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Broad learning system (BLS) is a novel and efficient model, which facilitates representation learning and classification by concatenating feature nodes and enhancement nodes. In spite of the efficient properties, BLS is still suboptimal when facing with imbalance problem. Besides, outliers and noises in imbalanced data remain a challenge for BLS. To address the above issues, in this paper we firstly propose a weighted BLS, which assigns a weight to each training sample, and adopt a general weighting scheme, which augments the weight of samples from the minority class. To further explore the prior distribution of original data, we design a density based weight generation mechanism to guide the specific weight matrix generation and propose the adaptive weighted broad learning system (AWBLS). This mechanism considers the inter-class and intra-class distance simultaneously in the density calculation. Finally, we propose the incremental weighted ensemble broad learning system (IWEB) by utilizing a progressive mechanism to further improve the stability and robustness of AWBLS. Extensive comparative experiments on 30 real-world data sets verfy that IWEB outperforms most of the imbalance ensemble classification methods.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been associated with respiratory diseases in humans, yet the mechanisms through which PFAS cause susceptibility to inhaled agents is unknown. Herein we investigated the effects of ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), an emerging PFAS, on the pulmonary immune response of mice to carbon black nanoparticles (CBNP). We hypothesized that pulmonary exposure to GenX would increase susceptibility to CBNP through suppression of innate immunity. METHODS: Male C57BL/6 mice were exposed to vehicle, 4 mg/kg CBNP, 10 mg/kg GenX, or CBNP and GenX by oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) was collected at 1 and 14 days post-exposure for cytokines and total protein. Lung tissue was harvested for histopathology, immunohistochemistry (Ki67 and phosphorylated (p)-STAT3), western blotting (p-STAT3 and p-NF-κB), and qRT-PCR for cytokine mRNAs. RESULTS: CBNP increased CXCL-1 and neutrophils in BALF at both time points evaluated. However, GenX/CBNP co-exposure reduced CBNP-induced CXCL-1 and neutrophils in BALF. Moreover, CXCL-1, CXCL-2 and IL-1β mRNAs were increased by CBNP in lung tissue but reduced by GenX. Western blotting showed that CBNP induced p-NF-κB in lung tissue, while the GenX/CBNP co-exposed group displayed decreased p-NF-κB. Furthermore, mice exposed to GenX or GenX/CBNP displayed increased numbers of BALF macrophages undergoing mitosis and increased Ki67 immunostaining. This was correlated with increased p-STAT3 by western blotting and immunohistochemistry in lung tissue from mice co-exposed to GenX/CBNP. CONCLUSIONS: Pulmonary exposure to GenX suppressed CBNP-induced innate immune response in the lungs of mice yet promoted the proliferation of macrophages and lung epithelial cells.

In this paper, we propose a general framework termed "Centroid Estimation with Guaranteed Efficiency" (CEGE) for Weakly Supervised Learning (WSL) with incomplete, inexact, and inaccurate supervision. The core of our framework is to devise an unbiased and statistically efficient risk estimator that is applicable to various weak supervision. Specifically, by decomposing the loss function (e.g., the squared loss and hinge loss) into a label-independent term and a label-dependent term, we discover that only the latter is influenced by the weak supervision and is related to the centroid of the entire dataset. Therefore, by constructing two auxiliary pseudo-labeled datasets with synthesized labels, we derive unbiased estimates of centroid based on the two auxiliary datasets, respectively. These two estimates are further linearly combined with a properly decided coefficient which makes the final combined estimate not only unbiased but also statistically efficient. This is better than some existing methods that only care about the unbiasedness of estimation but ignore the statistical efficiency. The good statistical efficiency of the derived estimator is guaranteed as we theoretically prove that it acquires the minimum variance when estimating the centroid. As a result, intensive experimental results on a large number of benchmark datasets demonstrate that our CEGE generally obtains better performance than the existing approaches related to typical WSL problems including semi-supervised learning, positive-unlabeled learning, multiple instance learning, and label noise learning.

