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Background: Inhibition of p38 alpha mitogen activated protein kinase (p38α) has shown great promise as a treatment for Alzheimer's disease (AD) in preclinical tests. However, previous preclinical studies were performed in "pure" models of AD pathology. A vast majority of AD patients have comorbid dementia-contributing pathologies, particularly some form of vascular damage. The present study therefore aimed to test the potential of p38α inhibition to address dysfunction in the context of comorbid amyloid and vascular pathologies. Methods: An amyloid overexpressing mouse strain (5xFAD) was placed on an 8-week long diet to induce the hyperhomocysteinemia (HHcy) model of small vessel disease. Mice were treated with the brain-penetrant small molecule p38α inhibitor MW150 for the duration of the HHcy diet, and subsequently underwent behavioral, neuroimaging, electrophysiological, or biochemical/immunohistochemical analyses. Results: MW150 successfully reduced behavioral impairment in the Morris Water Maze, corresponding with attenuation of synaptic loss, reduction in tau phosphorylation, and a partial normalization of electrophysiological parameters. No effect of MW150 was observed on the amyloid, vascular, or neuroinflammatory endpoints measured. Conclusions: This study provides proof-of-principle that the inhibition of p38α is able to provide benefit even in the context of mixed pathological contributions to cognitive impairment. Interestingly, the benefit was mediated primarily via rescue of neuronal function without any direct effects on the primary pathologies. These data suggest a potential use for p38 inhibitors in the preservation of cognition across contexts, and in particular AD, either alone or as an adjunct to other AD therapies (i.e. anti-amyloid approaches). Future studies to delineate the precise neuronal pathways implicated in the benefit may help define other specific comorbid conditions amenable to this type of approach or suggest future refinement in pharmacological targeting.
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Despite efforts to expand naloxone access, opioid-related overdoses remain a significant contributor to mortality. We study state efforts to expand naloxone distribution through pharmacies by reducing the non-monetary costs to prescribers, dispensers, and/or potential recipients of naloxone. We find that laws that only address liability costs have small and insignificant effects on the volume of naloxone dispensed through pharmacies. In contrast, we estimate large effects of laws removing the need for patients to obtain prescriptions from traditional prescribers (e.g., primary care physicians): laws authorizing non-patient-specific prescription distribution and laws granting pharmacists prescriptive authority. We test whether areas designated as primary care shortage areas-where it would be costlier to obtain a prescription-were disproportionately impacted. Shortage areas experienced sharper growth in pharmacy naloxone dispensing in states adopting prescriptive authority policies. These gains were primarily due to those facing low out-of-pocket costs, suggesting that price barriers also must be addressed to increase naloxone purchases.
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Melengestrol acetate (MGA) implants are a progestin-based reversible contraceptive used to manage fertility in animals. MGA implants are recommended for replacement every 2 years; however, reproduction may be suppressed longer if implants are not removed. In this study, we investigated whether the probability of reproducing (pR) differed among nonimplanted females, females with MGA implants removed, and females whose implants were not removed. In addition, since implant loss in hamadryas baboons is a concern, we explored whether female age, institution, implant placement year, implant location, or implant placement type (intramuscular vs. subcutaneous) differed for females whose implants were lost compared to those that were not. The pR differed significantly across all three treatment conditions with the nonimplanted group having the highest pR. The pR plateaued at 63% after 40 months for the implant-removed group compared to 96% after 84 months in the nonimplanted group. There was no reproduction after contraception if implants were not removed (7.83-45.53 months). In the nonimplanted group, pR was significantly higher for older and parous females. In terms of implant loss, we found that implant placement type was significantly associated with implant loss, such that there were fewer losses when implants were placed intramuscularly (IM) as compared to subcutaneously. Our results suggest that placing MGA implants IM is likely to reduce loss. When loss is prevented, MGA implants are an effective form of contraception and are reliably reversibly in most individuals when removed. However, if not removed, they can prevent reproduction longer than 2 years.
