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Theranostics 2017; 7(1):23-30. doi:10.7150/thno.16577
Research Paper
Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT)
1. Department of Physics, Norwegian University of Science and Technology (NTNU), Trondheim, Norway;
2. Phoenix Solutions AS, Oslo, Norway;
3. Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway;
4. Department of Laboratory Medicine, Children's and Women's Health, NTNU, Trondheim, Norway.
Åslund AKO, Snipstad S, Healey A, Kvåle S, Torp SH, Sontum PC, Davies CdL, van Wamel A. Efficient Enhancement of Blood-Brain Barrier Permeability Using Acoustic Cluster Therapy (ACT). Theranostics 2017; 7(1):23-30. doi:10.7150/thno.16577. Available from http://www.thno.org/v07p0023.htm
The blood-brain barrier (BBB) is a major obstacle in drug delivery for diseases of the brain, and today there is no standardized route to surpass it. One technique to locally and transiently disrupt the BBB, is focused ultrasound in combination with gas-filled microbubbles. However, the microbubbles used are typically developed for ultrasound imaging, not BBB disruption. Here we describe efficient opening of the BBB using the promising novel Acoustic Cluster Therapy (ACT), that recently has been used in combination with Abraxane® to successfully treat subcutaneous tumors of human prostate adenocarcinoma in mice. ACT is based on the conjugation of microbubbles to liquid oil microdroplets through electrostatic interactions. Upon activation in an ultrasound field, the microdroplet phase transfers to form a larger bubble that transiently lodges in the microvasculature. Further insonation induces volume oscillations of the activated bubble, which in turn induce biomechanical effects that increase the permeability of the BBB. ACT was able to safely and temporarily permeabilize the BBB, using an acoustic power 5-10 times lower than applied for conventional microbubbles, and successfully deliver small and large molecules into the brain.
Keywords: Blood-brain barrier opening, focused ultrasound, acoustic cluster therapy (ACT), enhanced drug delivery
The blood-brain barrier (BBB) maintains the homeostasis of the brain and protects it from unwanted or harmful substances. Unfortunately, the BBB also blocks >98% of small drugs (<600 Da) and all larger therapeutic molecules from entering the brain, unless active transport of the substances is possible [1]. Thus, the presence of an intact BBB limits the distribution of a large number of therapeutic agents, including anti-cancer and anti-viral drugs, as well as novel therapeutic approaches that do not translate to clinical practice because of this biological barrier. For this reason, diseases like brain cancer, Alzheimer's disease, amyotrophic lateral sclerosis (ALS) and more, remain untreatable. New ways to pass the BBB have to be explored for every single drug lead, resulting in a severe restriction on the development of medicinal therapies for brain diseases. Since its introduction in 2001 [2], focused ultrasound (FUS) in combination with microbubbles has been explored to increase the permeability of the BBB in various pre-clinical settings [3]. In brief, insonation of the vascular compartment containing microbubbles leads to a variety of biomechanical effects that increase the permeability of the endothelial barrier both paracellularly and transcellularly [4]. The increased permeability leads to enhanced extravasation, distribution and uptake of drug molecules in the target tissue [5-7]. This approach is currently being evaluated in two separate clinical trials (ClinicalTrials.gov identifier NCT02343991 [8] and NCT02253212) [9, 10]. Most studies using FUS for BBB disruption (BBBD) are employing commercial ultrasound contrast agent microbubbles, such as Definity®, Sonovue® and Optison® [2, 11-16]. To improve treatment strategies, incorporation of drugs into custom-made microbubbles has also been investigated [17-19]. Whereas the concept clearly holds merit, it also has limitations. The microbubbles need to be close to the endothelial wall to maximize biomechanical effects [20, 21]. However, regular contrast microbubbles are small (1-3 µm), and their average distance to the vessel wall is often too large to induce a significant biomechanical effect. Furthermore, the circulation lifetime of most microbubbles is typically in the order of 2-3 min, thus limiting the exposure time. Although conventional microbubbles have shown promise for opening the BBB and for drug delivery to the brain, these microbubbles were developed for diagnostic imaging, not for therapy. Microbubble formulations designed for therapy are likely to be needed to enable optimal treatment regimens.
A recently proposed concept for ultrasound mediated, targeted drug delivery; Acoustic Cluster Therapy (ACT), makes use of similar mechanisms as regular microbubbles, but addresses important shortcomings of the latter. Details of the ACT formulation concept are described previously [22-24]. In brief, the ACT formulation is produced by electrostatic complexation between negatively charged microbubbles and positively charged oil microdroplets. The active moiety comprises microbubble/microdroplet clusters engineered to be stable in vivo. After intravenous injection of the clusters, ultrasound is applied to the diseased area and the microbubbles transfer acoustic energy to the attached droplets, which undergo a liquid-to-gas phase shift (the "Activation" Step). The resulting ACT-bubbles undergo a rapid expansion to approximately 25 μm and are temporarily deposited in the local capillary network, transiently blocking blood flow for up to 10 min. Further application of ultrasound (the "Enhancement" step) induces volume oscillations of the ACT-bubbles, which result in non-thermal mechanisms such as cavitation and shear forces that increase the local permeability of the vasculature, increasing transport of co-administered drugs across the capillary wall and through the extracellular matrix [23, 24]. Being approx. three orders of magnitude larger in volume than regular contrast microbubbles, ACT bubbles will deliver a significantly larger biomechanical effect. In addition, the ACT bubble is in close contact with the endothelial wall over a significant segment, ensuring optimal coupling between the vessel wall and the oscillating bubble. Finally, the ACT bubble stays for typically 10 minutes, prolonging the treatment time window compared to regular contrast microbubbles. We have recently shown that this concept can be utilized to induce a strong enhancement of the therapeutic efficacy of paclitaxel and nab-paclitaxel (Abraxane®) for treatment of solid tumors such as human prostate adenocarcinoma growing subcutaneously in athymic mice [25]. When combining the ACT treatment with a clinically relevant dose of Abraxane®, all of the treated mice were alive at the end of the study (120 days after treatment start, 99 days after treatment end) and 67% were in complete remission. Conversely, the group treated with Abraxane, without ACT treatment, had a median survival time 72 days' post treatment start (0% survival at the end of the study). Furthermore, during treatment, this group showed little tumor regression and more importantly, tumor growth continued immediately after the treatment was stopped. The median survival of the control group time was 28 days'.
In the current paper, we have investigated the ACT concept for opening the BBB for model drugs in rats. With the new ACT approach, it is possible to generate bubbles, in-situ, that more effectively deliver small and large model drugs into the brain, compared to regular contrast microbubbles. In addition, the applied ultrasound pressure in this study is 5 to 10 times lower than typical levels used with regular microbubbles, potentially making the treatment safer.
Materials and Methods
ACT and Sonazoid™
The ACT formulation consisted of a dispersion of microbubble/microdroplet clusters made from reconstituting the ultrasound contrast agent Sonazoid™ with 2 ml of perfluoromethylcyclopentane (PFMCP) microdroplets (3 µl/ml) stabilized with a distearoyl-phosphatidylcholine (DSPC) phospholipid membrane with 3% (mol/mol) stearylamine (SA), dispersed in 5 mM Tris(hydroxymethyl)aminomethane (TRIS) buffer. ACT was diluted 1/8 in (TRIS)-HCl buffer (pH 7.4) before injection [23].
Sonazoid™ (GE Healthcare AS, Norway) is an ultrasound contrast agent comprising perfluorobutane (PFB) microbubbles, stabilized with a hydrogenated egg phosphatidylserine-sodium (HEPS-Na) phospholipid membrane, embedded in a lyophilized sucrose matrix [26]. Sonazoid™ was diluted 1/8 in TRIS-HCl buffer (pH 7.4) before injection. Further details on the ACT formulation and the microbubble/microdroplet ratio are provided by Sontum et al [23]. ACT and Sonazoid™ were kindly provided by Phoenix Solution AS, Oslo, Norway.
Healthy female Sprague Dawley rats (NTac:SD; Taconic), 8-12 weeks old with a weight of 240-280 grams, were used. All experimental procedures were conducted in compliance with protocols approved by the Norwegian Animal Research Authorities. Animals were housed in a specific pathogen free environment at a 12h night/day cycle with controlled temperature and humidity. Food and water were provided ad libitum.
Ultrasound Setup and Treatment Regimen
A 1 MHz FUS transducer (Imasonic SAS) with a diameter of 50 mm and a focal length of 125 mm (f-number 2.5) was used. The transducer was positioned in a water bath and a specially designed magnetic resonance imaging (MRI) bed [19], with the animal in a supine position, placed on top of the water tank. The skull of the animal was positioned approximately 120 mm from the transducer.
The animal was sedated by gas anesthesia (isoflurane ~ 4% and 2% induction and maintenance, respectively, in 78% medical air/20% O2). The head of the animal was shaved using a trimmer, and depilatory cream was applied to the shaved area for 1 min to remove remaining hair. The tail vein was cannulated (BD Neoflon 24G, Becton Dickinson & Co), and the animal placed on the MRI bed. Omniscan (1 ml/kg, 0.5 mmol gadododiamide/kg) was injected and MR images were recorded. Sonazoid™ (1 ml/kg) or ACT (1 ml/kg) was injected and the cannula was flushed with 0.1 ml of 1 U/ml heparin. Immediately after injection, the ultrasound treatment was initiated. The treatment was divided into an activation step followed by an enhancement step using the same transducer and the same sonication sequence with two different mechanical indexes (MIs). The MI was calculated from the estimated in situ pressure, assuming 40% attenuation of the ultrasound power through the skull of the animal [19]. For the activation step, the parameters were: MI 0.28, 4 µs pulse length, pulse repetition frequency (PRF) 1 kHz, sonication time 30 s. For the enhancement step, MI was 0.09, 4 µs pulse length, PRF 1 kHz, sonication time 10 min. Each animal was treated two times in two different positions, posterior and anterior of the cerebrum, and the two treatments were sometimes from different treatment groups. The contralateral side of the treated position was used as an internal negative control. After treatment, MR images were recorded. The animals were intravenously injected with pentobarbital and perfused with phosphate saline buffer 1x (PBS) and 4% paraformaldehyde (PFA) in PBS and the brain was submerged in formalin (10%) for at least 24 h, before being sectioned for histology. The experimental timeline is shown in Fig. 1.
Five treatment groups were investigated.
1. ACT + Activation ultrasound + Enhancement ultrasound (ACT+A+E) (8 animals for BBBD, 4 animals for BBB recovery, 2 animals for bioluminescence of IRDye 800CW-PEG).
2. ACT + Activation ultrasound (ACT+A). (4 animals for BBBD, 2 animals for bioluminescence of IRDye 800CW-PEG).
3. ACT + Enhancement (ACT+E) (5 animals).
4. Sonazoid™ + Activation ultrasound + Enhancement ultrasound (Sonazoid™+A+E) (3 animals).
5. Saline + Activation ultrasound + Enhancement ultrasound (Saline+A+E) (3 animals).
MR images were acquired using a 7.05 T horizontal bore magnet (Biospec 70/20 Avance III, Bruker Biospin) with an 86 mm volume resonator for RF transmission and a phased array rat brain surface coil for reception. A pressure sensitive- and a temperature probe recorded respiration and temperature, respectively, of the rat (SA Instruments). Gas anesthesia (isoflurane ~2% in 78% medical air/20% O2) was adjusted appropriately and the body temperature was maintained at 37 °C by water circulation in the MRI bed. The animal was placed in the scanner, coils were tuned and matched and a tri-pilot with navigator scan (30 s) was acquired. MRI was acquired pre- and post-treatment. To verify BBBD and to detect hemorrhage in vivo, a Fast-Low Angle Shot (FLASH) sequence was used (Flip angle of 60°, TE/TR 5/350 ms, zero fill acceleration of 1.3, 10 averages, lasting 6 min and 8 s). The geometry of the MR sequence had a field of view of 40x27 mm, matrix size of 200x135 and 12 slices á 1 mm.
