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1.
Artículo en Inglés | MEDLINE | ID: mdl-38816961

RESUMEN

Clinical flow cytometry laboratories require quality control materials for assay development, validation, and performance monitoring, including new reagent lot qualification. However, finding suitable controls for populations with uncommonly expressed antigens or for rare populations, such as mast cells, can be difficult. To that end, we evaluated synthetic abnormal mast cell particles (SAMCP), developed together with, and manufactured by, Slingshot Biosciences. The SAMCP's were designed to phenotypically mimic abnormal neoplastic mast cells: they were customized to have the same light scatter and autofluorescence properties of mast cells, along with surface antigen levels of CD45, CD33, CD117, CD2, CD25, and CD30 consistent with that seen in mast cell disease. We evaluated several performance characteristics of these particles using ARUP's high sensitivity clinical mast cell assay, including limit of detection, off-target activity and FMO controls, precision, scatter properties of the particles utilizing several different cytometer platforms, and particle antigen stability. The phenotype of the SAMCP mimicked abnormal mast cells, and they could be distinguished from normal native mast cells. FMO controls demonstrated specificity of each of the markers, and no off-target binding was detected. The limit of detection of the particles spiked into normal bone marrow was found to be ≤0.003% in a limiting dilution assay. The mast cell particles were found to perform similarly on Becton Dickinson Lyric, Cytek Aurora, and Beckman Coulter Navios and CytoFLEX platforms. Within run and between run precision were less than 10% CV. SAMCP were stable up to 13 days with minimal loss of antigen fluorescence intensity. The SAMCP's were able to successfully mimic neoplastic mast cells based on the results of our high sensitivity mast cell flow cytometry panel. These synthetic cell particles represent an exciting and innovative technology, which can fulfill vital needs in clinical flow cytometry such as serving as standardized control materials for assay development and performance monitoring.

3.
J Perinatol ; 44(5): 650-658, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38383575

RESUMEN

OBJECTIVE: This study measured staff understanding and integration of trauma-informed care following comprehensive education. STUDY DESIGN: This mixed method design used the validated Attitudes Related to Trauma-Informed Care (ARTIC) scale and open-ended survey questions via REDCap optional surveys. Trauma-informed care education was made available to staff members in a level IV NICU. Pre- and post-intervention ARTIC scores were compared and post-intervention REDCap surveys were analyzed. RESULT: There were 245 multi-disciplinary NICU team members who completed the ARTIC survey before and/or after the educational intervention; and 764 REDCap surveys were completed throughout the study time. ARTIC scores increased from pre- to post-training both for participants with data at both time points (0.5 SD mean increase) and among those with data at only one time point (0.4 SD mean increase). Content analysis of the REDCap survey corroborated the ARTIC results. CONCLUSION: System-wide trauma-informed education can achieve measurable effect in a NICU setting.


Asunto(s)
Actitud del Personal de Salud , Unidades de Cuidado Intensivo Neonatal , Humanos , Recién Nacido , Encuestas y Cuestionarios , Grupo de Atención al Paciente , Femenino , Masculino , Heridas y Lesiones/terapia , Adulto
4.
Sci Transl Med ; 15(705): eadd7900, 2023 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-37467316

RESUMEN

T cells expressing chimeric antigen receptors (CARs) have shown remarkable therapeutic activity against different types of cancer. However, the wider use of CAR T cells has been hindered by the potential for life-threatening toxicities due to on-target off-tumor killing of cells expressing low amounts of the target antigen. CD229, a signaling lymphocyte-activation molecule (SLAM) family member, has previously been identified as a target for CAR T cell-mediated treatment of multiple myeloma (MM) due to its high expression on the surfaces of MM cells. CD229 CAR T cells have shown effective clearance of MM cells in vitro and in vivo. However, healthy lymphocytes also express CD229, albeit at lower amounts than MM cells, causing their unintended targeting by CD229 CAR T cells. To increase the selectivity of CD229 CAR T cells for MM cells, we used a single amino acid substitution approach of the CAR binding domain to reduce CAR affinity. To identify CARs with increased selectivity, we screened variant binding domains using solid-phase binding assays and biolayer interferometry and determined the cytotoxic activity of variant CAR T cells against MM cells and healthy lymphocytes. We identified a CD229 CAR binding domain with micromolar affinity that, when combined with overexpression of c-Jun, confers antitumor activity comparable to parental CD229 CAR T cells but lacks the parental cells' cytotoxic activity toward healthy lymphocytes in vitro and in vivo. The results represent a promising strategy to improve the efficacy and safety of CAR T cell therapy that requires clinical validation.


