text:
About the ACG
Thought you might appreciate this item(s) I saw at Clinical and Translational Gastroenterology.
ARTICLE: FUNCTIONAL GI DISORDERS
Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial
Palsson, Olafur S. PsyD1; Peery, Anne MD1; Seitzberg, Dorthe PhD2; Amundsen, Ingvild Dybdrodt MSc2; McConnell, Bruce MSc, MBA2; Simrén, Magnus MD, PhD1,3
1Center for Functional Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA;
2Glycom A/S, Horsholm, Denmark;
3Department of Internal Medicine and Clinical Nutrition, Institute of Medicine Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Correspondence: Olafur S. Palsson, PsyD. E-mail: [email protected].
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/CTG/A453; http://links.lww.com/CTG/A454; and http://links.lww.com/CTG/A455.
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Clinical and Translational Gastroenterology: December 2020 - Volume 11 - Issue 12 - p e00276
doi: 10.14309/ctg.0000000000000276
Treatment options for irritable bowel syndrome (IBS) are limited, causing many patients to remain symptomatic. This study assessed the potential of human milk oligosaccharides (HMOs) to normalize bowel habits. Secondary outcomes included IBS severity and health-related quality of life.
This multicenter, open-label trial recruited patients with IBS from 17 sites across the United States. Patients received daily orally administrated 5-g intervention of the HMOs 2'-fucosyllactose and lacto-N-neotetraose in a 4:1 mix. Bowel habits, IBS symptoms, and quality of life were assessed at baseline and every 4 weeks during the 12-week intervention.
A total of 317 patients (70.7% women; mean age of 44.0 years, range 18–93 years) received the trial product, and 245 patients completed the trial according to protocol. Patients had a significant improvement from baseline to 12 weeks in total percentage of bowel movements with abnormal stool consistency (mean and [95% confidence interval]: 90.7 [88.9–92.9] vs 57.2% [53.9–60.5], P < 0.0001), overall IBS Symptom Severity Score (323 [314–332] vs 144 [133–155], P < 0.0001) and health-rela,ted quality of life (50.4 [48.0–52.8] vs 74.6 [72.3–76.9], P < 0.0001). Improvement was similar across IBS subtypes. Symptoms improved most in the first 4 weeks of intervention. The most common side effects were mild gastrointestinal symptoms such as flatulence, abdominal pain and discomfort, and distension.
Supplementation with 2 selected HMOs improves IBS symptoms and quality of life without substantial side effects. These promising results suggest that this novel approach to IBS should be confirmed in a randomized, placebo-controlled trial.
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction, characterized by recurrent abdominal pain associated with altered bowel habits, including abnormal stool consistency and frequency (1–3). IBS is one of the most common disorders of the digestive tract, with an estimated worldwide population prevalence of 5%–11% (4,5). Thirty percent of those suffering from IBS have symptoms severe enough to consult a physician (6). For these patients, the disease has a large impact on quality of life, commonly leading to the need for medical treatment, frequent health care seeking, significant impairment of daily life, and work absenteeism. This in turn leads to economic consequences for the individual and for the society (7–9).
Although IBS is prevalent, effective treatment of the condition is lacking. Moreover, medications approved for treating IBS are often limited to a specific subgroup of patients, i.e., IBS with predominant constipation (IBS-C) or diarrhea (IBS-D), leaving the large subgroup of patients who have a mixed bowel habits (IBS-M) without a designated therapy option. Furthermore, the therapeutic benefits of IBS drugs are modest, and they do not treat the underlying pathophysiology (10). For these reasons, many patients remain symptomatic long-term regardless of medical treatment. Hence, there is a clear unmet need for alternative effective strategies for patients to manage their IBS symptoms. It is also worth considering that patients may prefer a dietary approach to manage their condition on a daily basis instead of consuming drugs.
The pathogenesis of IBS is unknown, but the gut microbiota are being increasingly seen as a potential contributing factor (11). This has been prompted by a number of clinical observations, such as de novo development of IBS after enteric infections (12), compositional differences in the gut microbiota of patients with IBS relative to healthy individuals (13,14), e.g., a depletion of fecal and mucosal bifidobacteria (15), and clinical responses to interventions that modify the gut microbiota (16). The role of the gut microbiota in IBS pathogenesis may, in part, involve changes in the production by bacteria of several nutrients (17) that are crucial for maintaining gut health (18). Diet is, together with genetics and environmental factors, one of the main contributors to the composition of the human gut microbiota (19). Despite the potential contribution of the gut microbiota to IBS pathogenesis, there is currently no therapy available to normalize IBS-specific dysbiosis, and a dietary approach to manage symptoms is worth further investigation.