Treatment timeline. Grey bar indicates activation step period and black bold bar indicates enhancement step period.(Click on the image to enlarge.)
Analysis of BBBD
To evaluate the effect of BBBD, the intensity of the contrast agent in the MR images from each treatment region was estimated. When BBBD was visibly detectable, an ROI was drawn around the opened area and the same ROI was used on the non-treated contralateral side of the brain. The ratio of the average intensities of the ROIs was calculated using ImageJ [27]. Positioning of the ultrasound was manual, thus the exact coordinates for the BBBD was not available. To quantify the BBBD, it was therefore required to be able to observe the contrast agent in the image. Hence, quantitative data is only available for 3 of the 5 groups in Fig. 2.
Bioluminescence optical imaging
Successful delivery of a near infrared pegylated macromolecule (IRDye 800CW-PEG, LI-COR Biosciences Ltd) was verified using bioluminescence imaging (Pearl Impulse Imager, LI-COR Biosciences Ltd.). The excitation and emission settings were 785 and 820 nm, respectively. Animals were treated according to treatment group 1 and 2 with IRDye 800CW-PEG (10 nmol/kg) injected immediately after gadodiamide. The pegylated dye of approximately 45 kDa was used for assessing macromolecule vascular permeability [28]. 1 h after FUS treatment, the animals were injected with pentobarbital and perfused with PBS, before the brain was removed and imaged.
BBB recovery
To evaluate recovery of the BBB, treated animals were taken off anesthesia and decannulated. The animals were imaged again approximately 24 h and 72 h post treatment. For each MRI session, the animals were sedated and cannulated as described and Omniscan (1 ml/kg) was injected to evaluate the BBB recovery.
Paraformaldehyde fixated brains were cast into paraffin and cut into 4 µm thick sections. The sections were stained by haematoxylin-eosin-saffron (HES). Sections were imaged on an EVOS FL Auto (objective, 20x/ 0.25, air, Invitrogen/ThermoFisher). Images were stitched using the built-in software.
Statistical analysis
All statistical analysis was performed using Prism 6 (GraphPad Software, Inc.). Mean, standard deviation (with N-1 degree's freedom), analysis of variance (ANOVA) and Bonferroni's multiple comparison test were calculated for the BBBD groups (Fig. 2). Mean, standard deviation and monoexponential decay (f(t)=a*e(-K*t) +b) were calculated for the BBB recovery group (Fig. 4).
Results and discussion
Gadodiamide extravasation to the brain
ACT in combination with the activation and enhancement step clearly opened the BBB allowing MRI contrast agent to enter into the brain tissue (Fig. 2). Fig. 2 shows strong gadodiamide signal in the brain treated with ACT and activation and enhancement FUS, whereas only giving ACT and the activation FUS exposure showed hardly any signal. ACT was also much more efficient than the commercial Sonazoid in opening the BBB in combination with ultrasound. To obtain more quantitative data, the ratio of gadodiamide signal in the treated part vs. the non-treated contralateral part of the brain was calculated. In average, the ratio increased 50% for ACT+A+E treatment, compared to 18% for the Sonazoid™+A+E treatment (Fig. 2d). The extravasation of gadodiamide into the brain caused by ACT+A+E was significantly higher (p<0.01, Figure 2d) than with Sonazoid™+A+E (groups 1 and 4, respectively). ACT+A (group 2) caused similar gadodimamide extravasation as for Sonazoid™+A+E. ACT+E only (group 3) and Saline+A+E (group 5) did not induce BBBD and are thus not included in Fig. 2.
With the ultrasound activation and enhancement regimes applied, the ACT treatment clearly induced a significantly higher extravasation of gadodiamide to the brain than regular, small contrast microbubbles. Several important distinctions may contribute to this difference in effect level. The ACT-bubbles are in close contact with the endothelium over a significant segment of the vessel wall, ensuring a large interfacing area between the oscillating bubble and the endothelial cells. Sonazoid™, on the other hand, is free flowing and the average distance between the microbubble surface and the endothelial cells may limit the biomechanical effect level. ACT-bubbles are approximately 1000 times larger (by volume) than Sonazoid™ microbubbles and the biomechanical effects these large bubbles induce, even at low ultrasound pressures, should be orders of magnitude larger than with regular contrast microbubbles. Moreover, the lodged ACT-bubble will cause an increased microvascular pressure on the arterial side of the bubble and the induced transcapillary pressure gradient will enhance extravasation.
Comparing ACT+A with ACT+A+E, the 10 min, low MI enhancement step in the later treatment scheme is clearly increasing extravasation. Whether this is due to generation of larger openings with prolonged treatment, greater influx from longer treatment time, or a combination, cannot be determined from these experiments. Moreover, the enhancement step alone fails to produce BBBD with ACT, indicating that the phase shift event is a prerequisite for an effective BBBD.
Comparison of gadodiamide signal intensities from MR-images. White rings indicate BBBD, (a) ACT+A+E, (b) ACT+A, (c) Sonazoid™ +A+E. (d) Scatter plot with mean and standard deviation. ** (p<0.01), *** (p<0.001).(Click on the image to enlarge.)
In this study, Sonazoid™ has been used to represent commercial microbubbles, as it is a constituent of ACT. The commercial microbubbles have different properties with respect to size, size-distribution and shell properties. Nonetheless, the acoustic parameters used for effective BBBD are often similar for these MBs. This has been investigated in the case of Optison vs. Definity by McDannold et al [16] and for microbubbles of different sizes by Samiotaki et al. [14]. Another phase shift microbubble, based on acoustically active oil nanodroplets, has previously been used to open the BBB [29]. The nanodroplets had a size of 100-200 nm and ultrasound activation of the volatile oil created a microbubble of similar size to those in conventional ultrasound contrast agents. The study found that the nanodroplets were less effective in opening the BBB than commercial contrast agents at similar ultrasound settings. The main advantages of phase shift nanodroplets are that their size makes it possible for the nanodroplet to enter into the interstitium and cells, enabling abluminal activation, and their long circulation time, hours compared to minutes for conventional microbubbles, enabling prolonged treatment time. Except for the phase shift, nanodroplets and ACT are not easily compared; for instance, the nanodroplet is similar in size and blood circulation half-life to standard contrast microbubbles after activation, while the size and circulation half-life of ACT are more similar before activation.
Extravasation of the fluorescent macromolecule IRDye 800CW-PEG to the brain after treatment with (left) ACT+A+E and (right) ACT+A.(Click on the image to enlarge.)
IRDye 800CW-PEG extravasation into the brain
To explore if ACT facilitate extravasation of larger molecules, IRDye 800CW-PEG was injected before the treatment. IRDye 800CW-PEG extravasated into brain tissue both after ACT+A+E and ACT+A treatment (Fig. 3), the former clearly at a much higher level. IRDye 800CW-PEG is a macromolecule with a molecular weight of approximately 45 kDa, which is a relevant size for many applications within medicinal therapy where macromolecules are used. In a number of therapeutic approaches, including immunotherapy, larger molecules such as proteins or other nanosized agents are applied, hence, enabling delivery of such large molecules to the brain is an imperative for the success of these therapeutic agents. Even though the literature states that the BBB can be open for several days post treatment, this is only true for smaller molecules, such as gadodiamide [19, 30, 31]. Larger openings generated, allowing larger molecules to enter the brain, are only present for a short time [32]. According to Marty et al. [32], any molecule larger than 15-20 nm would in principle only benefit from FUS mediated BBBD for the duration of the FUS treatment. Hence, the large and deposited ACT bubbles, which are present for a longer time than regular microbubbles and in closer contact with the endothelial wall, are likely to be more effective for delivery of large therapeutic molecules. Furthermore, the efficient delivery observed shows that larger molecules can be delivered to a specific volume of the brain.
Recovery of BBBD
The recovery after the BBBD following ACT+A+E procedure was not complete 1 day after treatment (Fig. 4a-c). At this point, the extravasation of gadodiamide revealed a spot like pattern, rather than a diffuse extravasation pattern, which was observed immediately after ultrasound exposure. This pattern was seen in all recovery animals, and can also be seen in animals injected with IRDye 800CW-PEG (Fig. 3). The spots might be a result of the in situ ultrasound beam profile being heterogenous in the sonication focus. Although the beam profile measured in a water thank is homogenous [19], penetrating the skull might generate a more heterogeneous beam profile. This resulted in some areas where the opening was more substantial and consequently prolonged the recovery time. At 3 days' post treatment, a little gadodiamide extravasation into the brain was detectable for some animals, indicating that the BBB was close to or fully recovered. A monoexponential fit (f(t)=0.73·e -0.85t +0.96, R2=0.89) gave a half-life of BBBD recovery of 0.82 days. Previous studies have shown that the BBB closes after 1 to several days [19, 30, 31]. The present recovery kinetics of BBBD are thus similar to those for regular FUS microbubble treatment.
The in situ MI applied in this study was well below the threshold for what has previously been published as risk for damage to the brain/vasculature [33]. This is corroborated by the T1-FLASH and HES-staining, which revealed no signs of hemorrhage. Brains from group 1, 2 and 4 were stained with HES and analyzed for any signs of damage from the different treatments. Group 2 (ACT+A) and 4 (Sonazoid™+A+E), that showed the weakest BBBD, had no signs of adverse effects. Group 1 (ACT+A+E) showed only a few occurrences of focal microhemorrhages (exemplified in Fig. 4a-c), but the damage scored mild and was of no clinical relevance. No signs of eosinophilic degeneration of neurons, gliosis, inflammation or microglial/macrophage reaction were detected.
The present study demonstrates that ACT can be utilized to open the BBB in a safe manner, using a lower pressure FUS regimen than regular contrast microbubbles. ACT is clearly more efficient than regular microbubbles in opening the BBB in combination with ultrasound. The ACT treatment induces a significantly enhanced extravasation of gadodiamide as well as delivery of macromolecules.
This study demonstrates a new application for ACT which previously has shown great promise in enhancing the delivery of co-injected drugs to solid tumors growing in mice [24] and in treating tumors growing in mice [25].
BBBD from a representative animal. (a) Immediately after treatment, (b) 1 day after treatment and (c) 3 days after treatment. (d) Ratio of treated vs non-treated side of the brain, mean and standard deviation from 4 animals.(Click on the image to enlarge.)
Histological analysis of ACT+A+E treatment. (a) T1-FLASH image showing BBB opening after treatment (magenta circle indicates treated area; magenta arrow indicates microhemorrhage). (b) HES stained image of the brain (magenta circle indicates treated area). (c) Magnified area of b showing two sites of extravasated erythrocytes (magenta arrow corresponds to the microhemorrhage in panel a, black arrow indicates small amount of extravasated erythrocytes; scale bar: 1 mm).(Click on the image to enlarge.)
Histological samples were prepared by the Cellular and Molecular Imaging Core Facility (CMIC), MRI was performed at the MR core facility, and housing and care of animals was provided by the Comparative Medicine Core Facility (CoMed), all at the Norwegian University of Science and Technology (NTNU) and funded by the Faculty of Medicine and Central Norway Regional Health Authority.
The project is supported by The Research Council of Norway, NANO2021 grant number 220005 and grant number 228604, Central Norway Regional Health Authority and Center for Innovative Ultrasound Solutions (CIUS).
Competing Interests
The authors have declared that no competing interest exists.
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Author contact
Corresponding author: andreas.aslundno, andreas.aaslundcom.
Received 2016-6-23
Accepted 2016-8-23
Published 2017-1-1


