Neural landscape is associated with functional outcomes in irradiated patients with oropharyngeal squamous cell carcinoma.

The incidence of human papilloma virus-mediated oropharyngeal squamous cell carcinoma (OPSCC) has increased over the past 40 years, particularly among young individuals with a favorable prognosis; however, current therapy often leads to unfortunate side effects, such as dysphagia. Despite the emphasis on dysphagia in previous studies, there is an important research gap in understanding the correlation between neuronal changes and patient-reported and functional outcomes in patients with OPSCC. To address this issue, we examined pathologic tissue samples from patients with OPSCC using multiplex immunofluorescence staining and machine learning to correlate tumor-associated neuronal changes with prospectively collected patient-reported and functional outcomes. We found that tumor enrichment of adrenergic (TH+) and CGRP+ sensory-afferent nerves correlated with poorer swallowing outcomes. Functional electromyography recordings showed correlations between growing (GAP43+) and immature cholinergic (ChAT+DCX+) nerves and denervation patterns in survivors of OPSCC. A murine model of radiation-induced dysphagia further confirmed that immature cholinergic and CGRP+ nerves were correlated with impaired swallowing. Preclinical interventional studies also supported the independent contributions of CGRP+ and cholinergic (ChAT+) nerves to dysphagia in treated mouse models of OPSCC. Our results suggest that CGRP+ and ChAT+ neuronal signaling play distinct roles in tumor- and radiation-induced dysphagia in OPSCC and offer a comprehensive dataset on the neural landscape of OPSCC. These insights may guide early interventions for swallow preservation and the repurposing of neurology-related drugs, such as CGRP blockers, in clinical oncology and survivorship.

Bright and Fast Emission from Robust Supramolecular J-Aggregate Nanostructures through Silica-Encapsulation.

We introduce a two-step silica-encapsulation procedure to optimize both the optical efficiency and structural robustness of 5,5',6,6'-tetrachloro-1,1'-diethyl-3,3'-di(4-sulfobutyl)-benzimidazolocarbocyanine (TDBC), a two-dimensional sheet-like J-aggregate. We report a fluorescence quantum yield of ∼98%, the highest quantum yield recorded for any J-aggregate structure at room temperature, and a fast, emissive lifetime of 234 ps. Silica, as an encapsulating matrix, provides optical transparency, chemical inertness, and robustness to dilution, while rigidifying the J-aggregate structure. Our in situ encapsulation process preserves the excitonic structure in TDBC J-aggregates, maintaining their light absorption and emission properties. The homogeneous silica coating has an average thickness of 0.5-1 nm around J-aggregate sheets. Silica encapsulation permits extensive dilutions of J-aggregates without significant disintegration into monomers. The narrow absorbance and emission line widths exhibit further narrowing upon cooling to 79 K, which is consistent with J-type coupling in the encapsulated aggregates. This silica TDBC J-aggregate construct signifies (1) a bright, fast, and robust fluorophore system, (2) a platform for further manipulation of J-aggregates as building blocks for integration with other optical materials and structures, and (3) a system for fundamental studies of exciton delocalization, transport, and emission dynamics within a rigid matrix.

Drug Screening Using Normal Cell and Cancer Cell Mixture in an Automated 3D Cell Culture System.

Three-dimensional (3D) cell culture creates a more physiologically relevant environment for enhanced drug screening capabilities using microcarriers. An automated 3D system that integrates robotic manipulators, liquid handling systems, sensors, and environment control systems has the capacity to handle multiple samples in parallel, perform repetitive tasks, and provide real-time monitoring and analysis. This chapter describes a potential 3D cell culture drug screening model by combining renal proximal tubule cells as a representative normal cell line with cancer cell lines. This combination is subjected to drug screening to evaluate the drug's efficacy in suppressing cancer cells while minimizing impact on normal cells with the added benefit of having the ability to separate the two cell types by magnetic isolation for high content screens including mass spectrometry-based proteomics. This study presents advancements in 3D cell culture techniques, emphasizing the importance of automation and the potential of microcarriers in drug screening and disease modeling.

