bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of route to diagnosis on treatment intent and 1-year survival in patients diagnosed with oesophagogastric cancer in England: a prospective cohort study
Authors: Palser Thomas R , Cromwell David A , Hardwick Richard H , Riley Stuart A , Greenaway Kimberley , van der Meulen Jan H P 
Published: February 2013

ObjectiveTo investigate the relationship between the route to diagnosis, patient characteristics, treatment intent and 1 -year survival among patients with oesophagogastric (O-G) cancer.SettingCohort study in 142 English NHS trusts and 30 cancer networks.ParticipantsPatients diagnosed with O-G cancer between October 2007 and June 2009.DesignProspective cohort study. Route to diagnosis defined as general practitioner (GP) referral—urgent (suspected cancer) or non-urgent, hospital consultant referral, or after an emergency admission. Logistic regression was used to estimate associations and adjust for differences in casemix.Main outcome measuresProportion of patients diagnosed by route of diagnosis; proportion of patients selected for curative treatment; 1-year survival.ResultsAmong 14 102 cancer patients, 66.3% were diagnosed after a GP referral, 16.4% after an emergency admission and 17.4% after a hospital consultant referral. Of the 9351 GP referrals, 68.8% were urgent. Compared to urgent GP referrals, a markedly lower proportion of patients diagnosed after emergency admission had a curative treatment plan (36% vs 16%; adjusted OR=0.62, 95% CI 0.52 to 0.74) and a lower proportion survived 1 year (43% vs 27%; OR 0.78; 95% CI 0.68 to 0.89). Urgency of GP referral did not affect treatment intent or survival. Routes to diagnosis varied across cancer networks, with the adjusted proportion of patients diagnosed after emergency admission ranging from 8.7 to 32.3%.ConclusionsOutcomes for cancer patients are worse if diagnosed after emergency admission. Primary care and hospital services should work together to reduce rates of diagnosis after emergency admission and the variation across cancer networks.
Randomised comparison of the effectiveness of the laryngeal mask airway supreme, i-gel and current practice in the initial airway management of prehospital cardiac arrest (REVIVE-Airways): a feasibility study research protocol
Authors: Benger Jonathan Richard , Voss Sarah , Coates David , Greenwood Rosemary , Nolan Jerry , Rawstorne Steven , Rhys Megan , Thomas Matthew 
Published: February 2013

IntroductionEffective cardiopulmonary resuscitation with appropriate airway management improves outcomes following out-of-hospital cardiac arrest (OHCA). Historically, tracheal intubation has been accepted as the optimal form of OHCA airway management in the UK. The Joint Royal Colleges Ambulance Liaison Committee recently concluded that newer supraglottic airway devices (SADs) are safe and effective devices for hospital procedures and that their use in OHCA should be investigated. This study will address an identified gap in current knowledge by assessing whether it is feasible to use a cluster randomised design to compare SADs with current practice, and also to each other, during OHCA.Methods and analysisThe primary objective of this study is to assess the feasibility of a cluster randomised trial to compare the ventilation success of two newer SADs: the i-gel and the laryngeal mask airway supreme to usual practice during the initial airway management of OHCA. The secondary objectives are to collect data on ventilation success, further airway interventions required, loss of a previously established airway during transport, airway management on arrival at hospital (or termination of the resuscitation attempt), initial resuscitation success, survival to intensive care admission, survival to hospital discharge and patient outcome at 3 months. Ambulance paramedics will be randomly allocated to one of the three methods of airway management. Adults in medical OHCA attended by a trial paramedic will be eligible for the study.Ethics and disseminationApproval for the study has been obtained from a National Health Service Research Ethics Committee with authority to review proposals for trials of a medical device in incapacitated adults. The results will be made publicly available on an open access website, and we will publish the findings in appropriate journals and present them at national and international conferences relevant to the subject field.Trial registrationISRCTN: 18528625.
Reduced overtriage and undertriage with a new triage system in an urban accident and emergency department in Botswana: a cohort study
Authors: Mullan Paul C , Torrey Susan B , Chandra Amit , Caruso Ngaire , Kestler Andrew 
Published: February 2013

