Physical activity and nutrition intervention for Singaporean women aged 50 years and above: study protocol for a randomised controlled trial

The majority of the older Singaporean women aged 50 years and above are physically inactive and have unhealthy dietary habits, placing them at ‘high risk’ of non-communicable diseases (NCDs). The adoption of regular physical activity (PA) and a healthy diet are essential lifestyle behaviours to reduce this risk. This randomised controlled trial (RCT) involves the development, implementation and evaluation of a PA and nutrition programme for community-dwelling Singaporean women who currently attend recreational centres (RCs are public facilities supporting social leisure activities) in their local area. The intervention will be developed after conducting formative evaluation with RC attendees and managers through focus group discussions and pilot testing of resources (i.e. surveys, accelerometers, and health booklets). Programme ambassadors (trained, certified fitness instructors and nutritionists) will deliver all sessions in English and Mandarin; implement classes to meet participants’ varying needs; and conduct sessions at different times at convenient venues. Social Cognitive Theory (SCT) has been selected as the theoretical framework to inform intervention strategies as it explores the interactions of human behaviour with the environment and has been found to be valuable when developing behavioural change interventions particularly in older adults (J Gerontol B Psychol Sci Soc Sci 67B(1):18–26, 2012; Obesity Reviews 15(12):983–95, 2014). Its major construct, self-efficacy, is invaluable in achieving successful behaviour change, such as increasing levels of PA or improving dietary intake (Trials. 2017; https://doi.org/10.1186/s13063-016-1771-9 ; Psychol Health Med 18(6):714–24, 2013)

Anomalous Zero Sound

We show that the anomalous term in the current, recently suggested by Son and Yamamoto, modifies the structure of the zero sound mode in the Fermi liquid in a magnetic field.Comment: 14 pages, 2 figure

Charged Magnetic Brane Solutions in AdS_5 and the fate of the third law of thermodynamics

We construct asymptotically AdS_5 solutions to 5-dimensional Einstein-Maxwell theory with Chern-Simons term which are dual to 4-dimensional gauge theories, including N=4 SYM theory, in the presence of a constant background magnetic field B and a uniform electric charge density \rho. For the solutions corresponding to supersymmetric gauge theories, we find numerically that a small magnetic field causes a drastic decrease in the entropy at low temperatures. The near-horizon AdS_2 \times R^3 geometry of the purely electrically charged brane thus appears to be unstable under the addition of a small magnetic field. Based on this observation, we propose a formulation of the third law of thermodynamics (or Nernst theorem) that can be applied to black holes in the AdS/CFT context. We also find interesting behavior for smaller, non-supersymmetric, values of the Chern-Simons coupling k. For k=1 we exhibit exact solutions corresponding to warped AdS_3 black holes, and show that these can be connected to asymptotically AdS_5 spacetime. For k\leq 1 the entropy appears to go to a finite value at extremality, but the solutions still exhibit a mild singularity at strictly zero temperature. In addition to our numerics, we carry out a complete perturbative analysis valid to order B^2, and find that this corroborates our numerical results insofar as they overlap.Comment: 45 pages v2: added note about subsequent results found in arXiv:1003.130

Semi-Holographic Fermi Liquids

We show that the universal physics of recent holographic non-Fermi liquid models is captured by a semi-holographic description, in which a dynamical boundary field is coupled to a strongly coupled conformal sector having a gravity dual. This allows various generalizations, such as a dynamical exponent and lattice and impurity effects. We examine possible relevant deformations, including multi-trace terms and spin-orbit effects. We discuss the matching onto the UV theory of the earlier work, and an alternate description in which the boundary field is integrated out.Comment: 26 pages, 4 figures; v2: typos corrected and report number adde

Boundary Conditions and Unitarity: the Maxwell-Chern-Simons System in AdS_3/CFT_2

We consider the holography of the Abelian Maxwell-Chern-Simons (MCS) system in Lorentzian three-dimensional asymptotically-AdS spacetimes, and discuss a broad class of boundary conditions consistent with conservation of the symplectic structure. As is well-known, the MCS theory contains a massive sector dual to a vector operator in the boundary theory, and a topological sector consisting of flat connections dual to U(1) chiral currents; the boundary conditions we examine include double-trace deformations in these two sectors, as well as a class of boundary conditions that mix the vector operators with the chiral currents. We carefully study the symplectic product of bulk modes and show that almost all such boundary conditions induce instabilities and/or ghost excitations, consistent with violations of unitarity bounds in the dual theory.Comment: 50+1 pages, 6 figures, PDFLaTeX; v2: added references, corrected typo

Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study.