Frailty progression in adults aged 40 years and older in rural Burkina Faso: a longitudinal, population-based study.

BACKGROUND: Little is known about ageing and frailty progression in low-income settings. We aimed to describe frailty changes over time in individuals living in rural Burkina Faso and to assess which sociodemographic, disability, and multimorbidity factors are associated with frailty progression and mortality. METHODS: This longitudinal, population-based study was conducted at the Nouna Health and Demographic Surveillance Systems (HDSS) site in northwestern Burkina Faso. Eligible participants were aged 40 years or older and had been primarily resident in a household within the HDSS area for at least the past 6 months before the baseline survey and were selected from the 2015 HDSS household census using a stratified random sample of adults living in unique households within the area. Participants were interviewed in their homes in 2018 (baseline), 2021 (follow-up), or both. We derived the Fried frailty score for each participant at each timepoint using data on grip strength, gait speed, self-reported weight loss, self-reported exhaustion, and physical activity, and described changes in frailty status (no frailty, pre-frailty, or frailty) between 2018 and 2021. We used multivariate regression models to assess factors (ie, sex, age, marital status, educational attainment, wealth quintile, WHO Disability Assessment Schedule (WHODAS) score, and multimorbidity) associated with frailty progression (either worsening frailty status or dying, compared with frailty status remaining the same or improving) and with mortality, and developed sequential models: unadjusted, adjusting for sociodemographic factors (sex, age, marital status, educational attainment, and wealth quintile), and adjusting for sociodemographic factors, disability, and multimorbidity. FINDINGS: Between May 25 and July 19, 2018, and between July 1 and Aug 22, 2021, 5952 individuals were invited to participate: 1709 (28·7%) did not consent, 1054 (17·8%) participated in 2018 only and were lost to follow-up, 1214 (20·4%) participated in 2021 only, and 1975 (33·2%) were included in both years or died between years. Of 1967 participants followed up with complete demographic data, 190 (9·7%) were frail or unable to complete the frailty assessment in 2018, compared with 77 (3·9%) in 2021. Between 2018 and 2021, frailty status improved in 567 (28·8%) participants and worsened in 327 (16·6%), and 101 (5·1%) participants died. The relative risk of frailty status worsening or of dying (compared with frailty impRoving or no change) increased with age and WHODAS score, whereas female sex appeared protective. After controlling for all sociodemographic factors, multimorbidity, and WHODAS score, odds of mortality were 1·07 (odds ratio 2·07, 95% CI 1·05-4·09) times higher among pre-frail individuals and 1·1 (2·21, 0·90-5·41) times higher among frail individuals than among non-frail individuals. INTERPRETATION: Frailty status was highly dynamic in this low-income setting and appears to be modifiable. Given the rapid increase in the numbers of older adults in low-income or middle-income countries, understanding the behaviour of frailty in these settings is of high importance for the development of policies and health systems to ensure the maintenance of health and wellbeing in ageing populations. Future work should focus on designing context-appropriate interventions to improve frailty status. FUNDING: Alexander Von Humboldt Foundation, Institute for Global Innovation, University of Birmingham, and Wellcome Trust.

National Population Growth Rate, Its Components, and Subnational Contributions: A Research Note.

A population's current growth rate is determined jointly by changes in fertility, mortality, and migration. This overall growth rate is also the average of age-specific growth rates, which can be decomposed into the result of historical changes in fertility, mortality, and migration. However, doing so requires more than 100 years of historical data, meaning that such analyses are possible only in a select few populations. In this research note, we propose an adapted version of the variable-r model to measure contributions to the population growth rate for countries with shorter demographic series. In addition, we extend this model to explore the contribution of subnational changes to the national population growth rate. Our results demonstrate that the age-specific growth rates obtained from short historical series, say 25 years, closely match those of the longer series. These abbreviated age-specific growth rates closely resemble the growth rate at birth of their respective cohorts, which is the major determinant of population growth, except at older ages where mortality becomes the main explanatory element. Exploring subnational populations, we find considerable heterogeneity in the age profile of the components of growth and find that the most populous regions tend to have an outsized impact on national-level growth.

