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1.
Nature ; 627(8004): 505-509, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38418881

ABSTRACT

The Double Asteroid Redirection Test (DART) had an impact with Dimorphos (a satellite of the asteroid Didymos) on 26 September 20221. Ground-based observations showed that the Didymos system brightened by a factor of 8.3 after the impact because of ejecta, returning to the pre-impact brightness 23.7 days afterwards2. Hubble Space Telescope observations made from 15 minutes after impact to 18.5 days after, with a spatial resolution of 2.1 kilometres per pixel, showed a complex evolution of the ejecta3, consistent with other asteroid impact events. The momentum enhancement factor, determined using the measured binary period change4, ranges between 2.2 and 4.9, depending on the assumptions about the mass and density of Dimorphos5. Here we report observations from the LUKE and LEIA instruments on the LICIACube cube satellite, which was deployed 15 days in advance of the impact of DART. Data were taken from 71 seconds before the impact until 320 seconds afterwards. The ejecta plume was a cone with an aperture angle of 140 Ā± 4Ā degrees. The inner region of the plume was blue, becoming redder with increasing distance from Dimorphos. The ejecta plume exhibited a complex and inhomogeneous structure, characterized by filaments, dust grains and single or clustered boulders. The ejecta velocities ranged from a few tens ofĀ metres per second to about 500 metres per second.

2.
J Gen Intern Med ; 38(4): 970-977, 2023 03.
Article in English | MEDLINE | ID: mdl-35641720

ABSTRACT

BACKGROUND: The 21st Century Cures Act and the OpenNotes movement have brought patients immediate access to their electronic health records (EHRs). The experiences of marginalized people, including transgender people, accessing and reviewing their EHRs could inform documentation guidelines to improve patient-clinician rapport and reduce harm. OBJECTIVE: To investigate the experiences of transgender people reviewing EHRs. DESIGN: Qualitative study using community-engaged research and an interpretive description methodology. Participants were recruited via social media, snowball sampling was employed, and purposive sampling was used to ensure diversity in terms of age, race/ethnicity, and other factors. In focus groups, participants were asked to discuss their experiences reviewing their EHRs and, for those participants who were clinicians, their experiences reviewing other clinicians' documentation. PARTICIPANTS: Thirty transgender adults aged 20 to 67 years, including 10 clinicians. APPROACH: Digital audio-recordings of focus groups were transcribed verbatim. Content was analyzed to identify emerging essential elements and analysis was continued until no new themes emerged (i.e., saturation). KEY RESULTS: Four themes were noted. (1) Using the wrong name, pronoun, or gender marker for patients is common in the EHR, erodes trust, and causes trauma. (2) Various aspects of clinicians' notes contradict, blame, or stigmatize patients, across multiple axes of oppression. (3) Limitations of EHR capabilities create barriers to quality care. (4) Certain medical customs set the stage for marginalizing, objectifying, and pathologizing transgender people. CONCLUSIONS: Transgender people experience harm via various aspects of EHR documentation, suggesting that changes must be made to improve patient-clinician relationships and reduce ill-effects for patients.


Subject(s)
Transgender Persons , Adult , Humans , Electronic Health Records , Qualitative Research , Focus Groups , Gender Identity
3.
Ann Fam Med ; 21(5): 408-415, 2023.
Article in English | MEDLINE | ID: mdl-37748898

