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1.
Cell ; 171(7): 1663-1677.e16, 2017 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-29224779

RESUMO

Social behaviors are crucial to all mammals. Although the prelimbic cortex (PL, part of medial prefrontal cortex) has been implicated in social behavior, it is not clear which neurons are relevant or how they contribute. We found that PL contains anatomically and molecularly distinct subpopulations that target three downstream regions that have been implicated in social behavior: the nucleus accumbens (NAc), amygdala, and ventral tegmental area. Activation of NAc-projecting PL neurons (PL-NAc), but not the other subpopulations, decreased the preference for a social target. To determine what information PL-NAc neurons convey, we selectively recorded from them and found that individual neurons were active during social investigation, but only in specific spatial locations. Spatially specific manipulation of these neurons bidirectionally regulated the formation of a social-spatial association. Thus, the unexpected combination of social and spatial information within the PL-NAc may contribute to social behavior by supporting social-spatial learning.


Assuntos
Sistema Límbico , Neurônios/citologia , Núcleo Accumbens/citologia , Córtex Pré-Frontal/citologia , Comportamento Social , Comportamento Espacial , Tonsila do Cerebelo/fisiologia , Animais , Aprendizagem , Camundongos , Vias Neurais , Neurônios/fisiologia , Núcleo Accumbens/fisiologia , Córtex Pré-Frontal/fisiologia , Área Tegmentar Ventral/fisiologia
2.
Nano Lett ; 24(3): 920-928, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38207109

RESUMO

Organic nanoparticles are used in nanomedicine, including for cancer treatment and some types of COVID-19 vaccines. Here, we demonstrate the scalable, rapid, reproducible, and cost-effective synthesis of three model organic nanoparticle formulations relevant to nanomedicine applications. We employed a custom-made, low-cost fluid mixer device constructed from a commercially available three-dimensional printer. We investigated how systematically changing aqueous and organic volumetric flow rate ratios determined liposome, polymer nanoparticle, and solid lipid nanoparticle sizes, size distributions, and payload encapsulation efficiencies. By manipulating inlet volumes, we synthesized organic nanoparticles with encapsulation efficiencies approaching 100% for RNA-based payloads. The synthesized organic nanoparticles were safe and effective at the cell culture level, as demonstrated by various assays. Such cost-effective synthesis approaches could potentially increase the accessibility to clinically relevant organic nanoparticle formulations for personalized nanomedicine applications at the point of care, especially in nonhospital and low-resource settings.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas , Humanos , Sistemas de Liberação de Medicamentos/métodos , Nanomedicina/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Vacinas contra COVID-19 , Análise Custo-Benefício , Lipossomos
3.
Opt Express ; 32(10): 16702-16711, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38858869

RESUMO

Polarization management, and in particular polarization rotation, is becoming increasingly important for photonic integrated circuits (PICs). While fiber-optic networks are generally polarization insensitive, the large aspect ratio of high-index-contrast PIC waveguides leads to a large polarization-dependent response of integrated components such as waveguides, optical cavities, couplers, etc. Although foundry-processed polarization rotators operating at telecom and datacom wavelengths (C- and O-band) have been demonstrated, to date, there have been few reports of devices operating at shorter wavelengths. This work demonstrates silicon nitride (SiN) polarization rotators operating from λ=700-1000 nm (the I/Z-band) that take advantage of optical coupling between two waveguiding layers in a standard foundry process. We demonstrate a broadband white-light polarization measurement setup that enables precise characterization of the polarization-dependent transmission of photonic waveguide devices. Measurements on foundry-processed devices confirm full TE-to-TM rotation exhibiting a maximum polarization extinction ratio (PER) approaching 20 dB (limited by our measurement setup), and an exceptionally large bandwidth of up to 160 nm with an insertion loss less than 0.2 dB. Beam propagation method (3D-BPM) simulations show good agreement with experimental data and enable the device parameters to be adjusted to accommodate different operating wavelengths and geometries with no changes to the existing foundry process. This work opens up opportunities for applications in quantum information and bio-sensing where operation at λ<1000nm is needed.