Human milk oligosaccharides (HMOs) are a heterogenous mix of glycans naturally occurring in high concentration in human breast milk (20). As HMOs are largely indigestible in the upper gastrointestinal (GI) tract (21–23), the majority of ingested HMOs reach the large intestine undigested. Here, they serve multiple roles, including modulation of the microbiota and the immune system, and prevention of epithelial adhesion of intestinal pathogens (20,24,25). Because of these characteristics, these HMOs potentially have a beneficial role in the management of IBS; particularly the symptoms relating to bowel function. Based on a recent, small proof-of-principle trial in patients with IBS (26), 2 HMOs, 2'-fucosyllactose (2'FL), and lacto-N-neotetraose (LNnT), can be expected to support normal bowel function in adults suffering from IBS without causing tolerance issues. They may also, through modulation of intestinal microbiota and associated metabolites, improve general gut health resulting in better management of IBS-related symptoms and thereby overall wellbeing.
The aim of this open-label trial was to assess the potential of a daily intake of 5 g of a 4:1 mix of 2'FL and LNnT to normalize bowel habits in a real-world setting in patients diagnosed with IBS. Furthermore, the impact on overall IBS symptom severity, other GI symptoms, and disease-specific health-related quality of life was also assessed.
Trial design and conduct
This was a prospective, open-label, single-arm clinical trial to evaluate the efficacy and safety of daily oral intake of a 5-g combination of 2 HMOs, 2'FL, and LNnT in a 4:1 mix, in adults with IBS. Patients were recruited in medical clinics and clinical research centers at 17 sites across the United States. An e-pharmacy distributed the trial product to patients. The trial was conducted in accordance with the Declaration of Helsinki (27) and approved by the independent institutional review board IntegReview. The trial was registered at ClinicalTrials.gov with registration number NCT03550742.
Written informed consent was obtained from all participants at a screening visit. After inclusion in the trial, the patients completed surveys at baseline, and 4, 8, and 12 weeks after start of intervention to collect data on current symptoms, wellbeing, and medication use. All surveys were administered online through a password-protected patient web page. Validated questionnaires were used, including the Bristol Stool Form Scale (BSFS) (28), IBS Symptom Severity Score (IBS-SSS) (29), the IBS-specific version of the Gastrointestinal Symptom Rating Scale (GSRS-IBS) (30), and the IBS Quality of Life questionnaire (IBS-QOL) (31). Patients also answered questions related to health, medication usage, adherence to the intervention, perception of the trial product, and adverse events (AEs). A trial duration of 12 weeks was selected to provide sufficient time for stabilization of symptoms and decrease of the placebo effect, while retaining the exploratory nature of the trial.
Inclusion and exclusion criteria
Patients were eligible for participation in the trial if they were aged 18 years and older, had a diagnosis of IBS from a health care provider, and met the Rome IV diagnostic criteria for IBS (32). All IBS subtypes were included. No minimum IBS-SSS score was required. Lactose intolerant patients were eligible because of the low content of lactose in the trial product. In addition, patients had to be fluent in English and have access to the Internet through computer, tablet, or smartphone. Patients were excluded from participation if they had been diagnosed with celiac disease, diverticulitis, inflammatory bowel disease, or Clostridium difficile infection. Women who were pregnant or lactating were also excluded from participation.
Efficacy and safety evaluation
The primary endpoint in the trial was the mean change from baseline in the proportion of bowel movements with abnormal stool consistency as measured by BSFS (stool types 1 and 2 [hard stools], and types 6 and 7 [loose stools]), in all patients and in IBS subtypes. This endpoint was selected, rather than a combined pain and stool consistency endpoint as often used in current IBS clinical trials, because the aim of the trial was not to test the HMO blend as an overall IBS intervention but as nutritional support for normalizing bowel movements in patients with IBS. To assess stool consistency, patients were asked to report the percentage of all stools falling within the classification of hard stools and loose stools, respectively, during the previous 4 weeks. Secondary endpoints included change from baseline in the overall IBS-SSS score and the IBS-SSS parameters of abdominal pain severity and frequency, and bloating severity; severity of gastrointestinal symptoms measured by GSRS-IBS; and the patients' disease-specific health-related quality of life measured by IBS-QOL. Safety was assessed by collecting and monitoring AEs throughout the course of the trial.
