tbuckley/cabot-search huggingface dataset:
Diagnosing Pneumonia during Mechanical Ventilation
Authors: Muriel Fartoukh, Bernard Maître, Stéphanie Honoré, Charles Cerf, Jean-Ralph Zahar, Christian Brun-Buisson
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

The clinical pulmonary infection score-original or modified-has been proposed for the diagnosis and management of ventilator-associated pneumonia. In 79 episodes of suspected pneumonia, we prospectively assessed the diagnostic accuracy of the physicians' clinical assessment of probability and of the modified clinical pulmonary infection score, both measured before (pretest) and after (post-test) incorporating gram stains results, using bronchoalveolar lavage fluid culture as the reference test. The pretest clinical estimate was inaccurate (sensitivity 50%, specificity 58%); the mean clinical pulmonary infection score at baseline was 6.5 +/- 1.3 (range, 3-9) and 5.9 +/- 1.7 (range, 3-9), respectively, for the 40 confirmed and the 39 nonconfirmed episodes (p = 0.07), and only slightly more accurate (sensitivity 60%, specificity 59%) than the clinical prediction. Incorporating the gram stain results of either directed or blind protected sampling increased the diagnostic accuracy (sensitivity and specificity of 85% and 49% and 78% and 56%, respectively) of the clinical score and increased the likelihood ratio for pneumonia of a score of more than six from 1.46 to 1.67 and 1.77. The clinical pulmonary infection score has low diagnostic accuracy; however, incorporating gram stains results into the score may help clinical decision making in patients with clinically suspected pneumonia.
Relationship of hepatocyte steatosis with viral load and genotype in chronic hepatitis C (CHC)
Authors: M. Daimonakou, I.K. Deladetsima, N.C. Tassopoulos, G. Karvountzis, D. Tsantoulas, I. Vafiadis, G. Hatzis, E. Akriviadis, P. Aggelis, V. Sypsa, A. Hatzakis
Journal: Journal of Hepatology (2001)
Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases
Authors: R. Adam
Journal: Annals of Oncology (2003)

Liver metastases concern half of patients with colorectal cancer, and are frequently unresectable, jeopardizing patient outcome. Owing to increased efficacy, chemotherapy can render initially inoperable patients amenable to potentially curative resection. The 34% 5-year and 20% 10-year survival of patients resected following neoadjuvant chronomodulated chemotherapy with 5-fluorouracil, folinic acid and oxaliplatin is similar to that of patients whose disease was operable at diagnosis. Recently, a group of 16 patients were treated with irinotecan and became resectable after treatment. Their survival (56% at 3 years) matches that of patients treated with other forms of chemotherapy. The poor prognosis of patients with non-resectable hepatic metastases might now be improved by the combination of chemotherapy and surgery.
Type A Behavior and Risk of All-Cause Mortality, CAD, and CAD-Related Mortality in a Type 1 Diabetic Population: 22 Years of Follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study
Authors: Catherine E. Fickley, Cathy E. Lloyd, Tina Costacou, Rachel G. Miller, Trevor J. Orchard
Journal: Diabetes Care (2013)

OBJECTIVE To determine whether type A behavior predicts all-cause mortality and incident coronary artery disease (CAD) in a type 1 diabetic population. RESEARCH DESIGN AND METHODS Follow-up data (22 years) from the Pittsburgh Epidemiology of Diabetes Complications (EDC) study of childhood-onset type 1 diabetes were analyzed for the 506 participants who completed the Bortner Rating Scale (measuring type A behavior) and Beck Depression Inventory (BDI) at baseline (1986–1988). CAD comprised myocardial infarction as determined by hospital records/Q waves on electrocardiogram (ECG), CAD death (determined by a mortality classification committee), angiographic stenosis, ischemic ECG, and angina. RESULTS There were 128 deaths (25.3%) during follow-up. Univariate analysis showed an inverse relationship between Bortner scores and all-cause mortality (P = 0.01), which remained significant after allowing for age, sex, duration, HbA1c, education, smoking, BMI, and physical activity (P = 0.03). However, the addition of BDI scores attenuated the relationship (P = 0.11) with a significant interaction (P = 0.03) such that any protective effect against mortality was limited among individuals with lower BDI scores (bottom three quintiles) (P = 0.07), whereas no effect was seen in those with higher BDI scores (P = 0.97). Bortner scores showed only a borderline association with incident CAD (P = 0.09). CONCLUSIONS Those with higher type A behavior have lower all-cause mortality in our type 1 diabetic population, an effect that interacts with depressive symptomatology such that it is only operative in those with low BDI scores. Further research should focus on understanding this interaction.
Multinational Study of Cancer Patients and Their Children: Factors Associated With Family Functioning
Authors: Florence Schmitt, Jorma Piha, Hans Helenius, Christiane Baldus, Christian Kienbacher, Barbara Steck, Mikael Thastum, Maggie Watson, Georg Romer
Journal: Journal of Clinical Oncology (2008)

