Production can enhance semantic encoding: Evidence from forced-choice recognition with homophone versus synonym lures.

The production effect-better memory for words read aloud rather than silently-has been attributed to responses at test being guided by memory for the act of production. In Experiment 1, we evaluated this distinctiveness account by comparing production effects in forced-choice recognition when lures were either homophones of the targets (toad or towed?) or unrelated words (toad or seam?). If the production effect at test was driven solely by memory for the productive act (e.g., articulation, auditory processing), then the effect should be reduced with homophone lures. Contrary to that prediction, the production effect did not differ credibly between homophone-lure and unrelated-lure groups. Experiment 1 led us to hypothesize that production may also boost semantic encoding, and that participants use memory of semantic encoding to guide their forced-choice responses. Consistent with these hypotheses, using synonym lures to interfere with semantic-based decisions (poison or venom?) reduced the production effect relative to using unrelated lures (poison or ethics?) in Experiment 2. Our findings suggest that enhanced conceptual encoding may be another useful product of production.

Mitigating Racial Inequity by Addressing Racism in the Criminal Justice System: A Behavior Analytic Approach.

Racial inequity in the U.S. criminal justice system is a long-standing problem that has recently garnered international attention. This article frames the problem of racial inequity in a behavior analytic context and offers potential solutions based on existent research and behavior analytic principles. We draw a parallel between the analysis of racist behavior enabled by the definitions provided by Kendi in How to Be an Antiracist and the analysis of verbal behavior made possible by the terminology posited by Skinner in Verbal Behavior in order to highlight the pertinence of applying a behavior analytic approach to the problem of racial inequity upheld by racist behavior. Immediately actionable steps to address racism in the criminal justice system and beyond are offered on a cultural, organizational, and individual level.

The venous system of E14.5 mouse embryos-reference data and examples for diagnosing malformations in embryos with gene deletions.

Approximately one-third of randomly produced knockout mouse lines produce homozygous offspring, which fail to survive the perinatal period. The majority of these die around or after embryonic day (E)14.5, presumably from cardiovascular insufficiency. For diagnosing structural abnormalities underlying death and diseases and for researching gene function, the phenotype of these individuals has to be analysed. This makes the creation of reference data, which define normal anatomy and normal variations the highest priority. While such data do exist for the heart and arteries, they are still missing for the venous system. Here we provide high-quality descriptive and metric information on the normal anatomy of the venous system of E14.5 embryos. Using high-resolution digital volume data and 3D models from 206 genetically normal embryos, bred on the C57BL/6N background, we present precise descriptive and metric information of the venous system as it presents itself in each of the six developmental stages of E14.5. The resulting data shed new light on the maturation and remodelling of the venous system at transition of embryo to foetal life and provide a reference that can be used for detecting venous abnormalities in mutants. To explore this capacity, we analysed the venous phenotype of embryos from 7 knockout lines (Atp11a, Morc2a, 1700067K01Rik, B9d2, Oaz1, Celf4 and Coro1c). Careful comparisons enabled the diagnosis of not only simple malformations, such as dual inferior vena cava, but also complex and subtle abnormalities, which would have escaped diagnosis in the absence of detailed, stage-specific referenced data.

Artefacts in Volume Data Generated with High Resolution Episcopic Microscopy (HREM).

High resolution episcopic microscopy (HREM) produces digital volume data by physically sectioning histologically processed specimens, while capturing images of the subsequently exposed block faces. Our study aims to systematically define the spectrum of typical artefacts inherent to HREM data and to research their effect on the interpretation of the phenotype of wildtype and mutant mouse embryos. A total of 607 (198 wildtypes, 409 mutants) HREM data sets of mouse embryos harvested at embryonic day (E) 14.5 were systematically and comprehensively examined. The specimens had been processed according to essentially identical protocols. Each data set comprised 2000 to 4000 single digital images. Voxel dimensions were 3 × 3 × 3 µm3. Using 3D volume models and virtual resections, we identified a number of characteristic artefacts and grouped them according to their most likely causality. Furthermore, we highlight those that affect the interpretation of embryo data and provide examples for artefacts mimicking tissue defects and structural pathologies. Our results aid in optimizing specimen preparation and data generation, are vital for the correct interpretation of HREM data and allow distinguishing tissue defects and pathologies from harmless artificial alterations. In particular, they enable correct diagnosis of pathologies in mouse embryos serving as models for deciphering the mechanisms of developmental disorders.

