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The current version of the Declaration of Helsinki states that ‘the benefits, risks, burdens and effectiveness of a new intervention must be tested against those of the best current proven intervention(s) … ’. This wording implies that it is acceptable for patients to be assigned to receive an unproven new intervention and to be denied a best current proven intervention. We assert that patients being invited to participate in controlled trials cannot, ethically, be expected to forego proven beneficial forms of care. Patients being treated in controlled trials should not knowingly be disadvantaged compared with similar patients being treated in usual clinical care, where they have access to beneficial care. In this article, we have tried to separate for discussion ‘the withholding of effective care from trial participants’, ‘informed consent to treatment’, ‘blinding’ and ‘use of placebos’.

To assess the prevalence of abortion among population groups and changes in rates between 2008 and 2014.We used secondary data from the Abortion Patient Survey, the American Community Survey, and the National Survey of Family Growth to estimate abortion rates. We used information from the Abortion Patient Survey to estimate the lifetime incidence of abortion.Between 2008 and 2014, the abortion rate declined 25%, from 19.4 to 14.6 per 1000 women aged 15 to 44 years. The abortion rate for adolescents aged 15 to 19 years declined 46%, the largest of any group. Abortion rates declined for all racial and ethnic groups but were larger for non-White women than for non-Hispanic White women. Although the abortion rate decreased 26% for women with incomes less than 100% of the federal poverty level, this population had the highest abortion rate of all the groups examined: 36.6. If the 2014 age-specific abortion rates prevail, 24% of women aged 15 to 44 years in that year will have an abortion by age 45 years.The decline in abortion was not uniform across all population groups.

The regenerative capabilities of the liver represent a paradigm for understanding tissue repair in solid organs. Regeneration after partial hepatectomy in rodent models is well understood, while regeneration in the context of clinically relevant chronic injuries is less studied. Given the growing incidence of fatty liver disease, cirrhosis, and liver cancer, interest in liver regeneration is increasing. Here, we will review the principles, genetics, and cell biology underlying liver regeneration, as well as new approaches being used to study heterogeneity in liver tissue maintenance and repair.

Hematopoietic stem cell (HSC) regeneration is the remarkable process by which extremely rare, normally inactive cells of the bone marrow can replace an entire organ if called to do so by injury or harnessed by transplantation. HSC research is arguably the first quantitative single-cell science and the foundation of adult stem cell biology. Bone marrow transplant is the oldest and most refined technique of regenerative medicine. Here we review the intertwined history of the discovery of HSCs and bone marrow transplant, the molecular and cellular mechanisms of HSC self-renewal, and the use of HSCs and their derivatives for cell therapy.

Microscopy and genomic approaches provide detailed descriptions of the three-dimensional folding of chromosomes and nuclear organization. The fundamental question is how activity of molecules at the nanometer scale can lead to complex and orchestrated spatial organization at the scale of chromosomes and the whole nucleus. At least three key mechanisms can bridge across scales: (1) tethering of specific loci to nuclear landmarks leads to massive reorganization of the nucleus; (2) spatial compartmentalization of chromatin, which is driven by molecular affinities, results in spatial isolation of active and inactive chromatin; and (3) loop extrusion activity of SMC (structural maintenance of chromosome) complexes can explain many features of interphase chromatin folding and underlies key phenomena during mitosis. Interestingly, many features of chromosome organization ultimately result from collective action and the interplay between these mechanisms, and are further modulated by transcription and topological constraints. Finally, we highlight some outstanding questions that are critical for our understanding of nuclear organization and function. We believe many of these questions can be answered in the coming years.

Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.

The apparent virilization of the female spotted hyena raises questions about sex differences in behavior and morphology. We review these sex differences to find a mosaic of dimorphic traits, some of which conform to mammalian norms. These include space-use, dispersal behavior, sexual behavior, and parental behavior. By contrast, sex differences are reversed from mammalian norms in the hyena's aggressive behavior, social dominance, and territory defense. Androgen exposure early in development appears to enhance aggressiveness in female hyenas. Weapons, hunting behavior, and neonatal body mass do not differ between males and females, but females are slightly larger than males as adults. Sex differences in the hyena's nervous system are relatively subtle. Overall, it appears that the "masculinized" behavioral traits in female spotted hyenas are those, such as aggression, that are essential to ensuring consistent access to food; food critically limits female reproductive success in this species because female spotted hyenas have the highest energetic investment per litter of any mammalian carnivore. Evidently, natural selection has acted to modify traits related to food access, but has left intact those traits that are unrelated to acquiring food, such that they conform to patterns of sexual dimorphism in other mammals.

