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We examined the long‐term direct and indirect links between coparenting (conflict, communication, and shared decision‐making) and preschoolers' school readiness (math, literacy, and social skills). The study sample consisted of 5,650 children and their biological mothers and fathers who participated in the Early Childhood Longitudinal Study‐Birth Cohort. Using structural equation modeling and controlling for background characteristics, we found that our conceptual model of the pathways from coparenting to child outcomes is structurally the same for cohabiting and married families. Controlling for a host of background characteristics, we found that coparenting conflict and shared decision‐making were negatively and positively, respectively, linked to children's academic and social skills and co‐parental communication was indirectly linked to academic and social skills through maternal supportiveness. Coparenting conflict was also indirectly linked to children's social skills through maternal depressive symptoms. The overall findings suggest that for both cohabiting and married families, the context of conflicted coparenting may interfere with the development of children's social competencies and academic skills, whereas collaborative coparenting promotes children's school readiness because mothers are more responsive to their children's needs. These findings have implications for programs aimed at promoting positive family processes in cohabiting and married families. 摘要我们考察了共同养育(冲突、交流和共同决策)与学龄前儿童入学准备(数学、识字和社交技能)之间的长期直接和间接联系。研究样本包括5,650名儿童及其亲生父母。这些父母参与了早期儿童纵向研究——出生队列。通过使用结构等式模拟及控制背景特征,我们发现,从共同养育到儿童发展成果路径的概念模式在结构上与同居和已婚家庭一致。我们在控制众多背景特征后发现,共同养育冲突和共同决策与孩子的学业和社交技能消极和积极关联,而共同养育交流通过母亲的支持间接地与学业和社交技能关联。共同养育冲突也通过母亲的抑郁症状间接地与孩子的社交技能关联。综合发现表明,对于同居和已婚家庭,冲突性共同养育的环境可能干扰孩子的社交能力和学业技能,而协作式共同养育则促进孩子做好入学准备,因为母亲对孩子的需求反应更为灵敏。这些发现对促进同居和已婚家庭的正面家庭运作过程有意义。 ResumenAnalizamos los vínculos directos e indirectos a largo plazo entre la cocrianza (el conflicto, la comunicación y la toma de decisiones compartida) y la madurez para la escolaridad de los niños en edad preescolar (matemática, lectoescritura y habilidades sociales). La muestra del estudio consistió en 5650 niños y sus madres y padres biológicos que participaron en el “Estudio Longitudinal de la Primera Infancia, Cohorte de Nacimiento”. Utilizando modelos de ecuaciones estructurales y controlando las características del entorno, descubrimos que nuestro modelo conceptual de las vías que abarcan desde la cocrianza hasta los resultados de los niños es estructuralmente el mismo tanto para las familias formadas por padres concubinos como para las formadas por padres casados. Mediante la evaluación de un sinfín de características del entorno, descubrimos que el conflicto en la cocrianza y la toma de decisiones compartida estuvieron ligados de manera negativa y positiva, respectivamente, a las habilidades académicas y sociales de los niños, y que la comunicación entre el padre y la madre estuvo ligada indirectamente a las habilidades académicas y sociales a través del apoyo materno. El conflicto en la cocrianza también estuvo asociado indirectamente con las habilidades sociales de los niños mediante síntomas depresivos de la madre. Los resultados generales sugieren que tanto para las familias formadas por padres concubinos como para las formadas por padres casados el contexto de cocrianza conflictiva puede obstaculizar el desarrollo de las competencias sociales y las habilidades académicas de los niños, mientras que la cocrianza colaboradora fomenta la madurez para la escolaridad porque las madres responden mejor a las necesidades de sus hijos. Estos resultados tienen consecuencias para los programas orientados a promover los procesos familiares positivos en las familias formadas por parejas en concubinato y las formadas por parejas casadas.

Reviews and updates the treatment pathway of transplant-eligible patients with newly diagnosed multiple myeloma as recommended by the New Zealand Myeloma Interest Group. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.