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Genes regulating body fat are shared with high fidelity by mice and humans, indicating that mouse knockout (KO) phenotyping might identify valuable antiobesity drug targets. Male Mrs2 magnesium transporter (Mrs2) KO mice were recently reported as thin when fed a high-fat diet (HFD). They also exhibited increased energy expenditure (EE)/body weight and had beiged adipocytes that, along with isolated hepatocytes, demonstrated increased oxygen consumption, suggesting that increased EE drove the thin phenotype. Here we provide our data on these and additional assays in Mrs2 KO mice. We generated Mrs2 KO mice by homologous recombination. HFD-fed male and female Mrs2 KO mice had significantly less body fat, measured by quantitative magnetic resonance, than wild-type (WT) littermates. HFD-fed Mrs2 KO mice did not demonstrate increased EE by indirect calorimetry and could not maintain body temperature at 4 °C, consistent with their decreased brown adipose tissue stores but despite increased beige white adipose tissue. Instead, when provided a choice between HFD and low-fat diet (LFD), Mrs2 KO mice showed a significant 15% decrease in total energy intake resulting from significantly lower HFD intake that offset numerically increased LFD intake. Food restriction studies performed using WT mice suggested that this decrease in energy intake could explain the loss of body fat. Oral glucose tolerance test studies revealed significantly improved insulin sensitivity in Mrs2 KO mice. We conclude that HFD-fed Mrs2 KO mice are thin with improved insulin sensitivity, and that this favorable metabolic phenotype is driven by hypophagia. Further evaluation is warranted to determine the suitability of MRS2 as a drug target for antiobesity therapeutics.
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Dieta Hiperlipídica , Metabolismo Energético , Camundongos Knockout , Animais , Feminino , Masculino , Camundongos , Tecido Adiposo/metabolismo , Peso Corporal , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/genética , Camundongos Endogâmicos C57BLRESUMO
This case-control study analyzes disruptive ransomware attacks against hospitals in California from 2014 to 2020 and emergency department (ED) and inpatient admissions in attacked and nearby hospitals.
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Segurança Computacional , Serviço Hospitalar de Emergência , Hospitalização , Hospitais , Humanos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Estados Unidos/epidemiologia , Segurança Computacional/economia , Segurança Computacional/estatística & dados numéricos , CaliforniaRESUMO
Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of ß-amyloid (Aß) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.
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Envelhecimento , Atrofia , Encéfalo , Tacrolimo , Animais , Cães , Feminino , Atrofia/patologia , Masculino , Envelhecimento/patologia , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Tacrolimo/farmacologia , Comportamento Animal/efeitos dos fármacos , Imageamento por Ressonância MagnéticaRESUMO
A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states is delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death is over, chondroprogenitor differentiation is accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlates with, and is necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.
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Cartilagem , Condrócitos , Animais , Camundongos , Condrócitos/metabolismo , Diferenciação Celular , Osso e Ossos , Morte CelularRESUMO
OBJECTIVE: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current corticocentric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural magnetic resonance imaging in 1602 adults with epilepsy and 1022 healthy controls across 22 sites from the global ENIGMA-Epilepsy working group. METHODS: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in (1) all epilepsies, (2) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), (3) nonlesional temporal lobe epilepsy, (4) genetic generalized epilepsy, and (5) extratemporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. RESULTS: Across all epilepsies, reduced total cerebellar volume was observed (d = .42). Maximum volume loss was observed in the corpus medullare (dmax = .49) and posterior lobe gray matter regions, including bilateral lobules VIIB (dmax = .47), crus I/II (dmax = .39), VIIIA (dmax = .45), and VIIIB (dmax = .40). Earlier age at seizure onset ( η ρ max 2 = .05) and longer epilepsy duration ( η ρ max 2 = .06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE, with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. SIGNIFICANCE: We provide robust evidence of deep cerebellar and posterior lobe subregional gray matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in nonmotor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellar subregional damage into neurobiological models of epilepsy.
