Epidemiological and Evolutionary Dynamics of Influenza B Viruses in Malaysia, 2012-2014

Epidemiological and evolutionary dynamics of influenza B Victoria and Yamagata lineages remained poorly understood in the tropical Southeast Asia region, despite causing seasonal outbreaks worldwide. From 2012-2014, nasopharyngeal swab samples collected from outpatients experiencing acute upper respiratory tract infection symptoms in Kuala Lumpur, Malaysia, were screened for influenza viruses using a multiplex RT-PCR assay. Among 2,010/3,935 (51.1%) patients infected with at least one respiratory virus, 287 (14.3%) and 183 (9.1%) samples were tested positive for influenza A and B viruses, respectively. Influenza-positive cases correlate significantly with meteorological factors-total amount of rainfall, relative humidity, number of rain days, ground temperature and particulate matter (PM10). Phylogenetic reconstruction of haemagglutinin (HA) gene from 168 influenza B viruses grouped them into Yamagata Clade 3 (65, 38.7%), Yamagata Clade 2 (48, 28.6%) and Victoria Clade 1 (55, 32.7%). With neuraminidase (NA) phylogeny, 30 intra-clade (29 within Yamagata Clade 3, 1 within Victoria Clade 1) and 1 inter-clade (Yamagata Clade 2-HA/Yamagata Clade 3-NA) reassortants were identified. Study of virus temporal dynamics revealed a lineage shift from Victoria to Yamagata (2012-2013), and a clade shift from Yamagata Clade 2 to Clade 3 (2013-2014). Yamagata Clade 3 predominating in 2014 consisted of intra-clade reassortants that were closely related to a recent WHO vaccine candidate strain (B/Phuket/3073/2013), with the reassortment event occurred approximately 2 years ago based on Bayesian molecular clock estimation. Malaysian Victoria Clade 1 viruses carried H274Y substitution in the active site of neuraminidase, which confers resistance to oseltamivir. Statistical analyses on clinical and demographic data showed Yamagata-infected patients were older and more likely to experience headache while Victoria-infected patients were more likely to experience nasal congestion and sore throat. This study describes the evolution of influenza B viruses in Malaysia and highlights the importance of continuous surveillance for better vaccination policy in this region.published_or_final_versio

Forecasting Tunisian type 2 diabetes prevalence to 2027: validation of a simple model.

BACKGROUND: Most projections of type 2 diabetes (T2D) prevalence are simply based on demographic change (i.e. ageing). We developed a model to predict future trends in T2D prevalence in Tunisia, explicitly taking into account trends in major risk factors (obesity and smoking). This could improve assessment of policy options for prevention and health service planning. METHODS: The IMPACT T2D model uses a Markov approach to integrate population, obesity and smoking trends to estimate future T2D prevalence. We developed a model for the Tunisian population from 1997 to 2027, and validated the model outputs by comparing with a subsequent T2D prevalence survey conducted in 2005. RESULTS: The model estimated that the prevalence of T2D among Tunisians aged over 25 years was 12.0% in 1997 (95% confidence intervals 9.6%-14.4%), increasing to 15.1% (12.5%-17.4%) in 2005. Between 1997 and 2005, observed prevalence in men increased from 13.5% to 16.1% and in women from 12.9% to 14.1%. The model forecast for a dramatic rise in prevalence by 2027 (26.6% overall, 28.6% in men and 24.7% in women). However, if obesity prevalence declined by 20% in the 10 years from 2013, and if smoking decreased by 20% over 10 years from 2009, a 3.3% reduction in T2D prevalence could be achieved in 2027 (2.5% in men and 4.1% in women). CONCLUSIONS: This innovative model provides a reasonably close estimate of T2D prevalence for Tunisia over the 1997-2027 period. Diabetes burden is now a significant public health challenge. Our model predicts that this burden will increase significantly in the next two decades. Tackling obesity, smoking and other T2D risk factors thus needs urgent action. Tunisian decision makers have therefore defined two strategies: obesity reduction and tobacco control. Responses will be evaluated in future population surveys

