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1.
Proc Natl Acad Sci U S A ; 121(4): e2317773121, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38227668

RESUMEN

The retina and primary visual cortex (V1) both exhibit diverse neural populations sensitive to diverse visual features. Yet it remains unclear how neural populations in each area partition stimulus space to span these features. One possibility is that neural populations are organized into discrete groups of neurons, with each group signaling a particular constellation of features. Alternatively, neurons could be continuously distributed across feature-encoding space. To distinguish these possibilities, we presented a battery of visual stimuli to the mouse retina and V1 while measuring neural responses with multi-electrode arrays. Using machine learning approaches, we developed a manifold embedding technique that captures how neural populations partition feature space and how visual responses correlate with physiological and anatomical properties of individual neurons. We show that retinal populations discretely encode features, while V1 populations provide a more continuous representation. Applying the same analysis approach to convolutional neural networks that model visual processing, we demonstrate that they partition features much more similarly to the retina, indicating they are more like big retinas than little brains.


Asunto(s)
Corteza Visual , Animales , Ratones , Corteza Visual/fisiología , Percepción Visual/fisiología , Redes Neurales de la Computación , Neuronas/fisiología , Retina/fisiología , Estimulación Luminosa
2.
Prehosp Emerg Care ; : 1-5, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38776421

RESUMEN

OBJECTIVES: Despite limited supporting data, hospitals continue to apply ambulance diversion (AD). Thus, we examined the impact of three different diversion policies on diversion hours, transport time (TT; leaving scene to arrival at the hospital), and ambulance patient offload time (APOT; arrival at the hospital to patient turnover to hospital staff) for 9-1-1 transports in a 22-hospital county Emergency Medical Services (EMS) system. METHODS: This retrospective study evaluated metrics during periods of three AD policies, each 27 days long: hospital-initiated (Period 1), complete suspension (Period 2), and County EMS-initiated (Period 3). We described the median transports and diversion hours, and compared the daily average and daily 90th percentile TT and APOT during the three study periods. RESULTS: Over the study period, there were 50,992 total transports in the county; Period 3 had fewer median transports per day than Period 1 (581 vs 623, p < 0.001), while Period 2 was similar to Period 1 (606 vs 623, p = 0.108). Median average daily diversion hours decreased from 98.1 h during Period 1 to zero hours during both Periods 2 (p < 0.001) and 3 (p < 0.001). Median daily average TT decreased from 18.3 min in Period 1 to 16.9 min in both Periods 2 (p < 0.001) and 3 (p < 0.001). Median daily 90th percentile TT showed a similar decrease from 30.2 min in Period 1 to 27.5 in Period 2 (p < 0.001), and to 28.1 in Period 3 (p = 0.001). Median average daily APOT was 26.0 min during Period 1, similar at 25.2 min during Period 2 (p = 0.826) and decreased to 20.4 min during Period 3 (p < 0.001). The median daily 90th percentile APOT was 53.9 min during Period 1, similar at 51.7 min during Period 2 (p = 0.553) and decreased to 40.3 min during Period 3 (p < 0.001). CONCLUSIONS: Compared to hospital-initiated AD, enacting no AD or County EMS-initiated AD was associated with less diversion time; TT and APOT showed statistically significant improvement without hospital-initiated AD but were of unclear clinical significance. EMS-initiated AD was difficult to interpret as that period had significantly fewer transports. EMS systems should consider these findings when developing strategies to improve TT, APOT, and system use of diversion.

3.
Prehosp Emerg Care ; : 1-11, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38727731

RESUMEN

Improving health and safety in our communities requires deliberate focus and commitment to equity. Inequities are differences in access, treatment, and outcomes between individuals and across populations that are systemic, avoidable, and unjust. Within health care in general, and Emergency Medical Services (EMS) in particular, there are demonstrated inequities in the quality of care provided to patients based on a number of characteristics linked to discrimination, exclusion, or bias. Given the critical role that EMS plays within the health care system, it is imperative that EMS systems reduce inequities by delivering evidence-based, high-quality care for the communities and patients we serve. To achieve equity in EMS care delivery and patient outcomes, the National Association of EMS Physicians recommends that EMS systems and agencies: make health equity a strategic priority and commit to improving equity at all levels.assess and monitor clinical and safety quality measures through the lens of inequities as an integrated part of the quality management process.ensure that data elements are structured to enable equity analysis at every level and routinely evaluate data for limitations hindering equity analysis and improvement.involve patients and community stakeholders in determining data ownership and stewardship to ensure its ongoing evolution and fitness for use for measuring care inequities.address biases as they translate into the quality of care and standards of respect for patients.pursue equity through a framework rooted in the principles of improvement science.