BackgroundImprovements in triage have demonstrated improved clinical outcomes in resource-limited settings. In 2009, the Accident and Emergency (A&E) Department at the Princess Marina Hospital (PMH) in Botswana identified the need for a more objective triage system and adapted the South African Triage Scale to create the PMH A&E Triage Scale (PATS).AimThe primary purpose was to compare the undertriage and overtriage rates in the PATS and pre-PATS study periods.MethodsData were collected from 5 April 2010 to 1 May 2011 for the PATS and compared with a database of patients triaged from 1 October 2009 to 24 March 2010 for the pre-PATS. Data included patient disposition outcomes, demographics and triage level assignments.Results14 706 (pre-PATS) and 25 243 (PATS) patient visits were reviewed. Overall, overtriage rates improved from 53% (pre-PATS) to 38% (PATS) (p<0.001); likewise, undertriage rates improved from 47% (pre-PATS) to 16% (PATS) (p<0.001). Statistically significant decreases in both rates were found when paediatric and adult cases were analysed separately. PATS was more predictive of inpatient admission, Intensive Care Unit (ICU) admission and death rates in the A&E than was the pre-PATS. The lowest acuity category of each system had a 0.6% (pre-PATS) and 0% (PATS) chance of death in the A&E or ICU admission (p<0.001). No change in death rate was seen between the pre-PATS and PATS, but ICU admission rates decreased from 0.35% to 0.06% (p<0.001).ConclusionsPATS is a more predictive triage system than pre-PATS as evidenced by improved overtriage, undertriage and patient severity predictability across triage levels.
Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus
Authors: Qvarlander Sara , Lundkvist Bo , Koskinen Lars-Owe D , Malm Jan , Eklund Anders 
Published: February 2013

BackgroundIt is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH.Methods51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase ≥0.1 m/s.ResultsThe pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (−3.0±2.9 mm Hg; −1.1±1.5 mm Hg; p<0.05, n=51). Amplitude reduction was larger for gait improvers (−1.2±1.6 mm Hg, n=42) than non-improvers (−0.2±0.5 mm Hg, n=9) (p<0.05) although mean ICP reduction did not differ.ConclusionsThe pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.
Postcranial skeleton of
Postosuchus kirkpatricki
(Archosauria: Paracrocodylomorpha), from the Upper Triassic of the United States
Authors: Weinbaum Jonathan C. 
Published: February 2013

Abstract

Postosuchus kirkpatricki
is a Late Triassic (Norian) ‘rauisuchid’ archosaur from North America. The initial description of the
Postosuchus
type material included elements from two poposaurids. This confusion has prevented adequate description of the material. Recent examination of the type material and other specimens of
Postosuchus
, and of related taxa, has helped clarify the osteology of
Postosuchus
. The type specimens represent
c.
75% of the skeleton. Together with other referred material,
Postosuchus
remains one of the most completely known rauisuchids. The paratype skeleton, which is relatively complete, would have been
c.
3.5–4 m in length, and the holotype would have been closer to 5–6 m.

Analysis of the postcranial skeleton of
Postosuchus
suggests that it may have been an obligate biped (based in part on limb proportions, which are similar to some theropod dinosaurs, the size of the manus (30% of the size of the pes) and the highly reduced nature of the digits and vertebral measurements). Possible postcranial autapomorphies of
Postosuchus
include a large, rugose triangular supra-acetabular buttress confluent with the dorsal margin of the iliac blade, and a symmetrical pes with digits two and three being roughly equal in length.
Non-dinosaurian Dinosauromorpha
Authors: Langer Max C. , Nesbitt Sterling J. , Bittencourt Jonathas S. , Irmis Randall B. 
Published: February 2013

