114 research outputs found

    Kajian Keprihatinan Ahli Akademik Terhadap Tatacara Berpakaian, Sahsiah dan Rupa Diri Pelajar Universiti Malaysia Pahang

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    Tamadun adalah perkataan Arab “Maddana” yang bermaksud adab, akhlaq, moral dan mempunyai agama yang baik. Manakala hidup bertamadun bermaksud kehidupan yang penuh dengan adab sopan, moral dan berakhlak. Dalam konteks dunia pendidikan hari ini isu tatacara berpakaian, rupa diri, sahsiah dan akhlak pelajar pernah dibincangkan dan diketengahkan di peringkat institusi pengajian tinggi amnya, namun masih tidak menampakkan hasil positif. Kelihatan seolah-olah tiada keseriusan daripada pelbagai pihak untuk mengendalikan dan menjayakan isu ini sebaik mungkin sehingga ke akar umbinya dan secara tidak langsung untuk berusaha menyelesaikannya. Justeru, satu kajian berfokus telah dijalankan terhadap pelajar di Universiti Malaysia Pahang dari pelbagai fakulti. Kajian ini bertujuan meninjau sejauh mana komitmen pensyarah selaku aset penting yang berintegriti tinggi, bernilai dan berakhlak mulia dalam menjalankan amanah mereka mendidik anak bangsa khususnya dalam membangunkan akhlak dan sahsiah diri terpuji dalam kalangan mahasiswa. Kajian ini dilakukan secara tinjauan melalui aplikasi internet iaitu SurveyMonkey kepada lebih dari 100 orang pelajar. Melalui kajian ini terdapat enam perkara yang diperhatikan dan dikaji secara terperinci. Kajian ini berkisar komitmen pelajar dan pensyarah di kampus antaranya ialah komitmen pelajar terhadap pemakaian kad pelajar universiti (kad matrik), komitmen pensyarah memperuntukkan masa dalam kelas bagi menyatakan kepentingan tatacara berpakaian dan rupa diri di kampus, komitmen mengambil tindakan terhadap pelajar yang gagal mematuhi peraturan tatacara berpakaian dan rupa diri, komitmen mengambil tindakan terhadap pelajar yang lewat atau gagal hadir dalam kelas, dan amanah dalam mengisi ruang di slip kehadiran rakan sekuliah dalam kelas. Hasil kajian mendapati bahawa komitmen di kalangan pelajar dan pensyarah kurang memberangsangkan. Perkara ini harus dipandang serius dan sangat membimbangkan kerana penekanan terhadap isu-isu tersebut sangat penting dalam melahirkan pelajar bertamadun iaitu berpengetahuan luas, berkemahiran tinggi dan bersikap, berakhlak serta bersahsiah terpuji

    A Versatile Method for Viral Transfection of Calcium Indicators in the Neonatal Mouse Brain

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    The first three postnatal weeks in rodents are a time when sensory experience drives the maturation of brain circuits, an important process that is not yet well understood. Alterations in this critical period of experience-dependent circuit assembly and plasticity contribute to several neurodevelopmental disorders, such as autism, epilepsy, and schizophrenia. Therefore, techniques for recording network activity and tracing neuronal connectivity over this time period are necessary for delineating circuit refinement in typical development and how it deviates in disease. Calcium imaging with GCaMP6 and other genetically encoded indicators is rapidly becoming the preferred method for recording network activity at the single-synapse and single-cell level in vivo, especially in genetically identified neuronal populations. We describe a protocol for intracortical injection of recombinant adeno-associated viruses in P1 neonatal mice and demonstrate its use for longitudinal imaging of GCaMP6s in the same neurons over several weeks to characterize the developmental desynchronization of cortical network activity. Our approach is ideally suited for chronic in vivo two-photon calcium imaging of neuronal activity from synapses to entire networks during the early postnatal period

    Tactile defensiveness and impaired adaptation of neuronal activity in the Fmr1 knockout mouse model of autism

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    Sensory hypersensitivity is a common symptom in autism spectrum disorders (ASDs), including Fragile X Syndrome (FXS), and frequently leads to tactile defensiveness. In mouse models of ASDs, there is mounting evidence of neuronal and circuit hyperexcitability in several brain regions, which could contribute to sensory hypersensitivity. However, it is not yet known whether or how sensory stimulation might trigger abnormal sensory processing at the circuit level or abnormal behavioral responses in ASD mouse models, especially during an early developmental time when experience-dependent plasticity shapes such circuits. Using a novel assay, we discovered exaggerated motor responses to whisker stimulation in young Fmr1 knockout (KO) mice (postnatal days (P) 14-16), a model of FXS. Adult Fmr1 KO mice actively avoided a stimulus that was innocuous to wild-type controls, a sign of tactile defensiveness. Using in vivo two-photon calcium imaging of Layer 2/3 barrel cortex neurons expressing GCaMP6s, we found no differences between wild-type and Fmr1 KO mice in overall whisker-evoked activity, though 45% fewer neurons in young Fmr1 KO mice responded in a time-locked manner. Notably, we identified a pronounced deficit in neuronal adaptation to repetitive whisker stimulation in both young and adult Fmr1 KO mice. Thus, impaired adaptation in cortical sensory circuits is a potential cause of tactile defensiveness in autism