4.
Prehosp Emerg Care ; 27(8): 1058-1071, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36369725

RESUMEN

BACKGROUND: Emergency medical services (EMS) often serve as the first medical contact for ill or injured patients, representing a critical access point to the health care delivery continuum. While a growing body of literature suggests inequities in care within hospitals and emergency departments, limited research has comprehensively explored disparities related to patient demographic characteristics in prehospital care. OBJECTIVE: We aimed to summarize the existing literature on disparities in prehospital care delivery for patients identifying as members of an underrepresented race, ethnicity, sex, gender, or sexual orientation group. METHODS: We conducted a scoping review of peer-reviewed and non-peer-reviewed (gray) literature. We searched PubMed, CINAHL, Web of Science, Proquest Dissertations, Scopus, Google, and professional websites for studies set in the U.S. between 1960 and 2021. Each abstract and full-text article was screened by two reviewers. Studies written in English that addressed the underrepresented groups of interest and investigated EMS-related encounters were included. Studies were excluded if a disparity was noted incidentally but was not a stated objective or discussed. Data extraction was conducted using a standardized electronic form. Results were summarized qualitatively using an inductive approach. RESULTS: One hundred forty-five full-text articles from the peer-reviewed literature and two articles from the gray literature met inclusion criteria: 25 studies investigated sex/gender, 61 studies investigated race/ethnicity, and 58 studies investigated both. One study investigated sexual orientation. The most common health conditions evaluated were out-of-hospital cardiac arrest (n = 50), acute coronary syndrome (n = 36), and stroke (n = 31). The phases of EMS care investigated included access (n = 55), pre-arrival care (n = 46), diagnosis/treatment (n = 42), and response/transport (n = 40), with several studies covering multiple phases. Disparities were identified related to all phases of EMS care for underrepresented groups, including symptom recognition, pain management, and stroke identification. The gray literature identified public perceptions of EMS clinicians' cultural competency and the ability to appropriately care for transgender patients in the prehospital setting. CONCLUSIONS: Existing research highlights health disparities in EMS care delivery throughout multiple health outcomes and phases of EMS care. Future research is needed to identify structured mechanisms to eliminate disparities, address clinician bias, and provide high-quality equitable care for all patient populations.


Asunto(s)
Servicios Médicos de Urgencia , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Estados Unidos , Atención a la Salud , Calidad de la Atención de Salud , Hospitales
5.
Cancer ; 128(13): 2520-2528, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35385137

RESUMEN

BACKGROUND: Breast cancer (BC) survivors frequently report changes in cognition after chemotherapy. Mindfulness may benefit survivors by mitigating cancer-related cognitive impairment. As part of a larger study investigating the effects of mindfulness-based stress reduction (MBSR) for BC survivors living with neuropathic pain, the authors assessed whether MBSR would have an effect on cognitive outcomes. METHODS: Participants were randomized to an MBSR intervention group (n = 30) or a waitlist control group (n = 30). Cognitive assessments were administered at 3 time points: at baseline, 2 weeks, and 3 months post-MBSR in the intervention group and at equivalent time intervals for the control group. Multilevel models were used to assess whether MBSR significantly improved task performance at each time point. RESULTS: MBSR participants showed a significantly greater reduction in prospective and retrospective memory failures at 2 weeks postintervention. No effects of MBSR were noted for objective assessments. CONCLUSIONS: These results suggest that MBSR training reduces subjective (but not objective) memory-related impairments in BC survivors who receive treatment with chemotherapy. This study provides insight into a noninvasive intervention to ameliorate memory difficulties in BC survivors.