Perfectly Secure Oblivious RAM with Sublinear Bandwidth Overhead

Oblivious RAM (ORAM) has established itself as a fundamental cryptographic building block. Understanding which bandwidth overheads are possible under which assumptions has been the topic of a vast amount of previous works. In this work, we focus on perfectly secure ORAM and we present the first construction with sublinear bandwidth overhead in the worst-case. All prior constructions with perfect security require linear communication overhead in the worst-case and only achieve sublinear bandwidth overheads in the amortized sense. We present a fundamentally new approach for construction ORAM and our results significantly advance our understanding of what is possible with perfect security. Our main construction, Lookahead ORAM, is perfectly secure, has a worst-case bandwidth overhead of $\mathcal{O}(\sqrt{n})$, and a total storage cost of $\mathcal{O}(n)$ on the server-side, where $n$ is the maximum number of stored data elements. In terms of concrete server-side storage costs, our construction has the smallest storage overhead among all perfectly and statistically secure ORAMs and is only a factor 3 worse than the most storage efficient computationally secure ORAM. Assuming a client-side position map, our construction is the first, among all ORAMs with worst-case sublinear overhead, that allows for a $\mathcal{O}(1)$ online bandwidth overhead without server-side computation. Along the way, we construct a conceptually extremely simple statistically secure ORAM with a worst-case bandwidth overhead of $\mathcal{O}(\sqrt{n}\frac{\log{n}}{\log{\log{n}}})$, which may be of independent interest

ES-Cell Derived Hematopoietic Cells Induce Transplantation Tolerance

Background: Bone marrow cells induce stable mixed chimerism under appropriate conditioning of the host, mediating the induction of transplantation tolerance. However, their strong immunogenicity precludes routine use in clinical transplantation due to the need for harsh preconditioning and the requirement for toxic immunosuppression to prevent rejection and graft-versus-host disease. Alternatively, embryonic stem (ES) cells have emerged as a potential source of less immunogenic hematopoietic progenitor cells (HPCs). Up till now, however, it has been difficult to generate stable hematopoietic cells from ES cells. Methodology/Principal Findings: Here, we derived CD45 + HPCs from HOXB4-transduced ES cells and showed that they poorly express MHC antigens. This property allowed their long-term engraftment in sublethally irradiated recipients across MHC barriers without the need for immunosuppressive agents. Although donor cells declined in peripheral blood over 2 months, low level chimerism was maintained in the bone marrow of these mice over 100 days. More importantly, chimeric animals were protected from rejection of donor-type cardiac allografts. Conclusions: Our data show, for the first time, the efficacy of ES-derived CD45 + HPCs to engraft in allogenic recipient

Phasic Phosphorylation of Caldesmon and ERK 1/2 during Contractions in Human Myometrium

Human myometrium develops phasic contractions during labor. Phosphorylation of caldesmon (h-CaD) and extracellular signal-regulated kinase 1/2 (ERK 1/2) has been implicated in development of these contractions, however the phospho-regulation of these proteins is yet to be examined during periods of both contraction and relaxation. We hypothesized that protein phosphorylation events are implicated in the phasic nature of myometrial contractions, and aimed to examine h-CaD and ERK 1/2 phosphorylation in myometrium snap frozen at specific stages, including; (1) prior to onset of contractions, (2) at peak contraction and (3) during relaxation. We aimed to compare h-CaD and ERK 1/2 phosphorylation in vitro against results from in vivo studies that compared not-in-labor (NIL) and laboring (L) myometrium. Comparison of NIL (n = 8) and L (n = 8) myometrium revealed a 2-fold increase in h-CaD phosphorylation (ser-789; P = 0.012) during onset of labor in vivo, and was associated with significantly up-regulated ERK2 expression (P = 0.022), however no change in ERK2 phosphorylation was observed (P = 0.475). During in vitro studies (n = 5), transition from non-contracting tissue to tissue at peak contraction was associated with increased phosphorylation of both h-CaD and ERK 1/2. Furthermore, tissue preserved at relaxation phase exhibited diminished levels of h-CaD and ERK 1/2 phosphorylation compared to tissue preserved at peak contraction, thereby producing a phasic phosphorylation profile for h-CaD and ERK 1/2. h-CaD and ERK 1/2 are phosphorylated during myometrial contractions, however their phospho-regulation is dynamic, in that h-CaD and ERK 1/2 are phosphorylated and dephosphorylated in phase with contraction and relaxation respectively. Comparisons of NIL and L tissue are at risk of failing to detect these changes, as L samples are not necessarily preserved in the midst of an active contraction

