Deciphering platinum dissolution in neural stimulation electrodes: Electrochemistry or biology?

Platinum (Pt) is the metal of choice for electrodes in implantable neural prostheses like the cochlear implants, deep brain stimulating devices, and brain-computer interfacing technologies. However, it is well known since the 1970s that Pt dissolution occurs with electrical stimulation. More recent clinical and in vivo studies have shown signs of corrosion in explanted electrode arrays and the presence of Pt-containing particulates in tissue samples. The process of degradation and release of metallic ions and particles can significantly impact on device performance. Moreover, the effects of Pt dissolution products on tissue health and function are still largely unknown. This is due to the highly complex chemistry underlying the dissolution process and the difficulty in decoupling electrical and chemical effects on biological responses. Understanding the mechanisms and effects of Pt dissolution proves challenging as the dissolution process can be influenced by electrical, chemical, physical, and biological factors, all of them highly variable between experimental settings. By evaluating comprehensive findings on Pt dissolution mechanisms reported in the fuel cell field, this review presents a critical analysis of the possible mechanisms that drive Pt dissolution in neural stimulation in vitro and in vivo. Stimulation parameters, such as aggregate charge, charge density, and electrochemical potential can all impact the levels of dissolved Pt. However, chemical factors such as electrolyte types, dissolved gases, and pH can all influence dissolution, confounding the findings of in vitro studies with multiple variables. Biological factors, such as proteins, have been documented to exhibit a mitigating effect on the dissolution process. Other biological factors like cells and fibro-proliferative responses, such as fibrosis and gliosis, impact on electrode properties and are suspected to impact on Pt dissolution. However, the relationship between electrical properties of stimulating electrodes and Pt dissolution remains contentious. Host responses to Pt degradation products are also controversial due to the unknown chemistry of Pt compounds formed and the lack of understanding of Pt distribution in clinical scenarios. The cytotoxicity of Pt produced via electrical stimulation appears similar to Pt-based compounds, including hexachloroplatinates and chemotherapeutic agents like cisplatin. While the levels of Pt produced under clinical and acute stimulation regimes were typically an order of magnitude lower than toxic concentrations observed in vitro, further research is needed to accurately assess the mass balance and type of Pt produced during long-term stimulation and its impact on tissue response. Finally, approaches to mitigating the dissolution process are reviewed. A wide variety of approaches, including stimulation strategies, coating electrode materials, and surface modification techniques to avoid excess charge during stimulation and minimise tissue response, may ultimately support long-term and safe operation of neural stimulating devices.

Patient Education Practices and Preferences of Radiation Oncologists and Interprofessional Radiation Therapy Care Teams: A Mixed-Methods Study Exploring Strategies for Effective Patient Education Delivery.

PURPOSE: Patients' understanding of radiation therapy (RT) and data regarding optimal approaches to patient education (PE) within radiation oncology (RO) are limited. We aimed to evaluate PE practices of radiation oncologists and interprofessional RT care team members to inform recommendations for delivering inclusive and accessible PE. METHODS AND MATERIALS: An anonymous survey was administered to all Radiation Oncology Education Collaborative Study Group members (10/5/22-11/23/22). Respondent demographics, individual practices/preferences, and institutional practices were collected. Qualitative items explored strategies, challenges, and desired resources for PE. Descriptive statistics summarized survey responses. The Fisher exact test compared PE practices by respondent role and PE timing. Thematic analysis was used for qualitative responses. RESULTS: One hundred thirteen Radiation Oncology Education Collaborative Study Group members completed the survey (28.2% response rate); RO attendings comprised 68.1% of respondents. Most practiced in an academic setting (85.8%) in North America (80.5%). Institution-specific materials were the most common PE resource used by radiation oncologists (67.6%). Almost half (40.2%) reported that their PE practices differed based on clinical encounter type, with paper handouts commonly used for in-person and multimedia for telehealth visits. Only 57.7% reported access to non-English PE materials. PE practices among radiation oncologists differed according to RT clinical workflow timing (consultation versus simulation versus first RT, respectively): one-on-one teaching: 88.5% versus 49.4% versus 56.3%, P < .01, and paper handouts: 69.0% versus 28.7% versus 16.1%, P < .01. Identified challenges for PE delivery included limited time, administrative barriers to the development or implementation of new materials or practices, and a lack of customized resources for tailored PE. Effective strategies for PE included utilization of visual diagrams, multimedia, and innovative education techniques to personalize PE delivery/resources for a diverse patient population, as well as fostering interprofessional collaboration to reinforce educational content. CONCLUSIONS: Radiation oncologists and interprofessional RO team members engage in PE, with most using institution-specific materials often available only in English. PE practices differ according to clinical encounter type and RT workflow timing. Increased adoption of multimedia materials and partnerships with patients to tailor PE resources are needed to foster high-quality, patient-centered PE delivery.