Comorbid obsessive-compulsive disorder in individuals with eating disorders: An epidemiological meta-analysis.

The present study aimed to provide a precise, meta-analytic estimate of the prevalence of obsessive-compulsive disorder (OCD) amongst those with a current primary eating disorder (ED) diagnosis, and to isolate its predictors. An online search of PubMed and PsycINFO was conducted with a Boolean search phrase incorporating keywords related to OCD, EDs, comorbidity, prevalence, and epidemiology, complemented by references coded from related review articles and contact with experts in the field. Articles were included if they (a) reported an observational study examining current ED diagnoses, (b) used a semi-structured or structured diagnostic interview for OCD and ED diagnosis, (c) applied DSM or ICD criteria, (d) included adolescent or adult samples (age > 12), (e) included patient or community samples, and (f) reported lifetime or current OCD comorbidity. From the 846 articles identified, 35 lifetime and 42 current estimates were calculated. OCD prevalence was extracted from each study for each ED diagnostic category, along with eleven additional potential moderators. Analyses revealed an aggregate lifetime OCD prevalence of 13.9% CI95% [10.4 to 18.1] and current OCD prevalence of 8.7% CI95% [5.8 to 11.8] across EDs. Moderator analyses revealed the prevalence of and risk for OCD in EDs to be greatest in anorexia nervosa binge-eating purging type (ANBP). Further, OCD is most prevalent amongst patient samples than samples recruited from the community.

The Col4a2em1(IMPC)Wtsi mouse line: lessons from the Deciphering the Mechanisms of Developmental Disorders program.

The Deciphering the Mechanisms of Developmental Disorders (DMDD) program uses a systematic and standardised approach to characterise the phenotype of embryos stemming from mouse lines, which produce embryonically lethal offspring. Our study aims to provide detailed phenotype descriptions of homozygous Col4a2em1(IMPC)Wtsi mutants produced in DMDD and harvested at embryonic day 14.5. This shall provide new information on the role Col4a2 plays in organogenesis and demonstrate the capacity of the DMDD database for identifying models for researching inherited disorders. The DMDD Col4a2em1(IMPC)Wtsi mutants survived organogenesis and thus revealed the full spectrum of organs and tissues, the development of which depends on Col4a2 encoded proteins. They showed defects in the brain, cranial nerves, visual system, lungs, endocrine glands, skeleton, subepithelial tissues and mild to severe cardiovascular malformations. Together, this makes the DMDD Col4a2em1(IMPC)Wtsi line a useful model for identifying the spectrum of defects and for researching the mechanisms underlying autosomal dominant porencephaly 2 (OMIM # 614483), a rare human disease. Thus we demonstrate the general capacity of the DMDD approach and webpage as a valuable source for identifying mouse models for rare diseases.

Evaluating the replicability of social science experiments in Nature and Science between 2010 and 2015.

Being able to replicate scientific findings is crucial for scientific progress1-15. We replicate 21 systematically selected experimental studies in the social sciences published in Nature and Science between 2010 and 201516-36. The replications follow analysis plans reviewed by the original authors and pre-registered prior to the replications. The replications are high powered, with sample sizes on average about five times higher than in the original studies. We find a significant effect in the same direction as the original study for 13 (62%) studies, and the effect size of the replications is on average about 50% of the original effect size. Replicability varies between 12 (57%) and 14 (67%) studies for complementary replicability indicators. Consistent with these results, the estimated true-positive rate is 67% in a Bayesian analysis. The relative effect size of true positives is estimated to be 71%, suggesting that both false positives and inflated effect sizes of true positives contribute to imperfect reproducibility. Furthermore, we find that peer beliefs of replicability are strongly related to replicability, suggesting that the research community could predict which results would replicate and that failures to replicate were not the result of chance alone.

Intrinsic MYH7 expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy.

HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the ß-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.

A staging system for correct phenotype interpretation of mouse embryos harvested on embryonic day 14 (E14.5).