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I have a 20-factor split-plot test where 15 factors are ready and 5 are delayed. The 5 delayed factors all have existing nominal as one of the levels. We must start getting data, so how can I design test that forces 5 delayed factors to nominal. This seems like a very common real world situation, so there must be a standard approach.
Thanks, Paul A.
I may not totally understand your question. Are you asking how to organize the runs so that the 5 delayed factors have settings that are "none" as a level? If so could you just set up the experiment as a hard to change and hard or very hard to change setting and see if that gives you the order which is more experimentally doable logistically. At the end of the day being the boss and getting started is reality one has to give in on randomness. That is why we verify the experiment.
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subset: commoncrawl


text:
There is a beautiful line in Kafka, which helps to gloss what I mean by Beckett's prose as a kind of gasping, a kind of breathing (but not an imitation of the rhythm of breathing or of gasping):
I live only here and there in a small word in whose vowel ('thrust' above, for instance) I lose my useless head for a moment. The first and last letters are the beginning and end of my fishlike emotion.
The soul lights up and flickers only in language, in the shapes traced on the page, or the voice traced in the silence of the head. Each clause is the catch in breath of this fish-like soul.


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Dial Down Dust And Noise Exposure - Open-Structure Designs May Lower Worker Exposure Levels In Aggregate Operations.
Published Date:0/1/1900
Description:Many different types of structures and materials have been used to build mineral processing facilities throughout the years. Although structure type and building material were not viewed as significant factors affecting the health of employees in these facilities when they were built, the National Institute for Occupational Safety and Health (NIOSH) has found that building type can impact respirable dust and noise levels. NIOSH performed a study in which it evaluated three building types: masonry, an open-structure design, and a steel-sided design. This study indicated that an open-structure design (no walls) was superior from both a dust and noise (health) standpoint when compared to the other two structure types. Therefore, companies may want to consider this design when building new structures.
Main Document Checksum:urn:sha256:073568b77b657e32576368f1a87ded72e881d470d575875d1f716cc3443868dc
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This upcoming weekend, Adrian Peterson looks to stay on pace in hopes to becoming the all-time season leader in rushing yards. With only two games remaining, Peterson has racked up 1,812 yards, putting him 294 … MORE ►
Posted: December 21st, 2012
Peterson Chasing Dickerson's Record
Tags: adrian peterson, eric dickerson
Posted: December 18th, 2012
Best NFL Films Shots of Week 15
Minnesota Vikings running back Adrian Peterson had another dynamic touchdown run in Week 15, but was it enough to land him in the top spot of NFL Films' best shots of the week?
Tags: adrian peterson
Posted: December 12th, 2012
First Look at Week 14 of 'NFL Turning Point'
This week on "NFL Turning Point", we analyze the Ravens/Redskins match-up and how rookie back-up Kirk Cousins saved Washington's season in the closing seconds of regulation. We also analyze Adrian Peterson's remarkable recovery from … MORE ►
Posted: November 20th, 2012
TDIF: Walter Payton Runs Into Record Books
On this date in football thirty-five years ago, Walter Payton rushed for a stunning 275 yards during a game against the Minnesota Vikings – an NFL record for rushing yards in a game. Developing the … MORE ►
Posted: November 7th, 2012
Week 9 of 'NFL Turning Point' – Sneak Peek
Don't forget to check out an all-new "NFL Turning Point" – tonight at 10:30 PM/ET on NBC Sports Network. Feel free to join the conversation on Twitter. #NFLTurningPoint
To see which matchups we are … MORE ►
Tags: nfl turning point
Posted: November 7th, 2012
Tonight on 'NFL Turning Point': Week 9
Yesterday, we gave you the sneak peek while we were still working on the segment here at NFL Films, but now here's the finished product in its entirety – a unique look at the on-field … MORE ►
Posted: October 17th, 2012
Week 6 of 'NFL Turning Point' – Sneak Peek
Once again, don't forget to check out NFL Turning Point – tonight at 10 PM ET on NBC Sports Network. You don't want to miss it!
Now, here's a sneak peek segment from the … MORE ►
Posted: October 17th, 2012
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Tags: nfl turning point
Posted: October 16th, 2012
This Week on 'NFL Turning Point'
This week on NFL Turning Point, premiering Wednesday at 10 pm ET, on NBC Sports Network:
Cowboys/Ravens – Joe Flacco mic'd up… an analysis of Baltimore's run defense… and a closer look at … MORE ►
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The Vault Keeper's Pick Six for Week 5
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The Adventures of Tintin: The Secret of the Unicorn, based on the classic Belgian comic strips by Georges Remi (aka Hergé), directed by Steven Spielberg, and co-produced by Peter Jackson
Enjoy the video:
Bonus Feature:
Just for fun
The Unofficial Title Sequence for 'The Adventures of Tintin'
Made by James Curran, this features elements from each of the 24 Tintin books. Music composed by Ray Parker and Tom Szczeniak. — Love the simplicity of the style, while still managing to nail all the details of the original artwork…
Enjoy the video:


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KL Bird Park 2009
KL Bird Park is dubbed as World's Largest free-flight walk-in aviary. It houses more than 3000 birds of 200 local and foreign species in approximately 21 acres of valley terrain.
Kuala Lumpur (KL) Bird Park
3 May 2009
It's located at Lake Garden and nearby a lot of others tourist attraction. The operating hour is start from 9.00am – 6.00pm. Entrance is RM15 (for adult) and RM6 (for kid) with MyKad. Without MyKad will be RM39 (for adult) and RM29 (for kid).
My visit to KL Bird Park is due to two discounted tickets that I bought in MATTA Fair recently. It's only cost RM10 each. It's a fair deal even though you can get the same price if you're Jusco Card member.
I reach there at 10.30am. The weather is very good. No direct sun heat and no sign of raining.
After I get tag from the ticket booth, I entered the first section of Zone 1. The park is divided into 4 different zones.
This is Love Aviary section.
Love Bird can be found here.
This colorful group of parrots are originated from Africa. It's often kept as pets due to their adorable appearance. When they kept in pairs, they will constantly groom each other and sit closely as possible when sleeping and resting. Lovebirds can live up to 10 to 20 years.
A mini landscape is created to make the environment harmony and close to nature.
Bird species such as peacock can be seen running around. It's harmless to human anyway.
Under the Zone 1, there is a big pond dedicated to Flamingo. A very nice landscape here.
Flamingo Pond.
Flamingos are resting or maybe sleeping using one leg.
You will never get lost with an illustrated guide on your hand. In fact, there is some big map like below at around the park.
Zone 2 has nothing much to see except those Egret spread around. I'm not able to see any Brahminy (Eagle), one of the local bird of prey species flying around.
It's reminding me about 15 years ago since I went here. It's has been changed a lot.
Zone 3 is where the HornBill park located.
Daily activities are shown on this board.
Dustbin here is so cute. You would enjoy throwing your rubbish inside.
Just look and follow the direction in the park.
World of Parrots (Zone 4) – This mini aviary is specially designed to accommodate various species of parrots in our collection consisting of macaws, cockatoos, lories and parakeets.
We're given some kuaci for the parrots to eat from our hand. They will not hesitate to land on your shoulder or hand anytime to get the food or probably welcoming you.
The next section is Oriental Bird Aviaries. Most birds here are kept in aviary.
Catch a glimpse of Flamingos gracefully sun-bathing in a beautifully landscape pond complete with a scenic man-made waterfall.
Bird show here is on daily basis. It's happening at the semi-open air Amphitheater with 400 seating capacity.
Egg & Incubation Room & Nursery is where the chicken eggs are artificially incubated using incubators.
Emu is the second largest living bird after the ostrich.
There is an entrance where the vegetables are prepared for visitors to feed them.
It's such a waste I do not have any DSLR on my hand to test during this visit. Many beginner photographers would like to take this opportunity test out their camera ability here.
This World's Largest Covered Bird Park is the best bird park I ever been. KL Bird Park is a great place for shaping your photography skill. Do visit KL bird park for your shooting, I mean photo shooting.


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It's just been a real, chicken parm-y kind of week, guys. First I went bonkers for the Burger King Italian Chicken Sandwich, and then my husband pointed me to George's Pastaria on South Dairy Ashford, where he promised me that the chicken parmesan was the best he has had since moving to Texas.
Generally speaking, I'm the one dragging my husband around the city, telling him where and what to eat. Between the writers here at EOW, the commenters (you guys know your stuff), and the various other Houston food blogs I read while I should be working in my spare time, that's a lot of stuff to eat. Josh is in charge of food at home, but I definitely take the lead when it comes to restaurant dining, so he was pretty psyched to discover George's on his own and he insisted I get the chicken parmesan.
"But, honey, you know I don't really do chicken parm at restaurants. What else is good?" I inquired. Josh replied, "I have no idea -- I've never ordered anything else."
Sitting down outside for a late afternoon lunch, I had a crisis: The menu was full of dishes I would normally order, like Tuscan ziti, eggplant parm and an Italian beef sandwich that sorely tempted my willpower. I persevered and ordered the chicken parmesan with a side of veggies but couldn't resist adding a bowl of George's "Famous" chicken and leek soup, as I have a real thing for leeks.
Like most cream-based soups, this one doesn't photograph terribly well but it does taste in-freaking-credible. This was a hearty and comforting way to start my meal, and so rich it made me glad I ordered veggies, not pasta, on the side of my entrée. My waitress claimed that this soup has been on the menu since George's opened, 25 years ago, and it's not hard to taste why: It's creamy, studded with chunks of potato, and begging for a piece of bread to be dragged through it (I obliged).
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The chicken parmesan was truly the chicken parm of my childhood -- it tasted like Sunday at Gram's house. Pounded out thin, perfectly coated with Italian breadcrumbs (not too much, not too little), covered in bubbling, toasty mozzarella cheese and smothered in a clearly homemade tomato sauce; you can see the small dice of fresh tomatoes peeking out from under the hood of the cheese. It's a trick of perfect parm, getting the breading properly stuck-on enough to withstand the moisture of sauce and the weight and pull of melted mozzarella, and George's doesn't miss the trick. The portions were big (I took half home), the prices reasonable ($20 including tip, all told), and I've finally solved the mystery of why Josh isn't always hungry for dinner when he gets home from work.
Between the neighborhood feel of the restaurant, and the solid homestyle-Italian menu, I've been very much charmed by George's Pastaria; it's not hard to see why they've been around for a quarter-century. This was a pleasure to discover, and proof yet again of how much great food is outside the loop.
Follow Eating Our Words on Facebook and on Twitter @EatingOurWords


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Last month I spent a week in Dar Es Salaam at FOSS4G 2018, incorporating the HOT (Humanitarian OpenStreetMap Team) Summit. It was one of an increasing number of occasions where I find my Astun Technology and MapAction roles overlapping, and made more enjoyable by being able to spend some of the time with colleagues from both organisations.
This was my fourth FOSS4G, and was a very different experience to the first three. Tanzania is the second African country to have hosted FOSS4G after South Africa, and so nationals of African countries made up a significant proportion of the delegates, most of whom, judging from those I spoke to, were attending for the first time. Their travel experiences were also a little different to mine - one delegate told me she had travelled for two days on a bus from northern Tanzania with no overnight stop, putting into perspective gripes from those of us flying in about stopovers and connections. The age and gender demographic was also significantly different - it was refreshing to see so many young people, and so many women among the delegates, and also to see this reflected in the choice of keynote speakers, all of whom were women. This report from a delegate from Lesotho, partly funded by the fantastic FOSS4G Travel Grant programme, gives a flavour of the kind of impact the conference had. Of course 'the usual suspects' were also there in force - they are the backbone of FOSS4G and it's always good to see, and listen to, the familiar faces who are behind many of the applications we use every day.
There was a strong emphasis on humanitarian issues, particularly on the HOT track. My MapAction colleague Steve Penson covers this well in an excellent blog post on some of the work HOT is doing in Tanzania - it's pragmatic, large-scale, and genuinely innovative, involving hundreds of communities and university students in Dar Es Salaam.
Other than that, a few things caught my eye/ear:
- A new version of QField, a version of QGIS optimised for use on Android tablets and particularly for field data collection, is coming soon, with better synchronisation with a QGIS project (using a plugin), improved forms, and integration with mobile device sensors. QField is largely developed by OPENGIS.ch, and they would welcome contributions of any kind.
- Coming at field data collection from the other direction (and maybe meeting in the middle?) is continuing development of ODK (OpenDataKit) and its branded version KoBo Toolbox, the 'go to' data collection app in the humanitarian world. The geo capabilities of ODK in particular are developing fast, improving the ability of users to collect accurate and relevant location data in the field.
- A team from Heidelberg University gave a great presentation on OpenRouteService, which uses (of course) OpenStreetMap as the basis for a routing UI and a series of APIs. It's still relatively new, but it gave me a pretty good bike route from my house into Bristol, and the APIs include isochrones and geocoding, so it's one to watch.
- Drones were everywhere, including in Zanzibar where the entire island has been captured by fixed-wing drones using football pitches as airstrips, and aerospatial.io and the associated opendronemap.com among the tools on show.
With over 1,000 delegates, FOSS4G is going from strength to strength, and there's no doubt that the enthusiasm of Mark Iliffe and the Dar Es Salaam LOC is going to be carried forward by Vasile Crăciunescu and the Romanian team for FOSS4G 2019 in Bucharest - the website is up, the venues are booked, all that remains is for you to be there!


text: On a sloping lot perched above San Francisco airport and overlooking the bay, this tired 1970s 3-bedroom, 2-bath house was transformed into a modern 5-bedroom, 5-bath gem with trimless doors and windows and flush baseboards. The new home features live-in maid's quarters, butler's pantry, home office with bathroom, laundry room, en suite bathrooms for each bedroom, exterior fire pit and patio heaters, and attached 3-car garage. To allow for a combined open-concept living room/kitchen/dining room, an existing girder plywood floor system with 1½" variations in height among rooms was leveled and ceilings of various slopes were feathered.


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At Riverside Ranch Apartments, enjoy student living tailored to your lifestyle. Our spacious one and two bedroom apartments offer luxurious finishes, free Internet, cable and HBO®.
Each apartment has fully equipped kitchens as well as a washer and dryer. You can study in our parks or play a quick pickup game with friends on our full-size basketball court. We are located minutes from Texas State University and directly on the university bus route. Residents also enjoy a resort style pool, and a 24-hour fitness center. Resident satisfaction is our top priority at Riverside Ranch Apartments. We offer simple to use online services that are quick, reliable, and secure. From paying your rent to making a maintenance request our online resident portal helps to make your monthly routine easier.
Call us to schedule a tour and design the lifestyle you desire at Riverside Ranch Apartments today.


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1324 Portage Street, Kalamazoo MI 49001
Edison Neighborhood | Acreage: .1 | Year Built: 1935 | 3,900 SF
The former Kalamazoo Color Lab has been vacant since 2015. It is located within an emerging vibrant commercial node in the Edison Neighborhood. Previously a bustling hub in its heyday, Washington Square is experiencing a revival with 6 new businesses that have opened in the last 5 years.
- Over $1 million has been invested on the block in the last few years: improving landscaping, interior renovations of adjacent properties for new businesses and new outdoor furniture, planters and other aesthetic enhancements
- As a result of the Fare Games restaurant competition, Pho on the Block opened their doors in 2017. This Vietnamese Asian fusion restaurant has been greeted with warm support and large crowds
- Washington Square businesses Community Promise Credit Union, Kazoo Nutrition, Jersey Giant Subs, Tremolo Music Shop, Bellydance Kalamazoo, Pho on the Block, and a local barbershop all keep the square bustling on a daily basis
- The Land Bank together with its partners has hosted dozens of block-wide events in the last 3 years, bringing thousands of people to the block to enjoy outdoor performances, harvest festivals and holiday shopping. The businesses benefit from increased traffic during these events and exposure to crowds of people from Edison neighborhood and beyond to generate new and repeat business.
Washington Square—Upcoming Investments
- The City will be completing an alley enhancement project in the fall of 2017. Approximately $70,000 will be invested to enhance the alley adjacent to the Color Lab to create a unique place for patrons to sit outside, enjoy the Inside Out Art exhibit and the urban environment. The alley is available for use by both the owners of 1356 Portage and the Color Lab
- New sidewalks and bump outs will be completed in the square in 2018 by the City of Kalamazoo
- The Color Lab will be one of the primary sites associated with the Inside Out Project:We Are Edison art installation. This space will be highlighted through large-scale black and white portraits of Edison residents pasted onto the exterior. It will be highly visible to passing traffic and during Washington Square events in 2017.
Requirements to Apply
Interested parties are invited to submit applications that include a retail or restaurant component to the Land Bank via its business accelerator program. The asking price of the property is $100,000.00, which is negotiable depending on the concept presented and its alignment with the vision for Washington Square. We will also accept applications for rental of the space for a business that aligns with the vision, with a negotiable lease price. Call Michelle Tombro Tracy at (269)216-9870 to start the process or schedule a viewing of the property.
(Above) The Color Lab storefront with Inside Out installation.
(Left) residents excited to see their photo.
(Right) the storefront as it existed around 1957.