ABSTRACT

PURPOSE: Investigating transgender people's experiences sharing health information in clinical encounters may yield insights for family medicine clinicians. METHODS: This was a qualitative study using a community-based participatory research approach and interpretive description methodology. Seven qualitative focus groups were conducted with 30 transgender adults living in North America. We used purposive sampling to ensure diversity. The focus groups were transcribed verbatim, and 2 investigators independently reviewed and coded each transcript, then they mutually reviewed the transcripts, reconciled their coding, and summarized the codes into themes. Themes were reviewed with community members, participants, and uninvolved clinically oriented investigators for member checking and peer debriefing. RESULTS: Four themes were noted: (1) transgender people often perceive clinicians' questions as voyeuristic, stigmatizing, or self-protective; (2) patients describe being pathologized, denied or given substandard care, or harmed when clinicians learned they are transgender; (3) transgender people frequently choose between risking stigma when sharing information and risking ineffective clinical problem solving if clinicians do not have all the information about their medical histories; (4) improving the safety of transgender people is difficult in the context of contemporary medical systems. CONCLUSIONS: Transgender people often must choose between stigma and potentially suboptimal care. Improvements in medical culture, policies, procedures, and data collection tools are necessary to improve the quality and safety of clinical care for transgender people. Institutional and systems changes may be required to safely and effectively implement sexual orientation and gender identity (SOGI) data collection in clinical settings.


Subject(s)
Transgender Persons , Adult , Humans , Male , Female , Focus Groups , Gender Identity , Qualitative Research , Sexual Behavior
4.
Nature ; 504(7478): 122-5, 2013 Dec 05.
Article in English | MEDLINE | ID: mdl-24196707

ABSTRACT

Olivine is a major component of the mantle of differentiated bodies, including Earth. Howardite, eucrite and diogenite (HED) meteorites represent regolith, basaltic-crust, lower-crust and possibly ultramafic-mantle samples of asteroid Vesta, which is the lone surviving, large, differentiated, basaltic rocky protoplanet in the Solar System. Only a few of these meteorites, the orthopyroxene-rich diogenites, contain olivine, typically with a concentration of less than 25 per cent by volume. Olivine was tentatively identified on Vesta, on the basis of spectral and colour data, but other observations did not confirm its presence. Here we report that olivine is indeed present locally on Vesta's surface but that, unexpectedly, it has not been found within the deep, south-pole basins, which are thought to be excavated mantle rocks. Instead, it occurs as near-surface materials in the northern hemisphere. Unlike the meteorites, the olivine-rich (more than 50 per cent by volume) material is not associated with diogenite but seems to be mixed with howardite, the most common surface material. Olivine is exposed in crater walls and in ejecta scattered diffusely over a broad area. The size of the olivine exposures and the absence of associated diogenite favour a mantle source, but the exposures are located far from the deep impact basins. The amount and distribution of observed olivine-rich material suggest a complex evolutionary history for Vesta.

5.
Nature ; 491(7422): 83-6, 2012 Nov 01.
Article in English | MEDLINE | ID: mdl-23128228

ABSTRACT

Localized dark and bright materials, often with extremely different albedos, were recently found on Vesta's surface. The range of albedos is among the largest observed on Solar System rocky bodies. These dark materials, often associated with craters, appear in ejecta and crater walls, and their pyroxene absorption strengths are correlated with material brightness. It was tentatively suggested that the dark material on Vesta could be either exogenic, from carbon-rich, low-velocity impactors, or endogenic, from freshly exposed mafic material or impact melt, created or exposed by impacts. Here we report Vesta spectra and images and use them to derive and interpret the properties of the 'pure' dark and bright materials. We argue that the dark material is mainly from infall of hydrated carbonaceous material (like that found in a major class of meteorites and some comet surfaces), whereas the bright material is the uncontaminated indigenous Vesta basaltic soil. Dark material from low-albedo impactors is diffused over time through the Vestan regolith by impact mixing, creating broader, diffuse darker regions and finally Vesta's background surface material. This is consistent with howardite-eucrite-diogenite meteorites coming from Vesta.

6.
Psychol Med ; 47(8): 1357-1369, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27998326

ABSTRACT

BACKGROUND: Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth. METHOD: LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. RESULTS: Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. CONCLUSIONS: These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.


