Arms Industry

A summary assessment of the dimensions and concentrations of military equipment manufacture primarily in the United States and western Europe and the extent of availability of this equipment to buyers throughout the world. Treaty-based limitations are also listed

Modeling of mode-locking in a laser with spatially separate gain media

We present a novel laser mode-locking scheme and discuss its unusual properties and feasibility using a theoretical model. A large set of single-frequency continuous-wave lasers oscillate by amplification in spatially separated gain media. They are mutually phase-locked by nonlinear feedback from a common saturable absorber. As a result, ultra short pulses are generated. The new scheme offers three significant benefits: the light that is amplified in each medium is continuous wave, thereby avoiding issues related to group velocity dispersion and nonlinear effects that can perturb the pulse shape. The set of frequencies on which the laser oscillates, and therefore the pulse repetition rate, is controlled by the geometry of resonator-internal optical elements, not by the cavity length. Finally, the bandwidth of the laser can be controlled by switching gain modules on and off. This scheme offers a route to mode-locked lasers with high average output power, repetition rates that can be scaled into the THz range, and a bandwidth that can be dynamically controlled. The approach is particularly suited for implementation using semiconductor diode laser arrays.Comment: 13 pages, 5 figures, submitted to Optics Expres

Social relationships and social support among post-war youth in Northern Uganda

Although social relationships and social support are salient factors for post-war adolescents' psychosocial coping and adjustment, there is only limited information regarding war-affected adolescents' views on social support and the relationships within which social support is provided. This study therefore explored both elements among a clinical sample of 20 adolescents living in post-war Northern Uganda. Following Braun and Clarke's thematic analysis, we found a prominent role of the biological mother and other primary biological family members in the upbringing of our participants. Spiritual and material support were perceived to be the most important type of support, respectively, while the adolescents were growing up and in their current lives. These findings provide support for the perception that caregiving systems are adaptable to particular sociocultural contexts. Further, the importance of particular functions of social support could signify a potentially selective buffering effect of these functions in adverse contexts. Because of the importance of the primary biological family and the salient role of parent–child relationships in the face of adversity, future research needs to focus on this particular kind of social relationship in contexts of prolonged collective violence

A Mathematical Model of Liver Cell Aggregation In Vitro

The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work

A multiscale analysis of drug transport and response for a multiphase tumor model

In this article we consider the spatial homogenization of a multi- phase model for avascular tumour growth and response to chemother- apeutic treatment. The key contribution of this work is the derivation of a system of homogenized partial differential equations describing macroscopic tumour growth, coupled to transport of drug and nutri- ent, that explicitly incorporates details of the structure and dynamics of the tumour at the microscale. In order to derive these equations we employ an asymptotic homogenization of a microscopic description under the assumption of strong interphase drag, periodic microstructure, and strong separation of scales. The resulting macroscale model com- prises a Darcy flow coupled to a system of reaction-advection partial differential equations. The coupled growth, response, and transport dynamics on the tissue scale are investigated via numerical experi- ments for simple academic test cases of microstructural information and tissue geometry, in which we observe drug- and nutrient-regulated growth and response consistent with the anticipated dynamics of the macroscale system

The effect of social media communication on consumer perceptions of brands

Researchers and brand managers have limited understanding of the effects social media communication has on how consumers perceive brands. We investigated 504 Facebook users in order to observe the impact of firm-created and user-generated social media communication on brand equity, brand attitude and purchase intention by using a standardized online survey throughout Poland. To test the conceptual model, we analyzed 60 brands across three different industries: non-alcoholic beverages, clothing and mobile network operators. When analyzing the data, we applied the structural equation modeling technique to both investigate the interplay of firm-created and user-generated social media communication and examine industry-specific differences. The results of the empirical studies showed that user-generated social media communication had a positive influence on both brand equity and brand attitude, whereas firm-created social media communication affected only brand attitude. Both brand equity and brand attitude were shown to have a positive influence on purchase intention. In addition, we assessed measurement invariance using a multi-group structural modeling equation. The findings revealed that the proposed measurement model was invariant across the researched industries. However, structural path differences were detected across the models