The regenerative capacity of the vertebrate retina varies substantially across species. Whereas fish and amphibians can regenerate functional retina, mammals do not. In this perspective piece, we outline the various strategies nonmammalian vertebrates use to achieve functional regeneration of vision. We review key differences underlying the regenerative potential across species including the cellular source of postnatal progenitors, the diversity of cell fates regenerated, and the level of functional vision that can be achieved. Finally, we provide an outlook on the field of engineering the mammalian retina to replace neurons lost to injury or disease.

Dramatic nuclear reorganization occurs during early development to convert terminally differentiated gametes to a totipotent zygote, which then gives rise to an embryo. Aberrant epigenome resetting severely impairs embryo development and even leads to lethality. How the epigenomes are inherited, reprogrammed, and reestablished in this critical developmental period has gradually been unveiled through the rapid development of technologies including ultrasensitive chromatin analysis methods. In this review, we summarize the latest findings on epigenetic reprogramming in gametogenesis and embryogenesis, and how it contributes to gamete maturation and parental-to-zygotic transition. Finally, we highlight the key questions that remain to be answered to fully understand chromatin regulation and nuclear reprogramming in early development.

Objective: To evaluate the effects of uncoupling protein (UCP) 1, UCP2 and UCP3 gene variants on body composition and metabolic changes in response to chronic overfeeding and the recovery after the period of overfeeding. Subjects and design: Twenty-four normal weight men (21±2 y), who constituted 12 pairs of identical twins, ate a 4.2 MJ/day energy surplus, 6 days a week, during a period of 100 days. The subjects were asked to return to the laboratory for testing at 4 months and for a final examination 5 y after completion of the overfeeding protocol. Methods: Resting metabolic rate (RMR) measurements were performed before and after overfeeding. A 4.2 MJ test meal was consumed, after which calorimetric measurements were continued for 240 min. Total body fat was assessed by hydrodensitometry and total subcutaneous fat by the sum of eight skinfolds. Polymorphisms were typed by PCR and PCR-RFLP-techniques. Thyroid stimulating hormone (TSH) concentrations after a thyrotropin releasing hormone (TRH) injection were measured by radioimmunoassay (RIA). Results: The changes in body weight and adiposity were not different between UCP1 Bcl I, UCP2 alanine to valine (A55V), UCP2 insertion/deletion (I/D) or UCP3 Rsa I genotypes. However, the recovery from overfeeding was worse among G-allele carriers of the UCP1 Bcl I, I allele non-carriers of the UCP2 I/D, AV heterozygote subjects of the UCP2 A55V and CC subjects of the UCP3 Rsa I polymorphisms. RMR was lower both before (P=0.01) and after (P=0.001) overfeeding in subjects with the CC genotype of the UCP3 Rsa I polymorphism. Moreover, after overfeeding, the UCP2 A55V heterozygote and UCP3 Rsa I CC homozygote subjects had significantly higher respiratory quotient (RQ) values at rest (P

Objective: To study the relationship between consumption of milk and milk products, calcium, lactose and vitamin D and occurrence of colorectal cancers. Design: Prospective cohort study. Subjects: A total of 9959 men and women aged 15 y or older without history of cancer at baseline. During a 24 y follow-up, 72 new cancers of the large bowel (38 in the colon and 34 in the rectum) were detected. Results: Consumption of milk and total milk products was suggested to be inversely related to colon cancer incidence, whereas no similar association was seen for rectal cancer. The relative risk between the highest and lowest quartiles of intake adjusted for potential confounding factors was 0.46 (95% confidence interval 0.14–1.46, P for trend 0.09) for milk and 0.37 (95% CI=0.12–1.39, P for trend 0.06) for total milk products. Lactose intake showed a similar inverse relationship with colon cancer: the relative risk was 0.31 (95% CI=0.08–1.15, P for trend 0.03). Intake of vitamin D or total dietary calcium was not significantly related to colorectal cancer risk, whereas calcium provided by fermented milk products was associated with increased colorectal cancer incidence; in the highest quartile the multivariate adjusted relative risk for colorectal cancer was 2.07 (95% CI=1.00–4.28). Conclusions: Our results indicate that individuals showing high consumption of milk have a potentially reduced risk of colon cancer; however, the association does not appear to be due to intake of calcium, vitamin D, or to specific effects of fermented milk. Sponsorship: This study was supported by a grant from the Swedish Cancer Foundation. European Journal of Clinical Nutrition (2001) 55, 1000–1007