Subject(s)
Adolescent Behavior/physiology , Affective Symptoms/physiopathology , Cerebral Cortex , Depression/physiopathology , Problem Behavior , Reward , Substance-Related Disorders/diagnosis , Adolescent , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiology , Cerebral Cortex/physiopathology , Child , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Substance-Related Disorders/diagnostic imaging , Substance-Related Disorders/pathology , Substance-Related Disorders/physiopathology
7.
Mol Psychiatry ; 21(9): 1194-201, 2016 09.
Article in English | MEDLINE | ID: mdl-26903272

ABSTRACT

Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0 (s.d.=2.0) from three clinical sites. Linear regression using the LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection was used to predict severity of future behavioral and emotional dysregulation measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)) at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained ~1/3 of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions.


Subject(s)
Affective Symptoms/physiopathology , White Matter/physiopathology , Adolescent , Affective Symptoms/genetics , Bipolar Disorder/diagnosis , Brain/physiopathology , Child , Emotions/physiology , Female , Forecasting/methods , Humans , Longitudinal Studies , Male , Parents/psychology , Psychiatric Status Rating Scales , Reward , Treatment Outcome
8.
Healthc Manage Forum ; 28(6): 265-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26347478

ABSTRACT

The ability to provide quality cancer care largely depends on how accessible the services are to those in need. In the current state, disparities exist in access to Canadian cancer services, and this poses an ethical challenge. This article highlights ethical and strategic considerations related to equity in access to Canadian cancer care. Based on the principles of bioethics-beneficence, non-maleficence, and justice-various action strategies have been recommended in order to improve access to cancer care nationally.

9.
Healthc Manage Forum ; 28(6): 270-4, 2015 Nov.
Article in French | MEDLINE | ID: mdl-26429989

ABSTRACT

La capacitĆ© d'offrir des soins du cancer de qualitĆ© dĆ©pend en grande partie de l'accessibilitĆ© des services Ć  ceux qui en ont besoin. Dans l'Ć©tat actuel des choses, on constate des disparitĆ©s en matiĆØre d'accĆØs aux services de cancĆ©rologie au Canada, ce qui constitue un problĆØme sur le plan de l'Ć©thique. Le prĆ©sent article fait ressortir les points de vue Ć©thiques et stratĆ©giques liĆ©s Ć  l'Ć©quitĆ© dans l'accĆØs aux soins du cancer au Canada. S'inspirant des principes de la bioĆ©thique, soit la bĆ©nĆ©ficience, la non-malĆ©ficience et la justice, plusieurs stratĆ©gies sont recommandĆ©es pour amĆ©liorer l'accĆØs aux soins du cancer au pays.

10.
Psychol Med ; 44(12): 2603-15, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24468022

ABSTRACT

BACKGROUND: Neuroimaging measures of behavioral and emotional dysregulation can yield biomarkers denoting developmental trajectories of psychiatric pathology in youth. We aimed to identify functional abnormalities in emotion regulation (ER) neural circuitry associated with different behavioral and emotional dysregulation trajectories using latent class growth analysis (LCGA) and neuroimaging. METHOD: A total of 61 youth (9-17 years) from the Longitudinal Assessment of Manic Symptoms study, and 24 healthy control youth, completed an emotional face n-back ER task during scanning. LCGA was performed on 12 biannual reports completed over 5 years of the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M), a parental report of the child's difficulty regulating positive mood and energy. RESULTS: There were two latent classes of PGBI-10M trajectories: high and decreasing (HighD; n=22) and low and decreasing (LowD; n=39) course of behavioral and emotional dysregulation over the 12 time points. Task performance was >89% in all youth, but more accurate in healthy controls and LowD versus HighD (p<0.001). During ER, LowD had greater activity than HighD and healthy controls in the dorsolateral prefrontal cortex, a key ER region, and greater functional connectivity than HighD between the amygdala and ventrolateral prefrontal cortex (p's<0.001, corrected). CONCLUSIONS: Patterns of function in lateral prefrontal cortical-amygdala circuitry in youth denote the severity of the developmental trajectory of behavioral and emotional dysregulation over time, and may be biological targets to guide differential treatment and novel treatment development for different levels of behavioral and emotional dysregulation in youth.


Subject(s)
Adolescent Development/physiology , Affective Symptoms/physiopathology , Amygdala/physiopathology , Behavioral Symptoms/physiopathology , Prefrontal Cortex/physiopathology , Adolescent , Child , Female , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male
11.
Nat Commun ; 15(1): 6204, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080000

ABSTRACT

The bearing capacity - the ability of a surface to support applied loads - is an important parameter for understanding and predicting the response of a surface. Previous work has inferred the bearing capacity and trafficability of specific regions of the Moon using orbital imagery and measurements of the boulder tracks visible on its surface. Here, we estimate the bearing capacity of the surface of an asteroid for the first time using DART/DRACO images of suspected boulder tracks on the surface of asteroid (65803) Didymos. Given the extremely low surface gravity environment, special attention is paid to the underlying assumptions of the geotechnical approach. The detailed analysis of the boulder tracks indicates that the boulders move from high to low gravitational potential, and provides constraints on whether the boulders may have ended their surface motion by entering a ballistic phase. From the 9 tracks identified with sufficient resolution to estimate their dimensions, we find an average boulder track width and length of 8.9 Ā± 1.5 m and 51.6 Ā± 13.3 m, respectively. From the track widths, the mean bearing capacity of Didymos is estimated to be 70 N/m2, implying that every 1 m2 of Didymos' surface at the track location can support only ~70 N of force before experiencing general shear failure. This value is at least 3 orders of magnitude less than the bearing capacity of dry sand on Earth, or lunar regolith.

12.
Nat Commun ; 15(1): 6205, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080257

ABSTRACT

Asteroids smaller than 10 km are thought to be rubble piles formed from the reaccumulation of fragments produced in the catastrophic disruption of parent bodies. Ground-based observations reveal that some of these asteroids are today binary systems, in which a smaller secondary orbits a larger primary asteroid. However, how these asteroids became binary systems remains unclear. Here, we report the analysis of boulders on the surface of the stony asteroid (65803) Didymos and its moonlet, Dimorphos, from data collected by the NASA DART mission. The size-frequency distribution of boulders larger than 5 m on Dimorphos and larger than 22.8 m on Didymos confirms that both asteroids are piles of fragments produced in the catastrophic disruption of their progenitors. Dimorphos boulders smaller than 5 m have size best-fit by a Weibull distribution, which we attribute to a multi-phase fragmentation process either occurring during coalescence or during surface evolution. The density per km2 of Dimorphos boulders ≥1 m is 2.3x with respect to the one obtained for (101955) Bennu, while it is 3.0x with respect to (162173) Ryugu. Such values increase once Dimorphos boulders ≥5 m are compared with Bennu (3.5x), Ryugu (3.9x) and (25143) Itokawa (5.1x). This is of interest in the context of asteroid studies because it means that contrarily to the single bodies visited so far, binary systems might be affected by subsequential fragmentation processes that largely increase their block density per km2. Direct comparison between the surface distribution and shapes of the boulders on Didymos and Dimorphos suggest that the latter inherited its material from the former. This finding supports the hypothesis that some asteroid binary systems form through the spin up and mass shedding of a fraction of the primary asteroid.

13.
Nat Commun ; 15(1): 6206, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39080275

ABSTRACT

Spacecraft observations revealed that rocks on carbonaceous asteroids, which constitute the most numerous class by composition, can develop millimeter-to-meter-scale fractures due to thermal stresses. However, signatures of this process on the second-most populous group of asteroids, the S-complex, have been poorly constrained. Here, we report observations of boulders' fractures on Dimorphos, which is the moonlet of the S-complex asteroid (65803) Didymos, the target of NASA's Double Asteroid Redirection Test (DART) planetary defense mission. We show that the size-frequency distribution and orientation of the mapped fractures are consistent with formation through thermal fatigue. The fractures' preferential orientation supports that these have originated in situ on Dimorphos boulders and not on Didymos boulders later transferred to Dimorphos. Based on our model of the fracture propagation, we propose that thermal fatigue on rocks exposed on the surface of S-type asteroids can form shallow, horizontally propagating fractures in much shorter timescales (100 kyr) than in the direction normal to the boulder surface (order of Myrs). The presence of boulder fields affected by thermal fracturing on near-Earth asteroid surfaces may contribute to an enhancement in the ejected mass and momentum from kinetic impactors when deflecting asteroids.

14.
Med Phys ; 38(7): 4215-24, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21859023

ABSTRACT

PURPOSE: To extend the concept of deflecting the tip of a catheter with the magnetic force created in an MRI system through the use of an array of independently controllable steering coils located in the catheter tip, and to present methods for visualization of the catheter and/or surrounding areas while the catheter is deflected. METHODS: An array of steering coils made of 42-gauge wire was built over a 2.5 Fr (0.83 mm) fiber braided microcatheter. Two of the coils were 70 turn axial coils separated by 1 cm, and the third was a 15-turn square side coil that was 2 x 4 mm2. Each coil was driven independently by a pulse width modulation (PWM) current source controlled by a microprocessor that received commands from a MATLAB routine that dynamically set current amplitude and direction for each coil. The catheter was immersed in a water phantom containing 1% Gd-DTPA that was placed at the isocenter of a 1.5 T MRI scanner. Deflections of the catheter tip were measured from image-based data obtained with a real-time radio frequency (RF) spoiled gradient echo sequence (GRE). The small local magnetic fields generated by the steering coils were exploited to generate a hyperintense signal at the catheter tip by using a modified GRE sequence that did not include slice-select rewinding gradients. Imaging and excitation modes were implemented by synchronizing the excitation of the steering coil array with the scanner by ensuring that no current was driven through the coils during the data acquisition window; this allowed visualization of the surrounding tissue while not affecting the desired catheter position. RESULTS: Deflections as large as 2.5 cm were measured when exciting the steering coils sequentially with a 100 mA maximum current per coil. When exciting a single axial coil, the deflection was half this value with 30% higher current. A hyperintense catheter tip useful for catheter tracking was obtained by imaging with the modified GRE sequence. Clear visualization of the areas surrounding the catheter was obtained by using the excitation and imaging mode even with a repetition time (TR) as small as 10 ms. CONCLUSIONS: A new system for catheter steering is presented that allows large deflections through the use of an integrated array of steering coils. Additionally, two imaging techniques for tracking the catheter tip and visualization of surrounding areas, without interference from the active catheter, were shown. Together the demonstrated steerable catheter, control system and the imaging techniques will ultimately contribute to the development of a steerable system for interventional MRI procedures.


Subject(s)
Catheterization, Peripheral/instrumentation , Magnetic Resonance Imaging/instrumentation , Magnetics/instrumentation , Computer-Aided Design , Equipment Design , Equipment Failure Analysis , Reproducibility of Results , Sensitivity and Specificity
15.
J Cell Biol ; 114(1): 143-53, 1991 Jul.
Article in English | MEDLINE | ID: mdl-2050739

ABSTRACT

We have proposed previously that the polysialic acid (PSA) moiety of NCAM can influence membrane-membrane apposition, and thereby serve as a selective regulator of a variety of contact-dependent cell interactions. In this study, cell and tissue culture models are used to obtain direct evidence that the presence of PSA on the surface membrane can affect both cell-cell and cell-substrate interactions. Using a neuroblastoma/sensory neuron cell hybrid, it was found that removal of PSA with a specific neuraminidase (endo-N) augments cell-cell aggregation mediated by the L1 cell adhesion molecule as well as cell attachment to a variety of tissue culture substrates. In studies of embryonic spinal cord axon bundling, which involves both cell-cell and cell-substrate interactions, the pronounced defasciculation produced by removal of PSA is most easily explained by an increase in cell-substrate interaction. The fact that in both studies NCAM's intrinsic adhesion function was found not to be an important variable further illustrates that regulation of the cell surface by PSA can extend beyond binding mediated by the NCAM polypeptide.