This study examined factors associated with family functioning in cancer patients' families with dependent children.A sample of 381 families (639 parents and 489 children) was recruited simultaneously in six European countries. Patients and family members completed a background questionnaire, the Family Assessment Device (FAD), the Beck Depression Inventory, and the short form version of the Medical Outcomes Health Survey. Descriptive statistics and a multilevel model that allowed a multi-informant design were used. Analyses were carried out with all participants, and separately with parent-rated and children-rated FAD scores.In descriptive analyses, children reported more impairment in family functioning than parents, but the difference was not significant. Depression prevalence was 35% for ill mothers and 28% for ill fathers. In the multilevel analyses with all participants (ie, adults and children) the ill parent's depression was significantly associated with impaired family functioning on five of seven FAD subscales. In analyses with only children, the perception of impairment of family functioning was not associated with parental depression. Additionally, poorer physical status of the ill parent was significantly associated with impairment on roles and communication.The ill parent's depression was the most significant factor associated with impairment in family functioning. Screening for depression, active diagnostics, and appropriate treatment of cancer patient's and partner's depression may be important to protect their children from mental disorders. Therefore, support systems need to be more family-oriented and child-centered in their approaches to cancer psychosocial care.
Why do humans reason? Arguments for an argumentative theory
Authors: Hugo Mercier, Dan Sperber
Journal: Behavioral and Brain Sciences (2011)

Abstract Reasoning is generally seen as a means to improve knowledge and make better decisions. However, much evidence shows that reasoning often leads to epistemic distortions and poor decisions. This suggests that the function of reasoning should be rethought. Our hypothesis is that the function of reasoning is argumentative. It is to devise and evaluate arguments intended to persuade. Reasoning so conceived is adaptive given the exceptional dependence of humans on communication and their vulnerability to misinformation. A wide range of evidence in the psychology of reasoning and decision making can be reinterpreted and better explained in the light of this hypothesis. Poor performance in standard reasoning tasks is explained by the lack of argumentative context. When the same problems are placed in a proper argumentative setting, people turn out to be skilled arguers. Skilled arguers, however, are not after the truth but after arguments supporting their views. This explains the notorious confirmation bias. This bias is apparent not only when people are actually arguing, but also when they are reasoning proactively from the perspective of having to defend their opinions. Reasoning so motivated can distort evaluations and attitudes and allow erroneous beliefs to persist. Proactively used reasoning also favors decisions that are easy to justify but not necessarily better. In all these instances traditionally described as failures or flaws, reasoning does exactly what can be expected of an argumentative device: Look for arguments that support a given conclusion, and, ceteris paribus, favor conclusions for which arguments can be found.
<i>TGFBR1</i>☆6A May Contribute to Hereditary Colorectal Cancer
Authors: Yansong Bian, Trinidad Caldes, Juul Wijnen, Patrick Franken, Hans Vasen, Virginia Kaklamani, Khédoudja Nafa, Paolo Peterlongo, Nathan Ellis, John A. Baron, John Burn, Gabriela Moeslein, Patrick J. Morrison, Yu Chen, Habibul Ahsan, Patrice Watson, Henry T. Lynch, Albert de la Chapelle, Riccardo Fodde, Boris Pasche
Journal: Journal of Clinical Oncology (2005)