Objective: To demonstrate sexual dimorphism in serum leptin levels not only during puberty, but also in childhood in Japan. Design: Cross-sectional study. Setting: Hamamatsu-Hokuen study in Japan. Subjects: Body weight and height were measured in normal-weight Japanese children and adolescents (143 boys, 178 girls), and 161 boys and 129 girls whose percentage of overweight for the standard (%Wt) was more than+25%. Serum leptin levels were compared with %Wt. Subjects were divided into group 1 (6–10 y of age) and group 2 (11–15 y of age) according to their age. Results: In overweight subjects, leptin was more highly correlated with %Wt in boys of group 2 (r=0.67, P

Aims: To determine the efficacy of XPro1595 to improve pathophysiological and functional outcomes in a mouse model of traumatic brain injury (TBI). Background: Symptoms associated with TBI can be debilitating, and treatment without off-target side effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI. Objectives: Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation and dendritic plasticity and associated functional impairments. Methods: Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically relevant window (60 minutes post-injury). The animals were assessed for differences in neurological function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as neuronal degeneration and plasticity. Results: We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology’s within the hippocampus consistent with the observed neurological outcomes, including glial reactivity, enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity (spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were prevented in mice treated with XPro1595. Conclusion: Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use in patients with TBI.

OBJECTIVES: Following the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and the subsequent global spread of the 2019 novel coronavirus disease (COVID-19), health systems and the populations who use them have faced unprecedented challenges. We aimed to measure the impact of COVID-19 on the uptake of hospital-based care at a national level. DESIGN: The study period (weeks ending 5 January to 28 June 2020) encompassed the pandemic announcement by the World Health Organization and the initiation of the UK lockdown. We undertook an interrupted time-series analysis to evaluate the impact of these events on hospital services at a national level and across demographics, clinical specialties and National Health Service Health Boards. SETTING: Scotland, UK. PARTICIPANTS: Patients receiving hospital care from National Health Service Scotland. MAIN OUTCOME MEASURES: Accident and emergency (A&E) attendances, and emergency and planned hospital admissions measured using the relative change of weekly counts in 2020 to the averaged counts for equivalent weeks in 2018 and 2019. RESULTS: Before the pandemic announcement, the uptake of hospital care was largely consistent with historical levels. This was followed by sharp drops in all outcomes until UK lockdown, where activity began to steadily increase. This time-period saw an average reduction of −40.7% (95% confidence interval [CI]: −47.7 to −33.7) in A&E attendances, −25.8% (95% CI: −31.1 to −20.4) in emergency hospital admissions and −60.9% (95% CI: −66.1 to −55.7) in planned hospital admissions, in comparison to the 2018–2019 averages. All subgroup trends were broadly consistent within outcomes, but with notable variations across age groups, specialties and geography. CONCLUSIONS: COVID-19 has had a profoundly disruptive impact on hospital-based care across National Health Service Scotland. This has likely led to an adverse effect on non-COVID-19-related illnesses, increasing the possibility of potentially avoidable morbidity and mortality. Further research is required to elucidate these impacts.

Limb loss due to traumatic injury or amputation is a major biomedical burden. Many vertebrates exhibit the ability to form and pattern normal limbs during embryogenesis from amorphous clusters of precursor cells, hinting that this process could perhaps be activated later in life to rebuild missing or damaged limbs. Indeed, some animals, such as salamanders, are proficient regenerators of limbs throughout their life span. Thus, research over the last century has sought to stimulate regeneration in species that do not normally regenerate their appendages. Importantly, these efforts are not only a vital aspect of regenerative medicine, but also have fundamental implications for understanding evolution and the cellular control of growth and form throughout the body. Here we review major recent advances in augmenting limb regeneration, summarizing the degree of success that has been achieved to date in frog and mammalian models using genetic, biochemical, and bioelectrical interventions. While the degree of whole limb repair in rodent models has been modest to date, a number of new technologies and approaches comprise an exciting near-term road map for basic and clinical progress in regeneration.

