Dynamical Approach to the Jamming Problem.

A simple dynamical model, biased random organization (BRO), appears to produce configurations known as random close packing (RCP) as BRO's densest critical point in dimension d=3. We conjecture that BRO likewise produces RCP in any dimension; if so, then RCP does not exist in d=1-2 (where BRO dynamics lead to crystalline order). In d=3-5, BRO produces isostatic configurations and previously estimated RCP volume fractions 0.64, 0.46, and 0.30, respectively. For all investigated dimensions (d=2-5), we find that BRO belongs to the Manna universality class of dynamical phase transitions by measuring critical exponents associated with the steady-state activity and the long-range density fluctuations. Additionally, BRO's distribution of near contacts (gaps) displays behavior consistent with the infinite-dimensional theoretical treatment of RCP when d≥4. The association of BRO's densest critical configurations with random close packing implies that RCP's upper-critical dimension is consistent with the Manna class d_{uc}=4.

Prognostic communication about lung cancer in the precision oncology era: A multiple-perspective qualitative study.

BACKGROUND: Although most patients with cancer prefer to know their prognosis, prognostic communication between oncologists and patients is often insufficient. Targeted therapies for lung cancer improve survival yet are not curative and produce variable responses. This study sought to describe how oncologists communicate about prognosis with patients receiving targeted therapies for lung cancer. METHODS: This qualitative study included 39 patients with advanced lung cancer with targetable mutations, 14 caregivers, and 10 oncologists. Semistructured interviews with patients and caregivers and focus groups or interviews with oncologists were conducted to explore their experiences with prognostic communication. One oncology follow-up visit was audio-recorded per patient. A framework approach was used to analyze interview transcripts, and a content analysis of patient-oncologist dialogue was conducted. Themes were identified within each source and then integrated across sources to create a multidimensional description of prognostic communication. RESULTS: Six themes in prognostic communication were identified: Patients with targetable mutations develop a distinct identity in the lung cancer community that affects their information-seeking and self-advocacy; oncologists set high expectations for targeted therapy; the uncertain availability of new therapies complicates prognostic discussions; patients and caregivers have variable information preferences; patients raise questions about progression by asking about physical symptoms or scan results; and patients' expectations of targeted therapy influence their medical decision-making. CONCLUSIONS: Optimistic patient-oncologist communication shapes the expectations of patients receiving targeted therapy for lung cancer and affects their decision-making. Further research and clinical guidance are needed to help oncologists to communicate uncertain outcomes effectively.

Harnessing Peptide Binding to Capture and Reclaim Phosphate.

With rising consumer demands, society is tapping into wastewater as an innovative source to recycle depleting resources. Novel reclamation technologies have been recently explored for this purpose, including several that optimize natural biological processes for targeted reclamation. However, this emerging field has a noticeable dearth of synthetic material technologies that are programmed to capture, release, and recycle specified targets; and of the novel materials that do exist, synthetic platforms incorporating biologically inspired mechanisms are rare. We present here a prototype of a materials platform utilizing peptide amphiphiles that has been molecularly engineered to sequester, release, and reclaim phosphate through a stimuli-responsive pH trigger, exploiting a protein-inspired binding mechanism that is incorporated directly into the self-assembled material network. This material is able to harvest and controllably release phosphate for multiple cycles of reuse, and it is selective over nitrate and nitrite. We have determined by simulations that the binding conformation of the peptide becomes constrained in the dense micelle corona at high pH such that phosphate is expelled when it otherwise would be preferentially bound. However, at neutral pH, this dense structure conversely employs multichain binding to further stabilize phosphate when it would otherwise be unbound, opening opportunities for higher-order conformational binding design to be engineered into this controllably packed corona. With this work, we are pioneering a new platform to be readily altered to capture other valuable targets, presenting a new class of capture and release materials for recycling resources on the nanoscale.

Knowledge About Risks, Benefits, and Curative Potential of Immunotherapy Among Patients with Advanced Cancer.

