Publications by authors named "David Rose"

331 Publications

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer.

J Immunother Cancer 2021 Mar;9(3)

Medical Oncology, City of Hope National Medical Center, Duarte, California, USA

Background: Single-agent pembrolizumab treatment of hormone receptor-positive metastatic breast cancer (MBC) has demonstrated modest clinical responses. Little is known about potential biomarkers or mechanisms of response to immune checkpoint inhibitors (ICIs) in patients with HR+ MBC. The present study presents novel immune correlates of clinical responses to combined treatment with CDK4/6i and ICI.

Methods: A combined analysis of two independent phase I clinical trials treating patients with HR+ MBC was performed. Patients treated with the combination of the CDK4/6i palbociclib+the ICI pembrolizumab+the aromatase inhibitor (AI) letrozole (palbo+pembro+AI) were compared with patients treated with pembrolizumab+AI (pembro+AI). Peripheral blood mononuclear cells collected at pretreatment, 3 weeks (cycle 2 day 1) and 9 weeks (cycle 4 day 1) were characterized by high-parameter flow cytometry to assess baseline immune subset composition and longitudinal changes in response to therapy.

Results: In the peripheral blood, higher pretreatment frequencies of effector memory CD45RA CD8 T cells and effector memory CD4 T cells were observed in responders to palbo+pembro+AI. In contrast, this was not observed in pembro+AI-treated patients. We further characterized T-cell subsets of effector-like killer cell lectin-like receptor subfamily G member 1 (KLRG1) ICOS CD4 T cells and KLRG1 CD45RA CD8 T cells as baseline biomarkers of response. In comparison, pretreatment levels of tumor-infiltrating lymphocyte, tumor mutation burden, tumor programmed death-ligand 1 expression, and overall immune composition did not associate with clinical responses. Over the course of treatment, significant shifts in myeloid cell composition and phenotype were observed in palbo+pembro+AI-treated patients, but not in those treated with pembro+AI. We identified increased fractions of type 1 conventional dendritic cells (cDC1s) within circulating dendritic cells and decreased classical monocytes (cMO) within circulating monocytes only in patients treated with palbociclib. We also demonstrated that in palbociclib-treated patients, cDC1 and cMO displayed increased CD83 and human leukocyte antigen-DR isotype (HLA-DR) expression, respectively, suggesting increased maturation and antigen presentation capacity.

Conclusions: Pre-existing circulating effector CD8 and CD4 T cells and dynamic modulation of circulating myeloid cell composition denote response to combined pembrolizumab and palbociclib therapy for patients with HR+ MBC.

Trial Registration Number: NCT02778685 and NCI02648477.
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http://dx.doi.org/10.1136/jitc-2020-002084DOI Listing
March 2021

Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial.

Stroke 2021 Apr 25;52(4):1164-1171. Epub 2021 Feb 25.

Division of Stroke and Vascular Neurology, Department of Neurology (D.Z.R., S.R., A.C.B., T.M., W.S.B.), University of South Florida.

Background And Purpose: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals.

Methods: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS.

Results: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, =0.78), death (4.9% versus 8.5%, =0.68), fatal strokes (2.4% versus 8.5%, =0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, =0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm.

Conclusions: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.
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http://dx.doi.org/10.1161/STROKEAHA.120.030042DOI Listing
April 2021

Letter by Rose et al Regarding Article, "Acute Cerebrovascular Events in Hospitalized COVID-19 Patients".

Stroke 2021 01 25;52(2):e70-e71. Epub 2021 Jan 25.

Department of Neurology, University of South Florida College of Medicine, Tampa, FL.

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http://dx.doi.org/10.1161/STROKEAHA.120.032363DOI Listing
January 2021

Cause and burn.

Cognition 2021 Feb 9;207:104517. Epub 2020 Dec 9.

Department of Philosophy Cornell University, USA. Electronic address:

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http://dx.doi.org/10.1016/j.cognition.2020.104517DOI Listing
February 2021

An audit of ventilation and perfusion SPECT reporting for the diagnosis of pulmonary embolism in a tertiary cardiothoracic centre.

Intern Med J 2020 11;50(11):1419-1422

Intensive Care Services, The Prince Charles Hospital, Brisbane, Queensland, Australia.

