What maternal educational mobility tells us about the mother's parenting routines, offspring school achievement and intelligence.

BACKGROUND: Educational mobility at the macro-level is a common measure of social inequality. Nonetheless, the correlates of mobility of education at the individual level are less well studied. We evaluated whether educational mobility of the second generation (compared to the first generation level) predicts differences in parenting practices of the second generation and school achievement and intelligence in the third generation. METHODS: Data from a population-based cohort of children in the Netherlands (N = 3547; 49.4% boys) were analyzed. Maternal, grandparental education and family routines, a parenting practice, were reported by the mother. Child school achievement at the end of primary school (∼12 years, with the national Dutch academic test score) and child intelligence (∼6 and 13 years) were measured in a standardized manner. Also, a child genome-wide polygenic score of academic attainment was calculated. To estimate the effect of educational mobility, inverse probability-weighted linear models and Diagonal Reference Models (DRM) were used. RESULTS: Upward maternal educational mobility was associated with better offspring school achievement, higher intelligence, and more family routines if compared to offspring of mothers with no upward mobility. However, mothers did not implement the same level of family routines as similarly educated mothers and grandfathers who already had achieved this educational level. Likewise, children of mothers with upward educational mobility had lower school achievement and intelligence than children of similarly educated mothers with no mobility. Child's genetic potential for education followed a similar association pattern with higher potential in children of upward mobile mothers. CONCLUSION: Policymakers might overlook social inequalities when focused on parental socioeconomic status. Grandparental socioeconomic status, which independently predicts child school achievement, intelligence, and parental family routines, should also be assessed. The child's genetic endowment reflects the propensity for education across generations that partly underlies mobility and some of its effect on the offspring.

HER2-positive apocrine carcinoma of the breast: a population-based analysis of treatment and outcome.

PURPOSE: Apocrine carcinoma of the breast (APO) expresses HER2 in 30-50% of cases. This study explored the clinicopathological features and outcome of HER2+/APO and matched HER2+/NST cohort. METHODS: We used the SEER database to explore the cohorts. Univariate and multivariate analyses were used to assess the survival. Based on ER and PR [steroid receptors/SR/] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons. RESULTS: We retrieved 259 cases of HER2+/APO. Most HER2+/APO were SR negative (65%). HER2+/APO were more prevalent in the 80+ age group (24.7% vs. 15.7%, p < 0.001). HER2+/SR-/APO had a significantly lower histological grade than the HER2+/SR-/NST (p < 0.001). Breast cancer-related deaths were more prevalent in HER2+/NST (7.8% vs. 3.9%, p = 0.019). This was particularly evident between SR- subgroups (10.4% in HER2+/SR-/NST vs. 4.2% in HER2+/SR-/APO, p = 0.008) and was reaffirmed in breast cancer-specific survival in univariate analysis (p = 0.03). Other than race and SR status, HER2+/APO subgroups did not differ in clinicopathological parameters. CONCLUSIONS: Our study confirms the rarity of the APO and reveals that SR status in APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity.

Diet quality and all-cause mortality among US adults, estimated from National Health and Nutrition Examination Survey (NHANES), 2003-2008.

OBJECTIVE: We assessed the ability of the Prime Diet Quality Score (PDQS) to predict mortality in the US population and compared its predictiveness with that of the Healthy Eating Index-2015 (HEI-2015). DESIGN: PDQS and HEI-2015 scores were derived using two 24-h recalls and converted to quintiles. Mortality data were obtained from the 2015 Public-Use Linked Mortality File. Associations between diet quality and all-cause mortality were evaluated using multivariable Cox proportional hazards models, and predictive performance of the two metrics was compared using a Wald test of equality of coefficients with both scores in a single model. Finally, we evaluated associations between individual metric components and mortality. SETTING: A prospective analysis of the US National Health and Nutrition Examination Survey (NHANES) data. PARTICIPANTS: Five-thousand five hundred and twenty-five participants from three survey cycles (2003-2008) in the NHANES aged 40 years and over. RESULTS: Over the 51 248 person-years of follow-up (mean: 9·2 years), 767 deaths were recorded. In multivariable models, hazard ratios between the highest and lowest quintiles of diet quality scores were 0·70 (95 % CI 0·51, 0·96, Ptrend = 0·03) for the PDQS and 0·77 (95 % CI 0·57, 1·03, Ptrend = 0·20) for the HEI-2015. The PDQS and HEI-2015 were similarly good predictors of total mortality (Pdifference = 0·88). CONCLUSION: Among US adults, better diet quality measured by the PDQS was associated with reduced risk of all-cause mortality. Given that the PDQS is simpler to calculate than the HEI-2015, it should be evaluated further for use as a diet quality metric globally.

