The feasibility of radiolabeling for human serum albumin (HSA) adsorption studies

Human serum albumin (HSA) was labeled in various ways and with different radioactive labels (Technetium-99m and Iodine-125). Characterization with electrophoresis on polyacryl gel and immunoelectrophoresis did not reveal differences between labeled and nonlabeled HSA. The release of the label from labeled proteins in phosphate buffer (pH 7.4) was studied as a function of time. 125I-labeled proteins were stable and 99mTc-labeled proteins showed different stabilities depending on the labeling method which was used. The adsorption behavior of labeled HSA and HSA onto polystyrene (PS) and silicon rubber (SR) was studied by using two methods. It appeared that all labeled HSA compounds showed a preferential adsorption onto PS (and SR) substrates. The 99mTc-labeled HSA showed a high value of the preferential adsorption factor (φ 1). The φ value for 125I-labeled HSA was about 1.4. It was also shown that φ was dependent on the kind of substrate used. The methods developed to determine preferential adsorption of labeled proteins compared to their nonlabeled analogs are also generally applicable for different types of compounds

Prenatal origin of childhood AML occurs less frequently than in childhood ALL

Background While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers. Methods We analysed Guthrie cards of 12 ALL patients aged 2–6 years using immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements (n = 15) and/or intronic breakpoints of TEL/AML1 fusion gene (n = 3). In AML patients (n = 13, age 1–14 years) PML/RARalpha (n = 4), CBFbeta/MYH11 (n = 3), AML1/ETO (n = 2), MLL/AF6 (n = 1), MLL/AF9 (n = 1) and MLL/AF10 (n = 1) fusion genes and/or internal tandem duplication of FLT3 gene (FLT3/ITD) (n = 2) were used as clonotypic markers. Assay sensitivity determined using serial dilutions of patient DNA into the DNA of a healthy donor allowed us to detect the pre-leukemic clone in Guthrie card providing 1–3 positive cells were present in the neonatal blood spot. Results In 3 patients with ALL (25%) we reproducibly detected their leukemic markers (Ig/TCR n = 2; TEL/AML1 n = 1) in the Guthrie card. We did not find patient-specific molecular markers in any patient with AML. Conclusion In the largest cohort examined so far we used identical approach for the backtracking of non-infant childhood ALL and AML. Our data suggest that either the prenatal origin of AML is less frequent or the load of pre-leukemic cells is significantly lower at birth in AML compared to ALL cases

Using economic evidence to set healthcare priorities in low-income and lower-middle-income countries: a systematic review of methodological frameworks

Policy makers in low-income and lower-middle-income countries (LMICs) are increasingly looking to develop 'evidence-based' frameworks for identifying priority health interventions. This paper synthesises and appraises the literature on methodological frameworks - which incorporate economic evaluation evidence - for the purpose of setting healthcare priorities in LMICs. A systematic search of Embase, MEDLINE, Econlit and PubMed identified 3968 articles with a further 21 articles identified through manual searching. A total of 36 papers were eligible for inclusion. These covered a wide range of health interventions with only two studies including health systems strengthening interventions related to financing, governance and human resources. A little under half of the studies (39%) included multiple criteria for priority setting, most commonly equity, feasibility and disease severity. Most studies (91%) specified a measure of 'efficiency' defined as cost per disability-adjusted life year averted. Ranking of health interventions using multi-criteria decision analysis and generalised cost-effectiveness were the most common frameworks for identifying priority health interventions. Approximately a third of studies discussed the affordability of priority interventions. Only one study identified priority areas for the release or redeployment of resources. The paper concludes by highlighting the need for local capacity to conduct evaluations (including economic analysis) and empowerment of local decision-makers to act on this evidence

Whistleblowing as a countermeasure strategy against food crime

Purpose The purpose of this paper is to undertake a two-phase desktop review of literature sources in order to conceptualise, frame, and critique existing whistleblowing models and strategies and consider how whistleblowing strategies form part of an effective food crime management system (FCMS) especially for small and medium sized organisations. Design/methodology/approach Existing literature from academic sources, financial, healthcare, food industries has been reviewed and critiqued in order to construct a conceptual framework that can inform future empirical research. Findings Whistleblowing strategies can form an effective part of a FCMS. Appropriate regulatory protection of those who whistleblow is crucial to not only safeguard individuals but also to mitigate food crime and protect consumers from loss and potential harm. Barriers to whistleblowing exist and if these are not addressed then individuals will be reluctant to report food crime. Further empirical research is required to assess the influence of these and other factors identified in this research and how they can be overcome. Originality/value The framework will provide food industry practitioners with guidance on the effective application of whistleblowing strategies within a FCMS

Hadronic production of bottom-squark pairs with electroweak contributions

We present the complete computation of the tree-level and the next-to-leading order electroweak contributions to bottom-squark pair production at the LHC. The computation is performed within the minimal supersymmetric extension of the Standard Model. We discuss the numerical impact of these contributions in several supersymmetric scenarios.Comment: 33 pages, v2: preprint numbers correcte

Interactions between the Nse3 and Nse4 Components of the SMC5-6 Complex Identify Evolutionarily Conserved Interactions between MAGE and EID Families