Abstract

Ichnological evidence suggests that dinosauromorphs originated by the Early Triassic, and skeletal remains of non-dinosaur representatives of the clade occur from the Anisian to the end of the Triassic. These taxa are small- to medium-sized, vary in feeding and locomotor features, and occurred over most of western Pangaea. They include the small lagerpetids from the Mid–Late Triassic of Argentina and the United States, and the larger, quadrupedal Silesauridae, with records in the Middle Triassic of Africa and Argentina, and in the Late Triassic of Europe, the Americas and northern Africa. The former group represents the earliest diverging dinosauromorphs, whereas silesaurids are more closely related to Dinosauria. Other dinosauromorphs include the archetypal early dinosauriform
Marasuchus lilloensis
(Middle Triassic of Argentina) and poorly known/controversial taxa such as
Lewisuchus admixtus
and
Saltopus elginensis
. The earliest diverging dinosauromorphs may have preyed on small animals (including insects), but cranio-dental remains are rare; by contrast, most silesaurids probably included plant material in their diet, as indicated by their modified jaw apparatus and teeth. Our knowledge of the anatomy and thus relationships of non-dinosaurian Dinosauromorpha is still deficient, and we suspect that future discoveries will continue to reveal novel patterns and hypotheses of palaeobiology and biogeography.
Molecular Pathways: JAK/STAT Pathway: Mutations, Inhibitors, and Resistance
Authors: Quintás-Cardama Alfonso , Verstovsek Srdan 
Published: February 2013

Abstract
Aberrant activation of the JAK/STAT pathway has been reported in a variety of disease states, including inflammatory conditions, hematologic malignancies, and solid tumors. For instance, a large proportion of patients with myeloproliferative neoplasms (MPN) carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of the pathogenesis of MPNs and has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK/STAT pathway, now recognized as a common underlying biologic abnormality in MPNs. Ruxolitinib is an oral JAK1 and JAK2 inhibitor that has recently been approved for the treatment of myelofibrosis and has been tested against other hematologic malignancies. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials for patients with MPNs, lymphoma, and solid tumors such as breast or pancreatic cancer. Despite the significant clinical activity exhibited by these agents in myelofibrosis, some patients fail to respond or progress during JAK kinase inhibitor therapy. Recent reports have shed light into the mechanisms of resistance to JAK inhibitor therapy. Several approaches hold promise to overcome such resistance. Clin Cancer Res; 19(8); 1933–40. ©2013 AACR.
Molecular circuits in thrombosis and inflammation
Authors: Esmon Charles 
Published: February 2013

SummaryInflammatory cytokines promote the activation of coagulation through the induction of tissue factor, downregulation of thrombomodulin and upregulation of plasminogen activator inhibitor. In addition to these mechanisms, infections can trigger the release of extracellular traps from leukocytes consisting of DNA and histones. Tissue injury results in release of nucleosomes. Either of these histone containing structures activate platelets and form a potent procoagulant surface on polyphosphates secreted from the platelets, thereby augmenting thrombus formation. In addition, the histones can inhibit thrombomodulin function. The combination of augmenting the platelet procoagulant activity and impairing thrombomodulin activity probably explains the microvascular thrombotic problems observed when histones are infused into mice. Of the histones, H4 is the most potent in all of these activities. DNAase or blocking histone H4 can decrease the thrombotic response initiated by either the extracellular traps or nucleosomes. In addition to the direct prothrombotic activity of histone-DNA complexes, the complexes trigger activation of the toll-like receptors 2, 4 and 9 thereby increasing inflammatory cytokine formation and fostering thrombotic responses through the mechanisms mentioned previously. Furthermore, these cytokines are likely to increase cell necrosis and apoptosis releasing nucleosomes and further augmenting the activation of leukocytes with the subsequent release of extracellular traps. Blocking this histone-mediated cascade has the potential to impact a variety of clinical conditions including sepsis, trauma, chemical toxicity, transplant injury and reperfusion injury.
Non-invasive imaging for studying anti-angiogenic therapy effects
Authors: Ehling Josef , Lammers Twan , Kiessling Fabian 
Published: February 2013

