics. Moreover, actionable genomic events are present in almost half of CUP patients. This study investigated the clinical value of whole genome sequencing (WGS) in terms of primary tumor identification and detection of actionable events, in the routine diagnostic work-up of CUP patients. PATIENTS AND METHODS: A WGS-based tumor type 'cancer of unknown primary prediction algorithm' (CUPPA) was developed based on previously described principles and validated on a large pan-cancer WGS database of metastatic cancer patients (>4000 samples) and 254 independent patients, respectively. We assessed the clinical value of this prediction algorithm as part of routine WGS-based diagnostic work-up for 72 CUP patients. RESULTS: CUPPA correctly predicted the primary tumor type in 78% of samples in the independent validation cohort (194/254 patients). High-confidence predictions (>95% precision) were obtained for 162/254 patients (64%). When integrated in the diagnostic work-up of CUP patients, CUPPA could identify a primary tumor type for 49/72 patients (68%). Most common diagnoses included non-small-cell lung (n = 7), gastroesophageal (n = 4), pancreatic (n = 4), and colorectal cancer (n = 3). Actionable events with matched therapy options in clinical trials were identified in 47% of patients. CONCLUSIONS: Genome-based tumor type prediction can predict cancer diagnoses with high accuracy when integrated in the routine diagnostic work-up of patients with metastatic cancer. With identification of the primary tumor type in the majority of patients and detection of actionable events, WGS is a valuable diagnostic tool for patients with CUP.

Diversifying academic medicine: One search committee at a time.

Despite increasing attention to lack of diversity among medical education faculty, those traditionally underrepresented in medicine remain so. In 2017, the University of Nevada, Reno School of Medicine approved a new policy to increase diversity in the faculty search process, which includes a mandatory 2-h workshop on best practices in search processes and implicit bias training. Workshop participants were 179 search committee members making up 55 committees from February 2017 to March 2020. Participants completed two separate social validity surveys, one immediately following the workshop and another following the close of their search, and rated various aspects of the workshop. Each search committee completed a Diversity Checklist (DCL) of various mandatory and best practices to be implemented during each search. Historical data on diversity of job applicants, interviewees, and hires over the 5-year period immediately preceding workshop implementation were compared with corresponding diversity data from the participant search committees for a 3-year period following implementation of the workshop. Social validity surveys indicated high ratings pertaining to the benefits of the workshop (means 3.82-4.39 out of 5). Implementation of practices outlined in the DCL were high (94% of mandatory and 87% of best practices). Chi-square analyses of diversity data before and after implementation revealed significant increases in overall diversity (both race and gender) of applicants (p < 0.001), interviewees (p = 0.002), and those offered a position (p = 0.002), in the time period following implementation. Follow-up comparisons found greater increases for gender relative to race/ethnicity.

[The association between religious coping styles and psychopathological symptomatology within a Christian population]. / De samenhang tussen religieuze coping­stijlen en psychische klachten in een christelijke bevolkingsgroep.

BACKGROUND: Religious coping can be seen as a method which applies religious resources, including prayer, and trust and appeals to God, in order to deal with stressful situations. AIM: To gain insight into the associations between religious coping styles and mental health and to investigate whether the use of the coping styles differs between mental health care clients and non-mental health care clients with a Christian background. METHOD: The sample consisted of 655 Dutch participants with a Christian worldview, aged 18 to 79 years (M = 42.6, SD = 14.2). 60.9% were female and 49.5% higher educated. Intra- and extramural clients in mental health care were involved. A cross-sectional, online survey was used, combined with an available client database. RESULTS: More use of the collaborative coping style was associated with less psychological complaints. More use of the (passive-)deferring and selfdirecting coping styles was associated with more psychological complaints. Christian mental health care clients used the collaborative and the deferring coping styles less often compared to Christian non-clients. CONCLUSION: The collaborative religious coping style is positively associated with mental health. Mental health care clients amongst them use this style less often compared to non-clients. Awareness of religious coping styles and appropriate support are indicated.

