Direct evidence for thymic function in adult humans.

The understanding of human thymic function and evaluation of its contribution to T cell homeostasis are matters of great importance. Here we report the development of a novel assay to quantitate the frequency and diversity of recent thymic emigrants (RTEs) in the peripheral blood of humans. Such cells were defined by the presence of T cell receptor (TCR) rearrangement deletion circles (DCs), episomal byproducts of TCR-beta V(D)J rearrangement. DCs were detected in T cells in the thymus, cord blood, and adult peripheral blood. In the peripheral blood of adults aged 22 to 76 years, their frequency was highest in the CD4(+)CD45RA(+) CD62L(+) subpopulation of naive T cells. TCR DCs were also observed in other subpopulations of peripheral blood T cells, including those with the CD4(+)CD45RO(-)CD62L(+) and CD4(+)CD45RO(+)CD62L(+) phenotypes. RTEs were observed to have more than one Vbeta rearrangement, suggesting that replenishment of the repertoire in the adult is at least oligoclonal. These results demonstrate that the normal adult thymus continues to contribute, even in older individuals, a diverse set of new T cells to the peripheral circulation

Evaluation of canonical siRNA and Dicer substrate RNA for inhibition of hepatitis C virus genome replication - a comparative study

Hepatitis C virus (HCV) frequently establishes persistent infections in the liver, leading to the development of chronic hepatitis and, potentially, to liver cirrhosis and hepatocellular carcinoma at later stages. The objective of this study was to test the ability of five Dicer substrate siRNAs (DsiRNA) to inhibit HCV replication and to compare these molecules to canonical 21 nt siRNA. DsiRNA molecules were designed to target five distinct regions of the HCV genome - the 5′ UTR and the coding regions for NS3, NS4B, NS5A or NS5B. These molecules were transfected into Huh7.5 cells that stably harboured an HCV subgenomic replicon expressing a firefly luciferase/neoR reporter (SGR-Feo-JFH-1) and were also tested on HCVcc-infected cells. All of the DsiRNAs inhibited HCV replication in both the subgenomic system and HCVcc-infected cells. When DsiRNAs were transfected prior to infection with HCVcc, the inhibition levels reached 99.5%. When directly compared, canonical siRNA and DsiRNA exhibited similar potency of virus inhibition. Furthermore, both types of molecules exhibited similar dynamics of inhibition and frequencies of resistant mutants after 21 days of treatment. Thus, DsiRNA molecules are as potent as 21 nt siRNAs for the inhibition of HCV replication and may provide future approaches for HCV therapy if the emergence of resistant mutants can be addressed

Determination of thermal conductivity of inhomogeneous orthotropic materials from temperature measurements

We consider the two-dimensional inverse determination of the thermal conductivity of inhomogeneous orthotropic materials from internal temperature measurements. The inverse problem is general and is classified as a function estimation since no prior information about the functional form of the thermal conductivity is assumed in the inverse calculation. The least-squares functional minimizing naturally the gap between the measured and computed temperature leads to a set of direct, sensitivity and adjoint problems, which have forms of direct well-posed initial boundary value problems for the heat equation, and new formulas for its gradients are derived. The conjugate gradient method employs recursively the solution of these problems at each iteration. Stopping the iterations according to the discrepancy principle criterion yields a stable solution. The employment of the Sobolev -gradient is shown to result in much more robust and accurate numerical reconstructions than when the standard -gradient is used

Direct metallisation of polyetherimide substrates by activation with different metals