Clinical outcomes after 1 versus 2-3 lines of neoadjuvant therapy in stage III inflammatory breast cancer.

PURPOSE: Many stage III inflammatory breast cancer (IBC) patients experience a sufficient response to first-line (1L) neoadjuvant chemotherapy (NAC) to allow surgery, while some require additional NAC. We evaluated the pathologic complete response (pCR), breast cancer-free survival (BCFS) and overall survival (OS) among patients requiring 1 vs. 2-3 lines (L) of NAC prior to surgery. METHODS: Stage III IBC patients from 2 institutions who received 1L or 2-3L of NAC prior to surgery were identified. Hormone receptor and HER2 status, grade, and pCR were evaluated. BCFS and OS were evaluated by the Kaplan-Meier method. Multivariable Cox models were utilized to estimate the hazard ratio (HR). RESULTS: 808 eligible patients (1997-2020) were identified (median age 51 years, median follow-up 69 months). 733 (91%) had 1L and 75 (9%) had 2-3L of NAC. Grade III, triple-negative and HER2-positive disease were more prevalent in 2-3L patients. 178 (24%) 1L and 14 (19%) 2-3L patients had pCR. 376 1L patients and 41 2-3L patients had recurrences. The 5-year BCFS was worse for the 2-3L group (33 vs. 46%, HR = 1.37; 95% CI 0.99-1.91). However, in 192 patients with a pCR, BCFS was similar (76 vs. 83% in 1L vs. 2-3L, respectively). There were 308 deaths (276 among 1L and 32 among 2-3L patients). The 5-year OS in 1L vs. 2-3L was 60 vs. 53% (HR = 1.32, 95% CI 0.91-1.93). CONCLUSIONS: Among stage III IBC patients, pCR rates were similar, irrespective of the NAC lines number, and BCFS and OS were comparable with pCR after 1L and 2-3L.

Effect of Hydrogel-based Model Fibrosis on Electrical Properties of Bioelectrodes.

Fibrous tissue encapsulation can impact the performance of bioelectrodes following implantation. For example, significant increases in electrode impedance can occur within four weeks post-implantation. A key limitation hindering the understanding of host response-mediated impedance change is the reliance on animal models or complex in vitro cell cultures for electrode testing. This study aimed to develop an in vitro acellular model that can reproduce the changes in electrical properties of bioelectrodes that occur due to host responses following implantation. Specifically, the effect of synthetic, biological, and bio-synthetic co-polymer hydrogel coatings on electrode impedance was measured. Poly(vinyl alcohol) (PVA), gelatin, and PVA-gelatin co-polymers (10 and 20 wt%) were coated onto platinum (Pt) electrodes. Polarisation and access voltage, key components of the voltage response that relate to cell adhesion and protein adsorption respectively, were measured pre and post hydrogel coating and the impedance change was calculated. Results showed that increasing the polymer concentration affects the access resistance regardless of the hydrogel chemistry but only high content gelatin hydrogels increased the polarisation resistance. The increase in total impedance was ~ 2-fold of bare Pt, similar to clinical observations. This study demonstrated that an acellular fibrosis model using hydrogels could reproduce the impedance changes observed in vivo. Such a model system will support research to better understand in vivo changes in electrical properties and the longer term function of neuroprosthetic electrodes.Clinical Relevance-This study proposes an acellular fibrosis model for preclinical research. This will support the design of improved clinical stimulation strategies and better understanding of the mechanisms of impedance change at the device-tissue interface.

Bioelectronic Neural Interfaces: Improving Neuromodulation Through Organic Conductive Coatings.