Inequalities in Mortality in the Asia-Pacific: A Cross-National Comparison of Socioeconomic Gradients.

OBJECTIVES: Social inequalities in mortality are poorly studied in much of the Asia-Pacific. Using data from harmonized nationally representative longitudinal health and aging surveys our study systematically assesses mortality disparities across 3 standardized measures of socioeconomic status in 7 Asia-Pacific countries. METHODS: We used data from multiple waves of 7 representative sample surveys: the Health, Income and Labour Dynamics in Australia survey, China Health and Retirement Longitudinal Study, the Indonesian Family Life Survey, the New Zealand Health, Work and Retirement survey, the Korean Longitudinal Study on Ageing and the Health, Aging and Retirement in Thailand survey, and the Japanese Study of Aging and Retirement. We use Cox proportional hazards modeling to examine how the hazard of mortality differs across domains of social stratification including educational attainment, wealth, and occupational status across countries. RESULTS: We found consistent and pervasive gradients in mortality risk in the high-income countries by all available measures of social stratification. In contrast, patterns of inequality in adult mortality in middle-income and recently transitioned high-income countries investigated varied depending on the measure of social stratification, with strong gradients by wealth but mixed gradients by education. DISCUSSION: Analyzing social gradients in mortality in the Asia-Pacific shows that inequalities, especially wealth-based inequalities, in later-life health are present across the region, and that the magnitude of social gradients in mortality is overall larger in high-income countries as compared to middle-income countries.

Disability and morbidity among US birth cohorts, 1998-2018: A multidimensional test of dynamic equilibrium theory.

A substantial body of prior research has explored patterns of disability-free and morbidity-free life expectancy among older populations. However, these distinct facets of later-life health are almost always studied in isolation, even though they are very likely to be related. Using data from the US Health and Retirement Study and a multistate life table approach, this paper explores the interactions between disability, morbidity, and mortality by sex and education among four successive US birth cohorts, born from 1914 to 1923 to 1944-1953 and compared in the periods 1998-2008 and 2008-2018. We find little compression of disability but a marked expansion of morbidity across cohorts. However, disability-free life expectancy (DFLE) among those living with chronic morbidities has increased, even though at the population-level DFLE is largely unchanged. Broadly, these patterns suggest that successive cohorts of older populations in the US are experiencing a dynamic equilibrium, where the link between chronic morbidities and disability has weakened over successive cohorts. Investigating patterns by educational attainment, we find marked disparities where the least educated individuals not only live significantly fewer years free of disabilities or chronic morbidities but also have experienced an expansion in morbidity and disability. Our findings suggest that the future trajectory of disability-free life expectancy in the US is increasingly contingent on efforts to improve disease management and control the severe consequences of chronic morbidities.

Decomposition of Differentials in Health Expectancies From Multistate Life Tables: A Research Note.

Multistate modeling is a commonly used method to compute healthy life expectancy. However, there is currently no analytical method to decompose the components of differentials in summary measures calculated from multistate models. In this research note, we propose a derivative-based method to decompose the differentials in population-based health expectancies estimated via a multistate model into two main components: the proportion resulting from differences in initial health structure and the proportion resulting from differences in health transitions. We illustrate the method using data on activities of daily living from the U.S. Health and Retirement Study to decompose the sex differential in disability-free life expectancy (HLE) among older Americans. Our results suggest that the sex gap in HLE results primarily from differences in transition rates between disability states rather than from the initial health distribution of female and male populations. The methods introduced here will enable researchers, including those working in fields other than health, to decompose the relative contribution of initial population structure and transition probabilities to differences in state-specific life expectancies from multistate models.

A growing divide: Trends in social inequalities in healthy longevity in Australia, 2001-20.

