We formulate haptotaxis models of cancer invasion wherein the infiltrating cancer cells can occupy a spectrum of states in phenotype space, ranging from ‘fully mesenchymal’ to ‘fully epithelial’. The more mesenchymal cells are those that display stronger haptotaxis responses and have greater capacity to modify the extracellular matrix (ECM) through enhanced secretion of matrix-degrading enzymes (MDEs). However, as a trade-off, they have lower proliferative capacity than the more epithelial cells. The framework is multiscale in that we start with an individual-based model that tracks the dynamics of single cells, which is based on a branching random walk over a lattice representing both physical and phenotype space. We formally derive the corresponding continuum model, which takes the form of a coupled system comprising a partial integro-differential equation for the local cell population density function, a partial differential equation for the MDE concentration and an infinite-dimensional ordinary differential equation for the ECM density. Despite the intricacy of the model, we show, through formal asymptotic techniques, that for certain parameter regimes it is possible to carry out a detailed travelling wave analysis and obtain invading fronts with spatial structuring of phenotypes. Precisely, the most mesenchymal cells dominate the leading edge of the invasion wave and the most epithelial (and most proliferative) dominate the rear, representing a bulk tumour population. As such, the model recapitulates similar observations into a front to back structuring of invasion waves into leader-type and follower-type cells, witnessed in an increasing number of experimental studies over recent years.

Fetal and child development are shaped by early life exposures, including maternal health states, nutrition and educational and home environments. We aimed to determine if suboptimal pre-pregnancy maternal body mass index (BMI; underweight, overweight, obese) would associate with poorer cognitive outcomes in children, and whether early life nutritional, educational and home environments modify these relationships. Self-reported data were obtained from mother-infant dyads from the pan-Canadian prospective Maternal-Infant Research on Environmental Chemicals cohort. Relationships between potential risk factors (pre-pregnancy maternal BMI, breastfeeding practices and Home Observation Measurement of the Environment [HOME] score) and child cognitive development at age three (Weschler’s Preschool and Primary Scale of Intelligence, Third Edition scale and its subcategories) were each evaluated using analysis of variance, multivariable regression models and moderating analyses. Amongst the 528 mother−child dyads, increasing maternal pre-pregnancy BMI was negatively associated with scores for child full-scale IQ (β [95% CI]; −2.01 [−3.43, −0.59], p = 0.006), verbal composite (−1.93 [−3.33, −0.53], p = 0.007), and information scale (−0.41 [−0.70, −0.14], p = 0.003) scores. Higher maternal education level or HOME score attenuated the negative association between maternal pre-pregnancy BMI and child cognitive outcome by 30%–41% and 7%–22%, respectively, and accounted for approximately 5%–10% greater variation in male children’s cognitive scores compared to females. Maternal education and higher quality home environment buffer the negative effect of elevated maternal pre-pregnancy BMI on child cognitive outcomes. Findings suggest that relationships between maternal, social and environmental factors must be considered to reveal pathways that shape risk for, and resiliency against, suboptimal cognitive outcomes in early life.

Prenatal exposure to persistent organic pollutants (POPs) has been associated with the development of metabolic syndrome-related diseases in offspring. According to epidemiological studies, father’s transmission of environmental effects in addition to mother’s can influence offspring health. Moreover, maternal prenatal dietary folic acid (FA) may beneficially impact offspring health. The objective is to investigate whether prenatal FA supplementation can overcome the deleterious effects of prenatal exposure to POPs on lipid homeostasis and inflammation in three generations of male rat descendants through the paternal lineage. Female Sprague-Dawley rats (F0) were exposed to a POPs mixture (or corn oil) +/− FA supplementation for 9 weeks before and during gestation. F1 and F2 males were mated with untreated females. Plasma and hepatic lipids were measured in F1, F2, and F3 males after 12-h fast. Gene expression of inflammatory cytokines was determined by qPCR in epididymal adipose tissue. In F1 males, prenatal POPs exposure increased plasma lipids at 14 weeks old and hepatic lipids at 28 weeks old and prenatal FA supplementation decreased plasma total cholesterol at 14 weeks old. Prenatal POPs exposure decreased plasma triglycerides at 14 weeks old in F2 males. No change was observed in inflammatory markers. Our results show an impact of the paternal lineage on lipid homeostasis in rats up to the F2 male generation. FA supplementation of the F0 diet, regardless of POPs exposure, lowered plasma cholesterol in F1 males but failed to attenuate the deleterious effects of prenatal POPs exposure on plasma and hepatic lipids in F1 males.