Asunto(s)
Antineoplásicos , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Humanos , Mieloma Múltiple/patología , Aminoácidos/metabolismo , Linfocitos T , Receptores Quiméricos de Antígenos/metabolismo , Inmunoterapia Adoptiva/métodos , Antineoplásicos/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Línea Celular Tumoral
5.
JMIR Form Res ; 7: e43101, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36649162

RESUMEN

BACKGROUND: Health inequalities are rooted in historically unjust differences in economic opportunities, environment, access to health care services, and other social determinants. Owing to these health inequalities, the COVID-19 pandemic has disproportionately affected underserved populations, notably people of color, incarcerated and formerly incarcerated individuals, and those unable to physically distance themselves from others. However, people most strongly impacted by health disparities, and the pandemic, are not frequently engaged in research, either as researchers or as participants, resulting in slow progress toward improving health equity. Establishing ways to foster the engagement of historically excluded people is crucial to improving health equity through patient-centered health research. OBJECTIVE: This study aimed to assess the use of equity-centered design thinking (EDT) for engaging community members in research prioritization related to COVID-19. The co-design methods and subsequent production of a toolkit that can be used for engagement were assessed through process evaluation and qualitative methods. METHODS: Process evaluation and qualitative inquiry, using reflexive thematic analysis, were undertaken to examine the use of EDT. Patient community members and stakeholders remotely partnered with design and health researchers in a year-long digital process to cocreate capacity-building tools for setting agenda for research regarding the impact of COVID-19 on health outcomes. Through a series of 3 workshops, 5 community partners engaged in EDT activities to identify critical challenges for the health and well-being of their communities. The subsequent tools were tested with 10 health researchers who provided critical input over the course of 2 workshops. Interviews with co-designers, project materials, and feedback sessions were used in the process evaluation and finalization of an equity-centered toolkit for community engagement in research. Data from the co-design process, meetings, workshops, and interviews were analyzed using reflexive thematic analysis to identify salient themes. RESULTS: Process evaluation illustrated how the EDT co-design process offered an approach to engage patient partners and community stakeholders in health-related research around COVID-19. The participants expressed satisfaction with design thinking approaches, including creative activities and iterative co-design, as a means of working together. Thematic analysis identified 3 key themes: the value of authentic partnerships, building trust and empathy through design, and fostering candid dialogue around health and social issues impacting historically underrepresented and underinvested communities. CONCLUSIONS: The project addressed the need to test EDT strategies for fostering inclusive community engagement in health research agenda setting and provided an alternative to traditional top-down models. Despite the increasing use of human-centered design in health, few projects explicitly include equity in design thinking approaches. The use of methods and tools to intentionally engage underrepresented stakeholders in the process of research agenda setting and equitably sharing power between researchers and community members may improve health research, ultimately improving health equity.

