Fracture Liaison Service and Its Role in Secondary Fracture Prevention in Malaysia: A Scoping Review

Introduction: Fragility fractures, which occur after a low- trauma injury, increases with advancing age. Such fracture doubles the life-time risk of sustaining another fracture. This risk is highest in the immediate 18 months after the index fracture. However, most patients do not receive the appropriate risk assessment and intervention to reduce this risk. A coordinated model of care termed Fracture Liaison Service (FLS) has been reported to address this treatment gap. Materials and methods: This scoping review aims to explore the potential role and delivery of FLS services in Malaysia. Scientific and non-scientific sources relevant to FLS were identified from electronic bibliographic databases, specialist journals and relevant websites. Findings were categorised into themes and presented narratively. Results: FLS services remain concentrated in the Klang Valley. Even within FLS services, many do not have extensive coverage to risk assess all fracture patients. These services are multidisciplinary in nature where there are links between different departments, such as orthopaedics, osteoporosis expertise, bone densitometry, rehabilitation, falls services and primary care. FLS was able to increase the number of people undergoing fracture risk assessment and treatment. The importance of FLS was highlighted by local experts and stakeholders. Its implementation and delivery are supported by a number of national guidelines. Conclusion: FLS is central to our national efforts to reduce the impending fragility fracture crisis in the coming years. Continued effort is needed to increase coverage within FLS services and across the country. Training, awareness of the problem, research, and policy change will support this endeavour

An initial study of current Malaysian occupational therapy off-road driving assessments

An off-road driving assessment includes a variety of tests. However, in Malaysia, the availability of standardised tools is still lacking. Some standardised driving assessment tools are costly, and the contents are less suitable for Malaysian settings. Therefore, this study aimed to develop a standardised, sensitive to local culture, affordable, and comprehensive pre-driving assessment for occupational therapists in Malaysia. The research design for this study was an explanatory sequential design. The initial draft of the Malaysia Pre-driving Occupational Therapy Assessment (M-POTA) was developed based on the literature review and validated by the ten experts. The initial draft was refined using a focus group discussion of ten expert panels. The recorded data were transcribed verbatim and analysed using thematic analysis and member-checking procedures to refine the items, structures, and scoring of the M-POTA. The second draft of M-POTA then went through the content and face validation process by the six expert panels. The M-POTA 1.0 version was produced from this process. The M-POTA 1.0 version was found to have good content and face validity, S-CVI/Ave= 0.998; S-CVI/UA= 0.986; modified kappa= 0.81 to 1.000). The validated M-POTA 1.0 version is a standardised, local culture-sensitive, and cost-effective off-road driving assessment that is hoped to improve Malaysia’s current driving rehabilitation practice

The Naming Game in Social Networks: Community Formation and Consensus Engineering

We study the dynamics of the Naming Game [Baronchelli et al., (2006) J. Stat. Mech.: Theory Exp. P06014] in empirical social networks. This stylized agent-based model captures essential features of agreement dynamics in a network of autonomous agents, corresponding to the development of shared classification schemes in a network of artificial agents or opinion spreading and social dynamics in social networks. Our study focuses on the impact that communities in the underlying social graphs have on the outcome of the agreement process. We find that networks with strong community structure hinder the system from reaching global agreement; the evolution of the Naming Game in these networks maintains clusters of coexisting opinions indefinitely. Further, we investigate agent-based network strategies to facilitate convergence to global consensus.Comment: The original publication is available at http://www.springerlink.com/content/70370l311m1u0ng3

Lineage Divergence and Historical Gene Flow in the Chinese Horseshoe Bat (Rhinolophus sinicus)

PMCID: PMC3581519This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Genetic studies of hypertrophic cardiomyopathy in Singaporeans identify variants in TNNI3 and TNNT2 that are common in Chinese patients

Background - To assess the genetic architecture of hypertrophic cardiomyopathy (HCM) in patients of predominantly Chinese ancestry. Methods - We sequenced HCM disease genes in Singaporean patients (n=224) and Singaporean controls (n=3,634), compared findings with additional populations and Caucasian HCM cohorts (n=6,179) and performed in vitro functional studies. Results - Singaporean HCM patients had significantly fewer confidently interpreted HCM disease variants (Pathogenic (P)/Likely Pathogenic (LP):18%, p<0.0001) but an excess of variants of unknown significance (exVUS: 24%, p<0.0001), as compared to Caucasians (P/LP: 31%, exVUS: 7%). Two missense variants in thin filament encoding genes were commonly seen in Singaporean HCM (TNNI3:p.R79C, disease allele frequency (AF)=0.018; TNNT2:p.R286H, disease AF=0.022) and are enriched in Singaporean HCM when compared with Asian controls (TNNI3:p.R79C, Singaporean controls AF=0.0055, p=0.0057, gnomAD-East Asian (gnomAD-EA) AF=0.0062, p=0.0086; TNNT2:p.R286H, Singaporean controls AF=0.0017, p<0.0001, gnomAD-EA AF=0.0009, p<0.0001). Both these variants have conflicting annotations in ClinVar and are of low penetrance (TNNI3:p.R79C, 0.7%; TNNT2:p.R286H, 2.7%) but are predicted to be deleterious by computational tools. In population controls, TNNI3:p.R79C carriers had significantly thicker left ventricular walls compared to non-carriers while its etiological fraction is limited (0.70, 95% CI: 0.35-0.86) and thus TNNI3:p.R79C is considered a VUS. Mutant TNNT2:p.R286H iPSC-CMs show hypercontractility, increased metabolic requirements and cellular hypertrophy and the etiological fraction (0.93, 95% CI: 0.83-0.97) support the likely pathogenicity of TNNT2:p.R286H. Conclusions - As compared to Caucasians, Chinese HCM patients commonly have low penetrance risk alleles in TNNT2 or TNNI3 but exhibit few clinically actionable HCM variants overall. This highlights the need for greater study of HCM genetics in non-Caucasian populations

Novel differential linear B-cell epitopes to identify Zika and dengue virus infections in patients

Objectives Recent Zika virus (ZIKV ) outbreaks challenged existing laboratory diagnostic standards, especially for serology‐based methods. Because of the genetic and structural similarity of ZIKV with other flaviviruses, this results in cross‐reactive antibodies, which confounds serological interpretations. Methods Plasma from Singapore ZIKV patients was screened longitudinally for antibody responses and neutralising capacities against ZIKV . Samples from healthy controls, ZIKV patients and DENV patients were further assessed using ZIKV and DENV peptides of precursor membrane (prM), envelope (E) or non‐structural 1 (NS 1) viral proteins in a peptide‐based ELISA for epitope identification. Identified epitopes were re‐validated and diagnostically evaluated using sera of patients with DENV , bacteria or unknown infections from Thailand. Results Long‐lasting ZIKV ‐neutralising antibodies were elicited during ZIKV infection. Thirteen potential linear B‐cell epitopes were identified, and of these, four common flavivirus, three ZIKV ‐specific and one DENV ‐specific differential epitopes had more than 50% sensitivity and specificity. Notably, ZIKV ‐specific peptide 26 on domain I/II of E protein (amino acid residues 271–288) presented 80% sensitivity and 85.7% specificity. Importantly, the differential epitopes also showed significance in differentiating non‐flavivirus patient samples. Conclusion Linear B‐cell epitope candidates to differentiate between ZIKV and DENV infections were identified, providing the first step towards the design of a much‐needed serology‐based assay

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Systematic Identification of Spontaneous Preterm Birth-Associated RNA Transcripts in Maternal Plasma

<div><h3>Background</h3><p>Spontaneous preterm birth (SPB, before 37 gestational weeks) is a major cause of perinatal mortality and morbidity, but its pathogenesis remains unclear. Studies on SPB have been hampered by the limited availability of markers for SPB in predelivery clinical samples that can be easily compared with gestational age-matched normal controls. We hypothesize that SPB involves aberrant placental RNA expression, and that such RNA transcripts can be detected in predelivery maternal plasma samples, which can be compared with gestational age-matched controls.</p> <h3>Principal Findings</h3><p>Using gene expression microarray to profile essentially all human genes, we observed that 426 probe signals were changed by >2.9-fold in the SPB placentas, compared with the spontaneous term birth (STB) placentas. Among the genes represented by those probes, we observed an over-representation of functions in RNA stabilization, extracellular matrix binding, and acute inflammatory response. Using RT-quantitative PCR, we observed differences in the RNA concentrations of certain genes only between the SPB and STB placentas, but not between the STB and term elective cesarean delivery placentas. Notably, 36 RNA transcripts were observed at placental microarray signals higher than a threshold, which indicated the possibility of their detection in maternal plasma. Among them, the <em>IL1RL1</em> mRNA was tested in plasma samples taken from 37 women. It was detected in 6 of 10 (60%) plasma samples collected during the presentation of preterm labor (≤32.9 weeks) in women eventually giving SPB, but was detected in only 1 of 27 (4%) samples collected during matched gestational weeks from women with no preterm labor (Fisher exact test, p = 0.00056).</p> <h3>Conclusion</h3><p>We have identified 36 SPB-associated RNA transcripts, which are possibly detectable in maternal plasma. We have illustrated that the <em>IL1RL1</em> mRNA was more frequently detected in predelivery maternal plasma samples collected from women resulting in SPB than the gestational-age matched controls.</p> </div

A miRNA Signature of Prion Induced Neurodegeneration

MicroRNAs (miRNAs) are small, non-coding RNA molecules which are emerging as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. We used microarrays and RT-PCR to profile miRNA expression changes in the brains of mice infected with mouse-adapted scrapie. We determined 15 miRNAs were de-regulated during the disease processes; miR-342-3p, miR-320, let-7b, miR-328, miR-128, miR-139-5p and miR-146a were over 2.5 fold up-regulated and miR-338-3p and miR-337-3p over 2.5 fold down-regulated. Only one of these miRNAs, miR-128, has previously been shown to be de-regulated in neurodegenerative disease. De-regulation of a unique subset of miRNAs suggests a conserved, disease-specific pattern of differentially expressed miRNAs is associated with prion–induced neurodegeneration. Computational analysis predicted numerous potential gene targets of these miRNAs, including 119 genes previously determined to be also de-regulated in mouse scrapie. We used a co-ordinated approach to integrate miRNA and mRNA profiling, bioinformatic predictions and biochemical validation to determine miRNA regulated processes and genes potentially involved in disease progression. In particular, a correlation between miRNA expression and putative gene targets involved in intracellular protein-degradation pathways and signaling pathways related to cell death, synapse function and neurogenesis was identified