Addressing Microaggressions in Academic Health: A Workshop for Inclusive Excellence.

Introduction: Health profession schools have acknowledged the need for a diverse workforce by increasing diversity in recruitment, but little has been done to build inclusive excellence in learning environments. Microaggressions and other forms of mistreatment can increase stress levels and depression and negatively impact academic performance. To increase student performance, retention, and wellness, mitigating microaggressions is needed to promote an inclusive culture. Methods: We designed this workshop as a framework to think critically about microaggressions, how they impact the health professions academic environment, and how administrators, faculty, and students can promote inclusion excellence. The workshop included a presentation discussing microaggression theory, seven cases describing microaggressions in the health professions education environment, and discussion and facilitator guides. Cases were based on prior research conducted by the primary author and upon interactions authors shared from their professional experience. Participants completed pre- and postsurveys. Results: During six workshops at three different institutions, 138 out of 190 participants (73% response rate), including nursing and medicine faculty, students, and leadership, completed the pre- and postsurveys. Pre- and posttraining measurements found statistically significant improvements in participants' knowledge of the impact of microaggressions, self-efficacy in responding to microaggressions, and commitment to being an active bystander in the face of microaggressions. Participants were highly satisfied with the training. Discussion: This humanistic, case-based learning curriculum allows facilitators to guide faculty, student, and leadership conversations to build skills to promote inclusion excellence through preventing microaggressions, repairing and reestablishing relationships, and restoring reputations once microaggressions occur.

Motivational Interviewing Training: A Case-Based Curriculum for Preclinical Medical Students.

Introduction: With the rise of chronic medical problems involving lifestyle behaviors and the benefits of patient involvement in preventative care, medical students need to learn how to help patients change health risk behaviors and improve patient involvement in order to improve health outcomes. Motivational interviewing (MI) is a patient-centered therapeutic approach that is effective in the treatment of lifestyle behaviors and diseases. Methods: This 2-hour didactic training session, along with a 3-hour case-based practice session involving role-plays and a 3-hour evaluated session utilizing standardized patients, was delivered to 68 preclinical medical students. Knowledge, attitudes, and self-efficacy were evaluated via pre- and posttraining surveys, and satisfaction with the training was assessed upon completion. Results: Students who completed both pre- and postsurveys (n = 48) showed a statistically significant improvement in knowledge of MI (t = -29.73, df = 47, p < .001), attitudes regarding implementing MI in health care settings (t = -3.04, df = 47, p < .005), and self-efficacy (t = -10.699, df = 47, p < .001) in talking with patients about behavior change. Students were also highly satisfied with the MI training package (M of 4.4, SD = 0.6, out of 5.0). Discussion: A training package to teach preclinical medical students about MI was effective in helping students learn the knowledge and skills necessary to deliver MI in a broad range of clinical cases.

The incidence of postoperative nausea and vomiting after caesarean section in patients with hyperemesis gravidarum: a retrospective cohort study.

BACKGROUND: Postoperative nausea and vomiting is one of the most common anaesthetic complications of caesarean section. This study examined the association between hyperemesis gravidarum during pregnancy and nausea and vomiting after caesarean section. METHODS: A single-centre, retrospective cohort study, using electronic databases of patients with and without hyperemesis gravidarum, undergoing caesarean section from 2015 to 2019. The incidence and severity of postoperative nausea and vomiting were established by a review of the documentation of administration of postoperative anti-emetics within the 24-h period after surgery, and examined using univariable, multivariable binary and ordered logistic regression models. RESULTS: Data were compared for 76 patients with hyperemesis gravidarum and 315 patients without the condition. The incidence of postoperative nausea and vomiting in the hyperemesis group versus the non-hyperemesis group was 43.4% vs 29.6%, respectively. The odds of experiencing postoperative nausea and vomiting was 1.95 times higher in women with hyperemesis gravidarum than in those without (aOR 1.95, 95% CI 1.13 to 3.36, P=0.016). The odds of having more severe postoperative nausea and vomiting were greater in the hyperemesis gravidarum group (aOR 1.91, 95% CI 1.14 to 3.20, P=0.014). CONCLUSION: Patients with hyperemesis gravidarum are more likely to develop nausea and vomiting after caesarean section, and this is likely to be of greater severity than in those without the condition. This finding should assist the effective provision of intra-operative and postoperative anti-emetics for patients with hyperemesis gravidarum undergoing caesarean section.

