Floquet generation of Majorana end modes and topological invariants

We show how Majorana end modes can be generated in a one-dimensional system by varying some of the parameters in the Hamiltonian periodically in time. The specific model we consider is a chain containing spinless electrons with a nearest-neighbor hopping amplitude, a p-wave superconducting term and a chemical potential; this is equivalent to a spin-1/2 chain with anisotropic XY couplings between nearest neighbors and a magnetic field applied in the z-direction. We show that varying the chemical potential (or magnetic field) periodically in time can produce Majorana modes at the ends of a long chain. We discuss two kinds of periodic driving, periodic delta-function kicks and a simple harmonic variation with time. We discuss some distinctive features of the end modes such as the inverse participation ratio of their wave functions and their Floquet eigenvalues which are always equal to +/- 1 for time-reversal symmetric systems. For the case of periodic delta-function kicks, we use the effective Hamiltonian of a system with periodic boundary conditions to define two topological invariants. The first invariant is a well-known winding number while the second invariant has not appeared in the literature before. The second invariant is more powerful in that it always correctly predicts the numbers of end modes with Floquet eigenvalues equal to +1 and -1, while the first invariant does not. We find that the number of end modes can become very large as the driving frequency decreases. We show that periodic delta-function kicks in the hopping and superconducting terms can also produce end modes. Finally, we study the effect of electron-phonon interactions (which are relevant at finite temperatures) and a random noise in the chemical potential on the Majorana modes.Comment: 15 pages, 11 figures; added more numerical and analytical results about second topological invariant, and a discussion of effects of electron-phonon interactions and noise on Majorana end mode

DEVELOPMENT OPTIMIZATION AND EVALUATION OF EFFERVESCENT TABLETS OF CHLORPHENIRAMINE MALEATE USING BOX BEHNKEN DESIGN

Objective: The objective of present study was to develop effervescent tablets of Chlorpheniramine maleate (CPM) for the treatment of dysphasia.Methods: Effervescent tablets were prepared by direct compression method and were optimized using box behnken design. Amount to sodium bicarbonate (X1), amount of tartaric acid (X2) and amount of fumaric acid (X3) were selected as independent variables, whereas disintegration time (Y1), amount of carbon dioxide (Y2) and drug release in 5 minutes (Y3) were selected as dependent variables. All the batches were also evaluated for general post compression evaluation of tablet such as-weight variation, thickness, friability and hardness. From the results of design batches, best batch was selected and evaluated for in vivo pharmacokinetic study in rabbit model.Results: The disintegration time ranged from 103.33 ± 0.24 sec to 157.00 ± 0.75 sec while amount of carbon dioxide ranged from 0.26±0.014 g to 2.03±0.056 g in all the design batches. From the results of design batches, batch B4 was selected as optimized batch due to higher amount of released carbon dioxide and faster drug release as compared to other batches. Batch B4 was showing higher AUC and Cmax while lower tmax as compared to drug suspension while performing in vivo study of optimized batch in rabbit model.Conclusion: The study concluded that the combination of sodium bicarbonate, tartaric acid and fumaric acid approach for development of effervescent tablet aids to achieve faster disintegration and faster drug release property for CPM.Â

Identifying common impairments in frail and dependent older people: validation of the COPE assessment for non-specialised health workers in low resource primary health care settings.

BACKGROUND: Frail and dependent older people in resource-poor settings are poorly served by health systems that lack outreach capacity. The COPE (Caring for Older PEople) multidimensional assessment tool is designed to help community health workers (CHWs) identify clinically significant impairments and deliver evidence-based interventions METHODS: Older people (n = 150) identified by CHWs as frail or dependent, were assessed at home by the CHW using the structured COPE assessment tool, generating information on impairments in nutrition, mobility, vision, hearing, continence, cognition, mood and behaviour. The older people were reassessed by local physicians who reached a clinical judgment regarding the presence or absence of the same impairments based upon clinical examination guided by the EASY-Care assessment tool. RESULTS: The COPE tool was considered easy to administer, and gave CHWs a sense of empowerment to understand and act upon the needs of older people. Agreement between COPE assessment by CHW and clinician assessors was modest (ranged from 45.8 to 91.3 %) for most impairments. However, the prevalence of impairments was generally higher according to clinicians, particularly for visual impairment (98.7 vs 45.8 %), cognitive impairment (78.4 vs. 38.2 %) and depression (82.0 vs. 59.9 %). Most cases identified by WHO-COPE were clinician confirmed (positive predictive values - 72.2 to 98.5 %), and levels of disability and needs for care among those identified by COPE were higher than those additionally identified by the clinician alone. CONCLUSIONS: The COPE is a feasible tool for the identification of specific impairments in frail dependent older people in the community. Those identified are likely to be confirmed as having clinically relevant problems by clinicians working in the same service, and the COPE may be particularly effective at targeting attention upon those with the most substantial unmet needs

The development and pilot testing of a multicomponent health promotion intervention (SEHER) for secondary schools in Bihar, India.

BACKGROUND: Schools can play an important role in health promotion by improving students' health literacy, attitudes, health-related behaviours, social connection and self-efficacy. These interventions can be particularly valuable in low- and middle-income countries with low health literacy and high burden of disease. However, the existing literature provides poor guidance for the implementation of school-based interventions in low-resource settings. This paper describes the development and pilot testing of a multicomponent school-based health promotion intervention for adolescents in 75 government-run secondary schools in Bihar, India. METHOD: The intervention was developed in three stages: evidence review of the content and delivery of effective school health interventions; formative research to contextualize the proposed content and delivery, involving intervention development workshops with experts, teachers and students and content analysis of intervention manuals; and pilot testing in situ to optimize its feasibility and acceptability. RESULTS: The three-stage process defined the intervention elements, refining their content and format of delivery. This intervention focused on promoting social skills among adolescents, engaging adolescents in school decision making, providing factual information, and enhancing their problem-solving skills. Specific intervention strategies were delivered at three levels (whole school, student group, and individual counselling) by either a trained teacher or a lay counsellor. The pilot study, in 50 schools, demonstrated generally good acceptability and feasibility of the intervention, though the coverage of intervention activities was lower in the teacher delivery schools due to competing teaching commitments, the participation of male students was lower than that of females, and one school dropped out because of concerns regarding the reproductive and sexual health content of the intervention. CONCLUSION: This SEHER approach provides a framework for adolescent health promotion in secondary schools in low-resource settings. We are now using a cluster-randomized trial to evaluate its effectiveness and cost-effectiveness

A multicomponent secondary school health promotion intervention and adolescent health: An extension of the SEHER cluster randomised controlled trial in Bihar, India.

