MODELLING GLOBAL DEMOGRAPHIC CHANGE:RESULTS FOR JAPAN

In earlier papers (McKibbin and Nguyen (2001, (2002)) we introduced demographic features into the MSG3 model of the world economy, following the approach of Bryant and McKibbin (2001). In this paper we use the same theoretical technique to develop a series of models based on a consistent database from a simple two country symmetric theoretical model to the complete 4 country MSG3 model, which represents the empirical characteristics of Japan, United States, Rest of OECD and Rest of World. We explore a stylized decline in fertility similar to that experienced by Japan since the 1950 (exactly the same shock as the stylized shock used in Bryant (2004)). We first explore the properties of the theoretical model with both a global and a single country shock. This gives similar results to that found in the basic framework underlying the Bryant (2004) approach. We then move from the simplest fully optimizing framework to increasing add complexity to the model until we build a model of Japan. We explore the same shock across the models of increasing complexity in this paper and compare our results to the Bryant approach. We find that although the basic insights from the sequences of theoretical papers in the Brooking-ANU project continue to hold, the quantitative results change significantly as the model is adapted to have more characteristics of Japan. In a final section, we use the complete model to explore the likely impacts on Japan of the demographic change already experienced from 1970 and look to the likely changes to be experienced out to 2040.

Lovastatin for adult patients with dengue: protocol for a randomised controlled trial.

BACKGROUND: Dengue is the most important vector-borne viral infection of man, with approximately 2 billion people living in areas at risk. Infection results in a range of manifestations from asymptomatic infection through to life-threatening shock and haemorrhage. One of the hallmarks of severe dengue is vascular endothelial disruption. There is currently no specific therapy and clinical management is limited to supportive care. Statins are a class of drug initially developed for lipid lowering. There has been considerable recent interest in their effects beyond lipid lowering. These include anti-inflammatory effects at the endothelium. In addition, it is possible that lovastatin may have an anti-viral effect against dengue. Observational data suggest that the use of statins may improve outcomes for such conditions as sepsis and pneumonia. This paper describes the protocol for a randomised controlled trial investigating a short course of lovastatin therapy in adult patients with dengue. METHODS/DESIGN: A randomised, double-blind, placebo-controlled trial will investigate the effects of lovastatin therapy in the treatment of dengue. The trial will be conducted in two phases with an escalation of dose between phases if an interim safety review is satisfactory. This is an exploratory study focusing on safety and there are no data on which to base a sample size calculation. A target sample size of 300 patients in the second phase, enrolled over two dengue seasons, was chosen based on clinical judgement and feasibility considerations. In a previous randomised trial in dengue, about 10% and 30% of patients experienced at least one serious adverse event or adverse event, respectively. With 300 patients, we will have 80% power to detect an increase of 12% (from 10% to 22%) or 16% (from 30% to 46%) in the frequency of adverse events. Furthermore, this sample size ensures some power to explore the efficacy of statins. DISCUSSION: The development of a dengue therapeutic that can attenuate disease would be an enormous advance in global health. The favourable effects of statins on the endothelium, their good safety profile and their low cost make lovastatin an attractive therapeutic candidate. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN03147572

A Dense Gas Trigger for OH Megamasers

HCN and CO line diagnostics provide new insight into the OH megamaser (OHM) phenomenon, suggesting a dense gas trigger for OHMs. We identify three physical properties that differentiate OHM hosts from other starburst galaxies: (1) OHMs have the highest mean molecular gas densities among starburst galaxies; nearly all OHM hosts have = 10^3-10^4 cm^-3 (OH line-emitting clouds likely have n(H2) > 10^4 cm^-3). (2) OHM hosts are a distinct population in the nonlinear part of the IR-CO relation. (3) OHM hosts have exceptionally high dense molecular gas fractions, L(HCN)/L(CO)>0.07, and comprise roughly half of this unusual population. OH absorbers and kilomasers generally follow the linear IR-CO relation and are uniformly distributed in dense gas fraction and L(HCN), demonstrating that OHMs are independent of OH abundance. The fraction of non-OHMs with high mean densities and high dense gas fractions constrains beaming to be a minor effect: OHM emission solid angle must exceed 2 pi steradians. Contrary to conventional wisdom, IR luminosity does not dictate OHM formation; both star formation and OHM activity are consequences of tidal density enhancements accompanying galaxy interactions. The OHM fraction in starbursts is likely due to the fraction of mergers experiencing a temporal spike in tidally driven density enhancement. OHMs are thus signposts marking the most intense, compact, and unusual modes of star formation in the local universe. Future high redshift OHM surveys can now be interpreted in a star formation and galaxy evolution context, indicating both the merging rate of galaxies and the burst contribution to star formation.Comment: 5 pages, 3 figures, 1 table, accepted by ApJ Letter

A dose-ranging, parallel group, split-face, single-blind phase II study of light emitting diode-red light (LED-RL) for skin scarring prevention: study protocol for a randomized controlled trial.