SARS-CoV-2 virus outbreak and the emergency public health measures in Bosnia and Herzegovina: January - July, 2020.

Between March 5th and July 25th, 2020, the total number of SARS-CoV-2 confirmed cases in Bosnia and Herzegovina (BH) was 10,090, corresponding to a cumulative incidence rate of 285.7/100,000 population. Demographic and clinical information on all the cases along with exposure and contact information were collected using a standardized case report form. In suspected SARS-CoV-2 cases, respiratory specimens were collected and tested by real-time reverse-transcriptase polymerase chain reaction assay. The dynamic of the outbreak was summarized using epidemiological curves, instantaneous reproduction number Rt, and interactive choropleth maps for geographical distribution and spread. The rate of hospitalization was 14.0%(790/5646) in the Federation of Bosnia and Herzegovina (FBH) and 6.2% (267/4299) in the Republic of Srpska (RS). The death rate was 2.2% (122/5646) in FBH and 3.6% in the RS (155/4299). After the authorities lifted mandatory quarantine restrictions, the instantaneous reproduction number increased from 1.13 on May 20th to 1.72 on May 31st. The outbreak concerns both entities, FBH and RS, and it is more pronounced in those aged 20-44 years. It is important to develop the communication and emergency plan for the SARS-CoV-2 outbreak in BH, including the mechanisms to allow the ongoing notification and updates at the national level.

Spatio-temporal data visualization for monitoring of control measures in the prevention of the spread of COVID-19 in Bosnia and Herzegovina.

Aim The damage caused by the COVID-19 pandemic has made the prevention of its further spread at the top of the list of priorities of many governments and state institutions responsible for health and civil protection around the world. This prevention implies an effective system of epidemiological surveillance and the application of timely and effective control measures. This research focuses on the application of techniques for modelling and geovisualization of epidemic data with the aim of simple and fast communication of analytical results via geoportal. Methods The paper describes the approach applied through the project of establishing the epidemiological location-intelligence system for monitoring the effectiveness of control measures in preventing the spread of COVID-19 in Bosnia and Herzegovina. Results Epidemic data were processed and the results related to spatio-temporal analysis of the infection spread were presented by compartmental epidemic model, reproduction number R, epi-curve diagrams as well as choropleth maps for different levels of administrative units. Geovisualization of epidemic data enabled the release of numerous information from described models and indicators, providing easier visual communication of the spread of the disease and better recognition of its trend. Conclusion The approach involves the simultaneous application of epidemic models and epidemic data geovisualization, which allows a simple and rapid evaluation of the epidemic situation and the effects of control measures. This contributes to more informative decision-making related to control measures by suggesting their selective application at the local level.

Preoperative predictors that impact the survival and outcome of patients undergoing secondary cytoreduction for ovarian cancer.

This study aimed to examine the factors affecting feasibility of optimal and complete secondary cytoreductive surgery (SCRS) and to characterise the prognostic factors that correlate with improved survival in patients who underwent SCRS. This is a retrospective single-institutional cohort study of patients who underwent SCRS for recurrent epithelial ovarian cancer (EOC). One hundred and forty-eight patients met inclusion criteria. Platinum sensitivity was associated with complete cytoreduction at SCRS. Factors associated with suboptimal cytoreduction (SOC) were age >55 years, serous histology, largest tumour implant size >4 cm, and SOC at primary surgery. Overall survival analysis showed significantly longer survival with complete cytoreduction compared to optimal and SOC. Surgical outcome of SCRS was an independent predictor of survival regardless of the outcome of primary cytoreduction. Location of the largest implant, DFI and timing of chemotherapy also impact on survival.

A Randomized Controlled Trial of Opt-In Versus Opt-Out Enrollment Into a Diabetes Behavioral Intervention.

