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The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research
Experimental & Translational Stroke Medicine volume 2, Article number: 17 (2010)
Background and purpose
Reliable models are essential for translational stroke research to study the pathophysiology of ischaemic stroke in an effort to find therapies that may ultimately reduce oedema, infarction and mortality in the clinic. The purpose of this study was to investigate the relation between the site of arterial embolization and the subsequent oedema, infarction and clinical outcome in a rat embolic stroke model.
Thirty-six male Sprague-Dawley rats were thromboembolized into the internal carotid artery. The site of occlusion was demonstrated by arteriography. Following histological preparation and evaluation, the size of the hemispheres and the infarcts were measured by quantitative histology and planimetry. Another parallel stroke model study was subsequently examined to investigate if the conclusions from the first study could be applied to the second study.
The median size of the infarct was 40% of the ipsilateral hemisphere in both the 19 animals with occlusion localised to the intracranial part of the internal carotid artery and in the 11 animals where the main trunk of the middle cerebral artery was occluded. In 5 animals, occlusion of the extracranial part of the internal carotid artery resulted in significantly smaller infarcts compared to other groups (p < 0.01). Another independent study re-confirmed these results. Furthermore, significant correlations (R > 0.76, p < 0.0001) were found between 1) cortical, subcortical, and total infarct volumes, 2) oedema in percent of the left hemisphere, 3) clinical score before termination and 4) postoperative weight loss.
Distal occlusions of the intracranial part of the internal carotid or middle cerebral arteries resulted in comparable large sized infarctions and oedema. This indicates that investigators do not need a similar number of such occlusions in each experimental group. Contrary to observations in the clinic, distal internal carotid artery occlusions did not result in worse outcome than middle cerebral stem occlusions, but this finding may be explained by the controlled emboli size in this experimental stroke model.
Commonly human stroke patients suffer from direct occlusion of the middle cerebral artery (MCAO), or from occlusions of the internal carotid artery (ICAO), which reduce or prevent sufficient blood flow through the middle cerebral artery (MCA).
Recently, the importance of establishing reliable animal models is clear, as hundreds of effective neuroprotective therapies in animals failed to show beneficial effect in the treatment of human stroke . It has been argued, that the quality of many animal models provided unreliable results due to insufficient study design and type of model, randomisation, blinding, inclusion and exclusion criteria, measurement of physiological parameters etc. . The animal model used in the present investigation is different from several other MCAO animal models by using obstructing autologous blood clots that compromise cerebral arterial circulation in focal brain regions. The advantage of this model in translational stroke research is its similarity to human ischaemic stroke, and this advantage has been exemplified by the fact that this model provided results of thrombolytic efficacy in rats before benefit of human thrombolytic treatment was documented [3–5]. The primary disadvantage of this embolic stroke model is a large variation of infarct volumes, but although the variation in infarct volume makes it necessary to use relatively large animal group sizes, the model may provide a sound basis for translational stroke research.
The main purpose of this study was to investigate the relationship between the site of arterial occlusion and the subsequent size of the resulting infarct in a rat embolic stroke model. If the consequences of embolization in this animal model are shown to be similar to consequences of embolization in humans, the model will be of high translational significance due to its prognostic abilities.
Measurement of infarct volumes generally has been the main endpoint of investigations in animal stroke models, but many factors may interfere with measurements of infarcted tissue such as brain swelling by oedema or brain shrinkage by resorption. In this study we investigated several aspects associated to the embolic location, namely infarct volume, oedema size, mortality and effects of re-embolization. An endpoint to the investigation was to examine whether or not evenly distributed locations of the emboli and the consequently degrees of ischemia among treatment and control groups were necessary to avoid unwanted selection bias, especially when groups are relatively small in numbers. Thus, in the present study, the consequences of emboli localisation especially upon infarct volume were investigated for the first time and further related to both the formation of oedema and the clinical outcome.
Materials and methods
Animals in this study have previously been investigated for other purposes . Re-using animals to provide extended results and observations is in favour of the methodology encompassed in the concepts of refinement, reduction and replacement within animal laboratory science [7, 8]. This ethical methodology corresponds to the aim of medical researchers to use as few animals and as responsibly as possible.
All experiments were approved and conducted according to the guidelines by the Animal Research Committee of University of Copenhagen. Thirty-six male Sprague-Dawley rats weighing from 240 to 420 grams were used. The rats were housed in a 12-hour light-dark cycle at a room temperature of 22 ± 1°C, with unrestricted access to water and chow before and after surgery. Anaesthesia was induced with subcutaneous administration of Hypnorm® (fluanison 4 mg/kg and fentanyl 0.12 mg/kg, Janssen Pharmaceutica, Beerse, Belgium) combined with atropine 0.05 mg/kg and intraperitoneal administration of diazepam 2 mg/kg (Apozepam 5 mg/ml; Apothekernes Laboratorium, Lier, Norway). The body temperature was kept at 37 ± 0.5°C by rectal temperature monitoring and a thermostat controlled heating lamp.
Surgical procedure and preparation of the emboli
Small white 'arterial-like' elongated autologous microclots rich in fibrin were produced in vitro as reported earlier [4, 5, 9]. Then by modification and amendment of this method, the suspension of microclots was injected into a 120-cm long PP10 (PP10; ID 0.28 mm, also corresponding to clot diameter) air filled tube . The microclots in the suspension accumulated to several single macroclots of larger and variable length by this method . A macroclot with a length of about 8 mm (0.44 mm3) was selected for embolization by cutting a piece of the tube with the macroclot enclosed. Both the right femoral vein and the external carotid artery (ECA) were catheterised, while the pterygopalatine artery was ligated as described earlier . Clotting associated with the inserted catheters was avoided by continuous flow of heparinised (5 IU/ml) saline through the line at the speed of 0.5 ml/h until the catheter was removed at the end of surgery. The mean arterial blood pressure (MABP), blood glucose, haemoglobin, PaO2, O2-saturation, PaCO2 and pHa were measured (Radiometer ABL 2, Copenhagen).
Embolization produced arterial occlusion documented by arteriography
The right common carotid artery (CCA) was clamped temporarily using a ligature, and the embolus was gently injected through the saline-filled ECA catheter by the use of 0.3 ml saline. This procedure caused embolization of the right hemisphere by occlusion of the internal carotid artery (ICA) or MCA. After this procedure carotid arteriography was performed immediately by bolus injection of 0.20 ml heparinized (5 IU/ml) iohexol (Omnipaque, 300 mg I/ml; Nycomed, Roskilde, Denmark) through the ECA catheter. Angiograms were processed on high-resolution films (Retina XOE; Fotochemische Werke, Berlin, Germany). Since the CCA was unclamped during the angiographic procedure, this procedure did not affect the embolization.
Arteriograms were evaluated without knowledge of the fixation procedure in accordance with a modification of a previously reported topographically rank ordered scale . All arteriograms were evaluated individually and assigned one of the following scores: 0 = patent arteries, 1 = middle cerebral artery occlusion (MCAO in one or more branches), 2 = MCAO at the stem, 3 = distal and intracranial ICA occlusion, 4 = extracranial and proximal ICA occlusion. The angiographic scores are illustrated on Figure 1. During surgery using an unblinded evaluation of the arteriograms, fourteen (39%) of the animals achieved a score of 0, 1 or 1.5 with an occlusion in the distal half of the MCA. These 14 animals were considered poorly embolized and were embolized again by repeating all embolization procedures, and the final grade of occlusion was determined by the repeated arteriography. In two animals embolization and arteriography according to the above procedures were performed 3 times, while the other 12 animals were successfully embolized on the second attempt. In order not to expose animals to an excessive amount of dislocated embolus material, no more than three embolization attempts were allowed in this study. After the final arteriography and then ligations of vessels, femoral and neck wounds were closed. The effect of anaesthesia was reverted with naloxone 0.3 mg/kg s.c. (Narcanti®, Du Pont Pharmaceuticals, U.S.A.).
About two hours after recovering from anaesthesia, the clinical neurological status was evaluated using a rank ordered scale for rats developed by Bederson et al. ; a score of 0 reflected normal neurology and no observable deficit (grade 0), a score of 1 corresponded to moderate clinical damage observed by forelimb flexion (grade 1), a score of 2 reflected severe clinical damage and decreased resistance to lateral push (and forelimb flexion) without circling (grade 2), while a score of 3 corresponded to maximum clinical damage with the same behaviour as grade 2 with circling (grade 3). A Bederson score has been found to correlate to the infarct sizes . Twenty-four hours after anaesthesia all animals were weighted, re-evaluated clinically as above and terminated.
Preparation of brain tissue and measurement of infarct size
Twelve animals were perfusion fixed with formalin. In this group and in a second group of 13 other animals the brains were carefully removed and immersed in formalin. A third group of 11 animals was left dead for three hours at room temperature before the brains were dissected out and immersed in formalin. The 3 different fixation procedures were evenly distributed without significant differences between the 3 groups with different grades of vascular occlusion. As shown previously, fixation procedures had no influence on the results of this current investigation, because infarct and oedema volumes calculated as percentages of the corresponding hemisphere were independent of fixation procedures .
Standard histological procedures were used and coronal serial sections of the brain with a distance of 400 μm between each section (about 20-25 sections per brain) were stained with hematoxylin-eosin . This distance between sections was used, because a tripling of the distance between brain sections can decrease the accuracy of the measurements by up to 4% [13–15].
Volume calculations using image analysis and planimetry
All brain sections were examined carefully by conventional light microscopy by investigators blinded to the experimental protocol. Borderlines of the cortical and subcortical infarcts were delineated and separated from healthy brain regions using a pen, and the infarcted tissue could be recognised easily (Figure 2). All brain sections were scanned into a personal computer by the use of an image analysis program (Sidney Data, Copenhagen, Denmark), providing volume measurements of hemispheres and infarctions. The accuracy of the planimetry was secured by performing repeated control-scans of a rectangle sized 115 mm2 placed in a horizontal as well as in a diagonal position.
Calculations and analysis of weight, oedema and statistics
Animals were weighted preoperative and immediately before the animal was terminated at 24 hours. Postoperative weight loss in percent of preoperative weight was calculated as: 100 × (preoperative weight - pre-termination weight)/preoperative weight. Under the assumption that differences between right and left hemisphere volumes constituted oedema sizes, the volumes of oedema in percent of the left hemisphere was calculated as: 100 × (RH - LH)/LH, with RH and LH representing volumes of the right and left hemispheres, respectively. Oedema volumes in percent of infarct volumes were calculated as: 104 × (RH - LH)/(INF × RH), where INF represented infarct sizes in percent of RH. Non-parametric statistical analyses of data were performed, because all data were either categorical, or could be placed on rank ordinal or ratio-interval scales with no apparent normal distribution. Mann-Whitney U-test for unpaired observations, Wilcoxon matched-pairs test for paired observations and the Spearman test for correlation of ranked pairs were used. P-levels below 0.05 were considered significant.
On the final blinded evaluation of the arteriograms the surviving animals were divided into 3 different subgroups: one subgroup of 11 animals had a grade 2 (stem of the MCA) occlusion, a second subgroup of 19 animals had a grade 3 (intracranial ICA) occlusion and the remaining subgroup of 5 animals had a grade 4 (extracranial ICA) occlusion. One animal found dead at 20 hours was excluded from the results, and all other animals survived 24 hours. Figures 3A and 3B illustrate grade 2 and 3 embolizations. The 3 different fixation methods were evenly distributed without significant differences between the 3 groups on vascular occlusions.
No significant differences were observed between any of the 3 subgroups in physiological parameters. Results (median and interquartile range) in all 35 animals were: MABP: 76 mmHg (70-85), haemoglobin: 10.4 mmol/l (10.1-10.7), glucose: 11.3 mmol/l (11-13), pHa: 7.395 (7.38-7.41), PaCO2: 39 mmHg (37-42), PaO2: 87 mmHg (82-92), O2-saturation: 96% (96-97), preoperative weight of animals: 350 g (313-397), size of both hemispheres (excluding cerebellum, brainstem and olfactory bulbs): 795 mm3 (740-892), respectively (comparing all subgroups, all p > 0.05, ns). Similar to earlier reports by other investigators , we found no influence of rat age or preoperative weight on infarct volume.
Infarct size was dependent on the efficacy of embolization documented by grade of arteriographic occlusion
As shown in table 1 the 11 animals with a MCAO had median cortical, subcortical and total infarct volumes of: 17.2%, 20.5% and 40% respectively of the right hemisphere volume. The 19 animals with intracranial ICAO had almost identical median infarct volumes of 16.6%, 19.9% and 40% respectively (all p > 0.45). Thus animals with a grade 2 or 3 occlusion obtained similar infarct volumes.
Two of the 5 animals with an extracranial ICAO had in addition an unintended insufficient ligation of the pterygopalatine artery documented by the arteriography. One of the animals with an open pterygopalatine artery had a total infarct of only 1.7% of right hemisphere volume even embolized three times with the first two arteriograms showing patent arteries, the third showing extracranial ICA occlusion. These 5 animals all had significantly lower size of infarcts (table 1); total infarct was in all 5 animals below 7% (median 3.5%) of the right hemisphere volume.
Repeated embolization improved the occlusion rate
Three animals with MCAO, 8 animals with intracranial ICAO and 3 animals with extracranial ICAO were embolized more than once. In the animals with repeated embolization, the 3 animals with a final extracranial ICAO had a significantly (p < 0.02) lower initial angiographic score of median = 0 = patent arteries compared to all the other 11 repeatedly embolized animals on the arteriogram obtained after the initial embolization. These 14 animals submitted to repeated embolization had a significant higher final than initial arteriographic score value (p < 0.002). Repeating the embolization thus improved successful embolization. When these 14 animals were compared with all other animals embolized only once, the differences in the physiological or other main result parameters were not significant.