Asunto(s)
Neoplasias de la Mama , Supervivientes de Cáncer , Atención Plena , Neoplasias de la Mama/complicaciones , Neoplasias de la Mama/psicología , Neoplasias de la Mama/terapia , Supervivientes de Cáncer/psicología , Cognición , Femenino , Humanos , Atención Plena/métodos , Estudios Prospectivos , Estudios Retrospectivos , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Estrés Psicológico/terapia , Sobrevivientes/psicología , Resultado del Tratamiento
6.
Prehosp Emerg Care ; 26(2): 305-310, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33528300

RESUMEN

Objective: Accurate tracking of patients poses a significant challenge to prehospital and hospital emergency medical providers in planned and unplanned events. Previous reports on patient tracking systems are limited primarily to descriptive reports of post incident reviews or simulated exercises. Our objective is to report our experience with implementing a patient barcode tracking system during various planned events within a large urban EMS system.Methods: In 2018, representatives from the Chicago Department of Public Health, Chicago Fire Department EMS, private EMS agencies, and 27 hospitals in the Chicago EMS System were trained on the use of a web-based patient tracking system using barcoded triage tags and wristbands to monitor triage category and hospital destination during an event. The tracking system was used on two planned operational days and three pre-planned mass gathering events. The primary outcome was the percent of patients initially scanned by EMS that were scanned by the hospital. Descriptive statistics were collected. Barriers to patient tracking system use were identified.Results: Each event was reviewed for the number of patients assigned a barcode identifier and scanned by EMS that were then scanned by the hospital. In the first planned operational day, 57% (359/622) of patients initially scanned by EMS were scanned by the hospital. In the second planned operational day, 88% (355/402) of EMS scanned patients were scanned by the hospital and 37% (133/355) were assigned a final disposition. At three city mass gathering events, there were 79% (50/63), 95% (190/199), and 82% (46/56) of EMS scanned patients also scanned by hospitals. Logistical and technological challenges were documented.Conclusions: Use of a web-based system with barcode identifiers successfully tracked patients from prehospital to hospital during planned operational days and mass gathering events. Percent of scanned patients increased after the first operational day and remained consistent in subsequent events. Limitations to the patient tracking system included logistical and technological barriers. Similar patient tracking systems may be implemented to assist with event management in other EMS systems.


Asunto(s)
Servicios Médicos de Urgencia , Chicago , Hospitales , Humanos , Sistemas de Identificación de Pacientes , Triaje
7.
Am J Hum Genet ; 103(3): 328-337, 2018 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-30100086

RESUMEN

There is growing interest in communicating clinically relevant DNA sequence findings to research participants who join projects with a primary research goal other than the clinical return of such results. Since Geisinger's MyCode Community Health Initiative (MyCode) was launched in 2007, more than 200,000 participants have been broadly consented for discovery research. In 2013 the MyCode consent was amended to include a secondary analysis of research genomic sequences that allows for delivery of clinical results. Since May 2015, pathogenic and likely pathogenic variants from a set list of genes associated with monogenic conditions have prompted "genome-first" clinical encounters. The encounters are described as genome-first because they are identified independent of any clinical parameters. This article (1) details our process for generating clinical results from research data, delivering results to participants and providers, facilitating condition-specific clinical evaluations, and promoting cascade testing of relatives, and (2) summarizes early results and participant uptake. We report on 542 participants who had results uploaded to the electronic health record as of February 1, 2018 and 291 unique clinical providers notified with one or more participant results. Of these 542 participants, 515 (95.0%) were reached to disclose their results and 27 (5.0%) were lost to follow-up. We describe an exportable model for delivery of clinical care through secondary use of research data. In addition, subject and provider participation data from the initial phase of these efforts can inform other institutions planning similar programs.


Asunto(s)
Genoma Humano/genética , Estudios de Cohortes , Registros Electrónicos de Salud , Genómica/métodos , Personal de Salud , Humanos , Análisis de Secuencia de ADN/métodos
8.
BMC Neurol ; 21(1): 300, 2021 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-34344355