Trial intervention
The HMOs were produced by Glycom Manufacturing A/S, Denmark, under good manufacturing practice conditions, using fermentation followed by separation and purification resulting in products of greater than 97% purity, and provided as white powder. Capstone Nutrition, UT, filled under good manufacturing practice conditions the 2'FL and LNnT in a 4:1 mass ratio in single-serve stick packs. Each stick pack contained the daily dose of 5 g of HMOs. The single-serve stick packs were distributed in boxes that each contained 30 stick packs. Compound mix ratio and daily dose were determined based on internal data. All patients received the HMO mix after entering the trial and completing the baseline survey. The intervention was open-label, so all patients were aware they were taking the active HMO mix. Patients were instructed to consume the content of 1 stick pack daily for 12 weeks, either mixed in food or beverage or on its own. The final product contained less than 1% lactose, corresponding to less than 50 mg of lactose per day.
There were no previous data available to enable prediction of the size of the impact of 2'FL and LNnT on the primary outcome measure in this trial. In the absence of relevant pilot data, G*Power version 3.1.9.2 was used to calculate the sample size needed to achieve 95% power to detect a small effect size with the planned analysis method (assumptions: ANOVA: repeated measures, between factors; effect size f = 0.25; alpha = 0.05; number of groups = 3; number of measurement points = 2; correlation among measures = 0.5). This yielded a required total sample size of 189. Thus, the chosen sample size of 300 should be sufficient to detect even small intervention effects.
For both primary and secondary outcomes, analyses were conducted with a 2-factor mixed-design ANOVA, with the 3 IBS subtypes (corresponding to the number of groups) as the between-subject factor and 2 timepoints (baseline vs week 12) as within-subject factor. This was performed using an intention-to-treat (ITT) methodology, including data from all patients who received a shipment of the trial product regardless of whether they started the intervention, and carrying the last observations obtained forward to fill any missing data points from discontinued patients. Statistical analyses were performed using IBM SPSS Statistics Version 25.0.
Trial population
A total of 366 patients were screened for eligibility to participate in the trial between May 2018 and November 2018. Of these, 49 patients did not meet the inclusion criteria or met exclusion criteria after enrollment, or did not complete the baseline survey, leaving 317 patients to be included in the analyses. Thirteen of those subjects were discontinued after completing the baseline survey, as they did not start the intervention. Of the 304 subjects who started the intervention, 273 completed the trial and all assessments (Figure 1).
Figure 1.:
Patient flow. ITT, intention-to-treat; PP, per protocol.
The sample of 317 patients included in the analyses had a mean age of 44 years (range 18–93 years) and consisted predominantly of women (70.7%). The average IBS-SSS score was 323 (range 60–500), with 63.7% of the patients presenting with severe IBS (IBS-SSS >300). More than 65% of the patients in the analysis sample had experienced onset of IBS symptoms within the last 3 years before enrollment, and the distribution of IBS subtypes was 42.9% with IBS-C, 26.7% with IBS-D, 30.0% with IBS-M, and 0.3% with unspecified IBS. Most of the patients (88.3%) reported at baseline that they were taking medication regularly to manage their IBS symptoms, and they were allowed to continue to do so during the trial. Throughout the trial, 245 patients reported full adherence to the intervention. An overview of baseline demographics is shown in Table 1.
Table 1.:
Baseline characteristics and demographics of the trial population
Overall, the total proportion of bowel movements with abnormal stool consistency (BSFS 1, 2, 6 and 7) improved from baseline to week 12 (mean and [95% confidence interval]: 90.7 [88.9–92.9] vs 57.2% [53.9–60.5], P < 0.0001) (Figure 2), with no differences in improvement between IBS subtypes. The proportion of loose stools (BSFS 6 or 7) was reduced from baseline to week 12 in the total sample (Table 2). This change was mainly driven by the significant change in the IBS-D subgroup, followed by a smaller change in the patients with IBS-M, whereas no change was seen in the patients with IBS-C. The proportion of hard stools (BSFS 1 and 2) was also reduced from baseline to week 12 in the ITT population. This was mainly driven by the IBS-C subgroup, followed by the patients with IBS-M, whereas the patients with IBS-D showed an increase in the proportion of hard stools from baseline to 12 weeks. There were no differences in the change in the proportion of bowel movements with abnormal stool consistency between men and women (−32.6% vs −33.9%, P = 0.78), but younger patients (younger than 40 years) had a greater reduction in bowel movements with abnormal stool consistency than patients older than 40 years (37.6% vs 30.5%, P = 0.04).
