Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation

Background: Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH) and insulin-like growth factor I (IGF-1). It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG) is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods: Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results: One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was pound81,000/QALY and pound212,000/LYG. To reduce this to pound30K/QALY would require a reduction in drug cost by about one third. Conclusion: PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK) for determining cost-effectiveness of therapies were to be applied to PEG it would be considered not to represent good value for money

Delta-Function Bose Gas Picture of S=1 Antiferromagnetic Quantum Spin Chains Near Critical Fields

We study the zero-temperature magnetization curve (M-H curve) of the S=1 bilinear-biquadratic spin chain, whose Hamiltonian is given by $H=\sum_{i} S_i S_{i+1}+\beta (S_iS_{i+1})^2 with$0 \leq \beta <1$. We focus on validity of the delta-function bose-gas picture near the two critical fields: the saturation field$H_s$and the lower critical field$H_c$associated with the Haldane gap. Near$H_s$, we take ``low-energy effective S-matrix'' approach, which gives correct effective bose-gas coupling constant$c$, different from the spin-wave value. Comparing the M-H curve of the bose gas with the product-wavefunction renormalization group (PWFRG) calculation, excellent agreement is seen. Near$H_c$, comparing the PWFRG result with the bose-gas prediction, we find that there are two distinct regions of$\beta$separated by a critical value$\beta_c(\approx 0.41)$. In the region$0<\beta<\beta_c$, the effective coupling$c$is positive but rather small. The small value of$c$makes the ``critical region'' of the square-root behavior$M\sim \sqrt{H-H_c}$very narrow. Further, we find that in the$\beta \to \beta_c-0$, the square-root behavior transmutes to a different one,$M\sim (H-H_c)^{1/4}$. In the region$\beta_c<\beta <1$, the square-root behavior is rather distinct, but the effective coupling$c$ becomes negative.Comment: 6 pages, RevTeX, 8 ps figure

Radio Detection of the Fermi LAT Blind Search Millisecond Pulsar J1311-3430

We report the detection of radio emission from PSR J1311-3430, the first millisecond pulsar discovered in a blind search of Fermi Large Area Telescope (LAT) gamma-ray data. We detected radio pulsations at 2 GHz, visible for <10% of ~4.5-hrs of observations using the Green Bank Telescope (GBT). Observations at 5 GHz with the GBT and at several lower frequencies with Parkes, Nancay, and the Giant Metrewave Radio Telescope resulted in non-detections. We also report the faint detection of a steep spectrum continuum radio source (0.1 mJy at 5 GHz) in interferometric imaging observations with the Jansky Very Large Array. These detections demonstrate that PSR J1311-3430, is not radio quiet and provides additional evidence that the radio beaming fraction of millisecond pulsars is very large. The radio detection yields a distance estimate of 1.4 kpc for the system, yielding a gamma-ray efficiency of 30%, typical of LAT-detected MSPs. We see apparent excess delay in the radio pulsar as the pulsar appears from eclipse and we speculate on possible mechanisms for the non-detections of the pulse at other orbital phases and observing frequencies.Comment: 6 pages, 4 figures. ApJ Letters, in pres

Including pupils with special educational needs and/or disabilities in mainstream secondary physical education: A revisit study

Our research used an innovative methodological approach by revisiting an original study conducted 15 years previously (Morley et al., 2005). A purposive sample of 31 secondary school teachers in the UK were interviewed to explore their perceptions of including pupils with special educational needs and/or disabilities (SEND) in mainstream secondary physical education (PE). All interviews were transcribed verbatim and texts analysed thematically. Findings suggest that, despite significant policy developments, little has changed in teachers’ perceptions of their ability to include pupils with SEND in PE and there remain significant challenges to them achieving this. Some exceptions were documented, most notably an increased and positively received focus on inclusion within PE initial teacher education. The article concludes with recommendations for future practice, particularly in terms of teacher education and professional development, as well as the need for effective dissemination of research findings to key stakeholders

CanGEM: mining gene copy number changes in cancer

The use of genome-wide and high-throughput screening methods on large sample sizes is a well-grounded approach when studying a process as complex and heterogeneous as tumorigenesis. Gene copy number changes are one of the main mechanisms causing cancerous alterations in gene expression and can be detected using array comparative genomic hybridization (aCGH). Microarrays are well suited for the integrative systems biology approach, but none of the existing microarray databases is focusing on copy number changes. We present here CanGEM (Cancer GEnome Mine), which is a public, web-based database for storing quantitative microarray data and relevant metadata about the measurements and samples. CanGEM supports the MIAME standard and in addition, stores clinical information using standardized controlled vocabularies whenever possible. Microarray probes are re-annotated with their physical coordinates in the human genome and aCGH data is analyzed to yield gene-specific copy numbers. Users can build custom datasets by querying for specific clinical sample characteristics or copy number changes of individual genes. Aberration frequencies can be calculated for these datasets, and the data can be visualized on the human genome map with gene annotations. Furthermore, the original data files are available for more detailed analysis. The CanGEM database can be accessed at http://www.cangem.org/

Low-temperature properties of the spin-1 antiferromagnetic Heisenberg chain with bond-alternation

We investigate the low-temperature properties of the spin-1 antiferromagnetic Heisenberg chain with bond-alternation by the quantum Monte Carlo method (loop algorithm). The strength of bond-alternation at the gapless point is estimated as $\delta_{c}=0.2595\pm0.0005$. We confirm numerically that the low-temperature properties at the gapless point are consistent with field theoretical predictions. The numerical results are compared with those of the spin-1/2 antiferromagnetic Heisenberg chain and recent experimental results for [\{Ni(333-tet)($\mu$-N$_3$)\}$_n$](ClO$_4$)$_n$ (333-tet=tetraamine $N,N^{\prime}$-bis(3-aminopropyl)-1,3-propanediamine).Comment: 18 pages, RevTex, 9 figures, Submitted to Phys.Rev.

Heat Capacity of PbS: Isotope Effects

In recent years, the availability of highly pure stable isotopes has made possible the investigation of the dependence of the physical properties of crystals, in particular semiconductors, on their isotopic composition. Following the investigation of the specific heat ($C_p$, $C_v$) of monatomic crystals such as diamond, silicon, and germanium, similar investigations have been undertaken for the tetrahedral diatomic systems ZnO and GaN (wurtzite structure), for which the effect of the mass of the cation differs from that of the anion. In this article we present measurements for a semiconductor with rock salt structure, namely lead sulfide. Because of the large difference in the atomic mass of both constituents ($M_{\rm Pb}$= 207.21 and ($M_{\rm S}$=32.06 a.m.u., for the natural isotopic abundance) the effects of varying the cation and that of the anion mass are very different for this canonical semiconductor. We compare the measured temperature dependence of $C_p \approx C_v$, and the corresponding derivatives with respect to ($M_{\rm Pb}$ and $M_{\rm S}$), with \textit{\textit{ab initio}} calculations based on the lattice dynamics obtained from the local density approximation (LDA) electronic band structure. Quantitative deviations between theory and experiment are attributed to the absence of spin-orbit interaction in the ABINIT program used for the electronic band structure calculations.Comment: 17 pages including 10 Fig

Impurity Energy Level Within The Haldane Gap

An impurity bond $J{'}$ in a periodic 1D antiferromagnetic, spin 1 chain with exchange $J$ is considered. Using the numerical density matrix renormalization group method, we find an impurity energy level in the Haldane gap, corresponding to a bound state near the impurity bond. When $J{'}<J$ the level changes gradually from the edge of the Haldane gap to the ground state energy as the deviation $dev=(J-J{'})/J$ changes from 0 to 1. It seems that there is no threshold. Yet, there is a threshold when $J{'}>J$. The impurity level appears only when the deviation $dev=(J{'}-J)/J{'}$ is greater than $B_{c}$, which is near 0.3 in our calculation.Comment: Latex file,9 pages uuencoded compressed postscript including 4 figure