4.
Opt Express ; 32(4): 4745-4755, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439219

RESUMO

Waveguide-enhanced Raman spectroscopy (WERS) is an analytical technique frequently employed for chemical and biological sensing. Operation at visible wavelengths to harness the inverse fourth power with excitation wavelength signal scaling of Raman scattering intensity is desirable, to combat the inherent inefficiency of Raman spectroscopy. Until now, WERS demonstrations in the visible have required custom materials and fabrication, resulting in high losses and low yields. In this work, we demonstrate a silicon nitride (SIN) visible WERS platform fabricated in a 300 mm complementary metal-oxide semiconductor (CMOS) foundry. We measure the propagation loss, coupling loss, WERS signal, and background for WERS spirals designed for 532 nm and 633 nm pump wavelengths. We compare these results to the state-of-the-art near-infrared WERS platform at 785 nm. Further, we theoretically validate the relative performance of each of these WERS configurations, and we discuss the optimal WERS configuration at visible wavelengths. We conclude that a configuration optimized for 785 nm pumping provides the greatest signal-to-background ratio in the fingerprint region of the spectrum, and pumping at 633 nm maximizes Stokes signal out to 3000 cm-1.

5.
J Clin Gastroenterol ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38567890

RESUMO

OBJECTIVE: We examined the associations among advance directives (ADs) completion, coping, uncertainty in illness, and optimism and pessimism in patients with end-stage liver disease (ESLD). BACKGROUND: Although associations among ADs, coping, and uncertainty have been studied in patients with other life-limiting illnesses, these concepts have not been studied together in patients with ESLD. PATIENTS AND METHODS: Patients were recruited at 2 health care institutions as part of a larger prospective study. They were enrolled if they had a diagnosis of nonhepatocellular carcinoma ESLD, Sodium Model for End-Stage Liver Disease ≥15, and no prior history of liver transplantation. Uncertainty, coping, optimism, and pessimism were assessed using the Uncertainty in Illness Scale for Adults, Revised Ways of Coping Checklist, and Life Orientation Test-revised. AD documentation at the time of study enrollment was retrospectively extracted from patient medical records. RESULTS: In the sample [N = 181; median age = 57 y, 115 (64%) males], male sex [odds ratio (OR) = 4.66; 95% CI: 1.53, 14.17], being listed or under evaluation for liver transplantation (OR = 3.09; 95% CI: 1.10, 8.67), greater Sodium Model for End-Stage Liver Disease scores (OR = 1.10; 95% CI: 1.01, 1.20), and greater uncertainty (OR = 1.04; 95% CI: 1.01, 1.07) were positively associated with AD documentation. Higher coping avoidance was negatively associated with AD documentation (OR = 0.915; 95% CI: 0.840, 0.997). CONCLUSIONS: Clinicians should consider the role of uncertainty and coping measures to improve patient-specific advance care planning conversations and expand opportunities for all patients with ESLD to file an AD, especially women and patients not listed or under evaluation for transplantation.

6.
Support Care Cancer ; 32(7): 447, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902487

RESUMO

PURPOSE: Lung cancer is a disease with high mortality and morbidity, impacting both the patient and their closest contact, referred to in this paper as their care partner. There is limited evidence on how to support mental health and quality of life (QOL) for patient-care partner dyads during cancer treatment. This pilot study examines yoga as an intervention to improve well-being for the dyad. METHODS: A single-group, 12-week pilot trial of yoga for patients and their care partners recruited from two hospitals during cancer treatment (N = 23 patient-partner dyads or 46 individuals). Most care partners were spouses (70%), with the remainder being adult children (22%), a sibling (4%), or a friend (4%). Descriptive statistics, Cohen's d effect sizes, and paired t-tests for validated psychosocial measures were calculated at baseline and 12 weeks. RESULTS: Sixty-five percent of dyads (N = 13) completed the study, with withdrawals mostly due to disease progression. Among care partners, there was a decrease in depression symptomology on the PHQ-8 (p = 0.015, Cohen's d = 0.96) and improvement in QOL on the Caregiver QOL-Cancer scale (p = 0.001, Cohen's d = 0.61). Fifty percent of dyads experienced concordant improvement in depressive symptoms and 77% in QOL. CONCLUSION: Patient-partner yoga is a promising intervention for improving mental health and QOL for patient-partner dyads among lung cancer survivors. This study demonstrates yoga to be acceptable, feasible, and with high concordance within patient-partner dyads for improvements in QOL. Yoga shows promise for patients and care partners to alleviate the negative psychosocial impacts of lung cancer, though more research is needed to confirm effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03649737, 12/9/2020.


Assuntos
Cuidadores , Neoplasias Pulmonares , Qualidade de Vida , Yoga , Humanos , Feminino , Masculino , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/terapia , Projetos Piloto , Pessoa de Meia-Idade , Cuidadores/psicologia , Idoso , Depressão/etiologia , Depressão/terapia , Adulto
7.
Child Dev ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664925

RESUMO

Parental chronic pain is associated with adverse outcomes in children, but the mechanisms of transmission are largely untested. Mothers with chronic pain (N = 400, Mage = 40.3 years, 90.5% White) and their children (Mage = 10.33 years, 83.3% White, 50.2% female) were recruited in 2016-2018 to test longitudinal pathways of risk transmission from maternal chronic pain to children's psychological symptoms, examining roles of parenting, maternal depression, and child distress tolerance. Maternal pain was associated with positive (ß = .28) and pain-specific (ß = .10) parenting behaviors. Maternal depression was associated with lower child distress tolerance (ß = -.03), which was associated with greater child psychological symptoms (ß = -.62). Parenting and maternal pain were not prospectively associated with child outcomes. When considering the dual-generational impacts of chronic pain, physical and psychological functioning should be examined.

8.
Arch Phys Med Rehabil ; 105(6): 1106-1115, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38354878

RESUMO

OBJECTIVE: This study aimed to characterize mobility patterns using wearable inertial sensors and serial assessment across autologous hematopoietic cell transplant (autoHCT) and investigate the relation between mobility and perceived function in patients with hematologic cancer. DESIGN: Prospective longitudinal study. SETTING: Hospital adult transplant clinic followed by discharge. PARTICIPANTS: 78 patients with hematological cancer receiving autoHCT. MAIN OUTCOME MEASURES: Mobility was measured across 3 clinical phases (pretransplant, pre-engraftment, and post-engraftment) in using inertial sensors worn during prescribed performance tests in the hospital. Perceived function was assessed using validated provider-reported (Eastern Cooperative Oncology Group [ECOG] Performance Status Scale) and patient-reported [European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30]) measures. Trajectories of 5 selected mobility characteristics (turn duration, gait speed, stride time variability, double support time, and heel strike angle) across the clinical phases were also evaluated using piecewise linear mixed-effects models. RESULTS: Using Principal Components Analysis, 4 mobility patterns were identified pretransplant: Gait Limitation, Sagittal Sway, Coronal Sway, and Balance Control. Gait Limitation measured pretransplant was significantly inversely associated with perceived function reported by the provider- (ß = -0.11; 95% CI: -0.19, -0.02) and patient- (ß = -4.85; 95% CI: -7.72, -1.99) post-engraftment in age-adjusted linear regression models. Mobility characteristics demonstrated immediate declines early pre-engraftment with stabilization by late pre-engraftment. CONCLUSION: Patients with hematological cancer experiencing gait limitations pretransplant are likely to have worse perceived function post-engraftment. Mobility declines in early phases post-transplant and may not fully recover, indicating an opportunity for timely rehabilitation referrals. Wearable inertial sensors can be used to identify early mobility problems and patients who may be at risk for future functional decline who may be candidates for early physical rehabilitation.


Assuntos
Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Dispositivos Eletrônicos Vestíveis , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Hematológicas/reabilitação , Estudos Longitudinais , Adulto , Transplante Autólogo , Equilíbrio Postural/fisiologia , Idoso , Limitação da Mobilidade , Qualidade de Vida , Velocidade de Caminhada/fisiologia
9.
Nurs Res ; 73(4): E202-E211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38526959