A recent outbreak of Q fever was linked to an intensive goat and sheep dairy farm in Victoria, Australia, 2012-2014. Seventeen employees and one family member were confirmed with Q fever over a 28-month period, including two culture-positive cases. The outbreak investigation and management involved a One Health approach with representation from human, animal, environmental and public health. Seroprevalence in non-pregnant milking goats was 15% [95% confidence interval (CI) 7–27]; active infection was confirmed by positive quantitative PCR on several animal specimens. Genotyping of Coxiella burnetii DNA obtained from goat and human specimens was identical by two typing methods. A number of farming practices probably contributed to the outbreak, with similar precipitating factors to the Netherlands outbreak, 2007-2012. Compared to workers in a high-efficiency particulate arrestance (HEPA) filtered factory, administrative staff in an unfiltered adjoining office and those regularly handling goats and kids had 5·49 (95% CI 1·29–23·4) and 5·65 (95% CI 1·09–29·3) times the risk of infection, respectively; suggesting factory workers were protected from windborne spread of organisms. Reduction in the incidence of human cases was achieved through an intensive human vaccination programme plus environmental and biosecurity interventions. Subsequent non-occupational acquisition of Q fever in the spouse of an employee, indicates that infection remains endemic in the goat herd, and remains a challenge to manage without source control.

Folate is an essential B vitamin required for de novo purine and thymidylate synthesis, and for the remethylation of homocysteine to form methionine. Folate deficiency has been associated with placenta-related pregnancy complications, as have SNP in genes of the folate-dependent enzymes, methionine synthase (MTR) and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). We aimed to determine the effect of altered folate metabolism on placental cell proliferation, viability and invasive capacity and on progesterone and human chorionic gonadotropin (hCG) secretion. Human placental choriocarcinoma (JEG-3) cells cultured in low folic acid (FA) (2 nm) demonstrated 13 % (P<0·001) and 26 % (P<0·001) lower proliferation, 5·5 % (P=0·025) and 7·5 % (P=0·004) lower invasion capacity, and 5 to 7·5 % (P=0·004–0·025) lower viability compared with control (20 nm) or supplemented (100 nm) cells, respectively. FA concentration had no effect on progesterone or hCG secretion. Small interfering RNA (siRNA) knockdown of MTR gene and protein expression resulted in 17·7 % (P<0·0001) lower proliferation and 61 % (P=0·014) higher progesterone secretion, but had no effect on cell invasion and hCG secretion. siRNA knockdown of MTHFD1 gene expression in the absence of detectable changes in protein expression resulted in 10·3 % (P=0·001) lower cell proliferation, but had no effect on cell invasion and progesterone or hCG secretion. Our data indicate that impaired folate metabolism can result in lower trophoblast proliferation, and could alter viability, invasion capacity and progesterone secretion, which may explain in part the observed associations between folate and placenta-related complications.

TM-QTL is a quantitative trait locus (QTL) on ovine chromosome 18 (OAR18) known to affect loin muscling in Texel sheep. Previous work suggested that its mode of inheritance is consistent with paternal polar overdominance, but this has yet to be formally demonstrated. This study used purebred Texel sheep segregating for TM-QTL to confirm its presence in the chromosomal region in which it was first reported and to determine its pattern of inheritance. To do so, this study used the first available data from a Texel flock, which included homozygote TM-QTL carriers (TM/TM; n=34) in addition to homozygote non-carriers (+/+; n=40 and, heterozygote TM-QTL-carriers inheriting TM-QTL from their sire (TM/+; n=53) or their dam (+/TM; n=17). Phenotypes included a wide range of loin muscling, carcass composition and tissue distribution traits. The presence of a QTL affecting ultrasound muscle depth on OAR18 was confirmed with a paternal QTL effect ranging from +0.54 to +2.82 mm UMD (s.e. 0.37 to 0.57 mm) across the sires segregating for TM-QTL. Loin muscle width, depth and area, loin muscle volume and dissected M. longissimus lumborum weight were significantly greater for TM/+ than +/+ lambs (+2.9% to +7.9%; P<0.05). There was significant evidence that the effect of TM-QTL on the various loin muscling traits measured was paternally polar overdominant (P<0.05). In contrast, there was an additive effect of TM-QTL on both live weight at 20 weeks and carcass weight; TM/TM animals were significantly (P<0.05) heavier than +/+ (+11.1% and +7.3%, respectively) and +/TM animals (+11.9% and +11.7%, respectively), with TM/+ intermediate. Weights of the leg, saddle and shoulder region (corrected for carcass weight) were similar in the genotypic groups. There was a tendency for lambs inheriting TM-QTL from their sire to be less fat with slightly more muscle than non-carriers. For example, carcass muscle weight measured by live animal CT-scanning was 2.8% higher in TM/TM than +/+ lambs (P<0.05), carcass muscle weight measured by carcass CT-scanning was 1.36% higher in TM/+ than +/+ lambs (P<0.05), and weight of fat trimmed from the carcass cuts was significantly lower for TM/+ than +/+ lambs (−11.2%; P<0.05). No negative effects of TM-QTL on carcass traits were found. Optimal commercial use of TM-QTL within the sheep industry would require some consideration, due to the apparently different mode of action of the two main effects of TM-QTL (on growth and muscling).

