Factors affecting Confidence Index in EBSD analysis.

Automated EBSD analysis systems have been used for over two decades relying on the fact that the correctness of a particular orientation solution could be assessed through the calculation of a Confidence Index. However, such an index only reports whether a particular solution stands out among any other possible solutions, by receiving a larger number of votes than others, and does not necessarily imply that the corresponding orientation is correct. This issue is addressed in the present paper, where the correctness of solutions and the factors that might affect it have been studied for single crystal Si and polycrystalline Zn. The results were compared to those presented in previous papers where this matter was studied in particular for an FCC material. It was observed that about 90% of the solutions were correct if they were obtained using a confidence index of 0.1 using at least 8 Hough bands regardless of the crystallographic structure or orientation.

Nisin variants from Streptococcus and Staphylococcus successfully express in NZ9800.

AIMS: Increases in antimicrobial resistance have meant that the antimicrobial potential of lantibiotics is now being investigated irrespective of the nature of the producing organism. The aim of this study was to investigate whether natural nisin variants produced by non-Generally Recognized as Safe (GRAS) strains, such as nisin H, nisin J and nisin P, could be expressed in a well-characterized GRAS host. METHODS AND RESULTS: This study involved cloning the nisin A promoter and leader sequence fused to nisin H, nisin J or nisin P structural gene sequences originally produced by Streptococcus hyointestinalis DPC 6484, Staphylococcus capitis APC 2923 and Streptococcus agalactiae DPC 7040, respectively. This resulted in their expression in Lactococcus lactis NZ9800, a genetically modified strain that does not produce nisin A. CONCLUSIONS: Induction of the nisin controlled gene expression system demonstrates that these three nisin variants could be acted on by nisin A machinery provided by the host strain. SIGNIFICANCE AND IMPACT OF THE STUDY: Describes the first successful heterologous production of three natural nisin variants by a GRAS strain, and demonstrates how such systems could be harnessed not only for lantibiotic production but also in the expansion of their structural diversity and development for use as future biotherapeutics.

Librating dipoles as a probe of spontaneously electrical films and as a source of THz radiation.

Pulsed electrical excitation of films, composed of spontaneously oriented dipolar molecules, is predicted to cause libration of the constituent species about their fixed lattice sites, accompanied by an oscillating surface potential and emission of THz radiation. We focus on a 100 monolayer (ML) film of nitrous oxide, deposited at 53.5 K, containing oriented dipoles which sustain a spontaneous field of 4.77 × 107 V m-1 and an associated surface potential of 1.386 V. An external field of 108 V m-1, applied to the film, perturbs the angle of dipole orientation by ∼0.95°. Rapid removal of this field causes the dipoles to librate about their steady state orientation. The surface potential oscillates accordingly with a peak-to-peak amplitude of 0.587 V and a frequency of 2.090 THz. The librational motion of the dipoles generates 1.409 µW of THz power per cm2 of substrate, in 4π sr, composed of short bursts of radiation, at a repetition frequency of 4.181 THz. This power may be generated effectively continuously if the perturbing field is applied at a frequency of a few kHz. Observation of the amplitude and time structure of oscillatory surface potentials and of THz emission may potentially provide new and general probes of the spontelectric state, allowing direct observation of hindered molecular rotation and revealing the range of angles of dipole orientation in the crystalline environment.

A novel bioengineered derivative of nisin displays enhanced antimicrobial activity against clinical Streptococcus agalactiae isolates.

OBJECTIVES: Streptococcus agalactiae is the leading cause of neonatal disease worldwide, and infections caused by this opportunistic pathogen are becoming increasingly more prevalent in adults. With the global incidence of antimicrobial resistance continuing to rise, there is a recognised need for new therapeutic agents. Nisin is a potent antimicrobial peptide with demonstrated broad-spectrum activity against a range of clinically significant pathogens. This study aimed to examine the efficacy of nisin against a clinical population of S. agalactiae isolates and further to investigate the bioactivity of a novel bioengineered derivative of the peptide, designated nisin PV. METHODS: A deferred antagonism assay was used to assess the bioactivity of wild-type nisin and nisin PV against 122 S. agalactiae isolates. Minimum inhibitory concentrations (MICs) were evaluated to determine the specific activity of both peptides. The genetic basis of nisin resistance among the isolate collection was investigated by PCR detection of the nsr gene. RESULTS: In total, 91.0% (111/122) of the collection showed some level of susceptibility to nisin, whilst 9.0% (11/122) displayed complete resistance. Interestingly, the nisin derivative exhibited enhanced antimicrobial activity for 64.8% of the isolates. The frequency of the nsr gene conferring nisin resistance was 98.4% (120/122), suggesting that resistance may be linked to levels of expression of the protein or other regulatory elements. CONCLUSION: This study indicates that there is potential for the use of nisin and its derivatives as therapeutic agents against S. agalactiae infections.