This study examines two decades of change in social inequalities in life and health expectancy among older adults in Australia, one of the few countries that escaped an economic recession during the global financial crisis. We compare adults aged 45+ across three measures of individual socio-economic position-education, occupation, and household wealth-and use multistate life tables to estimate total life expectancy (TLE) and life expectancy free of limiting long-term illness (LLTI-free LE) based on 20 waves of the Household, Income and Labour Dynamics in Australia Survey (2001-20). Our findings highlight substantial social disparities in both TLE and LLTI-free LE in Australia. Grouping individuals by household wealth shows striking differentials in LLTI-free LE. We observe widening social disparities in healthy longevity over time by all three measures of socio-economic position. This diverging trend in healthy longevity is troubling against the backdrop of widening income and wealth inequalities in Australia.

Publication Rate of Abstracts Presented at the 2011-2019 Society for Education in Anesthesia Meetings.

Introduction: The Society for Education in Anesthesia (SEA) promotes dissemination of discoveries and innovations. We investigated the rate of publication of SEA Spring Meeting abstracts, hypothesizing that Research abstracts were published more frequently than Innovative Curriculum abstracts. We also studied the time between abstract presentation and publication and tracked the journals in which they were published. Methods: All abstracts presented at SEA spring meetings from 2011-2019 were included. We searched PubMed for published articles that were based on those SEA abstracts. We calculated the overall publication rate and the respective publication rates for Research and Innovative Curriculum abstracts. We calculated odds ratio (OR) and performed the Pearson χ2 test to compare publication rates between Research abstracts and Innovative Curriculum abstracts. We calculated the mean number of years between meeting presentation and publication and tabulated the number of works published in each journal. Results: A total of 351 abstracts (128 Research and 223 Curriculum) were presented at SEA spring meetings. The overall publication rate was 15% (52/351). Research abstracts were published more frequently than Curriculum abstracts: 24.2% (31/128) versus 9.4% (21/223); OR = 3.1 (95% confidence interval, 1.7-5.6); P = .0003. The mean time from presentation to publication was 1.7 ± 1.3 years. The works appeared in 20 different journals. Conclusion: SEA Spring Meeting abstracts were published less frequently than abstracts from other medical professional society meetings (21%-72.3%). Although the lower publication rate of Innovative Curriculum abstracts unique to the SEA meeting largely explains this shortfall, a relatively low publication rate, even for the Research abstracts, signals opportunities for growth.

Lead Halide Perovskite Nanocrystals with Low Inhomogeneous Broadening and High Coherent Fraction through Dicationic Ligand Engineering.

Lead halide perovskite nanocrystals (LHP NCs) are an emerging materials system with broad potential applications, including as emitters of quantum light. We apply design principles aimed at the structural optimization of surface ligand species for CsPbBr3 NCs, leading us to the study of LHP NCs with dicationic quaternary ammonium bromide ligands. Through the selection of linking groups and aliphatic backbones guided by experiments and computational support, we demonstrate consistently narrow photoluminescence line shapes with a full-width-at-half-maximum below 70 meV. We observe bulk-like Stokes shifts throughout our range of particle sizes, from 7 to 16 nm. At cryogenic temperatures, we find sub-200 ps lifetimes, significant photon coherence, and the fraction of photons emitted into the coherent channel increasing markedly to 86%. A 4-fold reduction in inhomogeneous broadening from previous work paves the way for the integration of LHP NC emitters into nanophotonic architectures to enable advanced quantum optical investigation.

Impact of diabetes on longevity and disability-free life expectancy among older South African adults: A prospective longitudinal analysis.