The SMC5-6 protein complex is involved in the cellular response to DNA damage. It is composed of 6-8 polypeptides, of which Nse1, Nse3 and Nse4 form a tight sub-complex. MAGEG1, the mammalian ortholog of Nse3, is the founding member of the MAGE (melanoma-associated antigen) protein family and Nse4 is related to the EID (E1A-like inhibitor of differentiation) family of transcriptional repressors.Using site-directed mutagenesis, protein-protein interaction analyses and molecular modelling, we have identified a conserved hydrophobic surface on the C-terminal domain of Nse3 that interacts with Nse4 and identified residues in its N-terminal domain that are essential for interaction with Nse1. We show that these interactions are conserved in the human orthologs. Furthermore, interaction of MAGEG1, the mammalian ortholog of Nse3, with NSE4b, one of the mammalian orthologs of Nse4, results in transcriptional co-activation of the nuclear receptor, steroidogenic factor 1 (SF1). In an examination of the evolutionary conservation of the Nse3-Nse4 interactions, we find that several MAGE proteins can interact with at least one of the NSE4/EID proteins.We have found that, despite the evolutionary diversification of the MAGE family, the characteristic hydrophobic surface shared by all MAGE proteins from yeast to humans mediates its binding to NSE4/EID proteins. Our work provides new insights into the interactions, evolution and functions of the enigmatic MAGE proteins

Hadronic production of squark-squark pairs: The electroweak contributions

We compute the electroweak (EW) contributions to squark--squark pair production processes at the LHC within the framework of the Minimal Supersymmetric Standard Model (MSSM). Both tree-level EW contributions, of O(alpha_s alpha + alpha^2), and next-to-leading order (NLO) EW corrections, of O(alpha_s^2 alpha), are calculated. Depending on the flavor and chirality of the produced quarks, many interferences between EW-mediated and QCD-mediated diagrams give non-zero contributions at tree-level and NLO. We discuss the computational techniques and present an extensive numerical analysis for inclusive squark--squark production as well as for subsets and single processes. While the tree-level EW contributions to the integrated cross sections can reach the 20% level, the NLO EW corrections typically lower the LO prediction by a few percent.Comment: 36 pages, 18 figure

Family-led rehabilitation after stroke in India (ATTEND): a randomised controlled trial

Background: Most people with stroke in India have no access to organised rehabilitation services. The effectiveness of training family members to provide stroke rehabilitation is uncertain. Our primary objective was to determine whether family-led stroke rehabilitation, initiated in hospital and continued at home, would be superior to usual care in a low-resource setting. Methods: The Family-led Rehabilitation after Stroke in India (ATTEND) trial was a prospectively randomised open trial with blinded endpoint done across 14 hospitals in India. Patients aged 18 years or older who had had a stroke within the past month, had residual disability and reasonable expectation of survival, and who had an informal family-nominated caregiver were randomly assigned to intervention or usual care by site coordinators using a secure web-based system with minimisation by site and stroke severity. The family members of participants in the intervention group received additional structured rehabilitation training—including information provision, joint goal setting, carer training, and task-specific training—that was started in hospital and continued at home for up to 2 months. The primary outcome was death or dependency at 6 months, defined by scores 3–6 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) as assessed by masked observers. Analyses were by intention to treat. This trial is registered with Clinical Trials Registry-India (CTRI/2013/04/003557), Australian New Zealand Clinical Trials Registry (ACTRN12613000078752), and Universal Trial Number (U1111-1138-6707). Findings: Between Jan 13, 2014, and Feb 12, 2016, 1250 patients were randomly assigned to intervention (n=623) or control (n=627) groups. 33 patients were lost to follow-up (14 intervention, 19 control) and five patients withdrew (two intervention, three control). At 6 months, 285 (47%) of 607 patients in the intervention group and 287 (47%) of 605 controls were dead or dependent (odds ratio 0·98, 95% CI 0·78–1·23, p=0·87). 72 (12%) patients in the intervention group and 86 (14%) in the control group died (p=0·27), and we observed no difference in rehospitalisation (89 [14%]patients in the intervention group vs 82 [13%] in the control group; p=0·56). We also found no difference in total non-fatal events (112 events in 82 [13%] intervention patients vs 110 events in 79 [13%] control patients; p=0·80). Interpretation: Although task shifting is an attractive solution for health-care sustainability, our results do not support investment in new stroke rehabilitation services that shift tasks to family caregivers, unless new evidence emerges. A future avenue of research should be to investigate the effects of task shifting to health-care assistants or team-based community care. Funding: The National Health and Medical Research Council of Australia

A voluntary use of insecticide-treated cattle can eliminate African sleeping sickness

Winner of the 2015-2016 UNCG University Libraries Open Access Publishing Fund Grant. African sleeping sickness is a vector-borne disease caused by the parasite Trypanosoma brucei. Itis transmitted by tsetse flies and one of the most effective strategies to combat the disease is theuse of insecticide-treated cattle (ITC). In this paper, we present a gametheoretical model, inwhich individual farmers choose their own level of ITC in order to maximize their own benefits,effectively balancing the cost of ITC and the risk of their cows contracting the disease. We findthat even when the usage of ITC is strictly voluntary, the optimal ITC usage will eliminate thedisease when the cost of ITC is not prohibitively large. This is in a sharp contrast with similarscenarios of vaccination games where a voluntary vaccination never eliminates a diseaseentirely

Waste Recycling Can Promote Group Living: A Cockroach Case Study

Animals live in groups for a wide variety of reasons. The main benefits are related to anti-predator behaviour, foraging, mate finding and/or reduction of energetic costs. In this paper we present a game-theoretical model that supports the waste recycling hypothesis. This hypothesis posits that the waste organic materials produced by the members of a group represent a valuable resource that is communally inherited and utilized by group members. Under this hypothesis and on the example of cockroaches, we determine evolutionarily stable strategies of social behavior and quantify conditions on natural parameter values such as food availability under which the group formation is beneficial