The purpose of this ethnonursing and ethnographic study was to discover the meanings, expressions and functions of care within the high context culture of the Old Order Amish. Leininger's theory of ...cultural care diversity and universality and Hall's concept of high context culture were conceptualized, with the prediction that culture care is closely related to high culture context. Further, it was predicted that social structure, environment and language contexts of the Old Order Amish are related to the lifeways, beliefs and practices about family and community care which promote health and well-being. The research questions focused on meanings, expressions and functions of care, social structure factors influencing professional and folk care services and generational and family differences in culture care. Ethnography, ethnonursing and life history research methods were used with 13 key informants and 23 general informants who lived near the center of an Old Order Amish settlement located in the Midwest of the United States. Leininger's data analysis model was used to abstract themes from the raw data, descriptors and patterns. Through the process of identifying descriptors and patterns, four major themes were abstracted namely, (1) centrality of care in the Old Order Amish world view and social structure, (2) anticipatory care which creates and maintains high context care environment, (3) active participation in culture care which daily promotes individual, family and community well-being and (4) principled pragmatism which guides culture care choices. Helping and visiting were major subthemes that were found to provide the context for learning about care needs of others in the family, church and community contexts. Although all informant families used professional, folk and alternative care services, diversity was found in the extent to which some families used specific types of care. There were minimal family and generational differences in culture care, indicating that change takes place slowly, which explained the predominance of universality in the meanings, expressions and functions of culture care. Long term relationships, shared cultural lifeways and boundary maintenance were high context features found to be related to culture care. Further research is recommended on culture care in Amish and non-Amish cultures and between high context and low context cultures.
Stable perovskites with ionic salts
Ionic liquids have been shown to stabilize organic-inorganic perovskite solar cells with metal oxide carrier-transport layers, but they are incompatible with more ...readily processible organic analogs. Lin
et al.
found that an ionic solid, a piperidinium salt, enhanced the efficiency of positive-intrinsic-negative layered perovskite solar cells with organic electron and hole extraction layers. Aggressive aging testing showed that this additive retarded segregation into impurity phases and pinhole formation in the perovskite layer.
Science
, this issue p.
96
An ionic compound additive improved perovskite solar cell longevity by inhibiting the generation of degradation products.
Longevity has been a long-standing concern for hybrid perovskite photovoltaics. We demonstrate high-resilience positive-intrinsic-negative perovskite solar cells by incorporating a piperidinium-based ionic compound into the formamidinium-cesium lead-trihalide perovskite absorber. With the bandgap tuned to be well suited for perovskite-on-silicon tandem cells, this piperidinium additive enhances the open-circuit voltage and cell efficiency. This additive also retards compositional segregation into impurity phases and pinhole formation in the perovskite absorber layer during aggressive aging. Under full-spectrum simulated sunlight in ambient atmosphere, our unencapsulated and encapsulated cells retain 80 and 95% of their peak and post-burn-in efficiencies for 1010 and 1200 hours at 60° and 85°C, respectively. Our analysis reveals detailed degradation routes that contribute to the failure of aged cells.
Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because ...models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART.
Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results.
Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: An estimated 4 to 5 million Americans have Alzheimer disease or another dementia. OBJECTIVE: To determine the health care utilization and cost outcomes of a comprehensive dementia care ...program for Medicare fee-for-service beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, we used a quasiexperimental design to compare health care utilization and costs for 1083 Medicare fee-for-service beneficiaries enrolled in the University of California Los Angeles Health System Alzheimer and Dementia Care program between July 1, 2012, and December 31, 2015, with those of 2166 similar patients with dementia not participating in the program. Patients in the comparison cohort were selected using the zip code of residence as a sampling frame and matched with propensity scores, which included demographic characteristics, comorbidities, and prior-year health care utilization. We used Medicare claims data to compare utilization and cost outcomes for the 2 groups. INTERVENTIONS: Patients in the dementia care program were comanaged by nurse practitioners and physicians, and the program consisted of structured needs assessments of patients and their caregivers, creation and implementation of individualized dementia care plans with input from primary care physicians, monitoring and revising care plans, referral to community organizations for dementia-related services and support, and access to a clinician for assistance and advice 24 hours per day, 7 days per week. MAIN OUTCOMES AND MEASURES: Admissions to long-term care facilities; average difference-in-differences per quarter over the 3-year intervention period for all-cause hospitalization, emergency department visits, 30-day hospital readmissions, and total Medicare Parts A and B costs of care. Program costs were included in the cost estimates. RESULTS: Program participants (n = 382 men, n = 701 women; mean SD age, 82.10 7.90 years; age range 54-101 years) were less likely to be admitted to a long-term care facility (hazard ratio, 0.60; 95% CI, 0.59-0.61) than those not participating in the dementia care program (n = 759 men, n = 1407 women; mean SD age, 82.42 8.50 years; age range, 34-103 years). There were no differences between groups in terms of hospitalizations, emergency department visits, or 30-day readmissions. The total cost of care to Medicare, excluding program costs, was $601 less per patient per quarter (95% CI, −$1198 to −$5). After accounting for the estimated program costs of $317 per patient per quarter, the program was cost neutral for Medicare, with an estimated net cost of −$284 (95% CI, −$881 to $312) per program participant per quarter. CONCLUSIONS AND RELEVANCE: Comprehensive dementia care may reduce the number of admissions to long-term care facilities, and depending on program costs, may be cost neutral or cost saving. Wider implementation of such programs may help people with dementia stay in their communities.
Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or ...in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.
This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).
After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.
R-FC significantly improved the outcome of patients with previously treated CLL.
TNF is a key inflammatory cytokine. Using a modified tandem affinity purification approach, we identified HOIL-1 and HOIP as functional components of the native TNF-R1 signaling complex (TNF-RSC). ...Together, they were shown to form a linear ubiquitin chain assembly complex (LUBAC) and to ubiquitylate NEMO. We show that LUBAC binds to ubiquitin chains of different linkage types and that its recruitment to the TNF-RSC is impaired in TRADD-, TRAF2-, and cIAP1/2- but not in RIP1- or NEMO-deficient MEFs. Furthermore, the E3 ligase activity of cIAPs, but not TRAF2, is required for HOIL-1 recruitment to the TNF-RSC. LUBAC enhances NEMO interaction with the TNF-RSC, stabilizes this protein complex, and is required for efficient TNF-induced activation of NF-κB and JNK, resulting in apoptosis inhibition. Finally, we demonstrate that sustained stability of the TNF-RSC requires LUBAC's enzymatic activity, thereby adding a third form of ubiquitin linkage to the triggering of TNF signaling by the TNF-RSC.
Mutations in TP53, NOTCH1, and SF3B1 were analyzed in the CLL8 study evaluating first-line therapy with fludarabine and cyclophosphamide (FC) or FC with rituximab (FCR) among patients with untreated ...chronic lymphocytic leukemia (CLL). TP53, NOTCH1, and SF3B1 were mutated in 11.5%, 10.0%, and 18.4% of patients, respectively. NOTCH1mut and SF3B1mut virtually showed mutual exclusivity (0.6% concurrence), but TP53mut was frequently found in NOTCH1mut (16.1%) and in SF3B1mut (14.0%) patients. There were few significant associations with clinical and laboratory characteristics, but genetic markers had a strong influence on response and survival. In multivariable analyses, an independent prognostic impact was found for FCR, thymidine kinase (TK) ≥10 U/L, unmutated IGHV, 11q deletion, 17p deletion, TP53mut, and SF3B1mut on progression-free survival; and for FCR, age ≥65 years, Eastern Cooperative Oncology Group performance status ≥1, β2-microglobulin ≥3.5 mg/L, TK ≥10 U/L, unmutated IGHV, 17p deletion, and TP53mut on overall survival. Notably, predictive marker analysis identified an interaction of NOTCH1 mutational status and treatment in that rituximab failed to improve response and survival in patients with NOTCH1mut. In conclusion, TP53 and SF3B1 mutations appear among the strongest prognostic markers in CLL patients receiving current-standard first-line therapy. NOTCH1mut was identified as a predictive marker for decreased benefit from the addition of rituximab to FC. This study is registered at www.clinicaltrials.gov as #NCT00281918.