Changes in total % of abnormal consistency stools (Bristol Stool Form Scale) during 12 weeks of daily supplementation of a 5-g mix of 2'-fucosyllactose and lacto-N-neotetraose. *Significantly reduced total % of abnormal stools (diarrhea + constipation) compared with baseline at P < 0.0001.
Percentage of bowel movements with hard stools (BSFS 1 and 2) and loose stools (BSFS 6 and 7) (mean [95% confidence interval]) at baseline and after 12 weeks of intervention
The overall severity of IBS symptoms on the IBS-SSS was reduced by 54.2% (323 [314–332] vs 144 [133–155], P < 0.0001) on average from baseline to week 12, and a similar pattern was seen in all 3 IBS subtypes with no differences between the subtypes (Figure 3). A reduction of at least 50 points in the total IBS-SSS score is considered a clinically significant improvement (29). By that standard, 260 (82.0%) of the patients had a clinically significant improvement in overall IBS severity. Abdominal pain and bloating severity were reduced by 59.4% (62.5 [60.1–64.9] vs 25.4 [22.6–28.2], P < 0.0001) and 59.2% (56.8 [53.8–59.8] vs 23.2 [20.5–25.8], P < 0.0001), respectively, with no differences between IBS subtypes (Figure 4a, c). Furthermore, significant reductions in number of days with abdominal pain during the last 10 days were observed in the total patient sample and in each of the IBS subtypes, with no differences between subtypes (Figure 4b). The GSRS-IBS score from baseline to week 12 also changed from 54.9 [53.6–56.1] to 34.0 [32.5–35.4] (P < 0.0001) in the overall sample, with no differences between subtypes (see Supplementary Figure 1, Supplementary Digital Content 1, http://links.lww.com/CTG/A453).
Changes in the overall IBS Symptom Severity Score during 12 weeks of daily supplementation with a 5-g mix of 2'-fucosyllactose and lacto-N-neotetraose in the different IBS subtypes. *Significantly different from baseline at P < 0.0001. Error bars: 95% confidence interval. IBS, irritable bowel syndrome; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; IBS-M, alternating/mixed-pattern IBS.
Changes in (a) abdominal pain severity (0–100 scale), (b) number of days with abdominal pain (out of 10 days), and (c) bloating severity (0–100 scale) during 12 weeks of daily supplementation with a 5-g mix of 2'-fucosyllactose and lacto-N-neotetraose in the different IBS subtypes. All subtypes and the overall sample were significantly improved on all these parameters at 12 weeks. *Significantly different from baseline at P < 0.0001. Error bars: 95% confidence interval. IBS, irritable bowel syndrome; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; IBS-M, alternating/mixed-pattern IBS.
Health-related quality of life (IBS-QOL) was significantly improved at week 12 compared with baseline, with scores rising from 50.4 [48.0–52.8] to 74.6 [72.3–76.9] (P < 0.0001). There were no differences among the 3 IBS subtypes in change in IBS-QOL scores (see Supplementary Figure 2, Supplementary Digital Content 2, http://links.lww.com/CTG/A454).
Overall, there were no incidents causing safety concerns in this trial, and the patients generally reported that the intervention was well tolerated. The number of reported AEs was relatively low; 46 patients (14.5% of the ITT sample) reported any AEs during the trial, with a combined total of 87 AEs. Of these, 65 AEs reported by 33 patients were considered to be possibly or probably related to the intervention on review. Most AEs (n = 61) were related to the gastrointestinal tract, and the most common side effect of the intervention was passing gas, followed by abdominal distension and abdominal pain (see Supplementary Figure 3, Supplementary Digital Content 3, http://links.lww.com/CTG/A455). Only 8 patients (2.5%) discontinued their participation in the trial prematurely due to AEs. One serious AE (brief hospitalization due to colitis) occurred during the trial, but this was considered on review by the study's medical safety officer of the available information to be unrelated to the intervention.