TGFBR16A is a tumor susceptibility gene that increases breast, colon, and ovarian cancer risk. Fourteen percent of the general population carries TGFBR16A, and TGFBR16A homozygotes have a greater than 100% increased colon cancer risk compared with noncarriers. Low-penetrance genes such as TGFBR16A may account for a sizable proportion of familial colorectal cancer occurrences. To test this hypothesis, we determined whether TGFBR16A contributes to a proportion of mismatch repair (MMR) gene mutation-negative hereditary nonpolyposis colorectal cancer (HNPCC) patients.A case-case study was performed of 208 index patients with HNPCC meeting the Amsterdam criteria. Patients were examined for mutations and genomic rearrangements in the MLH1, MSH2, and MSH6 genes and genotyped for TGFBR16A. Tumor microsatellite instability status was available for 95 patients.A total of 144 patients (69.2%) carried a deleterious mutation and were classified as positive for MMR gene mutation; 64 patients (30.8%) had no evidence of mutations and were classified as MMR negative. TGFBR16A allelic frequency was significantly higher among MMR-negative patients (0.195) than among MMR-positive patients (0.104; P = .011). The proportion of TGFBR16A homozygotes was nine-fold higher among MMR-negative (6.3%) than among MMR-positive patients (0.7%; P = .032). The highest TGFBR16A allelic frequency was found among MMR-negative patients with tumors exhibiting no microsatellite instability (0.211), and the lowest frequency was found among MMR-positive patients with tumors exhibiting microsatellite instability (0.121); the difference was not statistically significant (P = .17).TGFBR16A may be causally responsible for a proportion of HNPCC occurrences.
Conscientious objection in medicine: Doctors' freedom of conscience
Authors: Vaughan P Smith
Journal: BMJ (2006)

EDITOR—Since visiting Auschwitz, I have grappled with the question of how I would have behaved as a doctor in Nazi Germany or Stalinist Russia. I hope I would have had the moral courage to refuse to participate in the various perversions of medicine that these regimes demanded—for example, respectively, eugenic “research” and psychiatric “treatment” of dissidents.1 …
Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status
Authors: P.G. Nuciforo, C. Aura, E. Holmes, L. Prudkin, J. Jimenez, P. Martinez, H. Ameels, L. de la Peña, C. Ellis, H. Eidtmann, M.J. Piccart-Gebhart, M. Scaltriti, J. Baselga
Journal: Annals of Oncology (2015)
Mitochondrial PKCε and Mitochondrial ATP-Sensitive K <sup>+</sup> Channel Copurify and Coreconstitute to Form a Functioning Signaling Module in Proteoliposomes
Authors: Martin Jabůrek, Alexandre D.T. Costa, Jana R. Burton, Cinthia L. Costa, Keith D. Garlid
Journal: Circulation Research (2006)

Mitochondria are key mediators of the cardioprotective signal and the mitochondrial ATP-sensitive K + channel (mitoK ATP ) plays a crucial role in originating and transmitting that signal. Recently, protein kinase C ε (PKCε) has been identified as a component of the mitoK ATP signaling cascade. We hypothesized that PKCε and mitoK ATP interact directly to form functional signaling modules in the inner mitochondria membrane. To examine this possibility, we studied K + flux in liposomes containing partially purified mitoK ATP . The reconstituted proteins were obtained after detergent extraction of isolated mitochondria, 200-fold purification by ion exchange chromatography, and reconstitution into lipid vesicles. Immunoblot analysis revealed the presence of PKCε in the reconstitutively active fraction. Addition of the PKC activators 12-phorbol 13-myristate acetate, hydrogen peroxide, and the specific PKCε peptide agonist, ψεRACK, each activated mitoK ATP -dependent K + flux in the reconstituted system. This effect of PKCε was prevented by chelerythrine, by the specific PKCε peptide antagonist, εV 1-2 , and by the specific mitoK ATP inhibitor 5-hydroxydecanoate. In addition, the activating effect of PKC agonists was reversed by exogenous protein phosphatase 2A. These results demonstrate persistent, functional association of mitochondrial PKCε and mitoK ATP .
Importance of sleep stage- and body position-dependence of sleep apnoea in determining benefits to auto-CPAP therapy
Authors: F. Sériès, I. Marc
Journal: European Respiratory Journal (2001)