Funding Acknowledgements Type of funding sources: None. Background The optimal amount of exercise for preventing cardiovascular events in patients with pacemakers has not been revealed. Methods Using the Korean National Health Insurance Service database, patients who had newly implanted pacemakers between 2009 and 2018 were included. The amount of physical activity was measured by a self-reported questionnaire included in the national health examination. Performing regular exercise was defined as ≥5 days of moderate-intensity exercise or ≥3 days of vigorous-intensity exercise per week. The occurrence of major adverse cardiovascular events (MACE) defined as the composite of stroke, heart failure, myocardial infarction, and all-cause death was evaluated during follow-up. Results A total of 13,542 patients were included (mean age 68±11 years, 45% of men); 51% of patients were atrioventricular block and 39% of patients were sick sinus syndrome, and 85% of patients were implanted with dual-chamber pacemaker. During a median 2.5-year of follow-up, the incidence rates of MACE was 5.4 and 3.7 per 100 person-years in non-exerciser and exerciser, respectively (Figure A). Compared to non-exerciser, patients performing regular exercise were associated with a lower risk of MACE (hazard ratio, 95% confidence interval: 0.745, 0.661-0.839, p Conclusion Regular physical activity was related to the risk of MACE in patients with pacemaker. A proactive cardiac rehabilitation program would be considered for this population.

Nickel hydroxide nanosheets embedded with NiMoO4 nanoparticles with controllable composition were prepared. The optimized hybrid electrode exhibits high energy density.

ObjectivesTo develop and validate a values clarification tool, the Short Graphic Values History Tool (GVHT), designed to support person-centred decision making during serious illness.MethodsThe development phase included input from experts and laypersons and assessed acceptability with patients/family members. In the validation phase, we recruited additional participants into a before–after study. Our primary validation hypothesis was that the tool would reduce scores on the Decisional Conflict Scale (DCS) at 1–2 weeks of follow-up. Our secondary validation hypotheses were that the tool would improve values clarity (reduce scores) more than other DCS subscales and increase engagement in advance care planning (ACP) processes related to identification and discussion of one’s values.ResultsIn the development phase, the tool received positive overall ratings from 22 patients/family members in hospital (mean score 4.3; 1=very poor; 5=very good) and family practice (mean score 4.5) settings. In the validation phase, we enrolled 157 patients (mean age 71.8 years) from family practice, cancer clinic and hospital settings. After tool completion, decisional conflict decreased (−6.7 points, 95% CI −11.1 to −2.3, p=0.003; 0–100 scale; N=100), with the most improvement seen in the values clarity subscale (−10.0 points, 95% CI −17.3 to −2.7, p=0.008; N=100), and the ACP-Values process score increased (+0.4 points, 95% CI 0.2 to 0.6, p=0.001; 1–5 scale; N=61).ConclusionsThe Short GVHT is acceptable to end users and has some measure of validity. Further study to evaluate its impact on decision making during serious illness is warranted.

With the view of marriage as a legal institution to internalize externalities, I examine the effect of marriage on smoking. From analyzing the data of Panel Study of Income Dynamics, I found that unmarried individuals are more likely to smoke by 4.9% point than married individuals with stronger impact on females. The long-run impact of marriage also shows that the unmarried individuals smoke more than married individuals but some of its positive impact diminishes within two years. These results on the whole imply that marriage internalizes the negative externalities of smoking and thus leads smokers to reduce smoking.

This paper reports findings from a modified World Café conducted at a palliative care professional conference in 2019, where input on tools to support advance care planning (ACP) was solicited from healthcare practitioners, managers and family members of patients. Barriers to ACP tool use included insufficient structures and resources in healthcare, death-avoidance culture and inadequate patient and family member engagement. Recommendations for tool use included clarification of roles and processes, training, mandates and monitoring, leadership support, greater reflection of diversity in tools and methods for public engagement. This paper illuminates factors to consider when implementing ACP tools in healthcare.

Funding Acknowledgements Type of funding sources: None. Background Many studies to date have documented significant inflammatory vascular sequelae in association with COVID-19. Current guidelines suggest an initial strategy of therapeutic-dose anticoagulation to non-critically ill, hospitalized patients requiring low-flow oxygen and a concurrent D-dimer level above the upper limit of normal. However, the utility of D-dimer values in predicting thrombosis in severely obese patients are equivocal to poor, with prior evidence suggesting falsely elevated levels with greater BMI. Given the weight-based dosing of heparin, these patients may also be inadvertently at elevated risk for major bleeds. Purpose To examine the utility of D-dimer levels in risk stratification and anticoagulation therapy in non-critically ill COVID-19 patients with severe obesity. Methods In this single-center, retrospective study, 32 severely obese patients (defined as BMI > 40) hospitalized with COVID-19 and requiring low flow oxygen delivery, without ICU level of care were analyzed. Clinical outcomes were compared between groups receiving therapeutic versus prophylactic doses of anticoagulation. All were treated with low molecular weight heparin (LMWH) per hospital protocol. The following data points were examined: length of hospitalization, mortality, anticoagulation therapy, initial d-dimer levels, thrombotic events, minor/major bleeds, and oxygen modality. Results In total, 78% of patients initially presented with a D-dimer level above the upper limit of normal, with 53% of patients meeting criteria for therapeutic anticoagulation. However, there were no significant differences in incidence of thrombotic events, mean length of hospitalization or overall mortality. Furthermore, despite utilization of appropriate therapeutic anticoagulation, it did not reduce the overall use of oxygen support requirements, including high flow oxygen or non-invasive ventilation, when compared to individuals receiving prophylactic dosing. Conclusion The clinical utility of D-dimer levels for guiding anticoagulation therapy in severely obese patients with COVID-19 may be limited. Here, we demonstrate that therapeutic dose approaches have nonsignificant differences in clinical outcomes when compared to prophylactic doses in this distinct population.

Acute carbon monoxide poisoning can cause multiple organ damage due to hypoxia. In severe cases, it can be life-threatening and has a high fatality rate. Intestinal obstruction and thrombosis are rare complications of carbon monoxide poisoning. A case of carbon monoxide poisoning was reported. In addition to the central nervous system lesion, intestinal obstruction and lower limb thrombosis were also found. In the treatment of carbon monoxide poisoning patients, the clinician was able to treat the common complications, attention should be paid to gastrointestinal tract, thrombotic disease and other rare complications, so as to avoid missed diagnosis.急性一氧化碳中毒可造成多脏器缺氧损伤，严重时可危及生命，病死率较高。肠梗阻及深静脉血栓是一氧化碳中毒的少见继发症。本文探讨1例一氧化碳中毒患者除中枢神经系统损害以外，还继发肠梗阻及下肢深静脉血栓，临床医生在救治急性一氧化碳中毒患者时，在治疗常见继发症的同时，需关注胃肠道、血栓性疾病等少见继发症，以免漏诊。.

BACKGROUND: Many seriously ill hospitalized patients have cardiopulmonary resuscitation (CPR) as part of their care plan, but CPR is unlikely to achieve the goals of many seriously ill hospitalized patients. OBJECTIVE: To determine if a multicomponent decision support intervention changes documented orders for CPR in the medical record, compared to usual care. DESIGN: Open-label randomized controlled trial. PATIENTS: Patients on internal medicine and neurology wards at two tertiary care teaching hospitals who had a 1-year mortality greater than 10% as predicted with a validated model and whose care plan included CPR, if needed. INTERVENTION: Both the control and intervention groups received usual communication about CPR at the discretion of their care team. The intervention group participated in a values clarification exercise and watched a CPR video decision aid. MAIN MEASURE: The primary outcome was the proportion of patients who had a no-CPR order at 14 days after enrollment. KEY RESULTS: We recruited 200 patients between October 2017 and October 2018. Mean age was 77 years. There was no difference between the groups in no-CPR orders 14 days after enrollment (17/100 (17%) intervention vs 17/99 (17%) control, risk difference, − 0.2%) (95% confidence interval − 11 to 10%; p = 0.98). In addition, there were no differences between groups in decisional conflict summary score or satisfaction with decision-making. Patients in the intervention group had less conflict about understanding treatment options (decisional conflict knowledge subscale score mean (SD), 17.5 (26.5) intervention arm vs 40.4 (38.1) control; scale range 0–100 with lower scores reflecting less conflict). CONCLUSIONS: Among seriously ill hospitalized patients who had CPR as part of their care plan, this decision support intervention did not increase the likelihood of no-CPR orders compared to usual care. PRIMARY FUNDING SOURCE: Canadian Frailty Network, The Ottawa Hospital Academic Medical Organization. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11606-021-06605-y.