PURPOSE: To examine the effect of an opt-out default recruitment strategy compared to a conventional opt-in strategy on enrollment and adherence to a behavioral intervention for poorly controlled diabetic patients. DESIGN: Randomized controlled trial. SETTING: University of Pennsylvania primary care practices. PARTICIPANTS: Participants of this trial included those with (1) age 18 to 80 years; (2) diabetes diagnosis; and (3) a measured hemoglobin A1c (HbA1c) greater than 8% in the past 12 months. INTERVENTION: We randomized eligible patients into opt-in and opt-out arms prior to enrollment. Those in the opt-out arm received a letter stating that they were enrolled into a diabetes research study with the option to opt out, and those in the opt-in arm received a standard recruitment letter. MEASURES: Main end points include enrollment rate, defined as the proportion of participants who attended the baseline visit, and adherence to daily glycemic monitoring. ANALYSIS: We powered our study to detect a 20% difference in adherence to device usage between arms and account for a 10% attrition rate. RESULTS: Of the 569 eligible participants who received a recruitment letter, 496 were randomized to the opt-in arm and 73 to the opt-out arm. Enrollment rates were 38% in the opt-out arm and 13% in the opt-in arm ( P < .001). CONCLUSIONS: Opt-out defaults, where clinically appropriate, could be a useful approach for increasing the generalizability of low-risk trials testing behavioral interventions in clinical settings.

Infant Neuromotor Development and Childhood Problem Behavior.

BACKGROUND: Research of adults and school-aged children suggest a neurodevelopmental basis for psychiatric disorders. We examined whether infant neuromotor development predicted internalizing and externalizing problems in young children. METHODS: In Generation R, a population-based cohort in the Netherlands (2002-2006), trained research assistants evaluated the neuromotor development of 4006 infants aged 2 to 5 months by using an adapted version of Touwen's Neurodevelopmental Examination (tone, responses, and senses and other observations). We defined nonoptimal neuromotor development as scores in the highest tertile. Mothers and fathers rated their children's behavior at ages 1.5, 3, 6, and 10 years with the Child Behavior Checklist (n = 3474, response: 86.7%). The associations were tested with generalized linear mixed models. RESULTS: Overall, neuromotor development predicted internalizing scores, but no association was observed with externalizing scores. Nonoptimal muscle tone was associated with higher internalizing scores (mothers' report: ß = .07; 95% confidence interval [CI]: 0.01 to 0.13; fathers' report: ß = .09, 95% CI: 0.00 to 0.16). In particular, nonoptimal low muscle tone was associated with higher internalizing scores (mothers' report: ß = .11; 95% CI: 0.05 to 0.18; fathers' report: ß = .13; 95% CI: 0.04 to 0.22). We also observed an association between senses and other observations with internalizing scores. There was no relationship between high muscle tone or reflexes and internalizing scores. CONCLUSIONS: Common emotional problems in childhood have a neurodevelopmental basis in infancy. Neuromotor assessment in infancy may help identify vulnerability to early internalizing symptoms and offer the opportunity for targeted interventions.

Comparative clinical utility of tumor genomic testing and cell-free DNA in metastatic breast cancer.

PURPOSE: Breast cancer metastases differ biologically from primary disease; therefore, metastatic biopsies may assist in treatment decision making. Commercial genomic testing of both tumor and circulating tumor DNA have become available clinically, but utility of these tests in breast cancer management remains unclear. METHODS: Patients undergoing a clinically indicated metastatic tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood were collected at the time of disease progression before subsequent therapy, and patients were followed for response on subsequent treatment. Tumor testing (n = 53) and concurrent cell-free DNA (n = 32) in a subset of patients was performed using CLIA-approved assays. RESULTS: The proportion of patients with a genomic alteration was lower in tumor than in blood (69 vs. 91%; p = 0.06). After restricting analysis to alterations covered on both platforms, 83% of tumor alterations were detected in blood, while 90% of blood alterations were detected in tumor. Mutational load specific for the panel genes was calculated for both tumor and blood. Time to progression on subsequent treatment was significantly shorter for patients whose tumors had high panel-specific mutational load (HR 0.31, 95% CI 0.12-0.78) or a TP53 mutation (HR 0.35, 95% CI 0.20-0.79), after adjusting for stage at presentation, hormone receptor status, prior treatment type, and number of lines of metastatic treatment. CONCLUSIONS: Treating oncologists must distinguish platform differences from true biological heterogeneity when comparing tumor and cfDNA genomic testing results. Tumor and concurrent cfDNA contribute unique genomic information in metastatic breast cancer patients, providing potentially useful biomarkers for aggressive metastatic disease.

High ALDH1 expression correlates with better prognosis in tumorigenic malignant melanoma.

Aldehyde dehydrogenase 1 (ALDH1) has been proposed as biomarker of stem cells for certain human cancers. ALDH1 expression has been correlated with poor patient outcomes in a variety of malignancies but better patient outcomes in others, and its prognostic significance in malignant melanoma is unclear. Thus, 68 melanoma patients with comprehensive clinical and pathologic follow-up data were used to construct a tissue microarray. A modified histological score (H-score) with a maximum score of 300 was used to quantify immunohistochemical staining for ALDH1. Survival time was defined as the time between diagnosis and melanoma-specific death. Using univariate logistic regression, a low (<80 H-score) ALDH1 score showed 3.7-fold increase in risk for melanoma-specific death within 10 years when compared with high (>80) ALDH1 levels (P=0.017). Odds of MSD were lower by a factor of ~0.9 for each 10-point increase in H-Score. Median survival time was 44.1 months and 180.9 months for patients with low and high ALDH1 expression, respectively. Using multivariate analysis, ALDH1 H-score was found to be an independent prognostic factor. These findings suggest that ALDH1 expression in malignant melanoma has a favorable effect on patient survival. Further study is needed elucidate the function of this enzymatic protein in melanoma progression.

Translating the hemoglobin A1C with more easily understood feedback: a randomized controlled trial.

INTRODUCTION: Previous work has indicated that for patients with diabetes, there is value in understanding glycemic control. Despite these findings, patient understanding of the hemoglobin A1C value (A1C) is notably poor. In this study, we test the effect of two alternative communication formats of the A1C on improving glycemic control among patients with poorly controlled diabetes. METHODS: 177 patients with poorly controlled diabetes were randomized to one of three study arms that varied in the information they received: (1) a "diabetes report card" containing individualized information about glycemic control for each participant with letter grades ranging from A to F; (2) a "report card" containing a face whose emotion reflected current glycemic control; or (3) a "report card" with glycemic control expressed with the A1C value (standard arm). The primary study outcome was change in A1C at 6 months. Secondary outcomes included changes in participant perceptions of their glycemic control. RESULTS: The average A1C for enrolled participants was 9.9 % (S.D. 1.7) and did not differ significantly among study arms. We noted no significant differences in change in A1C at 6 months between the standard and experimental arms. Using multiple imputation to account for missing A1C values, the changes in A1C for the letter grade, face, and standard arms were -0.55 % (-1.15, 0.05), -0.89 % (-1.49, -0.29), and -0.74 % (-1.51, 0.029), respectively (p = 0.67 for control vs. grade, p = 0.76 for control vs. face). DISCUSSION: Feedback to patients with poorly controlled diabetes in the form of letter grades and faces did not differentially impact glycemic control at 6 months or participant perceptions of current control. These efforts to improve communication and patient understanding of disease management targets need further refinement to significantly impact diabetes outcomes. CLINICAL TRIAL ID: NCT01143870.

Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis.

OBJECTIVE: The presence of T cells within the epithelial component of tumors, as histologic evidence of anti-tumor immunity, has been associated with a survival advantage in multiple studies across diverse patient cohorts. We performed a meta-analysis of studies evaluating the prognostic value of tumor-infiltrating lymphocytes (TIL) on survival among women with ovarian cancer and to investigate factors associated with variations in this effect, including patient characteristics, surgical outcomes, tumor histology, and study protocols. METHOD: Published studies that evaluated the association between TIL and patient survival were identified. Descriptive statistics, outcome data, and study quality were extracted from studies that met inclusion criteria. Hazard ratios and 95% confidence intervals were pooled across studies using the random-effects model. Publication bias was investigated using a funnel plot and heterogeneity was assessed with subgroup analysis and I(2) statistics. RESULTS: Ten suitable studies comprising 1815 patients with ovarian cancer were analyzed. Our results demonstrate that a lack of intraepithelial TILs is significantly associated with a worse survival among patients (pooled HR: 2.24, 95% CI; 1.71-2.91). Variations in the prognostic value of TIL status based on debulking status, scoring method, and geographic regions were identified. CONCLUSIONS: Intraepithelial TILs are a robust predictor of outcome in ovarian cancer and define a specific class of patients, whose distinct tumor biology should be taken into account in devising appropriate therapeutic strategies.