Polygenic liability for schizophrenia and childhood adversity influences daily-life emotion dysregulation and psychosis proneness.

OBJECTIVE: To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures. METHODS: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models. RESULTS: Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures. CONCLUSION: Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness.

A Boltzmann Constant Determination Based on Johnson Noise Thermometry.

A value for the Boltzmann constant was measured electronically using an improved version of the Johnson Noise Thermometry (JNT) system at the National Institute of Standards and Technology (NIST), USA. This system is different from prior ones, including those from the 2011 determination at NIST and both 2015 and 2017 determinations at the National Institute of Metrology (NIM), China. As in all three previous determinations, the main contribution to the combined uncertainty is the statistical uncertainty in the noise measurement, which is mitigated by accumulating and integrating many weeks of cross-correlated measured data. The second major uncertainty contribution also still results from variations in the frequency response of the ratio of the measured spectral noise of the two noise sources, the sense resistor at the triple-point of water and the superconducting quantum voltage noise source. In this paper, we briefly describe the major differences between our JNT system and previous systems, in particular the input circuit and approach we used to match the frequency responses of the two noise sources. After analyzing and integrating 49 days of accumulated data, we determined a value: k = 1.380 642 9(69)×10-23 J/K with a relative standard uncertainty of 5.0×10-6 and relative offset -4.05×10-6 from the CODATA 2014 recommended value.

Is sensitivity to daily stress predictive of onset or persistence of psychopathology?

PURPOSE: The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology. METHODS: We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model. RESULTS: Linear analyses showed that emotional stress reactivity was not associated with onset (ß=.02; P=.56) or persistence (ß=-.01; P=.78) of symptoms. There was a significant effect of baseline symptom score (ß=.53; P<.001) and average negative affect (NA: ß=.19; P<.001) on follow-up symptoms. Using the categorical approach, we found that affective sensitivity to mild (ß=.25; P<.001), but not moderate (ß=-.03; P=.65) or severe (ß=-.06; P=.42), stressors was associated with symptom persistence one year later. DISCUSSION: We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.

[Henry Beecher and medical science: the 50th anniversary of a famous article]. / Henry Beecher en de medische wetenschap.

In 2016, it had been exactly half a century ago that Henry Beecher published his article 'Ethics and clinical research' in The New England Journal of Medicine. Today, this article is considered a turning point in the history of medical research ethics. On the occasion of the fiftieth anniversary of this famous article, we are looking back on this turbulent period in the history of medicine.

Downward trends in the prevalence of childhood overweight in two pilot towns taking part in the VIASANO community-based programme in Belgium: data from a national school health monitoring system.

BACKGROUND: Multilevel approaches involving environmental strategies are considered to be good practice to help reduce the prevalence of childhood overweight. OBJECTIVES: The objective of this study was to evaluate the effects of VIASANO, a community-based programme using the EPODE methodology, on the prevalence of overweight in two pilot towns in Belgium. METHODS: We analysed data from a national school health monitoring system to compare changes in the prevalence of overweight and obesity over a 3-year period (2007-2010) in children aged 3-4 and 5-6 years in the pilot towns with those of children of the same ages from the whole French-speaking community of Belgium. Heights and weights of all participants were measured by trained school nurses using a standardized method. RESULTS: The prevalence of overweight (-2.1%) and overweight + obesity (-2.4%) decreased in the pilot towns, but remained stable in the comparison population (+0.1% and +0.2%, respectively). After adjustment for lack of homogeneity between the study populations, there was a trend towards a decrease in overweight (P = 0.054) and overweight + obesity (P = 0.058) in the pilot towns compared with the general population. CONCLUSIONS: These results suggest that a community-based programme, such as VIASANO, may be a promising strategy for reducing the prevalence of childhood overweight even over a short period of time.

