The management of children with Spinal Muscular Atrophy Type 1 in Australia

Aims: To (1) estimate the prevalence of Spinal Muscular Atrophy Type 1 (SMA 1); (2) describe what practices characterise end-of-life care of patients with SMA 1; (3) ascertain whether a consistent approach to the management of these patients exists in Australia. Methods: An audit of the Australasian pathology laboratories offering the diagnostic SMN1 deletion test was conducted for patients diagnosed with SMA in Australia for 2010 and 2011. In addition, a retrospective clinical audit was conducted in eight major Australian paediatric hospitals of the end-of-life care provided to children with confirmed SMA 1 from 2005 to 2010. Results: 35 children were included in the clinical audit, accounting for an estimated 61% of children diagnosed with SMA 1 from 2005-2010. 26% were ventilated invasively, only two of whom were intubated after the diagnosis was confirmed. No children were ventilated long-term (>90 days) or had a tracheostomy performed. Nasogastric tube feeding was a common measure to support adequate nutritional intake. Total parenteral nutrition, gastrostomy and fundoplication were not provided for any children. Conflict over end-of-life care decisions was documented in one instance, without the involvement of a guardianship tribunal. Conclusion: There appears to be a consistent approach in the management of children with SMA 1 in Australia, which can be characterised as ‘actively managed dying.’ This study could contribute to the development of Australian consensus guidelines for the management of these children. These results also highlight a number of ethical issues related to the management of children with SMA 1

The diagnostic accuracy and cost-effectiveness of magnetic resonance spectroscopy and enhanced magnetic resonance imaging techniques in aiding the localisation of prostate abnormalities for biopsy : a systematic review and economic evaluation

Peer reviewedPublisher PD

Is self-monitoring an effective option for people receiving long-term vitamin K antagonist therapy? A systematic review and economic evaluation

OBJECTIVES: To investigate the clinical and cost-effectiveness of self-monitoring of coagulation status in people receiving long-term vitamin K antagonist therapy compared with standard clinic care. DESIGN: Systematic review of current evidence and economic modelling. DATA SOURCES: Major electronic databases were searched up to May 2013. The economic model parameters were derived from the clinical effectiveness review, routine sources of cost data and advice from clinical experts. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) comparing self-monitoring versus standard clinical care in people with different clinical conditions. Self-monitoring included both self-management (patients conducted the tests and adjusted their treatment according to an algorithm) and self-testing (patients conducted the tests, but received treatment recommendations from a clinician). Various point-of-care coagulometers were considered. RESULTS: 26 RCTs (8763 participants) were included. Both self-management and self-testing were as safe as standard care in terms of major bleeding events (RR 1.08, 95% CI 0.81 to 1.45, p=0.690, and RR 0.99, 95% CI 0.80 to 1.23, p=0.92, respectively). Self-management was associated with fewer thromboembolic events (RR 0.51, 95% CI 0.37 to 0.69, p </= 0.001) and with a borderline significant reduction in all-cause mortality (RR 0.68, 95% CI 0.46 to 1.01, p=0.06) than standard care. Self-testing resulted in a modest increase in time in therapeutic range compared with standard care (weighted mean difference, WMD 4.4%, 95% CI 1.71 to 7.18, p=0.02). Total health and social care costs over 10 years were pound7324 with standard care and pound7326 with self-monitoring (estimated quality adjusted life year, QALY gain was 0.028). Self-monitoring was found to have approximately 80% probability of being cost-effective compared with standard care applying a ceiling willingness-to-pay threshold of pound20,000 per QALY gained. Within the base case model, applying the pooled relative effect of thromboembolic events, self-management alone was highly cost-effective while self-testing was not. CONCLUSIONS: Self-monitoring appears to be a safe and cost-effective option. TRIAL REGISTRATION NUMBER: PROSPERO CRD42013004944

On the Relativistic Description of the Nucleus

We discuss a relativistic theory of the atomic nuclei in the framework of the hamiltonian formalism and of the mesonic model of the nucleus. Attention is paid to the translational invariance of the theory. Our approach is centered on the concept of spectral amplitude, a function in the Dirac spinor space. We derive a Lorentz covariant equation for the latter, which requires as an input the baryon self-energy. For this we either postulate the most general Lorentz-Poincar\'e invariant expression or perform a calculation via a Bethe-Salpeter equation starting from a nucleon-nucleus interaction. We discuss the features of the nuclear spectrum obtained in the first instance. Finally the general constraints the self-energy should satisfy because of analyticity and Poincar\'e covariance are discussed

Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic.

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental autoimmune encephalomyelitis, guanabenz alleviates clinical symptoms, which correlates with increased oligodendrocyte survival and diminished CNS CD4+ T cell accumulation. Moreover, guanabenz ameliorates relapse in relapsing-remitting experimental autoimmune encephalomyelitis. Our results provide support for a MS therapy that enhances the integrated stress response to protect oligodendrocytes against the inflammatory CNS environment

Effects of Short Range Correlations on Ca Isotopes

The effect of Short Range Correlations (SRC) on Ca isotopes is studied using a simple phenomenological model. Theoretical expressions for the charge (proton) form factors, densities and moments of Ca nuclei are derived. The role of SRC in reproducing the empirical data for the charge density differences is examined. Their influence on the depletion of the nuclear Fermi surface is studied and the fractional occupation probabilities of the shell model orbits of Ca nuclei are calculated. The variation of SRC as function of the mass number is also discussed.Comment: 11 pages (RevTex), 6 Postscript figures available upon request at [email protected] Physical Review C in prin