AIMS: We seek to understand the coexisting effects of population aging and a rising burden of diabetes on healthy longevity in South Africa. METHODS: We used longitudinal data from the 2015 and 2018 waves of the "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI) study to explore life expectancy (LE) and disability-free life expectancy (DFLE) of adults aged 45 and older with and without diabetes in rural South Africa. We estimated LE and DFLE by diabetes status using Markov-based microsimulation. RESULTS: We find a clear gradient in remaining LE and DFLE based on diabetes status. At age 45, a man without diabetes could expect to live 7.4 [95% CI 3.4 - 11.7] more years than a man with diabetes, and a woman without diabetes could expect to live 3.9 [95% CI: 0.8 - 6.9] more years than a woman with diabetes. Individuals with diabetes lived proportionately more years subject to disability than individuals without diabetes. CONCLUSIONS: We find large and important decrements in disability-free aging for people with diabetes in South Africa. This finding should motivate efforts to strengthen prevention and treatment efforts for diabetes and its complications for older adults in this setting.

Factors affecting providers' comfort and fear during intubations of patients with COVID-19.

BACKGROUND: Providers performing endotracheal intubation are at high risk of contracting SARS-CoV-2. The objective was to assess various demographic, exposure and institutional preparedness factors affecting intubators' comfort and fear level during COVID-19 intubations. METHODS: We conducted a cross-sectional, survey-based study during the COVID-19 pandemic from September 2020 to January 2021 at a single academic medical centre in Washington, DC, USA. Inclusion criteria were healthcare providers who had an experience in intubating patients confirmed with or suspected of COVID-19. The survey assessed various factors related to the providers' comfort with intubation and fear during COVID-19 intubations. RESULTS: A total of 329 surveys from 55 hospitals were analysed. Of the respondents, 173 (52.6%) were from emergency medicine providers. Factors that were associated with a higher comfort level of intubating patients with COVID-19 included attending physician position (adjusted OR (aOR)=2.6, 95% CI 1.4 to 4.8; p=0.003), performing more than 20 COVID-19 intubations (aOR=3.3, 95% CI 1.5 to 6.6; p=0.002), participation in an intubation team (aOR=1.6, 95% CI 1.1 to 2.7; p=0.031) and adequate levels of personal protective equipment (PPE) (aOR=4.3, 95% CI 2.0 to 8.8; p<0.0005). Compared with emergency physicians, anaesthesiology providers had higher fear levels of contracting SARS-CoV-2 during both first and subsequent SARS-CoV-2 intubations (first: OR=1.7, 95% CI 1.1 to 2.6, p=0.006; subsequent: OR=2.0, 95% CI 1.4 to3.2, p<0.0005). CONCLUSION: A higher degree of comfort in intubating patients suspected of or confirmed with COVID-19 was demonstrated in more senior physicians, members of intubation teams, providers who performed a higher number of intubations and providers who reported adequate PPE. These findings highlight potential targets for improving the experience of providers in this setting.

Differences in healthy longevity by HIV status and viral load among older South African adults: an observational cohort modelling study.

BACKGROUND: The population of people living with HIV in South Africa is rapidly ageing due to increased survivorship attributable to antiretroviral therapy (ART). We sought to understand how the combined effects of HIV and ART have led to differences in healthy longevity by HIV status and viral suppression in this context. METHODS: In this observational cohort modelling study we use longitudinal data from the 2015 baseline interview (from Nov 13, 2014, to Nov 30, 2015) and the 2018 longitudinal follow-up interview (from Oct 12, 2018, to Nov 7, 2019) of the population-based study Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) to estimate life expectancy and disability-free life expectancy (DFLE) of adults aged 40 years and older in rural South Africa. Respondents who consented to HIV testing, responded to survey questions on disability, and who were either interviewed in both surveys or who died between survey waves were included in the analysis. We estimate life expectancy and DFLE by HIV status and viral suppression (defined as <200 copies per mL) using Markov-based microsimulation. FINDINGS: Among the 4322 eligible participants from the HAALSI study, we find a clear gradient in remaining life expectancy and DFLE based on HIV serostatus and viral suppression. At age 45 years, the life expectancy of a woman without HIV was 33·2 years (95% CI 32·0-35·0), compared with 31·6 years (29·2-34·1) a woman with virally suppressed HIV, and 26·4 years (23·1-29·1) for a woman with unsuppressed HIV; life expectancy for a 45 year old man without HIV was 27·2 years (25·8-29·1), compared with 24·1 years (20·9-27·2) for a man with virally suppressed HIV, and 17·4 years (15·0-20·3) for a man with unsuppressed HIV. Men and women with viral suppression could expect to live nearly as many years of DFLE as HIV-uninfected individuals at ages 45 years and 65 years. INTERPRETATION: These results highlight the tremendous benefits of ART for population health in high-HIV-prevalence contexts and reinforce the need for continued work in making ART treatment accessible to ageing populations. FUNDING: National Institutes of Health.

Increasing Robustness of Brain-Computer Interfaces Through Automatic Detection and Removal of Corrupted Input Signals.

For brain-computer interfaces (BCIs) to be viable for long-term daily usage, they must be able to quickly identify and adapt to signal disruptions. Furthermore, the detection and mitigation steps need to occur automatically and without the need for user intervention while also being computationally tractable for the low-power hardware that will be used in a deployed BCI system. Here, we focus on disruptions that are likely to occur during chronic use that cause some recording channels to fail but leave the remaining channels unaffected. In these cases, the algorithm that translates recorded neural activity into actions, the neural decoder, should seamlessly identify and adjust to the altered neural signals with minimal inconvenience to the user. First, we introduce an adapted statistical process control (SPC) method that automatically identifies disrupted channels so that both decoding algorithms can be adjusted, and technicians can be alerted. Next, after identifying corrupted channels, we demonstrate the automated and rapid removal of channels from a neural network decoder using a masking approach that does not change the decoding architecture, making it amenable for transfer learning. Finally, using transfer and unsupervised learning techniques, we update the model weights to adjust for the corrupted channels without requiring the user to collect additional calibration data. We demonstrate with both real and simulated neural data that our approach can maintain high-performance while simultaneously minimizing computation time and data storage requirements. This framework is invisible to the user but can dramatically increase BCI robustness and usability.

Expansion, Compression, Neither, Both? Divergent Patterns in Healthy, Disability-Free, and Morbidity-Free Life Expectancy Across U.S. Birth Cohorts, 1998-2016.

This article explores how patterns of health, morbidity, and disability have changed across successive generations of older adults in the United States. Using a novel method for comparing state-specific partial life expectancies-that is, total life expectancy (LE), and health expectancies (HEs) in different health states, bounded between two ages-I explore changes in healthy life expectancy across successive birth cohorts of the U.S. population. Results show that little compression of disability is occurring across cohorts, LE with chronic morbidities has expanded considerably, and self-rated health is improving across cohorts, but only at ages 70+. These findings suggest that successive cohorts in the U.S. population may be on divergent paths in terms of late-life health and well-being. Exploring heterogeneity in these patterns, I find that less educated individuals have substantially lower partial LE and disability-free LE than those with more schooling, and that disability-free life is declining among those with less than a high school diploma. Differences in HEs are pervasive across racial and ethnic groups, and both disabled LE and unhealthy LE are expanding in some disadvantaged subgroups. The continued increases in partial LE with morbidities across successive cohorts, and the broad stagnation of disability-free and healthy LE, present a broad view of a U.S. population in which successive generations are not living healthier lives.

Bright, Magnetic NIR-II Quantum Dot Probe for Sensitive Dual-Modality Imaging and Intensive Combination Therapy of Cancer.

Improving the effectiveness of cancer therapy will require tools that enable more specific cancer targeting and improved tumor visualization. Theranostics have the potential for improving cancer care because of their ability to serve as both diagnostics and therapeutics; however, their diagnostic potential is often limited by tissue-associated light absorption and scattering. Herein, we develop CuInSe2@ZnS:Mn quantum dots (QDs) with intrinsic multifunctionality that both enable the accurate localization of small metastases and act as potent tumor ablation agents. By leveraging the growth kinetics of a ZnS shell on a biocompatible CuInSe2 core, Mn doping, and folic acid functionalization, we produce biocompatible QDs with high near-infrared (NIR)-II fluorescence efficiency up to 31.2%, high contrast on magnetic resonance imaging (MRI), and preferential distribution in 4T1 breast cancer tumors. MRI-enabled contrast of these nanoprobes is sufficient to timely identify small metastases in the lungs, which is critically important for preventing cancer spreading and recurrence. Further, exciting tumor-resident QDs with NIR light produces both fluorescence for tumor visualization through radiative recombination pathways as well as heat and radicals through nonradiative recombination pathways that kill cancer cells and initiate an anticancer immune response, which eliminates tumor and prevents tumor regrowth in 80% of mice.

Life Course Socioeconomic Status and Healthy Longevity in China.

In 2020, China's population aged 60 or older exceeded 264 million, representing 25% of the global population in that age-group. Older adults in China experienced periods of dramatic political and social unrest in early life, as well as economic transformations leading to drastic improvements in living standards during adulthood and older age. However, the implications of life course socioeconomic status (SES) trajectories for healthy longevity in later life have not been systematically studied in China. We utilize data from the China Health and Retirement Longitudinal Study (CHARLS) to comprehensively investigate how early-life conditions and adult SES combine to influence healthy longevity in later life. We find that both childhood and adulthood SES are associated with late-life health. The largest disparities in life expectancy (LE) and disability-free LE are found between those with persistently low SES throughout life and those with consistently high SES. At age 45, the gap in total LE between the most advantaged and least advantaged groups is six years for men and five years for women. Despite China's major policy changes prioritizing equity in income and health care in recent decades, our findings suggest that dramatic health inequalities among older adults remain. Our findings extend the literature on the effect of socioeconomic patterns across the life course on gradients in later-life health and highlight continuing disparities in healthy longevity among older adults in China.

Outcomes after definitive surgery for mandibular osteoradionecrosis.

OBJECTIVES: To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN). MATERIALS AND METHODS: Retrospective analysis of 76 patients who underwent segmental mandibulectomy with reconstruction from 2000 to 2009. RESULTS: Complications occurred in 49 (65%) patients and were associated with preoperative drainage (odds ratio [OR] 4.40, 95% confidence interval [CI] 1.01-19.27). The adjusted median charge was $343 000, and higher charges were associated with double flap reconstruction (OR 8.15, 95% CI 2.19-30.29) and smoking (OR 5.91, 95% CI 1.69-20.72). Improved swallow was associated with age <67 years (OR 3.76, 95% CI 1.16-12.17) and preoperative swallow (OR 3.42, 95% CI 1.23-9.51). Five-year ORN-recurrence-free survival was 93% while overall survival was 63% and associated with pulmonary disease (HR [hazard ratio] 3.57, 95% CI 1.43-8.94). CONCLUSIONS: Although recurrence of ORN is rare, surgical complications are common and charges are high. Poorer outcomes and higher charges are associated with preoperative factors.

The Components of Change in Population Growth Rates.

The demographic balance equation relates the population growth rate with crude rates of fertility, mortality, and net migration. All these rates refer to changes occurring between two time points, say, t and t + h. However, this fundamental balance equation overlooks the contribution of historical fertility, mortality, and migration in explaining these population counts. Because of this, the balance equation only partially explains a change in growth rate between time t and t + h as it does not include the contribution of historical population trends in shaping the population at time t. The overall population growth rate can also be expressed as the weighted average of age-specific growth rates. In this article, we develop a method to decompose the historical drivers of current population growth by recursively employing the variable-r method on the population's average age-specific growth rates. We illustrate our method by identifying the unique contributions of survival progress, migration change, and fertility decline for current population growth in Denmark, England and Wales, France, and the United States. Our results show that survival progress is mainly having an effect on population growth at older ages, although accounting for indirect historical effects illuminates additional contributions at younger ages. Migration is particularly important in Denmark and England and Wales. Finally, we find that across all populations studied, historical fertility decline plays the largest role in shaping recent reductions in population growth rates.