The aim of the study was to identify reporting patterns of ventilation and perfusion single-photon emission computed tomography (V/Q SPECT) scans done in our department over 3 months in 2016. Factors impacting on reporting and patient groups that would most benefit from the addition of low-dose computed tomography (CT) to V/Q SPECT were analysed. Among 178 patients, 173 (97.2%) had a definitive (positive/negative) report and 2.8% had an equivocal report. As the majority of the equivocal reports were seen in patients aged ≥70 years, we believe that addition of low-dose CT with V/Q SPECT to this patient group will reduce the non-diagnostic rate.
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http://dx.doi.org/10.1111/imj.15065DOI Listing
November 2020

Direct oral anticoagulant failure in stroke/transient ischaemic attack: neurologic and pharmacokinetic considerations.

Eur Heart J Case Rep 2020 Oct 21;4(5):1-2. Epub 2020 Aug 21.

Department of Neurology, Morsani College of Medicine, University of South Florida, 2 Tampa General Circle, Tampa, FL 33606, USA.

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http://dx.doi.org/10.1093/ehjcr/ytaa178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649459PMC
October 2020

Natural Compatibilism, Indeterminism, and Intrusive Metaphysics.

Cogn Sci 2020 08;44(8):e12873

Sage School of Philosophy, Cornell University.

The claim that common sense regards free will and moral responsibility as compatible with determinism has played a central role in both analytic and experimental philosophy. In this paper, we show that evidence in favor of this "natural compatibilism" is undermined by the role that indeterministic metaphysical views play in how people construe deterministic scenarios. To demonstrate this, we re-examine two classic studies that have been used to support natural compatibilism. We find that although people give apparently compatibilist responses, this is largely explained by the fact that people import an indeterministic metaphysics into deterministic scenarios when making judgments about freedom and responsibility. We conclude that judgments based on these scenarios are not reliable evidence for natural compatibilism.
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http://dx.doi.org/10.1111/cogs.12873DOI Listing
August 2020

Untreated Stroke as Collateral Damage of COVID-19: "Time Is Brain" Versus "Stay at Home".

Neurohospitalist 2020 Oct 26;10(4):291-292. Epub 2020 May 26.

Department of Neurology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

For decades, neurologists have been advocating that anyone with acute focal deficits report immediately to the closest hospital's emergency room. Major advancements in the hyperacute diagnosis and treatment of stroke have justified our call-to-action slogan of "Time is Brain"-faster therapy leads to superior outcomes. However, this mantra has been recently usurped by the catchphrase "Stay at Home" during the coronavirus disease 2019 (COVID-19) pandemic. Fewer patients are presenting to hospitals with acute stroke; our census is down. Presumably the etiology of this phenomenon is either strict "social distancing" that some people may misperceive to exclude even emergent situations, or fears of contracting the virus while hospitalized. In this Short Report, we describe the year-over-year drop in stroke volume (ischemic and hemorrhagic both) coinciding with a paradoxical rise in acute reperfusion therapies at our university hospital. These data imply that stroke patients with mild/moderate symptoms are most likely staying home, and not receiving urgent therapies, and correspondingly, only the most severely disabled stroke patients are ultimately seeking and receiving help. We must remind our patients and the general public that our services are essential and available, as stroke still remains a medical emergency, and carries a likely higher overall mortality risk than COVID-19. As neurologists, we also must be vigilant for the atypical presentations and varied etiologies of stroke associated with COVID-19 as well.
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http://dx.doi.org/10.1177/1941874420929199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495700PMC
October 2020

Deciding Without Intending.

J Cogn 2020 Jun 2;3(1):12. Epub 2020 Jun 2.

Philosophy Department and Cognitive Science Program, University of Waterloo, CA.

According to a consensus view in philosophy, "deciding" and "intending" are synonymous expressions. Researchers have recently challenged this view with the discovery of a counterexample in which ordinary speakers attribute deciding without intending. The aim of this paper is to investigate the strengths and limits of this discovery. The result of this investigation revealed that the evidence challenging the consensus view is strong. We replicate the initial finding against consensus and extend it by utilizing several new measures, materials, and procedures. Together this evidence strongly suggests that "deciding" is not synonymous with "intending" in ordinary language and that the consensus view should be rejected.
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http://dx.doi.org/10.5334/joc.101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274201PMC
June 2020

Antithrombotic Treatment of Embolic Stroke of Undetermined Source: RE-SPECT ESUS Elderly and Renally Impaired Subgroups.

Stroke 2020 06 14;51(6):1758-1765. Epub 2020 May 14.

Department of Neurology, Evangelisches Klinikum Bethel, Bielefeld, Germany (W.-R.S.).

Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction =0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction =0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.
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http://dx.doi.org/10.1161/STROKEAHA.119.028643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379165PMC
June 2020

Comparison of Ultrasound-Guided Vs Traditional Arterial Cannulation by Emergency Medicine Residents.

West J Emerg Med 2020 Feb 26;21(2):353-358. Epub 2020 Feb 26.

Johns Hopkins Hospital, Department of Emergency Medicine, Baltimore, Maryland.

Introduction: We sought to determine whether ultrasound-guided arterial cannulation (USGAC) is more successful than traditional radial artery cannulation (AC) as performed by emergency medicine (EM) residents with standard ultrasound training.

Methods: We identified 60 patients age 18 years or older at a tertiary care, urban academic emergency department who required radial AC for either continuous blood pressure monitoring or frequent blood draws. Patients were randomized to receive radial AC via either USGAC or traditional AC. If there were three unsuccessful attempts, patients were crossed over to the alternative technique. All EM residents underwent standardized, general ultrasound training.

Results: The USGAC group required fewer attempts as compared to the traditional AC group (mean 1.3 and 2.0, respectively; p<0.001); 29 out of 30 (96%) successful radial arterial lines were placed using USGAC, whereas 14 out of 30 (47%) successful lines were placed using traditional AC (p<0.001). There was no significant difference in length of procedure or complication rate between the two groups. There was no difference in provider experience with respect to USGAC vs traditional AC.

Conclusion: EM residents were more successful and had fewer cannulation attempts with USGAC when compared to traditional AC after standard, intern-level ultrasound training.
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http://dx.doi.org/10.5811/westjem.2019.12.44583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081869PMC
February 2020

Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels.

J Stroke Cerebrovasc Dis 2020 May 6;29(5):104747. Epub 2020 Mar 6.

Department of Neurology, Morsani College of Medicine, University of South Florida, Tampa, Florida. Electronic address:

Objectives: Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH.

Methods: At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be "cryptogenic" (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data.

Results: All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups.

Conclusions: In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient's pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104747DOI Listing
May 2020

Teleological Essentialism: Generalized.

Cogn Sci 2020 03;44(3):e12818

Department of Philosophy, Cornell University.

Natural/social kind essentialism is the view that natural kind categories, both living and non-living natural kinds, as well as social kinds (e.g., race, gender), are essentialized. On this view, artifactual kinds are not essentialized. Our view-teleological essentialism-is that a broad range of categories are essentialized in terms of teleology, including artifacts. Utilizing the same kinds of experiments typically used to provide evidence of essentialist thinking-involving superficial change (study 1), transformation of insides (study 2), and inferences about offspring (study 3)-we find support for the view that a broad range of categories-living natural kinds, non-living natural kinds, and artifactual kinds-are essentialized in terms of teleology. Study 4 tests a unique prediction of teleological essentialism and also provides evidence that people make inferences about purposes which in turn guide categorization judgments.
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http://dx.doi.org/10.1111/cogs.12818DOI Listing
March 2020

Immediate Transfer for Clot Extraction in a Young Woman With Leukemia and Asparaginase-Associated Acute Cerebral Vein Thrombosis.

Neurohospitalist 2020 Jan 30;10(1):58-63. Epub 2019 May 30.

Department of Neurology, University of South Florida, Tampa, FL, USA.

We present the case of an 18-year-old woman with B-cell acute lymphoblastic leukemia (ALL) who developed hemorrhagic stroke and epilepsia partialis continua due to acute cerebral vein thrombosis (CVT). The patient had 10 risk factors for CVT (including use of asparaginase chemotherapy for the ALL) and also unfortunately had 4 biomarkers for poor prognosis for outcome post-CVT diagnosis. Immediate transfer to a Comprehensive Stroke Center allowed for hyperacute neurointerventional clot extraction with rapid restoration of the patency of the superior sagittal sinus. This resulted in an unexpectedly favorable neurological outcome and simultaneously allowed for early resumption of chemotherapy for ALL after only a 5-day hiatus. Our case highlights the importance of immediate transfer of highest risk patients with multiple biomarkers for poor prognosis to a Comprehensive Stroke Center with endovascular and neurosurgical capabilities and the possibility of overcoming the odds of a poor outcome with venous clot extraction if medical management fails. Neurological deterioration due to escalating intracranial pressure with impending herniation may occur rapidly, and treatment at such facilities can be life-saving.
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http://dx.doi.org/10.1177/1941874419852196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900648PMC
January 2020

Hospital care and urinary incontinence in the elderly.