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A tool that could save your lifeOctober 09, 2012
Anissa MorrisOctober 04, 2012
Suffering in an Unthinkable Accident: How a Brain Injury Lawyer Can Help YouSeptember 28, 2012
A Brain Injury Attorney Can Help Ease Challenges for Victims and FamiliesSeptember 25, 2012
Cars with the highest injury ratesSeptember 25, 2012
14 year old driver has fatal accidentSeptember 18, 2012
What to do if you are a passenger in an automobile accidentSeptember 13, 2012
Florida Lawmakers, it's time for texting while driving ban!September 11, 2012
Patience may be a virtue. However, it makes for tragic road safety policy.Last year, texting behind the wheel led to at least 180 crashes in Florida, distracted driving led to 25,156 crashes—surely a low-ball estimate from the Department of Highway Safety and Motor Vehicles. A fair share of those involved […]
Drowsy Driving Prevention Week Sept. 1-7, 2012September 06, 2012
TALLAHASSEE, Fla.– A study by the National Highway Traffic Safety Administration found 37 percent of Americans admitted to falling asleep behind the wheel. Sleepiness slows reaction time, decreases awareness, impairs judgment and increases the risk of crashing. That is why the Florida Legislature designated the first week of September every […]
Brain Injury Attorney in FloridaAugust 27, 2012
Everyday, hundreds of people end up in the hospital because of a brain injury. The results of a brain injury can be devastating. Millions of people have had been permanently disabled after suffering a head injury. People whose head injury was caused by another person's negligence should call a brain […]
$1,491,054 Cervical fusion spine surgery
$1,000,000Femur and ankle fractures
$725,000 Lumbar laminectomy and discectomy surgery
$500,000Cervical discectomy surgery
$410,000 Hip fracture with surgery
$315,000 Cervical disc replacement surgery
$290,000 Ulnar nerve surgery
Wrongful death confidential
Settlement 2x policy limits


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The SpellingBee Ninja is an exciting new program that prepares and tests students on thousands of spelling words. This valuable tool enables spellers of all ages to practice words independently and track their success.
This easy-to-use software is THE way to boost spelling performance, for both the classroom and spelling bee competitions. If you, your child or your students need to improve your spelling skills, this program is for you!
This is the only spelling practice software endorsed by
The SpellingBee Ninja was designed for any speller who wants to boost his/her spelling skills.
Students can practice the thousands of words in our word bank. Parents and teachers can add even more.
Teachers can use this in their classroom to test students on random words from our word bank, or on special words that they input themselves.
ESL students can receive hours and hours of individualized practice on the words they most need to hear, learn and spell.
In this single piece of software you will receive:
I like that you can get SO MUCH practice and SO MUCH info all in one place. The software runs great, too!
Go here and click on Watch the Video to learn more.
As many of you know, I've been promoting good spelling and spelling bees for many years through this website. Over these years I've had many requests for a good, interactive online spelling practice program. I had not found any that I could endorse -- until now.
A few months ago, an expert programmer, who was also interested in promoting good spelling skills and spelling bee competitions, approached me with his idea for a powerful spelling training program.
I asked a lot of questions and liked the answers I was given. I've had the opportunity to "sneak preview" this software, and I like it a lot!
You can find other spelling quiz programs for slightly less money, but you cannot find one with more words and more features for any price, making this a truly great bargain.
I heartily endorse the SpellingBee Ninja !


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"When Adam and Eve were dispossessed
Of the garden hard by Heaven
They planted another one down in the West
Twas Devon, glorious Devon."
Edward German
Last time I kept a diary (as a train-track-wearing, mullet-haired 12-year-old), it was sacred and secret. So it feels a bit odd to be writing to such an infinite cyberspace. I can sort of hear my voice echoing.
Why Devon? My family spent idyllic summers in the wilds of North Devon when I was growing up. My sister and I nagged my parents until we eventually moved permanently when I was 6-years-old (even if it meant they had to commute 200 miles to London to work – that's love). It was heaven for little people: beach trips, horse-riding, freedom and space.
But being in the sticks wasn't so much fun for a Smirnoff Ice-drinking late teen (not-so-quietly resenting my parents for living in the middle of bloody nowhere). I went away to university ooop North and then moved to London.
I always knew I'd be back though (Devon has a funny way of getting under your skin). And now I am and I have two small boys who make me appreciate it even more.
This is my Diary of a Devon Mum.
Image: courtesy of Helen Lisk Photography who kindly allowed me to feature some of her photography from our family shoot on this blog. Helen's pics are easy to spot as they are much more professional than my own!
One last thing: this blog has recently had a makeover by the fabulous Dawn Li from East West Design. Now more of a blogzine, I'm hoping other Devon parents might like to contribute. So far Kate Berry from The Thatched Kitchen has joined me as guest food blogger. Please get in touch if you fancy doing a bit of blogging or vlogging. Fill in the contact form or email firstname.lastname@example.com.


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This is a 100% Natural fibre tie spun and woven in Caithness in the North of Scotland. A fabulous blend of colours.
This tie was made by the Ousdale woollen mill, the mill is sadly no longer in operation so these ties are no longer available. This would make a unique gift at an exceptional price.
Please buy with confidence, if you are not delighted we will refund or replace, no questions asked including your return postage
Composition: Silk/Wool/Cotton
This tie comes with a silk tab stating Ousdale as the manufacturer, Made in Caithness, Scotland and the fabric composition (Silk Wool Cotton)
Tie Length: 1035 cms
Tie Width: (widest point) 8 cms
Tie With: (narrowest point) 4 cms


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When you configure Barracuda NextGen Firewalls to send log data to USM Anywhere, you can use the Barracuda NextGen Firewall plugin to translate raw log data into normalized events for analysis. The table below provides some basic information for the plugin:
|Device Type
|Connection Type
Integrating Barracuda NextGen Firewalls
To configure Barracuda NextGen Firewalls to forward log data over Syslog to USM Anywhere
Go to the LOGS > Log Streaming.
In the Stream target field, type the hostname or IP address of your USM Anywhere Sensor.
Note: Only one target can be defined.
In Protocol / Port, enter
- port 514 if you're using UDP
- port 601 if you're using TCP
Select the log streams you want to enable.
Click Save Changes.
Verify that a connection exists between the device and the USM Anywhere Sensor.
- Go to BASIC > Recent Connections.
Filter the list of connections for the Protocol, Service, and Destination IP of your USM Anywhere Sensor.
Plugin Enablement
The Barracuda Next Gen (NG) Firewall plugin automatically processes all messages when the raw message contains "box_Firewall_Activity".
Available Plugin Fields
The following plugin fields are important attributes extracted from the syslog message. The USM Anywhere reports use these fields, and you can also reference them when creating custom reports. In addition to reporting, the USM Anywhere correlation rules make use of these fields.
- application
- application_protocol
- base_event_count
- bytes_in
- bytes_out
- content_category
- customfield_0
- customfield_1
- customheader_0
- customheader_1
- destination_address
- destination_nat_address
- destination_port
- destination_service_name
- device_inbound_interface
- duration
- event_category
- event_description
- event_name
- event_severity
- packets_received
- packets_sent
- rep_device_model
- rep_device_outbound_interface
- rep_device_rule_id
- source_address
- source_mac
- source_nat_address
- source_port
- source_username
- timestamp_occured
- timestamp_received
- transport_protocol
Additional Resources and Troubleshooting
For troubleshooting, refer to the vendor documentation:


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Our supplements are the best in class in terms of absorbability. They make an ideal addition to healthy (super) food diets and each boasts a number of unique properties.
Paratrex - Global Healing Center - 120 capsules€33.99
Oxy-Powder - Global Healing Center - 120 vcaps€44.95
Selenium - ORGANIC - Global Healing Center - 60 capsules€19.95
Many of our supplements are extracts from 100% natural products and are thus extremely effective in achieving their goal within the human body. Supplements can be used to plug shortfalls in our body, particularly where there is an additional need for specific nutrients or for cleansing and repair at a cellular level.


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Just in case you wanted proof that I made my baby a Halloween costume before she was even born...
I made a tiny cape, and bat ears on a headband that surprisingly fit her.
This is her scariest pose.
She really likes looking around at things, particularly lights and the ceiling.
Sometimes, she's had enough.
I made the ears out of some leftover pinstriped material, so I was joking that they were her "formal ears".
We all dressed up like vampires this year, including Lulu... but I don't have access to any of our group pictures yet. They will be awesome though! (I had my purple wig and everything!)
This one is my favorite:


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Our 4 hour Irish Heart Foundation Heartsaver CPR & AED course – First Aid Courses Dublin is dedicated to life saving cardio pulmonary resuscitation (CPR). You will also learn how to successfully use an AED (Automated External Defibrillator).
Additionally to CPR First Aid training you will learn how to handle situations of foreign body airway obstruction (choking) as well as stroke.
Do you know that 70% of cardiac arrests in Ireland occur out of hospital? This happens usually in the presence of a family member or friend. For this reason if you know how to perform CPR you may be able to help save a life of a loved one.
As an illustration here is one example how the life of a young man was saved. In brief he survived thanks to the quick reaction of his friends who took part in CPR First Aid training shortly before the event. An AED was at the scene straightaway. However this is the ideal case scenario but in reality most victims are not that fortunate. It is important to realise that you too can learn these skills!
We will teach you the Heartsaver CPR & AED – First Aid Courses Dublin by instructors who have many years of experience. In fact many of our instructor have ample experience in front line services. Hence the Heartsaver CPR & AED course follows specifically the recommendation of the American Heart Association, the Irish Heart Foundation and PHECC (Pre-Hospital Emergency Care Council).
In the event that you like to train with your friends and family you can host a CPR course in your own home.
In case you have more questions please contact us for more information.
Participants can buy their lunch at the hotel's restaurant.
Substitutions: At any stage, we are happy to change the participant where someone cannot attend. We will not charge for this name change which can be done up to the commencement day of the course.
Cancellations made:
5 working days or more before the course commencement date will be entitled to a full refund/credit
Between 5 and 1 day notice will incur a cancellation charge equal to 50% of the course fee.
Less than 1 days before a course or a "no show" on the commencement day of a course or cancellation during the course will incur a 100% cancellation fee.
Please note that you will have to confirm cancellations via email to firstname.lastname@example.com.
Any notice of cancellation will only be effective once it has been acknowledged by First Aid For Everyone.
From 9.30 – 13.30
Name *
E-Mail *
Subject *
Message *
2 + 4 = ? Please prove that you are human by solving the equation *
I attended the First aid for everyone Paediatric course in Bewleys Hotel on Saturday the 12th May 2012 . The course was very informative and very interesting in the delivery.
Siobhan made everyone feel at ease and there was excellent interaction. It was a revision course for a lot of the group but it was the best by far on information, delivery, visual information and equipment.
Thanks a million for delivering a fantastic First Aid course to us on Friday. Girls thoroughly enjoyed as did I.
You seemed to cover everything efficiently and managed to ensure we all participated in the practical aspects also.
Just thought it warranted a massive 'Thank You'.
Everything is so well organised and the extra little touches like all the goodies, you being there to meet and greet and all the personal stories the instructor has make the course really really good.
So thank you very much. I can go back to the crèche again with more confidence and knowledge should any first aid situation arise.
Tel : 01 282 5766
Mob: 086 404 5520
Mail: firstname.lastname@example.com
First Aid For Everyone
42 Corbawn Drive
Shankill, Dublin