Assigning a structural motif using spontaneous molecular dipole orientation in thin films.

Spontaneous orientation of molecular dipoles has been observed to produce bulk electric fields, termed 'spontelectric' fields, in a broad variety of molecular solid thin films formed by condensation from the gas phase. Such spontelectric fields are found in cis-methyl formate (cis-MF) and the present work combines observation of these fields with high quality ab initio studies of cis-MF monomers and dimers. This enables a prediction of the structural motif within the unit cell of the crystalline phase of solid cis-MF, showing it to be a non-polar dimer. Dimer formation at deposition temperatures of >90 K is therefore cited to contribute to the observed collapse of the spontelectric field at these temperatures. This is the first time that such a structural prediction has been made using observations of spontelectric behaviour as a key indicator.

Non-linear and non-local behaviour in spontaneously electrical solids.

Using reflection-absorption infrared spectroscopy (RAIRS), we show that solids displaying spontaneous dipole orientation possess quite general non-local and non-linear characteristics, exemplified through their internal electric fields. The most graphic illustration of this, uncovered originally through electron beam studies, may be found in films of cis-methyl formate (cis-MF), for which data demonstrated the counter-intuitive property that the degree of dipole order in the film does not monotonically decrease as the temperature of deposition rises, but rather increases sharply above ∼77 K. Here we show how RAIRS provides independent evidence to support this conclusion. These new data confirm (i) that the behaviour of spontelectrics is governed by an expression for the degree of dipole orientation, which is continuous in temperature, but with a discontinuity in the derivative, and (ii) that the temperature of deposition associated with this discontinuity matches the temperature above which dipole order switches from the expected reduction with temperature to an increase with temperature.

Effects of the community-based Wellspring Cancer Exercise Program on functional and psychosocial outcomes in cancer survivors.

PURPOSE: In this study, we examined the effects of a 30-week community-based exercise program on cancer-related fatigue, quality of life, and other health-related outcomes in a sample of adults with mixed cancer diagnoses. METHODS: This prospective cohort study looked at outcomes for participants involved in the Wellspring Cancer Exercise Program in southern Ontario. The program consisted of an initial phase of two supervised sessions weekly for 10 weeks and a transition phase of one supervised session weekly for the subsequent 20 weeks. Outcomes were measured at baseline and every 10 weeks throughout the intervention, as well as at 16 weeks after program completion. RESULTS: During a period of 13 months, 229 of the 355 cancer survivors who enrolled in the exercise program consented to participate in the study. Participants attended 71% of the supervised exercise sessions in the initial phase and 49% in the transition phase. From baseline to the end of the initial phase, significant improvements in cancer-related fatigue, 6-minute walk test, social well-being, systolic blood pressure, balance, and physical activity volume were observed. During the transition phase, health-related quality of life and emotional well-being improved significantly. CONCLUSIONS: The Wellspring Cancer Exercise Program is associated with clinically meaningful improvements in cancer-related fatigue and functional aerobic capacity. Several other aspects of well-being in cancer survivors also improved for participants in the program. Community-based cancer exercise programs such as the Wellspring Cancer Exercise Program can improve well-being for cancer survivors and can provide an effective option that enhances sustainability and accessibility to exercise services for this population.

Population assignment in autopolyploids.

Understanding the patterns of contemporary gene dispersal within and among populations is of critical importance to population genetics and in managing populations for conservation. In contrast to diploids, there are few studies of gene dispersal in autopolyploids, in part due to complex polysomic inheritance and genotype ambiguity. Here we develop a novel approach for population assignment for codominant markers for autotetraploids and autohexaploids. This method accounts for polysomic inheritance, unreduced gametes and unknown allele dosage. It can also utilise information regarding the origin and genotype of one parent for population assignment of maternal or paternal parents. Using simulations, we demonstrate that our approach achieves high levels of accuracy for assignment even when population divergence is low (FST~0.06) and with only 12 microsatellite loci. We also show that substantially higher accuracy is achieved when known maternal information is utilised, regardless of whether allele dosage is known. Although this novel method exhibited near identical levels of accuracy to Structure when population divergence was high, it performed substantially better for most parameters at moderate (FST=0.06) to low levels of divergence (FST=0.03). These methods fill an important gap in the toolset for autopolyploids and pave the way for investigating contemporary gene dispersal in a widespread group of organisms.

Wannier-Mott Excitons in Nanoscale Molecular Ices.

The absorption of light to create Wannier-Mott excitons is a fundamental feature dictating the optical and photovoltaic properties of low band gap, high permittivity semiconductors. Such excitons, with an electron-hole separation an order of magnitude greater than lattice dimensions, are largely limited to these semiconductors but here we find evidence of Wannier-Mott exciton formation in solid carbon monoxide (CO) with a band gap of >8 eV and a low electrical permittivity. This is established through the observation that a change of a few degrees K in deposition temperature can shift the electronic absorption spectra of solid CO by several hundred wave numbers, coupled with the recent discovery that deposition of CO leads to the spontaneous formation of electric fields within the film. These so-called spontelectric fields, here approaching 4×10^{7} V m^{-1}, are strongly temperature dependent. We find that a simple electrostatic model reproduces the observed temperature dependent spectral shifts based on the Stark effect on a hole and electron residing several nm apart, identifying the presence of Wannier-Mott excitons. The spontelectric effect in CO simultaneously explains the long-standing enigma of the sensitivity of vacuum ultraviolet spectra to the deposition temperature.

Glutamate Receptor Interacting Protein 1 Regulates CD4(+) CTLA-4 Expression and Transplant Rejection.

PDZ domains are common 80- to 90-amino-acid regions named after the first three proteins discovered to share these domains: postsynaptic density 95, discs large, and zonula occludens. PDZ domain-containing proteins typically interact with the C-terminus of membrane receptors. Glutamate receptor interacting protein 1 (GRIP1), a seven-PDZ domain protein scaffold, regulates glutamate receptor surface expression and trafficking in neurons. We have found that human and mouse T cells also express GRIP1. T cell-specific GRIP1(-/-) mice >11 weeks old had prolonged cardiac allograft survival. Compared with wild-type T cells, in vitro stimulated GRIP1(-/-) T cells had decreased expression of activation markers and increased apoptotic surface marker expression. Surface expression of the strong T cell inhibitory molecule cytotoxic T lymphocyte antigen-4 (CTLA-4) was increased on GRIP1(-/-) T cells from mice >11 weeks old. CTLA-4 increases with T cell stimulation and its surface expression on GRIP1(-/-) T cells remained high after stimulation was removed, indicating a possible internalization defect in GRIP1-deficient T cells. CTLA-4-blocking antibody treatment following heart transplantation led to complete rejection in T cell GRIP1(-/-) mice, indicating that increased CTLA-4 surface expression contributed to the extended graft survival. Our data indicate that GRIP1 regulates T cell activation by regulating CTLA-4 surface expression.

The dynamics of resource allocation and costs of reproduction in a sexually dimorphic, wind-pollinated dioecious plant.

Sexual dimorphism in resource allocation is expected to change during the life cycle of dioecious plants because of temporal differences between the sexes in reproductive investment. Given the potential for sex-specific differences in reproductive costs, resource availability may contribute to variation in reproductive allocation in females and males. Here, we used Rumex hastatulus, a dioecious, wind-pollinated annual plant, to investigate whether sexual dimorphism varies with life-history stage and nutrient availability, and determine whether allocation patterns differ depending on reproductive commitment. To examine if the costs of reproduction varied between the sexes, reproduction was either allowed or prevented through bud removal, and biomass allocation was measured at maturity. In a second experiment to assess variation in sexual dimorphism across the life cycle, and whether this varied with resource availability, plants were grown in high and low nutrients and allocation to roots, aboveground vegetative growth and reproduction were measured at three developmental stages. Males prevented from reproducing compensated with increased above- and belowground allocation to a much larger degree than females, suggesting that male reproductive costs reduce vegetative growth. The proportional allocation to roots, reproductive structures and aboveground vegetative growth varied between the sexes and among life-cycle stages, but not with nutrient treatment. Females allocated proportionally more resources to roots than males at peak flowering, but this pattern was reversed at reproductive maturity under low-nutrient conditions. Our study illustrates the importance of temporal dynamics in sex-specific resource allocation and provides support for high male reproductive costs in wind-pollinated plants.

Economic costs associated with moderate and late preterm birth: a prospective population-based study.

OBJECTIVE: We sought to determine the economic costs associated with moderate and late preterm birth. DESIGN: An economic study was nested within a prospective cohort study. SAMPLE: Infants born between 32(+0) and 36(+6)  weeks of gestation in the East Midlands of England. A sample of infants born at ≥37 weeks of gestation acted as controls. METHODS: Data on resource use, estimated from a National Health Service (NHS) and personal social services perspective, and separately from a societal perspective, were collected between birth and 24 months corrected age (or death), and valued in pounds sterling, at 2010-11 prices. Descriptive statistics and multivariable analyses were used to estimate the relationship between gestational age at birth and economic costs. MAIN OUTCOME MEASURES: Cumulative resource use and economic costs over the first two years of life. RESULTS: Of all eligible births, 1146 (83%) preterm and 1258 (79%) term infants were recruited. Mean (standard error) total societal costs from birth to 24 months were £12 037 (£1114) and £5823 (£1232) for children born moderately preterm (32(+0) -33(+6)  weeks of gestation) and late preterm (34(+0) -36(+6)  weeks of gestation), respectively, compared with £2056 (£132) for children born at term. The mean societal cost difference between moderate and late preterm and term infants was £4657 (bootstrap 95% confidence interval, 95% CI £2513-6803; P < 0.001). Multivariable regressions revealed that, after controlling for clinical and sociodemographic characteristics, moderate and late preterm birth increased societal costs by £7583 (£874) and £1963 (£337), respectively, compared with birth at full term. CONCLUSIONS: Moderate and late preterm birth is associated with significantly increased economic costs over the first 2 years of life. Our economic estimates can be used to inform budgetary and service planning by clinical decision-makers, and economic evaluations of interventions aimed at preventing moderate and late preterm birth or alleviating its adverse consequences. TWEETABLE ABSTRACT: Moderate and late preterm birth is associated with increased economic costs over the first 2 years of life.

Experiences with maternal and perinatal death reviews in the UK--the MBRRACE-UK programme.

Established in 1952, the programme of surveillance and Confidential Enquiries into Maternal Deaths in the UK is the longest running such programme worldwide. Although more recently instituted, surveillance and confidential enquiries into perinatal deaths are also now well established nationally. Recent changes to funding and commissioning of the Enquiries have enabled both a reinvigoration of the processes and improvements to the methodology with an increased frequency of future reporting. Close engagement with stakeholders and a regulator requirement for doctors to participate have both supported the impetus for involvement of all professionals leading to greater potential for improved quality of care for women and babies.

Source population characteristics affect heterosis following genetic rescue of fragmented plant populations.

Understanding the relative importance of heterosis and outbreeding depression over multiple generations is a key question in evolutionary biology and is essential for identifying appropriate genetic sources for population and ecosystem restoration. Here we use 2455 experimental crosses between 12 population pairs of the rare perennial plant Rutidosis leptorrhynchoides (Asteraceae) to investigate the multi-generational (F(1), F(2), F(3)) fitness outcomes of inter-population hybridization. We detected no evidence of outbreeding depression, with inter-population hybrids and backcrosses showing either similar fitness or significant heterosis for fitness components across the three generations. Variation in heterosis among population pairs was best explained by characteristics of the foreign source or home population, and was greatest when the source population was large, with high genetic diversity and low inbreeding, and the home population was small and inbred. Our results indicate that the primary consideration for maximizing progeny fitness following population augmentation or restoration is the use of seed from large, genetically diverse populations.

Aura attacks from acute convexity subarachnoid haemorrhage not due to cerebral amyloid angiopathy.