•Independent prognostic impact of biological markers, notably TP53 and SF3B1 mutations, in CLL patients requiring therapy.•NOTCH1 mutation as a predictive factor for reduced benefit from the addition of rituximab to FC chemotherapy.
A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces ...cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as β-farnesene (C
H
), a plant sesquiterpene with versatile industrial applications, is straightforward. However, S. cerevisiae uses a chemically inefficient pathway for isoprenoid biosynthesis, resulting in yield and productivity limitations incompatible with commodity-scale production. Here we use four non-native metabolic reactions to rewire central carbon metabolism in S. cerevisiae, enabling biosynthesis of cytosolic acetyl coenzyme A (acetyl-CoA, the two-carbon isoprenoid precursor) with a reduced ATP requirement, reduced loss of carbon to CO
-emitting reactions, and improved pathway redox balance. We show that strains with rewired central metabolism can devote an identical quantity of sugar to farnesene production as control strains, yet produce 25% more farnesene with that sugar while requiring 75% less oxygen. These changes lower feedstock costs and dramatically increase productivity in industrial fermentations which are by necessity oxygen-constrained. Despite altering key regulatory nodes, engineered strains grow robustly under taxing industrial conditions, maintaining stable yield for two weeks in broth that reaches >15% farnesene by volume. This illustrates that rewiring yeast central metabolism is a viable strategy for cost-effective, large-scale production of acetyl-CoA-derived molecules.
Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell ...lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycythaemia and anaemia. To overcome this limitation, we have generated a novel transgenic mouse model expressing Cre recombinase specifically in the active fraction of renal Epo-producing (REP) cells. Crossing with reporter mice confirmed the inducible and highly specific tagging of REP cells, located in the corticomedullary border region where there is a steep drop in oxygen bioavailability. A novel method was developed to selectively grow primary REP cells in culture and to generate immortalized clonal cell lines, called fibroblastoid atypical interstitial kidney (FAIK) cells. FAIK cells show very early hypoxia-inducible factor (HIF)-2α induction, which precedes Epo transcription. Epo induction in FAIK cells reverses rapidly despite ongoing hypoxia, suggesting a cell autonomous feedback mechanism. In contrast, HIF stabilizing drugs resulted in chronic Epo induction in FAIK cells. RNA sequencing of three FAIK cell lines derived from independent kidneys revealed a high degree of overlap and suggests that REP cells represent a unique cell type with properties of pericytes, fibroblasts, and neurons, known as telocytes. These novel cell lines may be helpful to investigate myofibroblast differentiation in chronic kidney disease and to elucidate the molecular mechanisms of HIF stabilizing drugs currently in phase III studies to treat anemia in end-stage kidney disease.
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Materials featuring anomalous suppression of density fluctuations over large length scales are emerging systems known as disordered hyperuniform. The underlying hidden order renders them appealing ...for several applications, such as light management and topologically protected electronic states. These applications require scalable fabrication, which is hard to achieve with available top-down approaches. Theoretically, it is known that spinodal decomposition can lead to disordered hyperuniform architectures. Spontaneous formation of stable patterns could thus be a viable path for the bottom-up fabrication of these materials. Here, we show that monocrystalline semiconductor-based structures, in particular Si1−x Gex layers deposited on silicon-on-insulator substrates, can undergo spinodal solid-state dewetting featuring correlated disorder with an effective hyperuniform character. Nano- to micrometric sized structures targeting specific morphologies and hyperuniform character can be obtained, proving the generality of the approach and paving the way for technological applications of disordered hyperuniform metamaterials. Phase-field simulations explain the underlying nonlinear dynamics and the physical origin of the emerging patterns.
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