bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac arrest management in general practice in Ireland: a 5-year cross-sectional study
Authors: Bury G , Headon M , Egan M , Dowling J 
Published: May 2013

ObjectiveTo document the involvement of general practitioners (GPs) in cardiac arrests with resuscitation attempts (CARAs) and to describe the outcomes.DesignA 5-year prospective cross-sectional study of GPs in Ireland equipped with automated external defibrillators (AEDs) and immediate care training by the MERIT Project, with data collection every 3 months over the 5-year period. Practices reported CARAs by quarterly survey with an 89% mean response rate (81–97% for the period).SettingGeneral practices throughout Ireland.Participants495 GP participated: 168 (33.9%) urban, 163 (32.9%) rural and 164 (33.1%) mixed.InterventionsAll participating practices received a standard AED and basic life support kit. Training in immediate care was provided for at least one GP in the practice.Main outcome measuresIncidence of CARA in participating practices. Return of spontaneous circulation (ROSC) and discharge alive from hospital.Results36% of practices were involved in a CARA during the 5-year period and 13% were involved in more than one CARA. Of the 272 CARAs reported, ROSC occurred in 32% (87/272) and discharge from hospital in 18.7% (49/262). In 45% of cases, the first AED was brought by the GP and in 65%, the GP arrived before the ambulance service. More cases occurred in rural and mixed settings than urban ones, but the survival rates did not differ between areas. In 65% of cases, the GP was on duty at the time of the incident and 47% of cases occurred in the patient's home.ConclusionsThese outcomes are comparable with more highly structured components of the emergency response system and indicate that GPs have an important role to play in the care of patients in their own communities. GPs experience cardiac arrest cases during the course of their daily work and provide prompt care which results in successful outcomes in urban, mixed and rural settings.
James Parkinson’s ‘system of successive creations’
Authors: Lewis Cherry 
Published: May 2013

Abstract
This paper presents a new look at how the apothecary surgeon, James Parkinson (1755–1824), integrated his geological understanding with his religious ideas. It is only through the intellectual questions raised by the emerging science of geology that we are able to examine his religious beliefs as these were not apparently challenged by, and consequently not discussed in, any of his other published works on politics, medicine or chemistry. Although Parkinson held ‘conventional’ Christian beliefs prevailing at the time, he did not permit these to stand in the way of the geological evidence; his later private views regarding how the Creation story came about were never fully revealed in his publications. By accepting that a ‘system of successive creations’ had occurred, which circumvented certain aspects of the biblical account of Creation, he adapted his faith to accommodate the indisputable facts of geology, concurring with then modern views about how the Earth had formed.
Dr Arthur Conan Doyle’s contribution to the popularity of pterodactyls
Authors: Martill David M. , Pointon Tony 
Published: May 2013

Abstract

Pterodactyls or pterosaurs, well-known flying reptiles of the Mesozoic, were already compared with dragons and vampires well before the discovery of the spectacularly large species from North America with wing spans of over 6 m. First described in 1784, they were not recognized as flying reptiles until 1801, when Baron Cuvier described a specimen that a few years later he called Ptero Dactyle which later became
Pterodactylus
. The name
Pterodactylus
is technically invalid – it is a junior synonym of
Ornithocephalus
Soemmerring 1812
– but it has stuck in the psyche of both palaeontologists and public alike. By the end of the nineteenth century numerous workers had compared pterosaurs with demons, dragons and vampires and life restorations had appeared in books, magazines and as gargoyles on the external architecture of the Natural History Museum, London. Sir Arthur Conan Doyle, famously the creator of Sherlock Holmes, was a polymath, with interests in science, sport, politics, travel, the occult and of course writing. He trained as, and became, a physician, with an eventually thriving general practice in Southsea, Hampshire from 1882 to 1890. In 1912, first as a series in
Sunday
magazines in the USA and in
Strand Magazine
in the UK, and shortly after as a hardback, he published
The Lost World
, an adventure story about the exploration of a South American tableland with prehistoric creatures that had persisted to the present. Although dinosaurs existed in this anachronistic fictional ecosystem, the ‘star’ animals were pterodactyls. Here we discuss the notoriety of pterodactyls generated by
The Lost World
, and hold Conan Doyle responsible for the widespread popularity of these iconic prehistoric reptiles right up to the present day.
From obstetrics to oryctology: inside the mind of William Hunter (1718–1783)
Authors: Liston J. J. 
Published: May 2013