RESUMEN

BACKGROUND: Executive functioning (EF) deficits are troubling for adolescents and young adults (AYAs) after cancer treatment. Physical activity (PA) may enhance neural activity underlying EF among older adults affected by cancer. Establishing whether PA enhances neural activity among AYAs is warranted. As part of a two-arm, mixed-methods pilot randomized controlled trial (RCT), this proof-of-concept sub-study sought to answer the following questions: (1) is it feasible to use neuroimaging with EF tasks to assess neural activity changes following a 12-week PA intervention? And (2) is there preliminary evidence that a 12-week PA intervention enhances neural activity among AYAs after cancer treatment? METHODS: AYAs in the pilot RCT were approached for enrollment into this sub-study. Those who were eligible and enrolled, completed functional magnetic resonance imaging (fMRI) with EF tasks (letter n-back, Go/No Go) pre- and post-PA intervention. Sub-study enrollment, adherence to scheduled fMRI scans, outliers, missing data, and EF task performance data were collected. Data were analyzed with descriptive statistics, blood oxygen level dependent (BOLD) analyses, and paired sample t-tests. RESULTS: Nine eligible participants enrolled into this sub-study; six attended scheduled fMRI scans. One outlier was identified and was subsequently removed from the analytical sample. Participants showed no differences in EF task performance from pre- to post-PA intervention. Increases in neural activity in brain regions responsible for motor control, information encoding and processing, and decision-making were observed post-PA intervention (p < 0.05; n = 5). CONCLUSIONS: Findings  show that fMRI scans during EF tasks detected neural activity changes (as assessed by the BOLD signal) from pre- to post-PA intervention. Results thus suggest future trials confirming that PA enhances neural activity underlying EF are needed, though feasibility issues require careful consideration to ensure trial success. TRIAL REGISTRATION: clinicaltrials.gov, NCT03016728. Registered January 11, 2017, clinicaltrials.gov/ct2/show/NCT03016728.


Asunto(s)
Ejercicio Físico , Neoplasias , Adolescente , Función Ejecutiva , Estudios de Factibilidad , Humanos , Neoplasias/terapia , Adulto Joven
9.
J Proteome Res ; 19(2): 708-718, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-31884793

RESUMEN

The efficacy of oncolytic viruses (OVs), such as reovirus, is dictated by host immune responses, including those mediated by the pro- versus anti-inflammatory macrophages. As such, a detailed understanding of the interaction between reovirus and different macrophage types is critical for therapeutic efficacy. To explore reovirus-macrophage interactions, we performed tandem mass tag (TMT)-based quantitative temporal proteomics on mouse bone marrow-derived macrophages (BMMs) generated with two cytokines, macrophage colony stimulating factor (M-CSF) and granulocytic-macrophage colony stimulating factor (GM-CSF), representing anti- and proinflammatory macrophages, respectively. We quantified 6863 proteins across five time points in duplicate, comparing M-CSF (M-BMM) and GM-CSF (GM-BMM) in response to OV. We find that GM-BMMs have lower expression of key intrinsic proteins that facilitate an antiviral immune response, express higher levels of reovirus receptor protein JAM-A, and are more susceptible to oncolytic reovirus infection compared to M-BMMs. Interestingly, although M-BMMs are less susceptible to reovirus infection and subsequent cell death, they initiate an antireovirus adaptive T cell immune response comparable to that of GM-BMMs. Taken together, these data describe distinct proteome differences between these two macrophage populations in terms of their ability to mount antiviral immune responses.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos , Factor Estimulante de Colonias de Macrófagos , Animales , Médula Ósea , Células de la Médula Ósea , Células Cultivadas , Ratones , Proteoma
10.
BMC Cancer ; 20(1): 711, 2020 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-32736542

