tbuckley/cabot-search huggingface dataset:
Family Perspectives on End-of-Life Care at the Last Place of Care
Authors: Joan M. Teno, Brian R. Clarridge, Virginia Casey, Lisa C. Welch, Terrie Wetle, Renee Shield, Vincent Mor
Journal: JAMA (2004)

Over the past century, nursing homes and hospitals increasingly have become the site of death, yet no national studies have examined the adequacy or quality of end-of-life care in institutional settings compared with deaths at home.To evaluate the US dying experience at home and in institutional settings.Mortality follow-back survey of family members or other knowledgeable informants representing 1578 decedents, with a 2-stage probability sample used to estimate end-of-life care outcomes for 1.97 million deaths from chronic illness in the United States in 2000. Informants were asked via telephone about the patient's experience at the last place of care at which the patient spent more than 48 hours.Patient- and family-centered end-of-life care outcomes, including whether health care workers (1) provided the desired physical comfort and emotional support to the dying person, (2) supported shared decision making, (3) treated the dying person with respect, (4) attended to the emotional needs of the family, and (5) provided coordinated care.For 1059 of 1578 decedents (67.1%), the last place of care was an institution. Of 519 (32.9%) patients dying at home represented by this sample, 198 (38.2%) did not receive nursing services; 65 (12.5%) had home nursing services, and 256 (49.3%) had home hospice services. About one quarter of all patients with pain or dyspnea did not receive adequate treatment, and one quarter reported concerns with physician communication. More than one third of respondents cared for by a home health agency, nursing home, or hospital reported insufficient emotional support for the patient and/or 1 or more concerns with family emotional support, compared with about one fifth of those receiving home hospice services. Nursing home residents were less likely than those cared for in a hospital or by home hospice services to always have been treated with respect at the end of life (68.2% vs 79.6% and 96.2%, respectively). Family members of patients receiving hospice services were more satisfied with overall quality of care: 70.7% rated care as "excellent" compared with less than 50% of those dying in an institutional setting or with home health services (P<.001).Many people dying in institutions have unmet needs for symptom amelioration, physician communication, emotional support, and being treated with respect. Family members of decedents who received care at home with hospice services were more likely to report a favorable dying experience.
David Gibb Vulliamy
Authors: C. V. D. G. Vulliamy
Journal: BMJ (2013)

<h3>Abstract</h3> <h3>Rationale</h3> The basolateral amygdala (BLA) and medial geniculate nucleus of the thalamus (MGN) have both been shown to be necessary for the formation of associative learning. While the role that the BLA plays in this process has long been emphasized, the MGN has been less well-studied and surrounded by debate regarding whether the relay of sensory information is active or passive. <h3>Objectives</h3> We seek to understand the role the MGN has within the thalamoamgydala circuit in the formation of associative learning. <h3>Methods</h3> Here, we use optogenetics to dissect the MGN-BLA circuit and explore the specific subpopulations for evidence of learning and synthesis of information that could impact downstream BLA encoding. We employ various machine learning techniques to investigate function within neural subpopulations. We introduce a novel method to investigate tonic changes across trial-by-trial structure, which offers an alternative approach to traditional trial-averaging techniques. <h3>Results</h3> We find that the MGN appears to encode arousal but not valence, unlike the BLA which encodes for both. We find that the MGN and the BLA appear to react differently to expected and unexpected outcomes; the BLA biased responses toward reward prediction error and the MGN focused on anticipated punishment. We uncover evidence of tonic changes by visualizing changes across trials during inter-trial intervals (baseline epochs) for a subset of cells. <h3>Conclusion</h3> We conclude that the MGN-BLA projector population acts as both filter and transferer of information by relaying information about the salience of cues to the amygdala, but these signals are not valence-specified. <h3>Preface</h3> In tribute to Nadia Chaudhri, and her discoveries regarding how contexts can modulate the representation of cues in the amygdala (Sciascia et al., 2015), and other mesolimbic circuit components (Chaudhri et al., 2009, 2008; Valyear et al., 2020), here we explore what information processing precedes entry into the basolateral amygdala (BLA) from the thalamus and develop visualization approaches for exploring across-trial temporal dynamics in addition to within-trial population activity.
Endothelial-Monocyte Activating Polypeptide Ii, a Novel Antitumor Cytokine That Suppresses Primary and Metastatic Tumor Growth and Induces Apoptosis in Growing Endothelial Cells
Authors: Margaret A. Schwarz, Jessica Kandel, Jerald Brett, Jun Li, Joanne Hayward, Roderich E. Schwarz, Olivier Chappey, Jean-Luc Wautier, John Chabot, Paul Lo Gerfo, David Stern
Journal: The Journal of Experimental Medicine (1999)