Unrelated donors (UDs) are the commonest source for allogeneic transplantation (alloSCT), with higher non-relapse mortality (NRM) than siblings. We analyzed data from the Australasian Bone Marrow Transplant Recipient Registry from adults receiving a first UD alloSCT during 2001–2015, to determine whether and how NRM has changed. Predictors of outcome were determined using cox regression, accounting for time-interactions and competing risks. A total of 2308 patients met inclusion criteria. Changes over time included increasing age, utilization of peripheral blood cells, reduced intensity conditioning, and T-cell depletion. Three-year OS increased significantly from 44% in 2001–2005 to 58% in 2011–2015 (p < 0.001). This was attributed to a reduction in NRM from 35% to 24% (p < 0.001) with no change in relapse. Factors associated with increased NRM included age, male sex, CMV seropositivity, HLA mismatch, transplant more than 6 months from diagnosis, and T-cell depletion when administered during 2001–2005. Survival following UD SCT has improved by almost 15% over the past decade, driven by improvements in NRM. This has occurred despite increasing recipient age and appears to be due to better donor selection, reduced delays to transplantation, and improved prevention and management of GVHD.

Many monogenic disorders cause a characteristic facial morphology. Artificial intelligence can support physicians in recognizing these patterns by associating facial phenotypes with the underlying syndrome through training on thousands of patient photographs. However, this ‘supervised’ approach means that diagnoses are only possible if the disorder was part of the training set. To improve recognition of ultra-rare disorders, we developed GestaltMatcher, an encoder for portraits that is based on a deep convolutional neural network. Photographs of 17,560 patients with 1,115 rare disorders were used to define a Clinical Face Phenotype Space, in which distances between cases define syndromic similarity. Here we show that patients can be matched to others with the same molecular diagnosis even when the disorder was not included in the training set. Together with mutation data, GestaltMatcher could not only accelerate the clinical diagnosis of patients with ultra-rare disorders and facial dysmorphism but also enable the delineation of new phenotypes. GestaltMatcher uses a deep convolutional neural network to improve recognition of rare disorders based on facial morphology. The framework detects similarities among patients with previously unseen syndromes, aiding discovery of new disease genes.

This research was supported by the NSF grants DEB-841933 and OCE-821374 to RS, OCE-0848703 to CA and by a Maine Technology Institute research infrastructure grant to the Bigelow Laboratory. The Los Alamos National Laboratory researchers were supported in part by the U.S. Department of Energy Joint Genome Institute through the Office of Science of the U.S. Department of Energy under Contract Number DE-AC02-05CH11231 and grants from the U.S. Defense Threat Reduction Agency under contract numbers B104153I and B084531I.

Primordial germ cells (PGCs) are the embryonic precursors of sperm and eggs. They transmit genetic and epigenetic information across generations. Given the prominent role of germline defects in diseases such as infertility, detailed understanding of human PGC (hPGC) development has important implications in reproductive medicine and studying human evolution. Yet, hPGC specification remains an elusive process. Here, we report the induction of hPGC-like cells (hPGCLCs) in a bioengineered human pluripotent stem cell (hPSC) culture that mimics peri-implantation human development. In this culture, amniotic ectoderm-like cells (AMLCs), derived from hPSCs, induce hPGCLC specification from hPSCs through paracrine signaling downstream of ISL1 . Our data further show functional roles of NODAL, WNT, and BMP signaling in hPGCLC induction. hPGCLCs are successfully derived from eight non-obstructive azoospermia (NOA) participant-derived hPSC lines using this biomimetic platform, demonstrating its promise for screening applications. Derivation of human primordial germ cell-like cells (hPGCLCs) is critical for reproductive medicine. Here, authors report the induction of hPGCLCs in a bioengineered human pluripotent stem cell culture that mimics peri-implantation human development.