Does EBV alter the pathogenesis of malaria?

Plasmodium falciparum infections have been implicated in immune deficiencies resulting in ineffective control of Epstein-Barr virus, thereby increasing the risk of endemic Burkitt lymphoma in children. However, the impact of Epstein-Barr virus infections on the development of immunity to P. falciparum has not been studied in depth. In this review, we examine novel findings from animal co-infection models and human immuno-epidemiologic studies to speculate on the impact of acute gammaherpesvirus co-infection on malarial disease severity. Children are often concurrently or sequentially infected with multiple pathogens, and this has implications for understanding the development of protective immunity as well as in the evaluation of vaccine efficacy.

Optically mediated hybridization between two mechanical modes.

In this Letter we study a system consisting of two nearly degenerate mechanical modes that couple to a single mode of an optical cavity. We show that this coupling leads to nearly complete (99.5%) hybridization of the two mechanical modes into a bright mode that experiences strong optomechanical interactions and a dark mode that experiences almost no optomechanical interactions. We use this hybridization to transfer energy between the mechanical modes with 40% efficiency.

Interleukin-32 expression is associated with a poorer prognosis in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) represent the sixth most common malignancy diagnosed worldwide. Patient's survival is low due the high frequency of tumor recurrence. Inflammation promotes carcinogenesis as well as the formation of metastasis. Indeed, proinflammatory mediators are known to stimulate the expression of specific transcription factors such as Snai1 and to increase the ability of tumor cells to migrate into distant organs. The atypical interleukin-32 (IL32) was mainly described to exacerbate inflammatory responses in rheumatoid arthritis and inflammatory bowel diseases. IL32 is expressed in various cancers but its role in HNSCC physiology is still unexplored. Here, we analyzed the expression of IL32 and its implication on HNSCC aggressiveness. We showed that patients with tumor expressing high amounts of IL32 exhibit decreased disease-free periods (20.5 mo vs. 41 mo, P = 0.0041) and overall survival (P = 0.0359) in comparison with individuals with weak IL32 tumor expression. This overexpression was negatively correlated with gender (P = 0.0292) and p53 expression (P = 0.0307). In addition, in vitro data linked IL32 expression to metastasis formation since IL32 inhibition decreased Snai1 expression and tumor cell migration in a Boyden chamber assay. Our data provide new insight into the role of IL32 in HNSCC aggressiveness.

Positive emotions from social company in women with persisting subclinical psychosis: lessons from daily life.

OBJECTIVE: Altered social reward functioning is associated with psychosis irrespective of stage and severity. Examining the role of social reward functioning prospectively in relation to psychotic experiences before these become persistent and potentially disabling can aid in elucidating social mechanisms that induce shifts toward more severe psychotic states, without the confounding effects of clinical disorder. METHOD: In a longitudinal general population sample (N = 566), the experience sampling method (repetitive random sampling of momentary emotions and social context) was used to assess daily life social functioning at baseline. Persistence of subclinical psychotic experiences was based on the Community Assessment of Psychic Experiences assessed three times over 14 months. Analyses examined to what degree i) social context and ii) appreciation thereof differentiated between those who did and did not develop persistent psychotic experiences. RESULTS: Although individuals with persistent psychotic experiences did not differ in overall level of positive effect, the amount of time spent alone or the level of social satisfaction compared to individuals without persistent psychotic experiences, they were more sensitive to the rewarding effects of social company. CONCLUSION: Alterations in social reward experience may form one of the mechanisms that precede the development of the extended psychosis phenotype over time.

