α,ω-Dihydroxy telechelic poly(methyl methacrylate) via β-scission (radical addition-fragmentation) chain transfer polymerisation by macromonomer chain transfer agents,as prepared by catalytic chain transfer polymerisation

α,ω-Dihydroxy telechelic poly(methyl methacrylate) has been prepared by β-scission (radical addition-fragmentation) chain transfer polymerisation. Hydroxyethyl methacrylate dimer macromonomer prepared from catalytic chain transfer polymerisation and isolated as a pure compound is shown to be an efficient chain transfer agent. The mode of chain transfer is via β-scission which results in the dimer breaking in half on addition to a propagating poly(methyl methacrylate) radical terminating the polymerisation and providing a hydroxyethyl methacrylate radical which reinitiates polymerisation. A combination of these two events leads to dihydroxy telechelic products, demonstrated to have a functionality of 2.05 by a combination of NMR and size exclusion chromatography (SEC). The chain transfer coefficients of these methacrylic macromonomers is concentration dependant exhibiting a type of “bootstrap” effect. This ultimately leads to a limiting low molecular weight telechelic product by the use of dimeric β-scission chain transfer agents. A combination of high field NMR and matrix assisted laser desorption time-of-flight mass spectrometry has been utilised to demonstrate the structure of the products. The combination of catalytic chain transfer polymerisation and β-scission chain transfer has been demonstrated to be a powerful tool in the controlled polymerisation of methacrylates by radical methodology.     

Direct replication of task‐dependent neural activation patterns during sadness introspection in two independent adolescent samples

Functional neuroimaging results need to replicate to inform sound models of human social cognition and its neural correlates. Introspection, the capacity to reflect on one's thoughts and feelings, is one process required for normative social cognition and emotional functioning. Engaging in introspection draws on a network of brain regions including medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), middle temporal gyri (MTG), and temporoparietal junction (TPJ). Maturation of these regions during adolescence mirrors the behavioral advances seen in adolescent social cognition, but the neural correlates of introspection in adolescence need to replicate to confirm their generalizability and role as a possible mechanism. The current study investigated whether reflecting upon one's own feelings of sadness would activate and replicate similar brain regions in two independent samples of adolescents. Participants included 156 adolescents (50% female) from the California Families Project and 119 adolescent girls from the Pittsburgh Girls Study of Emotion. All participants completed the Emotion Regulation Questionnaire (ERQ) and underwent a functional magnetic resonance imaging scan while completing the same facial emotion‐processing task at age 16–17 years. Both samples showed similar whole‐brain activation patterns when engaged in sadness introspection and when judging a nonemotional facial feature. Whole‐brain activation was unrelated to ERQ scores in both samples. Neural responsivity to task manipulations replicated in regions recruited for socio‐emotional (mPFC, PCC, MTG, TPJ) and attention (dorsolateral PFC, precentral gyri, superior occipital gyrus, superior parietal lobule) processing. These findings demonstrate robust replication of neural engagement during sadness introspection in two independent adolescent samples.     

Infection with live mycobacteria inhibits in vitro detection of Ia antigen on macrophages

Both antigen-specific and non-specific anergy are common features of disseminated mycobacterial infections, and the pathogenesis of such anergy is as yet not fully understood. To date, most studies have focused on the efferent limb of the immune response, and no detailed information is available on the early macrophage-T cell interaction and its consequence on T cell clonal proliferation. To gain information on this crucial phase of mycobacteriosis, we have conducted studies to evaluate the effect of M. kansasii infection on Ia expression induced by T cell-derived lymphokine and have assessed whether such cells can adequately present either mycobacterial or allogeneic antigens to T cells. In vitro infection of mouse resident peritoneal macrophages with live but not heat-killed M. kansasii resulted in a significantly reduced percentage of cells expressing monoclonal antibody detectable Ia antigen following optimal stimulation with crude lymphokine preparations or recombinant mouse gamma interferon. In parallel experiments, macrophages infected with the mycobacteria were co-cultured with syngeneic in vivo M. kansasii sensitized non-adherent, nylon-wool purified lymph node cells, and lymphoproliferation was measured by [3H]thymidine incorporation. It was shown that in co-cultures with macrophages infected with live M. kansasii, the lymphocyte proliferation was marked even in very low infection ratios. In contrast, the response to heat-killed bacilli was dose dependent, reaching peak levels only in high infection ratios. The ability of infected macrophages to present allogeneic antigens was assessed using the mixed leukocyte reaction. Macrophages infected with heat-killed M. kansasii were able to induce a mixed leukocyte reaction similar to uninfected macrophages whereas macrophages infected with live M. kansasii were unable to stimulate allogeneic T cells. These findings may have implications on immunological disturbances often seen in mycobacterial infections, such as leprosy, in which there can be large numbers of non-toxic viable intracellular bacilli.     

Guidelines for genomic array analysis in acquired haematological neoplastic disorders

Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single‐nucleotide polymorphism‐detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented. © 2016 Wiley Periodicals, Inc.     

Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury

Lipoma preferred partner (LPP) localizes to focal adhesions/dense bodies, is selectively expressed in smooth muscle cells (SMC) and enhances cell migration. SMCs cultured on denatured collagen or on a rigid substrate, up regulated expression of LPP, its partner palladin, tenascin C (TN-C), phosphorylated focal adhesion kinase (pFAK) and exhibited robust stress fibers. In an endothelial (EC)/SMC hemodynamic flow system, shear stress waveforms mimicking atheroprone flow, applied to the EC layer, significantly decreased expression of SMC LPP and palladin. They were also down regulated with TN-C, in an ApoE murine model of atherosclerosis and with oxidative stress but up regulated in an arterial injury model in response to upstream sequential changes in pFAK, Prx1 and TN-C. In conclusion, expression of LPP and palladin are modulated by a mix of mechanical cues, oxidative stress and substrate composition which translate into their up or down regulation in vessel wall injury and early atherogenesis.     

Prediction of hospital mortality from admission laboratory data and patient age: A simple model

Objective: To devise a simple clinical scoring system, using age of patients and laboratory data available on admission, to predict in‐hospital mortality of unselected medical and surgical patients. Methods: All patients admitted as emergencies to a large teaching hospital in Liverpool in the 5 months July–November 2004 were reviewed retrospectively, identifying all who died in hospital and controls who survived. Laboratory data available on admission were extracted to form a derivation dataset. Factors that predicted mortality were determined using logistic regression analysis and then used to construct models tested using receiver operating characteristic curves. Models were simplified to include only seven data items, with minimal loss of predictive efficiency. The simplified model was tested in a second validation dataset of all patients admitted to the same hospital in October and November 2004. Results: The derivation dataset included 550 patients who died and 1100 controls. After logistic regression comparisons, 22 dummy variables were given weightings in discriminant analysis and used to create a receiver operating characteristic curve with area under the curve (AUC) of 0.884. The model was simplified to include the seven most discriminant variables, which can each be assigned scores of 2, 3 or 4 to form an index predicting outcome; a validation dataset contained 4828 patients (overall mortality 4.7%), showed this simplified scoring system accurately predicted mortality with AUC 0.848, compared with an AUC of 0.861 in a model containing all 23 original variables. Conclusion: A simple scoring system accurately predicts in‐hospital mortality of unselected hospital patients, using age of patient and a small number of laboratory parameters available very soon after admission.     

Making the Pack the Hero, Tobacco Industry Response to Marketing Restrictions in the UK: Findings from a Long-Term Audit

The Tobacco Advertising and Promotion Act (TAPA), introduced between 2003 and 2005 in the UK, prohibits all tobacco advertising, promotion and sponsorship. Packaging, however, is not covered in the Act. Two strands of a long-term audit (trade press review and panel of smokers) are examined to monitor change in tobacco packaging from January 2002 to January 2009. The trade press provides numerous examples of value based (altered pack size or price marked packaging), image based (altered pack design) and innovation based (pack additions or modifications) packaging. Some examples of value, image and innovation based packaging are reported in the trade press from 2002 to 2004, but mention of all three forms of packaging increases markedly from 2005 onwards, as other forms of marketing were restricted. These developments have been observed by a panel of smokers, from across the UK, who have been particularly attentive to, and aware of, value based packaging. Packaging has become an increasingly important promotional tool for the tobacco industry as other channels have been shut off. It is clear therefore that any comprehensive and consistent tobacco strategy should include a mandatory move to generic packaging.     

The Malawi National Tuberculosis Programme: an equity analysis

Background  

Until 2005, the Malawi National Tuberculosis Control Programme had been implemented as a vertical programme. Working within the Sector Wide Approach (SWAp) provides a new environment and new opportunities for monitoring the equity performance of the programme. This paper synthesizes what is known on equity and TB in Malawi and highlights areas for further action and advocacy.     

A comparison of dynamic characteristics of fluconazole, itraconazole, and amphotericin B against Cryptococcus neoformans using time-kill methodology

This study evaluated the in vitro pharmacodynamics of fluconazole, itraconazole, and amphotericin B against Cryptococcus neoformans. MICs were determined for three clinical isolates according to NCCLS guidelines (M27). Time-kill studies were performed using antifungal concentrations of 0.25-32 x MIC and inocula of 10(3) and 10(5) CFU/ml. At predetermined time points over 72 hours, samples of each inoculum/drug combination were withdrawn and plated using a spiral plater. Colony counts were determined after incubation at 35 degrees C for 48 hours. Area under the kill curves (AUKCs) were plotted versus the AUC/MIC ratios. Inoculum effect was evaluated by calculating an estimated AUKC for the low inoculum then comparing it to the measured low inoculum using the unpaired Student's t-test. The MICs of fluconazole and itraconazole for isolate 97-1199, 97-1061, and 97-585 were 2, 4, 32 microg/ml and 0.03, 0.06, 0. 5 microg/ml, respectively. For amphotericin B, the MIC was 0. 25 microg/ml for each isolate. The triazoles demonstrated fungistatic activity against each isolate at both inocula with the exception of itraconazole against C. neoformans 97-585. Maximal suppression was noted at concentrations 8-16 x MIC correlating with an AUC/MIC of 192 for both inocula. Conversely, amphotericin B was fungicidal and displayed concentration-dependent activity against each isolate at both inocula. Maximal killing was observed at concentrations >4 x MIC for the low inoculum and >8 x MIC for the high inoculum for each isolate. No statistically significant differences were detected between the measured and estimated AUKCs for each antifungal agent. In conclusion, our results suggest that the triazoles were most effective against C. neoformans when concentrations were maintained at 8-16 x MIC. Amphotericin B, on the other hand, was concentration-dependent; thus, greater activity was exerted at higher concentrations.