Abstract
Today William Hunter is remembered mainly for his pioneering work in obstetrics and for our understanding of the lymphatic system, but his interests were wide-ranging, encompassing artworks (the first to collect Chardin), archaeological, numismatic and bibliographical items. As a key figure in the Enlightenment, he was one of the few in the mid-eighteenth century to advocate the concept of extinction as recorded in the fossil record. Of some 400 fossil specimens, written records attest to the presence of over 50 fossil vertebrates in his collection, including fish from ‘Monte’ Bolca as well as specimens reflecting his comparative anatomical writings on the mastodon and ‘Irish elk’. This paper will explore the significance of the presence of these specimens in this particular eighteenth century collector’s collection, using his writings and library as tools to shed light on the mind of this classic Scottish Enlightenment figure.
Cancer Risk in Patients with Manifest Vascular Disease: Effects of Smoking, Obesity, and Metabolic Syndrome
Authors: van Kruijsdijk Rob C.M. , van der Graaf Yolanda , Peeters Petra H.M. , Visseren Frank L.J. ,   on behalf of the Second Manifestations of ARTerial disease (SMART) study group
Published: May 2013

Abstract
Background: Patients with vascular disease may be at increased risk of cancer because of shared risk factors and common pathogenesis.
Methods: Patients with vascular disease (n = 6,172) were prospectively followed for cancer incidence. Standardized incidence ratios (SIRs) were calculated to compare the cancer incidence of the study population with that of the general population. Multivariable-adjusted hazard ratio's (HRs) of cancer were estimated for smoking status, pack-years, body mass index, waist circumference and visceral adipose tissue (VAT), and metabolic syndrome (MetS).
Results: During a median follow-up of 5.5 years, 563 patients were diagnosed with cancer. Patients with vascular disease were at increased risk of cancer [SIR = 1.19; 95% confidence interval (CI), 1.10–1.29]. Specifically, risk of lung cancer (SIR = 1.56; 95% CI, 1.31–1.83), as well as bladder cancer (SIR = 1.60; 95% CI, 1.11–2.24) and cancer of the lip, oral cavity, or pharynx in men (SIR = 1.51; 95% CI, 0.89–2.39), and colorectal (SIR = 1.71; 95% CI, 1.11–2.53) and kidney cancer (SIR = 2.92; 95% CI, 1.05–6.38) in women was increased. A relation between smoking and cancer risk was observed (HR for current smokers = 1.37; 95% CI, 1.05–1.73), whereas an increase in VAT was associated with higher breast cancer risk in women (HR = 1.42; 95% CI, 1.03–1.96). No relation between MetS and cancer risk was found.
Conclusions: Patients with vascular disease have a 19% higher cancer risk compared to the general population. Smoking increased cancer risk and abdominal obesity is a risk factor for breast cancer in female patients with vascular disease.
Impact: These results call for awareness of the increased cancer risk in patients with vascular disease among physicians and underline the necessity of lifestyle improvement not only for reducing cardiovascular risk. Cancer Epidemiol Biomarkers Prev; 22(7); 1267–77. ©2013 AACR.
Physical Activity and Risk of Lymphoma: A Meta-Analysis
Authors: Vermaete Nele V.H. , Wolter Pascal , Verhoef Gregor E.G. , Kollen Boudewijn J. , Kwakkel Gert , Schepers Leen , Gosselink Rik 
Published: May 2013

Abstract
Background: Physical activity has a protective effect on some types of cancer. The aim of the present meta-analysis was to explore the literature on the association between physical activity and risk of lymphoma.
Methods: A meta-analysis was conducted for cohort and case–control studies examining the association between self-reported physical activity and risk of lymphoma. Depending on statistical heterogeneity, a random or fixed effects model was used to estimate the summary OR and corresponding 95% confidence interval (CI).
Results: Seven case–control studies and 5 cohort studies were included. When data from both study designs were combined, no significant influence of physical activity on risk of lymphoma was found (pooled OR = 0.90; 95% CI: 0.79–1.02; P = 0.10). Subgroup analysis revealed a significant protective influence of physical activity on risk of lymphoma in case–control studies (pooled OR = 0.81; 95% CI: 0.68–0.96; P = 0.02). In contrast, cohort studies, which have a higher level of evidence than case–control studies, confirm the results of the primary meta-analysis (pooled OR = 1.02; 95% CI: 0.88–1.19; P = 0.76). A subsequent subgroup analysis found no significant differences between results for Hodgkin lymphoma and non-Hodgkin lymphoma (χ2 = 0.16; P = 0.69), nor between results for recreational and occupational activities (χ2 = 1.01; P = 0.31).
Conclusions: Epidemiologic research indicates no significant influence of physical activity on risk of lymphoma.
Impact: Future research should examine the association between sedentary behavior and risk of lymphoma and investigate the dose–response and timing effect of physical activity on risk of lymphoma. Cancer Epidemiol Biomarkers Prev; 22(7); 1173–84. ©2013 AACR.
C-Reactive Protein, Lipid-soluble Micronutrients, and Survival in Colorectal Cancer Patients
Authors: Cooney Robert V. , Chai Weiwen , Franke Adrian A. , Wilkens Lynne R. , Kolonel Laurence N. , Le Marchand Loïc 
Published: May 2013

AbstractBackground: Identification of biomarkers associated with survival in patients with cancer is important for elucidating the underlying mechanisms of cancer progression and identifying possible interventions to reduce cancer morbidity and mortality.Methods: Using stored patient plasma samples from a multiethnic population-based case–control study of invasive colorectal cancer, we measured posttreatment blood levels of C-reactive protein (CRP) and lipid-soluble micronutrients. Patients (n = 368) were followed after phlebotomy (mean of 8 years), during which time 47% died (25% colorectal cancer specific). HRs were estimated by Cox proportional hazards regression with adjustment for stage, age at diagnosis, ethnicity, sex, smoking status, and month of blood draw.Results: A positive association with overall risk of death was observed for CRP [HR for highest vs. lowest quintile: 1.80; 95% confidence interval (CI), 1.07–3.04; Ptrend = 0.01], whereas inverse associations were generally observed for retinol and carotenoids (HRs for overall risk of death for the highest quintile ranging from 0.5–0.8); these associations were significant for retinol (Ptrend = 0.0002), α-carotene (Ptrend = 0.02), and total carotenoids (Ptrend = 0.02) and were generally consistent across subgroups (sex, ethnicity, cancer anatomical subtype, and stage). HRs for retinol and carotenoids were attenuated somewhat after adjustment for CRP. Similar trends for CRP were observed for colorectal cancer-specific deaths (HR for highest vs. lowest tertile: 2.06; 95% CI, 1.18–3.61; Ptrend = 0.01) as for deaths from all other causes (Pheterogeneity = 0.78).Conclusions: These observations are consistent with a direct relationship between circulating CRP and overall survival among patients with colorectal cancer.Impact: These results, if reproduced, suggest that reduction of inflammation should be explored as a potential complementary treatment strategy. Cancer Epidemiol Biomarkers Prev; 22(7); 1278–88. ©2013 AACR.
The Clinical and Economic Burden of a Sustained Increase in Thyroid Cancer Incidence
Authors: Aschebrook-Kilfoy Briseis , Schechter Rebecca B. , Shih Ya-Chen Tina , Kaplan Edwin L. , Chiu Brian C.-H. , Angelos Peter , Grogan Raymon H. 
Published: May 2013

Abstract
Background: Thyroid cancer incidence is increasing worldwide at an alarming rate, yet little is known of the impact this increase will have on society. We sought to determine the clinical and economic burden of a sustained increase in thyroid cancer incidence in the United States and to understand how these burdens correlate with the National Cancer Institute's (NCI) prioritization of thyroid cancer research funding.
Methods: We used the NCI's SEER 13 database (1992–2009) and Joinpoint regression software to identify the current clinical burden of thyroid cancer and to project future incidence through 2019. We combined Medicare reimbursement rates with American Thyroid Association guidelines, and our clinical practice to create an economic model of thyroid cancer. We obtained research-funding data from the NCI's Office of Budget and Finance.
Results; By 2019, papillary thyroid cancer will double in incidence and become the third most common cancer in women of all ages at a cost of $18 to $21 billion dollars in the United States. Despite these substantial clinical and economic burdens, thyroid cancer research remains significantly underfunded by comparison, and in 2009 received only $14.7 million (ranked 30th) from the NCI.
Conclusion: The impact of thyroid cancer on society has been significantly underappreciated, as is evidenced by its low priority in national research funding levels.
Impact: Increased awareness in the medical community and the general public of the societal burden of thyroid cancer, and substantial increases in research on thyroid cancer etiology, prevention, and treatment are needed to offset these growing concerns. Cancer Epidemiol Biomarkers Prev; 22(7); 1252–9. ©2013 AACR.
Combined and independent impact of diabetes mellitus and chronic kidney disease on residual platelet reactivity
Authors: Baber Usman , Bander Jeffrey , Karajgikar Rucha , Yadav Kapil , Hadi Ali , Theodoropolous Kleanthis , Gukathasan Nilusha , Roy Swathi , Sayeneni Swapna , Scott Stuart , Kovacic Jason , Yu Jennifer , Sartori Samantha , Mehran Roxana , Uribarri Jaime , Badimon Juan , Muntner Paul , Moreno Pedro , Kini Annapoorna , Sharma Samin 
Published: May 2013

SummaryPatients with both chronic kidney disease (CKD) and diabetes mellitus (DM) are at increased risk for thrombotic events compared to those with one abnormality alone. Whether this can be attributed to changes in platelet reactivity among those with both CKD and DM is unknown. We prospectively studied 438 clopidogrel-naïve patients undergoing percutaneous coronary intervention (PCI). Platelet function tests were performed 4–6 hours after loading with 600 mg of clopidogrel. Platelet reactivity was assessed using the VerifyNow system and expressed as P2Y12 reaction units (PRU). High residual platelet reactivity (HRPR) was defined as PRU > 230. Patients were categorised into four groups by the presence or absence of CKD and DM. Among those without CKD or DM (n=166), DM alone (n=150), CKD alone (n=60) and both CKD and DM (n=62) the mean PRU levels were 201.6 ± 96.3, 220.5 ± 101.1, 254.9 ± 106.7 and 275.0 ± 94.5, respectively (p<0.001). Analogously, the prevalence of HRPR was 42.3%, 50.7%, 63.3% and 75.8%, respectively (p< 0.001). Associations between either CKD or DM alone and HRPR were attenuated after multivariable adjustment while the odds for HRPR associated with both CKD and DM remained significant (OR [95% CI]: 2.61 [1.16 – 5.86]). In conclusion, the presence of both CKD and DM confers a synergistic impact on residual platelet reactivity when compared to either condition alone. Whether more potent platelet inhibitors may improve outcomes among patients with both abnormalities warrants investigation.
Haemarthrosis stimulates the synovial fibrinolytic system in haemophilic mice
Authors: Roosendaal Goris , Coeleveld Katja , Lubberts Erik , Biesma Douwe , Lafeber Floris , Schutgens Roger , Nieuwenhuizen Laurens 
Published: May 2013

SummaryRecurrent joint bleeding is the most common manifestation of haemophilia resulting in haemophilic arthropathy (HA). The exact pathophysiology is unknown, but it is suggested that arthropathy is stimulated by liberation of fibrinolytic activators from the synovium during haemarthrosis. The aim of this study was to test the hypothesis that haemarthrosis activates the local synovial fibrinolytic system in a murine haemophilia model. The right knees of haemophilic and control mice were punctured to induce haemarthrosis. The left knees served as internal control joints. Synovial levels of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor 1 (PAI-1), plasmin, and alpha-2-antiplasmin (A2AP) were compared between the punctured and control knees. In haemophilic mice, an increase in synovial cells expressing urokinase-type plasminogen activator (uPA) in the right punctured knee versus the left unaffected knee was observed: (47% vs 43%) (p=0.03). Additionally, in haemophilic mice, haemar-throsis induced an increase in uPA (0.016 ng/ml vs 0.01 ng/ml) (p=0.03) and plasmin (0.53 μg/ml vs 0.46 μg/ml) (p=0.01) as promoters of fibrinolysis. Synovial levels of PAI-1 (0.32 ng/ml vs 0.17 ng/ ml) (p<0.01) was also increased, whereas synovial levels of A2AP were unchanged: (0.021 μg/ml vs 0.021 μg/ml) (p=0.15). Enhanced uPA production was confirmed in human stimulated synovial fibroblast cultures and elevated levels of plasmin were confirmed harmful to human cartilage tissue explants. In this study we demonstrate that haemarthrosis in haemophilic mice induces synovial uPA expression and results in an increase in synovial plasmin levels, making the joint more vulnerable to prolonged and subsequent bleedings, and adding directly to cartilage damage.
High incidence of venous thromboembolism despite electronic alerts for thromboprophylaxis in hospitalised cancer patients
Authors: Marqués Margarita , Panizo Elena , Alfonso Ana , García-Mouriz Alberto , Gil-Bazo Ignacio , Hermida José , Schulman Sam , Páramo José , Lecumberri Ramón 
Published: May 2013

SummaryMany cancer patients are at high risk of venous thromboembolism (VTE) during hospitalisation; nevertheless, thromboprophylaxis is frequently underused. Electronic alerts (e-alerts) have been associated with improvement in thromboprophylaxis use and a reduction of the incidence of VTE, both during hospitalisation and after discharge, particularly in the medical setting. However, there are no data regarding the benefit of this tool in cancer patients. Our aim was to evaluate the impact of a computer-alert system for VTE prevention in patients with cancer, particularly in those admitted to the Oncology/Haematology ward, comparing the results with the rest of inpatients at a university teaching hospital. The study included 32,167 adult patients hospitalised during the first semesters of years 2006 to 2010, 9,265 (28.8%) with an active malignancy. Appropriate prophylaxis in medical patients, significantly increased over time (from 40% in 2006 to 57% in 2010) and was maintained over 80% in surgical patients. However, while e-alerts were associated with a reduction of the incidence of VTE during hospitalisation in patients without cancer (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.15–0.64), the impact was modest in cancer patients (OR 0.89; 95% CI, 0.42–1.86) and no benefit was observed in patients admitted to the Oncology/Haematology Departments (OR 1.11; 95% CI, 0.45–2.73). Interestingly, 60% of VTE episodes in cancer patients during recent years developed despite appropriate prophylaxis. Contrary to the impact on hospitalised patients without cancer, implementation of e-alerts for VTE risk did not prevent VTE effectively among those with malignancies.
Incorporation of the factor IX Padua mutation into FIX-Triple improves clotting activity in vitro and in vivo
Authors: Kao Chung-Yang , Yang Shu-Jhu , Tao Mi-Hua , Jeng Yung-Ming , Yu I-Shing , Lin Shu-Wha 
Published: May 2013

SummaryUsing gain-of-function factor IX (FIX) for replacement therapy for haemophilia B (HB) is an attractive strategy. We previously reported a high-activity FIX, FIX-Triple (FIX-V86A/E277A/R338A) as a good substitute for FIX-WT (wild-type) in protein replacement therapy, gene therapy, and cell therapy. Here we generated a new recombinant FIXTripleL (FIX-V86A/E277A/R338L) by replacing the alanine at residue 338 of FIX-Triple with leucine as in FIX-Padua (FIX-R338L). Purified FIX-TripleL exhibited 22-fold higher specific clotting activity and 15-fold increased binding affinity to activated FVIII compared to FIXWT. FIX-TripleL increased the therapeutic potential of FIX-Triple by nearly 100% as demonstrated with calibrated automated thrombogram and thromboelastography. FIX-TripleL demonstrated a normal clearance rate in HB mice. The clotting activity of FIX-TripleL was consistently 2- to 3-fold higher in these mice than that of FIX-Triple or FIXR338L. Gene delivery of adeno-associated virus (AAV) in HB mice showed that FIX-TripleL had 15-fold higher specific clotting activity than FIX-WT, and this activity was significantly better than FIX-Triple (10-fold) or FIX-R338L (6-fold). At a lower viral dose, FIX-TripleL improved FIX activity from sub-therapeutic to therapeutic levels. Under physiological conditions, no signs of adverse thrombotic events were observed in long-term AAV-FIX-treated C57Bl/6 mice. Hepatocellular adenomas were observed in the high- but not the medium- or the lowdose AAV-treated mice expressing FIX-WT or FIX-Triple, indicating the advantages of using hyperfunctional FIX variants to reduce viral doses while maintaining therapeutic clotting activity. Thus, incorporation of the FIX Padua mutation significantly improves the clotting function of FIX-Triple so as to optimise protein replacement therapy and gene therapy.
Role of plasma kallikrein in diabetes and metabolism
Authors: Zhou Qunfang , Fickweiler Ward , Feener Edward P. 
Published: May 2013

SummaryPlasma kallikrein (PK) is a serine protease generated from plasma prekallikrein, an abundant circulating zymogen expressed by the Klkb1 gene. The physiological actions of PK have been primarily attributed to its production of bradykinin and activation of coagulation factor XII, which promotes inflammation and the intrinsic coagulation pathway. Recent genetic, molecular, and pharmacological studies of PK have provided further insight into its role in physiology and disease. Genetic analyses have revealed common Klkb1 variants that are association with blood metabolite levels, hypertension, and coagulation. Characterisation of animal models with Klkb1 deficiency and PK inhibition have demonstrated effects on inflammation, vascular function, blood pressure regulation, thrombosis, haemostasis, and metabolism. These reports have also identified a host of PK substrates and interactions, which suggest an expanded physiological role for this protease beyond the bradykinin system and coagulation. The review summarises the mechanisms that contribute to PK activation and its emerging role in diabetes and metabolism.