BACKGROUND: Strengthening Evidence base on scHool-based intErventions for pRomoting adolescent health (SEHER) is a multicomponent, whole-school health promotion intervention delivered by a lay counsellor or a teacher in government-run secondary schools in Bihar, India. The objective of this study is to examine the effects of the intervention after two years of follow-up and to evaluate the consistency of the findings observed over time. METHODS AND FINDINGS: We conducted a cluster randomised trial in which 75 schools were randomised (1:1:1) to receive the SEHER intervention delivered by a lay counsellor (SEHER Mitra [SM]) or a teacher (Teacher as SEHER Mitra [TSM]), respectively, alongside a standardised, classroom-based life skills Adolescence Education Program (AEP), compared to AEP alone (control group). The trial design was a repeat cross-sectional study. Students enrolled in grade 9 (aged 13-15 years) in the 2015-2016 academic year were exposed to the intervention for two years and the outcome assessment was conducted at three time points─at baseline in June 2015; 8-months follow-up in March 2016, when the students were still in grade 9; and endpoint at 17-months follow-up in December 2016 (when the students were in grade 10), the results of which are presented in this paper. The primary outcome, school climate, was measured with the Beyond Blue School Climate Questionnaire (BBSCQ). Intervention effects were estimated using mixed-effects linear or logistic regression, including a random effect to adjust for within-school clustering, minimisation variables, baseline cluster-level score of the outcome, and sociodemographic characteristics. In total, 15,232 students participated in the 17-month survey. Compared with the control group, the participants in the SM intervention group reported improvements in school climate (adjusted mean difference [aMD] = 7.33; 95% CI: 6.60-8.06; p < 0.001) and most secondary outcomes (depression: aMD = -4.64; 95% CI: -5.83-3.45; p < 0.001; attitude towards gender equity: aMD = 1.02; 95% CI: 0.65-1.40; p < 0.001; frequency of bullying: aMD = -2.77; 95% CI: -3.40 to -2.14; p < 0.001; violence victimisation: odds ratio [OR] = 0.08; 95% CI: 0.04-0.14; p < 0.001; and violence perpetration: OR = 0.16; 95% CI: 0.09-0.29; p < 0.001). There was no evidence of an intervention effect in the TSM group compared with control group. The effects of the lay counsellor-delivered intervention were larger for most outcomes at 17-months follow-up compared with those at 8 months: school climate (effect size [ES; 95% CI] = 2.23 [1.97-2.50] versus 1.88 [1.44-2.32], p < 0.001); depression (ES [95% CI] = -1.19 [-1.56 to -0.82] versus -0.27 [-0.44 to -0.11], p < 0.001); attitude towards gender equity (ES [95% CI] = 0.53 [0.27-0.79] versus 0.23 [0.10-0.36], p < 0.001); bullying (ES [95% CI] = -2.22 [-2.84 to -1.60] versus -0.47 [-0.61 to -0.33], p < 0.001); violence victimisation (OR [95% CI] = 0.08 [0.04-0.14] versus 0.62 [0.46-0.84], p < 0.001); and violence perpetration (OR [95% CI] = 0.16 [0.09-0.29] versus 0.68 [0.48-0.96], p < 0.001), suggesting incremental benefits with an extended intervention. A limitation of the study is that 27% of baseline participants did not complete the 17-month outcome assessment. CONCLUSIONS: The trial showed that the second-year outcomes were similar to the first-year outcomes, with no effect of the teacher-led intervention and larger benefits on school climate and adolescent health accruing from extending lay counsellor-delivered intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT02907125

Non-Esterified Fatty Acids Generate Distinct Low-Molecular Weight Amyloid-β (Aβ42) Oligomers along Pathway Different from Fibril Formation

Amyloid-beta (A beta) peptide aggregation is known to play a central role in the etiology of Alzheimer\u27s disease (AD). Among various aggregates, low-molecular weight soluble oligomers of A beta are increasingly believed to be the primary neurotoxic agents responsible for memory impairment. Anionic interfaces are known to influence the A beta aggregation process significantly. Here, we report the effects of interfaces formed by medium-chain (C9-C12), saturated non-esterified fatty acids (NEFAs) on A beta 42 aggregation. NEFAs uniquely affected A beta 42 aggregation rates that depended on both the ratio of A beta:NEFA as well the critical micelle concentration (CMC) of the NEFAs. More importantly, irrespective of the kind of NEFA used, we observed that two distinct oligomers, 12-18 mers and 4-5 mers were formed via different pathway of aggregation under specific experimental conditions: (i) 12-18 mers were generated near the CMC in which NEFAs augment the rate of A beta 42 aggregation towards fibril formation, and, (ii) 4-5 mers were formed above the CMC, where NEFAs inhibit fibril formation. The data indicated that both 12-18 mers and 4-5 mers are formed along an alternate pathway called \u27off-pathway\u27 that did not result in fibril formation and yet have subtle structural and morphological differences that distinguish their bulk molecular behavior. These observations, (i) reflect the possible mechanism of A beta aggregation in physiological lipid-rich environments, and (ii) reiterate the fact that all oligomeric forms of A beta need not be obligatory intermediates of the fibril formation pathway