Objectives
Tube feeding is prevalent among patients with advanced dementia despite empirical data that suggest its lack of benefit. To provide an alternative to tube feeding for end-of-life patients, ...a careful hand feeding program was launched in a Hong Kong geriatric convalescent hospital in February 2017. We aim to compare the rates of feeding tube insertion before and after program implementation and determine risk factors for feeding tube insertion. For patients on careful hand feeding, we evaluated their sustainability on oral feeding and the rates of hospital readmissions compared with tube feeding patients over the next 12 months.
Design
Retrospective cohort study.
Setting and Participants
Advanced dementia patients ≥60 years with indication for tube feeding due to feeding problems admitted from January 2015–June 2019.
Methods
Data was collected on demographic and clinical variables, initial feeding mode (careful hand feeding vs. tube feeding), subsequent feeding mode changes, and hospital admissions over the next 12 months. Rates of feeding tube insertion, sustainability on oral feeding, and hospital readmissions were compared using Chi-square test. Risk factors for feeding tube insertion were assessed using logistic regression models.
Results
Among 616 advanced dementia patients admitted with feeding problems, feeding tube insertion rate declined significantly after careful hand feeding program implementation (72% vs 51% p<.001). Independent risk factors for feeding tube insertion were admission prior to program implementation, presence of dysphagia alone, dysphagia combined with poor intake, and lack of advance care planning. Among patients on careful hand feeding, 91% were sustained on oral feeding over the next twelve months and did not differ significantly before or after careful hand feeding program implementation (p=.67). There was no significant difference in hospital readmission rates between careful hand feeding patients and tube feeding patients before (83% vs 86%, p=.55) and after careful hand feeding program implementation (87% vs 85%, p=.63).
Conclusions and Implications
A hospital careful hand feeding program significantly reduced the feeding tube insertion rate among advanced dementia patients with feeding problems. The vast majority of patients on careful hand feeding were sustained on oral feeding over the next 12 months but their rate of hospital readmissions remained similarly high after program implementation.
The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes. Comprehensive catalogs of ...IFN-stimulated genes have been established across species and cell types by transcriptomic and biochemical approaches, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to describe the effects of IFN signaling on the human proteome, and apply protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network.
We identify > 26,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer IFN-stimulated gene protein synthesis.
Our map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing IFN-stimulated genes in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease.
Silicon quantum dot spin qubits provide a promising platform for large-scale quantum computation because of their compatibility with conventional CMOS manufacturing and the long coherence times ...accessible using
Si enriched material. A scalable error-corrected quantum processor, however, will require control of many qubits in parallel, while performing error detection across the constituent qubits. Spin resonance techniques are a convenient path to parallel two-axis control, while Pauli spin blockade can be used to realize local parity measurements for error detection. Despite this, silicon qubit implementations have so far focused on either single-spin resonance control, or control and measurement via voltage-pulse detuning in the two-spin singlet-triplet basis, but not both simultaneously. Here, we demonstrate an integrated device platform incorporating a silicon metal-oxide-semiconductor double quantum dot that is capable of single-spin addressing and control via electron spin resonance, combined with high-fidelity spin readout in the singlet-triplet basis.
Self‐control is of vital importance for human wellbeing. Hare et al. (2009) were among the first to provide empirical evidence on the neural correlates of self‐control. This seminal study profoundly ...impacted theory and empirical work across multiple fields. To solidify the empirical evidence supporting self‐control theory, we conducted a preregistered replication of this work. Further, we tested the robustness of the findings across analytic strategies. Participants underwent functional magnetic resonance imaging while rating 50 food items on healthiness and tastiness and making choices about food consumption. We closely replicated the original analysis pipeline and supplemented it with additional exploratory analyses to follow‐up on unexpected findings and to test the sensitivity of results to key analytical choices. Our replication data provide support for the notion that decisions are associated with a value signal in ventromedial prefrontal cortex (vmPFC), which integrates relevant choice attributes to inform a final decision. We found that vmPFC activity was correlated with goal values regardless of the amount of self‐control and it correlated with both taste and health in self‐controllers but only taste in non‐self‐controllers. We did not find strong support for the hypothesized role of left dorsolateral prefrontal cortex (dlPFC) in self‐control. The absence of statistically significant group differences in dlPFC activity during successful self‐control in our sample contrasts with the notion that dlPFC involvement is required in order to effectively integrate longer‐term goals into subjective value judgments. Exploratory analyses highlight the sensitivity of results (in terms of effect size) to the analytical strategy, for instance, concerning the approach to region‐of‐interest analysis.