At the postoperative clinical score two animals had a score value of 2, all other animals had a score value of 3. Specifically, among animals in the MCA group, immediately after surgery the Bederson score was 3 (3-3), at 24 hours post-surgery the pre-termination score was 1 (0-2) revealing an improvement of 2 (1-3). For the intracranial ICA group the postoperative score was 3 (3-3), the pre-termination score was 2 (1-2) revealing an improvement of 1 (1-2), and in the extracranial ICA group the postoperative score was 3 (3-3), the pre-termination score 0 (0-1) resulting in an improvement of 2 (2-3). The improved pre-termination scores were significant in all groups (P < 0.05), but no group differed from each other when comparing post-surgery or pre-termination scores. Thus generally the neurological deficit remitted significantly as the clinical score decreased from the postoperative level to a median score value of 1 at the observation after 24 hours (all 35 animals; p < 0.0001). The subgroup of 5 animals with extracranial ICAO had a pre-termination median clinical score value of 0 compared to all other animals with a median score value of 1.5 (p = 0.09).
The pre-termination weight of all 35 animals was significantly (p < 0.001) lower than the initial weight of the animals, and the 5 animals with extracranial ICAO had a significantly smaller loss of weight compared to all the other 30 animals (table 1).
Correlations between infarct size and oedema, clinical outcome and weight loss
Significant correlations were found between cortical, subcortical and total infarct volumes (all animals; all R > 0.76, all p < 0.0001). Other important correlations are listed in table 2.
The embolized right hemisphere suffered from significant oedema depending on infarct size but not site of occlusion
The embolized right hemisphere was larger than the left in the 30 animals with an intracranial site of arterial occlusion (p < 0.001), except in the 5 animals with extracranial ICAO, where the median size of the hemispheres were 366 mm3 and 363 mm3, right and left respectively (p > 0.68). The magnitude of the oedema in each subgroup is presented in table 1. In all 3 subgroups of embolization the size of cerebral oedema ranged from median 11% to 13% of the size of the infarct, with no significant intergroup differences. In the subgroup of 5 animals with an extracranial ICAO the size of cerebral oedema measured in percent of the size of the left hemisphere was significantly smaller (all p < 0.02) in the subgroup of animals with extracranial ICAO compared to either or both subgroups of animals with an intracranial site of occlusion.
Comparing the present results with results from another experiment
We re-examined data from another experiment using a similar animal model, where different stroke treatments had no effect on infarct volumes and where the relationship between infarct volumes and different occlusion sites had not be investigated before . Although the study used smaller emboli of 4 to 6 mm instead of 8 mm , occlusion sites were the same and therefore results of emboli locations and the associated infarct volumes should be comparable. In 38 embolized animals  we found the results shown in Figure 4. Comparing 8 animals with a grade 2 occlusion with 14 animals with a grade 3 occlusion or 13 animals with a grade 3.5 occlusion we found no significant differences in infarct volumes (p = 0.23 and 0.25 respectively). Figure 1 illustrates different angiographic scores. Similarly a grade 3 occlusion did not differ from a grade 3.5 occlusion (p = 0.96). Occlusions in the right hemisphere of the ICA between the posterior cerebral artery (PCA) and the MCA was scored as 3 if the occlusions were in the upper half more proximal to the MCA, or 3.5 when occlusions happened in the lower half more proximal to the PCA (these types of occlusions would both block the entrance to the right MCA). Thus these results indicate that occlusions scoring from 1.5 to 3.5 provide similar infarct volumes. These independent results confirm and extend earlier findings in this study, where grade 2 or 3 occlusions resulted in similar infarct volumes.
The present study using a 'arterial-like' single macroclot model  demonstrated a significant relation between the sites of angiographically verified embolization and histologically verified cerebral infarction and oedema when comparing extracranial ICA occlusions to intracranial MCA or ICA occlusions. Consequently, the position of the arterial occlusion significantly influenced the size of the infarct and oedema in this rat embolic stroke model. The relation found between the location of the vascular occlusion, size of the infarct, oedema formation, clinical score and postoperative weight loss demonstrates the similarities to human stroke and the robustness of this model.
The lack of infarct volume differences when comparing animals with a grade 2 or 3 occlusion may seem contrary to clinical findings, where distal ICA occlusions have been associated with a worsening of outcome compared to MCA stem occlusions [17–19]. In human stroke the worsening of outcomes by ICA occlusions may be explained by larger emboli unable to propagate by the MCA and causing profound disturbances of blood flow in the circle of Willis. The size of emboli was similar for all animals in this experimental stroke model, but a possible fragmentation or folding of an embolus may affect its shape and explain the variance in embolus locations. Furthermore outcome in human stroke is generally measured by reperfusion or behavioural scores [17–19], which may or may not correlate well with infarct volumes. In humans with larger MCA infarcts, the ICA was occluded in 40% of the patients . If the collateral blood supply was sufficient as in an extracranial ICA occlusion, humans may show no symptoms of an ICA occlusion, similar to our present observations in rats. If an ICA occlusion had major impact upon collateral blood supply, corresponding to an embolus or thrombus extending into the circle of Willis, large infarctions have been shown in humans . These findings are similar to our present results of grade 3 or 3.5 occlusions in rats, where the ICA occlusion extended into the circle of Willis and blocked any collateral blood supply from entering the MCA.
In another study of 55 humans with complete MCA infarctions or more extended infarcts mortality was 78% , exemplifying the need for models with high translational value in order to facilitate treatment investigations of this severe disease.
In humans bad clinical outcome has been predicted by the presence of hemianopia and reduced consciousness, where especially coma predicted death . Such symptoms of hemianopia may be difficult to measure after embolization in rats, but reduced consciousness or coma may respond well to a Bederson score of 2 or 3, where an animal becomes less responsive and shows clear signs of neurological damage. The Bederson Grading System has been linked to infarct sizes (a Bederson score of 3 has been linked to larger infarcts and worse outcome than lower scores).
In older investigations where we used our multiple 'arterial-like' microclot method [5, 9] the mortality immediately after embolization was up to 20% caused by respiratory arrest, probably induced by massive embolization including the brain stem injuring the respiratory centre. In addition the infarcts were larger; 40-60% of the hemisphere volume, resulting in a further 30-90% mortality within the first 4-6 days following embolization, which correlated to the volume of suspension of emboli and the size of the infarct. This large technically induced mortality was a drawback of the multiple 'arterial-like' microclot method, but fortunately was not the result of the present model, where we used only one embolus per occlusion. Using the present single-clot model, and by comparing animals receiving one embolus with animals needing more than one embolus to obtain an occlusion, animals did not differ in infarct sizes or mortality. In theory, by the re-embolization of animals failing to show an occlusion after receiving the first embolus a bias may be introduced, but human stroke patients often experiences multiple infarcts and emboli [22–24]. Thus, using multiple embolizations was not a drawback of the present animal model, but may strengthen its translational capacities.
Theoretically we did not have to consider occlusions in the distal half of the MCA, corresponding to animals with less than a grade 2 occlusion, as poor, because grade 1 or 1.5 occlusions may generate a similar amount of brain damage as grade 2 or 3 occlusions. This trend is shown in Figure 4, where a grade 1.5 occlusion provided large brain damage. In practice it was difficult to verify occlusions of the distal half of the MCA, as the diameter of the MCA becomes gradually smaller and the MCA turns and continues out of the plane of the angiography. Radiation diffractions and reflections made it difficult to see the small and distal parts of the MCA clearly, and often we found that seemingly valid occlusions of the distal half of the MCA showed no evidence of occlusion by later examinations. Therefore we considered embolizations of less than grade 2 to be unreliable and chose to re-embolize those animals. If future investigations are able to measure occlusions of the distal half of the MCA reliably, such results may be of great translational interest to humans. Recently investigators found that M1 MCA occlusions in humans, corresponding to grade 1 to 2.5 occlusions in the rat, were independent risk factors of poor outcome, compared to M2 occlusions, corresponding to occlusion grades of less than 1 in the rat . Thus both in rats and humans occlusions of the proximal part of the MCA have been linked to the worst outcomes.
Though this experimental stroke model has been designed to mimic human stroke elaborately differences related to variation of emboli sizes and associated collateral blood supply may pose restrictions upon the similarity, which further strengthens the relevance of the present study as an evaluation of the translational capacities of this embolic stroke model. We have been unable to find a relation between infarct size and emboli location, comparing similar sizes of emboli occluding the stem of MCA or the distal part of ICA, in human stroke. This current animal model was the first to demonstrate that the time-window of thrombolysis in rats was identical to the time-window of thrombolysis in human ischaemic stroke reported a couple of years later (compare references  and ). Thus, should future investigations find that this rat model of embolic stroke differs from human stroke in outcome and infarct sizes, even if similar emboli locations are observed, there is still ample evidence to suggest a high degree of translational value of this animal model. Also, in studies of treatment effect after embolic stroke, documentation of evenly distributed degree of ischemia (e.g. by angiography) among treatment and control groups, before treatment is initiated, is favorable in order to secure a similar amount of brain damage among animals in each group, especially when groups are small in numbers. Our current study shows that an evenly distributed degree of ischemia is obtained from grade 2 (main stem MCA) and grade 3 (distal ICA) occlusions (even grades 2, 3 and 3.5 were found to result in similar infarctions). This important finding illustrates that investigators do not need to obtain a similar number of animals with a grade 2 or 3 in each experimental group as no significant differences when comparing subcortical, cortical or total infarct volumes were found, while animals with grade 4 occlusions should be evenly distributed or excluded.
In rats abundant collaterals exist between distal branches of the anterior cerebral artery, MCA and the posterior cerebral artery . A proximal extracranial ICAO increases the chance of collateral circulation also by the circle of Willis. In the rat, the pterygopalatine artery branches off from the ICA, ligation of the artery is therefore necessary to achieve embolization only of the ICA and MCA. The type of vascular occlusion might influence the extent of infarction.
Determining infarct size at 24 hours as done in this study carries the risk of overestimating the volume caused by oedema of the infarcted tissue. However, at day 7 the process of resorption  results in ~30% shrinkage of a large embolic infarct . We therefore chose 24 hours as an early time point where the infarct was fully recognised, before severe swelling or shrinkage occurs.
The magnitude of oedema depends of the choice of ischaemic model and the timing . Animals can die from herniation caused by large hemispheric infarcts and ipsilateral brain oedema within 24-48 hours . As shown previously the three different fixation procedures did not interfere with the measurement of oedema, which after 24 hours constituted 11% of the infarct volume , compared to 6% using comparable methods , provided all enlargement of the right hemisphere was located inside the infarction, which may not be absolutely valid . The calculations reported by Leach et al.  and Swanson et al.  compensate for these problems, and the volume effect of oedema is attempted weighted out. The grade of oedema was correlated to the clinical outcome and infarct volume, and the size of the right and the left hemisphere correlated significantly to each other, but not to the rat age or preoperative weight.
In conclusion, extracranial ICA occlusions (grade 4) provided significant less infarction than occlusions of the intracranial and distal part of ICA (grade 3) or the stem of the MCA (grade 2). No differences were found when comparing infarctions resulting from grade 2 or 3 occlusions. This observation was further strengthened by the re-examination of data from another study based upon a similar model. Thus when groups are small in numbers, animals with grade 4 occlusions should be evenly distributed among groups, while grade 2 and 3 occlusions may be intermixed at random. This observation was further strengthened as similar significant correlations were found between a) cortical, subcortical and total infarct volumes and oedema in percent of the left hemisphere, b) clinical score before termination and c) postoperative weight loss among animals with grade 2 or 3 occlusions.
The lack of differences between grade 2 and 3 occlusions simplify the surgical procedures, thereby making the use of this embolic stroke model or other MCAO models a valuable asset for translational stroke research.
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Coyle P, Jokelainen PT: Dorsal cerebral arterial collaterals of the rat. Anat Rec 1982, 203: 397–404. 10.1002/ar.1092030309
Zhang Z, Zhang RL, Jiang Q, Raman SBK, Cantwell L, Chopp M: A new rat model of thrombotic focal cerebral ischemia. J Cereb Blood Flow Metab 1997, 17: 123–135. 10.1097/00004647-199702000-00001
DeGirolami U, Crowell RM, Marcoux FW: Selective necrosis and total necrosis in focal cerebral ischemia. Neuropathologic observations on experimental middle cerebral artery occlusion in the Macaque monkey. J Neuropathol Exp Neurol 1984, 43: 57–71. 10.1097/00005072-198401000-00005
O'Brien MD, Waltz AG: Development and resolution of edema in experimental cerebral ischemia and infarction. In Cerebral Circulation & Metabolism. Edited by: Langfitt TW, McHenry LC Jr, Reivich M, Wollman H. New York Heidelberg Berlin: Springer-Verlag; 1975:68–70.
Leach MJ, Swan JH, Eisenthal D, Dopson M, Nobbs M: BW619C89, a glutamate release inhibitor, protects against focal cerebral ischemic damage. Stroke 1993, 24: 1063–1067.
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Shila Luther is thanked for excellent technical assistance. This publication was financially supported by The Danish Medical Research Council, The Danish Heart Foundations grant no: 96-1-6-145-22374, the Foundations of Augustinus, Hede Nielsen, Gangsted, Leo Research, Carl J. Becker, Werner Richter, E. Danielsen, J.P.A. and Dagny Espersen, Else and Mogens Wedell-Wedellsborg, Else Torp, Harald Jensen, Mimi and Victor Larsen and Mogens S. Mogensen.
The authors declare that they have no competing interests.
All authors have made substantive intellectual contributions to this study, including conception and design, acquisition of data, analysis and interpretation of data, writing and revising the manuscript. All authors have given final approval of this current version. Each author has participated sufficiently in acquisition of funding and the collection of data.
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Cite this article
Overgaard, K., Rasmussen, R.S. & Johansen, F.F. The site of embolization related to infarct size, oedema and clinical outcome in a rat stroke model - further translational stroke research. Exp & Trans Stroke Med 2, 17 (2010). https://doi.org/10.1186/2040-7378-2-17
- Internal Carotid Artery
- Middle Cerebral Artery
- Infarct Volume
- Mean Arterial Blood Pressure
- Internal Carotid Artery Occlusion


