Impact of beta-blockers on mortality and cardiovascular disease outcomes in patients with obstructive sleep apnoea: a population-based cohort study in target trial emulation framework.

Background: There is no real-world evidence regarding the association between beta-blocker use and mortality or cardiovascular outcomes in patients with obstructive sleep apnoea (OSA). We aimed to investigate the impact of beta-blocker use on all-cause mortality and cardiovascular diseases (CVDs) in patients with OSA. Methods: We conducted a target trial emulation study of 37,581 patients with newly diagnosed OSA from 1st January 2000 to 30th November 2021 using the IMRD-UK database (formerly known as the THIN database). We compared the treatment strategies of initiating beta-blocker treatment within one year versus non-beta-blocker treatment through the method of clone-censor-weight. Covariates, including patients' demographics, lifestyle, comorbidities, and recent medications, were measured and controlled. Patients were followed up for all-cause mortality or composite CVD outcomes (angina, myocardial infarction, stroke/transient ischaemic attack, heart failure, or atrial fibrillation). We estimated the five-year absolute risks, risk differences and risk ratio with 95% confidence intervals (CIs) with standardised, weighted pooled logistic regression, which is a discrete-time hazard model for survival analysis. Several sensitivity analyses were performed, including multiple imputation addressing the missing data. Findings: The median follow-up time was 4.1 (interquartile range, 1.9-7.8) years. The five-year absolute risk of all-cause mortality and CVD outcomes were 4.9% (95% CI, 3.8-6.0) and 13.0% (95% CI, 11.4-15.0) among beta-blocker users, and 4.0% (95% CI, 3.8-4.2) and 9.4% (95% CI, 9.1-9.7) among non-beta-blocker users, respectively. The five-year absolute risk difference and risk ratio between the two groups for all-cause mortality and CVD outcomes were 0.9% (95% CI, -0.2 to 2.1) and 1.22 (95% CI, 0.96-1.54), and 3.5% (95% CI, 2.1-5.5) and 1.37 (95% CI, 1.22-1.62), respectively. Findings were consistent across the sensitivity analyses. Interpretation: Beta-blocker treatment was associated with an increased risk of CVD and a trend for an increased risk of mortality among patients with OSA. Further studies are needed to confirm our findings. Funding: Innovation and Technology Commission of the Hong Kong Special Administration Region Government.

Association of night-time sleep duration and daytime napping with all-cause and cause-specific mortality in older British men: Findings from the British Regional HeartStudy.

Short and long night-time sleep and daytime napping in young and middle-aged populations were associated with increased mortality, but it is unclear in very older people. The aim of this prospective study was to assess the associations in people aged >70 years. We examined the data of British Regional Heart Study, which included 1722 men aged 71-92 years and had night-time sleep duration and daytime napping measured at baseline and were followed up for nine years. There were 597 deaths. Compared to night-time sleep at 7-<8 h, age-adjusted hazard ratio of all-cause mortality in participants sleeping <6 h was 1.04 (95% CI 0.80-1.35), 1.07 (0.85-1.34) in 6-<7 h, 1.04 (0.83-1.30) in 8-<9 h and 0.93 (0.65-1.33) in ≥9 h. Further adjustments for other co-variables still showed no association, and neither the association with cardiovascular mortality nor non-cardiovascular mortality. Daytime napping, however, was associated with mortality. After adjustment for age, smoking, physical activity, obesity, cardiovascular diseases, diabetes, frailty, general health, anti-hypertensive medication and C-reactive protein level, hazard ratio of all-cause mortality in participants with daytime napping >1-h versus no napping was 1.62 (1.18-2.22) and hazard ratio of non-cardiovascular mortality was 1.77 (1.22-2.57). The fully adjusted hazard ratio of cardiovascular mortality was not significantly increased 1.26 (0.69-2.28), although age-adjusted hazard ratio was significant 1.94 (1.20-3.16). In the elderly men, daytime napping was independently associated with increased all-cause and non-cardiovascular mortality, while its association with cardiovascular mortality could be explained by cardiovascular risk factors and co-morbidities. Night-time sleep duration was not associated with mortality risk.

Coordination of RNA modifications in the brain and beyond.