RESUMEN

BACKGROUND: Up to 75% of women diagnosed with breast cancer report chemotherapy-related cognitive changes (CRCC) during treatment, including decreased memory, attention, and processing speed. Though CRCC negatively impacts everyday functioning and reduces overall quality of life in women diagnosed with breast cancer, effective interventions to prevent and/or manage CRCC are elusive. Consequently, women seldom receive advice on how to prevent or manage CRCC. Aerobic exercise is associated with improved cognitive functioning in healthy older adults and adults with cognitive impairments. Accordingly, it holds promise as an intervention to prevent and/or manage CRCC. However, evidence from randomized controlled trials (RCTs) supporting a beneficial effect of aerobic exercise on CRCC is limited. The primary aim of the ACTIVATE trial is to evaluate the impact of supervised aerobic exercise on CRCC in women receiving chemotherapy for breast cancer. METHODS: The ACTIVATE trial is a two-arm, two-centre RCT. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy are recruited from hospitals in Ottawa (Ontario) and Vancouver (British Columbia), Canada. Recruits are randomized to the intervention group (aerobic exercise during chemotherapy) or the wait-list control group (usual care during chemotherapy and aerobic exercise post-chemotherapy). The primary outcome is cognitive functioning as measured by a composite cognitive summary score (COGSUM) of several neuropsychological tests. Secondary outcomes are self-reported cognitive functioning, quality of life, and brain structure and functioning (measured by magnetic resonance imaging (MRI)/functional MRI and electroencephalography). Assessments take place pre-chemotherapy (pre-intervention), mid-way through chemotherapy (mid-intervention/mid-wait period), end of chemotherapy (post-intervention/post-wait period; primary endpoint), 16-weeks post-chemotherapy, and at 1-year post-baseline. DISCUSSION: Aerobic exercise is a promising intervention for preventing and/or managing CRCC and enhancing quality of life among women diagnosed with breast cancer. The ACTIVATE trial tests several novel hypotheses, including that aerobic exercise can prevent and/or mitigate CRCC and that this effect is mediated by the timing of intervention delivery (i.e., during versus post-chemotherapy). Findings may support prescribing exercise during (or post-) chemotherapy for breast cancer and elucidate the potential role of aerobic exercise as a management strategy for CRCC in women with early-stage breast cancer. TRIAL REGISTRATION: The trial was registered with the ClinicalTrials.gov database ( NCT03277898 ) on September 11, 2017.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Trastornos del Conocimiento/terapia , Cognición/efectos de los fármacos , Ejercicio Físico/fisiología , Antineoplásicos/efectos adversos , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/prevención & control , Femenino , Humanos , Pruebas Neuropsicológicas , Selección de Paciente , Calidad de Vida , Tamaño de la Muestra , Autoinforme , Listas de Espera
11.
Adv Exp Med Biol ; 1131: 747-770, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31646533

RESUMEN

The pioneering work of Richard Altman on the presence of mitochondria in cells set in motion a field of research dedicated to uncovering the secrets of the mitochondria. Despite limitations in studying the structure and function of the mitochondria, advances in our understanding of this organelle prompted the development of potential treatments for various diseases, from neurodegenerative conditions to muscular dystrophy and cancer. As the powerhouses of the cell, the mitochondria represent the essence of cellular life and as such, a selective advantage for cancer cells. Much of the function of the mitochondria relies on Ca2+ homeostasis and the presence of effective Ca2+ signaling to maintain the balance between mitochondrial function and dysfunction and subsequently, cell survival. Ca2+ regulates the mitochondrial respiration rate which in turn increases ATP synthesis, but too much Ca2+ can also trigger the mitochondrial apoptosis pathway; however, cancer cells have evolved mechanisms to modulate mitochondrial Ca2+ influx and efflux in order to sustain their metabolic demand and ensure their survival. Therefore, targeting the mitochondrial Ca2+ signaling involved in the bioenergetic and apoptotic pathways could serve as potential approaches to treat cancer patients. This chapter will review the role of Ca2+ signaling in mediating the function of the mitochondria and its involvement in health and disease with special focus on the pathophysiology of cancer.


Asunto(s)
Señalización del Calcio , Calcio , Mitocondrias , Neoplasias , Apoptosis , Calcio/metabolismo , Señalización del Calcio/fisiología , Homeostasis , Humanos , Mitocondrias/fisiología , Neoplasias/fisiopatología
12.
J Biol Chem ; 293(10): 3637-3650, 2018 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-29343514

RESUMEN

A lack of effective treatment is one of the main factors contributing to gastric cancer-related death. Discovering effective targets and understanding their underlying anti-cancer mechanism are key to achieving the best response to treatment and to limiting side effects. Although recent studies have shown that the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial for cancer cell survival, the exact mechanism remains unclear, limiting its therapeutic potential. Here, using molecular and functional assays, we investigated the role of TRPM2 in survival of gastric cancer cells. Our results indicated that TRPM2 knockdown in AGS and MKN-45 cells decreases cell proliferation and enhances apoptosis. We also observed that the TRPM2 knockdown impairs mitochondrial metabolism, indicated by a decrease in basal and maximal mitochondrial oxygen consumption rates and ATP production. These mitochondrial defects coincided with a decrease in autophagy and mitophagy, indicated by reduced levels of autophagy- and mitophagy-associated proteins (i.e. ATGs, LC3A/B II, and BNIP3). Moreover, we found that TRPM2 modulates autophagy through a c-Jun N-terminal kinase (JNK)-dependent and mechanistic target of rapamycin-independent pathway. We conclude that in the absence of TRPM2, down-regulation of the JNK-signaling pathway impairs autophagy, ultimately causing the accumulation of damaged mitochondria and death of gastric cancer cells. Of note, by inhibiting cell proliferation and promoting apoptosis, the TRPM2 down-regulation enhanced the efficacy of paclitaxel and doxorubicin in gastric cancer cells. Collectively, we provide compelling evidence that TRPM2 inhibition may benefit therapeutic approaches for managing gastric cancer.


