Multiple dynamical time-scales in networks with hierarchically nested modular organization

Many natural and engineered complex networks have intricate mesoscopic organization, e.g., the clustering of the constituent nodes into several communities or modules. Often, such modularity is manifested at several different hierarchical levels, where the clusters defined at one level appear as elementary entities at the next higher level. Using a simple model of a hierarchical modular network, we show that such a topological structure gives rise to characteristic time-scale separation between dynamics occurring at different levels of the hierarchy. This generalizes our earlier result for simple modular networks, where fast intra-modular and slow inter-modular processes were clearly distinguished. Investigating the process of synchronization of oscillators in a hierarchical modular network, we show the existence of as many distinct time-scales as there are hierarchical levels in the system. This suggests a possible functional role of such mesoscopic organization principle in natural systems, viz., in the dynamical separation of events occurring at different spatial scales.Comment: 10 pages, 4 figure

Bilateral sternoclavicular joint septic arthritis secondary to indwelling central venous catheter: a case report

<p>Abstract</p> <p>Introduction</p> <p>Septic arthritis of the sternoclavicular joint is rare, comprising approximately 0.5% to 1% of all joint infections. Predisposing causes include immunocompromising diseases such as diabetes, HIV infection, renal failure and intravenous drug abuse.</p> <p>Case presentation</p> <p>We report a rare case of bilateral sternoclavicular joint septic arthritis in an elderly patient secondary to an indwelling right subclavian vein catheter. The insidious nature of the presentation is highlighted. We also review the literature regarding the epidemiology, investigation and methods of treatment of the condition.</p> <p>Conclusion</p> <p>SCJ infections are rare, and require a high degree of clinical suspicion. Vague symptoms of neck and shoulder pain may cloud the initial diagnosis, as was the case in our patient. Surgical intervention is often required; however, our patient avoided major intervention and settled with parenteral antibiotics and washout of the joint.</p

Steroid Concentrations in Plasma, Whole Blood and Brain: Effects of Saline Perfusion to Remove Blood Contamination from Brain

The brain and other organs locally synthesize steroids. Local synthesis is suggested when steroid levels are higher in tissue than in the circulation. However, measurement of both circulating and tissue steroid levels are subject to methodological considerations. For example, plasma samples are commonly used to estimate circulating steroid levels in whole blood, but steroid levels in plasma and whole blood could differ. In addition, tissue steroid measurements might be affected by blood contamination, which can be addressed experimentally by using saline perfusion to remove blood. In Study 1, we measured corticosterone and testosterone (T) levels in zebra finch (Taeniopygia guttata) plasma, whole blood, and red blood cells (RBC). We also compared corticosterone in plasma, whole blood, and RBC at baseline and after 60 min restraint stress. In Study 2, we quantified corticosterone, dehydroepiandrosterone (DHEA), T, and 17β-estradiol (E2) levels in the brains of sham-perfused or saline-perfused subjects. In Study 1, corticosterone and T concentrations were highest in plasma, significantly lower in whole blood, and lowest in RBC. In Study 2, saline perfusion unexpectedly increased corticosterone levels in the rostral telencephalon but not other regions. In contrast, saline perfusion decreased DHEA levels in caudal telencephalon and diencephalon. Saline perfusion also increased E2 levels in caudal telencephalon. In summary, when comparing local and systemic steroid levels, the inclusion of whole blood samples should prove useful. Moreover, blood contamination has little or no effect on measurement of brain steroid levels, suggesting that saline perfusion is not necessary prior to brain collection. Indeed, saline perfusion itself may elevate and lower steroid concentrations in a rapid, region-specific manner

Immune cells fold and damage fungal hyphae

This is the final version. Available on open access from the Evolutionary Computation Journal via the DOI in this recordData Availability: All study data are included in the article and/or supporting information.Innate immunity provides essential protection against life-threatening fungal infections. However, the outcomes of individual skirmishes between immune cells and fungal pathogens are not a foregone conclusion because some pathogens have evolved mechanisms to evade phagocytic recognition, engulfment, and killing. For example, Candida albicans can escape phagocytosis by activating cellular morphogenesis to form lengthy hyphae that are challenging to engulf. Through live imaging of C. albicans-macrophage interactions, we discovered that macrophages can counteract this by folding fungal hyphae. The folding of fungal hyphae is promoted by Dectin-1, β2-integrin, VASP, actin-myosin polymerization, and cell motility. Folding facilitates the complete engulfment of long hyphae in some cases and it inhibits hyphal growth, presumably tipping the balance toward successful fungal clearance.Medical Research Council (MRC)Wellcome TrustEuropean Research Council (ERC)Netherlands Organization for Scientific Researc

Mapping Dirac quasiparticles near a single Coulomb impurity on graphene

The response of Dirac fermions to a Coulomb potential is predicted to differ significantly from how non-relativistic electrons behave in traditional atomic and impurity systems. Surprisingly, many key theoretical predictions for this ultra-relativistic regime have not been tested. Graphene, a two-dimensional material in which electrons behave like massless Dirac fermions, provides a unique opportunity to test such predictions. Graphene’s response to a Coulomb potential also offers insight into important material characteristics, including graphene’s intrinsic dielectric constant, which is the primary factor determining the strength of electron–electron interactions in graphene. Here we present a direct measurement of the nanoscale response of Dirac fermions to a single Coulomb potential placed on a gated graphene device. Scanning tunnelling microscopy was used to fabricate tunable charge impurities on graphene, and to image electronic screening around them for a Q = +1|e| charge state. Electron-like and hole-like Dirac fermions were observed to respond differently to a Coulomb potential. Comparing the observed electron–hole asymmetry to theoretical simulations has allowed us to test predictions for how Dirac fermions behave near a Coulomb potential, as well as extract graphene’s intrinsic dielectric constant: ε[subscript g] = 3.0±1.0. This small value of ε[subscript g] indicates that electron–electron interactions can contribute significantly to graphene properties.United States. Office of Naval Research. Multidisciplinary University Research Initiative (Award N00014-09-1-1066)United States. Dept. of Energy. Office of Science (Contract DE-AC02-05CH11231)National Science Foundation (U.S.) (Award DMR-0906539

Women's health groups to improve perinatal care in rural Nepal

BACKGROUND: Neonatal mortality rates are high in rural Nepal where more than 90% of deliveries are in the home. Evidence suggests that death rates can be reduced by interventions at community level. We describe an intervention which aimed to harness the power of community planning and decision making to improve maternal and newborn care in rural Nepal. METHODS: The development of 111 women's groups in a population of 86 704 in Makwanpur district, Nepal is described. The groups, facilitated by local women, were the intervention component of a randomized controlled trial to reduce perinatal and neonatal mortality rates. Through participant observation and analysis of reports, we describe the implementation of this intervention: the community entry process, the facilitation of monthly meetings through a participatory action cycle of problem identification, community planning, and implementation and evaluation of strategies to tackle the identified problems. RESULTS: In response to the needs of the group, participatory health education was added to the intervention and the women's groups developed varied strategies to tackle problems of maternal and newborn care: establishing mother and child health funds, producing clean home delivery kits and operating stretcher schemes. Close linkages with community leaders and community health workers improved strategy implementation. There were also indications of positive effects on group members and health services, and most groups remained active after 30 months. CONCLUSION: A large scale and potentially sustainable participatory intervention with women's groups, which focused on pregnancy, childbirth and the newborn period, resulted in innovative strategies identified by local communities to tackle perinatal care problems

Some peace of mind: assessing a pilot intervention to promote mental health among widows of injecting drug users in north-east India

<p>Abstract</p> <p>Background</p> <p>HIV prevalence in north-east India is high and injecting drug use (IDU) is common. Due to HIV-related deaths there are increasing numbers of IDU widows, many of whom are HIV infected, and experiencing poor health, social isolation, discrimination and poverty, all factors likely to be compromising their mental health. There is increasing recognition of the links between HIV and mental health.</p> <p>Methods</p> <p>The aim of this study was to pilot a peer-facilitated, participatory action group (PAG) process and assess the impact of the intervention on the mental health of participants. The intervention consisted of 10 PAG meetings involving 74 IDU widows. Changes in quality of life (WHOQOL-BREF), mental health (GHQ12) and somatic symptoms were assessed. The value of the intervention from the perspective of the participants was captured using a qualitative evaluation method (Most Significant Change).</p> <p>Results</p> <p>Participants' quality of life, mental health and experience of somatic symptoms improved significantly over the course of the intervention, and the women told stories reflecting a range of 'significant changes'.</p> <p>Conclusion</p> <p>This pilot intervention study demonstrated that a participatory approach to mental health promotion can have a positive impact on the lives of vulnerable women, and the potential to contribute to HIV prevention. Further investigation is warranted.</p

Functional Characterization of FLT3 Receptor Signaling Deregulation in Acute Myeloid Leukemia by Single Cell Network Profiling (SCNP)