Rev Bras Enferm 2019 Nov;72(suppl 2):284-293

Universidade Federal da Bahia. Salvador, Bahia, Brazil.

Objective: to identify factors inherent in hospital care that favor urinary incontinence in the elderly.

Method: an integrative review with Scopus, CINAHL and Pubmed searches. Includes original articles, no language restriction, published between 2008 and 2018. Rated level of recommendation and level of evidence were assessed using the Oxford Center for Evidence-Based Medicine classification. Exploited content through thematic analysis in light of the Donabedian model.

Results: 13 articles constituted the sample. There were factors such as the unjustified and indiscriminate use of devices such as the geriatric diaper; hospital structure adversely affecting the needs of the elderly; and deficit in screening, risk identification and underreporting of the problem favor urinary incontinence in the hospitalized elderly.

Conclusion: modifiable factors related to hospital structures and care processes favor both the onset and worsening of urinary incontinence in the elderly.
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http://dx.doi.org/10.1590/0034-7167-2018-0273DOI Listing
November 2019

Incidental gastric diverticulum in a young female with chronic gastritis: A case report.

Int J Surg Case Rep 2020 27;66:63-67. Epub 2019 Nov 27.

University of Witwatersrand, Klerksdorp Tshepong Hospital Complex, Benji Oliphant Street, North West, South Africa. Electronic address:

Introduction: Gastrointestinal upset is a common presentation to surgical departments, often requiring investigation with endoscopy. Pathologies such as gastritis or ulcers are common culprits. Occasionally, rare or unusual pathologies, such as gastric diverticula as was seen in the case presented, are found.

Case Presentation: A 26 year old female, with no known co-morbid conditions presented with a two week history of abdominal pain associated with nausea and vomiting. On further inquiry, she had one episode of blood stained vomiting, prompting investigation with an oesophagogastroduodenoscopy (OGD). Findings included diffuse haemorrhagic gastritis with a single outpouching measuring 1-2 cm in the gastric fundus. A gastric diverticulum was confirmed on barium swallow. Investigation with sonar and a Computed Tomography (CT) scan reported the stomach as normal.

Conclusion: The patient was successfully treated non-operatively with proton pump inhibitor therapy for her concomitant gastritis. Gastric Diverticula are often associated with other gastric findings and their individual contribution varies from case to case.

Discussion: Gastric Diverticula are the manifestation of a common condition in an unusual location. Their clinical implications vary from being insignificant to life threatening when complicated by haemorrhage, perforation or malignant transformation. The associated symptoms are non-specific and diagnosis may be challenging. The case highlights the importance of selecting appropriate imaging modalities for luminal structures, being only diagnosed in 2 (OGD, Swallow) of the four modalities (incl. ultrasound and CT scan) used. Treatment may be conservative or surgical and is patient dependent. Written consent and ethical approval was obtained. The work is reported in line with the SCARE criteria.
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http://dx.doi.org/10.1016/j.ijscr.2019.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906696PMC
November 2019

For Whom Does Determinism Undermine Moral Responsibility? Surveying the Conditions for Free Will Across Cultures.

Front Psychol 2019 5;10:2428. Epub 2019 Nov 5.

School of Information Management, Sun Yat-sen University, Guangzhou, China.

Philosophers have long debated whether, if determinism is true, we should hold people morally responsible for their actions since in a deterministic universe, people are arguably not the ultimate source of their actions nor could they have done otherwise if initial conditions and the laws of nature are held fixed. To reveal how non-philosophers ordinarily reason about the conditions for free will, we conducted a cross-cultural and cross-linguistic survey ( = 5,268) spanning twenty countries and sixteen languages. Overall, participants tended to ascribe moral responsibility whether the perpetrator lacked sourcehood or alternate possibilities. However, for American, European, and Middle Eastern participants, being the ultimate source of one's actions promoted perceptions of free will and control as well as ascriptions of blame and punishment. By contrast, being the source of one's actions was not particularly salient to Asian participants. Finally, across cultures, participants exhibiting greater cognitive reflection were more likely to view free will as incompatible with causal determinism. We discuss these findings in light of documented cultural differences in the tendency toward dispositional versus situational attributions.
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http://dx.doi.org/10.3389/fpsyg.2019.02428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848273PMC
November 2019

Interaction between the effects of proton pump inhibitors and aspirin on gastric wall sestamibi uptake on myocardial perfusion imaging.

J Nucl Cardiol 2019 Nov 18. Epub 2019 Nov 18.

Department of Medical Imaging, The Prince Charles Hospital, Ground Floor, Rode Road, Chermside, QLD, 4032, Australia.

Background: Increased gastric wall activity on myocardial perfusion imaging (MPI) is associated with proton pump inhibitor (PPI) therapy; however, the mechanism is unknown. We proposed a role for gastric mucosal prostaglandin synthesis and asked whether concurrent use of aspirin would antagonize this effect.

Methods: An observational study was performed of 319 patients undergoing technetium-99m sestamibi (MIBI) rest/stress MPI. We assessed the effects of taking PPIs, aspirin and their interaction on the principle outcome of clinically significant gastric wall activity.

Results: The outcome was observed in 13% of patients taking neither a PPI nor aspirin, 22% of those taking aspirin only, 51% taking a PPI only and 33% of those taking both. Adjusted odd ratios (95% confidence intervals) were 6.3 (CI 2.8-14.0; p < .001) for taking a PPI only, 1.8 (CI 0.8-3.9; p = .16) for taking aspirin only, and 3.0 (CI 1.4-6.5; p = .005) for taking the combination of a PPI and aspirin. There was evidence of negative statistical interaction between the two drug effects using additive (p = .006) and multiplicative (p = .016) scales.

Conclusions: PPI use was strongly associated with enhanced gastric wall activity on MPI; however, concurrent aspirin appears to reduce the effect. Enhanced local prostaglandin synthesis may mediate the PPI effect.
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http://dx.doi.org/10.1007/s12350-019-01951-1DOI Listing
November 2019

Oesophageal tuberculosis with concomitant candidiasis: a rare cause of dysphagia.

BMJ Case Rep 2019 Nov 2;12(11). Epub 2019 Nov 2.

Department of Surgery, Klerksdorp Tshepong Hospital Complex, Klerksdorp, North West, South Africa.

We present a case of a 23-year-old woman with dysphagia. She was reportedly newly diagnosed with HIV and had been initiated on antiretroviral treatment and tuberculosis (TB) prophylaxis. Oesophagogastroduodenoscopy revealed an irregular, ulcerative oesophageal lesion. Subsequent histopathology revealed as well as A CT scan demonstrated widespread disease with miliary TB. She was subsequently initiated on antituberculous and antifungal medications. TB is one of the most common and deadly infectious diseases in the world, with the highest rates seen in the developing countries. It commonly occurs as an opportunistic infection of HIV. Despite its potential for systemic infection, infection of the oesophagus is incredibly rare, more so as a co-infection with candida. This case highlights the need to have a high index of suspicion in high risk groups, as early treatment is crucial in addressing this global health crisis.
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http://dx.doi.org/10.1136/bcr-2019-231435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827732PMC
November 2019

Protocol for AREST: Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation-A Randomized Controlled Trial of Early Anticoagulation After Acute Ischemic Stroke in Atrial Fibrillation.

Front Neurol 2019 20;10:975. Epub 2019 Sep 20.

Department of Cardiology, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.

Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe. This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation. Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0-3 for transient ischemic attack (TIA), 3-5 for small-sized AIS (<1.5 cm), and 7-9 for medium-sized AIS (1.5 cm or greater but less than a full cortical territory), or warfarin at 1 week post-TIA or 2 weeks post-stroke. Large AISs are excluded. Primary: recurrent ischemic stroke, TIA, and fatal stroke; secondary: intracranial hemorrhage (ICH); hemorrhagic transformation (HT) of ischemic stroke; cerebral microbleeds (CMBs); neurologic disability [e.g., modified Rankin Scores (mRS), National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life scale (SS-QOL)]; and cardiac biomarkers [e.g., AF burden, transthoracic echo (TTE)/transesophageal echo (TEE) abnormalities]. Enrollment goal was 120 for 80% power (two-sided type I error rate of 0.05) to detect an absolute risk reduction of 16.5% postulated to occur with apixaban in the primary composite outcome of fatal stroke/recurrent ischemic stroke/TIA within 180 days. Enrollment was suspended at 91 subjects in 2019 after a focused guideline update recommended direct oral anticoagulants (DOACs) over warfarin in AF, excepting valvular disease (Class I, level of evidence A). AREST will offer randomized controlled trial data about timeliness and safety of anticoagulation in AIS patients with AF. www.ClinicalTrials.gov, identifier NCT02283294.
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http://dx.doi.org/10.3389/fneur.2019.00975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763567PMC
September 2019

Relearning functional and symmetric walking after stroke using a wearable device: a feasibility study.

J Neuroeng Rehabil 2019 08 28;16(1):106. Epub 2019 Aug 28.

University of South Florida, Department of Mechanical Engineering, Tampa, FL, USA.

Background: Gait impairment is a common consequence of stroke and typically involves a hemiparetic or asymmetric walking pattern. Asymmetric gait patterns are correlated with decreased gait velocity and efficiency as well as increased susceptibility to serious falls and injuries.

Research Question: This paper presents an innovative device worn on a foot for gait rehabilitation post stroke. The device generates a backward motion to the foot, which is designed to exaggerate the existing step length asymmetry while walking over ground. We hypothesize this motion will decrease gait asymmetry and improve functional walking in individuals with chronic stroke.

Methods: Six participants with chronic stroke, more than one year post stroke, received four weeks of gait training with three sessions per week. Each session included 30 min of walking over ground using the wearable device. Gait symmetry and functional walking were assessed before and after training.

Results: All participants improved step length symmetry, and four participants improved double limb support symmetry. All participants improved on all three functional outcomes (gait velocity, Timed Up and Go Test, and 6-Minute Walk Test), and five participants improved beyond the minimal detectable change or meaningful change in at least one functional outcome.

Conclusion: The results indicate that the presented device may help improve stroke patients' walking ability and warrant further study. A gait training approach using this new device may enable and expand long-term continuous gait rehabilitation outside the clinic following stroke.

Trial Registration: NCT02185404. Registered July 9, 2014, https://clinicaltrials.gov/ct2/show/NCT02185404.
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http://dx.doi.org/10.1186/s12984-019-0569-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712835PMC
August 2019

Phylogenetic analysis reveals key residues in substrate hydrolysis in the isomaltase domain of sucrase-isomaltase and its role in starch digestion.

Biochim Biophys Acta Gen Subj 2019 09 27;1863(9):1410-1416. Epub 2019 Jun 27.

Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, ON N2L 3G1, Canada; Department of Physiological Chemistry, University of Veterinary Medicine Hannover, D-30559 Hannover, Germany. Electronic address:

Background: Starch constitutes one of the main sources of nutrition in the human diet and is broken down through a number of stages of digestion. Small intestinal breakdown of starch-derived substrates occurs through the mechanisms of small intestinal brush border enzymes, maltase-glucoamylase and sucrase-isomaltase. These enzymes each contain two functional enzymatic domains, and though they share sequence and structural similarities due to their evolutionary conservation, they demonstrate distinct substrate preferences and catalytic efficiency. The N-terminal isomaltase domain of sucrase-isomaltase has a unique ability to actively hydrolyze isomaltose substrates in contrast to the sucrase, maltase and glucoamylase enzymes.

Methods: Through phylogenetic analysis, structural comparisons and mutagenesis, we were able to identify specific residues that play a role in the distinct substrate preference. Mutational analysis and comparison with wild-type activity provide evidence that this role is mediated in part by affecting interactions between the sucrase and isomaltase domains in the intact molecule.

Results: The sequence analysis revealed three residues proposed to play key roles in isomaltase specificity. Mutational analysis provided evidence that these residues in isomaltase can also affect activity in the partner sucrase domain, suggesting a close interaction between the domains.

Major Conclusions: The sucrase and isomaltase domains are closely interacting in the mature protein. The activity of each is affected by the presence of the other.

General Significance: There has been little experimental evidence previously of the effects on activity of interactions between the sucrase-isomaltase enzyme domains. By extension, similar interactions might be expected in the other intestinal α-glucosidase, maltase-glucoamylase.
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http://dx.doi.org/10.1016/j.bbagen.2019.06.011DOI Listing
September 2019

Licorice Root Associated With Intracranial Hemorrhagic Stroke and Cerebral Microbleeds.

Neurohospitalist 2019 Jul 15;9(3):169-171. Epub 2018 Oct 15.

Department of Neurology, University of South Florida, Tampa, FL, USA.

Chinese Licorice root "gan zao" () is an ancient, medicinal herb utilized in Traditional Chinese Medicine for its presumably antiulcer, anti-inflammatory, antiviral, antibacterial, and expectorant properties. One of the major biologically active components is glycyrrhizin, which when hydrolyzed to glycyrrhetinic acid in the human body, possesses significant hypertensive effects due to interaction with the enzyme 11-β-hydroxysteroid dehydrogenase-2. Glycyrrhizin and glycyrrhetinic acid also show antithrombotic properties, as orally active, direct inhibitors of blood coagulation factor Xa as well as of thrombin. To our knowledge, this is the first reported case of intracranial hemorrhagic stroke associated with Chinese Licorice Root, and first reported case of cerebral microbleeds (CMB) associated with it as well.
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http://dx.doi.org/10.1177/1941874418805332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582380PMC
July 2019

Disparities and Temporal Trends in the Use of Anticoagulation in Patients With Ischemic Stroke and Atrial Fibrillation.

Stroke 2019 06 14;50(6):1452-1459. Epub 2019 May 14.

From the Department of Neurology (N.B.S., K.W., C.M.G., C.D., S.K., H.G., J.G.R., R.L.S., T.R.), University of Miami Miller School of Medicine, FL.

Background and Purpose- Ischemic stroke (IS) secondary to atrial fibrillation (AF) is largely preventable with the use of anticoagulation. We sought to identify race-ethnicity and sex disparities with the use of direct oral anticoagulants (DOACs), aspirin, and warfarin in IS patients with AF and to identify temporal trends in the utilization of these medications. Methods- The FLiPER-AF Stroke Study (Florida Puerto Rico Atrial Fibrillation) included 24 040 IS cases enrolled in the Florida-Puerto Rico Collaboration to Reduce Stroke Registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the effect of race-ethnicity and sex on utilization of DOACs, aspirin, and warfarin for stroke prevention in AF after adjustment for sociodemographic, hospital, and clinical factors. Results- Among 24 040 IS cases, 54% were women and 10% black, 12% FL-Hispanics, 4% PR-Hispanic, and 74% whites. From 2010 to 2016, DOAC use increased from 0% to 36%, warfarin use decreased from 51% to 17%, and aspirin use remained relatively stable (42%-40%). After adjustment, blacks had higher odds of warfarin (odds ratio, 1.22; 95% CI, 1.07-1.40) prescription at discharge compared with whites. Men had higher rates of aspirin (42.1% versus 38.8%), warfarin (33.6% versus 28.9%), and DOAC (21.3% versus 19.3%) use compared with women. After adjustment, women had lower odds of being discharged on aspirin (odds ratio, 0.92; 95% CI, 0.86-0.98) or warfarin (odds ratio, 0.91; 95% CI, 0.84-0.99). There was no sex difference in use of DOACs. Conclusions- Our study confirmed the increasing use of DOACs, downtrending use of warfarin, whereas aspirin use remained similar over the years. There are sex and race-ethnicity disparities in anticoagulation use in IS patients with AF. It is critical to understand underlying drivers of these disparities to develop better practice strategies for stroke prevention in patients with AF. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03627806.
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http://dx.doi.org/10.1161/STROKEAHA.118.023959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538423PMC
June 2019

The major barriers to evidence-informed conservation policy and possible solutions.

Conserv Lett 2018 Sep-Oct;11(5):e12564. Epub 2018 May 8.

Department of Zoology University of Cambridge The David Attenborough Building, Pembroke Street Cambridge CB2 3QZ United Kingdom.

Conservation policy decisions can suffer from a lack of evidence, hindering effective decision-making. In nature conservation, studies investigating why policy is often not evidence-informed have tended to focus on Western democracies, with relatively small samples. To understand global variation and challenges better, we established a global survey aimed at identifying top barriers and solutions to the use of conservation science in policy. This obtained the views of 758 people in policy, practice, and research positions from 68 countries across six languages. Here we show that, contrary to popular belief, there is agreement between groups about how to incorporate conservation science into policy, and there is thus room for optimism. Barriers related to the low priority of conservation were considered to be important, while mainstreaming conservation was proposed as a key solution. Therefore, priorities should focus on convincing the public of the importance of conservation as an issue, which will then influence policy-makers to adopt pro-environmental long-term policies.
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http://dx.doi.org/10.1111/conl.12564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473637PMC
May 2018

Teleological Essentialism.

Cogn Sci 2019 04;43(4):e12725

Department of Philosophy, University of Arizona.

Placeholder essentialism is the view that there is a causal essence that holds category members together, though we may not know what the essence is. Sometimes the placeholder can be filled in by scientific essences, such as when we acquire scientific knowledge that the atomic weight of gold is 79. We challenge the view that placeholders are elaborated by scientific essences. In our view, if placeholders are elaborated, they are elaborated by Aristotelian essences, a telos. Utilizing the same kind of experiments used by traditional essentialists-involving superficial change (study 1), transformation of insides (study 2), acquired traits (study 3), and inferences about offspring (study 4)-we find support for the view that essences are elaborated by a telos. And we find evidence (study 5) that teleological essences may generate category judgments.
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http://dx.doi.org/10.1111/cogs.12725DOI Listing
April 2019

The Painter in the Head: A New Fallacy?

Authors:
David Rose

Perception 2019 04 18;48(4):283-285. Epub 2019 Mar 18.

School of Psychology, University of Surrey, Guildford, Surrey, UK.

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http://dx.doi.org/10.1177/0301006619836354DOI Listing
April 2019

Disparities and Temporal Trends in Stroke Care Outcomes in Patients with Atrial Fibrillation: The FLiPER-AF Stroke Study.

Int J Cerebrovasc Dis Stroke 2019 22;2(1). Epub 2019 Jul 22.

Department of Neurology, University of Miami Miller School of Medicine, Florida, USA.

Background And Purpose: Atrial Fibrillation (AF) is the most common cardiac cause of ischemic stroke. However, the relation between AF and stroke care outcomes in diverse populations is understudied. We aimed to evaluate sex and race-ethnic disparities associated with AF in hospital stroke outcomes utilizing data from the FLorida PuErto Rico Atrial Fibrillation (FLiPER-AF) Stroke Study.

Methods: The study included 104,308 ischemic stroke cases with available information on AF status enrolled in a state-wide stroke registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the association between AF and stroke outcomes and the modification effects on the associations by sex and by race-ethnicity, adjusted for socio-demographic status, vascular risk factors and stroke severity.

Results: AF was present in 23% of ischemic stroke cases. AF was associated with worse disability at discharge (OR=1.11, 95% CI, 1.04-1.18), less discharge to home (OR=0.89, 0.85-0.92), and longer length of hospital stay (LOS>6 days, OR=1.53, 1.46-1.60). Interaction analyses showed that the association between AF and less discharge to home was stronger in women than men (p for interaction <0.001), as well as in FL-whites than in FL-blacks, FL-Hispanics or PR-Hispanics (p for interaction=0.002). The association between AF and prolonged LOS was more prominent in PR-Hispanics than in FL-blacks, FL-Hispanics, or FL-whites (p for interaction <0.001). From 2010 to 2016, the effects of AF on hospital length of stay attenuated (p for interaction<0.001).

Conclusions: AF was associated with poor disability at discharge, less discharge to home, and prolonged hospital length of stay for acute stroke care. The effect of AF on length of stay attenuated over time. Sex and race-ethnic disparities were observed in the effect of AF on being less discharge to home and prolonged hospital stay. Further research is needed to identify and modify the biologic and systems of care contributors to these disparities.
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http://dx.doi.org/10.29011/2688-8734.100017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730022PMC
July 2019

Has Publishing Surgeon-Specific Outcomes Had an Impact on Training in Cardiac Surgery?

Ann Thorac Surg 2019 May 20;107(5):1552-1558. Epub 2018 Dec 20.

Lancashire Cardiac Centre, Blackpool, United Kingdom.

Background: Surgeon-specific outcome data are now published for most surgical specialties in the United Kingdom. There are concerns that this initiative has had a negative impact on training. The primary objective of this study was to assess whether training activity has changed since the publication of surgeon-specific outcomes in cardiac surgery.

Methods: Prospectively collected data for cardiac surgical procedures performed at a single center from 2004 to 2016 were analyzed. The cohort was split into two halves according to operation date. Multivariable logistic regression was used to assess whether training activity had increased from the first to the second part of the study and to identify whether trainee first operator was associated with adverse outcomes.

Results: A total of 14,054 cardiac surgical procedures were included, of which 1,777 (12.6%) had a trainee as first operator. Despite an increase in the risk profile of patients undergoing surgical procedures, the proportion of cases performed by trainees increased from 11.7% (786 of 6,708) in the first half of the study to 13.5% (991 of 7,346) in the second half of the study (p = 0.002). This effect remained after adjustment for confounding variables. Trainee first operator was not significantly associated with an increased risk of any adverse short-term outcome.

Conclusions: Since surgeon-specific outcome publication began in United Kingdom, cardiac surgical training activity has significantly increased at the study center despite an increase in the risk profile of patients. This study demonstrates that it is possible to maintain or even increase training activity with good outcomes in the era of surgeon-specific outcome publication.
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http://dx.doi.org/10.1016/j.athoracsur.2018.11.043DOI Listing
May 2019