We present a simple and quick system for accurately scoring the developmental progress of mouse embryos harvested on embryonic day 14 (E14.5). Based solely on the external appearance of the maturing forelimb, we provide a convenient way to distinguish six developmental sub-stages. Using a variety of objective morphometric data obtained from the commonly used C57BL/6N mouse strain, we show that these stages correlate precisely with the growth of the entire embryo and its organs. Applying the new staging system to phenotype analyses of E14.5 embryos of 58 embryonic lethal null mutant lines from the DMDD research programme (https://dmdd.org.uk) and its pilot, we show that homozygous mutant embryos are frequently delayed in development. To demonstrate the importance of our staging system for correct phenotype interpretation, we describe stage-specific changes of the palate, heart and gut, and provide examples in which correct diagnosis of malformations relies on correct staging.

Highly variable penetrance of abnormal phenotypes in embryonic lethal knockout mice.

Background: Identifying genes that are essential for mouse embryonic development and survival through term is a powerful and unbiased way to discover possible genetic determinants of human developmental disorders. Characterising the changes in mouse embryos that result from ablation of lethal genes is a necessary first step towards uncovering their role in normal embryonic development and establishing any correlates amongst human congenital abnormalities. Methods: Here we present results gathered to date in the Deciphering the Mechanisms of Developmental Disorders (DMDD) programme, cataloguing the morphological defects identified from comprehensive imaging of 220 homozygous mutant and 114 wild type embryos from 42 lethal and subviable lines, analysed at E14.5. Results: Virtually all mutant embryos show multiple abnormal phenotypes and amongst the 42 lines these affect most organ systems. Within each mutant line, the phenotypes of individual embryos form distinct but overlapping sets. Subcutaneous edema, malformations of the heart or great vessels, abnormalities in forebrain morphology and the musculature of the eyes are all prevalent phenotypes, as is loss or abnormal size of the hypoglossal nerve.Conclusions: Overall, the most striking finding is that no matter how profound the malformation, each phenotype shows highly variable penetrance within a mutant line. These findings have challenging implications for efforts to identify human disease correlates.

Cancer patient age and family caregiver bereavement outcomes.

PURPOSE: This study drew on life course theory to argue that the strains of cancer caregiving and bereavement are modified by the age of the patient. We expected that caregivers of middle-aged patients would be more distressed than caregivers of older patients. METHODS: This panel study conducted 199 interviews with family caregivers of advanced cancer patients; first following diagnosis and again shortly after the patient's death. RESULTS: Among caregivers of middle-aged patients (40-59), grief mediated the relationship between baseline caregiving and bereavement depressed mood, with grief increasing risk of depression in bereavement. Among caregivers of young-old patients (60-79), grief had a suppressor effect on the relationship between caregiving and bereavement depressed mood, showing greater distress during caregiving than at bereavement. CONCLUSIONS: Caregiving for middle-aged cancer patients may increase the risk for severe grief and depression, whereas caregivers of young-old cancer patients appeared to experience relief at bereavement. After bereavement, continued observation may be warranted for caregivers of a middle-aged patient; grief, added to the ongoing demands of their lives (which may include those left behind by a middle-aged patient), may put such caregivers at risk for greater psychological and emotional distress.

The longitudinal relationship between quality of life and survival in advanced stage cancer.

OBJECTIVES: Quality of Life (QoL) at baseline is frequently found to be a prognostic factor in cancer studies. However, little is known about the relationship of the trajectory of QoL and survival in patients with advanced cancer. This study evaluates the effects of both level and change of QoL on survival to explore the potential of utilizing longitudinal information of QoL for prognosis. METHODS: A series of joint models were used in a sample (N = 512) of patients diagnosed with advanced cancer (sample consisted of nine different cancer sites) with assessments of QoL across six time points and with survival information recorded up to 28 months after diagnosis. We used FACT-G as the QoL measure, and we evaluated the effects of change in QoL controlling for the time-dependent effects of chemotherapy and radiation. RESULTS: The median survival for patients was 14.2 months, and 10% of the sample had survived beyond 28 months after the diagnosis of advanced cancer. The effect of change of QoL on survival was significant (hazard ratio = 0.98; p < 0.001) controlling for time-dependent treatment effects. Also, the slope of the trajectory in QoL was found to be a significant predictor of survival (hazard ratio = 0.18; p < 0.001). CONCLUSION: These preliminary findings suggest that the patient's longitudinal experience in QoL may be a significant prognostic factor of survival, a novel finding with potentially important implications in medical decision making. Longitudinal information on QoL can be used for updating the patient's prognosis of survival.

Grief and risk of depression in context: the emotional outcomes of bereaved cancer caregivers.