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Epilepsia do Lobo Temporal , Síndromes Epilépticas , Adulto , Humanos , Epilepsia do Lobo Temporal/complicações , Fenitoína , Estudos Transversais , Síndromes Epilépticas/complicações , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Convulsões/complicações , Imageamento por Ressonância Magnética/métodos , Atrofia/patologiaRESUMO
Importance: Despite their widespread adoption across the US, policies imposing one-size-fits-all limits on the duration of prescriptions for opioids have shown modest and mixed implications for prescribing. Objective: To assess whether a prescription duration limit policy tailored to different clinical settings was associated with shorter opioid prescription lengths. Design, Setting, and Participants: This cross-sectional study examined changes in opioid prescribing patterns for opioid-naive Medicaid enrollees aged 12 to 64 years before and after implementation of a statewide prescription duration limit policy in West Virginia in June 2018. Patients with cancer or Medicare coverage were excluded. The policy assigned a 7-day duration limit to opioid prescriptions for adults treated in outpatient hospital- or office-based practices, a 4-day limit for adults treated in emergency departments, and a 3-day limit for pediatric patients younger than 18 years regardless of clinical setting. Data were examined from January 1, 2017, through September 30, 2019, and data were analyzed from June 12 to October 30, 2023. Main Outcomes and Measures: Whether a patient's initial opioid prescription was longer in days than the June 2018 policy limit for a given care setting before and after policy implementation. Interrupted time series models were used to calculate the association between the policy's implementation and outcomes. Results: The analytic sample included 44â¯703 Medicaid enrollees (27â¯957 patients [62.5%] before policy implementation and 16â¯746 patients [37.5%] after policy implementation; mean [SD] age, 33.9 [13.4] years; 27 461 females [61.4%]). Among adults treated in outpatient hospital- or office-based settings, the duration limit policy was associated with a decrease of 8.83 (95% CI, -10.43 to -7.23) percentage points (P < .001), or a 56.8% relative reduction, in the proportion of prescriptions exceeding the 7-day limit. In the emergency department setting, the policy was associated with a decrease of 7.03 (95% CI, -10.38 to -3.68) percentage points (P < .001), a 37.5% relative reduction, in the proportion of prescriptions exceeding the 4-day limit. The proportion of pediatric opioid prescriptions longer than the 3-day limit decreased by 12.80 (95% CI, -17.31 to -8.37) percentage points (P < .001), a 26.5% relative reduction, after the policy's implementation. Conclusions and Relevance: Results of this cross-sectional study suggest that opioid prescription duration limits tailored to different clinical settings are associated with reduced length of prescriptions for opioid-naive patients. Additional research is needed to evaluate whether these limits are associated with reductions in the incidence of opioid use disorder or with unintended consequences, such as shifts to illicit opioids.
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Analgésicos Opioides , Medicare , Adulto , Feminino , Humanos , Idoso , Estados Unidos/epidemiologia , Criança , Analgésicos Opioides/uso terapêutico , Estudos Transversais , Padrões de Prática Médica , PrescriçõesRESUMO
Wild ungulates are managed in human care in a range of settings from traditional zoos to large ranches. These varied settings present different portfolios of risks for good or poor welfare, which leads some to question whether a particular setting is "good for welfare" and have frustrated others interested in comparing the welfare of ungulates across these settings. Differing housing and management scenarios present different challenges and opportunities in terms of welfare but this commentary posits that good welfare is possible in all of these settings. In this commentary, we also consider natural behaviors that may, at face value, compromise welfare and discuss how taking a long view on welfare addresses concerns about these behaviors, in part using arguments related to normal behavioral development that likely improves welfare at other life stages. We also highlight the role of motivation in seemingly welfare-compromising behaviors. Finally, some indicators of welfare that we believe transcend management scenarios, and are thus able to be compared across scenarios, are suggested.
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Bem-Estar do Animal , Animais de Zoológico , Animais , Humanos , Comportamento Animal , Mamíferos , Abrigo para AnimaisRESUMO
Nervous system function relies on the establishment of complex gene expression programs that provide neuron-type-specific and core pan-neuronal features. These complementary regulatory paradigms are controlled by terminal selector and parallel-acting transcription factors (TFs), respectively. Here, we identify the nuclear factor Y (NF-Y) TF as a pervasive direct and indirect regulator of both neuron-type-specific and pan-neuronal gene expression. Mapping global NF-Y targets reveals direct binding to the cis-regulatory regions of pan-neuronal genes and terminal selector TFs. We show that NFYA-1 controls pan-neuronal gene expression directly through binding to CCAAT boxes in target gene promoters and indirectly by regulating the expression of terminal selector TFs. Further, we find that NFYA-1 regulation of neuronal gene expression is important for neuronal activity and motor function. Thus, our research sheds light on how global neuronal gene expression programs are buffered through direct and indirect regulatory mechanisms.
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Sequências Reguladoras de Ácido Nucleico , Fatores de Transcrição , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Ligação a CCAAT/genética , Fator de Ligação a CCAAT/metabolismo , Neurônios/metabolismo , Expressão GênicaRESUMO
Objective: The intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. Methods: A state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. Results: Across all epilepsies, reduced total cerebellar volume was observed (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset (ηρ2max=0.05) and longer epilepsy duration (ηρ2max=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. Significance: We provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy.
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This article documents child suicide rates from 1980 to 2020 in the United States using the National Vital Statistics System Multiple Cause of Death database. After generally declining for decades, suicide rates among children aged 10-17 accelerated from 2011 to 2018 in an unprecedented rise in both duration and magnitude. I consider the role of the illicit opioid crisis in driving this mental health crisis. In August 2010, an abuse-deterrent version of OxyContin was introduced and the original formulation was removed from the market, leading to a shift to illicit opioids and stimulating growth in illicit opioid markets. Areas more exposed to reformulation-as measured by pre-reformulation rates of OxyContin misuse in the National Survey on Drug Use and Health-were more affected by the transition to illicit opioids and experienced sharper growth in child suicide rates. The evidence suggests that children's illicit opioid use did not increase, implying that the illicit opioid crisis engendered higher suicide propensities by increasing suicidal risk factors for children, such as increasing rates of child neglect and altering household living arrangements. In complementary analyses, I document how living conditions declined for children during this time period.