Molecular characterization of the FMS-like tyrosine kinase 3 receptor (FLT3) in cytogenetically normal acute myeloid leukemia (AML) has recently been incorporated into clinical guidelines based on correlations between FLT3 internal tandem duplications (FLT3-ITD) and decreased disease-free and overall survival. These mutations result in constitutive activation of FLT3, and FLT3 inhibitors are currently undergoing trials in AML patients selected on FLT3 molecular status. However, the transient and partial responses observed suggest that FLT3 mutational status alone does not provide complete information on FLT3 biological activity at the individual patient level. Examination of variation in cellular responsiveness to signaling modulation may be more informative.Using single cell network profiling (SCNP), cells were treated with extracellular modulators and their functional responses were quantified by multiparametric flow cytometry. Intracellular signaling responses were compared between healthy bone marrow myeloblasts (BMMb) and AML leukemic blasts characterized as FLT3 wild type (FLT3-WT) or FLT3-ITD. Compared to healthy BMMb, FLT3-WT leukemic blasts demonstrated a wide range of signaling responses to FLT3 ligand (FLT3L), including elevated and sustained PI3K and Ras/Raf/Erk signaling. Distinct signaling and apoptosis profiles were observed in FLT3-WT and FLT3-ITD AML samples, with more uniform signaling observed in FLT3-ITD AML samples. Specifically, increased basal p-Stat5 levels, decreased FLT3L induced activation of the PI3K and Ras/Raf/Erk pathways, decreased IL-27 induced activation of the Jak/Stat pathway, and heightened apoptotic responses to agents inducing DNA damage were observed in FLT3-ITD AML samples. Preliminary analysis correlating these findings with clinical outcomes suggests that classification of patient samples based on signaling profiles may more accurately reflect FLT3 signaling deregulation and provide additional information for disease characterization and management.These studies show the feasibility of SCNP to assess modulated intracellular signaling pathways and characterize the biology of individual AML samples in the context of genetic alterations

Community mobilisation and health management committee strengthening to increase birth attendance by trained health workers in rural Makwanpur, Nepal: study protocol for a cluster randomised controlled trial

Background: Birth attendance by trained health workers is low in rural Nepal. Local participation in improving health services and increased interaction between health systems and communities may stimulate demand for health services. Significant increases in birth attendance by trained health workers may be affected through community mobilisation by local women's groups and health management committee strengthening. We will test the effect of community mobilisation through women's groups, and health management committee strengthening, on institutional deliveries and home deliveries attended by trained health workers in Makwanpur District. Design: Cluster randomised controlled trial involving 43 village development committee clusters. 21 clusters will receive the intervention and 22 clusters will serve as control areas. In intervention areas, Female Community Health Volunteers are supported in convening monthly women's groups. The groups work through an action research cycle in which they consider barriers to institutional delivery, plan and implement strategies to address these barriers with their communities, and evaluate their progress. Health management committees participate in three-day workshops that use appreciative inquiry methods to explore and plan ways to improve maternal and newborn health services. Follow-up meetings are conducted every three months to review progress. Primary outcomes are institutional deliveries and home deliveries conducted by trained health workers. Secondary outcome measures include uptake of antenatal and postnatal care, neonatal mortality and stillbirth rates, and maternal morbidity

Exclusive Breastfeeding Practices in Relation to Social and Health Determinants: a Comparison of the 2006 and 2011 Nepal Demographic and Health Surveys

Background: Exclusive breastfeeding (EBF) for the first six months can have a significant impact on reducing child morbidity and mortality rates. The objective of this study was to compare the determinants of and trends in EBF in infants =5 months from the 2006 and 2011 Nepal Demographic and Health Surveys. Methods: Data on mother/infant pairs having infants of =5 months from 2006 (n = 482) and 2011 (n = 227) were analysed. The EBF rate, determinants of EBF, and changes in EBF rates between the 2006 and 2011 surveys were examined using Chi-square test and multiple logistic regression. Results: The EBF rate for =5 months in 2006 was 53.2% (95% CI, 47.1%-59.3%) and 66.3% (95% CI, 56.6%-74.8%) in 2011. In 2006, infants =4 months were more likely to be EBF [(aOR) 3.086, 95% CI (1.825-5.206)] after controlling for other factors. A geographic effect was also found in this study, with the odds of EBF higher for infants from the Hills [aOR 3.426, 95% CI (1.568-7.474)] compared to those form the mountains. The odds of EBF were also higher for higher order infants [aOR 1.968, 95% CI (1.020-3.799)]. Infants whose fathers belonged to non-agricultural occupation were less likely to be provided with EBF. Infants who were delivered in the home were more likely to experience EBF [aOR 1.886; 95% CI (1.044-3.407)]. In 2011, infants of age =4 months were more likely [aOR 4.963, 95% CI (2.317-10.629)] to have been breastfed exclusively. While there was an increase in the EBF rate between 2006 and 2011 surveys, the significant increase was noticed only among the infants of four months [32.0%; 95% CI (19.9%-47.0%)] in 2006 to [65.5%; 95% CI (48.1-79.6)] in 2011.Conclusions: The proportion of infants who were EBF was higher in Nepal in 2011survey compared to 2006 survey; however, this is still below the recommended WHO target of 90%. Infant’s age, ecological region, parity and father’s occupation were associated with EBF. Further interventions such as peer counselling, antenatal counselling and involving fathers in the community to promote EBF in Nepal are recommended