CRALBP supports the mammalian retinal visual cycle and cone vision

Mutations in the cellular retinaldehyde-binding protein (CRALBP, encoded by RLBP1) can lead to severe cone photoreceptor-mediated vision loss in patients. It is not known how CRALBP supports cone function or how altered CRALBP leads to cone dysfunction. Here, we determined that deletion of Rlbp1 in mice impairs the retinal visual cycle. Mice lacking CRALBP exhibited M-opsin mislocalization, M-cone loss, and impaired cone-driven visual behavior and light responses. Additionally, M-cone dark adaptation was largely suppressed in CRALBP-deficient animals. While rearing CRALBP-deficient mice in the dark prevented the deterioration of cone function, it did not rescue cone dark adaptation. Adeno-associated virus-mediated restoration of CRALBP expression specifically in Müller cells, but not retinal pigment epithelial (RPE) cells, rescued the retinal visual cycle and M-cone sensitivity in knockout mice. Our results identify Müller cell CRALBP as a key component of the retinal visual cycle and demonstrate that this pathway is important for maintaining normal cone-driven vision and accelerating cone dark adaptation

Improving quality of care and outcome at very preterm birth: the Preterm Birth research programme, including the Cord pilot RCT

BACKGROUND:Being born very premature (i.e. before 32 weeks’ gestation) has an impact on survival and quality of life. Improving care at birth may improve outcomes and parents’ experiences. OBJECTIVES:To improve the quality of care and outcomes following very preterm birth. DESIGN:We used mixed methods, including a James Lind Alliance prioritisation, a systematic review, a framework synthesis, a comparative review, qualitative studies, development of a questionnaire tool and a medical device (a neonatal resuscitation trolley), a survey of practice, a randomised trial and a protocol for a prospective meta-analysis using individual participant data. SETTING:For the prioritisation, this included people affected by preterm birth and health-care practitioners in the UK relevant to preterm birth. The qualitative work on preterm birth and the development of the questionnaire involved parents of infants born at three maternity hospitals in southern England. The medical device was developed at Liverpool Women’s Hospital. The survey of practice involved UK neonatal units. The randomised trial was conducted at eight UK tertiary maternity hospitals. PARTICIPANTS:For prioritisation, 26 organisations and 386 individuals; for the interviews and questionnaire tool, 32 mothers and seven fathers who had a baby born before 32 weeks’ gestation for interviews evaluating the trolley, 30 people who had experienced it being used at the birth of their baby (19 mothers, 10 partners and 1 grandmother) and 20 clinicians who were present when it was being used; for the trial, 261 women expected to have a live birth before 32 weeks’ gestation, and their 276 babies. INTERVENTIONS:Providing neonatal care at very preterm birth beside the mother, and with the umbilical cord intact; timing of cord clamping at very preterm birth. MAIN OUTCOME MEASURES:Research priorities for preterm birth; feasibility and acceptability of the trolley; feasibility of a randomised trial, death and intraventricular haemorrhage. REVIEW METHODS:Systematic review of Cochrane reviews (umbrella review); framework synthesis of ethics aspects of consent, with conceptual framework to inform selection criteria for empirical and analytical studies. The comparative review included studies using a questionnaire to assess satisfaction with care during childbirth, and provided psychometric information. RESULTS:Our prioritisation identified 104 research topics for preterm birth, with the top 30 ranked. An ethnographic analysis of decision-making during this process suggested ways that it might be improved. Qualitative interviews with parents about their experiences of very preterm birth identified two differences with term births: the importance of the staff appearing calm and of staff taking control. Following a comparative review, this led to the development of a questionnaire to assess parents’ views of care during very preterm birth. A systematic overview summarised evidence for delivery room neonatal care and revealed significant evidence gaps. The framework synthesis explored ethics issues in consent for trials involving sick or preterm infants, concluding that no existing process is ideal and identifying three important gaps. This led to the development of a two-stage consent pathway (oral assent followed by written consent), subsequently evaluated in our randomised trial. Our survey of practice for care at the time of birth showed variation in approaches to cord clamping, and that no hospitals were providing neonatal care with the cord intact. We showed that neonatal care could be provided beside the mother using either the mobile neonatal resuscitation trolley we developed or existing equipment. Qualitative interviews suggested that neonatal care beside the mother is valued by parents and acceptable to clinicians. Our pilot randomised trial compared cord clamping after 2 minutes and initial neonatal care, if needed, with the cord intact, with clamping within 20 seconds and initial neonatal care after clamping. This study demonstrated feasibility of a large UK randomised trial. Of 135 infants allocated to cord clamping ≥ 2 minutes, 7 (5.2%) died and, of 135 allocated to cord clamping ≤ 20 seconds, 15 (11.1%) died (risk difference –5.9%, 95% confidence interval –12.4% to 0.6%). Of live births, 43 out of 134 (32%) allocated to cord clamping ≥ 2 minutes had intraventricular haemorrhage compared with 47 out of 132 (36%) allocated to cord clamping ≤ 20 seconds (risk difference –3.5%, 95% CI –14.9% to 7.8%). LIMITATIONS:Small sample for the qualitative interviews about preterm birth, single-centre evaluation of neonatal care beside the mother, and a pilot trial. CONCLUSIONS:Our programme of research has improved understanding of parent experiences of very preterm birth, and informed clinical guidelines and the research agenda. Our two-stage consent pathway is recommended for intrapartum clinical research trials. Our pilot trial will contribute to the individual participant data meta-analysis, results of which will guide design of future trials. FUTURE WORK:Research in preterm birth should take account of the top priorities. Further evaluation of neonatal care beside the mother is merited, and future trial of alternative policies for management of cord clamping should take account of the meta-analysis. STUDY REGISTRATION:This study is registered as PROSPERO CRD42012003038 and CRD42013004405. In addition, Current Controlled Trials ISRCTN21456601. FUNDING:This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 8. See the NIHR Journals Library website for further project information