RESUMO

BACKGROUND: Chronic liver disease is a significant global neglected public health problem. End-stage liver disease is associated with substantial symptom complexity, disability, and care needs that require assistance from informal family care partners. Research on these care partners' caregiver burden or strain, symptoms, and quality of life is sparse and has not focused on these variables as co-occurring or in the context of the quality of the relationship care partners have with the patients. OBJECTIVES: The purpose of this study was to provide a collective presentation of patterns and determinants of well-being as measured by caregiver strain, depression, sleep, and quality of life in a cohort of informal family care partners for adult outpatients with end-stage liver disease. METHODS: Care partners (aged >18 years) were recruited from two liver clinics within two tertiary healthcare systems and invited to complete a cross-sectional survey. They completed the Multidimensional Caregiver Strain Index, Patient Health Questionnaire, Pittsburgh Sleep Quality Index, Short Form Health Survey, and Mutuality Scale. Descriptive statistics and latent class mixture modeling were used to analyze these data. RESULTS: The sample was predominantly female and White. The well-being of care partners was diminished. Three distinct classes of well-being were identified: mildly diminished (53.2%), moderately diminished (39.0%), and severely diminished (7.8%). Those at a greater risk of worse well-being were younger and spouses and had poorer relationship quality with the patients. DISCUSSION: To improve the well-being of care partners in moderately and severely diminished classes, assessing and addressing caregiver strain and co-occurring symptoms is essential. Addressing the strain and symptoms has the potential to maintain or optimize care partners' ability to provide care to patients. Future researchers should include longitudinal and dyadic studies to examine how patients' disease progression and symptoms may affect family care partners' well-being and vice versa.


Assuntos
Cuidadores , Doença Hepática Terminal , Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Cuidadores/psicologia , Qualidade de Vida/psicologia , Estudos Transversais , Doença Hepática Terminal/psicologia , Doença Hepática Terminal/complicações , Adulto , Idoso , Inquéritos e Questionários
10.
Proc Natl Acad Sci U S A ; 118(24)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34108241

RESUMO

Social scientists and community advocates have expressed concerns that many social and cultural impacts important to citizens are given insufficient weight by decision makers in public policy decision-making. In two large cross-sectional surveys, we examined public perceptions of a range of social, cultural, health, economic, and environmental impacts. Findings suggest that valued impacts are perceived through an initial lens that highlights both tangibility (how difficult it is to understand, observe, and make changes to an impact) and scope (how broadly an impact applies). Valued impacts thought to be less tangible and narrower in scope were perceived to have less support by both decision makers and the public. Nearly every valued impact was perceived to have more support from the public than from decision makers, with the exception of three economic considerations (revenues, profits, and costs). The results also demonstrate that many valued impacts do not fit neatly into the single-category distinctions typically used as part of impact assessments and cost-benefit analyses. We provide recommendations for practitioners and suggest ways that these results can foster improvements to the quality and defensibility of risk and impact assessments.


Assuntos
Cultura , Formulação de Políticas , Opinião Pública , Política Pública , Mudança Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Tomada de Decisões , Humanos , Pessoa de Meia-Idade , Análise de Componente Principal , Adulto Jovem
11.
Risk Anal ; 44(4): 918-938, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37507343

RESUMO

Uncertainty that arises from disputes among scientists seems to foster public skepticism or noncompliance. Communication of potential cues to the relative performance of contending scientists might affect judgments of which position is likely more valid. We used actual scientific disputes-the nature of dark matter, sea level rise under climate change, and benefits and risks of marijuana-to assess Americans' responses (n = 3150). Seven cues-replication, information quality, the majority position, degree source, experience, reference group support, and employer-were presented three cues at a time in a planned-missingness design. The most influential cues were majority vote, replication, information quality, and experience. Several potential moderators-topical engagement, prior attitudes, knowledge of science, and attitudes toward science-lacked even small effects on choice, but cues had the strongest effects for dark matter and weakest effects for marijuana, and general mistrust of scientists moderately attenuated top cues' effects. Risk communicators can take these influential cues into account in understanding how laypeople respond to scientific disputes, and improving communication about such disputes.


Assuntos
Atitude , Dissidências e Disputas , Humanos , Comunicação , Mudança Climática , Julgamento
12.
J Arthroplasty ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38401609

RESUMO

BACKGROUND: Synovial fluid analysis is important in diagnosing prosthetic joint infection (PJI). The rate of culture-positive PJI in patients who have a dry tap of a total hip arthroplasty (THA) is not well described. METHODS: We reviewed all image-guided THA aspirations, performed from 2014 to 2021 at a single academic institution. Aspirations were categorized as successful (≥ 0.5 mL) or unsuccessful (< 0.5 mL, "dry tap"). We analyzed culture data on all repeat aspirations and revision surgeries performed within 90 days of the initial dry tap. RESULTS: We reviewed 275 consecutive attempted THA aspirations of which 100 (36.4%) resulted in a dry tap. The dry tap cohort had a significantly higher percentage of fluoroscopic-guided aspirations (64%) and fewer ultrasound-guided aspirations (36%) compared to the successful aspiration cohort (48.9% fluoroscopic, 53.1% ultrasound, P = .0061). Of the 100 patients who have dry taps, 48 underwent revision surgery within 90 days of the initial dry tap, and 15 resulted in 2 or more positive cultures. The rate of PJI defined by MusculoSkeletal Infection Society major criteria in the dry tap cohort was 16.0%. CONCLUSIONS: Attempted aspiration of a THA resulted in a dry tap 36.4% of the time. Of those patients who had a dry tap, 16.0% were subsequently found to have PJI based on MusculoSkeletal Infection Society major criteria. Therefore, a "dry tap" does not exclude the diagnosis of infection and should not be considered reassuring for the absence of PJI.

13.
J Reconstr Microsurg ; 40(1): 59-69, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37186096

RESUMO

BACKGROUND: Limb-threatening lower extremity injuries often require secondary bone grafting after soft tissue reconstruction. We hypothesized that there would be fewer wound complications when performing secondary bone grafting via a remote surgical approach rather than direct flap elevation. METHODS: A retrospective cohort study was performed at a single Level 1 trauma center comparing complications after secondary bone grafting in patients who had undergone previous soft tissue reconstruction after open tibia fractures between 2006 and 2020. Comparing bone grafting via a remote surgical incision versus direct flap elevation, we evaluated wound dehiscence requiring return to the operating room as the primary outcome. Secondary outcomes were deep infection and delayed amputation. RESULTS: We identified 129 patients (mean age: 40 years, 82% male) with 159 secondary bone grafting procedures. Secondary bone grafting was performed via a remote surgical approach in 54% (n = 86) and direct flap elevation in 46% (n = 73) of cases. Wound dehiscence requiring return to the operating room occurred in one patient in the flap elevation group (1%) and none of the patients in the remote surgical approach. The odds of deep wound infection (OR, 1.77; p = 0.31) or amputation (OR, 1.43; p = 0.73) did not significantly differ between surgical approaches. No significant differences were found in complications between the reconstructive surgeon elevating and re-insetting the flap and the orthopaedic trauma surgeon performing the flap elevation and re-inset. CONCLUSION: Direct flap elevation for secondary bone grafting after soft tissue reconstruction for open tibia fractures did not result in more complications than bone grafting via a remote surgical approach. These findings should reassure surgeons to allow other clinical factors to influence the surgical approach for bone grafting.


Assuntos
Traumatismos da Perna , Lesões dos Tecidos Moles , Humanos , Masculino , Adulto , Feminino , Estudos Retrospectivos , Seguimentos , Retalhos Cirúrgicos , Traumatismos da Perna/cirurgia , Complicações Pós-Operatórias , Lesões dos Tecidos Moles/cirurgia , Extremidade Inferior , Resultado do Tratamento
14.
Ann Oncol ; 34(2): 173-185, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36414192

RESUMO

BACKGROUND: First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival. PATIENTS AND METHODS: Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed. RESULTS: In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population. CONCLUSION: Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Nivolumabe/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
15.
Opt Express ; 31(19): 31316-31328, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710654

RESUMO

Optical fibers are generally polarization-insensitive while photonic integrated circuits (PICs) often exhibit a large polarization dependence due to the high-aspect-ratio and high-index-contrast of integrated waveguides. As PICs become more mature there is an increasing need for tunable polarization management on-chip. Although micro-electro-mechanical systems (MEMS) are increasingly finding application in PICs for optical switching and phase shifting, they have so far not found wide application for polarization management. In this work we propose two optical MEMS architectures for polarization management enabling tunable polarization splitting and rotation - key functions so far lacking in PICs. The first structure consists of a directional coupler with a MEMS-tunable gap enabling a continuously-variable polarization splitting ratio. A second architecture consists of a symmetry-breaking MEMS perturber suspended over an air-cladded waveguide enabling tunable polarization rotation. For both architectures we simulate a polarization extinction exceeding 25 dB, and the operating bandwidth can be as large as 100 nm. We conclude with a discussion of actuation schemes and examine fabrication considerations for implementation in PIC foundries.

16.
Acta Neuropathol ; 145(4): 395-408, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36681782

RESUMO

Hippocampal sclerosis (HS) is associated with advanced age as well as transactive response DNA-binding protein with 43 kDa (TDP-43) deposits. Both hippocampal sclerosis and TDP-43 proteinopathy have also been described in chronic traumatic encephalopathy (CTE), a neurodegenerative disease linked to exposure to repetitive head impacts (RHI). However, the prevalence of HS in CTE, the pattern of TDP-43 pathology, and associations of HS and TDP-43 with RHI are unknown. A group of participants with a history of RHI and CTE at autopsy (n = 401) as well as a group with HS-aging without CTE (n = 33) was examined to determine the prevalence of HS and TDP-43 inclusions in CTE and to compare the clinical and pathological features of HS and TDP-43 inclusions in CTE to HS-aging. In CTE, HS was present in 23.4%, and TDP-43 inclusions were present in 43.3% of participants. HS in CTE occurred at a relatively young age (mean 77.0 years) and was associated with a greater number of years of RHI than CTE without HS adjusting for age (p = 0.029). In CTE, TDP-43 inclusions occurred frequently in the frontal cortex and occurred both with and without limbic TDP-43. Additionally, structural equation modeling demonstrated that RHI exposure years were associated with hippocampal TDP-43 inclusions (p < 0.001) through increased CTE stage (p < 0.001). Overall, RHI and the development of CTE pathology may contribute to TDP-43 deposition and hippocampal sclerosis.


Assuntos
Encefalopatia Traumática Crônica , Esclerose Hipocampal , Doenças Neurodegenerativas , Proteinopatias TDP-43 , Humanos , Idoso , Encefalopatia Traumática Crônica/patologia , Envelhecimento , Proteinopatias TDP-43/patologia , Proteínas de Ligação a DNA/metabolismo
17.
Opt Lett ; 48(2): 427-430, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36638474

RESUMO

Mode-division multiplexing (MDM) enables a large increase in the information-carrying capacity of an optical network. Recently, chip-scale MDM devices that can switch different mode orders to different output waveguides have been demonstrated. However, an important milestone showing dynamically tunable mode-order conversion in a single compact device has so far not been reported. In this work, we demonstrate via simulation and measurement a new, to the best of our knowledge, approach for reconfigurable mode conversion using optical micro-electro-mechanical systems (MEMS) to locally modify the effective index in an asymmetric coupler. Modeling shows that dynamic tuning to increase or decrease the mode order is possible. Measurements on fabricated devices are consistent with simulations of reconfigurable mode conversion based on tunable phase matching. Our experimental results demonstrate reconfigurable TE0-TE2 to TE0-TE1 conversion and validate this new tunable phase-matching approach for mode-division multiplexing.

18.
BMC Cancer ; 23(1): 1087, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37946117

RESUMO

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and dose-limiting side effect of systemic cancer therapy. In many cancer survivors, CIPN persists after treatment ends and is associated with functional impairments, abnormal gait patterns, falls, and diminished quality of life. However, little is known regarding which patients are most likely to develop CIPN symptoms that impair mobility and increase fall risk, when this risk develops, or the optimal timing of early intervention efforts to mitigate the impact of CIPN on functioning and fall risk. This study will address these knowledge gaps by (1) characterizing trajectories of symptoms, functioning, and falls before, during, and after treatment in adults prescribed neurotoxic chemotherapy for cancer; and (2) determining the simplest set of predictors for identifying individuals at risk for CIPN-related functional decline and falls. METHODS: We will enroll 200 participants into a prospective, observational study before initiating chemotherapy and up to 1 year after completing chemotherapy. Eligible participants are aged 40-85 years, diagnosed with stage I-III cancer, and scheduled to receive neurotoxic chemotherapy. We perform objective assessments of vibratory and touch sensation (biothesiometry, tuning fork, monofilament tests), standing and dynamic balance (quiet stance, Timed-Up-and-Go tests), and upper and lower extremity strength (handgrip dynamometry, 5-time repeated chair stand test) in the clinic at baseline, every 4-6 weeks during chemotherapy, and quarterly for 1 year post-chemotherapy. Participants wear devices that passively and continuously measure daily gait quality and physical activity for 1 week after each objective assessment and self-report symptoms (CIPN, insomnia, fatigue, dizziness, pain, cognition, anxiety, and depressive symptoms) and falls via weekly electronic surveys. We will use structural equation modeling, including growth mixture modeling, to examine patterns in trajectories of changes in symptoms, functioning, and falls associated with neurotoxic chemotherapy and then search for distinct risk profiles for CIPN. DISCUSSION: Identifying simple, early predictors of functional decline and fall risk in adults with cancer receiving neurotoxic chemotherapy will help identify individuals who would benefit from early and targeted interventions to prevent CIPN-related falls and disability. TRIAL REGISTRATION: This study was retrospectively registered with ClinicalTrials.gov (NCT05790538) on 3/30/2023.


