Restoring the Sense of Touch Using a Sensorimotor Demultiplexing Neural Interface.

Paralyzed muscles can be reanimated following spinal cord injury (SCI) using a brain-computer interface (BCI) to enhance motor function alone. Importantly, the sense of touch is a key component of motor function. Here, we demonstrate that a human participant with a clinically complete SCI can use a BCI to simultaneously reanimate both motor function and the sense of touch, leveraging residual touch signaling from his own hand. In the primary motor cortex (M1), residual subperceptual hand touch signals are simultaneously demultiplexed from ongoing efferent motor intention, enabling intracortically controlled closed-loop sensory feedback. Using the closed-loop demultiplexing BCI almost fully restored the ability to detect object touch and significantly improved several sensorimotor functions. Afferent grip-intensity levels are also decoded from M1, enabling grip reanimation regulated by touch signaling. These results demonstrate that subperceptual neural signals can be decoded from the cortex and transformed into conscious perception, significantly augmenting function.

Sensitization of silicon by singlet exciton fission in tetracene.

Silicon dominates contemporary solar cell technologies1. But when absorbing photons, silicon (like other semiconductors) wastes energy in excess of its bandgap2. Reducing these thermalization losses and enabling better sensitivity to light is possible by sensitizing the silicon solar cell using singlet exciton fission, in which two excited states with triplet spin character (triplet excitons) are generated from a photoexcited state of higher energy with singlet spin character (a singlet exciton)3-5. Singlet exciton fission in the molecular semiconductor tetracene is known to generate triplet excitons that are energetically matched to the silicon bandgap6-8. When the triplet excitons are transferred to silicon they create additional electron-hole pairs, promising to increase cell efficiencies from the single-junction limit of 29 per cent to as high as 35 per cent9. Here we reduce the thickness of the protective hafnium oxynitride layer at the surface of a silicon solar cell to just eight angstroms, using electric-field-effect passivation to enable the efficient energy transfer of the triplet excitons formed in the tetracene. The maximum combined yield of the fission in tetracene and the energy transfer to silicon is around 133 per cent, establishing the potential of singlet exciton fission to increase the efficiencies of silicon solar cells and reduce the cost of the energy that they generate.

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.

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.

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.

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.

Changes in Life Expectancy and Disability-Free Life Expectancy in Successive Birth Cohorts of Older Cancer Survivors: A Longitudinal Modeling Analysis of the US Health and Retirement Study.

The population of older cancer survivors in the United States is rapidly growing. However, little is currently known about how the health of older cancer survivors has changed over time and across successive birth cohorts. Using data from the US Health and Retirement Study, we parameterized a demographic microsimulation model to compare partial cohort life expectancy (LE) and disability-free LE for US men and women without cancer and with prevalent and incident cancer diagnoses for 4 successive 10-year birth cohorts, born 1918-1927 to 1948-1957. Disability was defined as being disabled in ≥1 activity of daily living. These cohorts had midpoint ages of 55-64, 65-74, and 75-84 years during the periods 1998-2008 (the "early" period) and 2008-2018 (the "later" period). Across all cohorts and periods, those with incident cancer had the lowest LE, followed by those with prevalent cancer and cancer-free individuals. We observed declines in partial LE and an expansion of life spent disabled among more recent birth cohorts of prevalent-cancer survivors. Our findings suggest that advances in treatments that prolong life for individual cancer patients may have led to population-level declines in conditional LE and disability-free LE across successive cohorts of older cancer survivors.

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.

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.

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.

Developing and evaluating a frailty index for older South Africans-findings from the HAALSI study.

BACKGROUND: despite rapid population ageing, few studies have investigated frailty in older people in sub-Saharan Africa. We tested a cumulative deficit frailty index in a population of older people from rural South Africa. METHODS: analysis of cross-sectional data from the Health and Ageing in Africa: Longitudinal Studies of an INDEPTH Community (HAALSI) study. We used self-reported diagnoses, symptoms, activities of daily living, objective physiological indices and blood tests to calculate a 32-variable cumulative deficit frailty index. We fitted Cox proportional hazards models to test associations between frailty category and all-cause mortality. We tested the discriminant ability of the frailty index to predict one-year mortality alone and in addition to age and sex. RESULTS: in total 3,989 participants were included in the analysis, mean age 61 years (standard deviation 13); 2,175 (54.5%) were women. The median frailty index was 0.13 (interquartile range 0.09-0.19); Using population-specific cutoffs, 557 (14.0%) had moderate frailty and 263 (6.6%) had severe frailty. All-cause mortality risk was related to frailty severity independent of age and sex (hazard ratio per 0.01 increase in frailty index: 1.06 [95% confidence interval 1.04-1.07]). The frailty index alone showed moderate discrimination for one-year mortality: c-statistic 0.68-0.76; combining the frailty index with age and sex improved performance (c-statistic 0.77-0.81). CONCLUSION: frailty measured by cumulative deficits is common and predicts mortality in a rural population of older South Africans. The number of measures needed may limit utility in resource-poor settings.

Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green.

Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000-2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.

Scalable Synthesis of InAs Quantum Dots Mediated through Indium Redox Chemistry.

Next-generation optoelectronic applications centered in the near-infrared (NIR) and short-wave infrared (SWIR) wavelength regimes require high-quality materials. Among these materials, colloidal InAs quantum dots (QDs) stand out as an infrared-active candidate material for biological imaging, lighting, and sensing applications. Despite significant development of their optical properties, the synthesis of InAs QDs still routinely relies on hazardous, commercially unavailable precursors. Herein, we describe a straightforward single hot injection procedure revolving around In(I)Cl as the key precursor. Acting as a simultaneous reducing agent and In source, In(I)Cl smoothly reacts with a tris(amino)arsenic precursor to yield colloidal InAs quantitatively and at gram scale. Tuning the reaction temperature produces InAs cores with a first excitonic absorption feature in the range of 700-1400 nm. A dynamic disproportionation equilibrium between In(I), In metal, and In(III) opens up additional flexibility in precursor selection. CdSe shell growth on the produced cores enhances their optical properties, furnishing particles with center emission wavelengths between 1000 and 1500 nm and narrow photoluminescence full-width at half-maximum (FWHM) of about 120 meV throughout. The simplicity, scalability, and tunability of the disclosed precursor platform are anticipated to inspire further research on In-based colloidal QDs.

Oropharyngeal hemorrhage in patients with COVID-19: A multi-institutional case series.

BACKGROUND: Patients with COVID-19 who are intubated and require mechanical ventilation have been observed to have oropharyngeal bleeding necessitating otolaryngology intervention. METHODS: We report five cases of oropharyngeal hemorrhage in COVID-19 patients on mechanical ventilation requiring evaluation by otolaryngologists at George Washington University Hospital (GWUH) and Boston Medical Center (BMC) from March to April 2020. Institutional Review Board at both institutions exempted this study from informed consent because there were no identifiable patient characteristics, photographs, or imaging studies included. RESULTS: All five patients were managed conservatively; four required packing with Kerlix gauze by an otolaryngologist. Two patients had the additional requirement of extracorporeal membrane oxygenation (ECMO) and associated anticoagulation. Three patients improved with oropharyngeal packing; two had persistent bleeding. Three patients expired. Endotracheal tubes were repositioned less frequently due to the COVID-19 pandemic. CONCLUSIONS: Intubated patients with COVID-19 may have an increased risk of oropharyngeal hemorrhage. This may be due to anticoagulation, prolonged intubation, or decreased frequency of endotracheal tube repositioning. Otolaryngologists should wear appropriate PPE when managing this hemorrhagic complication.

Local spikes in COVID-19 cases: Recommendations for maintaining otolaryngology clinic operations.

The Coronavirus Disease-2019 (COVID-19) pandemic has created an unprecedented economic and public health crisis in the United States. Following efforts to mitigate disease spread, with a significant decline in some regions, many states began reopening their economies. As social distancing guidelines were relaxed and businesses opened, local outbreaks of COVID-19 continue to place person on healthcare systems. Among medical specialties, otolaryngologists and their staff are among the highest at risk for becoming exposed to COVID-19. As otolaryngologists prepare to weather the storm of impending local surges in COVID-19 infections there are several practical measures that can be taken to mitigate the risk to ourselves and our staff.

Driven to near-experimental accuracy by refinement via molecular dynamics simulations.

Protein model refinement has been an essential part of successful protein structure prediction. Molecular dynamics simulation-based refinement methods have shown consistent improvement of protein models. There had been progress in the extent of refinement for a few years since the idea of ensemble averaging of sampled conformations emerged. There was little progress in CASP12 because conformational sampling was not sufficiently diverse due to harmonic restraints. During CASP13, a new refinement method was tested that achieved significant improvements over CASP12. The new method intended to address previous bottlenecks in the refinement problem by introducing new features. Flat-bottom harmonic restraints replaced harmonic restraints, sampling was performed iteratively, and a new scoring function and selection criteria were used. The new protocol expanded conformational sampling at reduced computational costs. In addition to overall improvements, some models were refined significantly to near-experimental accuracy.

Are China's oldest-old living longer with less disability? A longitudinal modeling analysis of birth cohorts born 10 years apart.

BACKGROUND: China has transitioned from being one of the fastest-growing populations to among the most rapidly aging countries worldwide. In particular, the population of oldest-old individuals, those aged 80+, is projected to quadruple by 2050. The oldest-old represent a uniquely important group-they have high demand for personal assistance and the highest healthcare costs of any age group. Understanding trends in disability and longevity among the oldest-old-that is, whether successive generations are living longer and with less disability-is of great importance for policy and planning purposes. METHODS: We utilized data from successive birth cohorts (n = 20,520) of the Chinese oldest-old born 10 years apart (the earlier cohort was interviewed in 1998 and the later cohort in 2008). Disability was defined as needing personal assistance in performing one or more of five essential activities (bathing, transferring, dressing, eating, and toileting) or being incontinent. Participants were followed for age-specific disability transitions and mortality (in 2000 and 2002 for the earlier cohort and 2011 and 2014 for the later cohort), which were then used to generate microsimulation-based multistate life tables to estimate partial life expectancy (LE) and disability-free LE (DFLE), stratified by sex and age groups (octogenarians, nonagenarians, and centenarians). We additionally explored sociodemographic heterogeneity in LE and DFLE by urban/rural residence and educational attainment. RESULTS: More recently born Chinese octogenarians (born 1919-1928) had a longer partial LE between ages 80 and 89 than octogenarians born 1909-1918, and octogenarian women experienced an increase in partial DFLE of 0.32 years (P = 0.004) across the two birth cohorts. Although no increases in partial LE were observed among nonagenarians or centenarians, partial DFLE increased across birth cohorts, with a gain of 0.41 years (P < 0.001) among nonagenarians and 0.07 years (P = 0.050) among centenarians. Subgroup analyses revealed that gains in partial LE and DFLE primarily occurred among the urban resident population. CONCLUSIONS: Successive generations of China's oldest-old are living with less disability as a whole, and LE is expanding among octogenarians. However, we found a widening urban-rural disparity in longevity and disability, highlighting the need to improve policies to alleviate health inequality throughout the population.

The Standardization of Outpatient Procedure (STOP) Narcotics: A Prospective Health Systems Intervention to Reduce Opioid Use in Ambulatory Breast Surgery.

BACKGROUND: During the past 15 years, opioid-related overdose death rates for women have increased 471%. Many surgeons provide opioid prescriptions well in excess of what patients actually use. This study assessed a health systems intervention to control pain adequately while reducing opioid prescriptions in ambulatory breast surgery. METHODS: This prospective non-inferiority study included women 18-75 years of age undergoing elective ambulatory general surgical breast procedures. Pre- and postintervention groups were compared, separated by implementation of a multi-pronged, opioid-sparing strategy consisting of patient education, health care provider education and perioperative multimodal analgesic strategies. The primary outcome was average pain during the first 7 postoperative days on a numeric rating scale of 0-10. The secondary outcomes included medication use and prescription renewals. RESULTS: The average pain during the first 7 postoperative days was non-inferior in the postintervention group despite a significant decrease in median oral morphine equivalents (OMEs) prescribed (2.0/10 [100 OMEs] pre-intervention vs 2.1/10 [50 OMEs] post-intervention; p = 0.40 [p < 0.001]). Only 39 (44%) of the 88 patients in the post-intervention group filled their rescue opioid prescription, and 8 (9%) of the 88 patients reported needing an opioid for additional pain not controlled with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) postoperatively. Prescription renewals did not change. CONCLUSION: A standardized pain care bundle was effective in minimizing and even eliminating opioid use after elective ambulatory breast surgery while adequately controlling postoperative pain. The Standardization of Outpatient Procedure Narcotics (STOP Narcotics) initiative decreases unnecessary and unused opioid medication and may decrease risk of persistent opioid use. This initiative provides a framework for future analgesia guidelines in ambulatory breast surgery.

Discovery of blue singlet exciton fission molecules via a high-throughput virtual screening and experimental approach.

Singlet exciton fission is a mechanism that could potentially enable solar cells to surpass the Shockley-Queisser efficiency limit by converting single high-energy photons into two lower-energy triplet excitons with minimal thermalization loss. The ability to make use of singlet exciton fission to enhance solar cell efficiencies has been limited, however, by the sparsity of singlet fission materials with triplet energies above the bandgaps of common semiconductors such as Si and GaAs. Here, we employ a high-throughput virtual screening procedure to discover new organic singlet exciton fission candidate materials with high-energy (>1.4 eV) triplet excitons. After exploring a search space of 4482 molecules and screening them using time-dependent density functional theory, we identify 88 novel singlet exciton fission candidate materials based on anthracene derivatives. Subsequent purification and characterization of several of these candidates yield two new singlet exciton fission materials: 9,10-dicyanoanthracene (DCA) and 9,10-dichlorooctafluoroanthracene (DCOFA), with triplet energies of 1.54 eV and 1.51 eV, respectively. These materials are readily available and low-cost, making them interesting candidates for exothermic singlet exciton fission sensitization of solar cells. However, formation of triplet excitons in DCA and DCOFA is found to occur via hot singlet exciton fission with excitation energies above ∼3.64 eV, and prominent excimer formation in the solid state will need to be overcome in order to make DCA and DCOFA viable candidates for use in a practical device.