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Description From NisoloWith a durable rubber outsole and hardy leather upper, the Chavito Chukka Boot is a rustic and unbeatably stylish wardrobe staple. The versatile men's chukka boot transitions easily between jeans and slacks, making it a no-nonsense shoe that will suit the needs of any man on the go.Shop all Essentials
Shop more from Nisolo's collection
Nisolo's Impact
Classic design combined with extraordinary craftsmanship makes for shoes that are perfect for both work and play. Nisolo pays above fair trade wages and healthcare benefits, as well as providing life-changing personal development programs. They see shoemaking as art--that shows through in their products, and the way they support their artists.
Nisolo's Return Policy
All unworn and unaltered items may be returned within 30 days of the original purchase date. If you choose to return an item, $5.95 will be held from your refund to cover shipping and restocking. Alternatively, you can choose to return an item for Nisolo on DoneGood credit at no additional cost to you.
Please email email@example.com to initiate a return or exchange.


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Vitamins & Supplements Center
Drugs and Medications Center
Related to Vitamins & Supplements
Alanyl-L-Histidine, B-Alanyl-L-Histidine, B-Alanyl Histidine, Beta-alanyl-L-histidine, Bêta-Alanyl-L-Histidine, Carnosina, L-Carnosine, Levo-Carnosine, N-Acetyl-Carnosine, N-Acétyl-Carnosine, N-Acetyl-L-Carnosine, N-Acétyl-L-Carnosine.
Overview InformationCarnosine is a protein building block that is naturally produced in the body. It is found in muscles when they are working, and it is also found in the heart, brain, and many other parts of the body.
Carnosine is used by mouth to prevent signs of aging, for diabetes, and many other conditions, but there is no good scientific evidence to support these uses.
How does it work?Carnosine is important for many normal body functions including the proper function and development of the muscles, heart, liver, kidneys, brain, and many other organs. There is some interest in using carnosine to prevent aging because it seems to interfere with certain chemicals that might play a role in the aging process.
Uses & Effectiveness
Insufficient Evidence for
- Autism. Early research shows that taking L-carnosine by mouth for 8 weeks may improve symptoms in children with autism. But not all research agrees.
- Heart failure. Taking carnosine by mouth for 6 months might help people with heart failure walk farther by helping the body take in more oxygen. This might also make people feel happier.
- A group of symptoms experienced by people fighting in the Gulf War (Gulf War illness). Taking carnosine along with other medicine by mouth does not improve most symptoms of this disease, like tiredness and pain. However, it might improve symptoms of irritable bowel syndrome, such as diarrhea. Also, it might help memory by a small amount.
- A type of anxiety marked by recurrent thoughts and repetitive behaviors (obsessive-compulsive disorder or OCD). Early research shows that taking carnosine twice daily by mouth for 10 weeks with the prescription drug fluvoxamine might reduce symptoms of repetition by a small amount in people with moderate to severe OCD.
- Bed sores (pressure ulcers). Taking carnosine alone or with zinc by mouth might help to speed up the healing of pressure ulcers.
- Schizophrenia. Taking carnosine by mouth does not seem to make people with schizophrenia feel happier. However, it might help to improve memory.
- Diabetes.
- Decline in memory and thinking skills that occurs normally with age.
- Athletic performance.
- Aging.
- Complications of diabetes.
- Dry skin.
- Glaucoma.
- Obesity.
- Ulcerative colitis.
- Other conditions.
Side Effects & SafetyWhen taken by mouth: Carnosine is POSSIBLY SAFE for most children and adults. However, there can be some rare side effects. These might include dry mouth, changes in appetite, feelings of tiredness, or vivid dreams.
When applied to the skin: Carnosine is POSSIBLY SAFE for most adults. However, there can be some rare side effects. These might include a rash or itchiness.
When given as an enema (rectally): Carnosine is POSSIBLY SAFE for most adults when used as an enema.
Special Precautions & Warnings:Pregnancy and breast-feeding: There isn't enough reliable information to know if carnosine is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.
Low blood pressure: Carnosine might lower blood pressure. In theory, taking carnosine might make blood pressure become too low in people with low blood pressure.
We currently have no information for CARNOSINE Interactions.
The appropriate dose of carnosine depends on several factors such as the user's age, health, and several other conditions. At this time there is not enough scientific information to determine an appropriate range of doses for carnosine. Keep in mind that natural products are not always necessarily safe and dosages can be important. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.
- Babizhayev, M. A. Antioxidant activity of L-carnosine, a natural histidine-containing dipeptide in crystalline lens. Biochim.Biophys.Acta 8-22-1989;1004(3):363-371. View abstract.
- Babizhayev, M. A., Deyev, A. I., and Linberg, L. F. Lipid peroxidation as a possible cause of cataract. Mech.Ageing Dev. 1988;44(1):69-89. View abstract.
- Babizhayev, M. A., Deyev, A. I., Yermakova, V. N., Semiletov, Y. A., Davydova, N. G., Kurysheva, N. I., Zhukotskii, A. V., and Goldman, I. M. N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides 2001;22(6):979-994. View abstract.
- Babizhayev, M. A., Seguin, M. C., Gueyne, J., Evstigneeva, R. P., Ageyeva, E. A., and Zheltukhina, G. A. L-carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) act as natural antioxidants with hydroxyl-radical-scavenging and lipid-peroxidase activities. Biochem.J 12-1-1994;304 ( Pt 2):509-516. View abstract.
- Babizhayev, M. A., Yermakova, V. N., Sakina, N. L., Evstigneeva, R. P., Rozhkova, E. A., and Zheltukhina, G. A. N alpha-acetylcarnosine is a prodrug of L-carnosine in ophthalmic application as antioxidant. Clin.Chim.Acta 10-15-1996;254(1):1-21. View abstract.
- Bauman, M. and Kemper, T. L. Histoanatomic observations of the brain in early infantile autism. Neurology 1985;35(6):866-874. View abstract.
- Begum, G., Cunliffe, A., and Leveritt, M. Physiological role of carnosine in contracting muscle. Int J Sport Nutr.Exerc.Metab 2005;15(5):493-514. View abstract.
- Bhuyan, K. C. and Bhuyan, D. K. Molecular mechanism of cataractogenesis: III. Toxic metabolites of oxygen as initiators of lipid peroxidation and cataract. Curr.Eye Res. 1984;3(1):67-81. View abstract.
- Boldyrev, A. A., Dupin, A. M., Bunin, A. Y., Babizhaev, M. A., and Severin, S. E. The antioxidative properties of carnosine, a natural histidine containing dipeptide. Biochem.Int. 1987;15(6):1105-1113. View abstract.
- Bowen, W. J. Effects of pH, buffers, carnosine, histidine, and beta-alanine on the shortening of glycerol-treated muscle fibers. Arch.Biochem.Biophys. 1965;112(3):436-442. View abstract.
- Chez, M. G., Buchanan, C. P., Aimonovitch, M. C., Becker, M., Schaefer, K., Black, C., and Komen, J. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J.Child Neurol. 2002;17(11):833-837. View abstract.
- Guiotto, A., Calderan, A., Ruzza, P., and Borin, G. Carnosine and carnosine-related antioxidants: a review. Curr.Med Chem. 2005;12(20):2293-2315. View abstract.
- Guo, Y. and Yan, H. [Preventive effect of carnosine on cataract development]. Yan.Ke.Xue.Bao. 2006;22(2):85-88. View abstract.
- Harris, R. C., Dunnett, M., and Greenhaff, P. L. Carnosine and taurine contents in individual fibres of human vastus lateralis muscle. J Sports Sci 1998;16:639-943.
- Himukai, M. The characteristics of carnosine transport and carnosine-induced electrical phenomena by the everted intestine of guinea pig. Jpn J Physiol 1985;35(6):945-952. View abstract.
- Hipkiss, A. R., Brownson, C., Bertani, M. F., Ruiz, E., and Ferro, A. Reaction of carnosine with aged proteins: another protective process? Ann.N.Y.Acad.Sci. 2002;959:285-294. View abstract.
- Jackson, M. C., Kucera, C. M., and Lenney, J. F. Purification and properties of human serum carnosinase. Clin.Chim.Acta 2-15-1991;196(2-3):193-205. View abstract.
- Lee, Y. T., Hsu, C. C., Lin, M. H., Liu, K. S., and Yin, M. C. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur.J Pharmacol. 4-18-2005;513(1-2):145-150. View abstract.
- Maichuk, IuF, Formaziuk, V. E., and Sergienko, V. I. [Development of carnosine eyedrops and assessing their efficacy in corneal diseases]. Vestn.Oftalmol. 1997;113(6):27-31. View abstract.
- Matsukura, T. and Tanaka, H. Applicability of zinc complex of L-carnosine for medical use. Biochemistry (Mosc.) 2000;65(7):817-823. View abstract.