BackgroundSkin fibrosis is a significant global health problem that affects over 100 million people annually and has a profoundly negative impact on quality of life. Characterized by excessive fibroblast proliferation and collagen deposition, skin fibrosis underlies a wide spectrum of dermatologic conditions ranging from pathologic scars secondary to injury (e.g., burns, surgery, trauma) to immune-mediated diseases. Effective anti-scarring therapeutics remain an unmet need, underscoring the importance of developing novel approaches to treat and prevent skin fibrosis. Our in vitro data show that light emitting diode-red light (LED-RL) can modulate key cellular and molecular processes involved in skin fibrosis. In two phase I clinical trials (STARS 1 and STARS 2), we demonstrated the safety and tolerability of LED-RL at fluences of 160 J/cm2 up to 480 J/cm2 on normal human skin.Methods/designCURES (Cutaneous Understanding of Red-light Efficacy on Scarring) is a dose-ranging, randomized, parallel group, split-face, single-blind, mock-controlled phase II study to evaluate the efficacy of LED-RL to limit post-surgical skin fibrosis in subjects undergoing elective mini-facelift surgery. Thirty subjects will be randomly allocated to three treatment groups to receive LED-RL phototherapy or temperature-matched mock irradiation (control) to either periauricular incision site at fluences of 160 J/cm2, 320 J/cm2, or 480 J/cm2. Starting one week post-surgery (postoperative days 4-8), treatments will be administered three times weekly for three consecutive weeks, followed by efficacy assessments at 30 days, 3 months, and 6 months. The primary endpoint is the difference in scar pliability between LED-RL-treated and control sites as determined by skin elasticity and induration measurements. Secondary outcomes include clinical and photographic evaluations of scars, 3D skin imaging analysis, histological and molecular analyses, and adverse events.DiscussionLED-RL is a therapeutic modality of increasing importance in dermatology, and has the potential to limit skin fibrosis clinically by decreasing dermal fibroblast activity and collagen production. The administration of LED-RL phototherapy in the early postoperative period may optimize wound healing and prevent excessive scarring. The results from this study may change the current treatment paradigm for fibrotic skin diseases and help to pioneer LED-RL as a safe, non-invasive, cost-effective, portable, at-home therapy for scars.Trial registrationClinicalTrials.gov, NCT03795116 . Registered on 20 December 2018

Prospective evaluation of GeneXpert for the diagnosis of HIV- negative pediatric TB cases

Background The GeneXpertMTB/RIF (Xpert) assay is now recommended by WHO for diagnosis of tuberculosis (TB) in children but evaluation data is limited. Methods One hundred and fifty consecutive HIV negative children (<15 years of age) presenting with suspected TB were enrolled at a TB referral hospital in Ho Chi Minh City, Vietnam. 302 samples including sputum (n = 79), gastric fluid (n = 215), CSF (n = 3), pleural fluid (n = 4) and cervical lymphadenopathic pus (n = 1) were tested by smear, automated liquid culture (Bactec MGIT) and Xpert. Patients were classified retrospectively using the standardised case definition into confirmed, probable, possible, TB unlikely or not TB categories. Test accuracy was evaluated against 2 gold standards: [1] clinical (confirmed, probable and possible TB) and [2] ‘confirmed TB’ alone. Results The median age of participants was 18 months [IQR 5–170]. When test results were aggregated by patient, the sensitivity of smear, Xpert and MGIT against clinical diagnosis as the gold standard were 9.2% (n = 12/131) [95%CI 4.2; 14.1], 20.6% (n = 27/131) [95%CI 13.7; 27.5] and 29.0% (n = 38/131) [21.2;36.8], respectively. Specificity 100% (n = 19/19), 94.7% (n = 18/19), 94.7% (n = 18/19), respectively. Xpert was more sensitive than smear (P = <0.001) and less sensitive than MGIT (P = 0.002). Conclusions The systematic use of Xpert will increase early TB case confirmation in children and represents a major advance but sensitivity of all tests remains unacceptably low. Improved rapid diagnostic tests and algorithm approaches for pediatric TB are still an urgent research priority