Integration of bioelectronic devices in clinical practice is expanding rapidly, focusing on conditions ranging from sensory to neurological and mental health disorders. While platinum (Pt) electrodes in neuromodulation devices such as cochlear implants and deep brain stimulators have shown promising results, challenges still affect their long-term performance. Key among these are electrode and device longevity in vivo, and formation of encapsulating fibrous tissue. To overcome these challenges, organic conductors with unique chemical and physical properties are being explored. They hold great promise as coatings for neural interfaces, offering more rapid regulatory pathways and clinical implementation than standalone bioelectronics. This study provides a comprehensive review of the potential benefits of organic coatings in neuromodulation electrodes and the challenges that limit their effective integration into existing devices. It discusses issues related to metallic electrode use and introduces physical, electrical, and biological properties of organic coatings applied in neuromodulation. Furthermore, previously reported challenges related to organic coating stability, durability, manufacturing, and biocompatibility are thoroughly reviewed and proposed coating adhesion mechanisms are summarized. Understanding organic coating properties, modifications, and current challenges of organic coatings in clinical and industrial settings is expected to provide valuable insights for their future development and integration into organic bioelectronics.

Improved Utilization of Serial Testing Without Increased Admissions after Implementation of High-Sensitivity Troponin I: a Controlled Retrospective Cohort Study.

BACKGROUND: Guidelines recommend high-sensitivity cardiac troponin (hs-cTn) for diagnosis of myocardial infarction. Use of hs-cTn is increasing across the U.S., but questions remain regarding clinical and operational impact. Prior studies have had methodologic limitations and yielded conflicting results. OBJECTIVE: To evaluate the impact of transitioning from conventional cardiac troponin (cTn) to hs-cTn on test and resource utilization, operational efficiency, and patient safety. DESIGN: Retrospective cohort study in two New York City hospitals during the months before and after transition from conventional cTn to hs-cTn at Hospital 1. Hospital 2 served as a control. PARTICIPANTS: Consecutive emergency department (ED) patients with at least one cTn test resulted. INTERVENTION: Multifaceted hs-cTn intervention bundle, including a 0/2-h diagnostic algorithm for non-ST-elevation myocardial infarction, an educational bundle, enhancements to the electronic medical record, and nursing interventions to facilitate timed sample collection. MAIN MEASURES: Primary outcomes included serial cTn test utilization, probability of hospital admission, ED length of stay (LOS), and among discharged patients, probability of ED revisit within 72 h resulting in hospital admission. Multivariable regression models adjusted for age, sex, temporal trends, and interhospital differences. KEY RESULTS: The intervention was associated with increased use of serial cTn testing (adjusted risk difference: 48 percentage points, 95% CI: 45-50, P < 0.001) and ED LOS (adjusted geometric mean difference: 50 min, 95% CI: 50-51, P < 0.001). There was no significant association between the intervention and probability of admission (adjusted relative risk [aRR]: 0.99, 95% CI: 0.89-1.1, P = 0.81) or probability of ED revisit within 72 h resulting in admission (aRR: 1.1, 95% CI: 0.44-2.9, P = 0.81). CONCLUSIONS: Implementation of a hs-cTn intervention bundle was associated with an improvement in serial cTn testing, a neutral effect on probability of hospital admission, and a modest increase in ED LOS.

Decoding biological age from face photographs using deep learning.

Because humans age at different rates, a person's physical appearance may yield insights into their biological age and physiological health more reliably than their chronological age. In medicine, however, appearance is incorporated into medical judgments in a subjective and non-standardized fashion. In this study, we developed and validated FaceAge, a deep learning system to estimate biological age from easily obtainable and low-cost face photographs. FaceAge was trained on data from 58,851 healthy individuals, and clinical utility was evaluated on data from 6,196 patients with cancer diagnoses from two institutions in the United States and The Netherlands. To assess the prognostic relevance of FaceAge estimation, we performed Kaplan Meier survival analysis. To test a relevant clinical application of FaceAge, we assessed the performance of FaceAge in end-of-life patients with metastatic cancer who received palliative treatment by incorporating FaceAge into clinical prediction models. We found that, on average, cancer patients look older than their chronological age, and looking older is correlated with worse overall survival. FaceAge demonstrated significant independent prognostic performance in a range of cancer types and stages. We found that FaceAge can improve physicians' survival predictions in incurable patients receiving palliative treatments, highlighting the clinical utility of the algorithm to support end-of-life decision-making. FaceAge was also significantly associated with molecular mechanisms of senescence through gene analysis, while age was not. These findings may extend to diseases beyond cancer, motivating using deep learning algorithms to translate a patient's visual appearance into objective, quantitative, and clinically useful measures.

Emerging trends in the development of flexible optrode arrays for electrophysiology.

Optical-electrode (optrode) arrays use light to modulate excitable biological tissues and/or transduce bioelectrical signals into the optical domain. Light offers several advantages over electrical wiring, including the ability to encode multiple data channels within a single beam. This approach is at the forefront of innovation aimed at increasing spatial resolution and channel count in multichannel electrophysiology systems. This review presents an overview of devices and material systems that utilize light for electrophysiology recording and stimulation. The work focuses on the current and emerging methods and their applications, and provides a detailed discussion of the design and fabrication of flexible arrayed devices. Optrode arrays feature components non-existent in conventional multi-electrode arrays, such as waveguides, optical circuitry, light-emitting diodes, and optoelectronic and light-sensitive functional materials, packaged in planar, penetrating, or endoscopic forms. Often these are combined with dielectric and conductive structures and, less frequently, with multi-functional sensors. While creating flexible optrode arrays is feasible and necessary to minimize tissue-device mechanical mismatch, key factors must be considered for regulatory approval and clinical use. These include the biocompatibility of optical and photonic components. Additionally, material selection should match the operating wavelength of the specific electrophysiology application, minimizing light scattering and optical losses under physiologically induced stresses and strains. Flexible and soft variants of traditionally rigid photonic circuitry for passive optical multiplexing should be developed to advance the field. We evaluate fabrication techniques against these requirements. We foresee a future whereby established telecommunications techniques are engineered into flexible optrode arrays to enable unprecedented large-scale high-resolution electrophysiology systems.

Looking Back: International Practice Patterns in Breast Radiation Oncology From a Case-Based Survey Across 54 Countries During the First Surge of the COVID-19 Pandemic.

PURPOSE: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries. MATERIALS AND METHODS: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests. RESULTS: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC. CONCLUSION: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

Clinical outcomes of de novo metastatic HER2-positive inflammatory breast cancer.

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer that presents as de novo metastatic disease in 20-30% of cases, with one-third of cases demonstrating HER2-positivity. There has been limited investigation into locoregional therapy utilization following HER2-directed systemic therapy for these patients, and their locoregional progression or recurrence (LRPR) and survival outcomes. Patients with de novo HER2-positive metastatic IBC (mIBC) were identified from an IRB-approved IBC registry at Dana-Farber Cancer Institute. Clinical, pathology, and treatment data were abstracted. Rates of LRPR, progression-free survival (PFS), overall survival (OS), and pathologic complete response (pCR) were determined. Seventy-eight patients diagnosed between 1998 and 2019 were identified. First-line systemic therapy comprised chemotherapy for most patients (97.4%) and HER2-directed therapy for all patients (trastuzumab [47.4%]; trastuzumab+pertuzumab [51.3%]; or trastuzumab emtansine [1.3%]). At a median follow-up of 2.7 years, the median PFS was 1.0 year, and the median OS was 4.6 years. The 1- and 2-year cumulative incidence of LRPR was 20.7% and 29.0%, respectively. Mastectomy was performed after systemic therapy in 41/78 patients (52.6%); 10 had a pCR (24.4%) and all were alive at last follow-up (1.3-8.9 years after surgery). Among 56 patients who were alive and LRPR-free at one year, 10 developed LRPR (surgery group = 1; no-surgery group = 9). In conclusion, patients with de novo HER2-positive mIBC who undergo surgery have favorable outcomes. More than half of patients received systemic and local therapy with good locoregional control and prolonged survival, suggesting a potential role for local therapy.

The Placenta in Congenital Langerhans Cell Histiocytosis: A Case Report of Unusual Involvement of Chorionic Plate and Umbilical Vein.