To solidify the empirical evidence supporting self‐control theory, we conducted a preregistered replication of the seminal study of Hare et al. (2009). Our replication data provide support for the notion that decisions are associated with a value signal in ventromedial prefrontal cortex but no strong support was found for the hypothesized role of left dorsolateral prefrontal cortex in self‐control. Exploratory analyses highlight the sensitivity of results (in terms of effect size) to the analytical strategy, for instance, concerning the approach to region‐of‐interest analysis.
This phase III randomized study compared concurrent cisplatin–radiotherapy (CRT) versus radiotherapy (RT) alone in patients with locoregionally advanced nasopharyngeal carcinoma. A total of 350 ...patients were randomly assigned to receive external RT alone or concurrently with cisplatin at a dosage of 40 mg/m2 weekly. The primary endpoint was overall survival, and the median follow-up was 5.5 years. The 5-year overall survival was 58.6% (95% confidence interval CI = 50.9% to 66.2%) for the RT arm and 70.3% (95% CI = 63.4% to 77.3%) for the CRT arm. In Cox regression analysis adjusted for T stage, age, and overall stage, the difference in overall survival was statistically significantly in favor of concurrent CRT (P = .049, hazard ratio HR = 0.71 95% CI = 0.5 to 1.0). Subgroup analysis demonstrated that there was no difference between overall survival in the arms for T1/T2 stage (P = .74, HR = 0.93 95% CI = 0.59 to 1.4), whereas there was a difference between the arms for T3/T4 stage (P = .013, HR = 0.51 95% CI = 0.3 to 0.88), favoring the CRT arm. The regimen of weekly concurrent CRT is a promising standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma patients.
Single-electron spin qubits employ magnetic fields on the order of 1 Tesla or above to enable quantum state readout via spin-dependent-tunnelling. This requires demanding microwave engineering for ...coherent spin resonance control, which limits the prospects for large scale multi-qubit systems. Alternatively, singlet-triplet readout enables high-fidelity spin-state measurements in much lower magnetic fields, without the need for reservoirs. Here, we demonstrate low-field operation of metal-oxide-silicon quantum dot qubits by combining coherent single-spin control with high-fidelity, single-shot, Pauli-spin-blockade-based ST readout. We discover that the qubits decohere faster at low magnetic fields with Formula: see text μs and Formula: see text μs at 150 mT. Their coherence is limited by spin flips of residual
Si nuclei in the isotopically enriched
Si host material, which occur more frequently at lower fields. Our finding indicates that new trade-offs will be required to ensure the frequency stabilization of spin qubits, and highlights the importance of isotopic enrichment of device substrates for the realization of a scalable silicon-based quantum processor.
Quantitative measurement of plasma Epstein–Barr virus (EBV) DNA by real-time PCR at the end of primary treatment is a robust prognostic marker for nasopharyngeal carcinoma (NPC) patients. However, up ...to 40% of patients who would later develop disease recurrence had undetectable post-treatment plasma EBV DNA. Targeted sequencing for the entire EBV genome potentially allows a more comprehensive and unbiased detection of plasma EBV DNA and enables the use of other parameters such as fragment size as biomarkers. Hence, we explored if plasma EBV DNA sequencing might allow more accurate prognostication of NPC patients.
Plasma samples collected from 769 patients with stage IIB-IVB NPC at 6-8 weeks after radiotherapy were analysed using targeted sequencing for EBV DNA.
The sensitivities of the PCR-based analysis, at a cut-off of any detectable levels of plasma EBV DNA, for prediction of local and distant recurrences were 42.3% and 85.3%, respectively. The sequencing-based analysis (involving quantitation and size profiling) achieved better performance for both local and distant recurrences than PCR. Using a cut-off of the proportion of plasma EBV DNA deduced by sequencing at 0.01%, the sensitivities of the sequencing-based analysis for local and distant recurrences were 88.5% and 97.1%, with the resultant negative predictive values of 99.1% and 99.4%, respectively. Among patients with undetectable EBV DNA on quantitative PCR, sequencing could further define a subgroup that enjoyed superior survival outcomes based on the proportion of plasma EBV DNA, with a 5-year progression-free survival (PFS) approaching 90%. On multivariate analysis, sequencing-based quantitative level of plasma EBV DNA was the independent prognostic factor with the highest hazard ratio for prediction of overall survival and PFS.
NPC prognostication using post-treatment plasma EBV DNA could be enhanced through sequencing.
•PCR-based analysis of plasma EBV DNA has limited sensitivity in predicting recurrences of NPC.•Sequencing analysis of post-treatment plasma EBV DNA improves the sensitivity for both local and distant relapses of NPC.•Sequencing analysis of post-treatment plasma EBV DNA could better stratify the mortality risk of NPC patients than PCR.
Background and Purpose
Inflammasomes are multimeric complexes that facilitate caspase‐1‐mediated processing of the pro‐inflammatory cytokines IL‐1β and IL‐18. Clinical hypertension is associated with ...renal inflammation and elevated circulating levels of IL‐1β and IL‐18. Therefore, we investigated whether hypertension in mice is associated with increased expression and/or activation of the inflammasome in the kidney, and if inhibition of inflammasome activity reduces BP, markers of renal inflammation and fibrosis.
Experimental Approach
Wild‐type and inflammasome‐deficient ASC−/− mice were uninephrectomized and received deoxycorticosterone acetate and saline to drink (1K/DOCA/salt). Control mice were uninephrectomized but received a placebo pellet and water. BP was measured by tail cuff; renal expression of inflammasome subunits and inflammatory markers was measured by real‐time PCR and immunoblotting; macrophage and collagen accumulation was assessed by immunohistochemistry.
Key Results
1K/DOCA/salt‐induced hypertension in mice was associated with increased renal mRNA expression of inflammasome subunits NLRP3, ASC and pro‐caspase‐1, and the cytokine, pro‐IL‐1β, as well as protein levels of active caspase‐1 and mature IL‐1β. Following treatment with 1K/DOCA/salt, ASC−/− mice displayed blunted pressor responses and were also protected from increases in renal expression of IL‐6, IL‐17A, CCL2, ICAM‐1 and VCAM‐1, and accumulation of macrophages and collagen. Finally, treatment with a novel inflammasome inhibitor, MCC950, reversed hypertension in 1K/DOCA/salt‐treated mice.
Conclusions and Implications
Renal inflammation, fibrosis and elevated BP induced by 1K/DOCA/salt treatment are dependent on inflammasome activity, highlighting the inflammasome/IL‐1β pathway as a potential therapeutic target in hypertension.
Linked Articles
This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4
In various practical applications, nanomaterials typically have functionalized surfaces. Yet, the studies of toxicity and antibacterial activity of functionalized nanoparticles are scarce. We ...investigated the effect of surface modifications on antibacterial activity of ZnO under ambient illumination, and we found that nanoparticles coated with different surface modifying reagents could exhibit higher or lower toxicity compared to bare ZnO, depending on the surface modifying reagent used. Different surface modifying reagent molecules resulted in differences in the release of Zn(2+) ions and the production of reactive oxygen species (ROS). However, the antibacterial activity did not correlate with the ROS levels or the Zn(2+) ion release. One of the surface-modified ZnO samples exhibited significantly lower Zn(2+) ion release while at the same time exhibiting improved antibacterial activity. In all cases, damage of the cell wall membranes and/or changes in the membrane permeability have been observed, together with the changes in ATR-FTIR spectra indicating differences in protein conformation. Mechanisms of antibacterial activity are discussed.
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