SummaryNoninvasive imaging plays an emerging role in preclinical and clinical cancer research and has high potential to improve clinical translation of new drugs. This article summarises and discusses tools and methods to image tumour angiogenesis and monitor anti-angiogenic therapy effects. In this context, micro-computed tomography (?CT) is recommended to visualise and quantify the micro-architecture of functional tumour vessels. Contrast-enhanced ultrasound (US) and magnetic resonance imaging (MRI) are favourable tools to assess functional vascular parameters, such as perfusion and relative blood volume. These functional parameters have been shown to indicate antiangiogenic therapy response at an early stage, before changes in tumour size appear. For tumour characterisation, the imaging of the molecular characteristics of tumour blood vessels, such as receptor expression, might have an even higher diagnostic potential and has been shown to be highly suitable for therapy monitoring as well. In this context, US using targeted microbubbles is currently evaluated in clinical trials as an important tool for the molecular characterisation of the angiogenic endothelium. Other modalities, being preferably used for molecular imaging of vessels and their surrounding stroma, are photoacoustic imaging (PAI), near-infrared fluorescence optical imaging (OI), MRI, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The latter two are particularly useful if very high sensitivity is needed, and/or if the molecular target is difficult to access. Carefully considering the pros and cons of different imaging modalities in a multimodal imaging setup enables a comprehensive longitudinal assessment of the (micro)morphology, function and molecular regulation of tumour vessels.
The effect of different hormonal contraceptives on plasma levels of free protein S and free TFPI
Authors: Helmerhorst Frans M. , Fleischer Kathrin , Dahm Anders E. A. , Rosendaal Frits R. , Rosing Jan , Reitsma Pieter , Sandset Per , van Vliet Huib A. A. M. , Raps Marjolein 
Published: February 2013

SummaryUse of combined oral contraceptives is associated with a three- to sixfold increased risk of venous thrombosis. Hormonal contraceptives induce acquired resistance to activated protein C (APC), which predicts the risk of venous thrombosis. The biological basis of the acquired APC resistance is unknown. Free protein S (PS) and free tissue factor pathway inhibitor (TFPI) are the two main determinants of APC. Our objective was to assess the effect of both hormonal and non-hormonal contraceptives with different routes of administration on free TFPI and free PS levels. We conducted an observational study in 243 users of different contraceptives and measured APC sensitivity ratios (nAPCsr), free TFPI and free PS levels. Users of contraceptives with the highest risk of venous thrombosis as reported in recent literature, had the lowest free TFPI and free PS levels, and vice versa, women who used contraceptives with the lowest risk of venous thrombosis had the highest free TFPI and free PS levels. An association was observed between levels of free TFPI and nAPCsr, and between free PS and nAPCsr. The effect of oral contraceptives on TFPI and PS is a possible explanation for the increased risk of venous thrombosis associated with oral contraceptives.
Alloantibodies against the B subunit of plasma factor XIII developed in its congenital deficiency
Authors: Matsumoto Rui , Sugihara Takashi , Wada Hideho , Souri Masayoshi , Ichinose Akitada 
Published: February 2013

SummaryFactor XIII (FXIII) is a fibrin-stabilising factor consisting of catalytic A subunits (FXIII-A) and carrier B subunits (FXIII-B). FXIII-B prevents the fast clearance of FXIII-A from the circulation. Congenital FXIII-A deficiency is a rare bleeding disorder, and congenital FXIII-B deficiency is even rarer. Through our recent nationwide survey on “acquired haemophilia-like disease due to anti-FXIII autoantibodies,” we newly diagnosed severe congenital FXIII-B deficiency in a Japanese man. He developed thrombocytopenia and gingival bleedings at the age of 73, and his FXIII activity was as low as 10% of the normal. When he suddenly developed spontaneous intramuscular haematoma, the bleeding was arrested by infusing FXIII concentrates. However, his FXIII activity remained around 10% of the normal. At the age of 74, ELISA and western blotting assay unexpectedly revealed complete absence of FXIII-B in the patient’s plasma. A dot blot assay detected anti-FXIII-B alloantibodies for the first time in this disease, which could be attributed to the infusion of exogenous FXIII. He was found to be homozygous for a Japanese founder-effect mutation of F13B. Repeated infusions of exogenous FXIII for hemostasis increased anti-FXIII-B alloantibodies that resisted FXIII substitution. To the best knowledge of the authors, none of the remaining 10 reported cases of congenital FXIII-B deficiency developed alloantibodies to exogenous FXIII-B of plasma FXIII. An originally mild bleeding phenotype of severe congenital FXIII-B deficiency can be exaggerated by additional acquired conditions. Physicians should consider congenital FXIII-B deficiency when they encounter cases of unexplained bleeding disorders.
Role of Leptin Signaling in the Pathogenesis of Angiotensin II–Mediated Atrial Fibrosis and Fibrillation
Authors: Fukui Akira , Takahashi Naohiko , Nakada Chisato , Masaki Takayuki , Kume Osamu , Shinohara Tetsuji , Teshima Yasushi , Hara Masahide , Saikawa Tetsunori 
Published: February 2013