The laboratory mouse ranks among the most important experimental systems for biomedical research and molecular reference maps of such models are essential informational tools. Here, we present a quantitative draft of the mouse proteome and phosphoproteome constructed from 41 healthy tissues and several lines of analyses exemplify which insights can be gleaned from the data. For instance, tissue- and cell-type resolved profiles provide protein evidence for the expression of 17,000 genes, thousands of isoforms and 50,000 phosphorylation sites in vivo. Proteogenomic comparison of mouse, human and Arabidopsis reveal common and distinct mechanisms of gene expression regulation and, despite many similarities, numerous differentially abundant orthologs that likely serve species-specific functions. We leverage the mouse proteome by integrating phenotypic drug ( n  > 400) and radiation response data with the proteomes of 66 pancreatic ductal adenocarcinoma (PDAC) cell lines to reveal molecular markers for sensitivity and resistance. This unique atlas complements other molecular resources for the mouse and can be explored online via ProteomicsDB and PACiFIC. This work presents a quantitative draft of the mouse proteome and phosphoproteome constructed from 41 healthy tissues covering 15 major anatomical systems and 66 cell lines.

Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD ( p  = 0.03), with a trend observed for NSDD ( p  = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.

The blood disorder, β-thalassaemia, is considered an attractive target for gene correction. Site-specific triplex formation has been shown to induce DNA repair and thereby catalyse genome editing. Here we report that triplex-forming peptide nucleic acids (PNAs) substituted at the γ position plus stimulation of the stem cell factor (SCF)/c-Kit pathway yielded high levels of gene editing in haematopoietic stem cells (HSCs) in a mouse model of human β-thalassaemia. Injection of thalassemic mice with SCF plus nanoparticles containing γPNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood haemoglobin levels into the normal range, reduced reticulocytosis, reversal of splenomegaly and up to 7% β-globin gene correction in HSCs, with extremely low off-target effects. The combination of nanoparticle delivery, next generation γPNAs and SCF treatment may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration. Gene editing approaches are widely used for correcting mutations, but their application is largely limited to cells and not living animals. Here the authors show that in vivo γPNA-mediated editing of a β-globin mutation is promoted by SCF and leads to sustained normalization of blood haemoglobin levels β-thalassemic mice.

Background Despite the progress in the Millennium Development Goals (MDGs) 4 and 5, inequity in the utilization of maternal, newborn and child health (MNCH) care services still remain high in sub-Saharan Africa (SSA). The continuum of care for MNCH that recognizes a tight inter-relationship between maternal, newborn and child health at different time periods and location is key towards reducing inequity in health. In this study, we explored the distributions in the utilization MNCH services in 12 SSA countries and further investigated the associations in the continuum of care for MNCH. Methods Using Demographic and Health Surveys data of 12 countries in SSA, structural equation modeling approach was employed to analyze the complex relationships in continuum of care for MNCH model. The Full Information Maximum Likelihood estimation procedure which account for the Missing at Random (MAR) and Missing Completely at Random (MCAR) assumptions was adopted in LISREL 8.80. The distribution of MNCH care utilization was presented before the estimated association in the continuum of care for MNCH model. Results Some countries have a consistently low (Mali, Nigeria, DR Congo and Rwanda) or high (Namibia, Senegal, Gambia and Liberia) utilization in at least two levels of MNCH care. The path relationships in the continuum of care for MNCH from ‘adequate antenatal care’ to ‘adequate delivery care’ (0.32) and to ‘adequate child’s immunization’ (0.36); from ‘adequate delivery care’ to ‘adequate postnatal care’ (0.78) and to ‘adequate child’s immunization’ (0.15) were positively associated and statistically significant at p  < 0.001. Only the path relationship from ‘adequate postnatal care’ to ‘adequate child’s immunization’ (−0.02) was negatively associated and significant at p  < 0.001. Conclusions In conclusion, utilization of each level of MNCH care is related to the next level of care, that is – antenatal care is associated with delivery care which is then associated with postnatal and subsequently with child’s immunization program. At the national level, identification of communities which are greatly contributing to overall disparity in health and a well laid out follow-up mechanism from pregnancy through to child’s immunization program could serve towards improving maternal and infant health outcomes and equity.