    Simplified HIV Testing and Treatment in China: Analysis of Mortality Rates Before and After a Structural Intervention.

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    BackgroundMultistage stepwise HIV testing and treatment initiation procedures can result in lost opportunities to provide timely antiretroviral therapy (ART). Incomplete patient engagement along the continuum of HIV care translates into high levels of preventable mortality. We aimed to evaluate the ability of a simplified test and treat structural intervention to reduce mortality.Methods and findingsIn the "pre-intervention 2010" (from January 2010 to December 2010) and "pre-intervention 2011" (from January 2011 to December 2011) phases, patients who screened HIV-positive at health care facilities in Zhongshan and Pubei counties in Guangxi, China, followed the standard-of-care process. In the "post-intervention 2012" (from July 2012 to June 2013) and "post-intervention 2013" (from July 2013 to June 2014) phases, patients who screened HIV-positive at the same facilities were offered a simplified test and treat intervention, i.e., concurrent HIV confirmatory and CD4 testing and immediate initiation of ART, irrespective of CD4 count. Participants were followed for 6-18 mo until the end of their study phase period. Mortality rates in the pre-intervention and post-intervention phases were compared for all HIV cases and for treatment-eligible HIV cases. A total of 1,034 HIV-positive participants (281 and 339 in the two pre-intervention phases respectively, and 215 and 199 in the two post-intervention phases respectively) were enrolled. Following the structural intervention, receipt of baseline CD4 testing within 30 d of HIV confirmation increased from 67%/61% (pre-intervention 2010/pre-intervention 2011) to 98%/97% (post-intervention 2012/post-intervention 2013) (all p < 0.001 [i.e., for all comparisons between a pre- and post-intervention phase]), and the time from HIV confirmation to ART initiation decreased from 53 d (interquartile range [IQR] 27-141)/43 d (IQR 15-113) to 5 d (IQR 2-12)/5 d (IQR 2-13) (all p < 0.001). Initiation of ART increased from 27%/49% to 91%/89% among all cases (all p < 0.001) and from 39%/62% to 94%/90% among individuals with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). Mortality decreased from 27%/27% to 10%/10% for all cases (all p < 0.001) and from 40%/35% to 13%/13% for cases with CD4 count ≤ 350 cells/mm3 or AIDS (all p < 0.001). The simplified test and treat intervention was significantly associated with decreased mortality rates compared to pre-intervention 2011 (adjusted hazard ratio [aHR] 0.385 [95% CI 0.239-0.620] and 0.380 [95% CI 0.233-0.618] for the two post-intervention phases, respectively, for all newly diagnosed HIV cases [both p < 0.001], and aHR 0.369 [95% CI 0.226-0.603] and 0.361 [95% CI 0.221-0.590] for newly diagnosed treatment-eligible HIV cases [both p < 0.001]). The unit cost of an additional patient receiving ART attributable to the intervention was US83.80.TheunitcostofadeathpreventedbecauseoftheinterventionwasUS83.80. The unit cost of a death prevented because of the intervention was US234.52.ConclusionsOur results demonstrate that the simplified HIV test and treat intervention promoted successful engagement in care and was associated with a 62% reduction in mortality. Our findings support the implementation of integrated HIV testing and immediate access to ART irrespective of CD4 count, in order to optimize the impact of ART