Background—
We examined the hypothesis that leptin signaling contributes to the atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AngII).

Methods and Results—

Eight-week-old male CL57/B6 (CNT) and leptin-deficient ob/ob mice (Ob) were subcutaneously infused with AngII (2.0 mg/kg per day). Two weeks later, transesophageal burst pacing and an electrophysiological study using isolated perfused hearts were performed. Left-atrial tissues were collected to determine interstitial fibrosis by Masson trichrome staining, and the expressions of mRNAs related to inflammatory profibrotic signals were assessed. Left-atrial fibroblasts were isolated from adult Sprague-Dawley and Zucker rats. The effects of leptin (100 ng/mL) or AngII (100 nmol/L) treatment were evaluated. In CNT-AngII mice, leptin expression in the left atrium was upregulated (
P
<0.01). Transesophageal burst pacing induced atrial fibrillation in 88% (7/8) of CNT-AngII mice, but not in Ob-AngII mice (0/8;
P
<0.01). In isolated perfused hearts, atrial fibrillation was induced only in CNT-AngII mice (4/6; 67%). Interatrial conduction time was prolonged in CNT-AngII mice (
P
<0.01), but not in Ob-AngII mice. The upregulation of collagen 1, collagen 3, transforming growth factor-β1, α-smooth muscle actin, MCP-1, F4/80, and RANTES mRNA, which was seen in CNT-AngII mice, was attenuated in Ob-AngII mice. In cultured Sprague-Dawley rat atrial fibroblasts, AngII treatment increased leptin expression (
P
<0.01). Addition of leptin increased transforming growth factor-β1, α-smooth muscle actin, MCP-1, and RANTES expressions in Sprague-Dawley rat atrial fibroblasts, but not in Zucker rat atrial fibroblasts.

Conclusions—
Our results demonstrate for the first time that leptin signaling is essential for the development of atrial fibrosis and atrial fibrillation evoked by AngII.
Neural Representation of Reward Probability: Evidence from the Illusion of Control
Authors: Kool Wouter , Getz Sarah J. , Botvinick Matthew M. 
Published: February 2013

Abstract
To support reward-based decision-making, the brain must encode potential outcomes both in terms of their incentive value and their probability of occurrence. Recent research has made it clear that the brain bears multiple representations of reward magnitude, meaning that a single choice option may be represented differently—and even inconsistently—in different brain areas. There are some hints that the same may be true for reward probability. Preliminary evidence hints that, even as systematic distortions of probability are expressed in behavior, these may not always be uniformly reflected at the neural level: Some neural representations of probability may be immune from such distortions. This study provides new evidence consistent with this possibility. Participants in a behavioral experiment displayed a classic “illusion of control,” providing higher estimates of reward probability for gambles they had chosen than for identical gambles that were imposed on them. However, an fMRI study of the same task revealed that neural prediction error signals, arising when gamble outcomes were revealed, were unaffected by the illusion of control. The resulting behavioral–neural dissociation reinforces the case for multiple, inconsistent internal representations of reward probability, while also prompting a reinterpretation of the illusion of control effect itself.