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Address: 2 North Salisbury Street, West Lafayette, IN 47906
I’d be remiss if I did not do a post on one of West Lafayette’s most well-known dining establishments for almost 80 years.
From my understanding, Triple XXX started out as a root beer brewing company, using a recipe involving pure cane sugar (which is still the same root beer sold at the restaurant today). The individual X’s in their name are from a rating scale of root beer quality back in the old days, with a triple X rating meaning that you possess the best quality root beer. Having heard about this place from the Guy Fieri’s Food Network program Diners, Drive-Ins, and Dives, my family went here during our first visit to campus.
One of the things that makes this restaurant great, especially on a college campus, is that it is open for 24 hours. Those four words alone are enough to make a college student smile. It is a pretty small restaurant, with a bar-style seating area that loops around inside. There’s pretty much a single aisle to get to the other side of the restaurant, so things can get pretty cramped if you’re trying to get through. I have found, however, that the staff has always been very friendly to everyone that dines here. This place will certainly get packed anytime there’s a sports game going on at Purdue or on various nights during the week. I’ve walked by on Thursday nights and this place is jam-packed like a can of sardines!
I’ve gotten my chance to have both their burgers and their breakfast here, and I think that I’m more of a fan of their breakfast. Don’t get me wrong, their 100% ground sirloin burgers are quite delicious by their own accord; I’m not sure if there’s just something about eating out for breakfast that intrigues me a bit more. But having tried the Boilermaker Pete, the Bert Burger, the Duane Purvis (one of their signatures that includes peanut butter spread on the bun), and the Bernie Flowers, I can say that each of those burgers are really fantastic. My go-to on the breakfast side of things is the Drew Brees Breakfast Platter, with eggs, chicken fried steak, potatoes, buttermilk biscuits, and gravy.
It’s a Purdue tradition to visit Triple XXX at some point during your college career or even if you are visiting the campus from out of town. The restaurant has also been named among USA Today’s list of 51 Great Burger Joints Across the USA. With a great menu that is available at all hours of the day, along with some great root beer (and root beer floats) to go along with it, you really can’t go wrong.
Here are my rankings for Triple XXX:
Food: 4.5 / 5
Serving some great options for all meals throughout the day, Triple XXX has food that will fulfill a variety of appetites.
Atmosphere: 4 / 5
It’s certainly much more of a retro feel when you walk in and sit at the counter to eat food, rather than at a table like many other restaurants nowadays.
Service: 5 / 5
The waitstaff have always been very nice and the food comes out of the kitchen very quickly.
Price: 4.5 / 5
I think that the prices for the food are very reasonable and money well spent. Quick note: Triple XXX is cash-only.
Overall: 18 / 20 (90%)

domain: food


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Sep 20, 2022 · Usgovernmentspending.com has updated its estimate of Medicare Part C, the Medicare Advantage program using data in the Medicare Trustees Report of 2022 that was released June 4, 2022.
Sep 25, 2022 · aberdeen, batesville, belzoni, brookhaven, canton, clarksdale, cleveland, collins, columbia, columbus, corinth, forest, greenville, greenwood, grenada, hazlehurst, holly springs, indianola, kosciusko, laurel, louisville, magee, mccomb, meridian, monticello, natchez, new albany, oxford, pascagoula, philadelphia, picayune, senatobia, starkville, …
Sep 24, 2022 · The map shows the location of following cities and towns in Missouri: Largest cities are Kansas City (467,000), St. Louis (318,000), Springfield (164,000), Independence (117,000), Columbia (115,000) Capital is Jefferson City (43,330) Population figures in 2014 Old County Courthouse with the Gateway Arch in St. Louis, Missouri.
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Sep 23, 2022 · The Louisiana Lottery Corporation isn’t the first lottery the Pelican State has known. The original Louisiana State Lottery was a private entity, founded in 1868 (and ending in 1890). The current incarnation of the lotto is a government-run corporation, established in 1991.
Sep 24, 2022 · The state's highest elevation point is on Black Mountain at 1,263 m (4,145 ft), located in Harlan County near the Virginia border. Nickname The state's nickname is Bluegrass State, the nickname is based on Kentucky bluegrass. Horses The state is home to the Kentucky Derby, a horse race, and "The Greatest Two Minutes in Sports."
Sep 23, 2022 · Click on the map to enlarge. Area The state occupies an area of 135,767 km² (52,420 sq mi), [ 1] making it somewhat larger than Greece (131,957 km²). Compared with other US states by area, Alabama is six times larger than New Jersey, but it would fit into Texas about five times. Nearly 70% of Alabama's landscape is covered by forest.

domain: geography


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The Seven Husbands of Evelyn Hugo by Taylor Jenkins Reid
This beautiful story follows a woman who struggles to be herself amidst the life she's created. It's raw, emotional, and makes you consider the choices you make to be with the ones you love.
We’re so excited to share everything we love with you! Please keep in mind that we sometimes receive commissions when you click our links and make purchases.
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domain: literature


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Every performance by French burlesque dancer Sucre d'Orge (“Candy Cane”) is a stunning example of style and elegance. Admire her feather fans dances and let her tease you…
Sucre d’Orge has collaborated with well-known and luxury brands such as Dior, Oliver’s people and Penhaligon’s and has performed at majors events such as the Versailles Carnival, la Fête de la danse de Blanca Li, Canal + events during the Cannes Film Festival.
She has appeared in numerous international and French venues, including:
Wilton Theatre (Londres), Salon Parisien (Milan), Casa do Alejandro (Lisbonnes), Gemini & Scorpio Loft (New York), le Papagayo (St Tropez), Silencio Club, Chez Raspoutine, Le Trianon, Le Carmen (Paris).
She has participated in burlesque revues such as La Petite Cour des Astres, Voodoo de Luxe (Milan), Glitter Fever, La Nouvelle Seine and Burlesque Beauties, and is a regular live model for Dr. Sketchy’s Anti-Art School (Paris & NYC).
Shows and private events
Your best friend’s big day is coming up, and you would like to offer her a glamourous Bachelorette or Hen party? You’re curious about burlesque and would like to try waving your first feathers?
Glitter, fans, garter belts: discover the accessories and movements that can make you a star for a night, or for a lifetime.
Sucre d’Orge proposes 1 1/2 to 2 hours classes (minimum 4 participants.)
The classes include
- Knowing your body and emphasizing your best features
- Femme fatale, ingénue, pin-up: which are you?
- How to have the world at your feet: walking in heels, the right way!
- Pratical advices for burlesque from a tango dancer
- Stockings, garters, corsets, retro make-up and hairstyles: all within your grasp!
Sucre d’Orge will then teach you an easy-to-learn choreography that will have your audience begging for more, and help you feel comfortable when you improvise.

domain: artistic


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Today's sneak peek is the shirt. I started with just finding the lightest and darkest big shapes, then brought them closer together with a wash of a medium gray, then started adding details and hard edges. I'll leave it at this level until I get the other arm in and know exactly how it reads. Of course in the book I will give you more information than this - I don't want to spoil it!
This portrait will be in the back of the book where I show how I put together a full portrait and what order I do things in. The previous chapters are: Supplies, Making A Reference Photograph/Drawing the Cartoon, Learning the 2 Step CP Technique, Proportions of the head, The Eyes in Detail, Other Features in Detail, Hands and Fabric. After these chapters will be full portrait WIP, some cropped in on the face and some further out like this one with all the supporting elements.
All the titles of the chapters have not been made yet so these are just descriptions of what will be in those chapters. So far I have 3 chapters in good shape and I am starting the 4th! At the moment it is 60 pages at 6" x 9" - a good format for an book.

domain: library


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Patrick Henningsen writes –
This is probably the most important fight for freedom of expression since the internet was invented. Many already agree that the UK gov’t’s latest move is a lunge towards an East Germany style censored society. Read this and let us know if you support blogging freedom, and support those whom the government wishes to silence…
Press regulation deal sparks fears of high libel fines for bloggers
EXTRACTS – Bloggers would not be at risk of exemplary damages for comments posted by readers.
Under sustained questioning on Monday night during the Commons debate about the courts bill, which includes the Leveson regulations, the culture secretary, Maria Miller, said the “publisher would have to meet the three tests of whether the publication is publishing news-related material in the course of a business, whether their material is written by a range of authors – this would exclude a one-man band or a single blogger – and whether that material is subject to editorial control”.
TAP – just work out the new rules and comply with them. It doesn’t look too hard. There is always the threat of dire retribution. Drawing attention to blogs by suing them seems a counterproductive strategy for news management. Ignoring and sidelining is the usual method employed, blocking blogs on Facebook, isolating on google and ensuring readers don’t get through, and people can’t easily comment.
In any case if Google is requested to delete a post by someone who’s unhappy, they usually oblige. Posts frequently disappear. Links are disconnected. The blog was once locked up for six months after I wrote about Rupert Murdoch controlling Blair’s European policy. At that time, such a theory was considered nuts. I’m only the first editor who suggests posts. Google are the main one.