BACKGROUND: Low-dose analgesic methoxyflurane (Penthrox®) was approved in Europe for emergency relief of moderate to severe pain in conscious adults with trauma in 2015. A comparative post-authorisation safety study (PASS) was conducted to assess the risk of hepatotoxicity and nephrotoxicity with methoxyflurane during routine clinical practice. METHODS: This was a comparative hybrid prospective-retrospective cohort study. The comparative cohorts consisted of adults who were given methoxyflurane (methoxyflurane cohort) or another analgesic (concurrent cohort) routinely used for moderate to severe trauma and associated pain in the emergency setting (ambulance and Emergency Department) in the UK between December 2016 and November 2018. Hepatic and renal events were captured in the ensuing 12 weeks. A blinded clinical adjudication committee assessed events. A historical comparator cohort (non-concurrent cohort) was identified from patients with fractures in the English Hospital Episode Statistics (HES) accident and emergency database from November 2013 and November 2015 (before commercial launch of methoxyflurane). Hepatic and renal events were captured in the ensuing 12 weeks via linkage with the Clinical Practice Research Datalink (CPRD) and HES hospital admissions databases. RESULTS: Overall, 1,236, 1,101 and 45,112 patients were analysed in the methoxyflurane, concurrent and non-concurrent comparator cohorts respectively. There was no significant difference in hepatic events between the methoxyflurane and concurrent cohorts (1.9% vs. 3.0%, P = 0.079) or between the methoxyflurane and non-concurrent cohorts (1.9% vs. 2.5%, P = 0.192). Renal events were significantly less common in the methoxyflurane cohort than in the concurrent cohort (2.3% vs. 5.6%, P < 0.001). For methoxyflurane versus non-concurrent cohort the lower occurrence of renal events (2.3% vs. 3.2%, P = 0.070) was not statistically significant. Multivariable adjustment did not change these associations. CONCLUSIONS: Methoxyflurane administration was not associated with an increased risk of hepatotoxicity or nephrotoxicity compared with other routinely administered analgesics and was associated with a reduced risk of nephrotoxicity compared with other routinely administered analgesics. TRIAL REGISTRATION: Study registered in the EU PAS Register (ENCEPP/SDPP/13040)

Risk factors for acquisition of hepatitis C virus infection: a case series and potential implications for disease surveillance

BACKGROUND: Transmission of hepatitis C vims (HCV) is strongly associated with use of contaminated blood products and injection drugs. Other "non-parental" modes of transmission including sexual activity have been increasingly recognized. We examined risk factors for acquiring HCV in patients who were referred to two tertiary care centers and enrolled in an antiviral therapy protocol. METHODS: Interviews of 148 patients were conducted apart from their physician evaluation using a structured questionnaire covering demographics and risk factors for HCV acquisition. RESULTS: Risk factors (blood products, injection/intranasal drugs, razor blades/ toothbrushes, body/ear piercing, occupational exposure, sexual activity) were identified in 141 (95.3%) of participants; 23 (15.5%) had one (most frequently blood or drug exposure), 41 (27.7%) had two, and 84 (53.4%) had more than two risk factors. No patient reported sexual activity as a sole risk factor. Body piercing accounted for a high number of exposures in women. Men were more likely to have exposure to street drugs but less exposure to blood products than women. Blood product exposure was less common in younger than older HCV patients. CONCLUSION: One and often multiple risk factors could be identified in nearly all HCV-infected patients seen in a referral practice. None named sexual transmission as the sole risk factor. The development of a more complete profile of factors contributing to transmission of HCV infection may assist in clinical and preventive efforts. The recognition of the potential presence of multiple risk factors may have important implications in the approach to HCV surveillance, and particularly the use of hierarchical algorithms in the study of risk factors

Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes

BACKGROUND: Early clinical trials, mostly in the setting of melanoma, have shown that dendritic cells (DCs) expressing tumor antigens induce some immune responses and some clinical responses. A major difficulty is the extension to other tumors, such as breast carcinoma, for which few defined tumor-associated antigens are available. We have demonstrated, using both prostate carcinoma and melanoma as model systems, that DCs loaded with killed allogeneic tumor cell lines can induce CD8(+ )T cells to differentiate into cytotoxic T lymphocytes (CTLs) specific for shared tumor antigens. METHODS: The present study was designed to determine whether DCs would capture killed breast cancer cells and present their antigens to autologous CD4(+ )and CD8(+ )T cells. RESULTS: We show that killed breast cancer cells are captured by immature DCs that, after induced maturation, can efficiently present MHC class I and class II peptides to CD8(+ )and CD4(+ )T lymphocytes. The elicited CTLs are able to kill the target cells without a need for pretreatment with interferon gamma. CTLs can be obtained by culturing the DCs loaded with killed breast cancer cells with unseparated peripheral blood lymphocytes, indicating that the DCs can overcome any potential inhibitory effects of breast cancer cells. CONCLUSION: Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens

Estimating pneumonia deaths of post-neonatal children in countries of low or no death certification in 2008

BACKGROUND: Pneumonia is the leading cause of child deaths globally. The aims of this study were to: a) estimate the number and global distribution of pneumonia deaths for children 1-59 months for 2008 for countries with low (85% coverage of death certification countries was used. For 87 high child-mortality countries pneumonia death estimates were obtained by applying a regression model developed from published and unpublished verbal autopsy data from high child-mortality settings. The total number of 1-59 months pneumonia deaths for the year 2008 for these 122 countries was estimated to be 1.18 M (95% CI 0.77 M-1.80 M), which represented 23.27% (95% CI 17.15%-32.75%) of all 1-59 month child deaths. The country level estimation correlation coefficient between these two methods was 0.40. INTERPRETATION: Although the overall number of post-neonatal pneumonia deaths was similar irrespective to the method of estimation used, the country estimate correlation coefficient was low, and therefore country-specific estimates should be interpreted with caution. Pneumonia remains the leading cause of child deaths and is greatest in regions of poverty and high child-mortality. Despite the concerns about gender inequity linked with childhood mortality we could not estimate sex-specific pneumonia mortality rates due to the inadequate data. Life-saving interventions effective in preventing and treating pneumonia mortality exist but few children in high pneumonia disease burden regions are able to access them. To achieve the United Nations Millennium Development Goal 4 target to reduce child deaths by two-thirds in year 2015 will require the scale-up of access to these effective pneumonia interventions

Insulin receptor substrate adaptor proteins mediate prognostic gene expression profiles in breast cancer

Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer