3,932 research outputs found
Stabilizing ITR elements in AAV transfer plasmids
No full textShankar R, Radukic M, Schäffer N, Schmeer M, Schleef M, Müller K. Stabilizing ITR elements in AAV transfer plasmids. Human Gene Therapy . 2025;36(3-4):E246
Thromboelastography in the assessment of coagulation changes in peripheral vascular disease
No full textStudies up to date in the western literature involving changes in coagulation
in patients with peripheral vascular disease(PVD) have consistently reported
activation of coagulation based on measurement of raised levels of markers
of activation of coagulation(clot formation), decreased fibrinolysis (breakdown
of fibrin), platelet activation leading to increased aggregation and defective
endothelial (arterial wall) function in patients with PVD that leads to
thrombosis in arterial circulation thus designating this group of patients as
hypercoagulable.‘ Interestingly these patients are not deemed as such in
clinical practice as the routine coagulation tests(RCTs) currently employed do
not identify these abnormalities. The overall purpose of the research
described in this thesis was to identify changes in coagulation in patients with
peripheral vascular disease using Thromboelastography (TEG), a technique
which exploits the visco-elastic properties of a blood clot as it forms, retracts
or lyses (breaks down) using a small volume of whole blood.
Validation of TEG technique employing citrated whole blood (CWB) and
heparinase modified (hepTEG) methods and standardisation of analysis to
overcome variability in TEG analysis, blood sample instability due to storage
times was carried out. TEG analysis after sample storage between 1-2 hours
showed no significant inter or intra sample assay variability confirming
excellent reproducibility( (p= NS; reliability coefficients (Alpha) greater than
0.9 for R time, K time, Angle, Maximal Amplitude (MA) and Coagulation
Index(CI)). hepTEG method confirmed complete reversal of heparin effect in
blood samples obtained from participants following heparin administration.(R
ii time: 9.16+/- 1.68 Vs 8.90 +/- 1.48 p=NS; K time: 2.98+/- 0.87 Vs 3.20 +/-
1.05 p=NS; Angle: 56.86+/- 6.39 Vs 56.90 +/- 5.30 p=NS; MA 56.34+/- 6.39
Vs 56.79+/-6.23 p=NS; CI: 0.59+/-1.19 Vs 0.88+/-1.00 p=NS). 50 age
matched controls to obtain reference values for comparison and
documentation of any significant changes in TEG parameters due to age,
gender anaesthesia and surgery was completed. Preparation /induction of
anaesthesia led to a significant trend towards activation of coagulation in all
age groups and gender (Angle 56.23 +/-0.89, CI 54.42, 58.04 Vs 58.21+/-
0.83, CI 56.54, 59.88;p=0.003 and MA 56.40 +/- 0.79 CI 54.80, 58.01 Vs
59.36 +/- 0.89, CI 57.56, 61.15; p=0.003 and CI 0.71 +/- 0.14, CI 0.42, 1.00
Vs 1.35 +/- 0.17, CI 1.00, 1.69;p=0.003)
Surgical stimulus led to a further activation of coagulation that followed
induction of anaesthesia (Angle: 58.21+/- 0.83, CI 56.54, 59.88 Vs 60.98 +/-
0.69, CI 59.59, 62.37; p=0.001). TEG parameter values obtained from
healthy controls aged over 45 are used as reference values for this study.
TEG showed no significant differences in TEG parameters when samples
obtained from an upper limb artery and a vein were analysed. However when
samples from the main lower limb artery (common femoral artery/CFA) and
the major vein that drains the same limb (common femoral vein/CFV) in
patients with symptomatic PVD, TEG identified significant activation of
coagulation in samples obtained from the vein that drains an ischaemic limb
(decrease in R time (p0.05), an increase in MA (p0.05) and an increase in
CI (p0.002)). This interesting finding led to a hypothesis that ischaemic
tissue has a prominent role in the activation of coagulation observed in
iii patients with PVD. To test this hypothesis, common femoral venous and
arterial samples from 30 patients with symptomatic PVD were analysed using
TEG. TEG identified significant activation of coagulation in samples obtained
from an artery downstream (CFA) when compared to those obtained from an
artery that is proximal (Aorta). This change towards hypercoagulation was
also found to be positively related to the degree of narrowing or stenotic
disease (quantified using angiography) between these two sampling
points(R, r=0.442, p0.05 / MA, r=0.379, p0.05 / CI r=0.429, p0.05). A
significant positive relationship in between degree of ischaemia (ABPI) and
difference in TEG parameter values in between arterial and venous blood
samples obtained from an ischaemic limb (ABPI) on that side (CI v ABPI r =
-0.427 p0.05, MA v ABPI r =-0.370 p0.05) was also found in this study.
These findings suggest activation of coagulation as the blood flows down an
atherosclerotic vessel and in combination with the observed changes due to
the presence of peripheral ischemia tissue suggested that the
hypercoagulability observed in PVD may have its origins in the ishaemic limb
itself.
To clarify the role of non-ionic contrast media (NICM) in the context of
conflicting findings regarding its thrombogenic potential especially in patients
with PVD undergoing angiography, aortic blood samples(n=30) were
obtained before and after injection of NICM. Heparinase modified TEG
analysis showed that there was no activation of coagulation immediately after
NICM exposure and in fact there was a significant trend towards
hypocoagulation in contrast to the published reports of increased
iv thrombogenicity after NICM exposure (increase in R time (time to fibrin
formation) (CI 7.8,10.18 minutes) (p=0.036), in K time (dynamics of clot
formation) (CI 2.2,2.8 minutes) (p=0.028), and a reduction in Angle
(decreased acceleration of fibrin build up) (CI 53.10,62.7 degrees)
(p=0.013),MA (reduced ultimate clot strength) (CI 54.5,62.7 mm) (p=0.013)
and (CI) (decreased overall coagulation status) (0.31,1.95) (p=0.032)). This
study also showed that despite this significant reduction in the activation of
coagulation after NICM exposure, PVD patients were consistently
procoagulant when compared to age- matched controls(n=30) who were not
exposed to NICM (R time: p=0.029/K time: p=0.001/Angle: p=0.003/MA:
p=0.020 and CI: p=0.014)
Patients with ischaemic heart disease, a consequence of significant coronary
artery atherosclerosis have reduced amounts of naturally occurring
anticoagulant substances like heparan, heparan-sulphate proteoglycan and
endogenous heparin. Since patients with PVD exhibit similar pathology in
addition to the presence of peripheral ischaemic tissue, to identify any similar
defect in PVD, blood samples from patients with symptomatic PVD(n=28)
and age matched control subjects were analysed using hepTEG. Heparinase
modified TEG analysis identified for the first time, heparinase sensitive
heparin-like activity in peripheral venous samples in patients with PVD (R
time 7.50 0.44 min / CI 6.54, 8.46 Vs 7.17 0.40 min / CI 6.30, 8.05 /
p=0.041). Endogenous heparin-like activity is found to be reduced in PVD
and this reduction also correlated with the degree of peripheral ischaemia
v(ABPI) (correlation coefficient: abpi: 1.000 / change in R time 0.350 /
p=0.021)TEG analysis of samples from 30 patients with aortic aneurysmal disease
and 14 aortic occlusive disease undergoing revascularisation and 30 controls
were carried out using hepTEG method. Baseline TEG parameter values in
the aneurysm group showed significant activation of coagulation when
compared to the controls (R time (p=0.001); K time (p=0.008) and (CI)
(p=0.047)). Following release of the aortic cross-clamp a significant trend
towards activation of coagulation was noted in the aneurysm group and a
similar but pronounced activation of coagulation was noted in the occlusive
group, confirming activation of coagulation following reperfusion of ischaemic
tissues (R time (p=0.042); K time (p=0.043) MA (p= 0.034) and CI (p=0.026)).
Further TEG analysis during postoperative period showed that both these
patient groups exhibit sustained periods of hypercoagulability. In addition to
these findings hepTEG method further revealed underlying
hypercoagulability, despite exogenous heparin administration, confirming
presence and activation of non- AT-III dependent pathways of activation of
coagulation in these patients.
TEG analysis of blood samples from 86 patients admitted with symptoms
peripheral ischaemia requiring revascularisation surgery or amputation were
carried out and TEG parameter values obtained from control group was used
for compari
Correction to: Recombinant expression of Barnase in Escherichia coli and its application in plasmid purifcation
No full textShankar R, Schafer N, Schmeer M, Risse JM, Friehs K, Schleef M. Correction to: Recombinant expression of Barnase in Escherichia coli and its application in plasmid purifcation. Microbial Cell Factories. 2021;20(1): 190
Relative trajectory analysis of dissimilar formation flying spacecraft
No full textThis paper deals with the differential acceleration effects on spacecraft formation flying. A mathematical model is developed to analyze relative trajectory of spacecraft in the presence of significant perturbative forces.The equations of relative coordinates are derived as a precise solution to the formation geometry problem and are valid for both close and long distance formation patterns and for rendezvous analysis. The coordinates of motion are propagated forward in time for identical and dissimilar spacecraft for different initial conditions. The results of this paper provide a physical insight into the actual behaviour of satellites in a cluster with differential drag-area
India’s Macroeconomic Performance and Policies since 2000
No full textThe paper reviews Indias macroeconomic performance and policies since 2000. The first section briefly summarizes key macroeconomic developments regarding economic growth, inflation, external balance, the fiscal situation and aggregate savings and investment. The second section considers some of the challenges posed to macroeconomic management in this period and the efficacy of the policy responses adopted. In particular, it analyses the progress in fiscal consolidation and the policies adopted to deal with the challenge of the unprecedented surge in external capital inflows into India. The final section outlines some of the major macro policy issues that need to be addressed in the years ahead, including : the resurgence of high fiscal deficits; the issues relating to external convertibility and exchange rate management; the role of the Reserve Bank of India in macroeconomic policy and coping with a weak international economic environment.economic growth, inflation, Fiscal Policy, savings and investment, Capital Inflows, exchange rate policy, central bank role
Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures
No full textBackground: The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic–clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). Objective: We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. Methods: Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). Results: Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. Conclusions: The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence
Magnetotransport of Dirac fermions on the surface of a topological insulator
No full textWe study the properties of Dirac fermions on the surface of a topological insulator in the presence of crossed electric and magnetic fields. We provide an exact solution to this problem and demonstrate that, in contrast to their counterparts in graphene, these Dirac fermions allow relative tuning of the orbital and Zeeman effects of an applied magnetic field by a crossed electric field along the surface. We also elaborate and extend our earlier results on normal-metal-magnetic film-normal metal (NMN) and
normal-metal-barrier-magnetic film (NBM) junctions of topological insulators [S. Mondal, D. Sen, K. Sengupta, and R. Shankar, Phys. Rev. Lett. 104, 046403 (2010)]. For NMN junctions, we show that for Dirac fermions with Fermi velocity vF, the transport can be controlled using the exchange field J of a ferromagnetic film over a region of
width d. The conductance of such a junction changes from oscillatory to a monotonically decreasing function of d beyond a critical J which leads to the possible realization of magnetic switches using these junctions. For NBM junctions with a potential barrier of width d and potential V-0, we find that beyond a critical J, the criteria of
conductance maxima changes from chi=eV(0)d/h upsilon(F)=n pi to chi=(n+1/2)pi for integer n. Finally, we compute the subgap tunneling conductance of a normal-metal-magnetic film-superconductor junctions on the surface of a topological insulator and show that the position of the peaks of the zero-bias tunneling conductance can be tuned using the magnetization of the ferromagnetic film. We point out that these phenomena have no analogs in either conventional two-dimensional materials or Dirac electrons in graphene and suggest experiments to test our theory
The weak dependence of velocity dispersion on disc fractions, mass-to-light ratio, and redshift: implications for galaxy and black hole evolution
No full textVelocity dispersion ( σ) is a key driver for galaxy structure and evolution. We here present a comprehensive semi-empirical approach to compute σvia detailed Jeans modelling assuming both a constant and scale-dependent mass-to-light ratio M ∗/ L . We compare with a large sample of local galaxies from MaNGA and find that both models can reproduce the Faber–Jackson (FJ) relation and the weak dependence of σon bulge-to-total (B/T) ratio (for B/T 0.25). The dynamical-to-stellar mass ratio within R R e can be fully accounted for by a gradient in M ∗/ L . We then build velocity dispersion evolutionary tracks σap [ M ∗, z] (within an aperture) along the main progenitor dark matter haloes assigning stellar masses, ef fecti ve radii, and S ́ersic indices via a variety of abundance matching and empirically moti v ated relations. We find: (1) clear e vidence for do wnsizing in σap [ M ∗, z] along the progenitor tracks; (2) at fixed stellar mass σ∝ (1 + z) 0.2 −0.3 depending on the presence or not of a gradient in M ∗/ L . We extract σap [ M ∗, z] from the TNG50 hydrodynamic simulation and find very similar results to our models with constant M ∗/ L . The increasing dark matter fraction within R e tends to flatten the σap [ M ∗, z] along the progenitors at z 1 in constant M ∗/ L models, while σap [ M ∗, z] have a steeper evolution in the presence of a stellar gradient. We then show that a combination of mergers and gas accretion is likely responsible for the constant or increasing σap [ M ∗, z] with time. Finally, our σap [ M ∗, z] are consistent with a nearly constant and steep M bh −σrelation at z 2, with black hole masses derived from the L X −M ∗relation
Silicon headrests are ideal lithotomy restraints for neonatal and infant cystoscopy
No full textArticle first published online: 17 DEC 2003H.L. Tan, P.J. Lopez, K.R. Shankar and H.A.P. Boucau
Renormalization-group approach to superconductivity: from weak to strong electron-phonon coupling
No full textWe present the numerical solution of the renormalization group (RG) equations derived in Tsai, Castro Neto, Shankar, et al. [Phys. Rev. B to appear], for the problem of superconductivity in the presence of both electron–electron and electron–phonon coupling at zero temperature. We study the instability of a Fermi liquid to a superconductor and the RG flow of the couplings in the presence of retardation effects and the crossover from weak to strong coupling. We show that our numerical results provide an ansatz for the analytic solution to the problem in the asymptotic limits of weak and strong coupling.First author draf
- …
