Controlled interfacial assembly of 2D curved colloidal crystals and jammed shells

Assembly of colloidal particles on fluid interfaces is a promising technique for synthesizing two-dimensional micro-crystalline materials useful in fields as diverse as biomedicine1, materials science2, mineral flotation3 and food processing4. Current approaches rely on bulk emulsification methods, require further chemical and thermal treatments, and are restrictive with respect to the materials employed5-9. The development of methods that exploit the great potential of interfacial assembly for producing tailored materials have been hampered by the lack of understanding of the assembly process. Here we report a microfluidic method that allows direct visualization and understanding of the dynamics of colloidal crystal growth on curved interfaces. The crystals are periodically ejected to form stable jammed shells, which we refer to as colloidal armour. We propose that the energetic barriers to interfacial crystal growth and organization can be overcome by targeted delivery of colloidal particles through hydrodynamic flows. Our method allows an unprecedented degree of control over armour composition, size and stability.Comment: 18 pages, 5 figure

Dynamics of Transformation from Segregation to Mixed Wealth Cities

We model the dynamics of the Schelling model for agents described simply by a continuously distributed variable - wealth. Agents move to neighborhoods where their wealth is not lesser than that of some proportion of their neighbors, the threshold level. As in the case of the classic Schelling model where segregation obtains between two races, we find here that wealth-based segregation occurs and persists. However, introducing uncertainty into the decision to move - that is, with some probability, if agents are allowed to move even though the threshold level condition is contravened - we find that even for small proportions of such disallowed moves, the dynamics no longer yield segregation but instead sharply transition into a persistent mixed wealth distribution. We investigate the nature of this sharp transformation between segregated and mixed states, and find that it is because of a non-linear relationship between allowed moves and disallowed moves. For small increases in disallowed moves, there is a rapid corresponding increase in allowed moves, but this tapers off as the fraction of disallowed moves increase further and finally settles at a stable value, remaining invariant to any further increase in disallowed moves. It is the overall effect of the dynamics in the initial region (with small numbers of disallowed moves) that shifts the system away from a state of segregation rapidly to a mixed wealth state. The contravention of the tolerance condition could be interpreted as public policy interventions like minimal levels of social housing or housing benefit transfers to poorer households. Our finding therefore suggests that it might require only very limited levels of such public intervention - just sufficient to enable a small fraction of disallowed moves, because the dynamics generated by such moves could spur the transformation from a segregated to mixed equilibrium.Comment: 12 pages, 7 figure

Validating child vaccination status in a demographic surveillance system using data from a clinical cohort study: evidence from rural South Africa

<p><b>Background:</b> Childhood vaccination coverage can be estimated from a range of sources. This study aims to validate vaccination data from a longitudinal population-based demographic surveillance system (DSS) against data from a clinical cohort study.</p> <p><b>Methods:</b> The sample includes 821 children in the Vertical Transmission cohort Study (VTS), who were born between December 2001 and April 2005, and were matched to the Africa Centre DSS, in northern KwaZulu-Natal. Vaccination information in the surveillance was collected retrospectively, using standardized questionnaires during bi-annual household visits, when the child was 12 to 23 months of age. DSS vaccination information was based on extraction from a vaccination card or, if the card was not available, on maternal recall. In the VTS, vaccination data was collected at scheduled maternal and child clinic visits when a study nurse administered child vaccinations. We estimated the sensitivity of the surveillance in detecting vaccinations conducted as part of the VTS during these clinic visits.</p> <p><b>Results:</b> Vaccination data in matched children in the DSS was based on the vaccination card in about two-thirds of the cases and on maternal recall in about one-third. The sensitivity of the vaccination variables in the surveillance was high for all vaccines based on either information from a South African Road-to-Health (RTH) card (0.94-0.97) or maternal recall (0.94-0.98). Addition of maternal recall to the RTH card information had little effect on the sensitivity of the surveillance variable (0.95-0.97). The estimates of sensitivity did not vary significantly, when we stratified the analyses by maternal antenatal HIV status. Addition of maternal recall of vaccination status of the child to the RTH card information significantly increased the proportion of children known to be vaccinated across all vaccines in the DSS.</p> <p><b>Conclusion:</b> Maternal recall performs well in identifying vaccinated children aged 12-23 months (both in HIV-infected and HIV-uninfected mothers), with sensitivity similar to information extracted from vaccination cards. Information based on both maternal recall and vaccination cards should be used if the aim is to use surveillance data to identify children who received a vaccination.</p&gt