Females have long been underrepresented in preclinical research and clinical drug trials. Directives by the U.S. National Institutes of Health have increased female participation in research protocols, although analysis of outcomes by sex remains infrequent. The long-held view that traits of female rats and mice are more variable than those of males is discredited, supporting equal representation of both sexes in most studies. Drug pharmacokinetic analysis reveals that, among subjects administered a standard drug dose, women are exposed to higher blood drug concentrations and longer drug elimination times. This contributes to increased adverse drug reactions in women and suggests that women are routinely overmedicated and should be administered lower drug doses than men. The past decade has seen progress in female inclusion, but key subsequent steps such as sex-based analysis and sex-specific drug dosing remain to be implemented.

Depression and related mood disorders constitute an enormous burden on health, quality of life, and the global economy, and women have roughly twice the lifetime risk of men for experiencing depression. Here, we review sex differences in human brain physiology that may be connected to the increased susceptibility of women to major depressive disorder (MDD). Moreover, we summarize decades of preclinical research using animal models for the study of mood dysfunction that uncover some of the potential molecular, cellular, and circuit-level mechanisms that may underlie sex differences and disease etiology. We place particular emphasis on a series of recent studies demonstrating the central contribution of the circuit projecting from ventral hippocampus to nucleus accumbens and how inherent sex differences in the excitability of this circuit may predict and drive depression-related behaviors. The findings covered in this review underscore the continued need for studies using preclinical models and circuit-specific strategies for uncovering molecular and physiological mechanisms that could lead to potential sex-specific diagnosis, prognosis, prevention, and/or treatments for MDD and other mood disorders.

This overview of the molecular pathology of lung cancer includes a review of the most salient molecular alterations of the genome, transcriptome, and the epigenome. The insights provided by the growing use of next-generation sequencing (NGS) in lung cancer will be discussed, and interrelated concepts such as intertumor heterogeneity, intratumor heterogeneity, tumor mutational burden, and the advent of liquid biopsy will be explored. Moreover, this work describes how the evolving field of molecular pathology refines the understanding of different histologic phenotypes of non-small-cell lung cancer (NSCLC) and the underlying biology of small-cell lung cancer. This review will provide an appreciation for how ongoing scientific findings and technologic advances in molecular pathology are crucial for development of biomarkers, therapeutic agents, clinical trials, and ultimately improved patient care.

Fresh fish, and especially fatty species, are highly perishable due to oxidative deterioration of fish flesh and the elevated microbial load on fish surface. The implementation of a variety of “mild hurdles” may significantly decrease the rates of fish chemical degradation and microbiological spoilage, by better retaining the initial quality, compared to more intense preservation techniques. The aim of this work is the comparative study of different, single or combined, treatments at 15 °C on the quality and shelf life of chilled eel fillets. Fish fillets were treated using osmotic solutions consisting of glycerol (30%–40%–45%) and 5% NaCl with and without former antioxidant impregnation by using Rosemary Serum. In all cases, water activity decreased to approximately 0.90 after 420 min of osmotic treatment. Untreated and osmotically treated fish fillets were subsequently stored at 4 °C and their stability under chill conditions was assessed based on microbial growth and oxidative deterioration. Microbial growth of treated samples was significantly delayed, especially due to the osmotic step (OS) and the derived water activity decrease. Lipid oxidation, a major cause of rejection for fatty fish such as eel, was greatly inhibited in treated fillets, owing to both ‘hurdles’, aw lowering (OS) and antioxidant impregnation with rosemary serum (RS/OS), showing the synergistic effect of these successive procedures. Shelf life of treated eel fillets exhibited a more than 10-fold increase, as compared to the untreated samples, based on chemical composition and a 2 to 3-fold shelf life improvement, in terms of microbial growth.

