Targeting BCL-2 regulated apoptosis in cancer

The ability of a cell to undergo mitochondrial apoptosis is governed by pro- and anti-apoptotic members of the BCL-2 protein family. The equilibrium of pro- versus anti-apoptotic BCL-2 proteins ensures appropriate regulation of programmed cell death during development and maintains organismal health. When unbalanced, the BCL-2 family can act as a barrier to apoptosis and facilitate tumour development and resistance to cancer therapy. Here we discuss the BCL-2 family, their deregulation in cancer and recent pharmaceutical developments to target specific members of this family as cancer therapy

Arterial Emboli Complicating Cisplatin Therapy

We report three cases of arterial emboli in patients with lung cancer treated with cisplatin chemotherapy. All three patients were managed without surgical intervention but subsequent oncological treatment was complicated by the sequelae of arterial emboli. We discuss the issues surrounding these patients and the importance of identifying patients at risk of arterial embolic phenomena with cisplatin treatment

Next-to-leading order corrections to Wt production and decay

We present the results of a next-to-leading order calculation of Wt production, including the decays of both the top quark and the W boson. The effects of radiation in the decay of the top quark are also included. The separation of diagrams which appear in the real corrections, into singly- and doubly-resonant contributions, is performed using a b-jet veto which is motivated by the use of the bottom quark distribution function. We find that, for a choice of scale which is suitable for this approach, the QCD corrections are very mild and only change the cross section by up to 10% at the LHC, depending on the severity of the b-jet veto. When further cuts are applied, applicable for a Higgs boson search in the H->WW channel, we find that the radiative effects greatly decrease the number of background events expected from this process. In addition, the shapes of relevant distributions can be significantly changed at next-to-leading order.Comment: 31 pages, 12 figure

Successful elimination of factor VIII inhibitor using cyclosporin A

No abstract available

Little Higgs models and single top production at the LHC

We investigate the corrections of the littlest Higgs(LH) model and the SU(3) simple group model to single top production at the CERN Large Hardon Collider(LHC). We find that the new gauge bosons $W_{H}^{\pm}$ predicted by the LH model can generate significant contributions to single top production via the s-channel process. The correction terms for the tree-level $Wqq'$ couplings coming from the SU(3) simple group model can give large contributions to the cross sections of the t-channel single top production process. We expect that the effects of the LH model and the SU(3) simple group model on single top production can be detected at the LHC experiments.Comment: 17pages, 5 figures, discussions and references added, typos correcte

Search for New Physics via Single Top Production at the LHC

We consider single-top production as a probe for new physics effects at the Large Hadron Collider (LHC). We argue that for natural theories a small deviation from the Standard Model tree-level couplings in this reaction can be parameterized by 3 higher dimension operators. Precision measurement of these effective couplings in the single-top events, via studying their interference effects with the SM contributions, can discriminate several new physics models. In particular, combining the production rate of three single-top production modes will provide a severe test of the Little Higgs model with T-parity. We find that at the LHC, a 5% accuracy in the measurement of the single-top cross sections would probe the new physics scale up to about $3 {\rm TeV}$.Comment: version to appear in Physics Letters

The Bulk RS KK-gluon at the LHC

We study the possibility of discovering and measuring the properties of the lightest Kaluza-Klein excitation of the gluon in a Randall-Sundrum scenario where the Standard Model matter and gauge fields propagate in the bulk. The KK-gluon decays primarily into top quarks. We discuss how to use the $t \bar{t}$ final states to discover and probe the properties of the KK-gluon. Identification of highly energetic tops is crucial for this analysis. We show that conventional identification methods relying on well separated decay products will not work for heavy resonances but suggest alternative methods for top identification for energetic tops. We find, conservatively, that resonances with masses less than 5 TeV can be discovered if the algorithm to identify high $p_T$ tops can reject the QCD background by a factor of 10. We also find that for similar or lighter masses the spin can be determined and for lighter masses the chirality of the coupling to $t\bar t$ can be measured. Since the energetic top pair final state is a generic signature for a large class of new physics as the top quark presumably couples most strongly to the electroweak symmetry breaking sector, the methods we have outlined to study the properties of the KK-gluon should also be important in other scenarios.Comment: 21 pages, 13 figure