BACKGROUND: Immunotherapy is the first-line treatment for melanoma and lung cancer and brings new risks of immune-related adverse events. We aimed to describe patients' knowledge about risks, benefits, and goals of immunotherapy. MATERIALS AND METHODS: We conducted a cross-sectional study of patients with advanced melanoma or non-small cell lung cancer that used a 9-item knowledge survey and questions from the Prognosis and Treatment Perceptions Questionnaire. RESULTS: We surveyed 105 participants (57 with melanoma, 48 with lung cancer) with median age 69 years (range 36-89). Participants' responses revealed knowledge deficits about immunotherapy mechanism of action and lack of awareness about the timing and severity of side effects. One third (34%; 36/105) of participants reported that the primary goal of their treatment is to cure their cancer. CONCLUSION: Given the widespread use of immunotherapy, patients would benefit from educational tools so that they know what to expect regarding side effects and prognosis.

Dear Pandemic: Nurses as key partners in fighting the COVID-19 infodemic.

The COVID-19 pandemic and subsequent proliferation of misinformation have created parallel public health crises. Social media offers a novel platform to amplify evidence-based communication to broader audiences. This paper describes the application of science communication engagement on social media platforms by an interdisciplinary team of female scientists in a campaign called Dear Pandemic. Nurses are trusted professionals trained in therapeutic communication and are central to this effort. The Dear Pandemic campaign now has more than 97,000 followers with international and multilingual impact. Public health strategies to combat misinformation and guide individual behavior via social media show promise, and require further investment to support this novel dissemination of science communication.

Extracting collective motions underlying nucleosome dynamics via nonlinear manifold learning.

The identification of effective collective variables remains a challenge in molecular simulations of complex systems. Here, we use a nonlinear manifold learning technique known as the diffusion map to extract key dynamical motions from a complex biomolecular system known as the nucleosome: a DNA-protein complex consisting of a DNA segment wrapped around a disc-shaped group of eight histone proteins. We show that without any a priori information, diffusion maps can identify and extract meaningful collective variables that characterize the motion of the nucleosome complex. We find excellent agreement between the collective variables identified by the diffusion map and those obtained manually using a free energy-based analysis. Notably, diffusion maps are shown to also identify subtle features of nucleosome dynamics that did not appear in those manually specified collective variables. For example, diffusion maps identify the importance of looped conformations in which DNA bulges away from the histone complex that are important for the motion of DNA around the nucleosome. This work demonstrates that diffusion maps can be a promising tool for analyzing very large molecular systems and for identifying their characteristic slow modes.

Free energy of metal-organic framework self-assembly.

Metal-organic frameworks (MOFs) represent an important class of materials. Careful selection of building blocks allows for tailoring of the properties of the resulting framework. The self-assembly process, however, is not understood, and without detailed knowledge of the underlying molecular mechanism, it is difficult to anticipate whether a particular design can be realized, or whether the material adopts a metastable, kinetically arrested state. We present a detailed examination of early-stage self-assembly pathways of the MOF-5. Enhanced sampling techniques are used to model a self-assembly in an explicit solvent (dimethylformamide, DMF). We identify several free energy barriers encountered during the assembly of the final MOF, which arise from structural rearrangements preceding MOF formation and from disrupted MOF-solvent interactions as formation proceeds. In all cases considered here, MOFs exhibit favorable entropic gains during the assembly. More generally, the strategy presented provides a step toward the experimental design characterizing the formation of ordered frameworks and possible sources of polymorphism.

Early-stage human islet amyloid polypeptide aggregation: Mechanisms behind dimer formation.

Amyloid aggregates of human islet amyloid polypeptide (hIAPP or human amylin) have long been implicated in the development of type II diabetes. While hIAPP is known to aggregate into amyloid fibrils, it is the early-stage prefibrillar species that have been proposed to be cytotoxic. A detailed picture of the early-stage aggregation process and relevant intermediates would be valuable in the development of effective therapeutics. Here, we use atomistic molecular dynamics simulations with a combination of enhanced sampling methods to examine the formation of the hIAPP dimer in water. Bias-exchange metadynamics calculations reveal relative conformational stabilities of the hIAPP dimer. Finite temperature string method calculations identify pathways for dimer formation, along with relevant free energy barriers and intermediate structures. We show that the initial stages of dimerization involve crossing a substantial free energy barrier to form an intermediate structure exhibiting transient ß-sheet character, before proceeding to form an entropically stabilized dimer structure.