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Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Humanos , Estados Unidos/epidemiologia , Criança , Analgésicos Opioides/efeitos adversos , Oxicodona/efeitos adversos , Epidemia de Opioides , Transtornos Relacionados ao Uso de Opioides/epidemiologiaRESUMO
Quasi-bound states in the continuum (QBICs) coupling into the propagating spectrum manifest themselves as high-quality factor (Q) modes susceptible to perturbations. This poses a challenge in predicting stable Fano resonances for realistic applications. Besides, where and when the maximum field enhancement occurs in real acoustic devices remains elusive. In this work, we theoretically predict and experimentally demonstrate the existence of a Friedrich-Wintgen BIC in an open acoustic cavity. We provide direct evidence for a QBIC by mapping the pressure field inside the cavity using a Laser Doppler Vibrometer (LDV), which provides the missing field enhancement data. Furthermore, we design a symmetry-reduced BIC and achieve field enhancement by a factor of about three compared to the original cavity. LDV measurements are a promising technique for obtaining high-Q modes' missing field enhancement data. The presented results facilitate the future applications of BICs in acoustics as high-intensity sound sources, filters, and sensors.
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The differentiation of naive CD8+ T lymphocytes into cytotoxic effector and memory CTL results in large-scale changes in transcriptional and phenotypic profiles. Little is known about how large-scale changes in genome organization underpin these transcriptional programs. We use Hi-C to map changes in the spatial organization of long-range genome contacts within naive, effector, and memory virus-specific CD8+ T cells. We observe that the architecture of the naive CD8+ T cell genome is distinct from effector and memory genome configurations, with extensive changes within discrete functional chromatin domains associated with effector/memory differentiation. Deletion of BACH2, or to a lesser extent, reducing SATB1 DNA binding, within naive CD8+ T cells results in a chromatin architecture more reminiscent of effector/memory states. This suggests that key transcription factors within naive CD8+ T cells act to restrain T cell differentiation by actively enforcing a unique naive chromatin state.
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Linfócitos T CD8-Positivos , Cromatina , Diferenciação Celular , Fatores de Transcrição/genética , Memória Imunológica/genéticaRESUMO
IMPORTANCE: There has been a decrease in healthcare-associated Clostridioides difficile infection in Australia, but an increase in the genetic diversity of infecting strains, and an increase in community-associated cases. Here, we studied the genetic relatedness of C. difficile isolated from patients at a major hospital in Melbourne, Australia. Diverse ribotypes were detected, including those associated with community and environmental sources. Some types of isolates were more likely to carry antimicrobial resistance determinants, and many of these were associated with mobile genetic elements. These results correlate with those of other recent investigations, supporting the observed increase in genetic diversity and prevalence of community-associated C. difficile, and consequently the importance of sources of transmission other than symptomatic patients. Thus, they reinforce the importance of surveillance for in both hospital and community settings, including asymptomatic carriage, food, animals, and other environmental sources to identify and circumvent important sources of C. difficile transmission.