This article reports the performance of different metallic ions and nanoparticles (Ag, Cu, Ni, Pd, Cr, Co, Au and Fe) used as seed layers, formed by chemical or optical reduction, for the electroless Cu plating of metal tracks onto polyetherimide (PEI). Plated Cu performance was tested by adhesion, electrical conductivity, plating rate, XPS, SEM, XRD and EDX analysis. The application of Cu and Ag seeds resulted in high quality electroless Cu deposits presenting strong adhesion properties and high conductivity ((2.0 ± 0.5) × 107 S/m and (3.6 ± 0.2) × 107 S/m, respectively) compared with bulk copper (5.96 × 107 S/m). Performance is attributed to the high surface density and uniformity of seed layers. Of the metals, only Ag ions were photoreduced under the conditions applied and were subsequently used to electroless Cu plate high quality track features of 150 μm width. The application of sulphuric acid pre-treatment to PEI prior to Ag ion exchange, improved the photoinitiated track formation process, as demonstrated by a threefold increase to both photoinduced Ag nanoparticle density on the surface and electroless Cu plating rate, as well as improved electroless Cu adhesion to PEI

A Rapid Photopatterning Method for Selective Plating of 2D and 3D Microcircuitry on Polyetherimide

In this work, a method for the rapid synthesis of metallic microtracks on polyetherimide is presented. The method relies on the photosynthesis of silver nanoparticles on the surface of the polymer substrates from photosensitive silver chloride (AgCl), which is synthesized directly on the polyetherimide surface. The study reveals that the use of AgCl as a photosensitive intermediate accelerates the reactions leading to the formation of silver nanoparticles by up to two orders of magnitude faster than other photodecomposition schemes. The patterning can be conducted under blue light, with notable advantages over UV exposure. Polymers of significant interest to the microelectronics and 3D printing industries can be directly patterned by light using this photography‐inspired technique at throughputs high enough to be commercially advantageous. Light exposures as short as a few seconds are sufficient to allow the direct metallization of the illuminated polyetherimide surface. The results show that the silver required for the seed layer is minimal, and the later copper electroless plating results in the selective growth of conductive tracks for circuitry on the light‐patterned areas, both on flexible films and 3D printed surfaces

Difficulties faced by older Rohingya (forcibly displaced Myanmar nationals) adults in accessing medical services amid the COVID-19 pandemic in Bangladesh

Background COVID-19 has seriously disrupted health services in many countries including Bangladesh. This research aimed to explore whether Rohingya (forcefully displaced Myanmar nationals) older adults in Bangladesh faced difficulties accessing medicines and routine medical care services amid this pandemic. Methods This cross-sectional study was conducted among 416 Rohingya older adults aged 60 years and above residing in Rohingya refugee camps situated in the Cox's Bazar district of Bangladesh and was conducted in October 2020. A purposive sampling technique was followed, and participants' perceived difficulties in accessing medicines and routine medical care were noted through face-to-face interviews. Binary logistic regression models determined the association between outcome and explanatory variables. Results Overall, one-third of the participants reported difficulties in accessing medicines and routine medical care. Significant factors associated with facing difficulties accessing medicine included feelings of loneliness (adjusted OR (AOR) 3.54, 95% CI 1.93 to 6.48), perceptions that older adults were at the highest risk of COVID-19 (AOR 3.35, 95% CI 1.61 to 6.97) and required additional care during COVID-19 (AOR 6.89, 95% CI 3.62 to 13.13). Also, the notable factors associated with difficulties in receiving routine medical care included living more than 30 min walking distance from the health centre (AOR 3.57, 95% CI 1.95 to 6.56), feelings of loneliness (AOR 2.20, 95% CI 1.25 to 3.87), perception that older adults were at the highest risk of COVID-19 (AOR 2.85, 95% CI 1.36 to 5.99) and perception that they required additional care during the pandemic (AOR 4.55, 95% CI 2.48 to 8.35). Conclusion Many Rohingya older adults faced difficulties in accessing medicines and routine medical care during this pandemic. This call for policy-makers and relevant stakeholders to re-assess emergency preparedness plans including strategies to provide continuing care

Bridging the data gaps in the epidemiology of hepatitis C virus infection in Malaysia using multi-parameter evidence synthesis