domain: politics


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‘So high we couldn’t believe it at first’: Professor Jules Blais
The long-term repercussions of gold mining in the Northwest Territories are still being studied more than a decade
after the closure of The Giant Mine located just outside of Yellowknife.
A study published in the scientific journal, PLOS ONE, this past week by a team of researchers from the University of Ottawa has found high levels of arsenic and methyl mercury, a toxic type of mercury that can accumulate in food chains, in lakes near the mine. The original study began in 2010 when researchers were looking at climate change and its thawing effect on permafrost, and how these issues were affecting the surrounding lakes.
Lead author and PhD candidate in the Department of Biology, Adam Houben, said the group began comparing water chemistry in proximity to The Giant Mine out of curiosity, and were surprised at how strong the correlation was between the distance of the mine and the concentration of arsenic.
“When we saw the results for the arsenic, it really became clear that the arsenic was going to be the big story,” said Jules Blais, director of the study and professor of biology
and environmental toxicology at the U of O.
Houben said some of the samples tested well over the guidelines for both aquatic life protection and acceptable drinking water. Water quality guidelines for drinking water are 10 micrograms per litre (μg/L) and 5 μg/L for the protection of aquatic life.
“We were up over, well over, 100 micrograms per litre, even some places that were over 200. So yeah, there was some very, very high arsenic, so high we couldn’t believe it at first,” said Blais.
The study also showed that larger lakes had lower levels of arsenic than smaller ones,most likely because they have
a larger surface area, therefore receiving more rain and snowfall, which is uncontaminated,” said Blais.
While most drinking water is derived from the Yellowknife River, a larger one presenting less of a risk, it’s communities that fish or use wells, which may get water from smaller lakes, that are at risk of contamination. Professor Laurie Chan, a specialist in toxicology and environmental health at U of O, is heading to Yellowknife
soon to meet with officials from the department of health and the chief medical officer, and begin a follow-up study on the effects of human exposure from arsenic.
“Any advisory to the people to do something or not to do something has to come from the chief medical officer, so I will be discussing with them the interpretation of the results,” he said.
Chan said although there have been cases of high arsenic contamination in other countries linked to bladder and skin cancers, they aren’t expecting to see such high levels around Yellowknife.
Because arsenic doesn’t stay in the body long, often only days or hours, it’s unknown
whether residents of the surrounding communities have already been affected by the contamination, as they previously weren’t being monitored, said Chan.
“We’re not expecting people currently exposed to the high level though. But historically, whether they’ve been exposed to such high levels or not, we don’t know.”

domain: chemistry


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Recently I was tagged by a friend to post a selfie, wearing no makeup. The idea behind this is to promote acceptance and self-esteem among our young women and girls who constantly struggle with being OK with who they are.
I really liked this idea and even being sick, I felt the need to post my No Makeup Selfie this morning…. I have a daughter who will turn 13 this summer and I am constantly aware of my influence on her and her friends. She is lucky as she has a full range of Other Mothers to take cues from, to learn and grow from.
But still, even being adamant that I wouldn’t EVER talk about feeling fat in front of her, or put myself down or bemoan my jiggly ass or chunky thighs, she is still hard on herself. I hear her talk about how she hates her face, she’s too tall, her legs are fat, she’s ugly. It tears my heart out. Not because she is the exact opposite of all this, but because despite me doing all the right things like talking about media influence and self-worth and how truly hard it is to be a girl sometimes and promoting her wit and empathy and intelligence above her looks, she STILL does what I did, what we all did.
I wonder, is it an inherent girl thing? Is it something we all go through on some level regardless of our upbringing? I deflected it as much as I could and here she is, still on a journey of self-hate and personal degradation.
We talk, her and I. I believe there is a little tiny jelly bean of hope in her heart that truly listens to my words. I say to her that she is kind and fun. That her mind is strong and smart. Her body can run and swim and kick a soccer ball and she can ski 90 k/hour with a lackadaisical manner that defies logic. I say she is loyal and sweet, but with a touch of stubbornness and temper that can be pruned and urged into a powerful force, which means she will never ever be pushed around. And lastly, I do tell her she is beautiful. That her eyes are the colour of the lake on a summer’s day and her smile brightens rooms, but that is never her most important attribute. I think that she does hear me, and while there is more powerful influences in her life right now, she knows she can always believe her Mama.


By now there have been countless rumors and leaks about the Samsung Galaxy F. This smartphone is believed to be the metal-touting variant of Samsung’s existing flagship. Today a purported first live photo of the Galaxy F has leaked online which gives us an idea of what this device may look like outside of renders. Over the past few weeks multiple renders of this device have been leaked.
The metal body will certainly be its biggest selling point, though the Galaxy F is believed to come with a Qualcomm Snapdragon 805 processor aided by 3GB of RAM. A Quad HD display is also expected.
The live photo shows us that the Galaxy F’s metal frame may actually be quite similar to that of the iPhone 5 and iPhone 5s. Even though the frame might be identical the Galaxy F is still believed to have a removable plastic back.
Samsung has revealed no details about this device so unofficial sources are all we have to go on at this point in time. The Galaxy F is expected to be released in the coming months.
Update: The leaked image of the Galaxy F turned out to be fake. It appears to be a Galaxy S4 with an aluminium bumper case. The images shown below explain how the tipster might have faked it. Notice the placement of sensors and the speaker grill as well as an unusual cut near the corner.


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eSwatini (Swaziland) City Map
eSwatini (Swaziland) is probably the most dynamic of all republics in the Southern Africa. Despite being the smallest African nation, the eSwatini (Swaziland) cities are not short of entertainment.
The Kingdom of eSwatini (Swaziland) is home to some of the most vibrant cities in Africa. The city of Mbabane serves as the administrative capital of eSwatini (Swaziland). Lobamba is the center of legislative power of the eSwatini (Swaziland) monarchy.
There are several other cities in eSwatini (Swaziland) that play a major role in influencing the economy of this beautiful country. Manzini is the biggest city in the territory of eSwatini (Swaziland). Among the other prominent cities of eSwatini (Swaziland), Big Bend is worth mentioning. This city is popular for its scenic beauty. Placed against the backdrop of rolling mountains, Big Bend is also known for its large-scale sugar crop production.
Shopaholics cannot afford to miss the shopping destinations of Mbabane. The roadside markets of Mbabane offer different types of handicrafts and fashionable clothing. Manzini is the main commercial hub of the Kingdom of eSwatini (Swaziland). Standing in the vicinity of the Matsapha International Airport, Manzini is a lively city in eSwatini (Swaziland).
Balegana, Gollel, Holobela, Matsapha, Piggs Peak, Silobela, Stegi, Rondspring, Nokwane, Lubuli, Kubuta, Granvalley, Darkton, Abercorn and Croydon are some of the other major eSwatini (Swaziland) cities.
Major Cities of Swaziland
|City Name||Population||City Name||Population|
|Big Bend||10342||Piggs Peak||5750|


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That defence procurements, like other government purchases, are not exempt from corruption is hardly a secret. But Army Chief General V.K. Singh's revelation that he was directly approached with an offer of a Rs. 14 crore bribe to clear the acquisition of sub-standard vehicles is a shocker. His disclosure, made to The Hindu in an interview and the subject of an uproar in Parliament, deserves a thorough and scrupulous investigation. While a CBI probe has been ordered, the controversy raises questions that are crying to be asked — both of the defence establishment and General Singh himself. For instance, if it is true that the Army Chief had reported the attempt to bribe him to Defence Minister A.K. Antony, why wasn't a probe ordered at once? Did it require a newspaper expose and a parliamentary upheaval to initiate one? What was Mr. Antony's response when he heard the Army Chief's story? As for General Singh, why did he choose to go public with the bribery charge now and not earlier? The question is pertinent because as early as March 6, 2012, the Army put out a press release accusing a retired Lt. General of offering a bribe on behalf of a company that supplies trucks. Inexplicably, while the press release did not fight shy of naming the person who allegedly offered the bribe, it was silent on who he tried to induce. Moreover, the bribery charge was virtually an aside in the press release, which focused on the alleged bribe-giver's role in putting out false stories relating to de-bugging operations at the Defence Minister's office.
An officer of impeccable integrity, General Singh's attempts to crack down on corruption in the Army, particularly the Sukna land and Adarsh Housing Society scams, shows he has what it takes to be a tough reform-oriented leader. Which is what makes the seemingly casual handling of an alleged attempt to bribe him somewhat puzzling. If the Raksha Mantri did not take his complaint seriously, the Army Chief could have pursued the matter in a variety of ways. Whatever the reason for this reluctance, it is clear that the controversy over his age — a matter strictly between himself and the defence establishment — has caused collateral damage in other areas and spawned unrelated disputes that have the potential of causing divisions in the Army, particularly in the top echelons, and in the Ministry of Defence between uniformed men and babus. Too much dirty linen has been already washed in public. While it is important to establish the truth about General Singh's allegation, it is just as important to ensure that civil-military relations are not unduly strained.