We investigated the relationships of grief and depression to cancer caregiving in early bereavement. We began with three expectations: (a) each outcome would reflect different situational predictors, (b) grief would be more directly related to such predictors, and (c) components of grief would relate differently to the caregiving context and depressed mood. We conducted telephone interviews with family caregivers of incurable cancer patients from two hospitals. A total of 199 family caregivers were interviewed at the time of the patient's diagnosis and reinterviewed 3 months after the patient's death. Results showed grief severity was predicted by caregiving circumstances, but bereavement depressed mood was largely unrelated to caregiving. Grief was the main predictor of depressed mood and mediated almost all other effects. We conclude that while grief may trigger depression, the dissimilar connection to context means that the two emotional states should not be equated based purely on similarity of expression.

Preferences for aggressive care in underserved populations with advanced-stage lung cancer: looking beyond race and resuscitation.

PURPOSE: This paper examines the relationship between race, religiousness, spiritual well-being, antitumor treatment and preference for aggressive care among Black and White patients with advanced stage lung cancer receiving ambulatory cancer care in an urban setting. METHODS: A cross-sectional exploration of patients enrolled in a Cleveland-based longitudinal study after initial diagnosis of advanced lung cancer were interviewed in Cleveland regarding religiousness, spiritual well-being, preferences for cardiopulmonary resuscitation (CPR), goals of aggressive care, and willingness to tolerate adverse health states. Receipt of antitumor treatment was identified from medical records. RESULTS: We analyzed data from 67 Black and 129 White patients (N=196). Regression analysis for CPR showed that race was not associated with preference for CPR (OR=1.12, CI 0.44-2.85). The odds of choosing CPR were three times higher among patients receiving antitumor treatment (OR=3.26, CI 1.12-9.44). Greater willingness to endure adverse health states was associated with higher spiritual well-being scores (b=0.12, CI 0.01-0.25). Choosing goals to extend life versus relieve pain was higher among persons with higher spiritual well-being as well (RRR=1.08, CI 1.01-1.16), yet the relationship with religiousness was negative (RRR=0.46, CI 0.22-0.98). CONCLUSIONS: After controlling for multiple factors, race was associated only with CPR, but not with other measures of preference for aggressive care. In addition, receipt of active antitumor treatment was positively associated with preference for CPR and spiritual well-being was important to setting end-of-life care goals and perspectives. Future directions for tailoring end-of-life care decision-making initiatives should move beyond race and discussions of CPR alone and focus on a full spectrum of patient beliefs and preferences at the end of life.

Sleepiness in elderly veterans.

PURPOSE: This observational study seeks to describe the distribution of sleepiness among elderly male veterans and to explain the relationship between sleepiness and age, function, mobility, and depression in this population. METHODS: Veterans who were age 60 or older and had two or more functional limitations based on their activities of daily living or instrumental activities of daily living were recruited in outpatient clinics. They were recruited as part of a longitudinal study and completed questionnaires reported here at the 18-month data collection time point. RESULTS: Veterans report higher sleepiness than normal controls. Self-reported sleepiness scores are similar to those of patients who have been diagnosed with sleep disturbances. CONCLUSIONS: Interventions to identify and support aging veterans with perceived sleepiness should be developed and carefully evaluated.

An Exploration of the relative influence of patient's age and cancer recurrence status on symptom distress, anxiety, and depression over time.

Past research suggests that psychosocial responses to advanced or recurrent cancer vary by age. This study compares the relative influences of patients' age and recurrence status on indicators of symptom distress, anxiety, and depression following a diagnosis of advanced cancer. A prospective study of advanced cancer support provided patient outcome data reported at baseline, 3-, and 6-month intervals. Cohorts were defined by age group and recurrence status and latent growth curves fit to anxiety, depression, and symptom distress outcomes. Middle-age recurrent patients reported the highest symptom distress, depression, and anxiety across time points. Older recurrent patients fared worse at baseline than older nonrecurrent patients, but outcome scores converged across time points. Recurrent cancer presents a distinct challenge that, for middle-age patients, persists across time. It may be beneficial to develop targeted educational and support resources for middle-age patients with recurrent disease.

Relationships and emotional wellbeing among African American and White advanced cancer caregivers.