Lobe Specific Ca2+-Calmodulin Nano-Domain in Neuronal Spines: A Single Molecule Level Analysis

Calmodulin (CaM) is a ubiquitous Ca2+ buffer and second messenger that affects cellular function as diverse as cardiac excitability, synaptic plasticity, and gene transcription. In CA1 pyramidal neurons, CaM regulates two opposing Ca2+-dependent processes that underlie memory formation: long-term potentiation (LTP) and long-term depression (LTD). Induction of LTP and LTD require activation of Ca2+-CaM-dependent enzymes: Ca2+/CaM-dependent kinase II (CaMKII) and calcineurin, respectively. Yet, it remains unclear as to how Ca2+ and CaM produce these two opposing effects, LTP and LTD. CaM binds 4 Ca2+ ions: two in its N-terminal lobe and two in its C-terminal lobe. Experimental studies have shown that the N- and C-terminal lobes of CaM have different binding kinetics toward Ca2+ and its downstream targets. This may suggest that each lobe of CaM differentially responds to Ca2+ signal patterns. Here, we use a novel event-driven particle-based Monte Carlo simulation and statistical point pattern analysis to explore the spatial and temporal dynamics of lobe-specific Ca2+-CaM interaction at the single molecule level. We show that the N-lobe of CaM, but not the C-lobe, exhibits a nano-scale domain of activation that is highly sensitive to the location of Ca2+ channels, and to the microscopic injection rate of Ca2+ ions. We also demonstrate that Ca2+ saturation takes place via two different pathways depending on the Ca2+ injection rate, one dominated by the N-terminal lobe, and the other one by the C-terminal lobe. Taken together, these results suggest that the two lobes of CaM function as distinct Ca2+ sensors that can differentially transduce Ca2+ influx to downstream targets. We discuss a possible role of the N-terminal lobe-specific Ca2+-CaM nano-domain in CaMKII activation required for the induction of synaptic plasticity