Asunto(s)
Adenocarcinoma/metabolismo , Apoptosis , Autofagia , Mitofagia , Proteínas de Neoplasias/metabolismo , Neoplasias Gástricas/metabolismo , Canales Catiónicos TRPM/metabolismo , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Antibióticos Antineoplásicos/farmacología , Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Registros Electrónicos de Salud , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Mitocondrias/metabolismo , Mitofagia/efectos de los fármacos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , Fosforilación Oxidativa/efectos de los fármacos , Paclitaxel/farmacología , Interferencia de ARN , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de Supervivencia , Canales Catiónicos TRPM/antagonistas & inhibidores , Canales Catiónicos TRPM/genética
13.
Genet Med ; 20(5): 554-558, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29261187

RESUMEN

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.


Asunto(s)
Bancos de Muestras Biológicas , Detección Precoz del Cáncer/métodos , Genes BRCA1 , Genes BRCA2 , Mutación , Neoplasias/diagnóstico , Neoplasias/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Síndrome de Cáncer de Mama y Ovario Hereditario/diagnóstico , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Humanos , Persona de Mediana Edad , Linaje , Secuenciación Completa del Genoma
14.
Can J Neurol Sci ; 45(5): 580-582, 2018 09.
Artículo en Inglés | MEDLINE | ID: mdl-30234464

RESUMEN

Multiple sclerosis (MS) is a chronic, progressive, autoimmune, neurodegenerative disorder that can interfere with physical and psychological functioning, negatively affecting health-related quality of life (HRQoL). Fostering mindfulness may mitigate the negative consequences of MS on HRQoL. The relationship between mindfulness, mood and MS-related quality of life was investigated. In total, 52 individuals with MS completed questionnaires to examine the relationship between trait mindfulness and wellness. Higher levels of trait mindfulness were associated with better HRQoL, lower depression and anxiety, lower fatigue impact and fewer perceived cognitive deficits. Mindfulness interventions have the potential to enhance wellness in those living with MS.


Asunto(s)
Concienciación , Atención Plena , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/psicología , Calidad de Vida/psicología , Adulto , Trastornos del Conocimiento/etiología , Fatiga/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/etiología , Dolor/etiología , Encuestas y Cuestionarios
15.
J Synchrotron Radiat ; 24(Pt 5): 963-974, 2017 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28862618

RESUMEN

EIGER is a single-photon-counting hybrid pixel detector developed at the Paul Scherrer Institut, Switzerland. It is designed for applications at synchrotron light sources with photon energies above 5 keV. Features of EIGER include a small pixel size (75 µm × 75 µm), a high frame rate (up to 23 kHz), a small dead-time between frames (down to 3 µs) and a dynamic range up to 32-bit. In this article, the use of EIGER as a detector for electrons in low-energy electron microscopy (LEEM) and photoemission electron microscopy (PEEM) is reported. It is demonstrated that, with only a minimal modification to the sensitive part of the detector, EIGER is able to detect electrons emitted or reflected by the sample and accelerated to 8-20 keV. The imaging capabilities are shown to be superior to the standard microchannel plate detector for these types of applications. This is due to the much higher signal-to-noise ratio, better homogeneity and improved dynamic range. In addition, the operation of the EIGER detector is not affected by radiation damage from electrons in the present energy range and guarantees more stable performance over time. To benchmark the detector capabilities, LEEM experiments are performed on selected surfaces and the magnetic and electronic properties of individual iron nanoparticles with sizes ranging from 8 to 22 nm are detected using the PEEM endstation at the Surface/Interface Microscopy (SIM) beamline of the Swiss Light Source.