Gene expression regulation is a critical process throughout the body, especially in the nervous system. One mechanism by which biological systems regulate gene expression is via enzyme-mediated RNA modifications, also known as epitranscriptomic regulation. RNA modifications, which have been found on nearly all RNA species across all domains of life, are chemically diverse covalent modifications of RNA nucleotides and represent a robust and rapid mechanism for the regulation of gene expression. Although numerous studies have been conducted regarding the impact that single modifications in single RNA molecules have on gene expression, emerging evidence highlights potential crosstalk between and coordination of modifications across RNA species. These potential coordination axes of RNA modifications have emerged as a new direction in the field of epitranscriptomic research. In this review, we will highlight several examples of gene regulation via RNA modification in the nervous system, followed by a summary of the current state of the field of RNA modification coordination axes. In doing so, we aim to inspire the field to gain a deeper understanding of the roles of RNA modifications and coordination of these modifications in the nervous system.

Influence of goals on modular brain network organization during working memory.

Introduction: Top-down control underlies our ability to attend relevant stimuli while ignoring irrelevant, distracting stimuli and is a critical process for prioritizing information in working memory (WM). Prior work has demonstrated that top-down biasing signals modulate sensory-selective cortical areas during WM, and that the large-scale organization of the brain reconfigures due to WM demands alone; however, it is not yet understood how brain networks reconfigure between the processing of relevant versus irrelevant information in the service of WM. Methods: Here, we investigated the effects of task goals on brain network organization while participants performed a WM task that required participants to detect repetitions (e.g., 0-back or 1-back) and had varying levels of visual interference (e.g., distracting, irrelevant stimuli). We quantified changes in network modularity-a measure of brain sub-network segregation-that occurred depending on overall WM task difficulty as well as trial-level task goals for each stimulus during the task conditions (e.g., relevant or irrelevant). Results: First, we replicated prior work and found that whole-brain modularity was lower during the more demanding WM task conditions compared to a baseline condition. Further, during the WM conditions with varying task goals, brain modularity was selectively lower during goal-directed processing of task-relevant stimuli to be remembered for WM performance compared to processing of distracting, irrelevant stimuli. Follow-up analyses indicated that this effect of task goals was most pronounced in default mode and visual sub-networks. Finally, we examined the behavioral relevance of these changes in modularity and found that individuals with lower modularity for relevant trials had faster WM task performance. Discussion: These results suggest that brain networks can dynamically reconfigure to adopt a more integrated organization with greater communication between sub-networks that supports the goal-directed processing of relevant information and guides WM.

Definition of Post-COVID-19 Condition Among Published Research Studies.

This cross-sectional study examines the differing definitions of a post­COVID-19 condition among published studies.

Tissue-engineered vocal fold replacement in swine: Methods for functional and structural analysis.

We have developed a cell-based outer vocal fold replacement (COVR) as a potential therapy to improve voice quality after vocal fold (VF) injury, radiation, or tumor resection. The COVR consists of multipotent human adipose-derived stem cells (hASC) embedded within a three-dimensional fibrin scaffold that resembles vocal fold epithelium and lamina propria layers. Previous work has shown improved wound healing in rabbit studies. In this pilot study in pigs, we sought to develop methods for large animal implantation and phonatory assessment. Feasibility, safety, and structural and functional outcomes of the COVR implant are described. Of eight pigs studied, six animals underwent COVR implantation with harvest between 2 weeks and 6 months. Recovery of laryngeal tissue structure was assessed by vibratory and histologic analyses. Recovery of voice function was assessed by investigating acoustic parameters that were derived specifically for pigs. Results showed improved lamina propria qualities relative to an injured control animal at 6 months. Acoustic parameters reflected voice worsening immediately after surgery as expected; acoustics displayed clear voice recovery in the animal followed for 6 months after COVR. These methods form the basis for a larger-scale long-term pre-clinical safety and efficacy study.

Are There Ultrasound Features to Distinguish Small (<3 cm) Peripheral Renal Angiomyolipomas From Renal Cell Carcinomas?