Occurrence of biogenic amines in fresh fish and fishery products constitute a significant safety concern. Ingestion of histamine is identified as the causative agent of several food poisoning incidences on an annual basis. In addition, cadaverine, putrescine and tyramine have been recognized as potentiators of histamine poisoning. Accumulation of biogenic amines in fresh fish and fishery products has been mainly attributed to growth of bacteria possessing amino acid decarboxylase activity, which is facilitated by lack of hygienic conditions and strict temperature control during their storage. To this end, the effectiveness of traditional and modern approaches to control biogenic amine accumulation has been in the epicenter of intensive study. The aim of the present review article is to update and integrate current knowledge regarding the biogenic amine content of fresh fish and fishery products as well as the capacity of traditional and emerging control strategies.

The average values of the seasonal flesh biochemical composition (%) of the pearl oyster Pinctada imbricata radiata originated form 2 sampling sites, the gulfs of Evoikos (E) and Saronikos (S) in the Western Aegean Sea, showed that is rich in proteins (64.00 ± 1.86 -(E), 64.67 ± 2.95-(S)) with low fat content (10.96 ± 1.04-(E), 11.86 ± 1.13-(S)) and carbohydrates (13.29 ± 2.48- (E), 9.94 ± 4.32 (S)). The condition index ranged from 26.16% ± 5.04 in the autumn in (E), to 44.73% ± 7.50 in the summer in (S). The meat yield varied from 20.49% ± 3.20% in the summer in (E) to 30.73% ± 3.47% in the summer in (S). Both results demonstrate the high nutritional profile of the pearl oyster, supporting its suitability as a potential new Mediterranean seafood source for human consumption.

Objective: Relational and emotional vulnerability represent essential problems among patients with personality disorder (PD). Group psychotherapy is a central component of evidence-based PD treatments. Generally, patient and therapist interrelationships predict improvement in therapy. However, although treatment of patients with PD is a more complex process, group processes are poorly elaborated in PD research. Documentation of the psychometric quality of group process measures in PD samples is an important precursor of such research. The Group Questionnaire—GQ is based on concepts of group cohesion and climate, empathy, and alliance and aims to capture the quality of member–member, member–group, and member–leader relationships in group therapy. A three latent factor structure (positive bond, positive work, and negative relationship) has generally been supported. This study aimed to perform a psychometric analysis of GQ administered in a clinical population of patients with PD. Method: The study included 369 patients with PDs attending group psychotherapy in 14 outpatient treatment units on a specialist mental health service level within the Norwegian Network of Personality Disorders in the period 2017–2020. Psychometric analyses included three latent factors and eight subfacets. Results: The three latent factors, positive bond, positive work, and negative relationship, were replicated. Psychometric integrity of the tripartite relationship structure—member–member, member–group, and member–leader, with eight subfacets, was supported. Conclusion: The GQ with three latent factors and eight subfacets can be recommended for future research and clinical practice in patient populations with PD.

Purpose To describe the use of glycerine in improving media clarity in cases with edematous cornea. Methods Retrospective case-series including patients with posterior segment pathologies needing surgical invention and having corneal edema. Each case was studied for the role of topical application of glycerine instead of viscoelastic agents and the course of surgery. The cases were followed up for minimum 3-months duration. Results Six cases with corneal edema having posterior segment pathology underwent surgery with intraoperative topical application of glycerine. The corneal edema was seen to clear with progression of surgery and was maintained until the end of surgery. Procedures like vitreoretinal surgery, identification of break, internal limiting membrane peeling, intraocular lens explantation, scleral indentation, DSEK graft removal, and subretinal band removal could be performed in these cases. Conclusion Intraoperative glycerine use during vitreoretinal surgeries is helpful in improving the corneal clarity and maintaining it till the end of surgery.

Objective The objective was to develop a novel scoring system that would be predictive of postoperative pulmonary complications in critically ill patients after cardiac and major vascular surgery. Methods A total of 17,433 postoperative patients after coronary artery bypass graft, valve, or thoracic aorta repair surgery admitted to the cardiovascular intensive care units at Cleveland Clinic Main Campus from 2009 to 2015. The primary outcome was the composite of postoperative pulmonary complications, including pneumonia, prolonged postoperative mechanical ventilation (>48 hours), or reintubation occurring during the hospital stay. Elastic net logistic regression was used on the training subset to build a prediction model that included perioperative predictors. Five-fold cross-validation was used to select an appropriate subset of the predictors. The predictive efficacy was assessed with calibration and discrimination statistics. Post hoc, of 13,353 adult patients, we tested the clinical usefulness of our risk prediction model on 12,956 patients who underwent surgery from 2015 to 2019. Results Postoperative pulmonary complications were observed in 1669 patients (9.6%). A prediction model that included baseline and demographic risk factors along with perioperative predictors had a C-statistic of 0.87 (95% confidence interval, 0.86-0.88), with a corrected Brier score of 0.06. Our prediction model maintains satisfactory discrimination (C-statistics of 0.87) and calibration (Brier score of 0.07) abilities when evaluated on an independent dataset of 12,843 recent adult patients who underwent cardiovascular surgery. Conclusions A novel prediction nomogram accurately predicted postoperative pulmonary complications after major cardiac and vascular surgery. Intensivists may use these predictors to allow for proactive and preventative interventions in this patient population.