OBJECTIVE: Advanced cancer family caregivers who have good relationships with other family members and with patient's health care providers (PHCPs) have less emotional distress than caregivers with poor relationships. Given a history of different experiences in medical settings among Whites and African Americans, we examined moderation effects by race. METHODS: Baseline data from an ongoing study were collected via telephone interviews with 397 family caregivers of advanced cancer patients at two cancer clinics. Depressed mood and anxiety were measured with the 14-item Profile of Mood States. RESULTS: Caregivers reporting good relationships with family (p<.001) and PHCPs (p<.001) had lower anxiety and less depressed mood (family, p<.01; PHCP, p<.001). Caregiver race moderated relationship quality: Whites with good PHCP relationships felt less depressed mood (p<.01) and anxiety (p<.01). African Americans with good family relationships showed less depressed mood (p<.05), but no association with anxiety. CONCLUSION: Good relationships are important for caregivers, but PHCPs may have more influence on the wellbeing of White than of African American caregivers. PRACTICE IMPLICATIONS: Developing relationships with caregivers of advanced cancer patients may improve wellbeing for caregivers. In addition, creating strategies to support family relationships may be a useful intervention, especially for African American advanced cancer caregivers.

Primary care physicians' involvement in the cancer care of older long-term survivors.

OBJECTIVE: This study investigated survivors' reports of primary care physicians' (PCPs) involvement in three key cancer survivorship activities: discussing cancer history, whether the PCP initiated discussions, and whether discussions led to tests/procedures. METHOD: The sample included 215 older survivors whose health care was maintained in primary care. Logistic regression explored predictors of the three activities, including demographics, cancer characteristics, survivor/PCP association characteristics, health characteristics, and psychosocial well-being. RESULTS: Nearly two thirds of survivors indicated discussing cancer history; most said discussions were PCP initiated and nearly half said discussions resulted in tests/procedures. Predictors of discussing cancer history were African American race and more comorbid conditions. PCP-initiated discussions were related to older age, surviving breast cancer, more years in the PCP's practice, and having less general health worry. The tests/procedures model was not significant. CONCLUSIONS: As older survivors focused more on other health concerns, PCPs remained attentive to cancer issues, prompting discussions about history and ordering tests.

Relationship quality and burden among caregivers for late-stage cancer patients.

OBJECTIVE: This study explores how caregiver relationship quality with family, patient, and patient's health care provider (HCP) is associated with subjective caregiver burden during the early treatment phase for late-stage cancer. METHOD: Burden and relationship quality were assessed in telephone interviews with family caregivers (FCGs) of advanced cancer patients. The five subscales of the Caregiver Reaction Assessment measured burden, while relationships were measured with the Family Relationship Index, the Family Inventory of Needs subscale of met needs, and a scale assessing family discord in cancer communication. RESULTS: Multiple linear regression analyses in SPSS (v16) of 420 FCGs showed that higher quality relationship with family was associated with lower burden in FCG abandonment, health, scheduling (p < 0.001) and finances (p < 0.01). Higher quality relationship with patients' HCPs was associated with lower burden in FCG abandonment (p < 0.05), health, and finances (p < 0.001). More discordant communication in patient relationship was associated with lower financial burden (p < 0.05). Relationship quality was not associated with caregiver self-esteem. CONCLUSIONS: Findings demonstrate that caregiver relationship quality with family and with HCP are important factors in understanding caregiver burden during the early treatment phase of late-stage cancer care.

Modeling patient-centered communication: oncologist relational communication and patient communication involvement in breast cancer adjuvant therapy decision-making.

OBJECTIVE: Relational communication refers to those messages communicators naturally express that carry meaning about the type and quality of relationship they share. It is expected that patients of oncologists who express positive relational communication will be more communicatively involved in their office visits, and regret their decision for adjuvant therapy following surgery less. METHODS: One hundred eighty (180) audio-recorded discussions between oncologists (n=40) and early stage (I-III) breast cancer patients were coded with the Siminoff Communication Content and Affect Program (SCCAP). The data were used to test the relationships between patient demographics, oncologist relational communication, patient communication involvement and self-reported patient decision regret. RESULTS: After controlling for clinician clusters, oncologists' verbal (i.e., confirming messages) and nonverbal (i.e., direct and inclusive speech) relational communication is indirectly associated with lower patient decision regret via the mediating effect of greater patient communication involvement. CONCLUSION: Clinician relational communication provides an influential affective climate for decision-making that appears to have important effects on patients' decision confidence. PRACTICE IMPLICATIONS: Clinicians should recognize the potential of their own relational messages to facilitate patients' communication involvement in decision-making during cancer care.