Assuntos
Antineoplásicos , Neoplasias , Síndromes Neurotóxicas , Doenças do Sistema Nervoso Periférico , Adulto , Humanos , Antineoplásicos/efeitos adversos , Força da Mão , Neoplasias/complicações , Estudos Observacionais como Assunto , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Estudos Prospectivos , Qualidade de Vida , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
19.
BMC Public Health ; 23(1): 1895, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37784086

RESUMO

BACKGROUND: Rural residents generally lack adequate physical activity to benefit health and reduce disparities in chronic diseases, such as cardiovascular disease and certain cancers. The Socioecological Model describes physical activity as involving a dynamic and reciprocal interaction between individual, social, and community factors. Community group-based walking programs and civic engagement interventions aimed at enhancing physical activity have been successful in rural communities but have not targeted all three socioecological levels. Public libraries can act as innovative public health partners in rural communities. However, challenges remain because rural libraries often lack the capacity to implement evidence-based health promotion programming. The goals of this study are (1) build the capacity for rural libraries to implement evidence-based health promotion programs, (2) compare changes in physical activity between a group-based walking program and a combined group-based walking and civic engagement program with rural residents, and (3) conduct an implementation evaluation. METHODS: We will conduct a comparative effectiveness study of a group-based walking (standard approach) versus a group-based walking plus civic engagement program (combined approach) aimed at enhancing walkability to increase physical activity among rural adults. Key mediators between the program effects and change in outcomes will also be identified. Finally, we will evaluate program implementation, conduct a cost effectiveness evaluation, and use a positive deviance analysis to understand experiences of high and low changers on key outcomes. Twenty towns will be matched and randomized to one of the two conditions and our aim is to enroll a total of 350-400 rural residents (15-20 per town). Study outcomes will be assessed at baseline, and 6, 12, and 24 months. DISCUSSION: This study will build the capacity of rural libraries to implement evidence-based walking programs as well as other health promotion programs in their communities. The study results will answer questions regarding the relative effectiveness and cost effectiveness of two multilevel physical activity interventions targeting rural communities. We will learn what works and how these multilevel interventions can be implemented in rural populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05677906.


Assuntos
População Rural , Caminhada , Adulto , Humanos , Exercício Físico , Promoção da Saúde/métodos , Comportamentos Relacionados com a Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
J Cardiovasc Nurs ; 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37639560

RESUMO

BACKGROUND: Adults with heart failure (HF) experience a constellation of symptoms; however, understanding of gender differences in HF symptoms remain elusive. The aim of this study was to determine whether there are gender differences in physical and depressive symptoms and symptom patterns in HF using 2 different analytic techniques. METHODS: We performed a secondary analysis of combined data from 6 studies of adults with HF. Physical symptoms were measured with the HF Somatic Perception Scale, and depressive symptoms were measured with the Patient Health Questionnaire-9. First, we performed propensity matching with the nearest neighbor to examine the average treatment effect for HF Somatic Perception Scale and Patient Health Questionnaire-9 in the matched sample of women and men. Next, we used the entire data set in a latent class mixture model to determine patterns of symptoms. Finally, we calculated predictors of class membership with multinomial logistic regression. RESULTS: The sample (n = 524, 86.5% systolic HF) was 37% women with a mean age of 58.3 ± 13.9 years and mean number of years with HF of 6.9 ± 6.9. Three hundred sixty-six participants were matched on propensity scores; there were no significant gender differences in symptom scores between matched women (n = 183) and men (n = 183). Among all 524 participants, 4 distinct latent classes of symptom patterns indicate that many patients with HF are fatigued, some have more depressive symptoms, and others have significantly more edema or cough. Gender did not predict membership to any symptom pattern. CONCLUSIONS: There were significant gender differences in sociodemographics, health behaviors, and clinical characteristics, but not HF symptoms or symptom patterns, using either analytic technique.

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