Hemophagocytic lymphohistiocytosis (HLH) covers a wide array of related life-threatening conditions featuring ineffective immunity characterized by an uncontrolled hyperinflammatory response. HLH is ...often triggered by infection. Familial forms result from genetic defects in natural killer cells and cytotoxic T-cells, typically affecting perforin and intracellular vesicles. HLH is likely under-recognized, which contributes to its high morbidity and mortality. Early recognition is crucial for any reasonable attempt at curative therapy to be made. Current treatment regimens include immunosuppression, immune modulation, chemotherapy, and biological response modification, followed by hematopoietic stem-cell transplant (bone marrow transplant). A number of recent studies have contributed to the understanding of HLH pathophysiology, leading to alternate treatment options; however, much work remains to raise awareness and improve the high morbidity and mortality of these complex conditions.
Polymer identification of plastic marine debris can help identify its sources, degradation, and fate. We optimized and validated a fast, simple, and accessible technique, attenuated total reflectance ...Fourier transform infrared spectroscopy (ATR FT-IR), to identify polymers contained in plastic ingested by sea turtles. Spectra of consumer good items with known resin identification codes #1–6 and several #7 plastics were compared to standard and raw manufactured polymers. High temperature size exclusion chromatography measurements confirmed ATR FT-IR could differentiate these polymers. High-density (HDPE) and low-density polyethylene (LDPE) discrimination is challenging but a clear step-by-step guide is provided that identified 78% of ingested PE samples. The optimal cleaning methods consisted of wiping ingested pieces with water or cutting. Of 828 ingested plastics pieces from 50 Pacific sea turtles, 96% were identified by ATR FT-IR as HDPE, LDPE, unknown PE, polypropylene (PP), PE and PP mixtures, polystyrene, polyvinyl chloride, and nylon.
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•We validate ATR FT-IR to identify polymers of weathered and ingested plastics.•We outline criteria to differentiate HDPE from LDPE samples.•Cutting or cleaning ingested plastics with water improves identification.•A database of standards is not required for polymer identification.•Collaborations of life and materials sciences address plastic debris issues.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Resident macrophages regulate homeostatic and disease processes in multiple tissues, including the kidney. Despite having well defined markers to identify these cells in mice, technical limitations ...have prevented identification of a similar cell type across species. The inability to identify resident macrophage populations across species hinders the translation of data obtained from animal model to human patients.
As an entry point to determine novel markers that could identify resident macrophages across species, we performed single-cell RNA sequencing (scRNAseq) analysis of all T and B cell-negative CD45
innate immune cells in mouse, rat, pig, and human kidney tissue.
We identified genes with enriched expression in mouse renal resident macrophages that were also present in candidate resident macrophage populations across species. Using the scRNAseq data, we defined a novel set of possible cell surface markers (Cd74 and Cd81) for these candidate kidney resident macrophages. We confirmed, using parabiosis and flow cytometry, that these proteins are indeed enriched in mouse resident macrophages. Flow cytometry data also indicated the existence of a defined population of innate immune cells in rat and human kidney tissue that coexpress CD74 and CD81, suggesting the presence of renal resident macrophages in multiple species.
Based on transcriptional signatures, our data indicate that there is a conserved population of innate immune cells across multiple species that have been defined as resident macrophages in the mouse. Further, we identified potential cell surface markers to allow for future identification and characterization of this candidate resident macrophage population in mouse, rat, and pig translational studies.
Advancing the long-term prospective study of explanations for the effects of marital conflict on children's functioning, relations were examined between interparental conflict in kindergarten, ...children's emotional insecurity in the early school years, and subsequent adolescent internalizing and externalizing problems. Based on a community sample of 235 mothers, fathers, and children (Ms = 6.00, 8.02, 12.62 years), and multimethod and multireporter assessments, structural equation model tests provided support for emotional insecurity in early childhood as an intervening process related to adolescent internalizing and externalizing problems, even with stringent autoregressive controls over prior levels of functioning for both mediating and outcome variables. Discussion considers implications for understanding pathways between interparental conflict, emotional insecurity, and adjustment in childhood and adolescence.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
This study addresses the links between destructive and constructive marital conflict and mothers' and fathers' parenting to understand associations with children's social and school adjustment. ...Multi‐method, longitudinal assessments of 235 mothers, fathers, and children (129 girls) were collected across kindergarten, first, and second grades (ages 5–7 at time 1; ages 7–9 at time 3). Whereas constructive marital conflict was related to both mothers' and fathers' warm parenting, destructive marital conflict was only linked to fathers' use of inconsistent discipline. In turn, both mothers' and fathers' use of psychological control was related to children's school adjustment, and mothers' warmth was related to children's social adjustment. Reciprocal links between constructs were also explored, supporting associations between destructive marital conflict and mothers' and fathers' inconsistent discipline. The merit of examining marital conflict and parenting as multidimensional constructs is discussed in relation to understanding the processes and pathways within families that affect children's functioning.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Based on previous findings, we hypothesised that radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer, and that the benefit would be greatest in patients ...with a low metastatic burden. We aimed to compare standard of care for metastatic prostate cancer, with and without radiotherapy.