In this prospective, open-label, single-arm clinical trial, daily ingestion of a 5-g mix of 2 HMOs, 2'FL and LNnT, in a 4:1 mass ratio reduced abnormal stool consistency, improved abdominal pain, bloating and overall IBS severity, and increased IBS-related quality of life. These improvements were seen in both the entire IBS group and in all IBS subtypes, with a similar degree of beneficial changes in all IBS subtypes. Most of the observed improvement in symptoms occurred within the first 4 weeks of intervention, and it then remained stable during the remainder of the 12-week intervention period. Furthermore, the low rate of reported AEs demonstrated that the HMOs are safe in adult patients with IBS.
This is the first large-scale trial to show that adult patients with IBS can achieve an improvement of IBS symptoms with supplementation of HMOs. A recent randomized, placebo-controlled proof-of-principle and safety trial including 61 adults diagnosed with IBS found that the same 4:1 mix of 2'FL and LNnT increased the abundance of fecal bifidobacteria without worsening GI symptoms (26), increasing the abundance of a bacterium that has been found to be depleted in individuals with IBS (15). The increase in Bifidobacterium abundance was driven by Bifidobacterium adolescentis and to a lesser degree Bifidobacterium longum (33).
There are several different effects of HMOs that can explain the beneficial effects on GI symptoms. Supplementation with a mix of 2'FL and LNnT has previously been shown to increase the abundance of fecal bifidobacteria, in healthy infants (34), children (data on file), healthy adults (35), and in adults with IBS (26). Bifidobacteria have been found to be depleted in individuals with IBS (15), which may influence the metabolites produced by the gut microbiota. In particular, bifidobacteria produce the short-chain fatty acid acetate (36). In addition to maintaining a beneficial environment by lowering the colonic pH, acetate is a substrate in the synthesis of butyrate, an important energy source for the colonocytes (18). Increasing the concentration of butyrate in the colon might support gut barrier integrity which has been reported to be compromised in patients with IBS (37). Supplementation with bifidobacteria has also previously been shown to have a beneficial impact on IBS symptoms (38). However, as supplementation with probiotics introduces a single or few bacterial strains, potentially foreign to the recipient, supplementation with prebiotics such as HMOs supports the growth of beneficial bacteria already present in the recipient's gut. These potential mechanisms posed through gut microbial modulation and function may, at least in part, explain why the intervention had a significant impact on bowel habits and IBS symptoms, irrespective of subtype, and it may further be speculated that the great symptom improvement leads to the observed improvement in health-related quality of life. Furthermore, it has been reported that patients with IBS may have an increased number of activated mast cells (39) and a low-grade mucosal inflammation (40), which in turn may affect enteric nerve function and the gut-brain interactions, thereby influencing GI motility and sensitivity (41). Fucosylated HMOs, such as 2'FL, have been shown to moderate nociceptive stimuli associated with activated mast cells and may therefore modulate gut motility and visceral pain (42). The observed improvement may also, at least in part, be explained by the statistical phenomenon of regression to the mean.
Although the large symptom improvement observed in this trial is very encouraging, the present trial has limitations. These include the open-label nature of the trial and absence of a placebo or comparator group, which make it impossible to determine how much of the impact can be ascribed placebo effect. However, the substantial effects of the HMO mix on bowel habits, other IBS symptoms, and health-related QOL, as well as the sustained nature of these effects during the entire 12-week intervention period, indicate that intervention with 2'FL and LNnT has a promising potential in the management of IBS. As the beneficial impacts of the intervention were seen across age, sex, race/ethnicity, and IBS subtypes, it seems likely that a broad range of patients with IBS will benefit from ingesting the 2'FL and LNnT mix.
In conclusion, daily oral administration of the 2 HMOs, 2'FL and LNnT in a 4:1 mix, for 12 weeks significantly improves bowel habits, other IBS symptoms, and health-related quality of life in adults who have clinical IBS diagnosis and fulfill the Rome IV criteria for IBS. Furthermore, our results indicate that the HMO mix tested is safe for use in adult patients with IBS. However, the encouraging findings from this open-label trial need to be confirmed in a randomized, placebo-controlled trial.
Guarantor of the article: Olafur S. Palsson, PsyD.
Specific author contributions: O.S.P., M.S., and B.M.: contributed in designing the trial. O.S.P.: responsible for data collection and database cleaning and analyzed the data. O.P. and I.D.A.: prepared the manuscript. All authors had full access to the study data, had input to the content of the manuscript, contributed in finalizing the manuscript, and approved the final version for submission.
Financial support: The trial was sponsored by Glycom, Inc., LA. The trial sponsor was involved in designing the trial and writing of the manuscript.
Potential competing interests: O. S. Palsson has received research support from Glycom and the Rome Foundation and served as Consultant/Advisory Board Member for Ironwood and metaMe Health. A. Peery declares no conflict of interest. D. Seitzberg, I. D. Amundsen, and B. McConnell are employed at Glycom A/S, Denmark. M. Simrén has received unrestricted research grants from Danone and Ferring Pharmaceuticals and served as a Consultant/Advisory Board member for AstraZeneca, Danone Nutricia Research, Nestlé, Almirall, Allergan, Albireo, Genetic Analysis AS, Biocodex, Glycom, Arena, and Shire and as a speaker for Tillotts, Takeda, Menarini, Kyowa Kirin, Allergan, Shire, Biocodex, Alimentary Health, AlfaSigma, and Almirall.
ClinicalTrials.gov identifier: NCT03550742.
Study Highlights
WHAT IS KNOWN
✓ Human milk oligosaccharides (HMOs) promote growth of Bifidobacterium spp., which is depleted in patients with irritable bowel syndrome (IBS).
✓ A mix of 2 HMOs, 2'-fucosyllactose (2'FL) and lacto-N-neotetraose (LNnT), increases the abundance of fecal Bifidobacterium spp. in patients with IBS without inducing gastrointestinal symptoms.
✓ The impact of HMOs on bowel habits and IBS symptoms in patients with IBS is unknown.
WHAT IS NEW HERE
✓ Daily supplementation with a mix of 2'FL and LNnT normalizes bowel habits in adult patients with IBS by decreasing the proportion of both hard and loose stools.
✓ Patients reported improvement of IBS symptoms and increased quality of life after ingestion of the HMO mix.
TRANSLATIONAL IMPACT
✓ The study findings suggest that HMOs may have value as nutritional support to improve bowel symptoms and wellbeing of clinical patients with IBS.
We thank the participating patients and investigators for their contribution to the trial.
1. Ford AC, Talley NJ. Irritable bowel syndrome. BMJ 2012;345:e5836.
Cited Here |
View Full Text | PubMed | CrossRef
2. Spinelli A Irritable bowel syndrome. Clin Drug Investig 2007;27(1):15–33.
3. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006;130(5):1480–91.
PubMed | CrossRef
4. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: A meta-analysis. Clin Gastroenterol Hepatol 2012;10(7):712–21.e4.
5. Palsson OS, Whitehead W, Törnblom H, et al. Prevalence of Rome IV functional bowel disorders among adults in the United States, Canada, and the United Kingdom. Gastroenterology 2020;158(5):1262–73.e3.
6. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol 2014;6:71–80.
Cited Here
7. Choung RS, Locke GR III. Epidemiology of IBS. Gastroenterol Clin North Am 2011;40(1):1–10.
8. Lea R, Whorwell PJ. Quality of life in irritable bowel syndrome. Pharmacoeconomics 2001;19(6):643–53.
9. Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: Systematic review and meta-analysis. Am J Gastroenterol 2012;107(7):991–1000.
10. Camilleri M, Ford AC. Pharmacotherapy for irritable bowel syndrome. J Clin Med 2017;6(11):101.
11. Hyland NP, Quigley EM, Brint E. Microbiota-host interactions in irritable bowel syndrome: Epithelial barrier, immune regulation and brain-gut interactions. World J Gastroenterol 2014;20(27):8859–66.
12. Thabane M, Simunovic M, Akhtar-Danesh N, et al. An outbreak of acute bacterial gastroenteritis is associated with an increased incidence of irritable bowel syndrome in children. Am J Gastroenterol 2010;105(4):933–9.
13. Casen C, Vebø H, Sekelja M, et al. Deviations in human gut microbiota: A novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Aliment Pharmacol Ther 2015;42(1):71–83.
14. Jeffery IB, O'Toole PW, Öhman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 2012;61(7):997–1006.
15. Pittayanon R, Lau JT, Yuan Y, et al. Gut microbiota in patients with irritable bowel syndrome—A systematic review. Gastroenterology 2019;157(1):97–108.
16. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol 2006;101(7):1581–90.
17. Vigsnæs LK, Salomonsson E, McConnell B. Human milk oligosaccharides; now as powerful, specific modulators of the adult gut microbial community. The 11th Vahouny Fiber Symposium, 2017. June 15, 2017, Bethesda, MD.
18. Astbury SM, Corfe BM. Uptake and metabolism of the short-chain fatty acid butyrate, a critical review of the literature. Curr Drug Metab 2012;13(6):815–21.
19. Turroni F, Peano C, Pass DA, et al. Diversity of bifidobacteria within the infant gut microbiota. PLoS One 2012;7(5):e36957.
20. Bode L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology 2012;22(9):1147–62.
21. Brand-Miller JC, McVeagh P, McNeil Y, et al. Digestion of human milk oligosaccharides by healthy infants evaluated by the lactulose hydrogen breath test. J Pediatr 1998;133(1):95–8.
22. Engfer MB, Stahl B, Finke B, et al. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr 2000;71(6):1589–96.
23. Gnoth MJ, Kunz C, Kinne-Saffran E, et al. Human milk oligosaccharides are minimally digested in vitro. J Nutr 2000;130(12):3014–20.
24. Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev 2015;91(11):619–22.
25. Bode L. Human milk oligosaccharides and their beneficial effects. In: Zibadi S, Watson RR, Preedy VR (eds). Handbook of Dietary and Nutritional Aspects of Human Breast Milk. Wageningen Academic Publishers: The Netherlands, 2013, pp 515–31.
26. Iribarren C, Törnblom H, Aziz I, et al. Human milk oligosaccharide supplementation in irritable bowel syndrome patients: A parallel, randomized, double‐blind, placebo‐controlled study. Neurogastroenterol Motil 2020;32(10):e13920.
27. World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013;310(20):2191–4.
28. Lewis S, Heaton K. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997;32(9):920–4.
29. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: A simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther 1997;11(2):395–402.
30. Dimenäs E, Glise H, Hallerbäck B, et al. Well-being and gastrointestinal symptoms among patients referred to endoscopy owing to suspected duodenal ulcer. Scand J Gastroenterol 1995;30(11):1046–52.
31. Patrick DL, Drossman DA, Frederick IO, et al. Quality of life in persons with irritable bowel syndrome (development and validation of a new measure). Dig Dis Sci 1998;43(2):400–11.
32. Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology 2016;150(6):1393–407.e5.
33. Iribarren C, Magnusson MK, Törnblom H, et al. Efficacy of human milk oligosaccharides on fecal microbiota in patients with IBS. Gastroenterology 2019;156(6):S-235.
34. Steenhout P, Sperisen P, Martin FP, et al. Term infant formula supplemented with human milk oligosaccharides (2′ fucosyllactose and lacto-N-neo tetraose) shifts stool microbiota and metabolic signatures closer to that of breastfed infants. FASEB J 2016;30(1_Suppl):275–7.
35. Elison E, Vigsnaes LK, Rindom Krogsgaard L, et al. Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota. Br J Nutr 2016;116(8):1356–68.
36. O'Callaghan A, van Sinderen D. Bifidobacteria and their role as members of the human gut microbiota. Front Microbiol 2016;7:925.
37. Dunlop SP, Hebden J, Campbell E, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 2006;101(6):1288–94.
38. Staudacher HM, Whelan K. Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet: Probiotics, prebiotics and the low FODMAP diet. Proc Nut Soc 2016;75(3):306–18.
39. Powell N, Walker MM, Talley NJ. Gastrointestinal eosinophils in health, disease and functional disorders. Nat Rev Gastroenterol Hepatol 2010;7(3):146–56.
40. Shulman RJ, Eakin MN, Czyzewski DI, et al. Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome. J Pediatr 2008;153(5):646–50.
41. Drossman DA, Camilleri M, Mayer EA, et al. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123(6):2108–31.
42. Bienenstock J, Buck RH, Linke H, et al. Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions. PLoS One 2013;8(10):e76236.