Role of the Nuclear and Electromagnetic Interactions in the Coherent Dissociation of the Relativistic 7^7Li Nucleus into the 3^3H + 4^4He Channel

The differential cross section in the transverse momentum $Q$ and a total cross section of $(31\pm4)$ mb for the coherent dissociation of a 3-A-GeV/$c$ $^7$Li nucleus through the $^3$H$+^4$He channel have been measured on emulsion nuclei. The observed $Q$ dependence of the cross section is explained by the predominant supposition of the nuclear diffraction patterns on light (C, N, O) and heavy (Br, Ag) emulsion nuclei. The contributions to the cross section from nuclear diffraction ($Q\le400$ MeV/$c$) and Coulomb $(Q\le50$ MeV/$c$) dissociations are calculated to be 40.7 and 4 mb, respectively.Comment: ISSN 0021-3640, Pleiades Publishing, Ltd., 200

Microscopic theories of neutrino-^{12}C reactions

In view of the recent experiments on neutrino oscillations performed by the LSND and KARMEN collaborations as well as of future experiments, we present new theoretical results of the flux averaged $^{12}C(\nu_e,e^-)^{12}N$ and $^{12}C(\nu_{\mu},{\mu}^-)^{12}N$ cross sections. The approaches used are charge-exchange RPA, charge-exchange RPA among quasi-particles (QRPA) and the Shell Model. With a large-scale shell model calculation the exclusive cross sections are in nice agreement with the experimental values for both reactions. The inclusive cross section for $\nu_{\mu}$ coming from the decay-in-flight of $\pi^+$ is $15.2 \times 10^{-40} cm^2$ to be compared to the experimental value of $12.4 \pm 0.3 \pm 1.8 \times 10^{-40} cm^2$, while the one due to $\nu_{e}$ coming from the decay-at-rest of $\mu^+$ is $16.4 \times 10^{-42} cm^2$ which agrees within experimental error bars with the measured values. The shell model prediction for the decay-in-flight neutrino cross section is reduced compared to the RPA one. This is mainly due to the different kind of correlations taken into account in the calculation of the spin modes and partially due to the shell-model configuration basis which is not large enough, as we show using arguments based on sum-rules.Comment: 17 pages, latex, 5 figure

Innovations and policy design for development for cross-value chain services (logistics and financial services)

WP3 intends to address the question: How can cross-food value chain and market services function better to increase employment and boost income of smallholders and SMEs? The WP focuses on two types of cross-value chain services, logistics and financial services. (1) logistics services – supply chain management, transportation, traceability, digital platforms for e-com merce, and (cold) storage. (2) value-chain financial services – mainly focusing on digital financial services (DFS) that facilitate trans actions, savings, access to and use of credit, and insurance. The logistics services in agri-food systems in low- and middle-income countries (LMICs) are often targeted at large-scale enterprises with greater market power and less accessible to smallholder farmers and small and micro enterprises (SMEs). WP3 aims to assess the ways in which these emerging logistics services (including digital platforms) can be cost-effectively targeted at smallholder farmers and agri-food SMEs. Regarding DFS, the WP will investigate cost-effective ways of improving access to and adoption of DFS among smallholders and agri-food SMEs, especially among women and youth. Though these emerging DFS appear to have a high potential to benefit smallholders and SMEs across the agri-food value chains in LMICs, they need a reliable internet connection, a suitable mobile phone network, and a broad network of mobile money agents to be effective. WP3 thus aims to identify innovations/emerging logistics and DFS and test their effectiveness to smallholders and SMEs using randomized control trials (RCTs) in pilots, with the goal of country-specific scalable designs

Estimating the Capacity for ART Provision in Tanzania with the Use of Data on Staff Productivity and Patient Losses

BACKGROUND: International targets for access to antiretroviral therapy (ART) have over-estimated the capacity of health systems in low-income countries in Sub-Saharan Africa. The WHO target for number on treatment by end 2005 for Tanzania was 10 times higher than actually achieved. The target of the national Care and Treatment Plan (CTP) was also not reached. We aimed at estimating the capacity for ART provision and created five scenarios for ART production given existing resource limitations. METHODS: A situation analysis including scrutiny of staff factors, such as available data on staff and patient factors including access to ART and patient losses, made us conclude that the lack of clinical staff is the main limiting factor for ART scale-up, assuming that sufficient drugs and supplies are provided by donors. We created a simple formula to estimate the number of patients on ART based on availability and productivity of clinical staff, time needed to initiate vs maintain a patient on ART and patient losses using five different scenarios with varying levels of these parameters. FINDINGS: Our scenario assuming medium productivity (40% higher than that observed in 2002) and medium loss of patients (20% in addition to 15% first-year mortality) coincides with the actual reported number of patients initiated on ART up to 2008, but is considerably below the national CTP target of 90% coverage for 2009, corresponding to 420,000 on ART and 710,000 life-years saved (LY's). Our analysis suggests that a coverage of 40% or 175,000 on treatment and 350,000 LY's saved is more achievable. CONCLUSION: A comparison of our scenario estimations and actual output 2006-2008 indicates that a simple user-friendly dynamic model can estimate the capacity for ART scale-up in resource-poor settings based on identification of a limiting staff factor and information on availability of this staff and patient losses. Thus, it is possible to set more achievable targets