16.
J Immunol ; 194(9): 4397-412, 2015 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-25825443

RESUMEN

Tumor-associated immunosuppression aids cancer cells to escape immune-mediated attack and subsequent elimination. Recently, however, many oncolytic viruses, including reovirus, have been reported to overturn such immunosuppression and promote the development of a clinically desired antitumor immunity, which is known to promote favorable patient outcomes. Contrary to this existing paradigm, in this article we demonstrate that reovirus augments tumor-associated immunosuppression immediately following its therapeutic administration. Our data show that reovirus induces preferential differentiation of highly suppressive CD11b(+), Gr-1(+), Ly6C(high) myeloid cells from bone marrow hematopoietic progenitor cells. Furthermore, reovirus administration in tumor-bearing hosts drives time-dependent recruitment of CD11b(+), Gr-1(+), Ly6C(high) myeloid cells in the tumor milieu, which is further supported by virus-induced increased expression of numerous immune factors involved in myeloid-derived suppressor cell survival and trafficking. Most importantly, CD11b(+), Gr-1(+), Ly6C(high) myeloid cells specifically potentiate the suppression of T cell proliferation and are associated with the absence of IFN-γ response in the tumor microenvironment early during oncotherapy. Considering that the qualitative traits of a specific antitumor immunity are largely dictated by the immunological events that precede its development, our findings are of critical importance and must be considered while devising complementary interventions aimed at promoting the optimum efficacy of oncolytic virus-based anticancer immunotherapies.


Asunto(s)
Vectores Genéticos , Inmunomodulación , Células Mieloides/inmunología , Células Mieloides/metabolismo , Neoplasias/inmunología , Virus Oncolíticos , Fenotipo , Animales , Antígenos Ly/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Antígeno CD11b/metabolismo , Diferenciación Celular , Quimiotaxis/inmunología , Femenino , Vectores Genéticos/administración & dosificación , Vectores Genéticos/inmunología , Humanos , Orthoreovirus Mamífero 3/genética , Orthoreovirus Mamífero 3/inmunología , Ratones , Células Mieloides/citología , Neoplasias/terapia , Viroterapia Oncolítica , Virus Oncolíticos/inmunología , Receptores de Quimiocina/metabolismo , Células Madre/citología , Células Madre/metabolismo , Microambiente Tumoral/inmunología
17.
Brain Inj ; 31(1): 57-67, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27880059

RESUMEN

PRIMARY OBJECTIVE: Repetition-lag memory training was developed to increase individuals' use of recollection as opposed to familiarity in recognition memory. The goals of this study were to examine the feasibility of repetition-lag training in patients with chronic stroke and to explore whether the training might show suggestions of transfer to non-trained tasks. RESEARCH DESIGN: Quasi-experimental. METHODS AND PROCEDURES: Patients (n = 17) took part in six repetition-lag training sessions and their gains on the training and non-trained tasks were compared to those of age-matched healthy controls (n = 30). MAIN OUTCOMES AND RESULTS: All but two patients completed the training, indicating that the method is feasible with a wide range of patients with stroke. The amount patients gained on the training task was similar to that of healthy controls (that is, the Group × Time interactions were by-and-large not significant), suggesting that patients with stroke might benefit to the same degree as healthy adults from this training. Both groups showed some indication of transfer to the non-trained backward digit span task and visuospatial memory. CONCLUSIONS: These findings show that repetition-lag memory training is a possible approach with patients with stroke to enhance recollection. Further research on the method's efficacy and effectiveness is warranted.


Asunto(s)
Aprendizaje/fisiología , Trastornos de la Memoria/rehabilitación , Recuerdo Mental/fisiología , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/psicología , Anciano , Femenino , Humanos , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Accidente Cerebrovascular/complicaciones , Resultado del Tratamiento
19.
BMC Med Educ ; 14: 39, 2014 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-24575827

RESUMEN

BACKGROUND: Intimate physical examination skills are essential skills for any medical graduate to have mastered to an appropriate level for the safety of his or her future patients. Medical schools are entrusted with the complex task of teaching and assessing these skills for their students. The objectives of this study were to explore a range of medical students' experiences of learning intimate physical examination skills and to explore their perceptions of factors which impede or promote the learning of these skills. METHODS: Individual semi-structured interviews (N = 16) were conducted with medical students in years two to five from the University of Newcastle, as part of a larger research project investigating how medical students develop their attitudes to gender and health. This was a self-selected sample of the entire cohort who were all invited to participate. A thematic analysis of the transcribed data was performed. RESULTS: Students reported differing levels of discomfort with their learning experiences in the area of intimate physical examination and differing beliefs about the helpfulness of these experiences. The factors associated with levels of discomfort and the helpfulness of the experience for learning were: satisfaction with teaching techniques, dealing with an uncomfortable situation and perceived individual characteristics in both the patients and the students. The examination causing the greatest reported discomfort was the female pelvic examination by male students. CONCLUSIONS: Student discomfort with the experience of learning intimate physical examination skills may be common and has ongoing repercussions for students and patients. Recommendations are made of ways to modify teaching technique to more closely match students' perceived needs.


