Measuring Economic Disadvantage During Childhood: A Group-Based Modeling Approach

Recent research suggest that child well-being and subsequent status attainment are influenced not only by the overall magnitude of exposure to family economic disadvantage during childhood, but also by the age of exposure and significant changes in family economic circumstances. Unfortunately, traditional measures of children's economic deprivation, such as permanent and transitory income, persistent or cumulative poverty, and the number and length of poverty spells, fail to differentiate between exposure to disadvantage at different stages in childhood and largely ignore how family economic circumstances are changing over time. In this paper, the authors propose a new method for assessing economic disadvantage during childhood that captures both children's overall levels of exposure to economic disadvantage and their patterns of exposure. This new method, which takes advantage of recent advances in finite mixture modeling, uses a longitudinal latent class model to classify children into a limited number of groups with similar histories of exposure to family economic disadvantage. Using this new methodology, group membership can be related to both family background characteristics and achievement in childhood and early adulthood, making it possible both to assess how family characteristics affect patterns of exposure to disadvantage during childhood and directly test alternative theories about the effect of different patterns of exposure on achievement. In this paper, the relationship between background factors, such as race, parental education, and family structure, and group membership is investigated, as is the association between group membership and achievement in early adulthood. The use of this technique is demonstrated using data from the Panel Study of Income Dynamics (PSID)

Let Digons be Bygones: The Fate of Excitons in Curved π-Systems

We explore the diverse origins of unpolarized absorption and emission of molecular polygons consisting of π-conjugated oligomer chains held in a bent geometry by strain controlled at the vertex units. For this purpose, we make use of atomistic nonadiabatic excited-state molecular dynamics simulations of a bichromophore molecular polygon (digon) with bent chromophore chains. Both structural and photoexcited dynamics were found to affect polarization features. Bending strain induces exciton localization on individual chromophore units of the conjugated chains. The latter display different transition dipole moment orientations, a feature not present in the linear oligomer counterparts. In addition, bending makes exciton localization very sensitive to molecular distortions induced by thermal fluctuations. The excited-state dynamics reveals an ultrafast intramolecular energy redistribution that spreads the exciton equally among spatially separated chromophore fragments within the molecular system. As a result, digons become virtually unpolarized absorbers and emitters, in agreement with recent experimental studies on the single-molecule level.Fil: Ondarse Alvarez, Dianelys.Fil: Nelson, Tammie.Fil: Lupton, John M..Fil: Tretiak, Sergei.Fil: Fernandez-Alberti, Sebastian

Analysis of the 5'UTR of HCV genotype 3 grown in vitro in human B cells, T cells, and macrophages

<p>Abstract</p> <p>Background</p> <p>Previously, we have reported the isolation and molecular characterization of human Hepatitis C virus genotype 1 (HCV-1) from infected patients. We are now reporting an analysis of HCV obtained from patients infected with HCV genotype 3 (HCV-3) as diagnosed by clinical laboratories.</p> <p>Results</p> <p>HCV was cultured <it>in vitro </it>using our system. HCV RNA was isolated from patients' blood and from HCV cultured in various cell types for up to three months. The 5'UTR of these isolates were used for comparisons. Results revealed a number of sequence changes as compared to the serum RNA. The HCV RNA produced efficiently by infected macrophages, B-cells, and T-cells had sequences similar to HCV-1, which suggests that selection of the variants was performed at the level of macrophages. Virus with sequences similar to HCV-1 replicated better in macrophages than HCV having a 5'UTR similar to HCV-3.</p> <p>Conclusions</p> <p>Although HCV-3 replicates in cell types such as B-cells, T-cells, and macrophages, it may require a different primary cell type for the same purpose. Therefore, in our opinion, HCV-3 does not replicate efficiently in macrophages, and patients infected with HCV-3 may contain a population of HCV-1 in their blood.</p

Discovery of significant variants containing large deletions in the 5'UTR of human hepatitis C virus (HCV)

We recently reported the isolation and in vitro replication of hepatitis C virus. These isolates were termed CIMM-HCV and analyzed to establish genotypes and subtypes, which are reported elsewhere. During this analysis, an HCV isolated from a patient was discovered that had large deletions in the 5'UTR. 57% of the HCV RNA found in this patient's sera had 113 or 116 bp deletions. Sequence data showed that domains IIIa to IIIc were missing. Previous studies have suggested that these domains may be important for translation. In vitro replicated HCV from this patient did not contain these deletions, however, it contained a 148 bp deletion in the 5'UTR. Whereas the patient HCV lacked domains IIIa through IIIc, the isolate lacked domains IIIa through IIId. HCV from this patient continues to produce large deletions in vitro, suggesting that the deletion may not be important for the assembly or replication of the virus. This is the first report describing these large deletions

Reversible DNA i-motif to hairpin switching induced by copper(II) cations

i-Motif DNA structures have previously been utilised for many different nanotechnological applications, but all have used changes in pH to fold the DNA. Herein we describe how copper(ii) cations can alter the conformation of i-motif DNA into an alternative hairpin structure which is reversible by chelation with EDTA

Analysis of in vitro replicated human hepatitis C virus (HCV) for the determination of genotypes and quasispecies

