text:
She barked and snatched his shirt.
He barked a laugh.
The most typical family is the Drepanidae, so named for the stout sickle-shaped beak with which the birds extract insects from heavy-barked trees; Gadow considers the family American in its origin, and thinks that the Moho,' a family of honey-suckers, were later corners and from Australia.
Talon barked at her, and she realized she'd stopped walking.
Horses stomped, dogs barked, and children scurried everywhere.
It is the common result of fires passing alongtoo rapidly to burn the trees; and thin-barked treeshornbeam, beech, firs, &c. may exhibit it as the results of sunburn, especially when exposed to the south-west after the removal of shelter.
I have heard of a dog that barked at every stranger who approached his master's premises with clothes on, but was easily quieted by a naked thief.
Striding to a tree, she barked an order.
There were small white houses here, one with a dog that barked as she passed.
Brutus barked and she hushed him.
"Don't!" she barked, tensing.
Cynthia barked, her face getting redder by the minute.
The man with silver eyes barked at Daniela.
After a series of clicks, the lieutenant barked into the phone.
"No, really –" "Back of the line!" a woman barked at her.
This may be due to frost, especially in thin-barked trees, and often occurs in beeches, pears, &c.; or it may result from bruising by wind, hailstones, gun-shot wounds in coverts, &c., the latter of course very local.
The Upper Coal Measures (Stephanian) are characterized among the Calamarieae, now more than ever abundant, by the prevalence of the Calamodendreae; new species of Sphenophyllum make their appearance; among the Lycopods, Lepidodendron and its immediate allies diminish, and smooth-barked Sigillariae are the characteristic representatives.
Sometimes one came near to my window, attracted by my light, barked a vulpine curse at me, and then retreated.
Look at those cramped dead firs, ever the same, and at me too, sticking out my broken and barked fingers just where they have grown, whether from my back or my sides: as they have grown so I stand, and I do not believe in your hopes and your lies.
Dusty barked into his mic.
To her surprise, he barked a laugh of half-pain from their fall and half-triumph.
They stopped in the shadow of a hill, and Mansr barked quiet orders at the dozen warriors with them.
As he barked a welcome, steam rolled out of his mouth in a cloud.
It is well known in England for its graceful habit, the slender, grey - or white - barked stem, the delicate, drooping branches and the quivering leaves, a bright, clear green in s p r i n g, becoming duller in the summer, but often keeping their greenness rather late into the 5 autumn.
A dog barked down the alley and Dean turned to see a man walking a collie as his wife looked on from a doorway.
"Dammit, Lana," she murmured with a look at her watch then barked, "Doc, hurry!"
Hilden barked, all but tearing the bow from Taran's shoulder.
Brutus didn't normally hang around the house, and he always barked at strangers.


text:
Diabetes mellitus is a chronic metabolic disease that occurs when the pancreas is not producing enough insulin or when the insulin that it does produce is not able to be used effectively in the body. This results in hyperglycemia and if the blood sugars are not controlled, then it can lead to serious damage of various body systems, especially the nerves and the blood vessels. Uncontrolled diabetes is a major cause of kidney failure, heart attacks, stroke and amputation. One of the most devastating complications for patients is diabetic retinopathy (DR) which represents the leading cause of preventable vision loss in people between 20 and 65 years of age. Sodium glucose transporter 2 (SGLT2) inhibitors have been shown to reduce the risk for cardiovascular and renal events, however literature highlighting their potential role to prevent DR is limited. We therefore used a relevant mouse model (Akimba) to explore the effects of the SGLT2 inhibitor, Empagliflozin (EMPA), on the development of diabetic retinal changes. Here we show that when given in the early stages of type 1 diabetes (T1D), EMPA reduced the weight loss usually associated with T1D, decreased diabetes-associated polydipsia, lowered fasting blood glucose levels, decreased kidney-to-body weight ratios and, most importantly in the current context, substantially reduced retinal abnormalities associated with DR. We show that EMPA reduces vascular leakage indicated by lower albumin staining in the vitreous humor and diminishes expression of the pathogenic factor VEGF in the retina. Additionally, EMPA significantly alters the retinal genetic signature. Our findings suggest that SGLT2 inhibition may be a useful therapeutic approach to prevent the development of DR and its severity if given early in the disease process.
In 2017, diabetes accounted for 9.9% of all-cause mortality worldwide (approximately 5 million deaths) . Diabetes is a major cause of kidney failure, heart attacks, stroke, amputation and diabetic retinopathy (DR) . DR occurs as a result of long-term accumulated damage to the small blood vessels in the retina and accounts for 2.6% of global blindness . On a global scale, the number of people with DR is estimated to grow from 126.6 million in 2011 to 191 million in 2030, with the number of vision-threatening cases increasing from 37.3 million in 2010 to 56.3 million in 2030 . Clinically, DR is divided into two stages: non-proliferative DR (NPDR) and proliferative DR (PDR). DR is both a vascular and neurodegenerative disease of the retina . The NDPR is characterized by capillary occlusion, microaneurysms, intraretinal microvascular abnormalities (IRMAs) and hemorrhages, while PDR is characterized by the hallmark feature of pathologic retinal neovascularization . These proliferative changes are usually accompanied by unavoidable vision loss.
At present, the three major therapeutic strategies effective in reducing DR-induced vision impairment include anti-vascular endothelial growth factor (VEGF) injections, panretinal laser photocoagulation and vitrectomy . As these therapies are not always effective and associated with various complications, additional effective therapies are warranted and novel therapeutic targets are sought for treatment and prevention of DR . Anti-VEGF treatment has been found to be very effective in the rapid reduction in retinal neovascularization in patients with PDR and reduces macular edema. However, it requires frequent intravitreal injections for several years and is therefore costly . Furthermore, anti-VEGF therapy has potential complications and does not reverse the underlying pathology of DR . Current DR treatment options are largely focused on the end stage of the disease and does not address the early and possibly reversible microvascular changes leading to DR. Therefore, therapeutic approaches that can be used in the early stages of the disease process, to prevent or slow down the progression of DR, would be most likely to result in a reduction in the devastating consequences of DR . As diabetes and its consequences are predominantly a result of excessive glucose levels in the bloodstream, a therapy that reduces glucose levels and improves insulin sensitivity while also affecting the pathophysiological pathways implicated in DR would be most useful. Sodium glucose transporter 2 (SGLT2) inhibitors clearly fulfil the first two criteria , however, whether they can also prevent the development of DR has not yet been thoroughly investigated. We have shown that SGLT2 inhibitors mediate their cardiovascular and renoprotective effects at least in part by sympathoinhibition , a pathway that may also be relevant for DR. It is well known that the sympathetic nervous system can influence endothelial function and ultimately ocular blood circulation. It has been shown that ocular sympathetic nerves are critical for the generation and maintenance of immune privilege in the eye through the facilitation of local transforming growth factor-β production . The transforming growth factor-β is a vital ligand involved in the modulation of cell migration and proliferation, cell death and protein synthesis during development, tissue repair and other physiological or pathological processes in the eye . Additionally, increased blood pressure via increased blood flow may damage the retinal capillary endothelial cells in eyes of people with diabetes. Therefore, it is plausible that SGLT2-mediated sympathoinhibition may be beneficial for DR. Future studies in the Akimba mouse model are required.
In the present study, we examine the influence that the SGLT2 inhibitor, Empagliflozin (EMPA), has on the prevention and development of retinopathy in a mouse model of early DR.
Materials and methods
Mice and genotyping
As a model system, we utilized the Akimba mouse (Ins2AkitaVEGF+/−), a novel transgenic model of DR that was generated by crossing the diabetic Akita (Ins2Akita) which develops hyperglycemia with Kimba (trVEGF029) mice. The Kimba mouse has transient photoreceptor-specific overexpression of human vascular endothelial growth factor 165 (VEGF165) and hence depicts changes associated with DR without the hyperglycemic background. The Akimba mouse (Ins2AkitaVEGF+/−) is a cross between the diabetic Akita and the Kimba model, and develops advance DR features due to the interplay between high blood glucose levels and overexpression of VEGF . The Akimba mouse model displays hallmark retinal microvascular abnormalities representative of human DR including microaneurysms, tortuous vessels, venous beading, vasodilation, capillary non-perfusion, increased retinal vascular leakage, edema and neovascularization [4,12,13]; this model is a highly relevant model for the study of retinal vascular disease. DNA was isolated from tail clips by using the Wizard Genomic DNA Purification Kit (Promega, Madison, WI). Genotyping of Kimba mice was carried out as previously described [14,15]. Akita mice were genotyped for the insulin 2 (Ins2) gene as described . Akimba mice were genotyped by using protocols for both Kimba and Akita mice.
Animal experimentation was carried out at the Harry Perkins Institute for Medical Research animal holding facility (Perth, WA). Animal ethics was approved by the Harry Perkins Institute for Medical Research Animal Ethics Committee (AE141/2019) and all procedures were performed in accordance with the Association for Research in Vision and Ophthalmology statement for use of animals in ophthalmic and vision research. Male Kimba and Akimba mice were bred and obtained from the Animal Resources Centre (Perth, WA, Australia) at 2–5 weeks of age. Mice were housed under a 12-h light/dark cycle, at 21 ± 2°C and were given a standard chow diet (Specialty Feeds, Glen Forrest, WA, Australia) with free access to food and water. Wet mash was replenished three times per week. Following a 7-day acclimatization period, the SGLT2 inhibitor EMPA (Ark Pharma Scientific Limited, China; 25 mg/kg/day) or vehicle (dimethylsulfoxide) was administered to the mice weekly via their drinking water for 8 weeks. Urine glucose levels were measured (Keto-Diastix; Bayer, Leverkusen, Germany) before treatment and 1 week post-treatment to establish the diabetic status of Akimba mice and the development of glucosuria induced by EMPA. Mice were weighed weekly. Fasting blood glucose levels were measured at the end of the experiment using the Accu-Chek Performa blood glucose monitoring system (Roche Diagnostics, North Ryde, Australia). Only male mice were used in the present study as disease progression is known to be slower and less uniform in female mice .
Tissue and serum sample collection
After 8 weeks of their respective treatments, the mice were fasted for 5 h and had access to treatment water. Mice were deeply anesthetized using isoflurane inhalation, underwent cardiac puncture to obtain blood and were killed by cervical dislocation. Blood samples were centrifuged, serum collected and stored at −80°C. Kidneys were harvested, weighed and fixed in 10% buffered paraformaldehyde (PFA) for histology. The right eye was collected into 10% buffered PFA for histology while the left eye was fixed in ice-cold 10% buffered PFA for 2 h at 4°C in preparation for retinal vascular assessment.
Gene expression assays
Firstly, the kidney medulla and cortex were dissected using springbow scissors while slightly frozen. RNA from murine eyes and kidneys was extracted using TRIzol reagent (Invitrogen, Thermo Fisher, Melbourne, Victoria, Australia) and cDNA synthesis was performed using the High Capacity RNA-to-cDNA kit (Applied Biosystems, Thermo Fisher, Melbourne, Victoria, Australia). Real-time PCR was performed to determine the mRNA abundance utilizing a Rotor-gene real-time PCR machine (Qiagen, Hilden, Germany) using pre-developed TaqMan probe (FAM-labeled) and primer sets for Hprt (Mm01545399_m1) and Sglt2 (Slc5a2; Mm00453831_m1) (Applied Biosystems). Quantitation was conducted as previously described .
Retinal isolation and whole mount preparation
Retinal flat-mounts were prepared with modification to a previously published method . In brief, the fixed eyes were washed in ice cold 1× PBS for 2 min and retinas were dissected in 1–2 ml of ice cold 1× PBS under a dissection microscope. The fully dissected retinas were washed twice in 1× PBS prior to staining. Fixed retinas were permeabilized for 2 h in PBS-BSA-Triton-X (1× PBS, 1% BSA, 1% Triton-X) at room temperature followed by washing in Wash Buffer (1× PBS, 0.5% Triton-X) for five times. Retinas were incubated overnight in the dark at 4°C with biotinylated GSL-1B4 (1:100 in Wash Buffer) with specificity for α-galactosylated glycoprotein residues on vascular endothelial cells and macrophages (Griffonia Simplicifolia Lectin I (GSL I) isolectin B4; Catalog#: B-1205-.5, Biotinylated; Vector Laboratories, Burlingame, CA, U.S.A.). Retinas were washed five times in 1× PBS and secondary antibody Cy3-Streptavidin (1:500 in 1× PBS; GE Healthcare, Amersham, U.K.) was added and incubated for 5 h in the dark at room temperature. Stained retinas were washed five times in 1× PBS, mounted and coverslipped with VECTASHIELD HardSet Anti-fade Mounting Medium (Vector Laboratories, Burlingame, CA, U.S.A.).
Retinal imaging and analysis
Retinal whole-mounts were imaged using the inverted fluorescent microscope Nikon Eclipse Ti (Nikon, Tokyo, Japan) with a digital camera CoolSNAP HQ2 (Photometrics, Tucson, AZ, U.S.A.) linked to a computer running the image analysis software ‘NIS-Elements Advanced Research’ (Nikon, Tokyo, Japan). Sequentially overlapping high-resolution images of the entire retinas were captured using the 4× objective. Images were merged to construct a montage of the retina. Montages were semi-quantified for vascular morphological abnormalities as previously published . Grading of retinas were based on vascular changes such as regions of capillary dropout, vascular leakage, vessel tortuosity, monocytes/macrophages, microaneurysms, IRMA, exceptionally dense vascular budding and neovascular tufts. Representative areas of the retinal vascular lesions were captured in the z-plane in 2-μm steps. The z-stacks were compiled into a focused image representing all superficial, intermediate and deep capillary layers.
The detection of SGLT2 protein expression in eyes was conducted. Briefly, eyes were fixed in 10% buffered formalin for 24 h, followed by wax embedding. Paraffin sections (5 μm) were collected and mounted on slides. Eyes were washed in xylene (2 × 10 min) and then rehydrated in 100% ethanol (2 × 5 min), 95% ethanol (1 × 5 min), 70% ethanol (3 min) and then water (5 min). For antigen retrieval, slides were heated for 5 min in a pre-heated 1× EDTA buffer (pH 8.5; Sigma–Aldrich, Sydney, Australia). After washing twice in PBS/0.1% Tween for 5 min, tissue sections were outlined with a paraffin pen. Sections were blocked with 3% H2O2 for 10 min, washed twice with PBS/0.1% Tween for 5 min and blocked with 5% FBS in PBS/0.1% Tween for 1 h in a humidified chamber. Sections were then incubated overnight at 4°C in a humidified chamber with both rabbit anti-SGLT2 (1:200; Novus Biologicals, Colorado, U.S.A.) and mouse anti-SGLT2 antibodies (1:50; Santa Cruz Biotechnology, California, U.S.A.) in 5% FCS/PBS/0.1% Tween. Following overnight incubation, sections were washed three times with PBS/0.1% Tween for 5 min and incubated with anti-rabbit (1:100, Santa Cruz Biotechnology, Sydney, Australia) and anti-mouse (1:100, Santa Cruz Biotechnology, Sydney, Australia) secondary antibodies conjugated with HRP in PBS/0.1% Tween for 1 h. This was followed by incubation with diaminobenzidine (DAB). Slides were counterstained with Hematoxylin, dehydrated and mounted with DPX (Sigma–Aldrich, Sydney, Australia).
Albumin and VEGF immunohistochemistry
The detection of albumin and VEGF protein in the Akimba mice was conducted. Paraffin sections (5 μm) of eyes were collected and mounted on slides. Eyes were washed in xylene (2 × 10 min) and then rehydrated in 100% ethanol (2 × 5 min), 95% ethanol (1 × 5 min), 70% ethanol (3 min) and then water (5 min). For antigen retrieval, slides were heated for 5 min in a pre-heated 1× EDTA buffer (pH 8.5; Sigma–Aldrich, Sydney, Australia). After washing twice in PBS/0.1% Tween for 5 min, tissue sections were outlined with a paraffin pen. Sections were blocked with 3% H2O2 for 10 min, washed twice with PBS/0.1% Tween for 5 min and blocked with 5% FBS in PBS/0.1% Tween for 1 h in a humidified chamber. Sections were then incubated overnight at 4°C in a humidified chamber with goat anti-albumin antibody (1:200; Novus Biologicals, Colorado, U.S.A.) or goat anti-VEGF antibody (1:40; R&D Systems, Minneapolis, Canada) in PBS/0.1% Tween. Following overnight incubation, sections were washed three times with PBS/0.1% Tween for 5 min and incubated with rabbit anti-goat HRP (1:500, Thermo Fisher Scientific, Victoria, Australia) secondary antibodies conjugated with HRP in PBS/0.1% Tween for 1 h. This was followed by incubation with DAB. Slides were counterstained with Hematoxylin, dehydrated and mounted with DPX (Sigma–Aldrich, Sydney, Australia). Quantitation of albumin and VEGF staining was conducted using ImageJ 1.43j (National Institutes of Health, Bethesda, Maryland, U.S.A).
Retinal RNA isolation and RNA sequencing
The total retinal RNA was extracted using TRIzol (Invitrogen, Massachusetts, U.S.A.) in accordance with the manufacturer’s protocol. TRIzol reagent-lysed retinas were mixed with chloroform and centrifuged to remove RNA upper aqueous phase from the lower organic phase. RNA in the upper aqueous phase was precipitated by isopropanol and centrifuged to precipitate RNA. This precipitated RNA was washed with 75% alcohol and dissolved in RNAse/DNAse-free water (Invitrogen). A Nanodrop ND-1000 spectrophotometer (Australian Biolab Group, Melbourne, Australia) was used to quantify the concentration of RNA. The RNA-Seq was performed by AGRF and the resulting RNA-Seq read was used to perform the analysis.
The Illumina Hi-seq 2500 platform was used for RNA-seq, and 100-bp reads were generated for the retinas. The data yield per individual mouse retina ranged from 2.18 to 3.56 Gb. The library for RNA-seq was prepared using Illumina’s Ribo Zero Gold protocol. The Illumina bcl2fastq 126.96.36.1992 pipeline was used to generate primary read sequence with Illumina quality scores (phred-like quality + 33). The reads were screened for the presence of any Illumina adapter/overrepresented sequences and cross-species contamination. The reads were compared with the Mus musculus genome (Build version mm10) using the STAR aligner (v2.5.3a). The transcripts were assembled using the StringTie tool v2.1.4 using read alignment with M6 and reference annotation-based assembly option (RABT). Cufflinks, Cuffmerge and cuffdiff were employed for the purposes of differential expression analysis.
Identification of SGLT2 in the eye of DR Akimba mice
The Akimba mouse strain is an established DR mouse model. The strain is generated by crossing Kimba and Akita mice. The Akita and Akimba mice both display hyperglycemia (Figure 1A) but interestingly only the Akimba mice possess elevated levels of SGLT2 mRNA in the eye and kidney (Figure 1B–D) highlighting the potential of SGLT2 as a valid therapeutic target for DR. Additionally, we were able to show that SGLT2 protein is expression in the retinal ganglion cells of the Akimba mice (Figure 2).
SGLT2 levels are elevated in the eyes of Akimba mice with DR
SGLT2 is expressed in the diabetic retina of vehicle-treated Akimba mice
EMPA treatment promotes glucose excretion in Kimba mice
Before treatment, urine glucose levels (via testing strips) were negative in the non-diabetic Kimba mice and positive in the diabetic Akimba mice. After 1 day of treatment, urine glucose levels tested positive in the Kimba mice receiving EMPA, while remaining negative in the Kimba mice receiving vehicle (Supplementary Figure S1). As expected, urine glucose levels of the diabetic Akimba mice were positive regardless of treatment.
EMPA treatment was well-tolerated by mice
Kimba and Akimba mice displayed normal responses to touch, smooth and healthy body coats, bright eyes and normal posture throughout the 8 weeks of vehicle or EMPA treatment.
EMPA treatment promoted weight gain and the ability to thrive in mice with DR
SGLT2 inhibition with EMPA promotes the ability to thrive in diabetic Akimba mice
EMPA significantly reduced excessive water intake in diabetic Akimba mice
Throughout the duration of the experiment, the daily water intake for non-diabetic Kimba mice was lower than 10 ml/day (Figure 4A) and was markedly lower than the diabetic Akimba mice (Figure 4B). This confirms the non-diabetic status of the Kimba mice. There was also no difference in water intake between the Kimba (Vehicle) and Kimba (EMPA) groups (Figure 4A). After testing water levels at 2, 4 and 5 weeks post-treatment, the Akimba (EMPA) mice showed a decrease in water intake, in comparison to the Akimba (Vehicle) mice. At week 5, Akimba (EMPA) mice drank significantly less than the Akimba (Vehicle) mice, highlighting the improved diabetic phenotype (Figure 4B).
Inhibition of SGLT2 with EMPA significantly reduces excessive water consumption in diabetic Akimba mice
EMPA reduces fasting blood glucose levels in diabetic mice
The Kimba blood glucose levels were consistently lower than 20 mmol/l (Figure 5A) and markedly lower than the diabetic Akimba mice (Figure 5B). This supports the non-diabetic status of the Kimba mice. In addition, there was no difference between the Kimba (Vehicle) and Kimba (EMPA) groups (Figure 5A). After 8 weeks of treatment, the fasting blood glucose levels of Akimba (EMPA) mice were significantly lower than the Akimba (Vehicle) mice (Figure 5B). This result highlights that EMPA was able to reduce diabetic hyperglycemia.
Fasting blood glucose levels are significantly reduced in diabetic Akimba mice after 8 weeks post-treatment
The renal effects of EMPA in young diabetic mice
The kidney-to-body weight ratios of Kimba mice (Figure 6A) were markedly lower than those in the Akimba mice and there was no effect of treatment in Kimba mice (Figure 6A). The lower kidney-to-body weight ratios confirmed the healthy renal phenotype of the Kimba mice. The increased kidney-to-body weight ratios in the Akimba mice confirmed the renal hypertrophy phenotype of the Akimba mouse. The Akimba (EMPA) mice displayed reduced kidney-to-body weight ratios compared with their vehicle-treated counterparts (Figure 6B), highlighting the renal benefits of EMPA.
Kidney/body weight ratios are reduced in diabetic Akimba mice treated with EMPA
Ophthalmic benefits of SGLT2 inhibition in mice with DR
As the aim of our study was to determine whether SGLT2 inhibition may prevent the development of DR, the severity of retinal vascular lesions was assessed 8 weeks post-treatment in Akimba mice treated with either vehicle or EMPA. The retinal vascular and pathological changes in EMPA and Vehicle-treated Akimba mice are compared and summarized in Table 1. Retinal whole mounts showing the vasculature of Akimba mice treated with vehicle compared with EMPA is illustrated in Figure 7. Table 1 was generated using measurements taken from similar images in Figures 7 and 8.
|Characteristic .||Akimba + Vehicle .||Akimba + EMPA .|
|.||1 .||2 .||3 .||4 .||5 .||6 .||1 .||2 .||3 .||47 .||5 .||6 .|
|Loss of vessel integrity and leakage3||+++||+||−||−||+||+||−||−||−||−||−||+|
|Vessel tortuosity and vessel tufts4||++6||++||++||++||+/++||++||+||+||+||−||−/+||+|
|Characteristic .||Akimba + Vehicle .||Akimba + EMPA .|
|.||1 .||2 .||3 .||4 .||5 .||6 .||1 .||2 .||3 .||47 .||5 .||6 .|
|Loss of vessel integrity and leakage3||+++||+||−||−||+||+||−||−||−||−||−||+|
|Vessel tortuosity and vessel tufts4||++6||++||++||++||+/++||++||+||+||+||−||−/+||+|
Not present; +, less than 120 microaneurysms/IRMA present; ++, more than 120 microaneurysms/IRMA present.
No regions; +, less than eight regions; ++, more than eight regions.
Not present; +, mild; ++, moderate; +++, severe.
Absent; + moderate; ++, severe.
Absent; +, present in two or less retinal quadrant; ++, present in three or more retinal quadrant.
Expensive retinopathy/capillary dropout resulted in the retina showing lower incident of vascular lesions.
Showed less than 50 microaneurysms/IRMA and the overall retinal vasculature was clearly organized.
Retinal photomontages of Akimba mice treated with vehicle or EMPA
Representative areas of the retinal vasculature are shown in the upper, middle and lower capillary beds in young Akimba mice treated with Vehicle and EMPA
In Akimba mice treated with vehicle (Figure 7), the overall retinal vasculature was severely disrupted and disorganized. The retinas consistently showed the presence of torturous vessels (Figure 8A,C; white arrows). Vascular lesions such as microaneurysm, IRMA and neovascular tufts were large and were composed of continuous and contorted capillaries that were folded upon themselves (Figures 7 and 8A,C; white boxes) and were noted throughout the retina, without favoring any retinal quadrant or region. Both the upper and middle capillary beds showed increased capillary non-profusion (Figures 7 and 8A,C,E; green asterisks). Highlighting monocytes or macrophages, positivity was observed in small round structures where some had dendrites (Figure 8A,C,E; blue arrow heads). Diffused staining (Figure 8C; yellow arrow) in vehicle-treated Akimba mice indicated the loss of vessel integrity and leakage.
In contrast, we found that Akimba mice treated with EMPA showed less pronounced vascular disorganization (Figure 7) and showed a marked reduction in microaneurysms, IRMA, neovascular tufts (Figures 7 and 8B,D; white boxes) that was often limited to the peripheral retina. In addition, there was a reduction in vessel tortuosity (Figure 8B,D; white arrows), regions of capillary non-profusion (Figures 7 and 8B,F; green asterisks), monocytes or macrophages (Figure 8F; blue arrow heads) and vascular leakage was absent.
We found that leakage of albumin was significantly decreased in vitreous humor in the EMPA-treated Akimba mice when compared with the vehicle-treated Akimba mice (Figure 9).
Assessment of vascular leakage in the eye
An intense VEGF expression was observed throughout the ganglion cell layer (GCL) of the retina. We observed a pronounced reduction in VEGF in the GCL, inner plexiform layer (IPL) and inner nuclear layer (INL) retinal layers of mice treated with EMPA (Figure 10).
Detection of the angiogenic factor VEGF in the retina
In an effort to determine whether EMPA altered the retinal genetic signature, we performed RNA-Seq analysis. We found that there were many genes  that were both up- and down-regulated with SGLT2 inhibition (Supplementary Tables S1 and S2). Numerous targets were affected by SGLT2 inhibition. Some of these include Tnfsf18, Ccr2 and Il12rb1. It is plausible that many of these genes may ultimately impact the pathogenesis of DR in our Akimba mouse model but requires further study.
Mortality rates in Akimba mice
We also aimed to determine whether EMPA impacts mortality in the Akimba mouse model of DR. There was a 20% mortality rate (one out of five mice) in vehicle-treated Akimba mice, whereas 100% survival in Akimba mice treated with EMPA was noted. This result mimics the positive effects that SGLT2 inhibition with EMPA has on reducing mortality rates in human diabetics . There was a 100% survival rate in all Kimba mice.
Diabetes is one of the fastest growing chronic metabolic diseases globally and the leading cause of preventable blindness. As such, therapies tackling underlying cardiovascular and renal complications and the related ophthalmic conditions like DR are urgently required. Although there is one study outlining the beneficial effects of the SGLT2 inhibitor, Ipragliflozin, on DR in male rats , there is overall limited data from either animal models or clinical trials regarding the effects of SGLT2 inhibition on DR. The aim in our current study was to explore whether SGLT2 inhibition in addition to its beneficial impact on glucose metabolism and insulin sensitivity, may also exert protective effects in regard to the development of DR.
We found that while the body weight of the non-diabetic Kimba mice was the same in both EMPA and Vehicle-treated groups, the diabetic Akimba mice exhibited an increase in weight between weeks 5 and 7 after EMPA treatment compared with vehicle-treated mice. One of the complications of type 1 diabetes (T1D) is a failure to thrive. Therefore, it is promising that EMPA prevents the weight loss associated with T1D. In fact, all mice exhibited normal behavior and showed no weight loss due to SGLT2 inhibition suggesting that SGLT2 inhibition does not promote detrimental side effects.
Highlighting the effectiveness of the SGLT2 inhibition therapy in our study, the fasting blood glucose levels in the diabetic Akimba mice treated with EMPA were significantly lower than the Akimba mice administered vehicle in their drinking water. Taking into account the glucose-lowering effects of EMPA along with the significant lowering of water intake in Akimba mice treated with EMPA, our findings highlight that EMPA reduces excessive thirst usually associated with diabetes and therefore shows improvement of the diabetic phenotype. However, SGLT2 inhibition did not completely halt diabetes development in Akimba mice. This is based on the observation that our Akimba mice which were obtained at a young age prior to demonstrating glucosuria (a natural hallmark of diabetic Akimba mice) subsequently all developed glucosuria over the course of our 8-week experimental regime.
Another complication associated with diabetes is renal failure. In the early stages of diabetes, the glomerular filtration rate (GFR) may be elevated and kidney size will be increased, due to heightened single-nephron GFR and expanded nephron size . This enlargement in the kidney size may contribute to nephropathy and therefore renal failure. We have found in this study that the kidney-to-body weight ratio in the Akimba mice treated with EMPA was lower in comparison to the Akimba mice administered vehicle, therefore indicating the protective renal effects of EMPA in our young DR mouse model.
We demonstrated in our current study that Akimba mice also have elevated ocular expression of SGLT2 compared with their parental Kimba and Akita mice (Figure 1). Therefore, we considered that SGLT2 inhibition may be a viable therapy for the prevention or reduction in the severity of DR. Excitingly, we showed that EMPA did improve the retinal vasculature in diabetic Akimba mice (Table 1; Figures 7 and 8). In order to further demonstrate the ocular benefits of EMPA, we assessed Albumin and VEGF retinal protein expression (Figures 9 and 10). Albumin is a marker of leakage  from the blood vessels whereby the albumin escapes from the blood vessels and binds to cells within the retina. VEGF is a marker which promotes blood vessel development and in DR there is an abundance of VEGF-mediated newly formed irregular blood vessels . In our study, we demonstrated that EMPA reduces both Albumin and VEGF protein in the different layers of the retina to reduce the pathogenesis of DR. There is also a possibility that SGLT2 inhibition may occur in the kidney of Akimba mice and promote ocular benefits by cross-talk from the kidney. Hence, we show that there is potential for SGLT2 inhibitors to be used as a therapy to treat DR. Further studies are required to ascertain whether these promising findings in our specific DR mouse model are translatable to the human scenario and may indeed represent an effective therapeutic approach to halt the development of DR at an early stage of the disease process. A major therapeutic that is clinically used currently is intravitreal administration of anti-VEGF antibody. Utilizing this knowledge, it is plausible that SGLT2 inhibitors may also ultimately be administered intravitreally . In DR, the blood–retinal barrier (BRB) is compromised and hyperglycemia may contribute to the BRB breakdown. Therefore, SGLT2 expression in the retina may be inhibited with SGLT2 inhibitors, reduce glucose reabsorption in the eye and ultimately decrease the damaging effects of hyperglycemia .
The present study investigated the potential utility of SGLT2 inhibition with EMPA to prevent or reduce the severity of early DR.
When the SGLT2 inhibitor, EMPA, is given in the early stages of T1D, it may promote the ability to thrive by reducing the weight loss associated with T1D, significantly decreased diabetes-associated polydipsia (excessive thirst), significantly lowered fasting blood sugar levels, decreased kidney weights and most importantly, in the current context, reduced retinal abnormalities associated with early DR.
We also show that EMPA reduces retinal vascular leakage indicated by lower albumin staining and diminishes expression of the pathogenic factor VEGF in the retina. Additionally, EMPA significantly alters the retinal genetic signature.
As EMPA demonstrates beneficial outcomes in our young DR mouse model, it may be a potential therapeutic approach for patients with diabetes to prevent or reduce the severity of retinopathy, a proposition that now needs to be verified in adequately designed human studies.
All supporting data are included within the main article and are available by contacting the corresponding author.
The authors declare that there are no competing interests associated with the manuscript.
This work was supported by the Royal Perth Hospital Research Foundation [grant number MRF2018 Matthews], Diabetes Australia [grant number Y20G-MATV], Diabetes Research WA [grant number DRWA Herat]; and the Raine Medical Research Foundation [grant number RPG 20-20].
Open access for this article was enabled by the participation of The University of Western Australia in an all-inclusive Read & Publish agreement with Portland Press and the Biochemical Society under a transformative agreement with CAUL.
CRediT Author Contribution
Jennifer Matthews: Investigation, Writing—original draft, Writing—review & editing. Lakshini Herat: Conceptualization, Formal analysis, Funding acquisition, Investigation, Writing—original draft, Writing—review & editing. Jennifer Rooney: Formal analysis, Investigation, Writing—review & editing. Elizabeth Rakoczy: Conceptualization. Markus Schlaich: Conceptualization, Funding acquisition, Investigation, Writing—review & editing. Vance B. Matthews: Conceptualization, Formal analysis, Funding acquisition, Investigation, Writing—original draft, Writing—review & editing.
The authors would like to thank Caroline Rudnicka, Aaron Magno, Lois Balmer and Wei Ern Ong for their technical advice and assistance.
These authors share equal first authorship.

domain: medical


Remember back when you were in school, you did something really outstanding, and maybe, just maybe, you got a treat?
About 125 eighth-graders from Carver Middle School got one of those treats on Tuesday. They got to spend most of the day rollerskating under disco lights to sounds of Tag Team and Mariah Carey.
Unlike their colleagues back in the classroom, they were being rewarded. Not because they did anything particularly wonderful, but because they went three whole weeks without getting a referral to the dean's office.
Introducing 1990's-style discipline: the stick is gone from the schools, so carrots are taking over. Gone is the paddle. Candy, pizza parties and limo rides are emerging as the popular inducements for good behavior.
"What's the point of being good if you don't get a reward for it?" said eighth-grader Elizabeth Ziegenfuss as she adjusted her skates. "I'm good because I want my parents to be proud. And they give me things when I'm good, like clothes and money when I ask for it."
Since paddling was banned in 1987, Palm Beach County school officials have adopted creative and colorful ways to keep order. Carver, in Delray Beach, has held dances and field trips for students with good conduct grades, and set up golf lessons for those who excel academically. The school doles out three-day automatic suspensions for fighting.
Teachers countywide write names of misbehaving students on the blackboard for all to gawk at.
But while embarrassment might work for younger students, middle-schoolers tend to be immune, said Carver counselor Rick Rose.
"They say, 'Go ahead and put my name on the board, I don't care,' he said. "In middle school, they respond more to positive reinforcement."
Otherwise known as a bribe? Absolutely, said eighth-grader Trisha Curtis, taking a break from skating.
"They're telling us we can go on a trip if we're good. That's a bribe."
And although she was having fun, she doesn't necessarily approve of the practice. "That's not what's going to happen in the real world, when you get a job. You have to do things on your own."
Old-timers might wistfully recall when children behaved just because they were supposed to, or they faced a licking. Now, children are threatening their parents with the child abuse hotline.
"Those days were way different," said eighth-grader Ann Marie Milano. "They didn't have as much violence, kids bringing guns to school. They're not going to do something just because you tell them to. If you can get out of school for a day, who wouldn't do it?"
Well, for starters, about 50 students who remained at Carver on Tuesday.
A troop of bored non-skaters, who sat in their language arts classroom watching Oliver Twist, said they wanted nothing to do with another rollerskating trip to The Palace.
Why not something different, like an outing at a nightclub, students wanted to know.
"They should do something fun except go skating," said J.J. Sarafinko, who said she got two referrals, one for fighting and one for cursing at a teacher. "Every time we have a field trip, we go skating. It gets boring. It gets kind of old."
Corelle Draper, who did go skating, suggested one way to lure his misbehaving friends.
"If they had bigger, exciting trips, then everybody would be good," he said. "Somewhere like Orlando."


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Pet Friendly Hotel
In a case you are thinking where to leave your beloved pet in Aeolis is the best solution due that we are a pet friendly hotel! Your pet is welcome here! Behind Aeolis apartments there many quite paths and you can enjoy a beautiful walk with your dog.
It is not only people that you will meet upon your arrival at the Aeolis flats; you will also meet our pet animals. Kaloulis and a few of our cats will be the first to greet you.
Our love for animals prevented us from staying indifferent towards the strays of Lesvos and led us to an organized action for animal welfare. We feed, heal and help animals get adopted, which is our ultimate goal. We often work with the animal welfare service of Lesvos, and with respective services abroad.
Here are a few stories of people who adopted an animal.
In 2015 we stayed at Aeolis for two wonderful weeks. The reason why we had chosen for Aeolis was partly because I read about the good work Daisy & Sofia do for street animals. My husband knows me en warned me we would definitely not return home with a dog
But immediately at check in, there she was, our Dora
She directly came to me, put her head on my lap and asked for attention. What can I say, it was love at first sight. Ten days earlier Dora followed a German couple to the Aeolis resort. A skinny dog with rasta hair. That’s why Daisy shaved her, and we met her with only a bit hair on her head and a brush tail
During the vacation Dora slept at our apartment, we went on trips and really enjoyed our time with the three of us. Luckily my husband agreed that we couldn’t return home without her. So we arranged a flight ticket, bought a flight case and went to the vet for the vaccination, chip and a European passport. It was easy to arrange, especially with the kind help of Daisy & Sofia.
Now Dora is already 1,5 year with us and we’re very grateful that we have her, every day again. A very friendly, happy and lovely dog. We’re crazy about her!
There are many animals on the street, which all deserve a home. It’s frustrating I can’t save them all, but one is the beginning.
Brord & Sanja van Hees
On the end of May 2013 we stayed for 12 days in your beautiful hotel on Lesbos.
On the first evening while we were sitting outside, a very cute cat came to visit us! He was so lovely and adorable!
Every evening he joined us! It was love at first sight. Sofia and Daisy did already know the cat well, he stopped regularly for some food and love. They took good care of him and a lot of other cats and dogs. Sofia called him chipchipshinel, I don’t think it’s the good spelling hihi. During the last days of our holiday we decide to take him with us.
Sofia was going with us to the veterinarian in Mytilini! There we give him the name mr. Aeolis, named after the hotel from Sofia and Daisy. By the veterinarian he get his entings and we arranged him a flight ticket back to the Netherlands.
While it’s a big stap, taking a cat with you on the airplane we never regretted it. He is a happy, lovely, playing, and sometimes a bit of a macho man. Now, in April 2017, mr Aeolis is still doing great. We now have a son of whoch is 2 years and they regularly play together.
Sofia and Daisy are doing very good work for the animals on Lesbos. It was a very special holiday for us!Lots of love, Arjan, Maaike, Luc and of course, Mr. Aeolis.
Adopt animals, don’t buy them. It’s that easy. Give a stray animal the chance to have a home full of love and care; they deserve it!

domain: pet


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It's recipe time! This was one of the last meals I made in Connecticut, and it turned out to be one of the most challenging I have ever attempted. Surprisingly enough, it was a sandwich - but don't let that fool you. The croque madame is a beast, though it is definitely worth the patience required to make it. Mr. G had to help me with this one, and thank goodness he did... I don't see how it's possible to make it with less than 4 arms. Timing is everything for this dish. After nearly burning the bread AND the sauce (which also seemed too thick), it was still the most delicious sandwich I have ever tasted.
I got inspired to make it after a wonderful date night in NYC with the husband. You see, once we made the decision to move to Minnesota, I told Mr. G we had to do 2 more things before leaving the East Coast - see a Broadway show in New York, and go to Boston for the day. Mr. G came through, of course, and New York was first up - my Valentines Day present this year was tickets to any show of my choice. :) I decided on Wicked, and it ended up being an all-around incredible night that started off with a surprise carriage ride through Central Park! For those of you who don't know, Central Park was where Mr. G proposed last January, and it was supposed to be after a romantic carriage ride; however, it was too cold for the carriages to run that night (1 degree too cold, in fact - they are unmerciful), so he promised me he would eventually take me on the carriage ride I was supposed to have. Thankfully, he remembered even though I had almost forgotten... I have a very romantic husband. :)
Anyway, after our chilly but sweet carriage ride through the park, we went to a cute little French restaurant called Maison. I had mushroom ravioli, and Mr. G had croque madame. My pasta was good, but his sandwich was out of this world! It looked easy to make, too, so I was determined to do it. Little did I know that sometimes the simplest meals can have the most complicated recipes...
Here is the recipe I used - I got it from the Epicurious app on my iPhone:
- 5 tbsp. unsalted butter
- 3 tbsp. all-purpose flour
- 2 cups whole milk (we used 1%)
- 1/4 tsp. salt
- 1/8 tsp. black pepper
- 1/8 tsp. freshly grated nutmeg
- 1 1/3 cups coarsely grated Gruyere cheese (we just used slices of swiss cheese - no Gruyere at Stop n Shop)
- 8 slices firm white sandwich bread (wheat and flimsy is also fine, but firm bread adds more texture)
- 4 tsp Dijon mustard
- 1/2 lb. thinly sliced cooked ham
- 4 large eggs
- Make sauce first:
- Melt 3 tbsp. butter in a 1 to 1 1/2 quart heavy saucepan over moderately low heat, then whisk in flour and cook roux, whisking, for 3 minutes.
- Whisk in milk and bring to a boil, whisking constantly.
- Reduce heat and simmer, whisking occasionally, for 5 minutes.
- Whisk in salt, pepper, nutmeg, and 1/3 cup cheese until cheese is melted (this was challenging with sliced cheese... definitely get grated).
- Remove from heat and set out wax paper to make sandwiches.
- Make sandwiches:
- Spread 1 1/2 tbsp. sauce evenly over 4 slices of bread, then sprinkle evenly with remaining cheese (1/4 cup per slice, or just slap on a piece of swiss like yours truly).
- Spread mustard evenly on remaining 4 bread slices and top with ham, then invert them onto cheese-topped bread to form sandwiches.
- Cook sandwiches on skillet:
- Melt 1 tbsp. butter in a 12-inch nonstick skillet over moderately low heat
- Cook sandwiches on skillet (we could fit 2 at a time), turning over once until golden - 3-4 minutes total.
- Remove sandwiches from heat and transfer to baking pan.
- Cook sandwiches in the oven:
- Preheat broiler.
- Top each sandwich with 1/3 cup sauce, spreading evenly.
- Broil sandwiches 4-5 inches from heat until sauce is bubbling and golden in spots for 2-3 minutes (ours took longer - depends on your oven).
- Turn off broiler and transfer pan to lower third of oven to keep warm.
- Fry eggs:
- Heat remaining tablespoon of butter in nonstick skillet over moderate heat.
- Crack eggs into skillet and season with salt and pepper.
- Fry eggs, covered (?), until whites are just set and yolks are still runny - should take 3 minutes.
- Take out sandwiches and top them all with fried eggs. Serve immediately, and enjoy!
In other news, my DIY projects are coming right along. I've bought all my supplies (see below), and I've even painted 2 tiles already for the kitchen! And would you believe it - they look awesome! Hope everything else turns out as well. I'll post pics of the tiles once I finish them all.
I also went thrift shopping for the first time ever, and it was so much fun! I had a great day all by myself haha. Check out these cool things I found at Unique Thrift:
Unique is actually a pretty popular thrift store in the Twin Cities area. I was there yesterday, and it was PACKED - in the middle of the day on a Tuesday! People sure love their bargains here. I will definitely be going back, though. As for what I bought, the mirrors I plan on hanging in my kitchen (in place of the window/mirror I saw at T.J. Maxx - I actually like these better!). They have the look of cathedral windows, which I feel goes along with the Mexican-esque theme I'm going for in the kitchen. The blue candlestick is what I'll use as the base of a cake plate I'm going to make - yet another DIY project haha. I guess I can now go on the record to say that I am crafty... and thrifty! Everything in that photo cost a total of $7. Can't beat that!
I hope I'm not turning into one of those budget-crazy women who obsess over finding the best deals. There is no harm in being budget savvy, but extreme couponing? Really?? Come on, now. (I do kinda want to watch that show, though.)
That's all for now. Can't wait to finally get our couch tomorrow! Yay!
<3 Mrs. G
P.S. I start work next week at the Mall of America, so (sadly) I probably won't be posting quite as often as I am now. But I'll try! Wish me luck at the new job! Still interviewing for others. I'll keep you posted!

domain: food


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Opposing views seldom win you many friends. Just ask Prime Minister Malcolm Turnbull.
The Prime Minister has received increasing pressure from both his colleagues and opponents for a national inquiry into high power prices and profiteering.
Malcolm Turnbull has taken a hard stance backing the National Energy Guarantee (NEG), reiterating the point that ‘we’ve turned the corner on electricity prices’.
The NEG faces the dilemma of balancing reliability, security and affordability. In other words, making sure there is enough energy, that it is getting to consumers, and at a price they can afford.
Obviously, reducing power prices is not the easiest problem to solve.
The Prime Minister believes ‘The NEG will provide a level playing-field, technology agnostic, certain environment for people to invest and deliver lower cost for generation over time.’
Malcolm Turnbull is facing the predicament of ‘damned if you do, damned if you don’t’.
That’s part of the job description when you become the Prime Minister of Australia. No one said it was going to be easy, and Mr. Turnbull is well aware of that.
A source from the Turnbull government advised it was not likely to consider a royal commission as it has already made efforts to combat the high prices of energy with the NEG, in addition to the prices inquiry by the Australian Competition & Consumer Commission that will be released this week.
Mr. Turnbull announced that, ‘It will be a very, very illuminating report.’
I take his word on it.
Turnbull is determined to lower energy prices
When the Prime Minister of the country tells the public that ‘there’s only one thing that matters: lower prices. Lower prices. Everything should be a means to that end,’ you know he’s serious.
That’s not to say that errors in judgments cannot be made. Look at the AMP Scandal that only happened a few months ago.
The calls for a royal commission on power prices are not unwarranted. Prices of electricity have continued to grow for households and businesses.
‘It’s time to get to the bottom of why power prices are going up, which is (because) we’re taking an essential service and treating it like a stock market,’ Greens energy spokesman Adam Brandt stated.
Environmental groups and also the states of Victoria and South Australia are concerned with the reliance of coal-fired generation as the building block of the east coast’s energy network.
These are both valid concerns. However power prices are a complicated matter that cannot be resolved without planning. Blindly attacking coal, while it is still so essential to Australia’s electricity infrastructure, won’t help Australians struggling with already too-high prices.
Even if it were possible, eliminating coal-fired power plants within Australia wouldn’t have the impact on emissions that some believe. Australia’s electricity use is a drop in the ocean compared to countries like China and India, both of which have and continue to use massive amounts of coal as they industrialise and modernise their nations. Coal is also a massive component of Australia’s exports, one that our economy would struggle to survive without.
Rushing to eliminate Australian coal power plants would do little to reverse climate change. But it would apply massive upward pressure on the price we pay for electricity.
The NEG had been put in place to address this complex issue. And, that’s what it will do. Leading to legislation that will make power prices more affordable and reliable for all of us who use it.
By Andre Abeyratne

domain: finance


Sliding patio doors are immensely useful because they make getting in and out of the room comfortable. They also enhance the ambience of a room or backyard. However, despite being a great addition to your home, these doors occasionally have some issues and need repair or replacement. In this blog, we will discuss some most common problems with sliding patio doors.
Sticking is the most common problem with sliding patio doors. Many times, the patio sliding doors get stuck. Therefore, it is important to know how to fix your sticking sliding door. The good news is, it is not that difficult. You can efficiently fix it with the help of DIY tutorials and some necessary home tools. The first step begins with removing the sliding doors by lifting them up and swinging them out from the bottom. The very same process will be used to remove the top.
Once you remove the doors, you should inspect it to find the cause of the sticking. It can be anything from malfunctioning of the gliding system to the corrosion of the hardware or simply the door wheels have tightened up. Once you discover the problem, you can quickly determine how you should fix them. For example, if you find the doors to have tightened up, then you should loosen up the screws that keep the wheels in their place. However, you should do it gently, or the screws may break. If you notice the glides are not working correctly, you should replace them.Replacement glides are easily available. Take your old glides with you to buy the right glides for your door. Now, you should apply some lubricant on them and then fix them. Now, you should place back the door like before in the frame and it should all work fine.
A bad or broken seal is quite a common problem with sliding patio doors. Buy replacement seals that can deal with severe weather conditions. Following the earlier told method, you need to separate the door from the panes. Now, remove staples with the help of a screwdriver as well as pliers. Pull off the seals. Scrape off any remnants and adhesive with a putty knife. Attach the new seals to the sliding door as per the directions mentioned on its packet. Now, place the door in its place.
The next most common problem with sliding patio doors, is cracks in the glass. As dealing with glass can be harmful, you should never try to repair this yourself. Also, you should not procrastinate the task because cracks can spread fast and lead to a higher risk of accidents and injuries. Moreover, a cracked patio door looks bad and reduces the security of your property. So, call an expert in patio door repair and replacement in Surrey. They will inspect your door and determine what the best thing to do.


Northern Ireland-based decommissioning specialist Decom Engineering has said it has developed tools that can make decommissioning in the energy sector greener, faster and safer, and is also looking at business opportunities in the offshore wind sector.
The company has said it has updated its Pipe Coating Removal (PCR) equipment, which cleans decommissioned or surplus pipelines of multiple coatings, so they can be repurposed for use on other projects.
Decom Engineering this week also said that it has upgraded its range of cold cutting saws which have been deployed on international decommissioning projects as oil and gas operators replace or remove aging infrastructure. It did not say who the clients were.
“The latest modifications to its single blade cutter will allow Decom Engineering to target a new revenue stream, assisting clients in recovering conductors from decommissioned oil and gas rigs. The company also believes there are opportunities for its patented saws to be deployed on offshore wind farm repair and maintenance projects as well as onshore pile cutting,” Decom Engineering said.
Established in 2011 by Chief Executive Officer Sean Conway, Decom Engineering has completed contracts in mainland Europe and Asia Pacific, and is tendering for new workscopes in Thailand, North America, Brazil and India.
Decom Engineering CEO, Sean Conway, said the company’s PCR machines can further reduce the carbon footprint and return value to the client, by cleaning and preparing steel pipelines so that they are suitable for use in other projects.
“For example, decommissioned pipelines can be used in piling and construction work, and in the last year our Dutch facility has processed and repurposed more than 20,000 tons of steel,” Conway said.
Nick McNally, Decom Engineering’s Commercial Director said the company’s technologies help recycle downgraded oil and gas pipes into a useable product instead of scrap steel, “hugely increasing the value chain for our partners and decreasing the carbon footprint of the industry.”
“We are now seeing the fruits of our labor with new contracts in Europe and Asia Pacific, and we expect that the latest upgrades to our tools and equipment will lead to further growth in the world’s major energy hubs, he said.
Decom Engineering is holding a series of showcase demonstrations in the coming weeks in Aberdeen to provide oil and gas clients with real-time knowledge of how the company’s technologies can benefit planned projects.
This post appeared first on Offshore Engineer News.


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Glen Burnie Bancorp to Issue Dividend of $0.10 (NASDAQ:GLBZ)
Glen Burnie Bancorp (NASDAQ:GLBZ) declared a dividend on Thursday, July 13th, Fidelity reports. Investors of record on Monday, July 24th will be paid a dividend of 0.10 per share by the financial services provider on Friday, August 4th. The ex-dividend date is Thursday, July 20th.
Shares of Glen Burnie Bancorp (NASDAQ:GLBZ) traded up 0.84% during trading on Friday, reaching $10.85. The company had a trading volume of 1,686 shares. The company has a market cap of $30.27 million, a P/E ratio of 26.66 and a beta of -0.08. Glen Burnie Bancorp has a 12-month low of $9.85 and a 12-month high of $12.55. The firm has a 50-day moving average of $11.21 and a 200-day moving average of $11.62.
Glen Burnie Bancorp (NASDAQ:GLBZ) last posted its earnings results on Monday, May 8th. The financial services provider reported $0.11 earnings per share (EPS) for the quarter. Glen Burnie Bancorp had a net margin of 7.63% and a return on equity of 3.28%. The company had revenue of $3.13 million during the quarter.
Separately, TheStreet cut shares of Glen Burnie Bancorp from a “b” rating to a “c+” rating in a research note on Tuesday, March 21st.
ILLEGAL ACTIVITY WARNING: “Glen Burnie Bancorp to Issue Dividend of $0.10 (NASDAQ:GLBZ)” was originally posted by American Banking News and is the sole property of of American Banking News. If you are reading this piece of content on another website, it was illegally stolen and reposted in violation of US and international trademark & copyright legislation. The original version of this piece of content can be read at https://www.americanbankingnews.com/2017/07/15/glen-burnie-bancorp-to-issue-dividend-of-0-10-nasdaqglbz.html.
About Glen Burnie Bancorp
Glen Burnie Bancorp is the bank holding company for The Bank of Glen Burnie (the Bank), a commercial bank. The Bank is engaged in the commercial and retail banking business, including the acceptance of demand and time deposits, and the origination of loans to individuals, associations, partnerships and corporations.
Receive News & Ratings for Glen Burnie Bancorp Daily - Enter your email address below to receive a concise daily summary of the latest news and analysts' ratings for Glen Burnie Bancorp and related companies with MarketBeat.com's FREE daily email newsletter.


Exa Vehicles can be used in combination with other 30MM kits to further customize your builds, or simply built and displayed on their own as vehicles. This entry in the lineup builds the Air Fighter in gray, a vehicle shaped much like a fighter aircraft. Or, use it as a flight backpack for your 30MM mechs!
- Vehicle x 1
- Face parts x1F
- Foil sticker sheet x1
Läs mer om 30 Minutes Missions under kategorin 30 Minutes Missions.


A biomechanical arm built out of found objects and stainless steel rods served as inspiration for one of the world's weirdest microphone stands.
Artist Chris Conte created the gleaming, sci-fi–looking mike holder for Adam Gontier, lead singer of Three Days Grace. Gontier found photos of Conte's original artwork online and inquired about a custom piece of gear based on the arm. "When he asked me over the phone if it can be done, I was like, 'Hell yeah, it can be done,'" Conte said in an e-mail interview with Wired.com.
See also: Creepy Cyberpunk Fantasies Come to Life
The only problem: The band wanted a left arm and the original was a right.
"I suggested we take molds and make casts from the original," said Conte, 40, who lives on New York's Long Island and worked in prosthetics before concentrating full-time on art. "I first needed to sacrifice the original arm and reverse-engineer it into a left arm. I also needed to construct it in such a way where it could be broken down into sub-assemblies that were practical for mold-making and casting."
Conte made three of the mike stands (Gontier bought a backup for the road). The mike stands are constructed primarily of stainless steel. One part of the quick-release mechanism is made of brass.
"The arm you see in the photos is actually a casting in stainless steel of the master using the lost-wax process," Conte said. "Eleven separate silicone molds were taken from the master to create the wax models needed for the casting process." The project took about three months, and Gontier used the stand onstage for the first time Feb. 19 at the Prudential Center in New Jersey.
Conte, who was previously profiled by Wired.com ("Creepy Cyberpunk Fantasies Come to Life"), said his work is a reflection of the things he loves.
"I simply build the things I wish I had," he said. "The work also expresses my fascination with advanced technology, specifically cybernetic organisms, combined with my admiration of relics from the past. Cybermechanical sculpture is perhaps one way to describe it."
Next up for Conte: He's building four insectoid creatures out of recycled watch parts for a print and television ad campaign for London retailer Harrods.


Have you ever tried watching a film with no sound? Even in the times of silent films, they even had scoresheets to be played alongside the movies showing, why? Because there´s no emotion in a mute film. That important is Music for a film. And for this nominees, it´s a homage to their great work:
Alexandre Desplat for The Grand Budapest Hotel, Alexandre Desplat for The Imitation Game, Hans Zimmer for Interstellar, Gary Yershon for Mr Turner and Johan Johannsson for The Theory of Everything.
A Big Lady Gaga number honoring the fifty years that have gone by since The Sound of Music, giving way for Julie Andrews to be on stage. She looks like no time has gone by for her.
And the Oscar goes to… Alexandre Desplat for The Grand Budapest Hotel, making it the fourth Academy Award for the film
What do you think? Are you happy that The Grand Budapest Hotel won the Academy Award 2015 for Best Music Original Score? Let me know in the comments section.
Follow me on Twitter for more scoop and live coverage.


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domain: game


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Local deals juggernaut Groupon and Live Nation have a formed a joint venture to develop a new online ticketing deals channel dubbed GrouponLive. The site will serve as a local resource for Live Nation events, ranging from concerts, sports, theater, arts and other live events, as well as clients of its ticketing business Ticketmaster, the companies said in a joint statement.
Visitors of the new marketplace will have access to limited-time discounts on a variety of Live Nation events, albeit limited to North America.
It isn’t clear exactly when GrouponLive will go fully live (pun intended), although the companies said they’re on schedule for the site to make its debut in time for the summer concert season.
According to the press release, the deal was struck in large part thanks to Madonna manager and angel investor Guy Oseary, who advised on the deal. Oseary is on Groupon’s advisory board, and has worked with Live Nation through his role as artist manager and event promoter.
Financial terms of the deal were not disclosed.
In 2010, Live Nation Entertainment’s concert ticket sales were down 10 percent, and for the year it reported a loss of $228.4 million on $5 billion in revenue. Last week, the company announced that the first quarter of 2011 reflected ‘improvement’ in ticket sales – Live Nation reported a 17.4 percent increase in revenue compared to Q1 2010.


There is perhaps no one alive who has contributed more to the art form of the selfie than Kim Kardashian, and her Instagram grid post bidding farewell to the year 2022 is a creative twist on a classic of the genre—the backward mirror shot. But instead of a mirror, Kardashian has captured the full hotness of her bikini-clad booty through the reflective surface of a darkly tinted window, which also shows off her tropical vacation locale. “Looking back at ’22,” she captioned the post, with a winky-face emoji, of course.
Whatever your personal feelings on Kardashian (all of which are certainly valid), there's no doubt that her ongoing divorce proceedings from the ex-husband-who-shall-not-be-named have made 2022 more stressful than average. Anyone would be glad to see the backside of a year like that, and I, for one, am happy the Skims founder appears to be celebrating in true Kardashian style—by looking hot in bikinis on the beach.
A week earlier, Kardashian captioned another vacation post, “Life tip- do you.” Because extremely unsubtle editing on photos of herself soaking in the tropical shoreline is just Kim doing Kim.


This is an extremely clean diesel Westy from the only year when VW actually offered an oil-burner straight from the factory. As opposed to the anemic original 1.6 liter, last year this received a heart update via a brand-new 1.9-liter diesel unit straight from Volkswagen. Despite being pretty early in the Vanagon life cycle, the chassis has just 84k miles, putting together a very tidy package with a complete, fully functioning interior and nearly flawless exterior. All of this comes together for a van that appears ready for several more decades of fun.
Here’s a nice, mostly-stock Westy that comes with a funny little bonus trailer on the back. I’m not sure how the “solar panel toolbox” works (is the battery inside?), but I like it already and dig the Westfalia badging. It seems a little excessive to just haul bikes on it – that’s what bike racks are for! – but there are plenty of uses for a good trailer. Dirtbike? Scooter? All the stuff you can’t fit inside? Anyway, it may not be the most minimalist, self-contained setup, but who cares when there’s no reserve on it? It looks clean in and out with the main detraction being rather high mileage.
Click for details: 1990 Volkswagen Vanagon Westfalia on eBay
After a day of reflection on independence, I see no better vehicle to represent the ideal than a good, clean Westfalia. Cars in general embody independence, the ability to get in and go, but a Westy means you can go and maybe decide to not come back. Many people live in Westfalias full time, exploring the world and staying in new zipcodes while their pop-top home stays the same. While many command serious new-car money, this 1984 example looks to be an incredible deal. If you can make it through the intimidatingly-long description, you’ll find that this van has been loved, gone through, and updated by someone who knows their stuff and truly cared about making a great, functional camper. This is the kind of independence I want in my future, and if bidding remains at such an approachable level, maybe it will be!
Click for details: 1984 Volkswagen Vanagon Westfalia on eBay
Here’s one of the best deals on a Syncro camper we’ve seen in a while (if not ever!) and it comes with a well-done Subaru boxer swap. These High Top campers are much more rare than their pop-top brethren, but it’s a pretty awesome look with more 4-season capability. Though listed with 290k miles, the engine was put in 20k miles ago and had a decent refresh at the time along with a rebuilt transmission. Clearly owned by a well-informed and diligent Vanagon enthusiast, this Syncro camper is going for about half of where most start. It’s caveat emptor with any swap, high-mileage car, or 80s Volkswagen in general, but anyone looking at this van should have a healthy level of project-excitement and an appreciation of getting this much Vanagon for a reasonable price.
Click for details: 1986 Volkswagen Vanagon Syncro on eBay
I like older cars that are loved, maintained, and well-used in the manner they were built for. This means that high mileage is, to me, a badge of honor, and replaced and upgrades parts are more a sign of perseverance and attention than decay. Like my old cars, this ’91 Westy appears to me as a shining example of just how good 200k+ miles can look. Sure, there are some stone chips and patina, and the engine and transmission have had to be replaced, but from the wheels to the tent and all through the inside it looks a great, functional adventure van. Instead of the 2.1-liter gas engine, it now has a 1.9-liter TDI conversion that was truly done right, with some nice engine mods along with a re-geared transmission and a Peloquin differential to resist those annoying one-wheel spins in traction-deficient situations. The condition and upgrades more than offset the high odometer reading, so the auction is starting at a strong $29k.