6.
Ophthalmology ; 129(8): 856-864, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35364222

RESUMEN

PURPOSE: Pediatric optic neuritis (ON) is a rare disease that has not been well characterized. The Pediatric ON Prospective Outcomes Study (PON1) was the first prospective study to our knowledge aiming to evaluate visual acuity (VA) outcomes, including VA, recurrence risk, and final diagnosis 2 years after enrollment. DESIGN: Nonrandomized observational study at 23 pediatric ophthalmology or neuro-ophthalmology clinics in the United States and Canada. PARTICIPANTS: A total of 28 (64%) of 44 children initially enrolled in PON1 (age 3-<16 years) who completed their 2-year study visit. METHODS: Participants were treated at the investigator's discretion. MAIN OUTCOMES MEASURES: Age-normal monocular high-contrast VA (HCVA). Secondary outcomes included low-contrast VA (LCVA), neuroimaging findings, and final diagnoses. RESULTS: A total of 28 participants completed the 2-year outcome with a median enrollment age of 10.3 years (range, 5-15); 46% were female, and 68% had unilateral ON at presentation. Final 2-year diagnoses included isolated ON (n = 11, 39%), myelin oligodendrocyte glycoprotein-associated demyelination (n = 8, 29%), multiple sclerosis (MS) (n = 4,14%), neuromyelitis optica spectrum disease (NMOSD) (n = 3, 11%), and acute disseminated encephalomyelitis (n = 2, 7%). Two participants (7%; 95% confidence interval [CI], 1-24) had subsequent recurrent ON (plus 1 participant who did not complete the 2-year visit); all had MS. Two other participants (7%) had a new episode in their unaffected eye. Mean presenting HCVA was 0.81 logarithm of the minimum angle of resolution (logMAR) (∼20/125), improving to 0.14 logMAR (∼20/25-2) at 6 months, 0.12 logMAR (∼20/25-2) at 1 year, and 0.11 logMAR (20/25-1) at 2 years (95% CI, -0.08 to 0.3 [20/20+1-20/40-1]). Twenty-four participants (79%) had age-normal VA at 2 years (95% CI, 60-90); 21 participants (66%) had 20/20 vision or better. The 6 participants without age-normal VA had 2-year diagnoses of NMOSD (n = 2 participants, 3 eyes), MS (n = 2 participants, 2 eyes), and isolated ON (n = 2 participants, 3 eyes). Mean presenting LCVA was 1.45 logMAR (∼20/500-2), improving to 0.78 logMAR (∼20/125+2) at 6 months, 0.69 logMAR (∼20/100+1) at 1 year, and 0.68 logMAR (∼20/100+2) at 2 years (95% CI, 0.48-0.88 [20/50+1-20/150-1]). CONCLUSIONS: Despite poor VA at presentation, most children had marked improvement in VA by 6 months that was maintained over 2 years. Associated neurologic autoimmune diagnoses were common. Additional episodes of ON occurred in 5 (18%) of the participants (3 relapses and 2 new episodes).


Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Neuritis Óptica , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Glicoproteína Mielina-Oligodendrócito , Recurrencia Local de Neoplasia , Neuritis Óptica/diagnóstico , Estudios Prospectivos , Estudios Retrospectivos , Trastornos de la Visión
7.
Semin Perinatol ; 46(3): 151527, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34895926

RESUMEN

Trauma-informed care responds to our current understanding of the ways in which people's traumatic life experiences influence both their health and their interactions with the health care system. Many ethics consults arise because those past traumatic life experiences are not recognized and addressed. In this paper, we present a NICU case that led to an ethics consultation about end-of-life decisions for a dying baby. We illustrate the ways in which a trauma-informed approach helped doctors, nurses and ethics consultants to better understand and care for the mother and baby.


Asunto(s)
Consultoría Ética , Femenino , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Madres
8.
J Asthma ; 59(12): 2386-2394, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34929114

RESUMEN

BACKGROUND: Asthma is a treatable chronic disease of airway inflammation with varying levels of control and severity. Biological therapy is an effective evidence-based treatment for patients with allergic and eosinophilic phenotypes of asthma who are classified as poorly controlled moderate to severe asthma. Yet, evidence-based treatments are infrequently used to support effective care of poorly controlled moderate and severe asthma. This quality improvement (QI) project aimed to increase the number of patients with uncontrolled moderate to severe asthma at an outpatient asthma center who are screened and referred for biologic therapy when appropriate. METHODS: A guideline-based biologic screening protocol was implemented using plan-do-study-act (PDSA) methodology allowing for a systematic approach for implementation, monitoring and making adjustments. A pre- and post-independent groups comparative design was utilized to evaluate screening and referral data. RESULTS: Screening improved significantly from pre- (n = 30, 23.8%) to post-implementation (n = 17, 70.8%), p < 0.001; phi = .372. Referrals to biologics also improved from 42.4% (n = 28) to 93.3% (n = 14), p < 0.001; phi = .396. Providers reported increased knowledge, confidence, and satisfaction with the asthma screening protocol at post-implementation. CONCLUSIONS: The implementation of an asthma screening protocol for asthma patients in an ambulatory center is an effective way of increasing screening for eligibility for biologic therapy. Adhering to the standard of care based on evidence-based guidelines increased access to biologic therapy with a higher percentage of patients being referred for therapy.


Asunto(s)
Antiasmáticos , Asma , Humanos , Asma/diagnóstico , Asma/tratamiento farmacológico , Mejoramiento de la Calidad , Terapia Biológica , Derivación y Consulta
9.
Open Forum Infect Dis ; 8(8): ofab313, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34458391

RESUMEN

We partnered with the US Department of Health and Human Services to treat high-risk, nonadmitted coronavirus disease 2019 (COVID-19) patients with bamlanivimab in the Bronx, New York per Emergency Use Authorization criteria. Increasing posttreatment hospitalizations were observed monthly between December 2020 and March 2021 in parallel to the emergence of severe acute respiratory syndrome coronavirus 2 variants in New York City.