The congenital presentation of Langerhans cell histiocytosis (LCH) is a rare presentation of an uncommon neoplastic process. Concurrent placental parenchymal involvement is even more rare, with just 2 cases of congenital multisystem LCH with placental involvement reported in English medical literature thus far. Here, we present a case of a liveborn male born at 37-weeks, 6-day gestation with congenital LCH focally involving the placenta. Langerhans cells were identified in an area of the placenta showing an unusual mononuclear cell infiltrate in the wall of the umbilical vein. Langerhans cells were also focally identified in areas of chronic villitis, as well as normal-appearing chorionic plate. The examination of the placenta in cases of clinical suspicion of LCH can be of paramount importance since it may provide the early diagnostic evidence of LCH. In this context, placental involvement by LCH should be considered even in the absence of abnormal histology.

Primary Vaginal Epithelioid Angiosarcoma: A Case Report and Literature Review of a Rare Neoplasm.

Angiosarcoma is a malignant neoplasm showing morphological or immunophenotypic evidence of endothelial differentiation with either a vascular or lymphatic origin. It has a strong predilection for skin and deep soft tissue. Angiosarcomas of the gynecologic tract are very uncommon, and very few cases have been described in medical literature up to this day. Primary vaginal angiosarcomas with no prior history of radiation are exceedingly rare. The epithelioid subtype of primary vaginal angiosarcomas is even more uncommon. Here we present a rare case of an epithelioid subtype of primary vaginal angiosarcoma in a 47-year-old woman with no prior history of radiation who presented with pelvic pain, malodorous vaginal discharge, and a vaginal mass.

Growing human-scale scala tympani-likein vitrocell constructs.

Emerging materials and electrode technologies have potential to revolutionise development of higher resolution next-generation, bionic devices. However, barriers associated with the extended timescales, regulatory constraints, and opportunity costs of preclinical and clinical studies, can inhibit such innovation. Development ofin vitromodels that mimic human tissues would provide an enabling platform to overcome many of these barriers in the product development pathway. This research aimed to develop human-scale tissue engineered cochlea models for high throughput evaluation of cochlear implants on the bench. Novel mould-casting techniques and stereolithography three-dimensional (3D) printing approaches to template hydrogels into spiral-shaped structures resembling the scala tympani were compared. While hydrogels are typically exploited to support 3D tissue-like structures, the challenge lies in developing irregular morphologies like the scala tympani, in which the cochlear electrodes are commonly implanted. This study successfully developed human-scale scala tympani-like hydrogel structures that support viable cell adhesion and can accommodate cochlear implants for future device testing.

HIV care cascade for women living with HIV in the Greater Toronto Area versus the rest of Ontario and Canada.

BACKGROUND: The Greater Toronto Area (GTA) is home to 39% of Canada's population living with HIV. To identify gaps in access and engagement in care and treatment, we assessed the care cascade of women living with HIV (WLWH) in the GTA versus the rest of Ontario and Canada (in this case: Quebec and British Columbia). METHODS: We analyzed 2013-2015 self-reported baseline data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study for six care cascade stages: linked to care, retained in care, initiated antiretroviral therapy (ART), currently on ART, ART adherence (≥90%), and undetectable (<50 copies/mL). Multivariable logistic regression was used to reveal associations with being undetectable. RESULTS: Comparing the GTA to the rest of Ontario and Canada, respectively: 96%, 98%, 100% were linked to care; 92%, 94%, 98% retained in care; 72%, 89%, 96% initiated ART; 67%, 81%, 90% were currently using ART; 53%, 66%, 77% were adherent; 59%, 69%, 81% were undetectable. Factors associated with viral suppression in the multivariable model included: living outside of the GTA (Ontario: aOR = 1.72, 95% CI: 1.09-2.72; Canada: aOR = 2.42, 95% CI: 1.62-3.62), non-Canadian citizenship (landed immigrant/permanent resident: aOR = 3.23, 95% CI: 1.66-6.26; refugee/protected person/other status: aOR = 4.77, 95% CI: 1.96-11.64), completed high school (aOR = 1.77, 95% CI: 1.15-2.73), stable housing (aOR = 2.13, 95% CI: 1.33-3.39), income of ≥$20,000 (aOR = 1.52, 95% CI: 1.00-2.31), HIV diagnosis <6 years (6-14 years: aOR = 1.75, 95% CI: 1.16-2.63; >14 years: aOR = 1.87, 95% CI: 1.19-2.96), and higher resilience (aOR = 1.02, 95% CI: 1.00-1.04). CONCLUSION: WLWH living in the GTA had lower rates of viral suppression compared to the rest of Ontario and Canada even after adjustment of age, ethnicity, and HIV diagnosis duration. High-impact programming for WLWH in the GTA to improve HIV outcomes are greatly needed.

Incidence, characteristics, and management of central nervous system metastases in patients with inflammatory breast cancer.

BACKGROUND: Patients with inflammatory breast cancer (IBC) have a high risk of central nervous system metastasis (mCNS). The purpose of this study was to quantify the incidence of and identify risk factors for mCNS in patients with IBC. METHODS: The authors retrospectively reviewed patients diagnosed with IBC between 1997 and 2019. mCNS-free survival time was defined as the date from the diagnosis of IBC to the date of diagnosis of mCNS or the date of death, whichever occurred first. A competing risks hazard model was used to evaluate risk factors for mCNS. RESULTS: A total of 531 patients were identified; 372 patients with stage III and 159 patients with de novo stage IV disease. During the study, there were a total of 124 patients who had mCNS. The 1-, 2-, and 5-year incidence of mCNS was 5%, 9%, and 18% in stage III patients (median follow-up: 5.6 years) and 17%, 30%, and 42% in stage IV patients (1.8 years). Multivariate analysis identified triple-negative tumor subtype as a significant risk factor for mCNS for stage III patients. For patients diagnosed with metastatic disease, visceral metastasis as first metastatic site, triple-negative subtype, and younger age at diagnosis of metastases were risk factors for mCNS. CONCLUSIONS: Patients with IBC, particularly those with triple-negative IBC, visceral metastasis, and those at a younger age at diagnosis of metastatic disease, are at significant risk of developing mCNS. Further investigation into prevention of mCNS and whether early detection of mCNS is associated with improved IBC patient outcomes is warranted.

Electromechanical Stability and Transmission Behavior of Transparent Conductive Films for Biomedical Optoelectronic Devices.

The application of transparent conductive films to flexible biomedical optoelectronics is limited by stringent requirements on the candidate materials' electromechanical and optical properties as well as their biological performance. Thin films of graphene and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) are sought as mechanically flexible alternatives to traditional indium tin oxide (ITO). However, they require more understanding of their suitability for biomedical optoelectronic devices in terms of transmission behavior and electromechanical stability. This study shows that the relative increase in sheet resistance under cyclic loading for ITO, graphene, and PEDOT:PSS was 3546±3908%,12±2.7%, and 62±68%, respectively. Moreover, graphene and PEDOT:PSS showed a transmission uniformity of 9.3% and 36.3% (380-2000 nm), respectively, compared with ITO film (61%). Understanding the optical, electrical, and mechanical limits of the transparent conductive films facilitates the optimization of flexible optoelectronic designs to fit multiple biomedical research and clinical applications.

Breast cancer awareness among Afghan refugee women in Turkey.

Background Refugees and asylum-seekers have lower levels of cancer awareness and this contributes to low rates of screening and more advanced cancers at diagnosis, compared to non-refugee populations, due largely to reduced access to medical information and care. The global Afghan refugee population is rapidly increasing with the ongoing Afghan political crisis. The present study investigates breast cancer (BC) awareness among Afghan refugee women. Methods: A cross-sectional survey of Afghan refugee women residing in Turkey was performed in September 2021. A validated BC patient awareness assessment, the Breast Cancer Awareness Measure (BCAM), was used to assess participants' knowledge of seven domains of BC: symptoms, self-examination, ability to notice breast changes, age-related risk of BC, urgency of addressing changes in the breast, BC risk factors, and BC screening. BCAM was translated into patients' native language and administered verbally by a physician with the assistance of an official interpreter. Routine statistical methods were employed for data analysis. Findings: A total of 430 patients were recruited to the study. The response rate was 97·7% (420 patients). The median participant age was 35 years (range: 18 to 68 years). The majority of participants (84%) had no formal education. Most participants (96%) were married, and most (95%) were not employed. Awareness of warning signs of BC was low: only seven to 18% of participants recognized 11 common warning signs of BC. Participant use of breast self-exam (BSE) was low, with 82% of participants stating they rarely or never complete BSE. Zero of 420 patients reported ever seeing a physician for a change in their breasts. Awareness of risk factors for BC was also low: only 15% of participants recognized increasing age as a risk factor for BC, and other risk factors were only recognized by four to 39% of participants. Interpretation: BC awareness among Afghan refugee women is critically low. There is an urgent need to target this population for practical interventions to increase BC awareness, in addition to screening and earlier diagnosis. Evidence-based interventions include educational sessions in patients' native language and use of BSE and clinical breast examination for screening. Funding: American Society for Radiation Oncology (ASTRO) - Association of Residents in Radiation Oncology (ARRO) Global Health Scholar Grant, Dana-Farber Cancer Institute Jay Harris Junior Faculty Research Grant.