Background Inhalation of multi-walled carbon nanotubes (MWCNTs) poses a potential risk to human health. In order to safeguard workers and consumers, the toxic properties of MWCNTs need to be identified. Functionalization has been shown to either decrease or increase MWCNT-related pulmonary injury, depending on the type of modification. We, therefore, investigated both acute and chronic pulmonary toxicity of a library of MWCNTs derived from a common pristine parent compound (NC7000). Methods MWCNTs were thermally or chemically purified and subsequently surface functionalized by carboxylation or amination. To evaluate pulmonary toxicity, male C57BL6 mice were dosed via oropharyngeal aspiration with either 1.6 or 4 mg/kg of each MWCNT type. Mitsui-7 MWCNT was used as a positive control. Necropsy was performed at days 3 and 60 post-exposure to collect bronchoalveolar lavage fluid (BALF) and lungs. Results At day 3 all MWCNTs increased the number of neutrophils in BALF. Chemical purification had a greater effect on pro-inflammatory cytokines (IL-1β, IL-6, CXCL1) in BALF, while thermal purification had a greater effect on pro-fibrotic cytokines (CCL2, OPN, TGF-β1). At day 60, thermally purified, carboxylated MWCNTs had the strongest effect on lymphocyte numbers in BALF. Thermally purified MWCNTs caused the greatest increase in LDH and total protein in BALF. Furthermore, the thermally purified and carboxyl- or amine-functionalized MWCNTs caused the greatest number of granulomatous lesions in the lungs. The physicochemical characteristics mainly associated with increased toxicity of the thermally purified derivatives were decreased surface defects and decreased amorphous content as indicated by Raman spectroscopy. Conclusions These data demonstrate that the purification method is an important determinant of lung toxicity induced by carboxyl- and amine-functionalized MWCNTs.

Nickel nanoparticles (NiNPs) are increasingly used in nanotechnology applications, yet information on sex differences in NiNP-induced lung disease is lacking. The goal of this study was to explore mechanisms of susceptibility between male and female mice after acute or subchronic pulmonary exposure to NiNPs. For acute exposure, male and female mice received a single dose of NiNPs with or without LPS by oropharyngeal aspiration and were necropsied 24 h later. For subchronic exposure, mice received NiNPs with or without LPS six times over 3 weeks prior to necropsy. After acute exposure to NiNPs and LPS, male mice had elevated cytokines (CXCL1 and IL-6) and more neutrophils in bronchoalveolar lavage fluid (BALF), along with greater STAT3 phosphorylation in lung tissue. After subchronic exposure to NiNPs and LPS, male mice exhibited increased monocytes in BALF. Moreover, subchronic exposure of male mice to NiNP only induced higher CXCL1 and CCL2 in BALF along with increased alveolar infiltrates and CCL2 in lung tissue. STAT1 in lung tissue was induced by subchronic exposure to NiNPs in females but not males. Males had a greater induction of IL-6 mRNA in liver after acute exposure to NiNPs and LPS, and greater CCL2 mRNA in liver after subchronic NiNP exposure. These data indicate that susceptibility of males to acute lung inflammation involves enhanced neutrophilia with increased CXCL1 and IL-6/STAT3 signaling, whereas susceptibility to subchronic lung inflammation involves enhanced monocytic infiltration with increased CXCL1 and CCL2. STAT transcription factors appear to play a role in these sex differences. This study demonstrates sex differences in the lung inflammatory response of mice to NiNPs that has implications for human disease.

BACKGROUND: Seriously ill patients in hospital have indicated that better communication with practitioners is vital for improving care. The aim of this study was to assess whether the quality of conversations about serious illness improved after implementation of the Serious Illness Care Program (SICP). METHODS: In this retrospective chart review study, we evaluated patients who were admitted to a medical ward at Hamilton General Hospital, had a stay of at least 48 hours, and were at risk for a lengthy stay or increased need for community-based services (inter-RAI Emergency Department Screener score of 5 or 6). The SICP study period was from Mar. 1, 2017, to Jan. 19, 2018. We used a validated codebook to assess the quality of documented conversations regarding serious illness for eligible patients before (usual care [control group]) and after SICP implementation (intervention group), specifically examining the following domains: patients’ values and goals, understanding of prognosis and illness, end-of-life care planning, and code status or desire for other life-sustaining treatments. RESULTS: The study sample included 56 patients in the control group and 56 patients in the intervention group. The overall quality of documented conversations about serious illness was significantly higher in the intervention group than in the control group (p < 0.001) and was significantly higher in the subdomains of values and goals (p < 0.001), understanding of prognosis and illness (p < 0.001) and life-sustaining treatments (p = 0.03) but not end-of-life care planning (p = 0.48). INTERPRETATION: Implementation of the SICP in a hospital setting was associated with higher quality of documented conversations regarding serious illness with patients at high risk for clinical or functional deterioration. The SICP is transferable and adaptable to a hospital setting, and was associated with an increase in adherence to best practices compared to usual care.