10.
Exp Biol Med (Maywood) ; 246(20): 2202-2206, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34233520

RESUMEN

A pathognomonic macular ripple sign has been reported with scanning laser ophthalmoscopy images in patients with foveal hypoplasia, though the optical basis of this sign is presently unknown. Here we present a case series of seven individuals with foveal hypoplasia (based on spectral domain optical coherence tomography). Each patient underwent infrared scanning laser ophthalmoscopy retinal imaging in both eyes, acquired with and without a polarization filter and assessment for a ripple-like effect in the fovea. On imaging, macular ripples were present in all eyes with foveal hypoplasia when using a polarization filter, but not when imaged without the filter. We conclude that the macular ripple sign is an imaging artifact attributable to the unique pattern of phase retardation of the Henle fiber layer in the setting of foveal hypoplasia. By utilizing a polarization filter with retinal photography, this feature can be exploited to promptly identify foveal hypoplasia in settings where OCT is not possible due to nystagmus.


Asunto(s)
Fóvea Central/patología , Tomografía de Coherencia Óptica/métodos , Trastornos de la Visión/diagnóstico por imagen , Trastornos de la Visión/diagnóstico , Adolescente , Adulto , Niño , Femenino , Fóvea Central/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Oftalmoscopía/métodos
11.
Nat Commun ; 11(1): 798, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-32034142

RESUMEN

Multiple myeloma (MM) is a plasma cell malignancy and most patients eventually succumb to the disease. Chimeric antigen receptor (CAR) T cells targeting B-Cell Maturation Antigen (BCMA) on MM cells have shown high-response rates, but limited durability. CD229/LY9 is a cell surface receptor present on B and T lymphocytes that is universally and strongly expressed on MM plasma cells. Here, we develop CD229 CAR T cells that are highly active in vitro and in vivo against MM plasma cells, memory B cells, and MM-propagating cells. We do not observe fratricide during CD229 CAR T cell production, as CD229 is downregulated in T cells during activation. In addition, while CD229 CAR T cells target normal CD229high T cells, they spare functional CD229neg/low T cells. These findings indicate that CD229 CAR T cells may be an effective treatment for patients with MM.


Asunto(s)
Inmunoterapia Adoptiva/métodos , Mieloma Múltiple/terapia , Receptores de Antígenos de Linfocitos T/inmunología , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/metabolismo , Animales , Anticuerpos/inmunología , Linfocitos B/metabolismo , Humanos , Células K562/inmunología , Masculino , Ratones Endogámicos NOD , Mieloma Múltiple/patología , Receptores de Antígenos de Linfocitos T/metabolismo , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/genética , Familia de Moléculas Señalizadoras de la Activación Linfocitaria/inmunología , Linfocitos T/inmunología , Linfocitos T/trasplante , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Reprod Sci ; 26(4): 551-559, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30296925

RESUMEN

OBJECTIVE: A multitude of factors promotes inflammation in the reproductive tract leading to preterm birth. Macrophages peak in the cervix prior to birth and their numbers are increased by the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF). We hypothesize GM-CSF is produced from multiple sites in the genital tract and is a key mediator in preterm birth. STUDY DESIGN: Ectocervical, endocervical, and amniotic fluid mesenchymal stem cells were treated with lipopolysaccharide (LPS), and the concentration and expression of GM-CSF was measured. Pregnant CD-1 mice on gestational day 17 received LPS and an intravenous injection of either anti-mouse GM-CSF or control antibody. After 6 hours, the preterm birth rate was recorded. RESULTS: Treatment with LPS increased the GM-CSF concentration and messenger RNA expression after 24 hours in all 3 cell lines ( P < .01). Mice treated with LPS and the GM-CSF antibody had a preterm birth rate of 25%, compared to a 66.7% preterm birth rate in controls, within 6 hours ( P < .05, χ2). Treatment with the anti-mouse GM-CSF antibody decreased the concentration of GM-CSF in the mouse serum ( P < .01) but did not alter the number of macrophages or collagen content in the cervix. CONCLUSION: These studies demonstrate that GM-CSF is produced from multiple sites in the genital tract and that treatment with an antibody to GM-CSF prevents preterm birth. Curiously, the anti-mouse GM-CSF antibody did not decrease the number of macrophages in the cervix. Further research is needed to determine whether antibodies to GM-CSF can be utilized as a therapeutic agent to prevent preterm birth.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Inflamación/metabolismo , Células Madre Mesenquimatosas/metabolismo , Parto/metabolismo , Nacimiento Prematuro/metabolismo , Animales , Línea Celular , Cuello del Útero/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Inflamación/inducido químicamente , Lipopolisacáridos/administración & dosificación , Ratones , Nacimiento Prematuro/etiología , ARN Mensajero/metabolismo
13.
Am J Ophthalmol ; 186: 104-115, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29196184