We did a randomised controlled phase 3 trial at 117 hospitals in Switzerland and the UK. Eligible patients had newly diagnosed metastatic prostate cancer. We randomly allocated patients open-label in a 1:1 ratio to standard of care (control group) or standard of care and radiotherapy (radiotherapy group). Randomisation was stratified by hospital, age at randomisation, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December, 2015), and regular aspirin or non-steroidal anti-inflammatory drug use. Standard of care was lifelong androgen deprivation therapy, with up-front docetaxel permitted from December, 2015. Men allocated radiotherapy received either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule that was nominated before randomisation. The primary outcome was overall survival, measured as the number of deaths; this analysis had 90% power with a one-sided α of 2·5% for a hazard ratio (HR) of 0·75. Secondary outcomes were failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival. Analyses used Cox proportional hazards and flexible parametric models, adjusted for stratification factors. The primary outcome analysis was by intention to treat. Two prespecified subgroup analyses tested the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule. This trial is registered with ClinicalTrials.gov, number NCT00268476.
Between Jan 22, 2013, and Sept 2, 2016, 2061 men underwent randomisation, 1029 were allocated the control and 1032 radiotherapy. Allocated groups were balanced, with a median age of 68 years (IQR 63–73) and median amount of prostate-specific antigen of 97 ng/mL (33–315). 367 (18%) patients received early docetaxel. 1082 (52%) participants nominated the daily radiotherapy schedule before randomisation and 979 (48%) the weekly schedule. 819 (40%) men had a low metastatic burden, 1120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved failure-free survival (HR 0·76, 95% CI 0·68–0·84; p<0·0001) but not overall survival (0·92, 0·80–1·06; p=0·266). Radiotherapy was well tolerated, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy. The proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) was similar by treatment group in the safety population (398 38% with control and 380 39% with radiotherapy).
Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer.
Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Astellas, Clovis Oncology, Janssen, Novartis, Pfizer, and Sanofi-Aventis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Examining children's physiological functioning is an important direction for understanding the links between interparental conflict and child adjustment. Utilizing growth mixture modeling, the ...present study examined children's cortisol reactivity patterns in response to a marital dispute. Analyses revealed three different patterns of cortisol responses, consistent with both a sensitization and an attenuation hypothesis. Child-rearing disagreements and perceived threat were associated with children exhibiting a rising cortisol pattern, whereas destructive conflict was related to children displaying a flat pattern. Physiologically rising patterns were also linked with emotional insecurity and internalizing and externalizing behaviors. Results supported a sensitization pattern of responses as maladaptive for children in response to marital conflict, with evidence also linking an attenuation pattern with increased family risk. The findings of the present study support children's adrenocortical functioning as one mechanism through which interparental conflict is related to children's coping responses and psychological adjustment.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Education may encourage personal and collective responses to climate change, but climate education has proven surprisingly difficult and complex. Self-perception of knowledge and intelligence ...represent one factor that may impact willingness to learn about climate change. We explored this possibility with a case study in Raleigh, North Carolina in 2015 (n = 200). Our goal was to test how gender and ethnicity influenced perceptions people had of their own climate change knowledge. Survey respondents were asked how strongly they agreed with the statement "I feel knowledgeable about climate change" (1 = strongly disagree, and 5 = strongly agree). Our survey instrument also included demographic questions about race, age, income, gender, and education, as well as respondent's experience with natural disasters and drought. We observed an interaction between education and gender where women's self-perceived knowledge was higher than men among people with low levels of educational attainment, but was higher for men than women among people with high levels of educational attainment. In addition, minority respondents self-reported lower perceived climate change knowledge than white respondents, regardless of educational attainment. This study enhances our understanding of the gender gap in self-perceptions of climate knowledge by suggesting it is contingent on educational attainment. This could be the result of stereotype-threat experienced by women and minorities, and exacerbated by educational systems. Because people who question their knowledge are often more able to learn, particularly in ideologically charged contexts, highly educated women and minorities may be more successful learning about climate change than white men.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long Interspersed Element 1 (L1) is a retrotransposon that comprises approximately 17% of the human genome. Despite its abundance in mammalian genomes, relatively little is understood about L1 ...retrotransposition in vivo. To study the timing and tissue specificity of retrotransposition, we created transgenic mouse and rat models containing human or mouse L1 elements controlled by their endogenous promoters. Here, we demonstrate abundant L1 RNA in both germ cells and embryos. However, the integration events usually occur in embryogenesis rather than in germ cells and are not heritable. We further demonstrate L1 RNA in preimplantation embryos lacking the L1 transgene and L1 somatic retrotransposition events in blastocysts and adults lacking the transgene. Together, these data indicate that L1 RNA transcribed in male or female germ cells can be carried over through fertilization and integrate during embryogenesis, an interesting example of heritability of RNA independent of its encoding DNA. Thus, L1 creates somatic mosaicism during mammalian development, suggesting a role for L1 in carcinogenesis and other disease.
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