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Clostridioides difficile , Infecções por Clostridium , Infecção Hospitalar , Animais , Humanos , Clostridioides difficile/genética , Infecções por Clostridium/epidemiologia , Genômica , Infecção Hospitalar/epidemiologia , AustráliaRESUMO
Importance: Educational attainment in the US is associated with life expectancy. As the opioid crisis worsens, it is critical to understand how overdose death rate trends evolve across education groups. Objective: To investigate the association between educational attainment and overdose death rates, with emphasis on trends during the COVID-19 pandemic. Design, Setting, and Participants: This cross-sectional study used National Vital Statistics System Mortality Multiple Cause-of-Death data describing overdose death rates in the US by educational attainment from January 1, 2000, to December 31, 2021, with a focus on 2018 to 2021. Overdose deaths were aggregated by year and educational level for decedents aged 25 years or older. Exposure: Educational attainment, categorized as no high school (HS) diploma, HS diploma (or General Educational Development) but no college, some college but no bachelor's degree, and bachelor's degree or more. Main Outcomes and Measures: The main outcomes were rates of all overdose deaths, overdose deaths involving opioids, and overdose deaths involving synthetic opioids. Results: Of 912â¯057 overdose deaths with education information from 2000 to 2021 (mean [SD] age at death, 44.9 [12.3] years; 64.1% male), there were 625â¯400 deaths (68.6%) among individuals with no college education and 286â¯657 deaths (31.4%) among those with at least some college. The overdose death rate was 19.9 per 100â¯000 population. From 2018 to 2021, there were 301â¯557 overdose deaths, including 58â¯319 (19.3%) among individuals without an HS diploma, 153â¯603 (50.9%) among people with an HS diploma, 64â¯682 (21.4%) among individuals with some college, and 24â¯953 (8.3%) among individuals with a bachelor's degree. There were 3324 overdose deaths (1.1%) among American Indian or Alaska Native individuals, 2968 (1.0%) among Asian American or Pacific Islander individuals, 49â¯152 (16.3%) among Black individuals, 31â¯703 (10.5%) among Hispanic individuals, 211â¯359 (70.1%) among White individuals, and 3051 (1.0%) among multiracial individuals. From 2018 to 2021, the overdose death rate was 33.4 per 100â¯000 population, the opioid-related overdose death rate was 24.2 per 100â¯000 population, and the synthetic opioid overdose death rate was 19.1 per 100â¯000 population. From 2018 to 2021, the overdose death rate for those without a HS diploma increased by 35.4 per 100â¯000 population compared with 1.5 per 100â¯000 population for those with a bachelor's degree. This differential growth was primarily due to increased rates of death involving synthetic opioids. Conclusions and Relevance: In this cross-sectional study, lower educational attainment was found to be associated with higher growth in overdose deaths. As the opioid crisis has transitioned to fentanyl and polysubstance use, overdose deaths have become more prevalent in groups with lower socioeconomic status, potentially exacerbating existing life-expectancy disparities.
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Overdose de Drogas , Overdose de Opiáceos , Humanos , Masculino , Feminino , Estudos Transversais , Pandemias , Analgésicos Opioides , EscolaridadeRESUMO
Arrangements of acoustic meta-atoms, better known as acoustic metamaterials, are commonly applied in acoustic cloaking, for the attenuation of acoustic fields or for acoustic focusing. A precise design of single meta-atoms is required for these purposes. Understanding the details of their interaction allows improvement of the collective performance of the meta-atoms as a system, for example, in sound attenuation. Destructive interference of their scattered fields, for example, can be mitigated by adjusting the coupling or tuning of individual meta-atoms. Comprehensive numerical studies of various configurations of a resonator pair show that the coupling can lead to degenerate modes at periodic distances between the resonators. We show how the resonators' separation and relative orientation influence the coupling and thereby tunes the sound attenuation. The simulation results are supported by experiments using a two-dimensional parallel-plate waveguide. It is shown that coupling parameters like distance, orientation, detuning, and radiation loss provide additional degrees of freedom for efficient acoustic meta-atom tuning to achieve unprecedented interactions with excellent sound attenuation properties.
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BACKGROUND: Physician Orders for Life Sustaining Treatment (POLST) document instructions for intensity of care based upon patient care preferences. POLST forms generally reflect patients' wishes and dictate subsequent medical care, but it is not known how POLST use and content among nursing home residents is associated with inpatient utilization across a large population. OBJECTIVE: Evaluate the relationship between POLST use and content with hospital utilization among nursing home residents in California. DESIGN: Retrospective cohort study using the Minimum Data Set linked to California Section S (POLST documentation), the Medicare Beneficiary Summary File, and Medicare line item claims. PATIENTS: California nursing home residents with Medicare fee-for-service insurance, 2011-2016. MAIN MEASURES: Hospitalization, days in the hospital, and days in the intensive care unit (ICU) after adjustment for resident and nursing home characteristics. KEY RESULTS: The 1,112,834 residents had a completed and signed (valid) POLST containing orders for CPR with Full treatment 29.6% of resident-time (in person-years) and a DNR order with Selective treatment or Comfort care 27.1% of resident-time. Unsigned POLSTs accounted for 11.3% of resident-time. Residents experienced 14 hospitalizations and a mean of 120 hospital days and 37 ICU days per 100 person-years. Residents with a POLST indicating CPR Full treatment had utilization nearly identical to residents without a POLST. A gradient of decreased utilization was related to lower intensity of care orders. Compared to residents without a POLST, residents with a POLST indicating DNR Comfort care spent 56 fewer days in the hospital and 22 fewer days in the ICU per 100 person-years. Unsigned POLST had a weaker and less consistent relationship with hospital utilization. CONCLUSIONS: Among California NH residents, there is a direct relationship between intensity of care preferences in POLST and hospital utilization. These findings emphasize the importance of a valid POLST capturing informed preferences for nursing home residents.