Seasonal effects of influenza on mortality in a subtropical city

<p>Abstract</p> <p>Background</p> <p>Influenza has been associated with a heavy burden of mortality. In tropical or subtropical regions where influenza viruses circulate in the community most of the year, it is possible that there are seasonal variations in the effects of influenza on mortality, because of periodic changes in environment and host factors as well as the frequent emergence of new antigenically drifted virus strains. In this paper we explored this seasonal effect of influenza.</p> <p>Methods</p> <p>A time-varying coefficient Poisson regression model was fitted to the weekly numbers of mortality of Hong Kong from 1996 to 2002. Excess risks associated with influenza were calculated to assess the seasonal effects of influenza.</p> <p>Results</p> <p>We demonstrated that the effects of influenza were higher in winter and late spring/early summer than other seasons. The two-peak pattern of seasonal effects of influenza was found for cardio-respiratory disease and sub-categories pneumonia and influenza, chronic obstructive pulmonary disease, cerebrovascular diseases and ischemic heart disease as well as for all-cause deaths.</p> <p>Conclusion</p> <p>The results provide insight into the possibility that seasonal factors may have impact on virulence of influenza besides their effects on virus transmission. The results warrant further studies into the mechanisms behind the seasonal effect of influenza.</p

A Lower Bound for One-Round Oblivious RAM

We initiate a fine-grained study of the round complexity of Oblivious RAM (ORAM). We prove that any one-round balls-in bins ORAM that does not duplicate balls must have either \Omega(\sqrt{N}) bandwidth or \Omega(\sqrt{N}) client memory, where N is the number of memory slots being simulated. This shows that such schemes are strictly weaker than general (multi-round) ORAMs or those with server computation, and in particular implies that a one-round version of the original square-root ORAM of Goldreich and Ostrovksy (J. ACM 1996) is optimal. We prove this bound via new techniques that differ from those of Goldreich and Ostrovksy, and of Larsen and Nielsen (CRYPTO 2018), which achieved an \Omega(\log N) bound for balls-in-bins and general multi-round ORAMs respectively. Finally we give a weaker extension of our bound that allows for limited duplication of balls, and also show that our bound extends to multiple-round ORAMs of a restricted form that include the best known constructions

Moving research into practice: lessons from the US Agency for Healthcare Research and Quality's IDSRN program

BACKGROUND: The U.S. Agency for Healthcare Research and Quality's (AHRQ) Integrated Delivery Systems Research Network (IDSRN) program was established to foster public-private collaboration between health services researchers and health care delivery systems. Its broad goal was to link researchers and delivery systems to encourage implementation of research into practice. We evaluated the program to address two primary questions: 1) How successful was IDSRN in generating research findings that could be applied in practice? and 2) What factors facilitate or impede such success? METHODS: We conducted in-person and telephone interviews with AHRQ staff and nine IDSRN partner organizations and their collaborators, reviewed program documents, analyzed projects funded through the program, and developed case studies of four IDSRN projects judged promising in supporting research implementation. RESULTS: Participants reported that the IDSRN structure was valuable in creating closer ties between researchers and participating health systems. Of the 50 completed projects studied, 30 had an operational effect or use. Some kinds of projects were more successful than others in influencing operations. If certain conditions were met, a variety of partnership models successfully supported implementation. An internal champion was necessary for partnerships involving researchers based outside the delivery system. Case studies identified several factors important to success: responsiveness of project work to delivery system needs, ongoing funding to support multiple project phases, and development of applied products or tools that helped users see their operational relevance. Factors limiting success included limited project funding, competing demands on potential research users, and failure to reach the appropriate audience. CONCLUSION: Forging stronger partnerships between researchers and delivery systems has the potential to make research more relevant to users, but these benefits require clear goals and appropriate targeting of resources. Trade-offs are inevitable. The health services research community can best consider such trade-offs and set priorities if there is more dialogue to identify areas and approaches where such partnerships may have the most promise. Though it has unique features, the IDSRN experience is relevant to research implementation in diverse settings