Adaptive enhanced sampling by force-biasing using neural networks.

A machine learning assisted method is presented for molecular simulation of systems with rugged free energy landscapes. The method is general and can be combined with other advanced sampling techniques. In the particular implementation proposed here, it is illustrated in the context of an adaptive biasing force approach where, rather than relying on discrete force estimates, one can resort to a self-regularizing artificial neural network to generate continuous, estimated generalized forces. By doing so, the proposed approach addresses several shortcomings common to adaptive biasing force and other algorithms. Specifically, the neural network enables (1) smooth estimates of generalized forces in sparsely sampled regions, (2) force estimates in previously unexplored regions, and (3) continuous force estimates with which to bias the simulation, as opposed to biases generated at specific points of a discrete grid. The usefulness of the method is illustrated with three different examples, chosen to highlight the wide range of applicability of the underlying concepts. In all three cases, the new method is found to enhance considerably the underlying traditional adaptive biasing force approach. The method is also found to provide improvements over previous implementations of neural network assisted algorithms.

SSAGES: Software Suite for Advanced General Ensemble Simulations.

Molecular simulation has emerged as an essential tool for modern-day research, but obtaining proper results and making reliable conclusions from simulations requires adequate sampling of the system under consideration. To this end, a variety of methods exist in the literature that can enhance sampling considerably, and increasingly sophisticated, effective algorithms continue to be developed at a rapid pace. Implementation of these techniques, however, can be challenging for experts and non-experts alike. There is a clear need for software that provides rapid, reliable, and easy access to a wide range of advanced sampling methods and that facilitates implementation of new techniques as they emerge. Here we present SSAGES, a publicly available Software Suite for Advanced General Ensemble Simulations designed to interface with multiple widely used molecular dynamics simulations packages. SSAGES allows facile application of a variety of enhanced sampling techniques-including adaptive biasing force, string methods, and forward flux sampling-that extract meaningful free energy and transition path data from all-atom and coarse-grained simulations. A noteworthy feature of SSAGES is a user-friendly framework that facilitates further development and implementation of new methods and collective variables. In this work, the use of SSAGES is illustrated in the context of simple representative applications involving distinct methods and different collective variables that are available in the current release of the suite. The code may be found at: https://github.com/MICCoM/SSAGES-public.

A Policy Analysis of Legally Required Supervision of Nurse Practitioners and Other Health Professionals.

The use of legally required supervision occurs across health professionals who provide similar services. Legally required supervision has the potential to disrupt the production of high-quality, cost-efficient, accessible health services across disciplines. This paper examines the effects of nurse practitioner collaborative practice agreements and similar models of health professional regulation, defined as legally required supervision, on the cost and delivery of health services. A policy analysis examines empirical, policy, and law literature between two health professionals providing a similar service. Analysis includes literature on dental hygienists, dentists, certified registered nurse anesthetists, midwives, nurse practitioners, physicians, and pharmacists. A framework for legally required supervision across health professionals is presented. Antecedents of legally required supervision include occupational licensure, reimbursement policy, and institutional policy. Legally required supervision inhibits provider entry to practice and the production of health services by supervised providers. The cost of care increases under legally required supervision. Costs are measured by wages for providers and the price of services for patients. This paper and proposed framework summarize the antecedents and consequences of legally required supervision. Discipline-specific antecedents and provider characteristics must be considered when calculating the full effect of legally required supervision on the delivery and cost of health services.

Why older adults may decline offers of post-acute care services: A qualitative descriptive study.

The most common post-acute care (PAC) services available to patients after hospital discharge include home care, skilled nursing facilities, nursing homes, inpatient rehabilitation, and hospice. Patients who need PAC and receive services have better outcomes, however almost one-third of those offered services decline. Little research exists on PAC decision-making and why patients may decline services. This qualitative descriptive study explored the responses of thirty older adults to the question: "Can you, from the patient point of view, tell me why someone would not want post hospital care?" Three themes emerged. Participants may decline due to 1) previous negative experiences with PAC, or 2) a preference to be home. Some participants stated, "I'd be there" and would not decline services. Participants also discussed 3) why other patients might decline PAC which included patients' past experiences, lack of understanding/preconceived ideas, and preferences. Clinical implications include assessing patients' knowledge and experience before providing recommendations.