Neovascularization is essential for growth and spread of primary and metastatic tumors. We have identified a novel cytokine, endothelial-monocyte activating polypeptide (EMAP) II, that potently inhibits tumor growth, and appears to have antiangiogenic activity. Mice implanted with Matrigel showed an intense local angiogenic response, which EMAP II blocked by 76% (P &amp;lt; 0.001). Neovascularization of the mouse cornea was similarly prevented by EMAP II (P &amp;lt; 0.003). Intraperitoneally administered EMAP II suppressed the growth of primary Lewis lung carcinomas, with a reduction in tumor volume of 65% versus controls (P &amp;lt; 0.003). Tumors from human breast carcinoma–derived MDA-MB 468 cells were suppressed by &amp;gt;80% in EMAP II–treated animals (P &amp;lt; 0.005). In a lung metastasis model, EMAP II blocked outgrowth of Lewis lung carcinoma macrometastases; total surface metastases were diminished by 65%, and of the 35% metastases present, ≈80% were inhibited with maximum diameter &amp;lt;2 mm (P &amp;lt; 0.002 vs. controls). In growing capillary endothelial cultures, EMAP II induced apoptosis in a time- and dose-dependent manner, whereas other cell types were unaffected. These data suggest that EMAP II is a tumor-suppressive mediator with antiangiogenic properties allowing it to target growing endothelium and limit establishment of neovasculature.
SELF ASSEMBLING PEPTIDE AMPHIPHILE NANOFIBERS AS A SCAFFOLD FOR ENDOTHELIAL PROGENITOR CELLS
Authors: Alberto Balbarini, Angela Magera, Maria Chiara Barsotti, Hossein Hosseinkhani, Federica Chiellini, Roberto Solaro, Rossella Di Stefano
Journal: Journal of the American College of Cardiology (2010)
Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes
Authors: Bruno Christ, Emine Yazici, Annegret Nath
Journal: Hepatology (2000)

The participation of phosphatidylinositol 3-kinase (PI3-kinase), protein kinase C, and mitogen-activated protein kinase (MAP-kinase) in the inhibition by interleukin 6 (IL-6) and insulin of phosphoenolpyruvate carboxykinase (PCK) gene expression was investigated in cultured rat hepatocytes. IL-6 or insulin inhibited the glucagon-stimulated increase in PCK messenger RNA (mRNA) by about 70%. In the presence of either the PI3-kinase inhibitor, wortmannin, or the protein kinase C inhibitor, GF109203x, the inhibition by IL-6 was only about 40%, although it was abolished with both inhibitors in combination. Wortmannin alone but not GF109203x prevented the inhibition by insulin of glucagon-stimulated PCK gene expression. The MAP-kinase pathway inhibitor, PD98059, did not affect IL-6 or insulin inhibition of PCK mRNA increase. When chlorophenylthio-cyclic 3′,5′ adenosine monophosphate (CPT-cAMP) was used instead of glucagon, IL-6 or insulin inhibited the increase in PCK mRNA by 75% and 85%, respectively. The inhibition by IL-6 was only about 50% in the presence of either wortmannin or GF109203x alone but was abolished with the combination of both inhibitors. The inhibition by insulin was only about 50% in the presence of GF109203x and was abolished by wortmannin. The inhibitors did not affect the inhibition by IL-6 or insulin of the glucagon-stimulated increase in cAMP. It is concluded that the inhibition by IL-6 of PCK gene expression involved both PI3-kinase and protein kinase C, whereas the inhibition by insulin required only PI3-kinase. The inhibition occurred downstream from cAMP formation. Hence, IL-6 and insulin may share, in part, common signal transduction pathways in the inhibition of PCK gene expression.
613 Cytokine response in chronic hepatitis C (CHC) patients treated with pegylated interferon plus ribavirin
Authors: M. Trapero-Marugan, L. Garcia-Buey, C. Muñoz, J.A. Moreno-Monteagudo, M.J. Borque, X. Salcedo-Mora, R. Moreno-Otero
Journal: Journal of Hepatology (2006)
Expression of transforming growth factor alpha in experimental gastric carcinogenesis.
Authors: J I Livingstone, M I Filipe, C Wastell
Journal: Gut (1994)