An Observational Cohort Study on the Incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and B.1.1.7 Variant Infection in Healthcare Workers by Antibody and Vaccination Status.

BACKGROUND: Natural and vaccine-induced immunity will play a key role in controlling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity. METHODS: In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, United Kingdom, we investigated the protection from symptomatic and asymptomatic polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after 1 versus 2 vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing. RESULTS: In total, 13 109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses), and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and 2 vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95% confidence interval {CI} < .01-.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [95% CI .02-.38]) and 85% (0.15 [95% CI .08-.26]), respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [95% CI .21-.52]) and any PCR-positive result by 64% (0.36 [95% CI .26-.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7. CONCLUSIONS: Natural infection resulting in detectable anti-spike antibodies and 2 vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

Impedance Properties of Multi-Optrode Biopotential Sensing Arrays.

Recording and monitoring electrically-excitable cells is critical to understanding the complex cellular networking within organs as well as the processes underlying many electro-physiological pathologies. Biopotential recording using an optical-electrode (optrode) is a novel approach which has potential to significantly improve interface-instrumentation impedance mismatching as recording contact-sizes become smaller and smaller. Optrodes incorporate a conductive interface that can sense extracellular potential and an underlying layer of liquid crystals that passively transduces electrical signals into measurable optical signals. This study investigates the impedance properties of this optical technology by varying the diameter of recording sites and observing the corresponding changes in the impedance values. The results show that the liquid crystals in this optrode platform exhibit input impedance values (1 MΩ - 100 GΩ) that are three orders of magnitude higher than the corresponding interface impedance, which is appropriate for voltage sensing. The automatic scaling of the input impedance enabled within the optrode system maintains a relatively constant ratio between input and total system impedance of about one for sensing areas with diameters ranging from 40 µm to 1 mm, at which the calculated signal loss is predicted to be <1%. This feature preserves the interface-transducer impedance ratio, regardless of the size of the recording site, allowing development of passive optrode arrays capable of very high spatial-resolution recordings.

Improving Deep Brain Stimulation Electrode Performance in vivo Through Use of Conductive Hydrogel Coatings.

Active implantable neurological devices like deep brain stimulators have been used over the past few decades to treat movement disorders such as those in people with Parkinson's disease and more recently, in psychiatric conditions like obsessive compulsive disorder. Electrode-tissue interfaces that support safe and effective targeting of specific brain regions are critical to success of these devices. Development of directional electrodes that activate smaller volumes of brain tissue requires electrodes to operate safely with higher charge densities. Coatings such as conductive hydrogels (CHs) provide lower impedances and higher charge injection limits (CILs) than standard platinum electrodes and support safer application of smaller electrode sizes. The aim of this study was to examine the chronic in vivo performance of a new low swelling CH coating that supports higher safe charge densities than traditional platinum electrodes. A range of hydrogel blends were engineered and their swelling and electrical performance compared. Electrochemical performance and stability of high and low swelling formulations were compared during insertion into a model brain in vitro and the formulation with lower swelling characteristics was chosen for the in vivo study. CH-coated or uncoated Pt electrode arrays were implanted into the brains of 14 rats, and their electrochemical performance was tested weekly for 8 weeks. Tissue response and neural survival was assessed histologically following electrode array removal. CH coating resulted in significantly lower voltage transient impedance, higher CIL, lower electrochemical impedance spectroscopy, and higher charge storage capacity compared to uncoated Pt electrodes in vivo, and this advantage was maintained over the 8-week implantation. There was no significant difference in evoked potential thresholds, signal-to-noise ratio, tissue response or neural survival between CH-coated and uncoated Pt groups. The significant electrochemical advantage and stability of CH coating in the brain supports the suitability of this coating technology for future development of smaller, higher fidelity electrode arrays with higher charge density requirement.