    EZcalcium: Open-Source Toolbox for Analysis of Calcium Imaging Data

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    Fluorescence calcium imaging using a range of microscopy approaches, such as two-photon excitation or head-mounted “miniscopes,” is one of the preferred methods to record neuronal activity and glial signals in various experimental settings, including acute brain slices, brain organoids, and behaving animals. Because changes in the fluorescence intensity of genetically encoded or chemical calcium indicators correlate with action potential firing in neurons, data analysis is based on inferring such spiking from changes in pixel intensity values across time within different regions of interest. However, the algorithms necessary to extract biologically relevant information from these fluorescent signals are complex and require significant expertise in programming to develop robust analysis pipelines. For decades, the only way to perform these analyses was for individual laboratories to write their custom code. These routines were typically not well annotated and lacked intuitive graphical user interfaces (GUIs), which made it difficult for scientists in other laboratories to adopt them. Although the panorama is changing with recent tools like CaImAn, Suite2P, and others, there is still a barrier for many laboratories to adopt these packages, especially for potential users without sophisticated programming skills. As two-photon microscopes are becoming increasingly affordable, the bottleneck is no longer the hardware, but the software used to analyze the calcium data optimally and consistently across different groups. We addressed this unmet need by incorporating recent software solutions, namely NoRMCorre and CaImAn, for motion correction, segmentation, signal extraction, and deconvolution of calcium imaging data into an open-source, easy to use, GUI-based, intuitive and automated data analysis software package, which we named EZcalcium

    Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

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    Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

    Privacy-Preserving Release of Spatio-temporal Density

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    International audienceIn today’s digital society, increasing amounts of contextually rich spatio-temporal information are collected and used, e.g., for knowledge-based decision making, research purposes, optimizing operational phases of city management, planning infrastructure networks, or developing timetables for public transportation with an increasingly autonomous vehicle fleet. At the same time, however, publishing or sharing spatio-temporal data, even in aggregated form, is not always viable owing to the danger of violating individuals’ privacy, along with the related legal and ethical repercussions. In this chapter, we review some fundamental approaches for anonymizing and releasing spatio-temporal density, i.e., the number of individuals visiting a given set of locations as a function of time. These approaches follow different privacy models providing different privacy guarantees as well as accuracy of the released anonymized data. We demonstrate some sanitization (anonymization) techniques with provable privacy guarantees by releasing the spatio-temporal density of Paris, in France. We conclude that, in order to achieve meaningful accuracy, the sanitization process has to be carefully customized to the application and public characteristics of the spatio-temporal data

    Allelic spectrum of the natural variation in CRP

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    With the recent completion of the International HapMap Project, many tools are in hand for genetic association studies seeking to test the common variant/common disease hypothesis. In contrast, very few tools and resources are in place for genotype–phenotype studies hypothesizing that rare variation has a large impact on the phenotype of interest. To create these tools for rare variant/common disease studies, much interest is being generated towards investing in re-sequencing either large sample sizes of random chromosomes or smaller sample sizes of patients with extreme phenotypes. As a case study for rare variant discovery in random chromosomes, we have re-sequenced ~1,000 chromosomes representing diverse populations for the gene C-reactive protein (CRP). CRP is an important gene in the fields of cardiovascular and inflammation genetics, and its size (~2 kb) makes it particularly amenable medical or deep re-sequencing. With these data, we explore several issues related to the present-day candidate gene association study including the benefits of complete SNP discovery, the effects of tagSNP selection across diverse populations, and completeness of dbSNP for CRP. Also, we show that while deep re-sequencing uncovers potentially medically relevant coding SNPs, these SNPs are fleetingly rare when genotyped in a population-based survey of 7,000 Americans (NHANES III). Collectively, these data suggest that several different types re-sequencing and genotyping approaches may be required to fully understand the complete spectrum of alleles that impact human phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at http://dx.doi.org/10.1007/s00439-006-0160-y and is accessible for authorized users

    Local Inflammation Induces Complement Crosstalk Which Amplifies the Antimicrobial Response

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    By eliciting inflammatory responses, the human immunosurveillance system notably combats invading pathogens, during which acute phase proteins (CRP and cytokines) are elevated markedly. However, the Pseudomonas aeruginosa is a persistent opportunistic pathogen prevalent at the site of local inflammation, and its acquisition of multiple antibiotic-resistance factors poses grave challenges to patient healthcare management. Using blood samples from infected patients, we demonstrate that P. aeruginosa is effectively killed in the plasma under defined local infection-inflammation condition, where slight acidosis and reduced calcium levels (pH 6.5, 2 mM calcium) typically prevail. We showed that this powerful antimicrobial activity is provoked by crosstalk between two plasma proteins; CRP∶L-ficolin interaction led to communication between the complement classical and lectin pathways from which two amplification events emerged. Assays for C4 deposition, phagocytosis, and protein competition consistently proved the functional significance of the amplification pathways in boosting complement-mediated antimicrobial activity. The infection-inflammation condition induced a 100-fold increase in CRP∶L-ficolin interaction in a pH- and calcium-sensitive manner. We conclude that the infection-induced local inflammatory conditions trigger a strong interaction between CRP∶L-ficolin, eliciting complement-amplification pathways which are autonomous and which co-exist with and reinforce the classical and lectin pathways. Our findings provide new insights into the host immune response to P. aeruginosa infection under pathological conditions and the potential development of new therapeutic strategies against bacterial infection
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