Tom Moriarity is a nationally recognized preservationist and urban development specialist. Trained as an architect, Tom was one of the founders of the National Trust’s pioneering Main Street Program. As Managing Principal at Retail & Development Strategies LLC, Tom has been involved in major restoration and urban rehabilitation projects across the U.S. and the world. He will bring his expertise on architecture, architectural history, historic preservation and adaptive use that will help each traveler better understand the beauty and significance of the places we will visit. Tom holds two degrees in Architecture from the University of Texas at Austin.


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Momentum 2015: Mass Workout (Zumba by Samantha Kan)
Always interested in Dance but never really known how to start? Our mass workouts cater to the masses who want to find an avenue to dance even without no experience. Join us, as well as many others, for the Mass workouts in Capoeira and Zumba taught by professionals.
5:00 PM - 6:00 PM SGT
- W1 Forum, Republic Polytechnic
- Venue Address
- Republic Polytechnic 9 Woodlands Avenue 9, Singapore 738964 Singapore
Momentum Dance Festival283 Followers

domain: hobby


text: Combine Wild Blueberries with sugar and water in a large saucepan and bring to a boil. Reduce heat and simmer until berries are soft and begin to thicken, about 5 minutes. Mix flour, baking powder, sugar and salt together. Cut in butter. Gradually stir in enough milk to make a soft dough. Drop the batter by tablespoons on top of the simmering berry sauce. Immediately cover saucepan and cook over low-medium heat 15-18 minutes. Old Fashioned Wild Blueberry Grunt serves 4 to 6.


Quincy Mae Long Sleeve Jumpsuit - Multiple Colors Available - AW20
Regular price $27.30 Sale price
Velvety soft long sleeve jumpsuit with wood buttons down the chest, and hidden snaps along the inseam for easy changing.
Available in: Clay, Fog Stripe & Honey with Suns
Care: Machine wash cold. Tumble dry low.
Made 100% certified organic cotton


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We can develop your private label solutions!
Research and development is an important part of our private label chemical manufacturing process. From beaker to bottle, at Nexstar we pay close attention to the quality, efficacy, and safety of our formulas. Nexstar's Specialty Products Division works very closely with our manufacturers throughout the entire process.
Nowhere is our innovation more evident than our Research and Development. We specialize in providing a full-service turnkey solution for transforming product concepts to finished products.
Our staff and network of partners include experts and some of the best chemists in the field for formulating your private label product. Nexstar has over 30 years of experience in developing products and has a data base of over 1,000 formulas that may already fit your product requirements. We can use one of our house formulas, match a sample you provide us, or develop a new private label product to meet your needs.
Nexstar has extensive experience analyzing, developing, manufacturing and distributing chemicals and related products. Plus our experts are knowledgeable and up to date on the various new regulations affecting consumer products (i.e. REACH, DFE, VOC, CARB, EPA)

domain: chemistry


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Christmas is the best time of the year for many people. It isn’t only about gathering with your family, but it’s a chance for Christmas book promotion. As we’re approaching the biggest buying holiday, you should think of your books as a part of the sales company that is already around the corner.
Do you still doubt that the Christmas holiday season perfectly fits the book promotion? Leave all the scruples!
I’ll tell you how to prepare and promote your books in the holiday season to make both your ebooks and hard copies a thrilling present under the tree.
Just keep reading.
Why the Christmas holiday season is the best time to market your book
The Christmas holiday season is well-known as a time covered with a sense of tenderness, care, and joy. It’s an excellent opportunity for you to market your book in the holiday season.
Here are two main points. Initially, your writing will be certainly in trend. All you need to do is to create a warm story that contains the best features of Christmas. Secondly, you can choose among different options on how to promote your book. And, of course, do not forget about book cover design.
Well, it’s time to make a list of essential preparations before writing your Christmas book.
What you should do before writing your Christmas book
Here are some necessary steps that will help you prepare for writing a Christmas story.
Sometimes it appears complicated to come up with the ideas of Christmas writing, especially several months before the very holiday. So what is the way out? You may start by analyzing the works of other writers in your genre. They might have published some holiday books, which can serve a decent bit of inspiration.
Yet, I realize not everyone writes Christmas stories, and you may find nothing or a few of them. Here’s another solution that will certainly work out in case if it’s hard to come up with ideas for your writing. You should recall the plots of your favorite holiday books.
Here’s our list of Christmas stories and novels that will inspire you with some focal themes and prototypes of the characters for your writing:
- “A Christmas Carol” by Charles Dickens
- “How the Grinch Stole Christmas!” By Dr Seuss
- “Letters from Father Christmas” by J.R.R. Tolkien
- “The Christmas Miracle of Jonathan Toomey” by Susan Wojciechowski
- “The Gift of the Magi” by O.Henry
- “The Fir Tree” by Hans Christian Andersen
- “The Greatest Gift” by Philip Van Doren Stern
- “A Letter from Santa Claus” by Mark Twain
I hope after reading these books, you’ll absorb in the holiday mood and find ideas for your works. And remember, Christmas is a time of the year when adults willingly read fairytales and undeniably believe in miracles. Don’t waste your chance to share a piece of bright hope with the world.
Do hashtag research
Use hashtags to find more information on the Christmas season. Jane Friedman suggests doing holiday-themed hashtag research as a means of inspiration. It’s preferable to use hashtags to increase relevance and searchability as well as reflect your personality. Add them to your posts so people will find you effortlessly. Moreover, the new audience may discover you quickly.
Have a glance at these bunch of hashtags you can begin using right now:
Do titles research
Your book title matters. In other words, it should be appealing and relate to the mood of the holiday. Unlike generating book titles at the time of the year, try to combine Christmas keywords with the theme of your writing to set this connection.
Besides, you may find best selling Christmas books on Amazon. Among this variety, you can choose the tiles that may work for you. Otherwise, you can use them to create something different. By the way, you may start with the list of Christmas readings regarded above.
With this in mind, I’m sure you’ll cope with writing your Christmas book. If you want to begin writing it right now, go ahead and make some notes.
For those who still wait on inspiration, let’s not waste time but learn about the ways on how to promote and sell your Christmas work.
Tips on how to promote and sell your book at Christmas
#1 Get a holiday-themed book cover design
What is a book without a cover? This time, it should be a holiday-themed one. That’s why you should customize typography, imagery, and color scheme of your fiction book cover design to the Christmas season.
Let’s dive into the world of Christmas design and opt for the best element for your holiday book cover.
The following fonts are the most popular ones. They include the miracle and warmth of the holiday. By the way, they perfectly match both fiction and non-fiction.
All the things you can associate with Christmas may be the elements of the imagery composition for your book cover. They may be a Christmas tree, snow, warm drinks and cocktails, presents, decorations, ribbons, snowflakes, a plaid, Santa Clause, and many others.
Also, you can choose the scene or the character that reflects the plot of your book and add one Christmas element to create this mood.
The Christmas color palette includes the traditional variety of colors. Red, blue, white, and green will give a hint at your Christmas writing.
Meanwhile, purple, turquoise, and pink serve as an unusual option.
#2 Create a Christmas mood on your site and social media accounts
It’s rather challenging to promote Christmas writing without holiday decorations on your social media accounts and site.
Will it work? By all means!
Plenty of businesses add a bit of festive flair to their brands. So, it’s an excellent chance for you to adopt this trend. Try to incorporate Christmas elements into the header and profile image. It will boost the overall mood, so you’ll induce your visitors to read your Christmas writing.
Get absorbed into the festive spirit and let your readers feel its scent.
#3 Collaborate with other indie authors in your genre and create a Christmas book with different short stories
It would be awesome to start a collaboration with another indie author and write your holiday story. And, Christmas is a perfect time to try creating something unusual. So, It may be either your common novel or several different stories. Of course, they should have some connection. And it’s not about writing but the sense of miracle and the spirit of the holiday.
#4 Use your current book characters and create a Christmas story with them
Let the Christmas season bring your writing a wind of changes. In other words, you may set your most popular book characters into the holiday time. For you, it’s a chance to develop a new plotline and endow your character with extra features or improve the current ones. For your readers, it’s a fresh breath of air. You can solve their problem of Christmas reading, providing a theme book for this time of the year. And, the adventure of the well-known character emerges a lovely bonus. Feel free to use this idea for your Christmas book and dare to create something unusual.
#5 Holiday Updates and Challenges
Christmas is almost the final holiday in a year. Thereby, it’s an excellent opportunity to plan and set challenges for the upcoming year. Why not share these ideas with your audience? Prepare a post for your blog or write about it on social media. For instance, inform your audience that you plan to publish four-six books per year. It will motivate you to write as well as add a sense of anticipation among your audience. You may also create a poll on what is more challenging: reading books or writing them. It will help you find out about your readers’ intentions. Needless to say, you’ll get the most valuable thing – engagement with your audience.
#6 Upgrade your current book covers
Add some element of Christmas decor to your print books or ebooks. For example, you can decorate the covers with a red ribbon, set the image of a holly plant or a reindeer in one of the book covers. You won’t spend much, but your book will get a festive upgrade. With this little trick, your book becomes a perfect Christmas present, attracting new and potential readers.
#7 Give Christmas gifts with each sold ebook
When you ask people about their associations with Christmas, the first thing they might think is gifts. So, it’s a chance for you to show your generosity to the world and, yes, give presents.
How can you manage that?
Provide a present as a bonus for buying your ebook. It may be a poster with a calendar or a gift card with a discount for purchasing your book. Additionally, you can prepare a PDF file with a holiday short story, Christmas recipes, holiday guides on how to decorate a house, or tips about choosing Christmas presents. Moreover, you can prepare a package of holiday stickers and bookmarks.
Use traditional Christmas elements or incorporate characters or sayings from your writing with the holiday motives. Address your imagination to create unique and unusual presents. As you’re aware of your readers’ preferences, you’ll be able to interest them.
#8 Create a Christmas newsletter series
A series of newsletters will boost your holiday marketing campaign. There are two things to keep in mind. Primarily, you have to decide on the term. For example, you can send your newsletters within 12 days or for a fortnight. Secondly, you should select an exciting theme. It can also be a challenge with different tasks for your audience. You may encourage them to write a review for your book, recommend a book on social media, and do other compelling stuff. Oh, and don’t forget to reward your subscribers for each completed task.
#9 Host a Christmas giveaway
People love the chance of winning, and running giveaway provides this exposure. For writers, it’s an excellent way to gather email addresses and enlarge the number of subscribers. Prepare the task for running a Christmas giveaway, such as following your page on Facebook, subscribing to newsletters, or leaving the email address. At last, select a random winner on Christmas morning and make a gift – one of your books.
#10 Organize a Christmas themed contest
The main idea of this promotion is to have fun and generating publicity. Try to manage the contest that requires more than just buying your books but engaging with your audience on social media.
Let people share their emotions. So you may ask people to submit their photos with their favorite books. Also, you can propose to post their pictures wearing an ugly Christmas sweater and holding your book. Or, it may be a photo of your work placed in some unusual location.
If you have only ebooks, then let your readers compete in the emotional reading of the passage from one of your works. Whatever option of the contest you choose, don’t forget to award the winners with decent presents.
#11 Give a Christmas promo code
Giving a Christmas promo code with a discount for the next purchase of your book is another excellent idea to show your warm care to your current subscribers. Also, you may use this trick to collect new email addresses. Just make a post in your social media with terms or create an interactive game on your site to refresh your mailing list and give a discount with the promo code.
You can agree on cross-promotion with other writers. It’s a mutually beneficial collaboration because your books gain visibility with relevant new readers. Team up with one or more writers on panels, post interviews in your blog or social media, or create a mutual series to reach a new audience. You may use these and think of other ways of co-working to market your Christmas books.
#13 Run “Bring a Friend” campaign
It would be great to encourage your current readers to engage their friends. Provide a discount or give a little present to a person who will bring a friend. Also, you should award a new member for joining your audience — people like presents, especially before Christmas.
I hope these tips help create and promote your Christmas writing. Different methods of marketing will bring joy to you and your readers. Get the most from this Christmas season, and don’t postpone the promotion of your books.
Don’t hesitate to contact us! We’ll willingly help with all your questions.

