A learning theory of attachment: Unraveling the black box of attachment development

Attachment is an inborn behavioral system that is biologically driven and essential for survival. During child development, individual differences in (in)secure attachment emerge. The development of different attachment behaviors has been traditionally explained as a process during which experiences with (lack of) responsive and supportive care are internalized into working models of attachment. However, this idea has been criticized for being vague and even untestable. With the aim of unraveling this black box, we propose to integrate evidence from conditioning research with attachment theory to formulate a Learning Theory of Attachment. In this review, we explain how the development of individual differences in attachment security at least partly follows the principles of classical and operant conditioning. We combine observed associations between attachment and neurocognitive and endocrinological (cortisol, oxytocin, and dopamine) processes with insights in conditioning dynamics to explain the development of attachment. This may contribute to the explanation of empirical observations in attachment research that are insufficiently accounted for by traditional attachment theory

Another step closer to measuring the ghosts in the nursery: preliminary validation of the Trauma Reflective Functioning Scale

The aim of this study was to examine preliminary evidence of the validity of the Trauma Reflective Functioning Scale and to investigate reflective functioning (RF) and attachment in pregnant women with histories of trauma, with a particular focus on the capacity to mentalize regarding trauma and its implications for adaptation to pregnancy and couple functioning. The Adult Attachment Interview was used to assess attachment, unresolved trauma and mentalization (measured as RF) regarding relationships with attachment figures (RF-G) and trauma (RF-T) in 100 pregnant women with histories of abuse and neglect. The majority (63%) of women had insecure attachment states of mind and approximately half were unresolved regarding trauma. Furthermore, the majority of women manifested deficits specific to RF-T. Their RF-T was significantly lower than their RF-G; the findings indicate that women with histories of childhood abuse and neglect do not manifest a generic inhibition of reflectiveness, but a collapse of mentalization specific to trauma. Low RF-T, indicative of difficulty in considering traumatic experiences in mental state terms, was associated with difficulty in investment in the pregnancy and lack of positive feelings about the baby and motherhood. In addition, low RF-T was also associated with difficulties in intimate relationships. Results of a regression analysis with RF indicated that RF-T was the best predictor of investment in pregnancy and couple functioning. In sum, the study provides preliminary evidence that RF-T can be reliably measured and is a valid construct that has potential usefulness for research and clinical practice. It highlights the importance of mentalization specifically about trauma and suggests that it is not the experience of trauma per se, but the absence of mentalization regarding trauma that is associated with difficulties in close relationships and in making the transition to parenthood

In vitro chemotherapy-associated muscle toxicity is attenuated with nutritional support, while treatment efficacy is retained.

PURPOSE: Muscle-wasting and treatment-related toxicities negatively impact prognosis of colorectal cancer (CRC) patients. Specific nutritional composition might support skeletal muscle and enhance treatment support. In this in vitro study we assess the effect of nutrients EPA, DHA, L-leucine and vitamin D3, as single nutrients or in combination on chemotherapy-treated C2C12-myotubes, and specific CRC-tumor cells. MATERIALS AND METHODS: Using C2C12-myotubes, the effects of chemotherapy (oxaliplatin, 5-fluorouracil, oxaliplatin+5-fluorouracil and irinotecan) on protein synthesis, cell-viability, caspase-3/7-activity and LDH-activity were assessed. Addition of EPA, DHA, L-leucine and vitamin D3 and their combination (SNCi) were studied in presence of above chemotherapies. Tumor cell-viability was assessed in oxaliplatin-treated C26 and MC38 CRC cells, and in murine and patient-derived CRC-organoids. RESULTS: While chemotherapy treatment of C2C12-myotubes decreased protein synthesis, cell-viability and increased caspase-3/7 and LDH-activity, SNCi showed improved protein synthesis and cell viability and lowered LDH activity. The nutrient combination SNCi showed a better overall performance compared to the single nutrients. Treatment response of tumor models was not significantly affected by addition of nutrients. CONCLUSIONS: This in vitro study shows protective effect with specific nutrition composition of C2C12-myotubes against chemotherapy toxicity, which is superior to the single nutrients, while treatment response of tumor cells remained

Specialized nutrition improves muscle function and physical activity without affecting chemotherapy efficacy in C26 tumour-bearing mice

Background: Skeletal muscle wasting and fatigue are commonly observed in cancer patients receiving chemotherapy and associated with reduced treatment outcome and quality of life. Nutritional support may mitigate these side effects, but potential interference with chemotherapy efficacy could be of concern. Here, we investigated the effects of an ω-3 polyunsaturated fatty acid (eicosapentaenoic acid and docosahexaenoic acid), leucine-enriched, high-protein (100% whey), additional vitamin D, and prebiotic fibres ‘specific nutritional composition’ (SNC) and chemotherapy on state-of-the-art tumour organoids and muscle cells and studied muscle function, physical activity, systemic inflammation, and chemotherapy efficacy in a mouse model of aggressive colorectal cancer (CRC). Methods: Tumour-bearing mice received a diet with or without SNC. Chemotherapy treatment consisted of oxaliplatin and 5-fluorouracil. Tumour formation was monitored by calliper measurements. Physical activity was continuously monitored by infrared imaging. Ex vivo muscle performance was determined by myography, muscle fatty acid composition by gas chromatography, and plasma cytokine levels by Luminex xMAP technology. Patient-derived CRC organoids and C2C12 myotubes were used to determine whether SNC affects chemotherapy sensitivity in vitro. Results: Specific nutritional composition increased muscle contraction capacity of chemotherapy-treated tumour-bearing mice (P < 0.05) and enriched ω-3 fatty acid composition in muscle without affecting treatment efficacy (P < 0.0001). Mice receiving SNC maintained physical activity after chemotherapy and showed decreased systemic inflammation. Therapeutic response of CRC organoids was unaffected by SNC nutrients, while cell viability and protein synthesis of muscle cells significantly improved. Conclusions: The results show that specialized nutritional support can be used to maintain muscle function and physical activity levels during chemotherapy without increasing tumour viability. Therefore, nutritional strategies have potential value in promoting cancer and chemotherapy tolerance

DNA methylation signatures of aggression and closely related constructs : A meta-analysis of epigenome-wide studies across the lifespan

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 x 10(-7); Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3-82%) of the aggression-methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.Peer reviewe

Spare parts inventory control under system availability constraints

Spare parts inventory is a difficult problem, including the supply chain elements of maintaining inventories of numerous spare parts. In today's global economy, spare parts are never next door, but can be across hemispheres. In addition to distance, the sheer volume of spare parts that are required to keep complex systems operational is huge - systems like the military, transportation, and industrial businesses include an immense number of separate parts many of which are worn out through use over time. Added to these complexities are the stochastic problems associated with budget constraints and the timing of maintaining inventory levels of the consumable spare parts of an operational system. SYSTEMS APPROACH TO BUDGET-CONSTRAINED SPARE PARTS MANAGEMENT develops a variety of multi-item models that optimize spare parts inventories so that target availability levels for specific systems and machine domains are met with minimal costs. The contributions of this systematic book treatment are as follows: Multi-item inventory models for the optimization of spare parts stock; Target availability levels for machines installed in the field are met against minimal costs for inventory holding of spare parts and for different forms of emergency shipments; Specific algorithms that produce optimal or close-to-optimal solutions for real-world problems; Case applications are provided for all of the primary types of models; Insights are developed for strategic decisions shipping decisions and these decisions are explored for possible critical-level policies (rationing policies) in situations with multiple classes of customers