domain: news


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Alpaca Pati's Fancy Fleece
Picturebook published by Running Press © 2019
Illustrated by Yoss Sánchez and Written by
An adorable picture book about an alpaca who loves to dress up and what happens when she learns her beautiful coat will be sheared.
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Surviving a sound check – useful tips & guidelines for players of all instruments
Purpose of Running a Soundcheck
- Assembly of all required gear for both the band and the sound crew
- Reducing the likelihood of malfunctions during the show
- Allowing the sound engineer to balance between all instruments in a way that serves the show in terms of style & genre while taking into consideration the acoustic characteristics of the venue
- Allowing the performers to find their comfort zone on stage in terms of hearing a good live mix of their performance, having enough space to move around and achieving their desired sound.
Preparations as a Performer
As you get more experienced as a live performer there are several things you can do to optimize this process. Try focusing your efforts onto the following areas:
- Understanding your ‘sound’ as an individual: Even if you’re not yet a walking encyclopedia of professional sound definitions, listen to players you’d like to resemble and try to characterize the qualities of their sound. Then, learn how to identify these qualities by name and also of those you’d like to avoid. The more you’re familiar with the sound you’d like to achieve on stage, the better you can express yourself to the sound engineer you’re working to create this with.
- Understanding your group sound: Take a step back from the edge of the mountain and listen to the way your instrument blends with the rest of the ensemble. Does is serve the style you’re aiming for as a group? Does it support the other players while they’re soloing? Whether you’re a part of a big band or a duo, be open to feedback regarding the way you fit in the big picture.
- Gear maintenance: What do a buzzing amp, a keyboard with no middle C and a drumstick held together with tape have in common? You leave them at home. Also, know your equipment well so you don’t find yourself looking for the ‘ON’ switch in front of an embarrassed crowd, and always bring backup. My rule of thumb is to bring an extra to every critical item within limits of weight & space. For example, you wouldn’t want to play a metal gig on a high-tuned jazz kit just because you forgot where you put your drum key, right? Same goes for guitar strings, cables, picks & such.
- Technical Specs: This document basically illustrates to the sound guys which instruments you’ll be bringing on stage and how you’d like to have them placed. The validity of this document varies from an act of good will to a binding legal agreement. This depends on whether this is a gig in the neighborhood bar or a full blown concert at a large venue. It’s best not to show up at the venue with an extra tuba player or a 20-piece drumset unless you made sure the venue can handle it in terms of space and amplification. Sending out a detailed technical specs document would help to get you on the same page with the venue.
Working With a Live Audio Technician/Engineer
There are two kinds of live sound technicians in this world. The first kind is attentive, patient and shares your goal of putting on a great show. The second thinks of you as their worst enemy who’s trying to make their lives miserable. They’re not entirely wrong, either. Sometimes you do. How can you avoid that? Be aware of their process, learn when and how to integrate with that without interfering.
Different Stages of Running a Soundcheck
Before you start playing your role, the sound technician has to finish setting up the amplification system and run some tests and calibrations. This would not be the time to burst onto the stage and start jamming. As soon as you arrive at the venue, introduce yourself and let them know you’re ready. At this stage they’re running the show, and this would probably follow:
1) Amplifying each instrument: This would probably start with the rhythm section, followed by guitars, keyboards/laptop, any other instruments such as a guest violinist or a brass section and finally the lead vocals. However, this order may change due to schedule, people running late or just the technician’s way of doing things.
2) Achieving a good live mix: during this stage, the entire band would play together, allowing the technician to balance things out, making sure no instrument gets lost in the mix or stands out too much.
3) On-stage monitoring: During the show, it’s crucial that you hear your own playing at a good, pleasant volume. Additionally, you have to be able to listen to the other players. That can’t always be taken for granted, especially when large stages or high volumes are involved. For that purpose, several monitors are usually placed on stage so you can ask for additional amplification of any instrument you’re missing. Be alert and make sure you can hear all that you should, especially band mates you have to work closely with who might be standing on the other side of the stage. If you can’t hear their playing well enough, ask to boost them in a monitor close to you.
4) Run-through of several songs: According to the time you have left before the soundcheck is over, now would be the time to play a few more songs so that the engineer can get a taste of different styles & volumes you might be playing in during the show.
Soundcheck DOs & DON’Ts
- Try not diverging from the technical specs you’ve sent prior to the show. Most chances are that the stage setup will be already half done by the time you get to the venue. It might be too late to change the layout on stage, switching between instrument positions or adding a last minute musical guest. That is, unless you really want to piss off the sound man.
- Electric guitarists & keyboard players: Make sure your effects and presets are in balance with each other. A soundcheck is not a good time to surprise everyone with crazy volume jumps between your effect pedals or sound presets. Same goes for samplers, computer operators and such. It’s recommended that you work on that balance in a similarly loud environment such as your favourite rehearsal space, beforehand.
- All instrumentalists & vocalists: when asked to play or sing for the sound guy, don’t stop until you’re told to. Even if that means playing just the left tom for 5 minutes or singing A Capella until he’s done adjusting your sound. Additionally, it’s best if you sing/play something that’s relevant to the show and not “Itsy Bitsy Spider”.
- Singers – make sure you don’t chose a song with many long pauses between sentences. Keeping time & song form is great, but the sound man needs to hear you non-stop.
- If you’re playing a setlist with a considerable dynamic range, plan ahead and initiate playing some examples for the sound man. There usually isn’t enough time to go over the entire set but let them know if some songs are considerably louder or quieter. It’s best if you print out an additional setlist and write this down for them.
- Some players prefer using an in-ear monitor on stage. Let the sound man know as early as possible so he or she can plan ahead. Maybe they’ll chose to eliminate some on-stage monitors, resulting in a quieter, more manageable stage.
- If your band’s volume goes up to 11, try choosing a venue that can handle that in terms of size and acoustics. In less than ideal cases, try to work with the sound man to minimize the feedbacks and create a live mix that’s still enjoyable for the audience, as well as for the band on stage.
- Some shows might feature mid-set instrument changes. Guitarists that switch from electric to acoustic, singers who play that one song on the piano, etc’.. mention that beforehand so that the sound guy can make this work out on stage in terms of space and connectivity. Quick tip: bring your own extra guitar stands; the venue might not hold any additional ones.
- While the sound man is busy solving problems or adjusting the sound for another instrument, don’t interrupt, practice scales or take a drum solo. That’s also not the time to ask for monitor adjustments. Wait your turn and don’t make them feel like a kindergarten teacher.
- Arrive on time. Most soundchecks are limited in time. Chances are that being late might be detrimental to the process, especially if your instrument goes up first (I’m talking to you, drummers).
Running a good, productive soundcheck is crucial to playing a great show afterwards. Additionally, remember that your conduct during soundchecks is an inseparable part of your professional persona. Unfortunately, I’ve encountered many talented musicians who proved to be serial soundcheck killers. Good musical chemistry on stage depends immensely on the time leading to the show. Your fellow musicians would prefer playing with people they can trust and have a good time with. Use this opportunity to be that kind of player.

domain: entertainment


Venue: Virtual Meeting
Contact: Linda Slowgrove 01473 432511
Apologies for Absence
Apologies for absence were received from Councillor Gage and Councillor Studd.
To consider the Minutes of the meeting held on 3 June 2020.
that the Minutes of the meeting held on 3 June 2020 be signed as a true record.
To Confirm or Vary the Order Of Business
that the Order of Business be confirmed as printed on the Agenda.
Declarations of Interest
Councillor Kreidewolf, being the Chair of the applicant company, declared an interest in Item 2 (IP/20/00299/FUL) and left the room during the consideration of this item.
Councillor Holmes, being known to the applicant, declared an interest in Item 1 (IP/19/01140/FUL) and left the room during the consideration of this item.
In considering the applications, the Committee took into consideration representations where indicated by the word “REPS” after the individual planning reference number.
The applications were considered in the order set out on the Agenda.
Car Parking Area, The Maltings, Princes Street
Proposal: Erection of four storey office building (Class B1).
Address: Car Parking Area, The Maltings, Princes Street
Applicant: Pertwee Park Ltd.
Agent: Mr Michael Smith, JCN Design & Planning
The Development Management Team Leader presented the report illustrated by drawings and photographs.
The report was updated to include a further condition: Finished floor level of upper ground floor shall be set no lower than what is required in terms of the flood risk assessment submitted.
Mr Michael Smith, agent for the application, spoke in support of the proposals:
- Site not allocated for development in the Local Plan.
- Site was accessible for sustainable forms of transport.
- Office use in this area deemed to be acceptable.
- Scheme addressed the public realm.
- Scheme provided good separation from listed building.
- Existing car park played no role in the setting of the listed building.
- Proposed building sat at an angle to allow views of the listed building.
- Large standalone buildings form part of the character of the area.
- The height of the proposal bridged the gap between the Maltings and the Crown Court.
- Proposed building did not compete with listed building in terms of appearance.
- Proposal provided soft landscaping to enhance biodiversity.
- Proposed building would be energy efficient in compliance with policy.
- Applicant has worked closely with officers and highways and has taken into account comments made at Conservation and Design Panel.
- Proposal would provide new jobs.
A) The completion of a legal agreement under the provisions of Section 106 of the Town and Country Planning Act (1990) dealing with the following matters:
(i) To prevent service vehicles from loading and unloading directly from the public highway, a S106 contribution of £11,500 is required to enable the County Council to progress a scheme to review loading restrictions locally. This will include West End Road, Chancery Road and Princes Street, as the current application will impact on delivery arrangements for The Maltings building.
B) Planning conditions in accordance with those set out below (briefly):-
1. Development to be in accordance with plans.
2. Details to be submitted and approved:- Secure covered cycle storage and PTW storage details; Details of storage lockers and shower facilities; External lighting, and CCTV coverage; Stairlift details (from West End Road); Fire hydrant; Landscape management and maintenance scheme; Renewable or low-carbon energy provision. All agreed details to be provided prior to occupation.
3. Details of external materials to be provided and agreed in advance and implemented.
4. Provision of the hard and soft landscaping scheme as shown on drawing no. JCN/1601/19A prior to first use of the building.
5. Site access to be laid out and completed in all respects in accordance with submitted drawing number P-11.
6. Provision of loading, unloading manoeuvring and parking of vehicles including secure cycle storage and electric vehicle recharging infrastructure to be submitted to and approved in writing.
7. Areas to be provided for storage of refuse ... view the full minutes text for item 16.
Land North of Bury Road, Anglia Parkway South
Proposal: Erection of single storey restaurant/takeaway unit (within Use Classes A3/A5) with drive-through facility, outdoor seating area, 2 grill bays, associated hard and soft landscaping and 7 lighting columns. Alterations to car parking layout to provide an additional 3 car parking spaces and retention of 3 ANPR cameras.
Address: Land North of Bury Road, Anglia Parkway South
Applicant: Ipswich Borough Assets Limited
Agent: Mr Daniel Hyde, Freeths LLP
The Senior Planning Officer presented the report illustrated by drawings and photographs.
Mr Daniel Hyde, agent for the application, spoke in support of the proposals:
- Proposals would complement offer at retail park
- Officers provided comprehensive report, but 2 areas of concern: landscaping and highway matters
- Lack of landscaping plan was done purposefully as landscaping would be considered across the entire park
- There would be a net gain in biodiversity, with 10 blackthorn trees to be planted to west of site
- Transport Assessment identified 47% of parking taken up, expected to be 50% when unit opens
- Linked trips were expected
- Proposals would have a limited highway impact
Councillor Jones proposed that an informative
be added to advise the applicant that 8 replacement trees should be
provided specifically on the application site as part of the wider
landscaping scheme for the remainder of the site, and this was
Councillor P Smart requested that the hours of operation as indicated in the report be secured by condition if other similar sites within the general area also had the hours of operation secured by condition. It was agreed to delegate the decision as to whether to apply an additional planning condition relating to operating hours (in accordance with other units) to Officers.
Grant of planning permission subject to the following conditions (briefly): -
1. Development in accordance with the approved plans.
2. Details of parking layout to show provision for powered two wheeled vehicles, cycle parking, electric vehicle charging points and future provision for electric vehicle charging points, to be provided before first use.
3. Details of hard and soft landscaping to show fencing for external seating area, bollards and additional trees and shrubs, to be provided before first use.
4. Details of external litter bins and external lighting, to be provided before first use.
5. Restriction of permitted development rights – no change of use to Class A1 shops.
1. Ipswich Borough Council supports the use of automatic sprinkler systems.
2. Comments from Suffolk Constabulary.
3. Landscaping scheme to provide 8 trees on the application site.
Councillor Jones highlighted that the Planning Inspector had
made reference to the North East
Character Area Ipswich Urban Characterisation Study within his
deliberation of the Bixley Road appeal
and had also supported that trees of biodiversity value should be
retained in line with Policy DM10 in the Council’s Local
that the information for Councillors be noted.


text:
Manage episode 315413559 series 3289055
Lawyer George Conway on Monday slammed previous President Donald Trump for documenting a claim against New York Attorney General Letitia James in a bid to stop her test into his possibly fake strategic policies.
Composing on Twitter, Conway reacted to one of his supporters who requested that he remark
On whether the Trump claim is one of "the stupidest and generally frantic" claims at any point documented.
Conway conceded that he didn't understand Trump's
Most recent objection, however he refered to the general
Point of reference set by Young v. Harris – the
High Court case that set extremely high bars
For government courts to convey injunctive help to
Offended parties being researched or indicted by
State authorities – as motivation to accept the
Claim would be immediately killed.
"I haven't read the cases of late, and I'm not actually keen on perusing this objection intently, yet I can say I'm almost certain there aren't any the-offended party is-cuckoo-for-Cocoa Puffs exemptions for Younger v. Harris and to the Anti-Injunction Act," he composed.
Conway then, at that point, highlighted an off the wall explanation from Trump about the claim where he provoked James for her purportedly "monstrous" survey numbers.
James in 2018 effectively sued the Trump Foundation and got it to intentionally disband subsequent to revealing a few occurrences of monetary inappropriateness.
As a feature of the repayment, Trump paid out $2 million in remuneration to eight distinct causes to compensate for the cash that the establishment abused over the range of quite a long while.--- Support this podcast: https://anchor.fm/mark-gowz/support


text:
We start with quality ingredients and end with a masterpiece.
We have over 22 choices of pre-made sandwiches. We start with freshly sliced meats, artisan cheeses and other premium gourmet ingredients. Then we layer them between fresh bread from New York's best bakers. If you can't find a sandwich you like, we'd be happy to prepare something special for you.
We offer complete gourmet turkey dinners, or convenient a la carte side dishes. Every order is cooked to perfection and guaranteed fresh. Call 1.866.446.3560 to speak with a Catering Associate for more information or to place an order. CLICK HERE to view our Menu.


text:
This is a collection of essays that I have been working on for over 12 years. There are also guest contributors. Instead of looking to publish it in book form, I will be posting the work here, providing the annotated bibliography. Check it out, share it, comment, dislike, but realize Hip-Hop has failed to create and sustain a movement and our generation and the one behind us is in serious trouble. The book is written in the form of a music CD, hence the titles. Christopher D. Burns, MFA
P.S. I may not publish all of the work, but this is just to create a discussion.
I am not professing to be the savior of Hip Hop by creating this book. My goal is to discuss several problems that have created a dysfunctional, inactive generation. The Jim Crow problems, intergenerational conflicts and Black on Black problems that have existed in the African-American community have begun to trickle down into the Hip-Hop generation. These problems will undoubtedly have lasting effects on the Hip-Hop culture, but the people who identify with Hip-Hop find themselves, if they acknowledge it, in a troubling position. I believe those people who are conscious of the possibilities of the genre agree that our generation has fallen way short of creating a meaningful movement.
The situations affecting the Hip-Hop generation are pretty basic albeit serious as hell: Promiscuity, illiteracy, lack of a sense of self and a failure to understand our importance in society. How will this book address these issues? Through a careful analysis of the culture as it relates to education and social issues, we will attempt to introduce several ideas and enough historical and contemporary references to show how our generation can begin to develop a movement, an individual movement that could have positive results for the culture. Now these references may not be related to Hip-Hop in a direct way, but we feel that we are of the culture and anything we write or create is Hip-Hop.
The insertion of the word individual may be bothersome for some people. For Hip-Hop to get right, self examination has to occur. We have to look at the way we represent ourselves and the way we learn and share to begin to change any part of the greater society. Deus ex machina doesn’t exist for the Hip Hop generation. There isn’t a god that will drop down, summarize and clear up the problems of our generation. The problem of Hip-Hop is the problem of individuals: capitalists willing to manipulate the masses to get paid are thoughtless people willing to pass poison through one bottle of water to ten people stranded in the desert. The problem of Hip-Hop begins and ends with the individual.
Prelude – Track 1
This is the slow music that fades in right before the bass drops. This is that brief moment when the music is so good you want it to continue but it stops…
There are sections in this album that will feel the same way, but my intent is to stimulate not solve in some instances. Fade

domain: sociology


text:
Warm smell of colitas, rising up through the air
“Colita” is literally a “little tail” in Spanish and in this case it means sweet, sweet marijuana. (The “colitas” are the clippings of the plant, the inexpensive, leafy buds)
Glenn Frey told the SF Chronicle in 2003 that:
Colitas….It means little tails, the very top of the plant. That was a dark, strange period of my life.
To help improve the quality of the lyrics, visit “Hotel California” by The Eagles Lyrics and leave a suggestion at the bottom of the page


Shmee gets an exclusive ride in the jaw-dropping McLaren P1 hybrid hypercar, and gosh it’s quick!
We know the McLaren P1 is damn fast. 0-62mph in 2.8 seconds and 0- 124mph in about the time it takes for a Ford Fiesta ST to hit sixty-two (6.8 seconds). The performance is just completely mad. And the 908hp P1 could even be the quickest production car ever to lap the Nuburgring if the current rumours are to be believed.
But, what does all of this physics-bending, face-melting performance look like on the road where there are blind pensioner drivers and men in vans? Well, pretty ruddy alarming actually – check out Shmee’s video below.
We quite like how the chap driving says “it’s fast, isn’t it?”…


text:
Food and Restaurant News
Starbucks Rewards changes: When it’s effective, what’s changing and how to earn cashback
Starbucks officially updates its rewards program
U.K. tries to get people to give up bottled water
The simple idea that could be the answer to our plastic problem: reusable packaging
Get $40 off your first HelloFresh meal kit box
Someone is selling avocado toast themed shoes
Skittles ice cream bars are coming to the U.K.
Krispy Kreme is offering lucky customers free doughnuts for a year as part of St. Patrick’s celebration — here’s how to win
FDA chief resigns
What’s the secret to this knife?
A dean has resigned because her college wouldn’t allow a Chick-Fil-A on campus
Why you should try a meal delivery service


text:
Setting Aside Our Preconceived Notions, We Take A Closer Look At What Poetry Is And What It Isn’t!
n the coming weeks, we’ll be covering a lot of poetry events and poets here at Soliquidas. However, I’ve realised a lot of people have massive misconceptions about what poetry is, who writes it, and what it’s all about. So, as silly as it may seem, I think it’s best to start at the beginning and ask the questions, “What is poetry?” and, “Who writes poetry?”.
Now, you can choose to watch the video above which outlines everything you need to know or you can continue reading, whichever suits your learning style best!
What is poetry? It’s a deceptively difficult question that might sound silly to some of you but I think it’s important to start from the very beginning so we’ve got some common ground moving forward. I find people often bring in a lot of baggage when considering what poetry is/isn’t and who does/doesn’t write poetry.
Many poets, writers, and critics have submitted their own definitions of what poetry and/or poets are over the years. These are some of my favourites:
In short, poetry is a powerful and mysterious communicative force, wielded by those who are compelled, for whatever reason, to push against the world around them. To pursue the truth at all costs and at all times.
So can you be a part-time poet? Or do we all have to quit our jobs and live out of our cars while searching for endless open mics to read at? I think the answer is yes and no. Yes, you can be a part-time poet. No, you can’t be a part-time creative.
The reason for this is because people are creative by nature and that creativity is infectious. So, once you inject a little bit of creativity into your daily or weekly routine, it’s bound to grow and pop up in unexpected times and places. This is a beautiful thing!
Think of it as another aspect of your self-care routine; you take vitamins, work out at the gym, get plenty of rest, AND you exercise your creativity. They’re all essential to living a full and vibrant existence.
So poetry is not reserved for academics, stuck in some stuffy ivory tower, far from it! Poetry is for anyone and everyone who sees, or longs for, hidden beauty in the world around them. And that includes you!