BACKGROUND: Collecting adequate information on key epidemiological indicators is a prerequisite to informing a public health response to reduce the impact of hepatitis C virus (HCV) infection in Malaysia. Our goal was to overcome the acute data shortage typical of low/middle income countries using statistical modelling to estimate the national HCV prevalence and the distribution over transmission pathways as of the end of 2009. METHODS: Multi-parameter evidence synthesis methods were applied to combine all available relevant data sources - both direct and indirect - that inform the epidemiological parameters of interest. RESULTS: An estimated 454,000 (95% credible interval [CrI]: 392,000 to 535,000) HCV antibody-positive individuals were living in Malaysia in 2009; this represents 2.5% (95% CrI: 2.2-3.0%) of the population aged 15-64 years. Among males of Malay ethnicity, for 77% (95% CrI: 69-85%) the route of probable transmission was active or a previous history of injecting drugs. The corresponding proportions were smaller for male Chinese and Indian/other ethnic groups (40% and 71%, respectively). The estimated prevalence in females of all ethnicities was 1% (95% CrI: 0.6 to 1.4%); 92% (95% CrI: 88 to 95%) of infections were attributable to non-drug injecting routes of transmission. CONCLUSIONS: The prevalent number of persons living with HCV infection in Malaysia is estimated to be very high. Low/middle income countries often lack a comprehensive evidence base; however, evidence synthesis methods can assist in filling the data gaps required for the development of effective policy to address the future public health and economic burden due to HCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-014-0564-6) contains supplementary material, which is available to authorized users

Awe and Wonder in Scientific Practice: Implications for the Relationship Between Science and Religion

This paper examines the role of awe and wonder in scientific practice. Drawing on evidence from psychological research and the writings of scientists and science communicators, I argue that awe and wonder play a crucial role in scientific discovery. They focus our attention on the natural world, encourage open-mindedness, diminish the self (particularly feelings of self-importance), help to accord value to the objects that are being studied, and provide a mode of understanding in the absence of full knowledge. I will flesh out implications of the role of awe and wonder in scientific discovery for debates on the relationship between science and religion. Abraham Heschel argued that awe and wonder are religious emotions because they reduce our feelings of self-importance, and thereby help to cultivate the proper reverent attitude towards God. Yet metaphysical naturalists such as Richard Dawkins insist that awe and wonder need not lead to any theistic commitments for scientists. The awe some scientists experience can be regarded as a form of non-theistic spirituality, which is neither a reductive naturalism nor theism. I will attempt to resolve the tension between these views by identifying some common ground

Tumor taxonomy for the developmental lineage classification of neoplasms

BACKGROUND: The new "Developmental lineage classification of neoplasms" was described in a prior publication. The classification is simple (the entire hierarchy is described with just 39 classifiers), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. A taxonomy is a list of the instances that populate a classification. The taxonomy of neoplasia attempts to list every known term for every known tumor of man. METHODS: The taxonomy provides each concept with a unique code and groups synonymous terms under the same concept. A Perl script validated successive drafts of the taxonomy ensuring that: 1) each term occurs only once in the taxonomy; 2) each term occurs in only one tumor class; 3) each concept code occurs in one and only one hierarchical position in the classification; and 4) the file containing the classification and taxonomy is a well-formed XML (eXtensible Markup Language) document. RESULTS: The taxonomy currently contains 122,632 different terms encompassing 5,376 neoplasm concepts. Each concept has, on average, 23 synonyms. The taxonomy populates "The developmental lineage classification of neoplasms," and is available as an XML file, currently 9+ Megabytes in length. A representation of the classification/taxonomy listing each term followed by its code, followed by its full ancestry, is available as a flat-file, 19+ Megabytes in length. The taxonomy is the largest nomenclature of neoplasms, with more than twice the number of neoplasm names found in other medical nomenclatures, including the 2004 version of the Unified Medical Language System, the Systematized Nomenclature of Medicine Clinical Terminology, the National Cancer Institute's Thesaurus, and the International Classification of Diseases Oncolology version. CONCLUSIONS: This manuscript describes a comprehensive taxonomy of neoplasia that collects synonymous terms under a unique code number and assigns each tumor to a single class within the tumor hierarchy. The entire classification and taxonomy are available as open access files (in XML and flat-file formats) with this article

Giant pyogenic granuloma of the thigh: a case report

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens