Explore the vast range of titles available.

Background: Understanding the lower level of happiness among older adults with cognitive impairment has been a largely neglected issue. This study (1) reports on the level of happiness among older adults in Singapore and (2) examines the potential mediating roles of depression, disability, social contact frequency, and loneliness in the relationship between cognitive scores and happiness. Methods: Data for this study were extracted from the Well-being of the Singapore Elderly (WiSE) study: a cross-sectional; comprehensive single-phase survey conducted among Singapore citizens and permanent residents that were aged 60 years and above (n = 2565). The Geriatric Mental State examination (GMS) was administered to the participants. Questions pertaining to socio-demographic characteristics; happiness; loneliness; social contact; depression; and, disability were utilized in this study. Logistic regression analyses and mediation analyses were used to explore the correlates of happiness and potential mediating factors. Results: Overall, 96.2% of older adults in Singapore reported feeling either fairly happy or very happy. In the regression analysis, individuals of Malay descent, those who were married/cohabiting, or had higher education levels were more likely to report feeling happy. After controlling for socio-demographic factors, higher cognitive scores were associated with higher odds of reporting happiness. We found that the positive association between cognition and happiness was fully mediated by disability, depression, loneliness, and frequency of contact with friends. Conclusion: The majority of the older adult population reported feeling fairly or very happy. While cognitive impairment has shown limited reversibility in past studies, unhappiness among older adults with cognitive impairment might be potentially mitigated through interventions addressing accompanying issues of social isolation, disability, and depression

Delaying intubation in patients who fail high-flow nasal cannula (HFNC) may result in increased mortality. The ROX index has been validated to predict HFNC failure among pneumonia patients with acute hypoxemic respiratory failure (AHRF), but little information is available for non-pneumonia causes. In this study, we validate the ROX index among AHRF patients due to both pneumonia or non-pneumonia causes, focusing on early prediction. This was a retrospective observational study in eight Singapore intensive care units from 1 January 2015 to 30 September 2017. All patients >18 years who were treated with HFNC for AHRF were eligible and recruited. Clinical parameters and arterial blood gas values at HFNC initiation and one hour were recorded. HFNC failure was defined as requiring intubation post-HFNC initiation. HFNC was used in 483 patients with 185 (38.3%) failing HFNC. Among pneumonia patients, the ROX index was most discriminatory in pneumonia patients one hour after HFNC initiation [AUC 0.71 (95% CI 0.64-0.79)], with a threshold value of <6.06 at one hour predicting HFNC failure (sensitivity 51%, specificity 80%, positive predictive value 61%, negative predictive value 73%). The discriminatory power remained moderate among pneumonia patients upon HFNC initiation [AUC 0.65 (95% CI 0.57-0.72)], non-pneumonia patients at HFNC initiation [AUC 0.62 (95% CI 0.55-0.69)] and one hour later [AUC 0.63 (95% CI 0.56-0.70)]. The ROX index demonstrated moderate discriminatory power among patients with either pneumonia or non-pneumonia-related AHRF at HFNC initiation and one hour later.

[This corrects the article DOI: 10.1371/journal.pone.0261234.].

The COVID-19 pandemic has underscored the need for a global agreement to strengthen international health regulations. However, progress towards such an agreement has been deferred to a future World Health Assembly and is likely to be further hampered by an increasingly uncertain global geopolitical context, a delay which we cannot afford. In the interim, urgent immediate action to intensify regional cooperation on pandemic preparedness and vaccine equity is needed. The three key aspects of intensified regional cooperation are: financial and economic sustainability, regulatory systems strengthening and legal frameworks that facilitate cooperation. While there is still momentum, the global community must act swiftly and cohesively, intensifying regional cooperation to strengthen governance on pandemic prevention, preparedness and response. •Progress towards a pandemic treaty has stalled admidst global uncertainties.•In the interim, it is imperative to strengthen regional cooperation.•Areas for cooperation include financial and economic sustainability, regulatory systems strengthening and legal frameworks.

Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor α (ER-α) in the human genome. We found that most high-confidence remote ER-α-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-α functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes. Gene regulation: the ER-α interactome Many transcription factors bind to regulatory DNA elements that are distant from gene promoters, and such distal binding sites are thought to regulate transcription through long-range chromatin interactions. In order to study how this remote control is organized in a complex genome, Fullwood et al . use a technique termed ChIA-PET (chromatin interaction analysis by paired-end tag sequencing) to detect and map the chromatin interaction network mediated by oestrogen receptor α (ER-α) in human cancer cells. In the resulting global chromatin interactome map, most high-confidence remote ER-α-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-α functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. Many transcription factors bind to regulatory DNA elements that are distant from gene promoters. These distal binding sites are thought to regulate transcription through long-range chromatin interactions, but, until now, the impact of chromatin interactions on transcription regulation has not been investigated in a genome-wide manner. A new strategy — chromatin interaction analysis by paired-end tag sequencing — is now described for the de novo detection of global chromatin interactions.

BackgroundDelaying intubation in patients who fail high-flow nasal cannula (HFNC) may result in increased mortality. The ROX index has been validated to predict HFNC failure among pneumonia patients with acute hypoxemic respiratory failure (AHRF), but little information is available for non-pneumonia causes. In this study, we validate the ROX index among AHRF patients due to both pneumonia or non-pneumonia causes, focusing on early prediction.MethodsThis was a retrospective observational study in eight Singapore intensive care units from 1 January 2015 to 30 September 2017. All patients >18 years who were treated with HFNC for AHRF were eligible and recruited. Clinical parameters and arterial blood gas values at HFNC initiation and one hour were recorded. HFNC failure was defined as requiring intubation post-HFNC initiation.ResultsHFNC was used in 483 patients with 185 (38.3%) failing HFNC. Among pneumonia patients, the ROX index was most discriminatory in pneumonia patients one hour after HFNC initiation [AUC 0.71 (95% CI 0.64-0.79)], with a threshold value of <6.06 at one hour predicting HFNC failure (sensitivity 51%, specificity 80%, positive predictive value 61%, negative predictive value 73%). The discriminatory power remained moderate among pneumonia patients upon HFNC initiation [AUC 0.65 (95% CI 0.57-0.72)], non-pneumonia patients at HFNC initiation [AUC 0.62 (95% CI 0.55-0.69)] and one hour later [AUC 0.63 (95% CI 0.56-0.70)].ConclusionThe ROX index demonstrated moderate discriminatory power among patients with either pneumonia or non-pneumonia-related AHRF at HFNC initiation and one hour later.

Genomes are organized into high-level three-dimensional structures, and DNA elements separated by long genomic distances can in principle interact functionally. Many transcription factors bind to regulatory DNA elements distant from gene promoters. Although distal binding sites have been shown to regulate transcription by long-range chromatin interactions at a few loci, chromatin interactions and their impact on transcription regulation have not been investigated in a genome-wide manner. Here we describe the development of a new strategy, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) for the de novo detection of global chromatin interactions, with which we have comprehensively mapped the chromatin interaction network bound by oestrogen receptor a (ER-a) in the human genome. We found that most high-confidence remote ER-a-binding sites are anchored at gene promoters through long-range chromatin interactions, suggesting that ER-a functions by extensive chromatin looping to bring genes together for coordinated transcriptional regulation. We propose that chromatin interactions constitute a primary mechanism for regulating transcription in mammalian genomes.