Asunto(s)
Educación de Pregrado en Medicina , Examen Físico/psicología , Estudiantes de Medicina/psicología , Adulto , Actitud del Personal de Salud , Tacto Rectal/psicología , Educación de Pregrado en Medicina/métodos , Femenino , Examen Ginecologíco/psicología , Humanos , Entrevistas como Asunto , Masculino , Nueva Gales del Sur , Investigación Cualitativa , Adulto Joven
20.
J Neurotrauma ; 41(5-6): 552-570, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38204176

RESUMEN

Emerging evidence suggests that advanced neuroimaging modalities such as arterial spin labelling (ASL) might have prognostic utility for pediatric concussion. This study aimed to: 1) examine group differences in global and regional brain perfusion in youth with concussion or orthopedic injury (OI) at 72 h and 4 weeks post-injury; 2) examine patterns of abnormal brain perfusion within both groups and their recovery; 3) investigate the association between perfusion and symptom burden within concussed and OI youths at both time-points; and 4) explore perfusion between symptomatic and asymptomatic concussed and OI youths. Youths ages 10.00-17.99 years presenting to the emergency department with an acute concussion or OI were enrolled. ASL-magnetic resonance imaging scans were conducted at 72 h and 4 weeks post-injury to measure brain perfusion, along with completion of the Health Behavior Inventory (HBI) to measure symptoms. Abnormal perfusion clusters were identified using voxel-based z-score analysis at each visit. First, mixed analyses of covariance (ANCOVAs) investigated the Group*Time interaction on global and regional perfusion. Post hoc region of interest (ROI) analyses were performed on significant regions. Second, within-group generalized estimating equations investigated the recovery of abnormal perfusion at an individual level. Third, multiple regressions at each time-point examined the association between HBI and regional perfusion, and between HBI and abnormal perfusion volumes within the concussion group. Fourth, whole-brain one-way ANCOVAs explored differences in regional and abnormal perfusion based on symptomatic status (symptomatic vs. asymptomatic) and OIs at each time-point. A total of 70 youths with a concussion [median age (interquartile range; IQR) = 12.70 (11.67-14.35), 47.1% female] and 29 with an OI [median age (IQR) = 12.05 (11.18-13.89), 41.4% female] were included. Although no Group effect was found in global perfusion, the concussion group showed greater adjusted perfusion within the anterior cingulate cortex/middle frontal gyrus (MFG) and right MFG compared with the OI group across time-points (ps ≤ 0.004). The concussion group showed lower perfusion within the right superior temporal gyrus at both time-points and bilateral occipital gyrus at 4 weeks, (ps ≤ 0.006). The number of hypoperfused clusters was increased at 72 h compared with 4 weeks in the concussion youths (p < 0.001), but not in the OIs. Moreover, Group moderated the HBI-perfusion association within the left precuneus and superior frontal gyrus at both time-points, (ps ≤ 0.001). No association was found between HBI and abnormal perfusion volume within the concussion group at any visits. At 4 weeks, the symptomatic sub-group (n = 10) showed lower adjusted perfusion within the right cerebellum and lingual gyrus, while the asymptomatic sub-group (n = 59) showed lower adjusted perfusion within the left calcarine, but greater perfusion within the left medial orbitofrontal cortex, right middle frontal gyrus, and bilateral caudate compared with OIs. Yet, no group differences were observed in the number of abnormal perfusion clusters or volumes at any visit. The present study suggests that symptoms may be associated with changes in regional perfusion, but not abnormal perfusion levels.


Asunto(s)
Conmoción Encefálica , Esfuerzo Físico , Adolescente , Humanos , Femenino , Niño , Masculino , Encéfalo/diagnóstico por imagen , Conmoción Encefálica/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Perfusión
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