- Ozonoff, S., Strayer, D. L., McMahon, W. M., and Filloux, F. Executive function abilities in autism and Tourette syndrome: an information processing approach. J Child Psychol.Psychiatry 1994;35(6):1015-1032. View abstract.
- Parkhouse, W. S., McKenzie, D. C., Hochachka, P. W., and Ovalle, W. K. Buffering capacity of deproteinized human vastus lateralis muscle. J Appl.Physiol 1985;58(1):14-17. View abstract.
- Petroff, O. A., Hyder, F., Rothman, D. L., and Mattson, R. H. Homocarnosine and seizure control in juvenile myoclonic epilepsy and complex partial seizures. Neurology 3-27-2001;56(6):709-715. View abstract.
- Quinn, P. J., Boldyrev, A. A., and Formazuyk, V. E. Carnosine: its properties, functions and potential therapeutic applications. Mol.Aspects Med. 1992;13(5):379-444. View abstract.
- Robertson, J. M., Donner, A. P., and Trevithick, J. R. A possible role for vitamins C and E in cataract prevention. Am.J Clin.Nutr. 1991;53(1 Suppl):346S-351S. View abstract.
- Suzuki, Y., Ito, O., Mukai, N., Takahashi, H., and Takamatsu, K. High level of skeletal muscle carnosine contributes to the latter half of exercise performance during 30-s maximal cycle ergometer sprinting. Jpn.J.Physiol 2002;52(2):199-205. View abstract.
- Suzuki, Y., Nakao, T., Maemura, H., Sato, M., Kamahara, K., Morimatsu, F., and Takamatsu, K. Carnosine and anserine ingestion enhances contribution of nonbicarbonate buffering. Med Sci Sports Exerc. 2006;38(2):334-338. View abstract.
- Takahashi, H. Studies on homocarnosine in cerebrospinal fluid in infancy and childhood. Part II. Homocarnosine levels in cerebrospinal fluid from children with epilepsy, febrile convulsion or meningitis. Brain Dev. 1981;3(3):263-270. View abstract.
- Trombley, P. Q., Horning, M. S., and Blakemore, L. J. Carnosine modulates zinc and copper effects on amino acid receptors and synaptic transmission. Neuroreport 10-26-1998;9(15):3503-3507. View abstract.
- Volkov, O. A., Neshkova, G. A., Moshetova, L. K., and Iarovaia, G. A. [The effect of carnosine on inflammatory processes during contusion of the eyeball]. Biomed.Khim. 2006;52(2):188-191. View abstract.
- Arabzadeh S, Shahhossenie M, Mesgarpour B, Rezaei F, Shalbafan MR, Ghiasi Z, et al. L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: A randomized double-blind study. Hum Psychopharmacol. 2017;32(4). doi: 10.1002/hup.2584. View abstract.
- Baguet A, Bourgois J, Vanhee L, Achten E, Derave W. Important role of muscle carnosine in rowing performance. J Appl Physiol (1985) 2010;109(4):1096-101. View abstract.
- Baraniuk JN, El-Amin S, Corey R, Rayhan R, Timbol C. Carnosine treatment for gulf war illness: a randomized controlled trial. Glob J Health Sci 2013;5(3):69-81. View abstract.
- Baye E, Ukropec J, de Courten MPJ, et al. Carnosine Supplementation Improves Serum Resistin Concentrations in Overweight or Obese Otherwise Healthy Adults: A Pilot Randomized Trial. Nutrients. 2018;10(9):E1258. View abstract.
- Baye E, Ukropec J, de Courten MPJ, et al. Carnosine supplementation reduces plasma soluble transferrin receptor in healthy overweight or obese individuals: a pilot randomised trial. Amino Acids. 2019;51(1):73-81. View abstract.
- Brownson C, Hipkiss AR. Carnosine reacts with a glycated protein. Free Radic Biol Med 2000;28:1564-1570.. View abstract.
- Chengappa KN, Turkin SR, DeSanti S, et al. A preliminary, randomized, double-blind, placebo-controlled trial of L-carnosine to improve cognition in schizophrenia. Schizophr Res 2012;142(1-3):145-52. View abstract.
- Chung W, Baguet A, Bex T, Bishop DJ, Derave W. Doubling of muscle carnosine concentration does not improve laboratory 1-hr cycling time-trial performance. Int J Sport Nutr Exerc Metab 2014;24(3):315-24. View abstract.
- Federici A, Federici G, Milani M. Use of a urea, arginine and carnosine cream versus a standard emollient glycerol cream for treatment of severe xerosis of the feet in patients with type 2 diabetes: a randomized, 8 month, assessor-blinded, controlled trial. Curr Med Res Opin 2015;31(6):1063-9. View abstract.
- Guliaeva NV. Superoxide-scavenging activity of carnosine in the presence of copper and zinc ions. Biokhimiia 1987;52:1216-1220.. View abstract.
- Harris RC, Tallon MJ, Dunnett M, et al. The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis. Amino Acids 2006;30:279-89. View abstract.
- Hipkiss AR, Chana H. Carnosine protects proteins against methylglyoxal-mediated modifications. Biochem Biophys Res Commun 1998;248:28-32. View abstract.
- Hipkiss AR, Preston JE, Himswoth DT, et al. Protective effects of carnosine against malondialdehyde-induced toxicity towards cultured rat brain endothelial cells. Neurosci Lett 1997;238:135-8.. View abstract.
- Hipkiss, A. R. Would carnosine or a carnivorous diet help suppress aging and associated pathologies? Ann.N.Y.Acad.Sci 2006;1067:369-374. View abstract.
- Hisatsune T, Kaneko J, Kurashige H, et al. Effect of anserine/carnosine supplementation on verbal episodic memory in elderly people. J Alzheimers Dis 2016;50(1):149-59. View abstract.
- Horning MS, Blakemore LJ, Trombley PQ. Endogenous mechanisms of neuroprotection: role of zinc, copper, and carnosine. Brain Res 2000;852:56-61. View abstract.
- Invernizzi PL, Limonta E, Riboli A, Bosio A, Scurati R, Esposito F. Effects of acute carnosine and ß-alanine on isometric force and jumping performance. Int J Sports Physiol Perform 2016;11(3):344-9. View abstract.
- Itagaki M, Saruta M, Saijo H, et al. Efficacy of zinc-carnosine chelate compound, Polaprezinc, enemas in patients with ulcerative colitis. Scand J Gastroenterol 2014;49(2):164-72. View abstract.
- Kantha SS, Wada S, Tanaka H, et al. Carnosine sustains the retention of cell morphology in continuous fibroblast culture subjected to nutritional insult. Biochem Biophys Res Commun 1996;223:278-82. View abstract.
- Karkabounas S, Papadopoulos N, Anastasiadou C, et al. Effects of a-lipoic Acid, carnosine, and thiamine supplementation in obese patients with type 2 diabetes mellitus: A randomized, double-blind study. J Med Food. 2018;21(12):1197-1203. View abstract.
- Liu Y, Cotillard A, Vatier C, et al. A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial. PLoS One. 2015;10(9):e0138646. View abstract.
- Lombardi C, Carubelli V, Lazzarini V, et al. Effects of oral administration of orodispersible levo-carnosine on quality of life and exercise performance in patients with chronic heart failure. Nutrition 2015;31(1):72-8. View abstract.
- Maynard LM, Boissonneault GA, Chow CK, Bruckner GG. High levels of dietary carnosine are associated with increased concentrations of carnosine and histidine in rat soleus muscle. J Nutr 2001;131:287-90. View abstract.
- Mehrazad-Saber Z, Kheirouri S, Noorazar SG. Effects of l-Carnosine Supplementation on Sleep Disorders and Disease Severity in Autistic Children: A Randomized, Controlled Clinical Trial. Basic Clin Pharmacol Toxicol. 2018;123(1):72-77. View abstract.
- Mutolo MG, Albanese G, Rusciano D, Pescosolido N. Oral administration of forskolin, homotaurine, carnosine, and folic acid in patients with primary open angle glaucoma: changes in intraocular pressure, pattern electroretinogram amplitude, and foveal sensitivity. J Ocul Pharmacol Ther 2016;32(3):178-83. View abstract.
- Narda M, Peno-Mazzarino L, Krutmann J, Trullas C, Granger C. Novel Facial Cream Containing Carnosine Inhibits Formation of Advanced Glycation End-Products in Human Skin. Skin Pharmacol Physiol. 2018;31(6):324-331. View abstract.
- Preston JE, Hipkiss AR, Himsworth DT, et al. Toxic effects of beta-amyloid(25-35) on immortalised rat brain endothelial cell: protection by carnosine, homocarnosine and beta-alanine. Neurosci Lett 1998;242:105-8.. View abstract.
- Sakae K, Agata T, Kamide R, Yanagisawa H. Effects of L-carnosine and its zinc complex (Polaprezinc) on pressure ulcer healing. Nutr Clin Pract 2013;28(5):609-16. View abstract.
- Sakae K, Yanagisawa H. Oral treatment of pressure ulcers with polaprezinc (zinc L-carnosine complex): 8-week open-label trial. Biol Trace Elem Res 2014;158(3):280-8. View abstract.
- Zaloga GP, Roberts PR, Black KW, et al. Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells. Am J Physiol 1997;272:H462-8. View abstract.
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Outsourcing Performance studies are based on a long history: Giarte will conduct the fourteenth study in 2016. As the IT outsourcing market is changing so rapidly, Giarte has adopted the principle that forecasts are of greater value than comprehensive historical reviews. For this reason changes have been implemented every year since the study began to obtain a good insight into the changing market conditions and to track best practices.
Giarte continually posts the latest insights from the benchmark study on the www.outsourcingperformance.nl website, which you can also readily compare with each other. The website also offers you comprehensive profiles of the service providers included in the benchmark study.


