Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: −0.4, −0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752.

Drinking water application of Denargard Tiamulin for control of Brachyspira pilosicoli infection of laying poultry

Avian intestinal spirochaetosis (AIS) caused by Brachyspira spp., and notably Brachyspira pilosicoli, is common in layer flocks and reportedly of increasing incidence in broilers and broiler breeders. Disease manifests as diar- rhoea, increased feed consumption, reduced growth rates and occasional mortality in broilers and these signs are shown in layers also associated with a delayed onset of lay, reduced egg weights, faecal staining of eggshells and non-productive ovaries. Treatment with Denagard® Tiamulin has been used to protect against B. pilosicoli colonisation, persistence and clinical presentation of AIS in commercial layers, but to date there has been no de- finitive study validating efficacy. Here, we used a poultry model of B. pilosicoli infection of layers to compare the impact of three doses of Denagard® Tiamulin. Four groups of thirty 17 week old commercial pre-lay birds were all challenged with B. pilosicoli strain B2904 with three oral doses two days apart. All birds were colonised within 2 days after the final oral challenge and mild onset of clinical signs were observed thereafter. A fifth group that was unchallenged and untreated was also included for comparison as healthy birds. Five days after the final oral Brachypira challenge three groups were given Denagard® Tiamulin in drinking water made up following the manufacturer's recommendations with doses verified as 58.7 ppm, 113 ppm and 225 ppm. Weight gain body condition and the level of diarrhoea of birds infected with B. pilosicoli were improved and shedding of the organism reduced significantly (p = 0.001) following treatment with Denagard® Tiamulin irrespective of dose given. The level and duration of colonisation of organs of birds infected with B. pilosicoli was also reduced. Confirming previous findings we showed that the ileum, caeca, colon, and both liver and spleen were colonised and here we demonstrated that treatment with Denagard® Tiamulin resulted in significant reduction in the numbers of Brachyspira found in each of these sites and dramatic reduction in faecal shedding (p b 0.001) to ap- proaching zero as assessed by culture of cloacal swabs. Although the number of eggs produced per bird and the level of eggshell staining appeared unaffected, egg weights of treated birds were greater than those of untreated birds for a period of approximately two weeks following treatment. These data conclusively demonstrate the ef- fectiveness of Denagard® Tiamulin in reducing B. pilosicoli infection in laying hens.

Drinking water application of Denagard® Tiamulin for control of Brachyspira pilosicoli infection of laying poultry

Avian intestinal spirochaetosis (AIS) caused by Brachyspira spp., and notably Brachyspira pilosicoli, is common in layer flocks and reportedly of increasing incidence in broilers and broiler breeders. Disease manifests as diarrhoea,increased feed consumption, reduced growth rates and occasional mortality in broilers and these signs are shown in layers also associated with a delayed onset of lay, reduced egg weights, faecal staining of eggshells and non-productive ovaries. Treatment with Denagard® Tiamulin has been used to protect against B. pilosicoli colonisation, persistence and clinical presentation of AIS in commercial layers, but to date there has been no definitive study validating efficacy. Here, we used a poultry model of B. pilosicoli infection of layers to compare the impact of three doses of Denagard® Tiamulin. Four groups of thirty 17 week old commercial pre-lay birds were all challengedwith B. pilosicoli strain B2904with three oral doses two days apart. All birdswere colonised within 2 days after the final oral challenge and mild onset of clinical signs were observed thereafter. A fifth group that was unchallenged and untreated was also included for comparison as healthy birds. Five days after the final oral Brachypira challenge three groups were given Denagard® Tiamulin in drinking water made up following the manufacturer's recommendations with doses verified as 58.7 ppm, 113 ppm and 225 ppm. Weight gain body condition and the level of diarrhoea of birds infected with B. pilosicoli were improved and shedding of the organism reduced significantly (p = 0.001) following treatment with Denagard® Tiamulin irrespective of dose given. The level and duration of colonisation of organs of birds infected with B. pilosicoli was also reduced. Confirming previous findings we showed that the ileum, caeca, colon, and both liver and spleen were colonised and here we demonstrated that treatment with Denagard® Tiamulin resulted in significant reduction in the numbers of Brachyspira found in each of these sites and dramatic reduction in faecal shedding (p b 0.001) to approaching zero as assessed by culture of cloacal swabs. Although the number of eggs produced per bird and the level of eggshell staining appeared unaffected, egg weights of treated birds were greater than those of untreated birds for a period of approximately two weeks following treatment. These data conclusively demonstrate the effectiveness of Denagard® Tiamulin in reducing B. pilosicoli infection in laying hens.

Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial

There is much speculation with regard to the potential cardioprotective benefits of equol, a microbial-derived metabolite of the isoflavone daidzein, which is produced in the large intestine after soy intake in 30% of Western populations. Although cross-sectional and retrospective data support favorable associations between the equol producer (EP) phenotype and cardiometabolic health, few studies have prospectively recruited EPs to confirm this association. The aim was to determine whether the acute vascular benefits of isoflavones differ according to EP phenotype and subsequently investigate the effect of providing commercially produced S-(–)equol to non-EPs. We prospectively recruited male EPs and non-EPs (n = 14/ group) at moderate cardiovascular risk into a double-blind, placebocontrolled crossover study to examine the acute effects of soy isoflavones (80-mg aglycone equivalents) on arterial stiffness [carotid-femoral pulse-wave velocity (cfPWV)], blood pressure, endothelial function (measured by using the EndoPAT 2000; Itamar Medical), and nitric oxide at baseline (0 h) and 6 and 24 h after intake. In a separate assessment, non-EPs consumed 40 mg S-(–)equol with identical vascular measurements performed 2 h after intake. After soy intake, cfPWV significantly improved in EPs at 24 h (cfPWV change from 0 h: isoflavone, 20.2 6 0.2 m/s; placebo, 0.6 6 0.2 m/s; P , 0.01), which was significantly associated with plasma equol concentrations (R = 20.36, P = 0.01). No vascular effects were observed in EPs at 6 h or in non-EPs at any time point. Similarly, no benefit of commercially produced S-(–)equol was observed in non-EPs despite mean plasma equol concentrations reaching 3.2 mmol/L. Acute soy intake improved cfPWV in EPs, equating to an 11–12% reduced risk of cardiovascular disease if sustained. However, a single dose of commercially produced equol had no cardiovascular benefits in non-EPs. These data suggest that the EP phenotype is critical in unlocking the vascular benefits of equol in men, and long-term trials should focus on confirming the implications of EP phenotype on cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01530893. Am J Clin Nutr doi: 10.3945/ajcn.115.125690.

On the parameterization of turbulent surface fluxes over heterogeneous sea ice surfaces

Turbulent surface fluxes of momentum and sensible and latent heat as well as surface temperature, air temperature, air humidity, and wind speed were measured by the German Falcon research aircraft over the marginal ice zone (MIZ) of the northern Baltic Sea and the Fram Strait. Applying the bulk formulas and the stability functions to the measurements, the roughness lengths for momentum z0, sensible heat zT, and latent heat zq were calculated. As mean values over a wide range of sea ice conditions, we obtain z0 = 5 � 10�4 m, zT = 1 � 10�8 m, and zq = 1 � 10�7 m. These correspond to the following mean values (± standard deviations) of neutral transfer coefficients reduced to 10 m height, CDN10 = (1.9 ± 0.8) � 10�3, CHN10 = (0.9 ± 0.3) � 10�3, and CEN10 = (1.0 ± 0.2) � 10�3. An average ratio of z0/zT � 104 was observed over the range of 10�6 m < z0 < 10�2 m and differs from previously published results over compact sea ice (10�1 < z0/zT < 103). Other observational results over heterogeneous sea ice do not exist. However, our z0/zT ratio approximately agrees with observations over heterogeneous land surfaces. Flux parameterizations based on commonly used roughness lengths ratios (z0 = zT = zq) overestimate the surface heat fluxes compared to our measurements by more than 100%.

Intermittent exotropia: are we underminusing by not overminusing?

In this invited commentary, the authors discuss whether the use of minus lenses to aid control of intermittent exotropia has an alternative method of action. Conventional theory suggests that the lenses induce accommodation and therefore accommodative convergence to reduce the angle of deviation. We discuss evidence which suggests that convergence is induced to control the primary deviation and that the minus lenses allow this control by correcting refractive blur caused by additional vergence accommodation.

世論という神話―望むのは「死刑」ですか？’ (Public opinion myth: is ‘death’ what we really want?)

This paper summarises Mai Sato's recent report on public attitudes to the death penalty in Japan.

Rapid selective separation of americium/curium from simulated nuclear forensic matrices using triazine ligands

In analysis of complex nuclear forensic samples containing lanthanides, actinides and matrix elements, rapid selective extraction of Am/Cm for quantification is challenging, in particular due the difficult separation of Am/Cm from lanthanides. Here we present a separation process for Am/Cm(III) which is achieved using a combination of AG1-X8 chromatography followed by Am/Cm extraction with a triazine ligand. The ligands tested in our process were CyMe4-BTPhen, CyMe4- BTBP, CA-BTP and CA-BTPhen. Our process allows for purification and quantification of Am and Cm (recoveries 80%–100%) and other major actinides in < 2d without the use of multiple columns or thiocyanate. The process is unaffected by high level Ca(II)/Fe(III)/Al(III) (10mg mL−1) and thus requires little pre-treatment of samples.

Civilian casualties – do we really care? The failure of the revolution in military affairs of non-lethal weapons in the U.S., Russia and Israel

Causing civilian casualties during military operations has become a much politicised topic in international relations since the Second World War. Since the last decade of the 20th century, different scholars and political analysts have claimed that human life is valued more and more among the general international community. This argument has led many researchers to assume that democratic culture and traditions, modern ethical and moral issues have created a desire for a world without war or, at least, a demand that contemporary armed conflicts, if unavoidable, at least have to be far less lethal forcing the military to seek new technologies that can minimise civilian casualties and collateral damage. Non-Lethal Weapons (NLW) – weapons that are intended to minimise civilian casualties and collateral damage – are based on the technology that, during the 1990s, was expected to revolutionise the conduct of warfare making it significantly less deadly. The rapid rise of interest in NLW, ignited by the American military twenty five years ago, sparked off an entirely new military, as well as an academic, discourse concerning their potential contribution to military success on the 21st century battlefields. It seems, however, that except for this debate, very little has been done within the military forces themselves. This research suggests that the roots of this situation are much deeper than the simple professional misconduct of the military establishment, or the poor political behaviour of political leaders, who had sent them to fight. Following the story of NLW in the U.S., Russia and Israel this research focuses on the political and cultural aspects that have been supposed to force the military organisations of these countries to adopt new technologies and operational and organisational concepts regarding NLW in an attempt to minimise enemy civilian casualties during their military operations. This research finds that while American, Russian and Israeli national characters are, undoubtedly, products of the unique historical experience of each one of these nations, all of three pay very little regard to foreigners’ lives. Moreover, while it is generally argued that the international political pressure is a crucial factor that leads to the significant reduction of harmed civilians and destroyed civilian infrastructure, the findings of this research suggest that the American, Russian and Israeli governments are well prepared and politically equipped to fend off international criticism. As the analyses of the American, Russian and Israeli cases reveal, the political-military leaderships of these countries have very little external or domestic reasons to minimise enemy civilian casualties through fundamental-revolutionary change in their conduct of war. In other words, this research finds that employment of NLW have failed because the political leadership asks the militaries to reduce the enemy civilian casualties to a politically acceptable level, rather than to the technologically possible minimum; as in the socio-cultural-political context of each country, support for the former appears to be significantly higher than for the latter.

Aesthetical and narrative uses of the trench in the Hollywood cinema of 1918-1930

Throughout history of painting, the representation of landscape has been considered a laboratory for the human gaze on the world. The First World War and its new approach to the battlefield altered deeply the classical forms of representation, and replaced them with a mechanised and fragmentary vision, which was related with the development of photography and cinema. As Vicente J. Benet has analysed, Hollywod cinema used these deep changes in its filmic versions of the conflict, although it organised them following a narrative logic. In this text we intend to study how the battlefield and, particularly, the trench, are inserted in this logic of the history of landscape painting. We do so through some Hollywood films from the period 1918-1930. Firstly, we approach the trench as a composition value which can structure the image and guide the camera movement. In the second place, we study how it creates a dialog between its inside, melodrama scenery, and the outside, battlefield and danger. In both cases, we conclude that the trench as a form and as a narrative element plays a structuring and integrative role with the storytelling logic.

Pooled analysis of recent studies on magnetic fields and childhood leukaemia

BACKGROUND: Previous pooled analyses have reported an association between magnetic fields and childhood leukaemia. We present a pooled analysis based on primary data from studies on residential magnetic fields and childhood leukaemia published after 2000. METHODS: Seven studies with a total of 10 865 cases and 12 853 controls were included. The main analysis focused on 24-h magnetic field measurements or calculated fields in residences. RESULTS: In the combined results, risk increased with increase in exposure, but the estimates were imprecise. The odds ratios for exposure categories of 0.1-0.2 mu T, 0.2-0.3 mu T and >= 0.3 mu T, compared with <0.1 mu T, were 1.07 (95% Cl 0.81-1.41), 1.16 (0.69-1.93) and 1.44 (0.88-2.36), respectively. Without the most influential study from Brazil, the odds ratios increased somewhat. An increasing trend was also suggested by a nonparametric analysis conducted using a generalised additive model. CONCLUSIONS: Our results are in line with previous pooled analyses showing an association between magnetic fields and childhood leukaemia. Overall, the association is weaker in the most recently conducted studies, but these studies are small and lack methodological improvements needed to resolve the apparent association. We conclude that recent studies on magnetic fields and childhood leukaemia do not alter the previous assessment that magnetic fields are possibly carcinogenic. British Journal of Cancer (2010) 103, 1128-1135. doi: 10.1038/sj.bjc.6605838 www.bjcancer.com (c) 2010 Cancer Research UK