domain: literature


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Growers’ Experiences Selling Crops Through Food Hubs
Thursday, April 16
3:30 – 4:45pm ET (12:30 – 1:45 PT)
Free! Register Now
What is it like to sell to or through a food hub? What are the benefits … and what is not so good? Learn directly from seasoned farmers!
We have assembled farmers representing a wide variety of experiences – different geographies (CA, MT, MI, and MA), different sizes (from 8 to 400 ac.), different products (vegetables, animals, and mixed) … who sell into different kinds of food hubs (non-profit, for profit, growers co-op) asking different services from them (simple transport, sell-through, and selling to the hub).
Each of these farms has different reasons to work with their local food hub. What works for them? What doesn’t work so well? How do they choose what to sell through the hub? We’ve asked these farmers to share their unedited experiences and advice with their fellow farmers across the country who might now be considering a relationship with a food hub.
Learn how they chose to start selling to the hub, why, what the hub demands of them, what they get in return, how they are managing risks, and how their business’ bottom line has been affected.
Considering selling through a hub? Learn from the experience of your peers. Advise farmers? Enrich the service you can provide.

domain: agronomy


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E&P | Markets | NGI All News Access | NGI The Weekly Gas Market Report
Raymond James Sees WTI Advancing to $80 in 2017, 2018
Raymond James & Associates has increased its 2017/2018 West Texas Intermediate oil price forecast by $5.00/bbl, but cautioned that given the U.S. unconventional industry’s ability to post efficiency gains, the bias over time is for prices to move lower.
Specifically, the 2017 and 2018 forecasts for WTI have been raised to $80/bbl from $75. Brent prices for 2017 are expected to average $83/bbl versus an earlier forecast of $79, while in 2018, prices should average $80/bbl from $75. In 2019 and beyond, the forecast is for $70 WTI and $75 Brent.
“Given the U.S. shale industry’s ability to post steady cost efficiency gains, our bias would be that, over time, oil prices move lower, or the futures curve becomes backwardated starting in mid-2017,” said analysts J. Marshall Adkins and Pavel Molchanov. “This $70 price deck should support sufficient long-term U.S. oil supply growth to offset slowly rising global oil demand and falling non-U.S. oil supply.”
At the beginning of 2016, Raymond James energy analysts had forecast WTI/Brent would average $75/$79. In early February, they had forecast WTI would reach $50/bbl later this year in the face of a futures strip that was considered “simply unsustainable” (see Shale Daily, Feb. 8).
“While our oil price bias is still to the upside for 2017, the U.S. oil and gas industry will work through the pending bottlenecks, and oil prices beyond 2017 should slowly revert down to a lower, more sustainable long-term price equilibrium,” analysts said. “In other words, we expect the oil futures markets will move into steeper backwardation (or lower outer year prices) as 2017 oil prices move higher.”
“The U.S. likely wouldn’t even need $80 crude to see a substantial bump in oil and associated gas production,” said NGI Markets Analyst Nate Harrison.
According to a report by Bloomberg, analyzing the breakeven prices in Bakken, Eagle Ford and Permian counties, about half of these major oil producing counties become profitable above $40/bbl, where prices are today.
“The lowest breakeven costs in the country were found in the Reeves, TX,” in the Permian Basin, where some of the Wolfcamp formation is found, Harrison said. “All counties they analyzed were profitable above $64/barrel. Although the analysis left out other major oil producing regions, such as the Niobrara (Denver-Julesburg) and the Oklahoma stacked plays, it seems fair to say that the supply-side response from $60-plus oil would be large and the $80 prices forecast from Raymond James could bring on a large-scale boost in U.S. production, assuming producers can meet the demand. One of the assumptions Raymond James had was that they wouldn’t be able to do so fast enough.”
One issue for long-term forecasts is the fact that it is going to take time to “fix the damage” to the energy industry caused by the severe downturn in pricing.
“While future U.S. efficiency gains could easily drive the long-term equilibrium price deck lower than $70, we remain of the view that $50 to $60 would definitely not support a sustainable level of global investment for the long run,” Adkins said.
Raymond James’ oil model is more bullish for three reasons:
“We continue to believe that 2017 WTI oil prices will average about $30/Bbl higher than current futures strip prices would indicate,” Adkins said. “When we factor in modestly higher 2016 global oil demand growth, our global oil model has become meaningfully more bullish (or tighter).”
Since Raymond James issued its forecast in January, the 2017 oil supply forecast has declined by 790,000 b/d, while the 2018 forecast has fallen by 1.4 million b/d. A big supply side issue is that the length and severity of the downcycle has created a lot of U.S. oilfield bottlenecks, created in part by average initial production rates climbing 30%-plus each year since 2011.
“As a result of increased productivity…many U.S. oil resource plays are offering some of the best field-level economics outside the Persian Gulf,” analysts said of the U.S. onshore. “It is also the case that U.S. onshore operations are a textbook example of ‘short-cycle’ activity. As prices rise into the $50-60/bbl range and beyond, operators will naturally respond by adding rigs. But there is no escaping the fact that the length and severity of the downturn have changed the landscape across the oil patch, resulting in numerous bottlenecks that will limit the extent to which drilling activity can accelerate.”
The “short-cycle” could result in a year or more before domestic output begins to respond to higher oil prices. Oilfield services and producers initially will choose to move cash flow toward balance sheet repair rather than to maximize growth. Also, the limited labor pool — combined with low U.S. unemployment — may make it difficult to undo the massive layoffs. As well, there will be shortages within the pressure pumping market because of cannibalization and attrition.
“While production efficiencies and a large inventory of drilled but uncompleted wells will certainly help U.S. supply growth, the aforementioned bottlenecks are real and must be taken into account,” Adkins and Molchanov said. The net impact to their model “is more subdued U.S. oil/liquids production growth, especially in 2018, versus our expectations from six months ago.”
Meanwhile, Societe Generale analysts Michael Wittner said last week the outlook for global oil fundamentals remained constructive, with slight global crude and product draws expected in the second half of this year, but “the current mood in the oil markets is risk averse,” with the most recent Energy Information Administration petroleum report doing little to change the sentiment.
U.S. crude output dropped by 29,000 b/d, with Lower 48 output down by 28,000 b/d. U.S. crude stocks remained “far above” the five-year highs.
“The U.S. crude draws continue to be nothing more than seasonal, and Canadian crude production is also recovering,” Wittner said. U.S. product demand “has been surprisingly strong,” but the Federal Reserve Bank’s “cautious tone” at last week’s meeting “tells a different story, and it seemed to resonate with the markets….” In addition, the referendum this week regarding Brexit, whether Great Britain leaves the European Union, has contributed to overall risk aversion and is weighing on the oil complex. “In the next week, it is becoming difficult to see how this will change.”
© 2023 Natural Gas Intelligence. All rights reserved.
ISSN © 2577-9877 | ISSN © 1532-1266 | ISSN © 2158-8023 |


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Carpet runners hallways lead the way and draw attention to the transition corridors and stairways. The carpet runners also draw attention to a focal point. They come in a multitude of colors and designs to match the decor of any home, and can vary widely in price, depending on the size of the carpet, the materials used and how they are made.
Persian carpet runners hallways are among the most sought after styles. Employers usually adorn ornate Persian carpet runners, which are often colored with brown or red tones. Usually they are made of silk and wool, and are woven by hand; so many brokers Persian rugs are one-of-a-kind. Because of the detailed craftsmanship, authentic Persian styles can cost thousands of dollars.
12 Photos Gallery of: Carpet Runners Hallways
However, imitations are available at much lower prices, around £ 65 and up. Persian styles typically found in more traditional homes, but the color and pattern of the right can also be fitted in a contemporary design. Carpet runners hallways are organic and are made from old clothes, bedding and other fabrics. They are a collage of different fabrics and patterns joined together to make a carpet runner hip looking.

domain: artistic


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Abbott held a comprehensive 1-day extracorporeal membrane oxygenation (ECMO) therapy program in August of 2021. The following videos are recordings of the program sessions and are intended for heart failure clinicians and/or administrators—including nurse practitioners, ECMO coordinators, nurses, perfusionists and other providers interested in ECMO education.
This state-of-the-art program is designed to enhance participants’ knowledge on all aspects of ECMO, providing educational content for those new to acute circulatory support while also challenging experienced clinicians.
Gary Schwartz, MD, explores the benefits of a collaborative approach to extra-corporeal cardiopulmonary resuscitation (ECPR), highlighting improved outcomes through delivery standardization.
Faraz Masood, MD, explores how the identification of appropriate patients for advanced heart failure therapies such as acute circulatory support is critical in ensuring positive outcomes.
Christian Bermudez, MD, presents how ECMO is a vital option for critically ill patients, acting as a bridge to more advanced treatments, such as heart and/or lung transplantation.