The body responds to changing circumstances and environmental threats both consciously and subconsciously. The cognitive response to a physical threat normally involves movement mediated by skeletal muscle. There are a number of control mechanisms ‘hardwired’ into the nervous system which enable muscle systems to respond in an integrated fashion without involving a conscious decision, although the subject is usually conscious of what has happened. These include the stretch reflex, the withdrawal reflex and the crossed extensor reflexes. Muscle spindles, Golgi tendon organs and cutaneous nociceptors provide the sensory input to these reflexes, and muscle spindles also play a role in the control of voluntary movement. The autonomic nervous system controls the internal environment in response to environmental change. It consists of the parasympathetic division, which controls basal and vegetative mechanisms, and the sympathetic nervous system, which controls visceral adaptive responses to any sort of environmental change or threat.

Alzheimer’s disease (AD) is a neurodegenerative disorder known to affect functional connectivity (FC) across many brain regions. Linear FC measures have been applied to study the differences in AD by splitting neurophysiological signals, such as electroencephalography (EEG) recordings, into discrete frequency bands and analysing them in isolation from each other. We address this limitation by quantifying cross-frequency FC in addition to the traditional within-band approach. Cross-bispectrum, a higher-order spectral analysis approach, is used to measure the nonlinear FC and is compared with the cross-spectrum, which only measures the linear FC within bands. This work reports the reconstruction of a cross-frequency FC network where each frequency band is treated as a layer in a multilayer network with both inter- and intra-layer edges. Cross-bispectrum detects cross-frequency differences, mainly increased FC in AD cases inδ-θcoupling. Overall, increased strength of low-frequency coupling and decreased level of high-frequency coupling is observed in AD cases in comparison to healthy controls (HC). We demonstrate that a graph-theoretic analysis of cross-frequency brain networks is crucial to obtain a more detailed insight into their structure and function. Vulnerability analysis reveals that the integration and segregation properties of networks are enabled by different frequency couplings in AD networks compared to HCs. Finally, we use the reconstructed networks for classification. The extra cross-frequency coupling information can improve the classification performance significantly, suggesting an important role of cross-frequency FC. The results highlight the importance of studying nonlinearity and including cross-frequency FC in characterising AD.

This study examined the prospective associations among the trajectories of maternal depressive symptoms, maternal sensitivity, and child executive function (EF) across early and middle childhood, and tested the mediating role of maternal sensitivity in the links between change in maternal depressive symptoms and the growth of child EF. Participants included 1,364 children and mothers from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development (NICHD SECCYD). We found that maternal depressive symptoms (from 6 months to Grade 5) and sensitivity (from 36 months to Grade 5) decreased, whereas child EF (planning skills; from Grade 1 to 5) increased over time. We also found several direct associations: (a) lower maternal depressive symptoms at 36 months predicted higher sensitivity at 54 months; (b) higher sensitivity at 54 months and a faster decrease in sensitivity from 36 months to Grade 5 predicted higher child EF in Grade 1; and (c) higher sensitivity at 54 months predicted greater growth of EF from Grade 1 to 5. In addition, two mediation effects were found as follows: Lower levels of maternal depressive symptoms at 36 months predicted both higher levels of child EF in Grade 1 and greater growth of EF from Grade 1 to 5 through higher levels of maternal sensitivity at 54 months. The results suggest that early maternal depressive symptoms may have long-term effects on the growth of EF, especially planning skills, during middle childhood, and that one important pathway that maternal depressive symptoms affect child EF outcomes through maternal sensitivity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).