The induction of adenocarcinomas in the glandular stomach of the adult male Wistar rat by N-methyl-N9-nitro-N-nitrosoguanidine (MNNG) was used as a model to study the expression of the growth promoting peptide, transforming growth factor alpha (TGF alpha), during experimental gastric carcinogenesis. TGF alpha was identified using the monoclonal antibody Ab-2 and standard immunohistochemistry, together with a semiquantitative assessment of the intensity of expression. Immunoreactivity was confined to the differentiated compartment of the mucosa while the carcinogen MNNG caused a significant increase in the intensity of TGF alpha expression (p &lt; 0.01), after as little as 16 weeks9 exposure. In experimental adenocarcinomas, a change to a previously undescribed pattern of perinuclear TGF alpha expression was found, which may represent the site of intense TGF alpha production in the Golgi apparatus after malignant transformation.
Early Results of a Chemoimmunotherapy Regimen of Fludarabine, Cyclophosphamide, and Rituximab As Initial Therapy for Chronic Lymphocytic Leukemia
Authors: Michael J. Keating, Susan O’Brien, Maher Albitar, Susan Lerner, William Plunkett, Francis Giles, Michael Andreeff, Jorge Cortes, Stefan Faderl, Deborah Thomas, Charles Koller, William Wierda, Michelle A. Detry, Alice Lynn, Hagop Kantarjian
Journal: Journal of Clinical Oncology (2005)

Fludarabine and cyclophosphamide (FC), which are active in treatment of chronic lymphocytic leukemia (CLL), are synergistic with the monoclonal antibody rituximab in vitro in lymphoma cell lines. A chemoimmunotherapy program consisting of fludarabine, cyclophosphamide, and rituximab (FCR) was developed with the goal of increasing the complete remission (CR) rate in previously untreated CLL patients to >/= 50%.We conducted a single-arm study of FCR as initial therapy in 224 patients with progressive or advanced CLL. Flow cytometry was used to measure residual disease. Results and safety were compared with a previous regimen using FC.The median age was 58 years; 75 patients (33%) had Rai stage III to IV disease. The CR rate was 70% (95% CI, 63% to 76%), the nodular partial remission rate was 10%, and the partial remission rate was 15%, for an overall response rate of 95% (95% CI, 92% to 98%). Two thirds of patients evaluated with flow cytometry had less than 1% CD5- and CD19-coexpressing cells in bone marrow after therapy. Grade 3 to 4 neutropenia occurred during 52% of courses; major and minor infections were seen in 2.6% and 10% of courses, respectively. One third of the 224 patients had >/= one episode of infection, and 10% had a fever of unknown origin.FCR produced a high CR rate in previously untreated CLL. Most patients had no detectable disease on flow cytometry at the end of therapy. Time to treatment failure analysis showed that 69% of patients were projected to be failure free at 4 years (95% CI, 57% to 81%).
Treatment of Maternal Depression in a Medication Clinical Trial and Its Effect on Children
Authors: Myrna M. Weissman, Priya Wickramaratne, Daniel J. Pilowsky, Ernest Poh, Lisa A. Batten, Mariely Hernandez, Martine F. Flament, Jessica A. Stewart, Patrick McGrath, Pierre Blier, Jonathan W. Stewart
Journal: American Journal of Psychiatry (2015)

Observational studies show that when a depressed mother's symptoms remit, her children's psychiatric symptoms decrease. Using randomized treatment assignment, the authors sought to determine the differential effects of a depressed mother's treatment on her child.The study was a randomized double-blind 12-week trial of escitalopram, bupropion, or the combination of the two in depressed mothers (N=76), with independent assessment of their children (N=135; ages 7-17 years).There were no significant treatment differences in mothers' depressive symptoms or remission. Children's depressive symptoms and functioning improved significantly among those whose mothers were in the escitalopram group (compared with those whose mothers were in the bupropion and combination treatment groups). Only in the escitalopram group was significant improvement of mother's depression associated with improvement in the child's symptoms. Exploratory analyses suggested that this may be due to changes in parental functioning: Mothers in the escitalopram group reported significantly greater improvement, compared with the other groups, in their ability to listen and talk to their children, who as a group reported that their mothers were more caring over the 12 weeks. Maternal baseline negative affectivity appeared to moderate the effect of maternal treatment on children, although the effect was not statistically significant. Children of mothers with low negative affectivity improved in all treatment groups. Children of mothers with high negative affectivity improved significantly only for those whose mothers were in the escitalopram group.The effects of the depressed mother's improvement on her children may depend on her type of treatment. Depressed mothers with high anxious distress and irritability may require medications that reduce these symptoms in order to show the effect of her remission on her children.
Research Misconduct Identified by the US Food and Drug Administration
Authors: Charles Seife
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Every year, the US Food and Drug Administration (FDA) inspects several hundred clinical sites performing biomedical research on human participants and occasionally finds evidence of substantial departures from good clinical practice and research misconduct. However, the FDA has no systematic method of communicating these findings to the scientific community, leaving open the possibility that research misconduct detected by a government agency goes unremarked in the peer-reviewed literature. <h3>Objectives</h3> To identify published clinical trials in which an FDA inspection found significant evidence of objectionable conditions or practices, to describe violations, and to determine whether the violations are mentioned in the peer-reviewed literature. <h3>Design and Setting</h3> Cross-sectional analysis of publicly available documents, dated from January 1, 1998, to September 30, 2013, describing FDA inspections of clinical trial sites in which significant evidence of objectionable conditions or practices was found. <h3>Main Outcomes and Measures</h3> For each inspection document that could be linked to a specific published clinical trial, the main measure was a yes/no determination of whether there was mention in the peer-reviewed literature of problems the FDA had identified. <h3>Results</h3> Fifty-seven published clinical trials were identified for which an FDA inspection of a trial site had found significant evidence of 1 or more of the following problems: falsification or submission of false information, 22 trials (39%); problems with adverse events reporting, 14 trials (25%); protocol violations, 42 trials (74%); inadequate or inaccurate recordkeeping, 35 trials (61%); failure to protect the safety of patients and/or issues with oversight or informed consent, 30 trials (53%); and violations not otherwise categorized, 20 trials (35%). Only 3 of the 78 publications (4%) that resulted from trials in which the FDA found significant violations mentioned the objectionable conditions or practices found during the inspection. No corrections, retractions, expressions of concern, or other comments acknowledging the key issues identified by the inspection were subsequently published. <h3>Conclusions and Relevance</h3> When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.
MRI Analysis of Cerebellar Vermal Abnormalities in Bipolar Disorder
Authors: Neil P. Mills, Melissa P. DelBello, Caleb M. Adler, Stephen M. Strakowski
Journal: American Journal of Psychiatry (2005)

The authors sought to expand previous findings of vermal abnormalities in bipolar disorder patients.Magnetic resonance imaging (MRI) morphometry was used to quantify vermal subregion volumes in 18 subjects with first-episode bipolar disorder, 21 subjects with multiple-episode bipolar disorder, and 32 healthy subjects.Vermal subregion V2 volume was significantly smaller in multiple-episode bipolar disorder subjects than in first-episode patients and healthy subjects. Vermal subregion V3 was significantly smaller in multiple-episode bipolar disorder subjects than in healthy subjects.These results suggest that posterior-inferior cerebellar vermal abnormalities are present in patients with multiple-episode bipolar disorder.
Longitudinal Analysis Casts Doubt on the Presence of Genetic Anticipation in Heritable Pulmonary Arterial Hypertension
Authors: Emma K. Larkin, John H. Newman, Eric D. Austin, Anna R. Hemnes, Lisa Wheeler, Ivan M. Robbins, James D. West, John A. Phillips, Rizwan Hamid, James E. Loyd
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Analysis of the age of onset in heritable pulmonary arterial hypertension (HPAH) has led to the hypothesis that genetic anticipation causes younger age of onset and death in subsequent generations. With accrual of pedigree data over multiple decades, we retested this hypothesis using analyses that eliminate the truncation of data that exists with shorter duration of follow-up.To analyze the pedigrees of families with mutations in bone morphogenetic protein receptor type 2 (BMPR2), afflicted in two or more generations with HPAH, eliminating time truncation bias by including families for whom we have at least 57 years of data.We analyzed 355 individuals with BMPR2 mutations from 53 families in the Vanderbilt Pulmonary Hypertension Registry. We compared age at diagnosis or death in affected individuals (n = 249) by generation within families with multigenerational disease. We performed linear mixed effects models and we limited time-truncation bias by restricting date of birth to before 1955. This allowed for 57 years of follow-up (1955-2012) for mutation carriers to develop disease. We also conducted Kaplan-Meier analysis to include currently unaffected mutation carriers (n = 106).Differences in age at diagnosis by generation were found in a biased analysis that included all birth years to the present, but this finding was eliminated when the 57-year observation limit was imposed. By Kaplan-Meier analysis, inclusion of currently unaffected mutation carriers strengthens the observation that bias of ascertainment exists when recent generations are included.Genetic anticipation is likely an artifact of incomplete time of observation of kindreds with HPAH due to BMPR2 mutations.
Development of the Satisfaction with Inhaled Asthma Treatment Questionnaire
Authors: J.L. Campbell, G.M. Kiebert, M.R. Partridge
Journal: European Respiratory Journal (2003)

For the management of a condition such as asthma, patients should feel confident with their medication, feel that the treatment is adequate in controlling symptoms and that side-effects of the treatment are minimal. As no comprehensive instrument to measure patient satisfaction with inhaled asthma medication existed, the Satisfaction with Asthma Treatment Questionnaire was developed. The procedures that were used are described, and the initial validation and reliability tests are reported. The study involved focus group meetings, development, testing and modification of a preliminary instrument, and testing of the revised instrument using different samples of patients with asthma. Factor analysis of the 26‐item questionnaire identified four domains reflecting four aspects of satisfaction: effectiveness of treatment, ease of use, medication burden, and side-effects and worries. Cronbach9s alpha showed evidence of internal consistency reliability. Test/retest reliability ranged from 0.66–0.74. Interscale correlations were moderate-to-high. Significant correlations were found between domain and overall scale scores and patients9 overall level of satisfaction. The Satisfaction with Asthma Treatment Questionnaire is potentially a useful instrument for gaining insight into patient satisfaction with inhaled treatment for asthma.
Bronchoscopy of symptom free patients infected with human immunodeficiency virus for detection of pneumocystosis.
Authors: J D Lundgren, M Orholm, T L Nielsen, J Iversen, J Hertz, J O Nielsen
Journal: Thorax (1989)

No evidence of Pneumocystis carinii infection was found in eight symptom free patients who were positive for the human immunodeficiency virus and who underwent bronchoscopy, bronchoalveolar lavage, and brush biopsy. This suggests that the presence of Pneumocystis carinii in bronchoscopy material is likely to indicate pneumocystis infection.
Trends in Cause-Specific Mortality in Oxygen-dependent Chronic Obstructive Pulmonary Disease
Authors: Magnus P. Ekström, Philippe Wagner, Kerstin E. Ström
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Since the introduction of long-term oxygen treatment (LTOT) in chronic obstructive pulmonary disease (COPD) with chronic hypoxia, the proportion of women and the age of patients starting LTOT have increased markedly. We hypothesize that this might have led to shifts in the causes of death over time.Objectives: To test for time trends in cause-specific mortality in COPD with LTOT.Methods: Patients starting LTOT for COPD in Sweden between January 1, 1987 and December 31, 2004 were included in a national prospective study and monitored until withdrawal of LTOT, death, or December 31, 2004. The primary end point was cause of death obtained from the Swedish Causes of Death Register.Measurements and Main Results: A total of 7,628 patients (53% women) were monitored for a median of 1.7 years (range, 0–18.0 yr). No patient was lost to follow-up and 5,457 patients died during the study. The crude overall mortality increased by 1.6%/year (95% confidence interval [CI], 0.9–2.2%/yr; P < 0.001). The absolute risk of death increased for circulatory disease by 2.8%/year (95% CI, 1.3–4.3%/yr; P < 0.001) and for digestive organ disease by 7.8%/year (95% CI, 1.9–14.0%/yr; P = 0.009). The absolute risk of death decreased for respiratory disease by 2.7%/year (95% CI, 2.0– 3.3%/yr; P < 0.001) and for lung cancer by 3.4%/year (95% CI, 1.1–5.7%/yr; P = 0.004).Conclusions: In oxygen-dependent COPD, mortality has increased over time both overall and of nonrespiratory causes, including cardiovascular disease. This highlights the importance of optimized diagnostics and treatment of comorbidities to decrease morbidity and mortality.