Subject(s)
Axons/physiology , Cell Adhesion Molecules, Neuronal/physiology , Cell Adhesion , Polysaccharides/physiology , Sialic Acids/physiology , Animals , Cell Aggregation , Chick Embryo , Culture Techniques , Hybrid Cells , Laminin/physiology , Models, Biological , Neuraminidase/metabolism , Spinal Cord/chemistry
16.
Science ; 267(5204): 1623-6, 1995 Mar 17.
Article in English | MEDLINE | ID: mdl-7886449

ABSTRACT

Through the application of new analytical techniques to high spatial resolution imaging spectrometer data, the ferrous mineralogy of major volcanic terrains on Mars is shown to consist of significant fractions of both low- and high-calcium pyroxene. Changes in the relative abundances of these pyroxenes are observed for units of different age and morphology, even in regions with higher degrees of alteration and contamination from dust. Volcanic rocks with these characteristics are uncommon on Earth but are typical of the basaltic SNC meteorites (shergottites, nakhlites, and chassignites) thought to be from Mars. Thus, it is possible to infer, even through the veil of dust, that the SNC meteorites have mineralogic affinities to major volcanic provinces on Mars and are therefore truly representative of the heterogeneity observed on the surface of the "red planet".


Subject(s)
Mars , Minerals/analysis , Solar System , Calcium/analysis , Spectrum Analysis
17.
Science ; 240(4848): 53-7, 1988 Apr 01.
Article in English | MEDLINE | ID: mdl-3281256

ABSTRACT

The neural cell adhesion molecule (NCAM) can influence a number of diverse intercellular events, including junctional communication, the association of axons with pathways and targets, and signals that alter levels of neurotransmitter enzymes. These pleiotropic effects appear to reflect the ability of NCAM to regulate membrane-membrane contact required to initiate specific interactions between other molecules. Such regulation can occur through changes in either NCAM expression or the molecule's content of polysialic acid (PSA). When NCAM with a low PSA content is expressed, adhesion is increased and contact-dependent events are triggered. In contrast, the large excluded volume of NCAM PSA can inhibit cell-cell interactions through hindrance of overall membrane apposition.


Subject(s)
Antigens, Surface/physiology , Cell Communication , Animals , Cell Adhesion , Cell Adhesion Molecules , Cell Membrane/physiology , Membrane Glycoproteins/physiology , Sialic Acids/metabolism
18.
Acta Radiol ; 49(5): 550-7, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18568542

ABSTRACT

BACKGROUND: Despite some limitations, a perfusion/diffusion mismatch can provide a working estimate of the ischemic penumbra in hyperacute stroke and has successfully been used to triage patients. PURPOSE: To evaluate whether the addition of magnetic resonance imaging (MRI) to clinical and non-contrast computed tomography (CT) data alters diagnosis and choice of therapy. MATERIAL AND METHODS: We retrospectively analyzed clinical records, and CT and MRI data fully available in 97 of 117 patients. Upon clinical examination and CT, a diagnosis and treatment path was scored and compared to treatment path after addition of MRI data. The MRI protocol included T2-weighted images, diffusion-weighted images (DWI), and perfusion-weighted images (PWI), and MR angiography (MRA). RESULTS: MRI data were acquired in less than 15 min. In 20 of 97 patients (21%), the diagnosis changed after MRI. In 25 of 97 patients (26%), the presumptive treatment plan was changed after MRI evaluation. Thirteen patients had their treatment changed from thrombolytic to nonthrombolytic therapy. Three patients were changed from nonthrombolytic to intraarterial (IA) thrombolysis. In one patient, treatment was changed from intravenous (IV) to IA thrombolysis, and in five patients it was changed from IA to IV thrombolysis. In two patients, systemic heparin was added to antiplatelet therapy. CONCLUSION: The expansion of the acute stroke protocol to include MRI altered the therapy plan in 26% of our patients. The utility of MRI, shown here to improve patient stratification into best-treatment options, demonstrates the value of using MRI to optimize care in hyperacute stroke patients.


Subject(s)
Magnetic Resonance Imaging/methods , Stroke/diagnosis , Stroke/drug therapy , Acute Disease , Adult , Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain/pathology , Contrast Media/administration & dosage , Diffusion Magnetic Resonance Imaging , Echo-Planar Imaging , Female , Gadolinium DTPA , Humans , Image Enhancement , Imaging, Three-Dimensional , Magnetic Resonance Angiography , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Thrombolytic Therapy , Tomography, X-Ray Computed
19.
Oncogene ; 37(11): 1409-1416, 2018 03.
Article in English | MEDLINE | ID: mdl-29321666

ABSTRACT

Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology. Importantly, dramatic differences in the genetics of these two MCC subtypes suggest fundamental differences in their pathophysiology. We review these recent works and find that they provocatively suggest that MCPyV-positive and MCPyV-negative MCCs arise from two different cells of origin: the MCPyV-negative MCC from epidermal keratinocytes and the MCPyV-positive MCC from dermal fibroblasts. If true, this would represent the first cancer that we are aware of that evolves from cells of origin from two distinct germ layers: MCPyV-negative MCCs from ectodermal keratinocytes and MCPyV-positive MCCs from mesodermal fibroblasts. Future epigenetic experiments may prove valuable in confirming these distinct lineages for these MCC subtypes, especially for the clinical importance the cell of origin has on MCC treatment and prevention.


Subject(s)
Carcinoma, Merkel Cell/etiology , Skin Neoplasms/etiology , Animals , Carcinoma, Merkel Cell/genetics , Carcinoma, Merkel Cell/pathology , Carcinoma, Merkel Cell/virology , Cell Transformation, Neoplastic/genetics , Cell Transformation, Viral/physiology , Humans , Merkel cell polyomavirus/physiology , Mice , Polyomavirus Infections/complications , Polyomavirus Infections/pathology , Skin Neoplasms/genetics , Skin Neoplasms/pathology , Skin Neoplasms/virology , Tumor Virus Infections/complications , Tumor Virus Infections/pathology
20.
Neuropsychopharmacology ; 43(11): 2212-2220, 2018 10.
Article in English | MEDLINE | ID: mdl-29795244

ABSTRACT

Bipolar disorder (BD) is highly heritable. Thus, studies in first-degree relatives of individuals with BD could lead to the discovery of objective risk markers of BD. Abnormalities in white matter structure reported in at-risk individuals could play an important role in the pathophysiology of BD. Due to the lack of studies with other at-risk offspring, however, it remains unclear whether such abnormalities reflect BD-specific or generic risk markers for future psychopathology. Using a tract-profile approach, we examined 18 major white matter tracts in 38 offspring of BD parents, 36 offspring of comparison parents with non-BD psychopathology (depression, attention-deficit/hyperactivity disorder), and 41 offspring of healthy parents. Both at-risk groups showed significantly lower fractional anisotropy (FA) in left-sided tracts (cingulum, inferior longitudinal fasciculus, forceps minor), and significantly greater FA in right-sided tracts (uncinate fasciculus and inferior longitudinal fasciculus), relative to offspring of healthy parents (P < 0.05). These abnormalities were present in both healthy and affected youth in at-risk groups. Only offspring (particularly healthy offspring) of BD parents showed lower FA in the right superior longitudinal fasciculus relative to healthy offspring of healthy parents (P < 0.05). We show, for the first time, important similarities, and some differences, in white matter structure between offspring of BD and offspring of non-BD parents. Findings suggest that lower left-sided and higher right-sided FA in tracts important for emotional regulation may represent markers of risk for general, rather than BD-specific, psychopathology. Lower FA in the right superior longitudinal fasciculus may protect against development of BD in offspring of BD parents.


Subject(s)
Bipolar Disorder/diagnostic imaging , Bipolar Disorder/psychology , Child of Impaired Parents/psychology , Diffusion Magnetic Resonance Imaging/trends , Adolescent , Bipolar Disorder/genetics , Child , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Male , Psychopathology , Risk Factors
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