BACKGROUND AND PURPOSE: Convexity subarachnoid haemorrhage (cSAH) has recently been recognised as a cause of recurrent aura-like symptoms, mimicking transient ischaemic attacks (TIAs). Subarachnoid haemorrhage and recurrent aura-like episodes can occur in patients with cerebral amyloid angiopathy (CAA), which has been the presumed cause in the majority of reported cases. However, this syndrome can occur following cSAH secondary to other conditions, and it is important for clinicians to investigate and manage such patients appropriately. METHOD: Case series. RESULTS: We describe two patients who presented with recurrent stereotyped transient neurological symptoms in the setting of acute cSAH identified on MRI. In one patient, SAH occurred secondary to cerebral venous sinus thrombosis. In the other, SAH was due to extension of a traumatic subdural haematoma. CONCLUSIONS: Conditions other than CAA can cause the clinicoradiological syndrome of cSAH with recurrent TIA-like events. Gradient echo or susceptibility-weighted imaging should be included in the diagnostic work-up of patients presenting with such events. When cSAH is detected, the full differential diagnosis for this should be considered. Aetiologies other than CAA can cause this syndrome and management can vary greatly depending on the underlying cause.

Patterns of hybridization and asymmetrical gene flow in hybrid zones of the rare Eucalyptus aggregata and common E. rubida.

The patterns of hybridization and asymmetrical gene flow among species are important for understanding the processes that maintain distinct species. We examined the potential for asymmetrical gene flow in sympatric populations of Eucalyptus aggregata and Eucalyptus rubida, both long-lived trees of southern Australia. A total of 421 adults from three hybrid zones were genotyped with six microsatellite markers. We used genealogical assignments, admixture analysis and analyses of spatial genetic structure and spatial distribution of individuals, to assess patterns of interspecific gene flow within populations. A high number of admixed individuals were detected (13.9-40% of individuals), with hybrid populations consisting of F(1) and F(2) hybrids and backcrosses in both parental directions. Across the three sites, admixture proportions were skewed towards the E. aggregata genetic cluster (x=0.56-0.65), indicating that backcrossing towards E. aggregata is more frequent. Estimates of long-term migration rates also indicate asymmetric gene flow, with higher migration rates from E. aggregata to hybrids compared with E. rubida. Taken together, these results indicate a greater genetic input from E. aggregata into the hybrid populations. This asymmetry probably reflects differences in style lengths (E. rubida: ~7 mm, E. aggregata: ~4 mm), which can prevent pollen tubes of smaller-flowered species from fertilizing larger-flowered species. However, analyses of fine-scale genetic structure suggest that localized seed dispersal (<40 m) and greater clustering between hybrid and E. aggregata individuals may also contribute to directional gene flow. Our study highlights that floral traits and the spatial distributions of individuals can be useful predictors of the directionality of interspecific gene flow in plant populations.

Neonatal intensive care outcomes and resource utilisation of infants born <26 weeks in the former Trent region: 2001-2003 compared with 1991-1993.

OBJECTIVES: To provide survival data and rates of severe disability at 2 years of corrected age in infants born prior to 26 weeks' gestation in 2001-2003 and to compare these outcomes with an earlier cohort from 1991 to 1993. DESIGN: Population-based prospective cohort study. SETTING: Former Trent region of UK covering a population of approximately five million and around 55 000 births per annum. PARTICIPANTS: The authors identified a 3-year cohort of infants born before 26 weeks' gestation between 1 January 2001 and 31 December 2003 from The Neonatal Survey (TNS). Questionnaires based on the Oxford minimum dataset were completed. MAIN OUTCOME MEASURES: Survival, service use and disability levels were compared between the 2001- 2003 cohort and the cohort from 1991 to 1993. RESULTS: In 2001-2003, 0%, 18% and 35% of live born babies were alive at 2 years without any evidence of severe disability at 23, 24 and 25 weeks' gestation, respectively. Overall, of those children admitted to neonatal care, the proportion with no evidence of severe disability at 2 years corrected age improved from 14.5% in 1991-1993 to 26.5% in 2001-2003. There was an increase in the proportion of children with at least one severe disability, out of total admissions to neonatal unit (8% vs 17%) and of those assessed at 2 years (35% vs 39%). CONCLUSIONS: This study has shown an improvement in survival to discharge in babies admitted for neonatal care. However, this improved survival has been associated with an increase in the proportion of children with at least one severe disability at a corrected age of 2 years.