The influence of sleep stage- and body position-dependence of sleep apnoea on treatment efficacy and compliance between conventional continuous positive airway pressure (CPAP) and auto CPAP therapy was evaluated. Thirty-three newly treated sleep apnoea hypopnoea syndrome (SAHS) patients were randomly allocated to conventional or auto-CPAP therapy. Six patients of each treatment group were classified as having sleep stage- and body position-dependent obstructive breathing abnormalities according to the results of the baseline sleep study. After 3 weeks of treatment, the Epworth sleepiness score tended to be higher (p=0.08) and the ability to stay awake lower (p=0.02) in patients with dependent breathing abnormalities treated with fixed CPAP, than in the other patients. The effective pressure/time index was significantly lower in sleep stage- and body position-dependent patients treated with fixed CPAP, than in the other patients (p=0.02). The number of hours the machine was turned on and a positive pressure applied, tended to be smaller in dependent patients treated with fixed CPAP than in independent patients of this treatment group and in patients treated with auto-CPAP. A night-to-night variability index (VI) of positive pressure changes was obtained in the auto-CPAP group. This index significantly decreased with time in the dependent patients while it remained unchanged in the independent group. It is concluded that auto-continuous positive airway pressure may have specific indications in a subset of obstructive sleep apnoea patients with sleep stage- and body position dependent nocturnal breathing abnormalities.
Patterns of Abuse Among Unintentional Pharmaceutical Overdose Fatalities
Authors: Aron J. Hall
Journal: JAMA (2008)

Use and abuse of prescription narcotic analgesics have increased dramatically in the United States since 1990. The effect of this pharmacoepidemic has been most pronounced in rural states, including West Virginia, which experienced the nation's largest increase in drug overdose mortality rates during 1999-2004.To evaluate the risk characteristics of persons dying of unintentional pharmaceutical overdose in West Virginia, the types of drugs involved, and the role of drug abuse in the deaths.Population-based, observational study using data from medical examiner, prescription drug monitoring program, and opiate treatment program records. The study population was all state residents who died of unintentional pharmaceutical overdoses in West Virginia in 2006.Rates and rate ratios for selected demographic variables. Prevalence of specific drugs among decedents and proportion that had been prescribed to decedents. Associations between demographics and substance abuse indicators and evidence of pharmaceutical diversion, defined as a death involving a prescription drug without a documented prescription and having received prescriptions for controlled substances from 5 or more clinicians during the year prior to death (ie, doctor shopping).Of 295 decedents, 198 (67.1%) were men and 271 (91.9%) were aged 18 through 54 years. Pharmaceutical diversion was associated with 186 (63.1%) deaths, while 63 (21.4%) were accompanied by evidence of doctor shopping. Prevalence of diversion was greatest among decedents aged 18 through 24 years and decreased across each successive age group. Having prescriptions for a controlled substance from 5 or more clinicians in the year prior to death was more common among women (30 [30.9%]) and decedents aged 35 through 44 years (23 [30.7%]) compared with men (33 [16.7%]) and other age groups (40 [18.2%]). Substance abuse indicators were identified in 279 decedents (94.6%), with nonmedical routes of exposure and illicit contributory drugs particularly prevalent among drug diverters. Multiple contributory substances were implicated in 234 deaths (79.3%). Opioid analgesics were taken by 275 decedents (93.2%), of whom only 122 (44.4%) had ever been prescribed these drugs.The majority of overdose deaths in West Virginia in 2006 were associated with nonmedical use and diversion of pharmaceuticals, primarily opioid analgesics.
Mapping Precursor Movement through the Postnatal Thymus Reveals Specific Microenvironments Supporting Defined Stages of Early Lymphoid Development
Authors: Evan F. Lind, Susan E. Prockop, Helen E. Porritt, Howard T. Petrie
Journal: The Journal of Experimental Medicine (2001)