RESUMEN

PURPOSE: To compare visual acuity (VA) improvement in teenagers with amblyopia treated with a binocular iPad game vs part-time patching. METHODS: One hundred participants aged 13 to <17 years (mean 14.3 years) with amblyopia (20/40 to 20/200, mean ∼20/63) resulting from strabismus, anisometropia, or both were enrolled into a randomized clinical trial. Participants were randomly assigned to treatment for 16 weeks of either a binocular iPad game prescribed for 1 hour per day (n = 40) or patching of the fellow eye prescribed for 2 hours per day (n = 60). The main outcome measure was change in amblyopic eye VA from baseline to 16 weeks. RESULTS: Mean amblyopic eye VA improved from baseline by 3.5 letters (2-sided 95% confidence interval [CI]: 1.3-5.7 letters) in the binocular group and by 6.5 letters (2-sided 95% CI: 4.4-8.5 letters) in the patching group. After adjusting for baseline VA, the difference between the binocular and patching groups was -2.7 letters (95% CI: -5.7 to 0.3 letters, P = .082) or 0.5 lines, favoring patching. In the binocular group, treatment adherence data from the iPad device indicated that only 13% of participants completed >75% of prescribed treatment. CONCLUSIONS: In teenagers aged 13 to <17 years, improvement in amblyopic eye VA with the binocular iPad game used in this study was not found to be better than patching, and was possibly worse. Nevertheless, it remains unclear whether the minimal treatment response to binocular treatment was owing to poor treatment adherence or lack of treatment effect.


Asunto(s)
Ambliopía/terapia , Computadoras de Mano , Juegos de Video , Visión Binocular/fisiología , Agudeza Visual , Adolescente , Ambliopía/complicaciones , Ambliopía/fisiopatología , Anisometropía/etiología , Anisometropía/fisiopatología , Anisometropía/terapia , Anteojos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Privación Sensorial , Estrabismo/etiología , Estrabismo/fisiopatología , Estrabismo/terapia , Resultado del Tratamiento
14.
Female Pelvic Med Reconstr Surg ; 24(6): 444-448, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-28914701

RESUMEN

OBJECTIVES: This study aims to identify risk factors for elevated preoperative postvoid residual (PVR) and persistently elevated postoperative PVR and to evaluate the resolution rate of elevated PVR urine volume in patients undergoing reconstructive surgery for pelvic organ prolapse (POP). METHODS: This was a retrospective cohort study comparing 50 women with elevated preoperative PVR (≥100 mL) and 50 women with normal PVR (<100 mL). Preoperative demographic, physical examination, urodynamic data, type of surgery performed, and postoperative trial of void data were collected. Variables were evaluated for association with elevated PVR using Student t test or Mann-Whitney U test, and χ or Fisher exact test. RESULTS: The elevated PVR cohort was older (65.5 ± 13.3 vs 60.6 ± 10.1 years, P = 0.04). The cohorts did not differ by body mass index, parity, number of cesarean deliveries, prior hysterectomy, incontinence, prolapse surgery, menopausal status, hormone replacement therapy, history of recurrent urinary tract infections, diabetes mellitus, or maximum bladder capacity. Most patients had preoperative anterior prolapse stage 2 or 3. Complaints of incontinence, incomplete bladder emptying, and overactive bladder did not differ between groups. Performed Surgical procedures, cystoscopy findings, and rate of postoperative trial of void failures did not differ between groups. One patient per cohort learned clean intermittent self-catheterization for persistently elevated PVR. CONCLUSIONS: All women undergoing surgery for POP had postoperative resolution of elevated PVR. Patients with nonneurogenic-elevated PVR can be reassured that bladder emptying will improve after surgical repair of POP.


Asunto(s)
Procedimientos Quirúrgicos Ginecológicos/efectos adversos , Prolapso de Órgano Pélvico/cirugía , Retención Urinaria/etiología , Anciano , Femenino , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Micción/fisiología
15.
PLoS One ; 12(12): e0190021, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29284017

RESUMEN

Fisheries bycatch is a widespread and serious issue that leads to declines of many important and threatened marine species. However, documenting the distribution, abundance, population trends and threats to sparse populations of marine species is often beyond the capacity of developing countries because such work is complex, time consuming and often extremely expensive. We have developed a flexible tool to document spatial distribution and population trends for dugongs and other marine species in the form of an interview questionnaire supported by a structured data upload sheet and a comprehensive project manual. Recognising the effort invested in getting interviewers to remote locations, the questionnaire is comprehensive, but low cost. The questionnaire has already been deployed in 18 countries across the Indo-Pacific region. Project teams spent an average of USD 5,000 per country and obtained large data sets on dugong distribution, trends, catch and bycatch, and threat overlaps. Findings indicated that >50% of respondents had never seen dugongs and that 20% had seen a single dugong in their lifetimes despite living and fishing in areas of known or suspected dugong habitat, suggesting that dugongs occurred in low numbers. Only 3% of respondents had seen mother and calf pairs, indicative of low reproductive output. Dugong hunting was still common in several countries. Gillnets and hook and line were the most common fishing gears, with the greatest mortality caused by gillnets. The questionnaire has also been used to study manatees in the Caribbean, coastal cetaceans along the eastern Gulf of Thailand and western Peninsular Malaysia, and river dolphins in Peru. This questionnaire is a powerful tool for studying distribution and relative abundance for marine species and fishery pressures, and determining potential conservation hotspot areas. We provide the questionnaire and supporting documents for open-access use by the scientific and conservation communities.


Asunto(s)
Documentación , Especies en Peligro de Extinción , Explotaciones Pesqueras , Animales , Especificidad de la Especie , Encuestas y Cuestionarios
16.
Stroke ; 48(4): 894-899, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28283605

RESUMEN

BACKGROUND AND PURPOSE: The purpose was to test the hypothesis that increased oxygen extraction fraction (OEF), a marker of severe hemodynamic impairment measured by positron emission tomography, is an independent risk factor for subsequent ischemic stroke in this population. METHODS: Adults with idiopathic moyamoya phenomena were recruited between 2005 and 2012 for a prospective, multicenter, blindly adjudicated, longitudinal cohort study. Measurements of OEF were obtained on enrollment. Subjects were followed up for the occurrence of ipsilateral ischemic stroke at 6-month intervals. Patients were censored at the time of surgical revascularization or at last follow-up. The primary analysis was time to ischemic stroke in the territory of the occlusive vasculopathy. RESULTS: Forty-nine subjects were followed up during a median of 3.7 years. One of 16 patients with increased OEF on enrollment had an ischemic stroke and another had an intraparenchymal hemorrhage. Three of 33 patients with normal OEF had an ischemic stroke. On a per-hemisphere basis, 21 of 79 hemispheres with moyamoya vasculopathy had increased OEF at baseline. No ischemic strokes and one hemorrhage occurred in a hemisphere with increased OEF (n=21). Sixteen patients (20 hemispheres), including 5 with increased OEF at enrollment, were censored at a mean of 5.3 months after enrollment for revascularization surgery. CONCLUSIONS: The risk of new or recurrent stroke was lower than expected. The low event rate, low prevalence of increased OEF, and potential selection bias introduced by revascularization surgery limit strong conclusions about the association of increased OEF and future stroke risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00629915.


Asunto(s)
Isquemia Encefálica/diagnóstico por imagen , Enfermedad de Moyamoya/diagnóstico por imagen , Acoplamiento Neurovascular , Tomografía de Emisión de Positrones/métodos , Accidente Cerebrovascular/diagnóstico por imagen , Adulto , Anciano , Isquemia Encefálica/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medio Oeste de Estados Unidos/epidemiología , Enfermedad de Moyamoya/epidemiología , Oxígeno/metabolismo , Recurrencia , Factores de Riesgo , Método Simple Ciego , Accidente Cerebrovascular/epidemiología
18.
JCI Insight ; 1(9): e87310, 2016 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-27699274

RESUMEN

Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease driven by both innate and adaptive immune cells. African Americans tend to present with more severe disease at an earlier age compared with patients of European ancestry. In order to better understand the immunological differences between African American and European American patients, we analyzed the frequencies of B cell subsets and the expression of B cell activation markers from a total of 68 SLE patients and 69 normal healthy volunteers. We found that B cells expressing the activation markers CD86, CD80, PD1, and CD40L, as well as CD19+CD27-IgD- double-negative B cells, were enriched in African American patients vs. patients of European ancestry. In addition to increased expression of CD40L, surface levels of CD40 on B cells were lower, suggesting the engagement of the CD40 pathway. In vitro experiments confirmed that CD40L expressed by B cells could lead to CD40 activation and internalization on adjacent B cells. To conclude, these results indicate that, compared with European American patients, African American SLE patients present with a particularly active B cell component, possibly via the activation of the CD40/CD40L pathway. These data may help guide the development of novel therapies.


Asunto(s)
Linfocitos B/citología , Lupus Eritematoso Sistémico/etnología , Negro o Afroamericano , Antígenos de Superficie/análisis , Antígeno B7-2/análisis , Antígenos CD40/análisis , Ligando de CD40/análisis , Humanos , Fenotipo
19.
Glob Heart ; 11(1): 17-25, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27102019

RESUMEN

Stemming the tide of noncommunicable diseases (NCDs) worldwide requires a multipronged approach. Although much attention has been paid to disease control measures, there is relatively little consideration of the importance of training the next generation of health-related researchers to play their important role in this global epidemic. The lack of support for early stage investigators in low- and middle-income countries interested in the global NCD field has resulted in inadequate funding opportunities for research, insufficient training in advanced research methodology and data analysis, lack of mentorship in manuscript and grant writing, and meager institutional support for developing, submitting, and administering research applications and awards. To address this unmet need, The National Heart, Lung, and Blood Institute-UnitedHealth Collaborating Centers of Excellence initiative created a Training Subcommittee that coordinated and developed an intensive, mentored health-related research experience for a number of early stage investigators from the 11 Centers of Excellence around the world. We describe the challenges faced by early stage investigators in low- and middle-income countries, the organization and scope of the Training Subcommittee, training activities, early outcomes of the early stage investigators (foreign and domestic) and training materials that have been developed by this program that are available to the public. By investing in the careers of individuals in a supportive global NCD network, we demonstrate the impact that an investment in training individuals from low- and middle-income countries can have on the preferred future of or current efforts to combat NCDs.


Asunto(s)
Academias e Institutos , Investigación Biomédica , Creación de Capacidad , Países en Desarrollo , Salud Global , Cardiopatías , Enfermedades Pulmonares , Investigadores/educación , Humanos , National Heart, Lung, and Blood Institute (U.S.) , Estados Unidos
20.
Ment Health Clin ; 6(5): 254-259, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29955479

RESUMEN

INTRODUCTION: Nonadherence with oral antipsychotics in patients with schizophrenia has been associated with symptom relapse and rehospitalizations, resulting in increased morbidity and health care costs. Long-acting injectable antipsychotics (LAIAs) are an alternative to enhance adherence and decrease relapse requiring hospitalization. The objectives of this study are to determine the impact of LAIAs on reducing length of stay, the rate of annual readmissions, and the number of failed annual discharges (defined as a readmission in less than 30 days) in patients with schizophrenia or schizoaffective disorder admitted to an acute inpatient psychiatric unit. METHODS: Using the hospital database, 52 patients receiving a diagnosis of schizophrenia or schizoaffective disorders treated with oral antipsychotics and later transitioned to LAIAs were evaluated retrospectively. RESULTS: Patients treated with LAIAs did not show a statistically significant reduction in length of stay compared with their length of stay on oral antipsychotics. Patients treated with LAIAs experienced a statistically significant reduction in the rate of annual readmissions and a reduction in the number of failed annual discharges, although the latter was not statistically significant (P = .076 when compared to treatment with oral antipsychotics). DISCUSSION: These findings suggest a potential role for maintaining patients with a diagnosis of schizophrenia or schizoaffective disorder on LAIAs to prevent relapse and rehospitalizations. The reduction in the number of failed annual discharges between the oral versus LAIA group, although not statistically significant, warrants further investigation to determine the impact of LAIAs on readmission within 30 days.

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