HISTORICALLY AND CONCEPTUALLY CONSTITUTIONAL GOVERNMENT IS presented as the antithesis of absolute sovereignty and the prophylactic to tyrannical oppression. The paradigm form for absolute sovereignty is rule by one man and, since everything turns on the character of that man, such rule is inherently liable to collapse through incapacity, or to degenerate into tyranny. Tyranny is an ill against which necessarily there can be no protection under conditions of absolute sovereignty. Constitutional government may, therefore, be conceived as an attempt to provide built-in safeguards to prevent, or at least reduce the chances of, absolute sovereignty assuming the corrupt andperverted form of tyranny. Such safeguards inevitably restrict the absolute nature of sovereign rule.

THE DENIAL OF HUMAN RIGHTS IN SOCIALIST STATES CAN BE seen as the natural outcome of Marxist praxis: Marxist teaching about the nature of the class struggle and the conditions necessary for the emancipation of the proletariat from bourgeois values is not only theoretically alien to the concept of universal human rights, but its implementation by Marxist revolutionaries in the circumstances expected to prevail is likely to require the denial of such rights to ever-widening sections of the society if political power is to be secured and retained.

During the 2009 influenza A (H1N1) pandemic, many pregnant women experienced severe illness and some gave birth while ill with suspected or confirmed pandemic (H1N1) 2009 influenza. Because of concerns about possible transmission of this novel virus to immunologically naïve newborns, and the absence of definitive studies regarding this risk, the Centers for Disease Control and Prevention (CDC) reviewed relevant literature to understand the potential burden of disease and routes of transmission affecting newborns. This report describes the issues considered during the 2009 H1N1 pandemic as CDC developed guidance to protect newborns in hospital settings. Also presented is a framework of protection efforts to prevent novel influenza infection in fetuses/newborns before birth and in hospital settings. Although developed specifically for the pandemic, the framework may be useful during future novel influenza outbreaks.

(Disaster Med Public Health Preparedness. 2012;6:97-103)

The ability to efficiently harvest heat as a source of sustainable energy would make a significant contribution to reducing our current reliance on fossil fuels. Waste heat sources, such as those produced in industrial processes or through geothermal activity, are extensive, often continuous, and at present severely underutilised. Thermoelectrochemical cells offer an alternative design to the traditional semiconductor-based thermoelectric devices and offer thepromise of continuous and cheap operation at moderate temperatures, low maintenance and with no carbon emissions. They utilise two electrodes, held at different temperatures, separated by an electrolyte containing a redox couple. It is the temperature dependence of the electrochemical redox potential that generates the potential difference across the device as a result of the appliedtemperature difference. The magnitude of this redox potential temperature dependence is given by the Seebeck coefficient, Se. Until recently, research into thermoelectrochemical cells had primarily focused on aqueous media, predominantly with the Fe(CN)63-/4- redox couple.[1] However, the good thermal and electrochemical stability, non-volatility and non-flammability ofmany ionic liquids make them promising alternative electrolytes for these devices. The use of ionic liquid (IL) electrolytes offers potential advantages that include increased thermoelectrochemical device efficiencies and lifetimes and the ability to utilise low temperature (often “waste”) heat sources in the 100 – 200 °C temperature range.[2] Here we discuss our research into the use of the Fe(CN)63-/4- redox couple in protic IL electrolytes, with different amounts of added water, in a thermoelectrochemical device with platinum and single walled carbon nanotube (SWNT) electrodes.

Inflammatory bowel disease (IBD) is a risk factor for the development of colon cancer. Environmental factors including diet and the microflora influence disease outcome. Folate and homocysteine have been associated with IBD-mediated colon cancer but their roles remain unclear. We used a model of chemically induced ulcerative colitis (dextran sodium sulphate (DSS)) with or without the colon carcinogen azoxymethane (AOM) to determine the impact of dietary folic acid (FA) on colonic microflora and the development of colon tumours. Male mice (n 15 per group) were fed a FA-deficient (0 mg/kg), control (2 mg/kg) or FA-supplemented (8 mg/kg) diet for 12 weeks. Folate status was dependent on the diet (P< 0·001) and colitis-induced treatment (P= 0·04) such that mice with colitis had lower circulating folate. FA had a minimal effect on tumour initiation, growth and progression, although FA-containing diets tended to be associated with a higher tumour prevalence in DSS-treated mice (7–20 v. 0 %, P= 0·08) and the development of more tumours in the distal colon of AOM-treated mice (13–83 % increase, P= 0·09). Folate deficiency was associated with hyperhomocysteinaemia (P< 0·001) but homocysteine negatively correlated with tumour number (r − 0·58, P= 0·02) and load (r − 0·57, P= 0·02). FA had no effect on the intestinal microflora. The present data indicate that FA intake has no or little effect on IBD or IBD-mediated colon cancer in this model and that hyperhomocysteinaemia is a biomarker of dietary status and malabsorption rather than a cause of IBD-mediated colon cancer.

An attraction to certain plant species by Bombus terricola, B. bimaculatus, B. perplexus, and B. ternarius was observed. The gathering of pollen was observed as a behavioural act distinct from nectar gathering. Pollen analyses indicated that pollen collectors restricted their activities to a small number of plant species. These bees’ life histories and flower preferences made them potentially effective pollinators of early-flowering economic crops, Ribes spp., and Pyrus Malus in particular, and of common weeds such as Solanum Dulcamara and Hypericum perforatum. The same reasons prevented them from being important in the pollination of Trifolium pratense and Medicago sativa.

Morley's theorem states that the points of intersection of adjacent trisectors of the angles of any triangle are the vertices of an equilateral triangle, known as Morley's triangle. See Figure 1.

Concise proofs of the theorem are given in recent papers [1, 2]. A good picture of important previous work can be obtained by looking at [3, p. 1999], and examining references cited there.

LoinMAX (LM) is a quantitative trait locus (QTL), which was found to be segregated in Australian Poll Dorset sheep, and maps to the distal end of sheep chromosome 18. LM-QTL was reported to increase Musculus longissimus dorsi area and weight by 11% and 8%, respectively. The aim of this study was to comprehensively evaluate the direct effects of LM-QTL in a genetic background typical of the stratified structure of the UK sheep industry, before it can be recommended for use in the United Kingdom. Crossbred lambs, either non-carriers or carrying a single copy of LM-QTL, were produced out of Scottish Mule ewes (Bluefaced Leicester × Scottish Blackface) artificially inseminated with semen from two Poll Dorset rams that were heterozygous for LM-QTL. Unexpectedly, one of these rams was also heterozygous for a QTL that affects the overall carcass muscling (MyoMAX™). This was accounted for by nesting MyoMAX™ status (carrier or non-carrier) within sire in the statistical analysis. Lambs were weighed and scanned by using X-ray computed tomography (CT) at an average age of 113 days. Ultrasound scan measurements, along with lamb weights, were taken at an average age of 140 days and lambs were then slaughtered. Carcasses were weighed and classified for fat cover and conformation scores, based on the Meat and Livestock Commission (MLC) carcass classification scheme, and then scanned by using a video image analysis (VIA) system. M. longissimus lumborum (MLL) width, as measured by CT scanning, was greater (P < 0.05) in lambs heterozygous for LM-QTL compared with non-carriers. MLL in LM-QTL carrier lambs was also significantly deeper, as measured by both ultrasound muscle depth at the third lumbar vertebrae (+3.7%; P < 0.05) and CT scanning at the fifth lumbar vertebrae (+3.4%; P < 0.01). Consequently, MLL area, was measured by using CT scanning, was significantly higher (+4.5%; P < 0.01) in lambs carrying a single copy of LM-QTL compared with non-carriers. Additional traits measured by CT, such as leg muscle dimensions, average muscle density and tissue proportions, were not significantly affected by LM-QTL. LM-QTL did not significantly affect total carcass lean or fat weights or MLC conformation and fat score classifications. Using previously derived algorithms, VIA could detect a significant effect of the LM-QTL on the predicted weight of saleable meat yield in the loin primal cut (+2.2%; P < 0.05), but not in the other primal cuts, or the total carcass.