Family Environment Variables as Predictors of School Absenteeism Severity at Multiple Levels: Ensemble and Classification and Regression Tree Analysis

School attendance problems, including school absenteeism, are common to many students worldwide, and frameworks to better understand these heterogeneous students include multiple classes or tiers of intertwined risk factors as well as interventions. Recent studies have thus examined risk factors at varying levels of absenteeism severity to demarcate distinctions among these tiers. Prior studies in this regard have focused more on demographic and academic variables and less on family environment risk factors that are endemic to this population. The present study utilized ensemble and classification and regression tree analysis to identify potential family environment risk factors among youth (i.e., children and adolescents) at different levels of school absenteeism severity (i.e., 1 + %, 3 + %, 5 + %, 10 + %). Higher levels of absenteeism were also examined on an exploratory basis. Participants included 341 youth aged 5–17 years (M = 12.2; SD = 3.3) and their families from an outpatient therapy clinic (68.3%) and community (31.7%) setting, the latter from a family court and truancy diversion program cohort. Family environment risk factors tended to be more circumscribed and informative at higher levels of absenteeism, with greater diversity at lower levels. Higher levels of absenteeism appear more closely related to lower achievement orientation, active-recreational orientation, cohesion, and expressiveness, though several nuanced results were found as well. Absenteeism severity levels of 10–15% may be associated more with qualitative changes in family functioning. These data may support a Tier 2-Tier 3 distinction in this regard and may indicate the need for specific family-based intervention goals at higher levels of absenteeism severity

Internalizing Symptoms as Predictors of School Absenteeism Severity at Multiple Levels: Ensemble and Classification and Regression Tree Analysis

School attendance problems are highly prevalent worldwide, leading researchers to investigate many different risk factors for this population. Of considerable controversy is how internalizing behavior problems might help to distinguish different types of youth with school attendance problems. In addition, efforts are ongoing to identify the point at which children and adolescents move from appropriate school attendance to problematic school absenteeism. The present study utilized ensemble and classification and regression tree analysis to identify potential internalizing behavior risk factors among youth at different levels of school absenteeism severity (i.e., 1+%, 3+%, 5+%, 10+%). Higher levels of absenteeism were also examined on an exploratory basis. Participants included 160 youth aged 6–19 years (M = 13.7; SD = 2.9) and their families from an outpatient therapy clinic (39.4%) and community (60.6%) setting, the latter from a family court and truancy diversion program cohort. One particular item relating to lack of enjoyment was most predictive of absenteeism severity at different levels, though not among the highest levels. Other internalizing items were also predictive of various levels of absenteeism severity, but only in a negatively endorsed fashion. Internalizing symptoms of worry and fatigue tended to be endorsed higher across less severe and more severe absenteeism severity levels. A general expectation that predictors would tend to be more homogeneous at higher than lower levels of absenteeism severity was not generally supported. The results help confirm the difficulty of conceptualizing this population based on forms of behavior but may support the need for early warning sign screening for youth at risk for school attendance problems

Reconciling Contemporary Approaches to School Attendance and School Absenteeism: Toward Promotion and Nimble Response, Global Policy Review and Implementation, and Future Adaptability (Part 1)

School attendance is an important foundational competency for children and adolescents, and school absenteeism has been linked to myriad short- and long-term negative consequences, even into adulthood. Many efforts have been made to conceptualize and address this population across various categories and dimensions of functioning and across multiple disciplines, resulting in both a rich literature base and a splintered view regarding this population. This article (Part 1 of 2) reviews and critiques key categorical and dimensional approaches to conceptualizing school attendance and school absenteeism, with an eye toward reconciling these approaches (Part 2 of 2) to develop a roadmap for preventative and intervention strategies, early warning systems and nimble response, global policy review, dissemination and implementation, and adaptations to future changes in education and technology. This article sets the stage for a discussion of a multidimensional, multi-tiered system of supports pyramid model as a heuristic framework for conceptualizing the manifold aspects of school attendance and school absenteeism

Effects of Citrate on the Different Phases of Calcium Oxalate Crystallization

Urinary citrate appears to be an important factor in the crystallization process of calcium oxalate and calcium phosphate. The urinary excretion of citrate was found to be significantly lower in patients with calcium oxalate stone disease as compared with normal subjects, and about 30 per cent of the calcium stone formers can be considered as hypocitraturic. The lowest excretion of citrate was recorded in urine collected during the night. Citrate has significant effects on supersaturation with respect to both calcium oxalate and calcium phosphate, it also inhibits the growth of these crystals. In addition, citrate appears to be capable of inhibiting the aggregation of crystals composed of calcium oxalate, brushite, and hydroxyapatite. The heterogenous growth of calcium oxalate on calcium phosphate is also counteracted by citrate. As a consequence of the crucial role of citrate in these processes, stone prevention with alkaline citrate has become an attractive form of treatment in patients with recurrent stone formation. Single evening dose administration of sodium potassium citrate resulted in an increased excretion of citrate, reduced levels of the calcium/citrate ratio as well as supersaturation with respect to calcium oxalate and a decreased rate of stone formation. However, conflicting results of stone preventive treatment with alkaline citrate have been reported by different groups, and long-term follow-up of patients treated in a randomized way is necessary to definitely assess the efficacy of alkaline citrate

Intratumor Heterogeneity of the Estrogen Receptor and the Long-term Risk of Fatal Breast Cancer.

Background:Breast cancer patients with estrogen receptor (ER)-positive disease have a continuous long-term risk for fatal breast cancer, but the biological factors influencing this risk are unknown. We aimed to determine whether high intratumor heterogeneity of ER predicts an increased long-term risk (25 years) of fatal breast cancer. Methods:The STO-3 trial enrolled 1780 postmenopausal lymph node-negative breast cancer patients randomly assigned to receive adjuvant tamoxifen vs not. The fraction of cancer cells for each ER intensity level was scored by breast cancer pathologists, and intratumor heterogeneity of ER was calculated using Rao's quadratic entropy and categorized into high and low heterogeneity using a predefined cutoff at the second tertile (67%). Long-term breast cancer-specific survival analyses by intra-tumor heterogeneity of ER were performed using Kaplan-Meier and multivariable Cox proportional hazard modeling adjusting for patient and tumor characteristics. Results:A statistically significant difference in long-term survival by high vs low intratumor heterogeneity of ER was seen for all ER-positive patients (P < .001) and for patients with luminal A subtype tumors (P = .01). In multivariable analyses, patients with high intratumor heterogeneity of ER had a twofold increased long-term risk as compared with patients with low intratumor heterogeneity (ER-positive: hazard ratio [HR] = 1.98, 95% confidence interval [CI] = 1.31 to 3.00; luminal A subtype tumors: HR = 2.43, 95% CI = 1.18 to 4.99). Conclusions:Patients with high intratumor heterogeneity of ER had an increased long-term risk of fatal breast cancer. Interestingly, a similar long-term risk increase was seen in patients with luminal A subtype tumors. Our findings suggest that intratumor heterogeneity of ER is an independent long-term prognosticator with potential to change clinical management, especially for patients with luminal A tumors

High-density lipoprotein proteome dynamics in human endotoxemia

BACKGROUND: A large variety of proteins involved in inflammation, coagulation, lipid-oxidation and lipid metabolism have been associated with high-density lipoprotein (HDL) and it is anticipated that changes in the HDL proteome have implications for the multiple functions of HDL. Here, SELDI-TOF mass spectrometry (MS) was used to study the dynamic changes of HDL protein composition in a human experimental low-dose endotoxemia model. Ten healthy men with low HDL cholesterol (0.7+/-0.1 mmol/L) and 10 men with high HDL cholesterol levels (1.9+/-0.4 mmol/L) were challenged with endotoxin (LPS) intravenously (1 ng/kg bodyweight). We previously showed that subjects with low HDL cholesterol are more susceptible to an inflammatory challenge. The current study tested the hypothesis that this discrepancy may be related to differences in the HDL proteome. RESULTS: Plasma drawn at 7 time-points over a 24 hour time period after LPS challenge was used for direct capture of HDL using antibodies against apolipoprotein A-I followed by subsequent SELDI-TOF MS profiling. Upon LPS administration, profound changes in 21 markers (adjusted p-value < 0.05) were observed in the proteome in both study groups. These changes were observed 1 hour after LPS infusion and sustained up to 24 hours, but unexpectedly were not different between the 2 study groups. Hierarchical clustering of the protein spectra at all time points of all individuals revealed 3 distinct clusters, which were largely independent of baseline HDL cholesterol levels but correlated with paraoxonase 1 activity. The acute phase protein serum amyloid A-1/2 (SAA-1/2) was clearly upregulated after LPS infusion in both groups and comprised both native and N-terminal truncated variants that were identified by two-dimensional gel electrophoresis and mass spectrometry. Individuals of one of the clusters were distinguished by a lower SAA-1/2 response after LPS challenge and a delayed time-response of the truncated variants. CONCLUSIONS: This study shows that the semi-quantitative differences in the HDL proteome as assessed by SELDI-TOF MS cannot explain why subjects with low HDL cholesterol are more susceptible to a challenge with LPS than those with high HDL cholesterol. Instead the results indicate that hierarchical clustering could be useful to predict HDL functionality in acute phase responses towards LPS

Surveillance for endometrial cancer with transvaginal ultrasonography of breast cancer patients under tamoxifen treatment

The association of endometrial thickness with the risk of developing endometrial cancer (EC) within 2 years was investigated in a consecutive cohort of 1205 breast cancer patients under tamoxifen treatment, undergoing transvaginal ultrasonography (TVUS) for follow-up purpose (asymptomatic, 1068) or for abnormal uterine bleeding (AUB, 137). Linkage with tumour registry allowed for the follow-up of 3184.3 person-years. According to underlying incidence, 1.85 EC cases were expected in the study cohort while 12 were observed (observed/expected ratio=6.49, 95% CI 3.35–11.33; asymptomatic=4.09, 95% CI 1.65–8.43, symptomatic=35.71, 95% CI 11.59–83.34). No EC was observed with thickness (half layer) <3 mm. Raising this threshold increased specificity with a substantial loss of sensitivity (⩾3, ⩾4, ⩾6, ⩾9 mm; spec.=25.8, 44.5, 76.1, 91.5%, sens.=100, 91.6, 75.0, 66.6%). The presence of AUB was rather specific (88.94%) but poorly sensitive (41.67%). A combination of AUB presence/absence and thickness allowed the best accuracy (AUB + thickness ⩾3, ⩾4 or ⩾5; sens.=100, 81.6 or 91.6%; spec.=22.8, 40.4, or 56.7%). Breast cancer patients under tamoxifen might be selected for further invasive assessment on the basis of AUB and endometrial thickness assessed at TVUS

Ovarian cysts in women receiving tamoxifen for breast cancer

Tamoxifen is a nonsteroidal anti-oestrogen with gynaecological side-effects. Only recently, ovarian cyst formation during tamoxifen treatment has been reported. The present study aimed to evaluate patient-related parameters that determine ovarian cyst formation in women using tamoxifen for breast cancer. A cross-sectional study was performed in 142 breast cancer patients using tamoxifen. Forty-five patients were also examined prior to tamoxifen treatment. Gynaecological assessment, transvaginal ultrasonography (TVU) and serum oestradiol (E2) and follicle stimulating hormone (FSH) analysis were performed. Follow-up assessments were performed twice a year. Uni- or bilateral ovarian cysts were detected by TVU in 24 tamoxifen-using patients and in one patient before tamoxifen treatment. Multiple regression analysis showed that cyst development is related (multiple R = 0.73) to high E2 (P < 0.001), younger age (P < 0.001) and absence of high-dose chemotherapy (P = 0.007). Patients with ovarian cysts had higher serum E2 levels compared to patients without cysts (1.95 vs 0.05 nmol l−1; P < 0.001). All patients after high-dose chemotherapy or older than 50 years had E2 < 0.10 nmol l−1 and/or amenorrhoea > 1 year and did not develop ovarian cysts. Patients still having a menstrual cycle during tamoxifen had a high chance (81%) of developing ovarian cysts. Breast cancer patients receiving tamoxifen only develop ovarian cysts if their ovaries are able to respond to FSH stimulation as shown by E2 production. © 1999 Cancer Research Campaig

Assessment of Long-term Distant Recurrence-Free Survival Associated with Tamoxifen Therapy in Postmenopausal Patients with Luminal A or Luminal B Breast Cancer

Importance: Patients with estrogen receptor (ER)-positive breast cancer have a long-term risk for fatal disease. However, the tumor biological factors that influence the long-term risk and the benefit associated with endocrine therapy are not well understood. Objective: To compare the long-term survival from tamoxifen therapy for patients with luminal A or luminal B tumor subtype. Design, Setting, and Participants: Secondary analysis of patients from the Stockholm Tamoxifen (STO-3) trial conducted from 1976 to 1990, which randomized postmenopausal patients with lymph node-negative breast cancer to receive adjuvant tamoxifen or no endocrine therapy. Tumor tissue sections were assessed in 2014 using immunohistochemistry and Agilent microarrays. Only patients with luminal A or B subtype tumors were evaluated. Complete long-term follow-up data up to the end of the STO-3 trial on December 31, 2012, were obtained from the Swedish National registers. Data analysis for the secondary analysis was conducted in 2017 and 2018. Interventions: Patients were randomized to receive at least 2 years of tamoxifen therapy or no endocrine therapy; patients without recurrence who reconsented were further randomized to 3 additional years of tamoxifen therapy or no endocrine therapy. Main Outcomes and Measures: Distant recurrence-free interval (DRFI) by luminal A and luminal B subtype and trial arm was assessed by Kaplan-Meier analyses and time-dependent flexible parametric models to estimate time-varying hazard ratios (HRs) that were adjusted for patient and tumor characteristics. Results: In the STO-3 treated trial arm, 183 patients had luminal A tumors and 64 patients had luminal B tumors. In the untreated arm, 153 patients had luminal A tumors and 62 had luminal B tumors. Age at diagnosis ranged from 45 to 73 years. A statistically significant difference in DRFI by trial arm was observed (log rank, P <.001 [luminal A subtype, n = 336], P =.04 [luminal B subtype, n = 126]): the 25-year DRFI for luminal A vs luminal B subtypes was 87% (95% CI, 82%-93%) vs 67% (95% CI, 56%-82%) for treated patients, and 70% (95% CI, 62%-79%) vs 54% (95% CI, 42%-70%) for untreated patients, respectively. Patients with luminal A tumors significantly benefited from tamoxifen therapy for 15 years after diagnosis (HR, 0.57; 95% CI, 0.35-0.94), and those with luminal B tumors benefited from tamoxifen therapy for 5 years (HR, 0.38; 95% CI, 0.24-0.59). Conclusions and Relevance: Patients with luminal A subtype tumors had a long-term risk of distant metastatic disease, which was reduced by tamoxifen treatment, whereas patients with luminal B tumors had an early risk of distant metastatic disease, and tamoxifen benefit attenuated over time