Water Retention Box WRB 150
Infiltration trough made of recycled PP intended for surface drainage in combination with a Flow Control System; high water retention potential, used for intensive green roofs with 0° roof pitch and varying layer heights.
|Material||polyamide monofilament (base), polymer PA/PET (filter fleece)|
|Thickness||ca. 20 mm|


text:
OUTSTANDING Russian WW2 M1927 Gun 76.2mm HEAT AP Round,case has nice ink stamps, no cracks, or any other damage. Head in good great condition.
INERT - F.F.E (Free From Explosives)
Shipping UK ONLY
BUYERS MUST BE 18+
The 76 mm regimental gun M1927 (Russian: 76-мм полковая пушка обр. 1927 г.) was a Soviet infantry support gun. The gun was developed in 1927 by the design bureau of Orudiyno-Arsenalny Trest (OAT) and entered production in 1928. A total of 18,116 pieces were built. On June 22, 1941, the Red Army had 4,708 of these guns. In 1943 the gun was replaced in production by the 76 mm regimental gun M1943, but remained in service until the end of the war. The Germans placed captured guns into service as the 7.62 cm Infanteriekanonehaubitze 290(r) (infantry gun-howitzer), while in the Finnish army they were known as 76 RK/27. The gun was intended for destruction of light field fortifications and openly placed personnel by direct fire. HEAT shell gave it limited anti-tank capabilities.

domain: history


text:
A new study provides additional support for universal germline genetic testing for women with breast cancer.
The study found that compliance with current restrictive guidelines for germline testing misses a significant number of women with pathogenic or probable pathogenetic (P/LP) variants, knowledge of which would transform patient management.
The study used Invitae’s multigene cancer panel, which funded the study.
Two oncologists not involved in the analysis said that based on this and other data, the debate about universal testing for breast cancer should be over.
Niloy Jewel Samadder, MD, narrates Medscape Medical News “This study continues to support the wider use of germline genetic testing in breast cancer patients, regardless of disease stage, family history of cancer, or age of diagnosis — the factors outlined in current guidelines.”
“These predictors will miss a significant number of patients with genetic predisposition,” said Samadder of the Mayo Clinic Comprehensive Cancer in Phoenix, Arizona.
Julia Smith, MD, agreed that the current prospective study, along with numerous others, “makes it clear that relying solely on the clinical judgment of healthcare providers, including genetic counselors, [who] consistently fail to identify a significant number of genetic mutations that would be clinically feasible.
“The push for universal genetic testing is definitely worth it, and the more we do, the more we learn about what else we can do,” said Smith of NYU Langone Perlmutter Cancer Center in New York City. She specializes in cancer risk assessment.
The study, published online in JAMA network openis a re-analysis of a prospective cohort of 952 unselected patients with breast cancer who underwent universal germline genetic testing using the Invitae large cancer panel.
The first study, published in 2019, found that about half of the P/LP germline genetic variants would have been missed if testing had only been done for patients who met the 2017 National Comprehensive Cancer Network (NCCN) guidelines would have met for genetic testing.
In the current study, Pat Whitworth, MD, of the Nashville Breast Center in Tennessee, and colleagues examined the clinical management changes that resulted from germline testing in this cohort. Participants were stratified based on whether or not the patients met NCCN criteria.
Whitworth and colleagues found that 84% of patients (31 of 37) with P/LP variants who met test criteria had their clinical recommendations changed.
Clinical recommendations were also changed in 68% of patients (23 of 34) who did not meet test criteria but had P/LP variants in cancer predisposition genes.
For patients who did not meet the criteria, clinical recommendations were changed based on genetic test results for 64% (14 out of 22) of those who had a variant of a breast cancer predisposition gene.
Overall, clinicians found that the tests were beneficial for about two-thirds of patients with P/LP variants.
No changes were made to the clinical recommendations for almost all patients with negative results (345 of 349) or variants of unclear significance (492 of 509).
There was no significant difference in the rate of P/LP variants between patients who met and those who did not meet the BRCAPRO risk model threshold, which helps clinicians make recommendations for genetic testing (P = 0.86).
Whitworth and colleagues concluded that their results suggest that “restrictive criteria for germline genetic testing deny data-supported clinical management of breast cancer patients.” Universal germline testing, on the other hand, “supports clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.”
Genetic testing guidelines have recently been expanded for colorectal cancer, Samadder said. The NCCN 2022 colorectal cancer guidelines now advocate that clinicians consider germline genetic testing for all colorectal cancer patients, regardless of age at diagnosis.
“This strategy could be the way forward for many cancers, including breast cancer,” Samadder said. “As more targeted, precision therapies are discovered for breast cancer and other cancers, it is imperative that genome sequencing, including germline testing and somatic or CT DNA in advanced cancer patients, be made widely available to inform care.”
The study was funded by Invitae. Whitworth and several co-authors have financial ties to Invitae. Samadder has relationships with Janssen Research and Development, Recursion Pharmaceuticals and Cancer Prevention Pharmaceuticals. Smith has not disclosed any relevant financial relationships.
JAMA network open. Published online September 22, 2022. Full text
For more updates, follow Medscape on Facebook, TwitterInstagram and YouTube.

domain: medical


Today OFW announced long-time designer Buf Reynolds will lead the organization as Producer. Reynolds is taking over the role from Brook Hudson, who had led the organization since 2011. Hudson stepped down this week to spend more time with family and take on new passion projects, including the OFW Investors Circle, a grant program for designers.
“Buf is probably the only person in Omaha who has been around OFW longer than I have. She has been involved in the organization in some capacity since its inception in 2008,” Hudson said. “In fact, she was producing her own underground fashion shows with other local designers many years before OFW came on the scene.”
Reynolds participated in OFW as a designer for 10 straight years, before taking a break to work on the OFW team where she eventually was promoted to director of talent and community outreach. During the pandemic she took some time off as a staff member with OFW and served during that time as a selection panelist.
Reynolds still designs as an OFW Headliner under her namesake label, Buf Reynolds. She is a graduate of the Fashion Business Program at Metropolitan Community College and was awarded the Sabrina Jones Spirit Award at OFW in 2023.
“We often call Buf the fairy godmother of Omaha fashion because she has a heart for mentoring young designers and building a positive and loving community around them,” Hudson said. “She is the perfect person lead OFW into the future because she understands its history and relevance to designers. She is in tune with what today’s designers need. She is a fantastic teacher and mentor; and she knows all the nuances of this show because she has participated on both sides of it for many years.”
Hudson says she will be involved in an advisory capacity for the remainder of the planning for the February 2024 season to ensure a smooth transition, but is looking forward to watching from the audience once shows begin. She and her husband, Nick Hudson, will remain owners of the company.


text:
Money Moves Markets
Ignore central bank hysteria: inflation risks are fading fast
September 21, 2022 by Simon Ward
Global six-month consumer price inflation peaked in June and fell further in August, reflecting pass-through of lower oil prices and a small decline in core momentum. Current commodity prices suggest a sizeable further drop into Q4 – see chart 1*.
Annual as well as six-month CPI inflation probably peaked in June, with the peak occurring within the expected time band following a major top in annual broad money growth in February 2021 – money trends lead inflation by two to three years, according to the monetarist rule of thumb.
G7 annual broad money growth is estimated to have fallen further to below 4% in August, widening an undershoot of its 4.5% average in the five years before the pandemic – chart 2. The suggestion is that G7 inflation rates will be back at or below target around end-2024, if not before.
Markets were spooked by last week’s news of a hefty monthly rise in US core CPI in August but six-month momentum was little changed and below a June peak, while PPI pressures continue to ease – chart 3.
Central bankers are supposedly focused on preventing high inflation from becoming embedded in expectations. The view here has been that expectations were unlikely to become “unanchored” against a backdrop of weak money growth. The latest consumer surveys by the New York Fed and University of Michigan show longer-term inflation expectations back within 2010s ranges – chart 4.
UK annual core CPI inflation made a marginal new high in August but money trends mirror the global picture and are signalling a 2023-24 collapse – chart 5. The latest Bank of England / Ipsos inflation attitudes survey, meanwhile, reported a fall in consumer longer-term inflation expectations, which have remained within the 2010s range – chart 6.
The apparent anchoring of longer-term US / UK expectations suggests that wage pressures will dissipate rapidly as current inflation rates fall sharply in 2023.
*The GSCI commodity price index uses US prices for the natural gas component; the series shown by the gold line in the chart incorporates an adjustment for European prices.