Endoscopic diagnosis and treatment of esophageal verrucous squamous cell cancer.

Verrucous squamous cell cancer (VSCC) of the esophagus is a variant of squamous cell carcinoma. This rare entity has been described in only a handful of case reports in the literature. We sought to evaluate the endoscopic features, treatment, and outcomes related to esophageal VSCC. The medical records of all patients with esophageal VSCC seen at our institution from January 1995 to December 2010 were reviewed retrospectively. A total of 11 patients (6 men; mean age 66 years [range 57-75 years]) were identified, with a mean follow up of 4 years (range 0.5-10 years) available in nine patients after diagnosis. About half the patients smoked or consumed alcohol on a regular basis. The median time interval from onset of symptoms to diagnosis of esophageal VSCC was 2.5 years (range 1-20 years), with dysphagia being present in all patients. The majority of tumors (8 of 11) exhibited a white, warty, plaque-like appearance with superimposed Candida at endoscopy, which led solely to a diagnosis of Candida esophagitis on initial presentation. The disease was either extensive (n = 5) throughout the esophagus or localized (n = 6) often by tumor nodules or projections, with the lower third of the esophagus being most commonly involved. Initial pinch biopsies were nondiagnostic in eight (73%) of the patients. Six patients underwent esophagectomy; neoadjuvant chemoradiation therapy was provided in two. In patients treated solely with surgery and who had a preoperative endoscopic ultrasound, the latter tended to overestimate staging of the lesion relative to surgical pathologic staging. Two patients were deemed to be poor operative candidates and received only chemoradiation treatment. One patient with a T2N0 tumor by endoscopic ultrasound staging was managed symptomatically with intermittent endoscopic dilation because of significant comorbidities that precluded surgery and oncologic therapy. There has been no evidence for residual or recurrent neoplastic disease in the eight patients who received treatment with surgery and/or chemoradiation therapy. Five of six patients who underwent surgery have required intermittent endoscopic dilation of anastomotic strictures during follow up. One of the two patients who received only chemoradiation therapy has required periodic endoscopic dilation for radiation-induced esophageal stricture. Two of the nine (22%) patients have died of causes unrelated to VSCC or its treatment at last follow up. In conclusion, a high index of suspicion for esophageal VSCC should be raised by the presence of long-standing symptoms coupled with white, warty esophageal lesions seen on endoscopic evaluation. Candida overgrowth can be expected to confound the diagnosis. Despite the long duration of symptoms, surgical resection typically shows relatively low-grade tumors, consistent with the rare propensity of this variant of esophageal squamous cell carcinoma to metastasize.

Lower limb injuries caused by improvised explosive devices: proposed 'Bastion classification' and prospective validation.

BACKGROUND: Complex lower limb injury caused by improvised explosive devices (IEDs) has become the signature wounding pattern of the conflict in Afghanistan. Current classifications neither describe this injury pattern well, nor correlate with management. There is need for a new classification, to aid communication between clinicians, and help evaluate interventions and outcomes. We propose such a classification, and present the results of an initial prospective evaluation. PATIENTS AND METHODS: The classification was developed by a panel of military surgeons whilst deployed to Camp Bastion, Afghanistan. Injuries were divided into five classes, by anatomic level. Segmental injuries were recognised as a distinct entity. Associated injuries to the intraperitoneal abdomen, genitalia and perineum, pelvic ring, and upper limbs, which impact on clinical management and resources, were also accounted for. RESULTS: Between 1 November 2010 and 20 February 2011, 179 IED-related lower limb injuries in 103 consecutive casualties were classified, and their subsequent vascular and musculoskeletal treatment recorded. 69% of the injuries were traumatic amputations, and the remainder segmental injuries. 49% of casualties suffered bilateral lower limb amputation. The most common injury was class 3 (involving proximal lower leg or thigh, permitting effective above-knee tourniquet application, 49%), but more proximal patterns (class 4 or 5, preventing effective tourniquet application) accounted for 18% of injuries. Eleven casualties had associated intraperitoneal abdominal injuries, 41 suffered genital or perineal injuries, 9 had pelvic ring fractures, and 66 had upper limb injuries. The classification was easy to apply and correlated with management. CONCLUSIONS: The 'Bastion classification' is a pragmatic yet clinically relevant injury categorisation, which describes current injury patterns well, and should facilitate communication between clinicians, and the evaluation of interventions and outcomes. The validation cohort confirms that the injury burden from IEDs in the Helmand Province of Afghanistan remains high, with most casualties sustaining amputation through or above the knee. The rates of associated injury to the abdomen, perineum, pelvis and upper limbs are high. These findings have important implications for the training of military surgeons, staffing and resourcing of medical treatment facilities, to ensure an adequate skill mix to manage these complex and challenging injuries.

Novel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue.

BACKGROUND: Recent data indicated that natural killer (NK) cells and chemokines could play a pivotal role in nasal inflammation. CX3CR1, the only receptor for fractalkine/CX3CL1, is abundantly expressed by NK cells, and was recently shown to also be a receptor for eotaxin-3/CCL26. However, no reports explored the NK cells-CX3CL1-CCL26 axis via CX3CR1 in allergy. OBJECTIVE: Our goals were first to determine specifically NK cell recruitment pattern in nasal tissue of allergic chronic rhinosinusitis (ACRS) and non-allergic chronic rhinosinusitis (NACRS) patients in comparison with healthy controls, and secondly, to investigate the function of CX3CR1 in NK cell migration. METHODS: Immunohistochemistry, microchemotaxis chambers, flow cytometry and confocal microscopy were used in this study. RESULTS: Herein, we showed that NK cells infiltrated the epithelial layers of nasal tissue only in ACRS patients and not in NACRS patients or controls. NK cells were also more numerous in the stroma of the nasal tissue from ACRS patients compared with NACRS patients or controls. This migration could be mediated by both CX3CL1 and CCL26, as these two chemokines induced NK cell migration. Moreover, both molecules also stimulated cytoskeleton changes and F-actin reorganisation in NK cells. Chemotaxis and cytoskeleton changes were sensitive to genistein, a tyrosine kinase inhibitor. By flow cytometry, we demonstrated that a single antigen nasal provocation challenge increased the expression of CX3CR1 on NK cells in allergic rhinitis (AR) patients. The function of this receptor was associated with a significant augmentation of NK cell chemotaxis against the optimal doses of CX3CL1 and CCL26. CONCLUSIONS AND CLINICAL RELEVANCE: Our results highlight a novel role for CX3CR1 in NK cell migration that may contribute to the NK cell trafficking to the allergic upper airway. This could be mediated largely by CX3CL1 and CCL26 stimulation of the tyrosine kinase pathway.

Deconstructing the familiality of variability in momentary negative and positive affect.

OBJECTIVE: The daily life, affective phenotypes of momentary negative affect (NA), positive affect (PA) variability and NA variability are associated with future depressive symptomatology. This study investigates the extent to which genetic and environmental factors contribute to the inter-individual differences in these daily life, affective phenotypes. METHOD: Two hundred and seventy-nine female twins from the Flemish (Belgium) general population participated in an experience sampling study measuring affect in daily life. Structural equation modelling was used to fit univariate and bivariate models. RESULTS: Genetic factors explained, respectively, 18%, 18% and 35% of the inter-individual differences in momentary NA, PA variability and NA variability. Non-shared environmental factors were found to explain the remaining inter-individual variation. In addition, 41% of the association between positive and NA variability was attributed to shared genetic factors. CONCLUSION: Results of this study show that daily life patterns of affective expression are subject to substantial environmental influence. Prospective assessments of the effect of interventions on these expressions may therefore represent a powerful tool to prevent transition from subclinical depressive symptomatology to a clinical outcome or to reduce symptomatology in those with clinical depression.