BACKGROUND: Small echogenic renal masses are usually angiomyolipomas (AMLs), but some renal cell carcinomas (RCCs) can be echogenic and confused with an AML. OBJECTIVES: This is a study to evaluate any distinguishing demographic and sonographic features of small (<3 cm) peripheral AMLs versus peripheral RCCs. METHODS: This is a HIPAA-compliant retrospective review of the demographics and ultrasound features of peripheral renal AMLs compared with a group of peripheral RCCs. All AMLs had confirmation of macroscopic fat as noted on thin-cut CT or fat-saturation MRI sequence images. All RCCs were pathologically proven. Statistical analysis was used to compare findings in the two groups. RESULTS: There were a total of 52 patients with 56 AMLs, compared with 42 patients with 42 RCCs. There were 42 females in the AML group versus 10 females in the RCC group (P < .0001). The AML diameters (15.7 mm × 12.0 mm) were statistically significantly smaller (Plargest = .0085, Psmallest < .001) than the diameters of the RCCs (19.9 mm × 18.5 mm). Ultrasound features found to be statistically different between the two groups were the ratio of the largest dimension to the smallest dimension (P < .001), a lobulated versus smooth margin of the AML (26 vs 30) compared with the RCC group (3 vs 39) (P = .0012), and an "unusual" versus a round shape (P < .001) of the AML group (45 vs 11) compared with the RCC group (9 vs 33). In the multivariable model, the patient sex, margin, and mass shape were predictive of AML, with an area under the receiver operating characteristic curve of 0.92. CONCLUSION: For a small (<3 cm) peripheral echogenic mass in a female patient, a lobulated lesion with an unusual shape is highly predictive of being an AML.

Did the mental health and well-being of young people increase after the COVID-19 vaccination campaign period? A cross-sectional multicentre study in Austria and Turkey.

In 2019, the global Coronavirus (COVID-19) pandemic and associated prevention measures affected the mental health and psychological well-being of young people with and without a migratory background. The present study aimed to compare the mental health and psychological well-being of migrant and non-migrant young people before and after the COVID-19 vaccination campaign period in two countries which had different policies to deal with the pandemic. The "Psychological General Well-being" of young people and their experiences during the pandemic were investigated using an anonymous online survey during two pandemic waves before the vaccination campaign and 6 months after its start. A majority of the 6154 participants (aged between 15 and 25 years in all study groups) reported a decrease of mental health from the time period before the vaccination (BV) to after the vaccination (AV) campaign (b = 0.27, p < .001). This association was higher in females (b = 0.04, p = 0.008) and in youth with financial problems (b = 0.13, p < .001). Furthermore, this decrease was more pronounced in people ≤17 years old (40% to 62%) than in those >17 years (59% to 67%). Contrary to expectation, vulnerable groups such as the economically disadvantaged, younger, and female participants did not experience a significant easing of the pandemic's psychological burden AV. Vaccination campaigns should continue emphasizing the beneficial effects of COVID-19 vaccination on general well-being, but with an acknowledgement that the road to recovery is still a long one. Concurrently, free access to psychological treatment and financial support should be offered, especially for vulnerable groups. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-023-04366-x.

Improvement in executive functioning after Goal-Oriented Attentional Self-Regulation training is associated with reduction in PTSD hyperarousal symptoms among veterans with comorbid PTSD and mild TBI.

Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that combines mindfulness-based attention regulation with individualized goal management strategies to improve functioning in daily life after traumatic brain injury (TBI). While not a specific target of GOALS training, previous research has indicated improvements in emotional functioning following GOALS training, specifically symptoms related to depression and posttraumatic stress disorder (PTSD). The current study is based on the hypothesis that improvements in cognitive control processes related to executive functioning and attention after GOALS training generalize to improvements in emotional functioning, thereby resulting in reductions in emotional distress. The current study analyzed archival data from 33 Veteran participants with a confirmed diagnosis of PTSD and a history of mild TBI who received either GOALS training or a psychoeducational intervention matched for time, therapist attention, and participation format. Regression analysis was used to assess the strength of the relationship between improvements in Overall Attention/Executive Functioning and decreases in hyperarousal symptoms associated with PTSD. Results from the regression analysis revealed that improvements in Overall Attention/Executive Functioning after GOALS was significantly associated with reductions in hyperarousal symptoms associated with PTSD (R2 = 0.26, F(1,15) = 5.01, ß = -.51, p < .05). The current findings suggest that cognitive improvements after GOALS training may lead to changes in emotional functioning, resulting in decreased emotional distress. This is important, particularly in VA settings, because the results potentially highlight additional areas of research and focus on the treatment of comorbid mild TBI and PTSD among Veterans.

Association of air pollution with dementia: a systematic review with meta-analysis including new cohort data from China.

It remains unclear whether a total exposure to air pollution (AP) is associated with an increased risk of dementia. Little is known on the association in low- and middle-income countries. Two cohort studies in China (in Anhui cohort 1402 older adults aged ≥ 60 followed up for 10 years; in Zhejiang cohort 6115 older adults followed up for 5 years) were conducted to examine particulate matter - PM2.5 associated with all dementia and air quality index (AQI) with Alzheimer's disease, respectively. A systematic literature review and meta-analysis was performed following worldwide literature searched until May 20, 2020 to identify 15 population-based cohort studies examining the association of AP with dementia (or any specific type of dementia) through PubMed, MEDLINE, PsycINFO, SocINDEX, CINHAL, and CNKI. The cohort studies in China showed a significantly increased relative risk (RR) of dementia in relation to AP exposure; in Anhui cohort the adjusted RR was 2.14 (95% CI 1.00-4.56) in people with PM2.5 exposure at ≥ 64.5 µg/m3 versus <63.5 µg/m3 and in Zhejiang cohort the adjusted RR was 2.28 (1.07-4.87) in AQI>90 versus ≤ 80. The systematic review revealed that all 15 studies were undertaken in high income countries/regions, with inconsistent findings. While they had reasonably good overall quality of studies, seven studies did not adjust smoking in analysis and 13 did not account for depression. Pooling all eligible data demonstrated that dementia risk increased with the total AP exposure (1.13, 1.08-1.19). Data analysis of air pollutants showed that the RR significantly increased with PM2.5 (1.06, 1.03-1.10 in 2nd tertile exposure; 1.13, 1.07-1.19 in 3rd tertile versus 1st tertile), PM10 (1.05, 0.86-1.29; 1.62, 0.60-4.36), carbon monoxide (1.69, 0.72-3.93; 1.52, 1.35-1.71), nitrogen dioxide (1.06, 1.03-1.09; 1.18, 1.10-1.28) and nitrogen oxides (1.09, 1.04-1.15; 1.26, 1.13-1.41), but not ozone. Controlling air pollution and targeting on specific pollutants would reduce dementia globally.

Atypical presentation of cutaneous meningioma.

Cutaneous meningiomas are rare tumors of ectopic meningeal tissue in the dermis or subcutis and are most commonly located on the scalp and around the eyes, ears, nose, and mouth. We present a case of cutaneous meningioma with an unusual presentation on the upper arm, but with positivity for epithelial membrane antigen to support the diagnosis of meningioma. Lack of pancytokeratin AE1/3 and p63 allowed us to rule out a keratinocytic tumor, such as squamous cell carcinoma and basal cell carcinoma. The absence of smooth muscle actin, FXIIIa, CD163, and CD34 allowed us to rule out a leiomyoma, dermatofibroma, and vascular neoplasm respectively. Weak staining of S100 allowed us to rule out a perineuroma. The purpose of this case report is to increase awareness of a rare presentation of cutaneous meningioma not located within the scalp/face region. This may broaden its inclusion within differential diagnoses of neoplasms of uncertain behavior and encourage correct clinical diagnosis, thus improving treatment outcomes.

A portable and low-cost solution for real-time manipulation of the vestibular sense.

BACKGROUND: The vestibular system encodes head motion in space which is naturally accompanied by other sensory cues. Electrical stimuli, applied across the mastoid processes, selectively activate primary vestibular afferents which has spurred clinical and biomedical applications of electrical vestibular stimulation (EVS). When properly matched to head motion, EVS may also manipulate the closed-loop relationship between actions and vestibular feedback to reveal the mechanisms of sensorimotor recalibration and learning. NEW METHOD: We designed a portable, low-cost real-time EVS system using an Arduino microcontroller programmed through Simulink that provides electrical currents based on head angular motion. We used well-characterized vestibular afferent physiological responses to head angular velocity and electrical current to compute head-motion equivalent of real-time modulatory EVS currents. We also examined if our system induced recalibration of the vestibular system during human balance control. RESULTS: Our system operated at 199.997 Hz ( ± 0.005 Hz) and delivered head-motion-equivalent electrical currents with ∼10 ms delay. The output driving the current stimulator matched the implemented linear model for physiological vestibular afferent dynamics with minimal background noise (<0.2% of ± 10 V range). Participants recalibrated to the modulated closed-loop vestibular feedback using visual cues during standing balance, replicating earlier findings. COMPARISON WITH EXISTING METHODS: EVS is typically used to impose external perturbations that are independent of one's own movement. We provided a solution using open-source hardware to implement a real-time, physiology based, and task-relevant vestibular modulations using EVS. CONCLUSIONS: Our portable, low-cost vestibular modulation system will make physiological closed-loop vestibular manipulations more accessible thus encouraging novel investigations and biomedical applications of EVS.

Rapid Antigen Screening of Students and Staff for SARS-CoV-2 in Rural School Districts, Pierce County, WA, 2020.

During fall 2020 in rural Pierce County, Washington, school districts and the county health department offered weekly rapid antigen screening to students and staff. Asymptomatic screening identified 42.5% of confirmed cases from the population. Parents reported it was a positive experience for their children. The program supported decisions to return to in-person learning, but screening ended because of resource and technical limitations. When planning in-school screening, stakeholder engagement and resource sustainability are important factors to consider. (Am J Public Health. 2022;112(8):1134-1137. https://doi.org/10.2105/AJPH.2022.306875).

Impact of fish consumption on all-cause mortality in older people with and without dementia: a community-based cohort study.

BACKGROUND: Increased fish consumption reduces the risk of dementia. However, it is unknown whether fish consumption reduced all-cause mortality in people with dementia. The purpose of the study is to investigate the association of fish consumption with all-cause mortality in older people with dementia versus those without dementia. METHODS: Using a standard method of the Geriatric Mental State, we interviewed 4165 participants aged ≥ 60 years who were randomly recruited from five provinces in China during 2007-2009 to collect the baseline data of socio-demography, disease risk factors, histories of disease, and details of dietary intakes, and diagnosed dementia (n = 406). They were followed up for vital status until 2012. RESULTS: The cohort follow-up documented 329 deaths; 61 were in participants with dementia (55.3 per 1000 person-years) and 224 were those without dementia (22.3). In all participants, the risk of all-cause mortality was reduced with fish intake at " ≥ twice a week" (multivariate-adjusted hazard ratio 0.58, 95% CI 0.34-0.96) and at "once a week or less" (0.79, 0.53-1.18) compared to "never eat" over the past two years. In participants without baseline dementia, the corresponding HRs for all-cause mortality were 0.57 (0.33-0.98) and 0.85 (0.55-1.31), while in participants with dementia were 1.36 (0.28-6.60) and 1.05 (0.30-3.66), respectively. CONCLUSION: This study reveals that consumption of fish in older age reduced all-cause mortality in older people without dementia, but not in people with dementia. Fish intake should be increased in older people in general, prior to the development of dementia in the hope of preventing dementia and prolonging life.

Possible stochastic sex determination in Bursaphelenchus nematodes.

Sex determination mechanisms evolve surprisingly rapidly, yet little is known in the large nematode phylum other than for Caenorhabditis elegans, which relies on chromosomal XX-XO sex determination and a dosage compensation mechanism. Here we analyze by sex-specific genome sequencing and genetic analysis sex determination in two fungal feeding/plant-parasitic Bursaphelenchus nematodes and find that their sex differentiation is more likely triggered by random, epigenetic regulation than by more well-known mechanisms of chromosomal or environmental sex determination. There is no detectable difference in male and female chromosomes, nor any linkage to sexual phenotype. Moreover, the protein sets of these nematodes lack genes involved in X chromosome dosage counting or compensation. By contrast, our genetic screen for sex differentiation mutants identifies a Bursaphelenchus ortholog of tra-1, the major output of the C. elegans sex determination cascade. Nematode sex determination pathways might have evolved by "bottom-up" accretion from the most downstream regulator, tra-1.

Impact of Older Age Adiposity on Incident Diabetes: A Community-Based Cohort Study in China.

BACKGROUND: Obesity classifications vary globally and the impact of older age adiposity on incident diabetes has not been well-studied. METHODS: We examined a random sample of 2,809 participants aged ≥60 years in China, who were free of diabetes at baseline and were followed up for up to 10 years to document diabetes (n=178). The incidence of diabetes was assessed in relation to different cut-off points of body mass index (BMI) and waist circumference (WC) in multiple adjusted Cox regression models. RESULTS: The diabetic risk in the cohort increased linearly with the continuous and quartile variables of BMI and WC. The BMI-World Health Organization (WHO) and BMI-China criteria analysis did not show such a linear relationship, however, the BMI-Asian/Hong Kong criteria did; adjusted hazards ratio (HR) was 0.42 (95% confidence interval [CI], 0.20 to 0.90) in BMI <20 kg/m2, 1.46 (95% CI, 0.99 to 2.14) in 23-≤26 kg/m2, and 1.63 (95% CI, 1.09 to 2.45) in ≥26 kg/m2. The WC-China criteria revealed a slightly better prediction of diabetes (adjusted HRs were 1.79 [95% CI, 1.21 to 2.66] and 1.87 [95% CI, 1.22 to 2.88] in central obese action levels 1 and 2) than the WC-WHO. The combination of the BMI-Asian/Hong Kong with WC-China demonstrated the strongest prediction. There were no gender differences in the impact of adiposity on diabetes. CONCLUSION: In older Chinese, BMI-Asian/Hong Kong criteria is a better predictor of diabetes than other BMI criterion. Its combination with WC-China improved the prediction of adiposity to diabetes, which would help manage bodyweight in older age to reduce the risk of diabetes.

Propranolol therapy for hemangiomas in infants with neonatal abstinence syndrome may produce intolerable side effects.

We report three infants with infantile hemangioma who experienced severe agitation and diarrhea following propranolol administration. Propranolol, a non-selective ß-adrenergic receptor blocker, is the first-line treatment for infantile hemangiomas. All three infants were exposed to opioids in utero and experienced neonatal abstinence syndrome at birth. We hypothesize that chronic opioid exposure in utero may cause protracted upregulation of ß2-adrenergic receptors in the central nervous system, resulting in increased susceptibility to adverse reactions to propranolol.

Impact of air pollution exposure on the risk of Alzheimer's disease in China: A community-based cohort study.

Alzheimer's disease (AD) is the most common type of dementia. Impact of air pollution (AP) on the risk of AD is unclear. It is unknown which air pollutants are independently associated with AD and whether fish consumption mitigated the association. We carried out a community-based cohort of 6115 participants aged ≥60 years in China to examine the association of PM2.5, PM10, CO, NO2, SO2 and O3 exposure with AD, and differences in the association between people with low and high consumption of fish. The participants were randomly recruited from six counties in Zhejiang province for health survey to document socio-demographic and disease risk factors in 2014, and were followed up to diagnose AD in 2019. A total of 986 cohort members were diagnosed with AD. Based on the daily mean air pollutants monitored in 2013-2015 in the counties, participants were divided into low, middle and high AP exposure groups for subsequent analysis. The multiple adjusted odds ratio (OR) of AD in participants living with the middle and high levels of PM2.5 exposure versus the low exposure were 1.50 (95% CI 0.90-2.50) and 3.92 (2.09-7.37). The increased ORs were also with PM10 (1.74, 0.65-4.64; 3.00, 1.22-7.41) and CO (2.86, 1.32-6.20; 1.19, 0.45-3.18), but not with NO2 (0.63, 0.17-2.27; 0.95, 0.28-3.19), SO2 (0.44, 0.19-1.001; 1.21, 0.56-2.62), and O3 (0.38, 0.20-0.74; 0.50, 0.21-1.21). There were no significant interaction effects of AP with fish consumption on AD. However, participants with low consumption of fish appeared to have higher ORs in PM2.5 exposure (1.80, 1.39-2.33; 5.18, 3.93-6.82) than those high consumption (1.38, 0.78-2.47; 2.89, 1.50-5.59). Our findings of PM2.5, PM10 and CO exposure significantly increased the risk of AD and the potential mitigating effect of fish consumption on the association provide evidence for developing effective strategies for AD reduction and air pollution control.

Modeling the α-max capacity of transportation networks: a single-level mathematical programming formulation.

Network capacity, defined as the largest sum of origin-destination (O-D) flows that can be accommodated by the network based on link performance function and traffic equilibrium assignment, is a critical indicator of network-wide performance assessment in transportation planning and management. The typical modeling rationale of estimating network capacity is to formulate it as a mathematical programming (MP), and there are two main approaches: single-level MP formulation and bi-level programming (BLP) formulation. Although single-level MP is readily solvable, it treats the transportation network as a physical network without considering level of service (LOS). Albeit BLP explicitly models the capacity and link LOS, solving BLP in large-scale networks is challenging due to its non-convexity. Moreover, the inconsideration of trip LOS makes the existing models difficult to differentiate network capacity under various traffic states and to capture the impact of emerging trip-oriented technologies. Therefore, this paper proposes the α-max capacity model to estimate the maximum network capacity under trip or O-D LOS requirement α. The proposed model improves the existing models on three aspects: (a) it considers trip LOS, which can flexibly estimate the network capacity ranging from zero to the physical capacity including reserve, practical and ultimate capacities; (b) trip LOS can intuitively reflect users' maximum acceptable O-D travel time or planners' requirement of O-D travel time; and (c) it is a convex and tractable single-level MP. For practical use, we develop a modified gradient projection solution algorithm with soft constraint technique, and provide methods to obtain discrete trip LOS and network capacity under representative traffic states. Numerical examples are presented to demonstrate the features of the proposed model as well as the solution algorithm.