Isolation and self-replication of infectious HCV has been a difficult task. However, this is needed for the purposes of developing rational drugs and for the analysis of the natural virus. Our recent report of an in vitro system for the isolation of human HCV from infected patients and their replication in tissue culture addresses this challenge. At California Institute of Molecular Medicine several isolates of HCV, called CIMM-HCV, were grown for over three years in cell culture. This is a report of the analysis of CIMM-HCV isolates for subtypes and quasispecies using a 269 bp segment of the 5'UTR. HCV RNA from three patients and eleven CIMM-HCV were analyzed for this purpose. All isolates were essentially identical. Isolates of HCV from one patient were serially transmitted into fresh cells up to eight times and the progeny viruses from each transmission were compared to each other and also to the primary isolates from the patient's serum. Some isolates were also transmitted to different cell types, while others were cultured continuously without retransmission for over three years. We noted minor sequence changes when HCV was cultured for extended periods of time. HCV in T-cells and non-committed lymphoid cells showed a few differences when compared to isolates obtained from immortalized B-cells. These viruses maintained close similarity despite repeated transmissions and passage of time. There were no subtypes or quasispecies noted in CIMM-HCV

Facilitators and barriers to teaching undergraduate medical students in general practice

CONTEXT Globally, primary health care is facing workforce shortages. Longer and higher-quality placements in primary care increase the likelihood of medical students choosing this specialty. However, the recruitment and retention of community primary care teachers are challenging. Relevant research was predominantly carried out in the 1990s. We seek to understand contemporary facilitators and barriers to general practitioner (GP) engagement with undergraduate education. Communities of practice (CoP) theory offers a novel conceptualisation, which may be pertinent in other community-based teaching settings. METHODS Semi-structured interviews were undertaken with 24 GP teachers at four UK medical schools. We purposively sampled GPs new to teaching, established GP teachers and GPs who had recently stopped teaching. We undertook NVivo-assisted deductive and inductive thematic analysis of transcripts. We used CoP theory to interpret data. RESULTS Communities of practice theory illustrated that teachers negotiate membership of three CoPs: (i) clinical practice; (ii) the medical school, and (iii) teaching. The delivery of clinical care and teaching may be integrated or exist in tension. This can depend upon the positioning of the teaching and teacher as central or peripheral to the clinical CoP. Remuneration, workload, space and the expansion of GP trainee numbers impact on this. Teachers did not identify strongly as members of the medical school or a teaching community. Perceptions of membership were affected by medical school communication and support. The findings demonstrate gaps in medical school recruitment. CONCLUSIONS This research demonstrates the marginalisation of primary care-based teaching and proposes a novel explanation rooted in CoP theory. Concepts including identity and membership may be pertinent to other community-based teaching settings. We recommend that medical schools review and broaden recruitment methods. Teacher retention may be improved by optimising the interface between medical schools and teachers, fostering a teaching community, increasing professional rewards for teaching involvement and altering medical school expectations of learning in primary care

Comparison of a point-of-care analyser for the determination of HbA1c with HPLC method

As the use of Point of Care Testing (POCT) devices for measurement of glycated haemoglobin (HbA1c) increases, it is imperative to determine how their performance compares to laboratory methods. This study compared the performance of the automated Quo-Test POCT device (EKF Diagnostics), which uses boronate fluorescence quenching technology, with a laboratory based High Performance Liquid Chromatography (HPLC) method (Biorad D10) for measurement of HbA1c.MethodsWhole blood EDTA samples from subjects (n=100) with and without diabetes were assayed using a BioRad D10 and a Quo-Test analyser. Intra-assay variation was determined by measuring six HbA1c samples in triplicate and inter-assay variation was determined by assaying four samples on 4 days. Stability was determined by assaying three samples stored at −20 °C for 14 and 28 days post collection.ResultsMedian (IQR) HbA1c was 60 (44.0–71.2) mmol/mol (7.6 (6.17–8.66) %) and 62 (45.0–69.0) mmol/mol (7.8 (6.27–8.46) %) for D10 and Quo-Test, respectively, with very good agreement (R2=0.969, P<0.0001). Mean (range) intra- and inter-assay variation was 1.2% (0.0–2.7%) and 1.6% (0.0–2.7%) for the D10 and 3.5% (0.0–6.7%) and 2.7% (0.7–5.1%) for the Quo-Test. Mean change in HbA1c after 28 days storage at −20 °C was −0.7% and +0.3% for D10 and Quo-Test respectively. Compared to the D10, Quo-Test showed 98% agreement for diagnosis of glucose intolerance (IGT and T2DM) and 100% for diagnosis of T2DM.ConclusionGood agreement between the D10 and Quo-Test was seen across a wide HbA1c range. The Quo-Test POCT device provided similar performance to a laboratory based HPLC method

Controlled dehydration of a ruthenium complex-DNA crystal induces reversible DNA kinking

Hydration-dependent DNA deformation has been known since Rosalind Franklin recognised that the relative humidity of the sample had to be maintained to observe a single conformation in DNA fibre diffraction. We now report for the first time the crystal structure, at the atomic level, of a dehydrated form of a DNA duplex and demonstrate the reversible interconversion to the hydrated form at room temperature. This system, containing d(TCGGCGCCGA) in the presence of Λ-[Ru(TAP)2(dppz)]2+ (TAP = 1,4,5,8-tetraazaphenanthrene, dppz = dipyridophenazine), undergoes a partial transition from an A/B hybrid to the A-DNA conformation, at 84-79% relative humidity. This is accompanied by an increase in kink at the central step from 22° to 51°, with a large movement of the terminal bases forming the intercalation site. This transition is reversible on rehydration. Seven datasets, collected from one crystal at room temperature, show the consequences of dehydration at near-atomic resolution. This result highlights that crystals, traditionally thought of as static systems, are still dynamic and therefore can be the subject of further experimentation