State scope of practice restrictions and nurse practitioner practice in nursing homes: 2012-2019.

Increased engagement of nurse practitioners (NPs) has been recommended as a way to address care delivery challenges in settings that struggle to attract physicians, such as primary care and rural areas. Nursing homes also face such physician shortages. We evaluated the role of state scope of practice regulations on NP practice in nursing homes in 2012-2019. Using linear probability models, we estimated the proportion of NP-delivered visits to patients in nursing homes as a function of state scope of practice regulations. Control variables included county demographic, socioeconomic, and health care workforce characteristics; state fixed effects; and year indicators. The proportion of nursing home visits conducted by NPs increased from 24% in 2012 to 42% in 2019. Expanded scope of practice regulation was associated with a greater proportion and total volume of nursing home visits conducted by NPs in counties with at least 1 NP visit. These relationships were concentrated among short-stay patients in urban counties. Removing scope of practice restrictions on NPs may address clinician shortages in nursing homes in urban areas where NPs already practice in nursing homes. However, improving access to advanced clinician care for long-term care residents and for patients in rural locations may require additional interventions and resources.

Disparities in Access to Highly Rated Skilled Nursing Facilities among Medicare Beneficiaries with Opioid Use Disorder.

OBJECTIVES: To investigate disparities in admissions to highly rated skilled nursing facilities (SNFs) between Medicare beneficiaries with and without opioid use disorder (OUD). DESIGN: Nationwide, retrospective observational cohort. SETTING AND PARTICIPANTS: Medicare Fee-for-Service beneficiaries aged ≥18 years admitted to SNFs following hospitalization during 2016-2020 (n = 30,922 with OUD and n = 137,454 without OUD). METHODS: Data used were 100% Medicare inpatient claims, nursing home administrative databases, and Nursing Home Compare. We identified hospitalized patients with and without OUD and matched them on age, sex, Part D low-income subsidy (LIS), and residential county. We compared the overall and component (quality, staffing, and health inspections) star ratings of SNFs that beneficiaries entered. Beneficiary-level regression models were conducted adjusting for race and ethnicity, Medicare-Medicaid dual status, comorbidity score, hospital length of stay, and state and year fixed effects. RESULTS: The overall study sample had a mean (SD) age of 71.4 (11.4) years, 63.9% were female, and 57.4% had LIS. Among beneficiaries with OUD, 50.3% entered SNFs with above-average (4 or 5) overall rating compared with 51.3% among those without OUD. Distributions of above-average ratings among beneficiaries with and without OUD were as follows: 63.9% vs 62.2% for quality, 32.8% vs 34.9% for health inspections, and 46.2% vs 45.0% for staffing, respectively. Adjusted regression models indicated that beneficiaries with OUD were less likely to be admitted to facilities with above-average overall (OR 0.90, 95% CI 0.87-0.92), health inspection (OR 0.90, 95% CI 0.88-0.93), and staffing (OR 0.91, 95% CI 0.89-0.94) ratings compared with beneficiaries without OUD, whereas quality (OR 0.98, 95% CI 0.95-1.01) ratings did not differ. CONCLUSIONS AND IMPLICATIONS: Despite mixed results on component ratings, our findings suggest a concerning disparity in the overall quality of SNFs admitting Medicare beneficiaries with OUD. Enhancing equitable access to high-quality SNF care for individuals with OUD is imperative amid rising demand and legal protections under the American Disabilities Act.

Effects Of An Employee COVID-19 Vaccination Mandate At A Long-Term Care Network.

We assessed COVID-19 vaccination and employment status among employees of a long-term care network that announced an employee vaccination mandate on July 29, 2021. The day before the announcement, 1,208 employees were unvaccinated; of these workers, 56.2 percent subsequently were vaccinated, whereas 20.9 percent (3.7 percent of active employees) were terminated because of noncompliance with the mandate.

Use of Post-Acute Care by Medicare Beneficiaries With a Diagnosis of Dementia.

OBJECTIVES: Hospitalized patients with dementia transitioning to post-acute care may be particularly vulnerable to changes in post-acute care utilization driven by payment reforms; however, use of post-acute care in this population is incompletely understood. We sought to describe post-acute care utilization in skilled nursing facilities (SNFs) and from home health (HH) agencies among Medicare beneficiaries with a diagnosis of dementia. DESIGN: Retrospective, observational study using 100% sample of Medicare beneficiaries from 2013 to 2016. SETTING AND PARTICIPANTS: We identified hospitalizations and diagnoses using Medicare Provider Analysis and Review (MedPAR), SNF stays using the Minimum Data Set, HH episodes using the Outcome and Assessment Information Set, and dementia diagnoses using the Medicare Beneficiary Summary File Chronic Conditions segment. METHODS: We calculated overall utilization and trends in post-acute care use over time, stratified by dementia diagnosis, type of post-acute care (SNF vs HH), and payer (fee-for-service vs Medicare Advantage). RESULTS: Of the 9,762,208 Medicare fee-for-service beneficiaries who received post-acute care from 2013 to 2016, 3,155,560 (32.3%) carried a diagnosis of dementia. Rates of post-acute care use were similar over time. More beneficiaries with a diagnosis of dementia received post-acute care (44.2% vs 27.7%) and proportionally more SNF care (71.7% vs 49.6%). Overall use and trends were similar in the Medicare Advantage population. CONCLUSIONS AND IMPLICATIONS: One-third of all fee-for-service Medicare beneficiaries receiving post-acute care have a diagnosis of dementia, and more than 7 in 10 receive this care in an SNF. These findings serve as a foundation for needed evaluations of how best to meet the post-hospital needs of older adults with dementia.

Younger Individuals Increase Their Use of Nursing Homes Following ACA Medicaid Expansion.

OBJECTIVES: This study examines the effect of Medicaid eligibility expansion under the Affordable Care Act (ACA) on the utilization of nursing home services by younger individuals and those covered by Medicaid. DESIGN: Compared the age of nursing home residents, proportion of individuals covered by Medicaid, annual nursing home admissions in those younger than 65, and nursing home length of stay in states that expanded Medicaid eligibility through the ACA to states that did not. We used data from LTCFocus (nursing home level), the Minimum Data Set (individual level), and Medicaid expansion status from the Kaiser Family Foundation. SETTING AND PARTICIPANTS: The study included 15,005,888 nursing home admissions, 2,446,950 of which were residents younger than 65, across 14,132 nursing homes between 2009 and 2016. METHODS: A time-varying difference-in-difference model including state and year fixed effects with effect modification by pre-2014 nursing home occupancy. RESULTS: Facilities in expansion states with a pre-ACA occupancy rate of more than 70% increased the fraction of residents younger than 65 by 2.74% to 6.32%, compared with similar facilities in nonexpansion states. Medicaid admissions varied, with an increase in year 2 after expansion compared with nonexpansion states. Among residents entering from an acute care hospital, the proportion younger than 65 increased in facilities with pre-2014 occupancy rates of more than 70%, compared with similar facilities in nonexpansion states, an increase of up to 6.51%. Median nursing home length of stay for individuals younger than 65 decreased relative to nonexpansion states across all occupancy categories, ranging from 1.68 to 6.06 days after Medicaid expansion. CONCLUSIONS AND IMPLICATIONS: Medicaid expansion increased access to nursing home post-acute care for individuals younger than 65. It remains unclear if the benefit of post-acute care is the same among this group, or if the needs of younger individuals can be adequately met in this setting.

Postacute care outcomes in home health or skilled nursing facilities in patients with a diagnosis of dementia.

OBJECTIVE: To compare the outcomes of postacute care between home health (HH) and skilled nursing facilities (SNFs) following hospitalization among Medicare beneficiaries with a diagnosis of dementia. DATA SOURCES: 100% MedPAR data, Minimum Data Set, and Outcome and Assessment Information Set assessment data from January 1, 2015 to December 31, 2016. STUDY DESIGN: Retrospective cohort analysis using an instrumental variable design to compare outcomes (30-day readmission and mortality, 100-day mortality) of HH versus SNF following acute hospitalization. We used the differential distance between patients' home and the closest HH agency and SNF to instrument for nonrandom allocation of patients. DATA COLLECTION/EXTRACTION METHODS: We identified hospital discharges followed by SNF and HH stays for Medicare fee-for-service beneficiaries with dementia. We excluded beneficiaries younger than age 65, admitted to the hospital from a nursing home, or enrolled in hospice. We identified dementia using validated diagnostic codes with a 3-year look-back. PRINCIPAL FINDINGS: Our sample included 977,946 beneficiaries with a diagnosis of dementia; 297,732 (30.4%) received HH, while 680,214 (69.6%) went to SNF. Overall, 16.8% were readmitted to the hospital and 6.1% died within 30 days, while 15.4% died within 100 days of hospital discharge. In the instrumental variable analysis, there were no differences in any outcome between the two postacute care settings. CONCLUSIONS: Medicare beneficiaries with a diagnosis of dementia receiving postacute care in HH or SNF experienced similar rates of readmission and mortality across settings. This finding raises important questions about current postacute care referral patterns, given 7 in 10 patients with a diagnosis of dementia in our sample were discharged to SNF.

Incidence and Outcomes of SARS-CoV-2 in Post-Acute Skilled Nursing Facility Care.

OBJECTIVES: To examine the risk of contracting SARS-CoV-2 during a post-acute skilled nursing facility (SNF) stay and the associated risk of death. DESIGN: Cohort study using Minimum Data Set and electronic health record data from a large multistate long-term care provider. Primary outcomes included testing positive for SARS-CoV-2 during the post-acute SNF stay, and death among those who tested positive. SETTING AND PARTICIPANTS: The sample included all new admissions to the provider's 286 SNFs between January 1 and December 31, 2020. Patients known to be infected with SARS-CoV-2 at the time of admission were excluded. METHODS: SARS-CoV-2 infection and mortality rates were measured in time intervals by month of admission. A parametric survival model with SNF random effects was used to measure the association of patient demographic factors, clinical characteristics, and month of admission, with testing positive for SARS-CoV-2. RESULTS: The sample included 45,094 post-acute SNF admissions. Overall, 5.7% of patients tested positive for SARS-CoV-2 within 100 days of admission, with 1.0% testing positive within 1-14 days, 1.4% within 15-30 days, and 3.4% within 31-100 days. Of all newly admitted patients, 0.8% contracted SARS-CoV-2 and died, whereas 6.7% died without known infection. Infection rates and subsequent risk of death were highest for patients admitted during the first and third US pandemic waves. Patients with greater cognitive and functional impairment had a 1.45 to 1.92 times higher risk of contracting SARS-CoV-2 than patients with less impairment. CONCLUSIONS AND IMPLICATIONS: The absolute risk of SARS-CoV-2 infection and death during a post-acute SNF admission was 0.8%. Those who did contract SARS-CoV-2 during their SNF stay had nearly double the rate of death as those who were not infected. Findings from this study provide context for people requiring post-acute care, and their support systems, in navigating decisions around SNF admission during the SARS-CoV-2 pandemic.

Lessons Learned From Dear Pandemic, a Social Media-Based Science Communication Project Targeting the COVID-19 Infodemic.

The World Health Organization has identified excessive COVID-19 pandemic-related information as a public health crisis, calling it an "infodemic." Social media allows misinformation to spread quickly and outcompete scientifically grounded information delivered via other methods. Dear Pandemic is an innovative, multidisciplinary, social media-based science communication project whose mission is to educate and empower individuals to successfully navigate the overwhelming amount of information circulating during the pandemic. This mission has 2 primary objectives: (1) to disseminate trustworthy, comprehensive, and timely scientific content about the pandemic to lay audiences via social media and (2) to promote media literacy and information-hygiene practices, equipping readers to better manage the COVID-19 infodemic within their own networks. The volunteer team of scientists publishes 8-16 posts per week on pandemic-relevant topics. Nearly 2 years after it launched in March 2020, the project has a combined monthly reach of more than 4 million unique views across 4 social media channels, an email newsletter, and a website. We describe the project's guiding principles, lessons learned, challenges, and opportunities. Dear Pandemic has emerged as an example of a promising new paradigm for public health communication and intervention. The contributors deliver content in ways that are personal, practical, actionable, responsive, and native to social media platforms. The project's guiding principles are a model for public health communication targeting future infodemics and can bridge the chasm between the scientific community and the practical daily decision-making needs of the general public.