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Modern Italian History seminar series
The British School at Rome and the Ecole française de Rome are pleased to announce the launch of a regular seminar series in Rome dedicated to Modern Italian History. To be hosted by various academies and conducted in English or Italian, its aims are:
- to bring together visiting and resident Italian modernists
- to showcase, promote and explore newly published and current research underway in Italy
- to inform on other relevant academic events
Seminar Programme 2018–19 (TERM 1)
Thursday 18 October 2018, Biblioteca di Storia Moderna e Contemporanea, 17.00–19.00
John Foot (Bristol University): Writing a history of contemporary Italy
Discussant: Umberto Gentiloni (Sapienza – Università di Roma)
Thrusday 15 November 2018, British School at Rome, 17.00–19.00
Hans Bonde (Københavns Universitet): IL CORPO ROMANO – Da Cesare a Silvio. L'estetica della politica nel corso di due millenni.
Discussant: Paola Salvatori (Pisa)
Thursday 22 November 2018, Royal Netherlands Institute in Rome, 17.00–19.00
Roberto Romani (Università di Teramo): Sensibilities of the Risorgimento: reason and passions in political thought.
Gabriella Romani (Seton Hall University): Erminia Fuà Fusinato: a Jewish patriot in Rome (1871-1876)
Thursday 13 December 2018, Ecole française de Rome, Crypta Balbi, via de Delfini 14 17.00–19.00
Elisa Tizzoni (European University Institute): La politica turistica del fascismo tra consenso interno e proiezione internazionale
Discussant: Annunziata Berrino (Federico II Napoli)
Seminar Programme 2017–18 (TERM 3)
Tuesday 15 May 2018, Accademia di Danimarca, 18.00–19.30
Anna Wegener (Accademia di Danimarca): Translating Scandinavian literature in Fascist Italy
Tuesday 29 May 2018, Biblioteca di Storia Moderna e Contemporanea, 17.15–19.15
Ilaria Favretto (Kingston University): La fabbrica in piazza: culture e metodi di lotta operaia nell'Italia repubblicana
Tuesday 5 June 2018, German Historical Institute in Rome, 17.30-19.30
Daniel Hedinger (LMU Munich/GHI Rome): War of empires. Towards a trans-imperial history of the Second World War
Seminar Programme 2017–18 (TERM 2)
Wednesday 24 January 2018, American Academy in Rome, 18.30–20.00
Leslie Cozzi (Hammer Museum, LA/AAR): Drawing/diaphragm: the art of Marisa and Mario Merz
Wednesday 14 February 2018, Royal Netherlands Institute in Rome (KNIR), 17.30–19.30
Nick Carter, (Australian Catholic University): Balbo's ghost: remembering and re-remembering Italo Balbo in post-war and contemporary Italy
Monday 26 March 2018, American Academy in Rome, 18.30–20.00
Diana Garvin, (University of Oregon/AAR): When cuisines collide. Food in Fascist Italy
Thursday 19 April 2018, British School at Rome, 17.30–19.30
Marie Bassi, (Ecole française de Rome) La « governance » dell'immigrazione e dell'asilo in Sicilia: all'incrocio tra logiche di accoglienza, di controllo e dimensioni economiche
Seminar Programme 2017–18 (TERM 1)
Tuesday 24 October, The British School at Rome, 17.30-19.00
Florian Mussgnug (UCL): Ghosts of the future: divergent temporalities in Modern Italian fiction
Tuesday 14 November, University of California in Rome, 17.30-19.30
Barbie Latza Nadeau (Rome Bureau Chief, Newsweek): Roadmap to hell: sex, drugs & guns on the Mafia Coast
Thursday 14 December, Ecole française de Rome, 17.00-19.00
Victoria Witkowski (European University Institute): Memorialising Fascism and empire: Rodolfo Graziani and selective memory in 20th century Italy
Seminar Programme 2016–17
7 November 2016, British School at Rome
Vanda Wilcox: Per una più grande Italia? Motivation and morale in the First World War
15 December 2016, Royal Netherlands Institute in Rome
Oskar Pollak e la sua collezione di guide di Roma
11 January 2017, Ecole française de Rome (Piazza Navona 62)
Marie Bossaert: Il nemico per antonomasia. I turchi nella storia locale italiana
4 April 2017, DHI Rom
Patrick Houlihan: Global Catholicism during the First World War
13 June 2017, British School at Rome
Paul Garfinkel: Criminal Law in Liberal and Fascist Italy
We welcome proposals from any resident or visiting scholar interested in presenting their research. For more informatino please contact:
Simon Martin, Research Fellow, British School at Rome
Email: firstname.lastname@example.com
Fabrice Jesné, Directeur des études pour les Époques moderne et contemporaine, École française de Rome
Email: email@example.com
Forthcoming conferences
Past conferences
Tuesday 28 January 2020
Thursday 12 December 2019
Cardinal Alessandro Albani: Collecting, Dealing and Diplomacy in Grand Tour Europe/ Il cardinale Alessandro Albani: collezionismo, diplomazia e mercato nell'Europa del Grand Tour
Wednesday 27 November 2019
Italy and the United Kingdom: Exchanges and Transcultural Influences in Postwar Architecture
Thursday 7 November 2019
Artificial Intelligence, Machine Learning, and Deep Learning in Archaeology
Monday 4 November 2019
Training in Action: Protecting Libyan and Tunisian Cultural Heritage


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Vol 352, Issue 6281
This Week in Science
Editors' Choice
Products & Materials
- New Products
A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.
In Brief
In Depth
- El Niño's warmth devastating reefs worldwide
Recent aerial surveys of Australia's Great Barrier Reef find massive coral bleaching.
- Sandy ripples point to Mars's past
Unique dune features emerge from rover's campaign in the sand.
- Brazil bill would legalize renegade cancer pill
Government races to put "fosfo" through clinical testing.
- Canadian scientists smile at Liberals' déjà vu budget
Trudeau offers warm support for basic research.
- No-strings awards at NIH draw concern
Some recipients say they didn't expect deep cuts in funding.
- Immunity goes local
The temporary immune command posts that form near infections or inflammation draw clinical interest.
- Occupational hazard
Farm workers are dying in southern India as an epidemic of a mysterious kidney disease goes global.
Working Life
Books et al.
- Identity theft
Inspired by true events, a new play explores a controversial case of gender reassignment
- Life in the lab
A new memoir revels in the joys, sorrows, and occasional absurdities that come with a career in science
Policy Forum
- Engage key social concepts for sustainability
Social indicators, both mature and emerging, are underused
- Mitochondrial disease therapy from thin air?
Low-oxygen treatment slows neurodegeneration in a model of a mitochondrial disorder
- Rethinking the SN2 reaction
The gas-phase dynamics of a paradigm organic reaction are more complex than expected
- How Antarctica got its ice
A complex set of interactions caused the rapid growth of the Antarctic ice sheet 34 million years ago
- Nursing the oocyte
Mammalian egg cells receive material from neighboring "nurse" cells via bridges and gaps
- An odd one out
An oxygen-rich white dwarf sets an important mark for stellar evolution
- Colloidal crystal ordering in a liquid crystal
A nematic phase promotes the formation of dilute, low-symmetry colloidal crystals
- A brain conditioned for social defeat
A brain circuit in vertebrates determines who wins or loses a fight
- A lncRNA links genomic variation with celiac disease
A long noncoding RNA is associated with an intestinal autoimmune disorder
Research Articles
- Long-read sequence assembly of the gorilla genome
A new approach to looking at the gorilla genome improves estimates of the differences between humans and gorillas.
- Genetic circuit design automation
A programming language is devised for biological regulatory circuits.
- Hypoxia as a therapy for mitochondrial disease
Chronic exposure to low oxygen levels improves the health and extends the survival of mice that model a human mitochondrial disease.
- On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system
Preparation of four common pharmaceuticals shows the versatility of an integrated system the size of a household refrigerator.
- A white dwarf with an oxygen atmosphere
The discovery of a long-sought oxygen white dwarf is an important test case for stellar evolution.
- Triclinic nematic colloidal crystals from competing elastic and electrostatic interactions
Competing elastic and electrostatic forces acting on gold nanorods in a nematic host yield triclinic colloidal crystals.
- Tuning the activity of Pt alloy electrocatalysts by means of the lanthanide contraction
Alloying platinum with lanthanide elements compresses its surface layer and boosts its oxygen reduction activity.
- Antarctic Ice Sheet variability across the Eocene-Oligocene boundary climate transition
The growth of the Antarctic Ice Sheet began only when atmospheric levels of carbon dioxide dropped low enough.
- A 21st-century shift from fossil-fuel to biogenic methane emissions indicated by 13CH4
The atmospheric methane level has resumed its increase after a plateau between 1999 and 2006.
- Consistent response of bird populations to climate change on two continents
The impact of climate change on population sizes of birds across continents can be predicted.
- Social conflict resolution regulated by two dorsal habenular subregions in zebrafish
The neuronal basis for keeping the aggression of fighting fish in check is elucidated.
- A long noncoding RNA associated with susceptibility to celiac disease
A specific RNA molecule can suppress inflammatory gene expression and may protect from gluten intolerance.
- Mouse oocytes differentiate through organelle enrichment from sister cyst germ cells
Sister germ cells provide organelles and cytoplasm to oocytes to augment their developmental potential.


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WASHINGTON — Teeing up a bipartisan rebuke of the U.S. president, the Senate's must-pass defense policy bill will include legislation to maintain penalties against Chinese telecommunications firm ZTE, lawmakers announced Monday.
"The fact that a bipartisan group of senators came together this quickly is a testament to how bad the Trump administration's ZTE deal is and how we will not shy away from holding the president's feet to the fire when it comes to keeping his promise to be tough on China," Senate Minority Leader Chuck Schumer tweeted Monday.
An amendment that would keep prior penalties in place against ZTE is expected to be part of the Senate's version of the National Defense Authorization Act, which is expected to pass the upper chamber this week. It was included in a "manager's package" of 44 bipartisan amendments to the bill, which reflects approval from Democratic and Republican leaders.
The action comes after U.S. Commerce Secretary Wilbur Ross announced earlier in the week that ZTE would pay a fine of $1 billion and the U.S. would end a ban preventing the firm from buying American parts. The deal was in place after the U.S. found that ZTE evaded sanctions on Iran and North Korea.
Instead, the amendment would ban U.S. government agencies from purchasing or leasing telecommunications equipment from Huawei and ZTE, and it would ban the U.S. government from using grants and loans to subsidize Huawei or ZTE.
"The threat Huawei and ZTE pose to our national security is too great to ignore. This amendment will help keep Americans' private information out of the hands of the Chinese Communist Party, and I'm pleased it will be included in the NDAA," said Sen. Tom Cotton, who co-sponsored the amendment with Sen. Chris Van Hollen, D-Md. Cotton chairs the Senate AirLand Subcommittee.
The manager's package and massive NDAA are likely to pass the Senate, but the language would still have to survive bicameral negotiations to reconcile the bill with its House counterpart.
Senate debate on the NDAA was expected to continue Tuesday.