Coagulation and fibrinolytic activity of tenecteplase and alteplase in acute ischemic stroke

Background and Purpose—We compared the fibrinolytic activity of tenecteplase and alteplase in patients with acute ischemic stroke, and explored the association between hypofibrinogenaemia and intracerebral hemorrhage. Methods—Venous blood samples from a subgroup of participants in the Alteplase–Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST) study were obtained at pretreatment, 3 to 12 hours, and 24±3 hours post-intravenous thrombolysis for analyses of plasminogen, plasminogen activator inhibitor-1, D-dimer, factor V, fibrinogen, and fibrin(ogen) degradation products, in addition to routine coagulation assays. Related sample Wilcoxon signed-rank tests were used to test the within-group changes, and independent Mann–Whitney tests for between-group differences. Results—Thirty patients were included (alteplase=14 and tenecteplase=16) with similar baseline demographics. Compared with baseline, alteplase caused significant hypofibrinogenaemia (P=0.002), prolonged prothrombin time (P=0.011), hypoplasminogenaemia (P=0.001), and lower factor V (P=0.002) at 3 to 12 hours after administration with persistent hypofibrinogenaemia at 24 hours (P=0.011), whereas only minor hypoplasminogenaemia (P=0.029) was seen in the tenecteplase group. Tenecteplase consumed less plasminogen (P<0.001) and fibrinogen (P=0.002) compared with alteplase. Conclusions—In patients with acute ischemic stroke, alteplase 0.9 mg/kg caused significant disruption of the fibrinolytic system, whereas tenecteplase 0.25 mg/kg did not, consistent with the trend toward lower intracerebral hemorrhage incidence with tenecteplase in the ATTEST study

Performance of the LumiraDx Platform INR test in an anticoagulation clinic point-of-care setting compared with an established laboratory reference method

Vitamin K antagonists, such as warfarin, have a narrow therapeutic window; patients on these therapies therefore require regular international normalized ratio (INR) monitoring to maintain optimal dosing. This involves periodic checks and laboratory testing using venepuncture, which are often perceived as a burden. This study aimed to determine the accuracy and precision of the LumiraDx INR Test, a new point-of-care in vitro diagnostic platform, in an anticoagulation clinic setting. In this observational, cross-sectional study, precision of the LumiraDx INR Test was assessed using paired replicate samples (n = 366) and 3 test strip lots. Accuracy was determined by comparing capillary blood INR, ascertained by the LumiraDx INR Test, with venous plasma INR, measured by the laboratory reference instrument, the IL ACL ELITE Pro. Furthermore, INR was assessed across a range of hematocrit (25%-55%). In addition, feedback was collected from health-care professionals via a self-completed questionnaire. This trial was registered at ClinicalTrials.gov (NCT03682419). The precision (% coefficient of variation) of the LumiraDx INR Test was <4 when samples were applied by direct application or via a capillary transfer pipette, as well as between test strip lots. Accuracy of the LumiraDx INR Test, across the INR range of 0.8 to 7.5, was confirmed by a strong correlation of 0.965 (95% confidence interval: 0.959-0.970) when compared with the IL ACL ELITE Pro, which was maintained across the hematocrit range. Feedback from health-care professionals indicated that the instructions given by the system were easy to follow. In conclusion, the strong agreement between the LumiraDx Platform INR point-of-care test and the IL ACL ELITE Pro laboratory reference system, as well as between the different application methods and test lots, indicates that it can provide a rapid, accurate, and reliable INR analysis

Single-top Wt-channel production matched with parton showers using the POWHEG method

We present results for the next-to-leading order calculation of single-top Wt-channel production interfaced to Shower Monte Carlo programs, implemented according to the POWHEG method. A comparison with MC@NLO is carried out. Results obtained using the PYTHIA shower are also shown and the effect of typical cuts is briefly discussed.Comment: 23 pages, 9 figure