Should mechanical dyssynchrony be assessed in patients with implantable cardioverter-defibrillators?

Cardiac Dysfunction and Arrhythmia

Increased capsaicin receptor TRPV1 in skin nerve fibres and related vanilloid receptors TRPV3 and TRPV4 in keratinocytes in human breast pain

BACKGROUND: Breast pain and tenderness affects 70% of women at some time. These symptoms have been attributed to stretching of the nerves with increase in breast size, but tissue mechanisms are poorly understood. METHODS: Eighteen patients (n = 12 breast reduction and n = 6 breast reconstruction) were recruited and assessed for breast pain by clinical questionnaire. Breast skin biopsies from each patient were examined using immunohistological methods with specific antibodies to the capsaicin receptor TRPV1, related vanilloid thermoreceptors TRPV3 and TRPV4, and nerve growth factor (NGF). RESULTS: TRPV1-positive intra-epidermal nerve fibres were significantly increased in patients with breast pain and tenderness (TRPV1 fibres / mm epidermis, median [range] – no pain group, n = 8, 0.69 [0–1.27]; pain group, n = 10, 2.15 [0.77–4.38]; p = 0.0009). Nerve Growth Factor, which up-regulates TRPV1 and induces nerve sprouting, was present basal keratinocytes: some breast pain specimens also showed NGF staining in supra-basal keratinocytes. TRPV4-immunoreactive fibres were present in sub-epidermis but not significantly changed in painful breast tissue. Both TRPV3 and TRPV4 were significantly increased in keratinocytes in breast pain tissues; TRPV3, median [range] – no pain group, n = 6, 0.75 [0–2]; pain group, n = 11, 2 [1-3], p = 0.008; TRPV4, median [range] – no pain group, n = 6, [0–1]; pain group, n = 11, 1 [0.5–2], p = 0.014). CONCLUSION: Increased TRPV1 intra-epidermal nerve fibres could represent collateral sprouts, or re-innervation following nerve stretch and damage by polymodal nociceptors. Selective TRPV1-blockers may provide new therapy in breast pain. The role of TRPV3 and TRPV4 changes in keratinocytes deserve further study

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death monitoring.

OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of death (CoD) in populations without routine medical certification. It has mainly been used in research contexts and involved relatively lengthy interviews. Our objective here is to describe the process used to shorten, simplify, and standardise the VA process to make it feasible for application on a larger scale such as in routine civil registration and vital statistics (CRVS) systems. METHODS: A literature review of existing VA instruments was undertaken. The World Health Organization (WHO) then facilitated an international consultation process to review experiences with existing VA instruments, including those from WHO, the Demographic Evaluation of Populations and their Health in Developing Countries (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium (PHMRC). In an expert meeting, consideration was given to formulating a workable VA CoD list [with mapping to the International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and utility of existing VA interview questions, with a view to undertaking systematic simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public health significance as well as potential for ascertainment from VA. A set of 221 indicators for inclusion in the revised VA instrument was developed on the basis of accumulated experience, with appropriate skip patterns for various population sub-groups. The duration of a VA interview was reduced by about 40% with this new approach. CONCLUSIONS: The revised VA instrument resulting from this consultation process is presented here as a means of making it available for widespread use and evaluation. It is envisaged that this will be used in conjunction with automated models for assigning CoD from VA data, rather than involving physicians