Cellular differentiation is a complex process involving integrated signals for lineage specification, proliferation, endowment of functional capacity, and survival or cell death. During embryogenesis, spatially discrete environments regulating these processes are established during the growth of tissue mass, a process that also results in temporal separation of developmental events. In tissues that undergo steady-state postnatal differentiation, another means for inducing spatial and temporal separation of developmental cues must be established. Here we show that in the postnatal thymus, this is achieved by inducing blood-borne precursors to enter the organ in a narrow region of the perimedullary cortex, followed by outward migration across the cortex before accumulation in the subcapsular zone. Notably, blood precursors do not transmigrate the cortex in an undifferentiated state, but rather undergo progressive developmental changes during this process, such that defined precursor stages appear in distinct cortical regions. Identification of these cortical regions, together with existing knowledge regarding the genetic potential of the corresponding lymphoid precursors, sets operational boundaries for stromal environments that are likely to induce these differentiative events. We conclude that active cell migration between morphologically similar but functionally distinct stromal regions is an integral component regulating differentiation and homeostasis in the steady-state thymus.
Clinicopathologic Characteristics of Malignant Mesotheliomas Arising in Patients With a History of Radiation for Hodgkin and Non-Hodgkin Lymphoma
Authors: Lucian R. Chirieac, Justine A. Barletta, Beow Y. Yeap, William G. Richards, Tamara Tilleman, Raphael Bueno, Elizabeth H. Baldini, John Godleski, David J. Sugarbaker
Journal: Journal of Clinical Oncology (2013)

Studies have reported an association between pleural diffuse malignant mesothelioma (PDMM) and chest radiation for lymphoma. The clinicopathologic characteristics of malignant mesotheliomas arising in these patients have not been established.We studied 1,618 consecutive patients diagnosed with pleural PDMM from July 1993 to February 2008 and identified patients with a history of radiation for Hodgkin and non-Hodgkin lymphoma. We evaluated the histology in the surgical resection specimens and compared clinicopathologic features with overall survival.We identified 22 patients who developed PDMM after chest radiation as part of their treatment for lymphoma (mean latency time, 21.4 years; 95% CI, 17.0 to 25.8 years). Asbestos bodies in lymphoma-associated PDMM were lower than in asbestos-associated PDMM (median count, 15 v 325 bodies, respectively; P < .001) and similar to an unexposed control group (median count, 15 v 10 bodies, respectively; P = .6). Seventeen lymphoma-associated PDMMs (77%) were epithelioid and five (23%) were biphasic. Seven PDMMs (32%) had unusual histologies (pleomorphic, myxoid, clear cell, and signet ring cell). Patients with lymphoma-associated PDMM were younger than patients with asbestos-associated PDMM (median age, 45 v 64 years, respectively; P < .001) and had a significantly longer overall survival time (median, 32.5 v 12.7 months, respectively; P = .018). In multivariate analysis, independent favorable predictors for overall survival were history of prior radiation (P = .022), female sex (P < .001), age ≤ 65 years (P = .005), cytoreductive surgery (P < .001), and epithelioid histology (P < .001).Patients with lymphoma-associated PDMM are likely to have unusual histologic features, are significantly younger, and seem to have a longer overall survival compared with patients with asbestos-associated PDMM.
S29 Mannose binding lectin deficiency in children with respiratory infection
Authors: S. Prudon, J. Wake, D. Barge, C. Simmister, S. Tremble, V. Stevenson, T. Flood, D. A. Spencer
Journal: Thorax (2010)

<h3>Introduction</h3> Mannose binding lectin (MBL) plays a crucial part in innate immunity by activating the complement pathway. MBL deficiency is common, it has been associated with pulmonary disease, but low levels may also be found in otherwise normal individuals. Little is known about the importance of MBL deficiency as a risk factor for recurrent upper and lower respiratory tract infections.12 We describe our experience of measuring MBL levels in children with recurrent upper and lower respiratory tract infections. <h3>Methods</h3> MBL levels and clinical data were extracted from immunology laboratory records, of children being investigated for acute or chronic recurrent respiratory tract infections between November 2008 and February 2010. MBL deficiency was defined as a level &lt;75 ng/ml. <h3>Results</h3> 489 children had serum MBL measured during this time period. 199 had recurrent respiratory infections and of those 36 were positive for MBL deficiency (Abstract S29 Figure 1). Deficiency was found in 29% of positive boys and 14% of positive girls. 20% of positive patients were &lt;2 years, 16% 2–5 years and 28% &gt;5 years at the time of investigation. <h3>Conclusions</h3> MBL deficiency is common in our population. The true significance of this abnormality as a risk factor for respiratory infection in children remains to be determined. Case–control studies will be required to evaluate the relative importance of this abnormality in different subgroups of patients.