Supplemental Digital Content
CTG_2020_10_27_PALSSON_1_SDC1.tif; [Other] (605 KB)
© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology
View full article text
Clinical and Translational Gastroenterology11(12):e00276, December 2020.
Articles in PubMed by Olafur S. Palsson, PsyD
Articles in Google Scholar by Olafur S. Palsson, PsyD
Other articles in this journal by Olafur S. Palsson, PsyD


Hi! Sign in to let us know how Music Unlimited was?
Robert L. Sep 03 .
As a musician, I can really appreciate this specialty store. I didn't see any instruments here, but what I did see was a whole store devoted to sheet music from every style and genre. They had KISS songbooks and they had Bach songbooks! A dedicated older man operates this shop that's just down the street from the Blind Faith Cafe and lots of other shops and restaurants.
If you've been to or used Music Unlimited, leave a review.


text:
Joshua 21-22
On March 17, 2016 May 11, 2016 By Oby BallingerIn Daily Bible
Good morning! Today's reading (Joshua 21-22) adds to the account of land designations by describing the cities from each tribe which belong to the Levites, then narrates a confrontation between the majority of Israel and those tribes who have settled on the east of the Jordan River.
The cities for the Levites are given by lot (chance) in Joshua 21. We don't hear the mechanics of how these cities were randomly chosen, but they also include the six cities of refuge identified yesterday. I can't help but think what trust would be required for the tribes to surrender control of these towns within their "inheritances" and provide space for the Levites. Were there jealousies and disagreements between these city-dwelling Levites (with their pasturelands) and the other tribes that surrounded them? We don't (yet) see evidence of that, but it seems likely to me since humans are involved! Chapter 21 closes by emphasizing God's faithfulness to the covenant promises of territory for the Hebrews.
Joshua 22 gives an example of human reliability to an earlier promise, and also reveals the negotiations needed to stay together despite evident mistrust between the tribes. The chapter begins with commendation of Reuben, Gad and the half-tribe of Manasseh for their faithfulness in fighting west of the Jordan while their land-holdings are on the east. They have been loyal to the other tribes of Israel in fighting valiantly alongside them, so now that fighting is over these tribes go home with the spoils of battle. They build a great altar on the east side of the Jordan, which raises the hackles of the rest of Israel. They interpret this action as idolatrous rebellion against the true altar and tabernacle of God's presence. Phinehas (the zealous warrior who spears an Israelite and Moabite in Numbers 25) reappears as a strongman emissary from the western tribes. He invokes examples of idolatry and disobedience from Hebrew history, including the "sin at Peor" (Numbers 25) and the rebellion of Achan (Joshua 7). Their concern seems to stem from an idea that God could only be manifest and truly worshipped in one geographic place, but also demonstrates a sensitivity to rival altars which reflects later conflict between Judah and Israel after the civil war. The eastern tribes respond that they have built this altar in order to keep faith with the rest of Israel, not to separate away. They fear that later generations might discount the eastern tribes and write them off from "really" belonging to Israel. Therefore, the altar is a visible reminder intended to mimic the altar of the tabernacle so as to convey their perpetual place among the tribes, even though they are east of the Jordan River. This story underscores again the desire of those tribes to be found faithful, and demonstrates unity across difference (communal loyalty which will later be in very short supply elsewhere in Israel). Happy reading!
Read Joshua 21-22.
Please join discussion of this passage at the Daily Bible Facebook group, or comment below. The passage for tomorrow is Joshua 23-24. Thanks for reading!

redpajama_set_name: RedPajamaCommonCrawl


Our designer MaryJane-style Ruffle Tights are too cute from top to bottom! These tights are the perfect accessory to her special occasion outfit.
Plus, they feature a comfort waistband and convenient diaper panel.


text:
Q: WOWZA: How to connect live edge repeater to another live edge repeater? I have setup live origin wowza instance and live edge (edge1) and that is working fine. I need to setup now another live edge instance (edge2) to fetch streams from edge1. So everything to be connected as following:
origin <-- edge1 <-- edge2 <--client
So when a client connect to edge2 it will initiate connection to edge1 and edge1 will pull stream from origin.
How to achieve above scenario? It is important to connection be on demand and not persistent.

A: You indicate that you've set up origin and edge applications, so the Primary Origin URL for the edge should be pointing to the origin.
Now, you can create a second edge application where the Primary Origin URL refers to the original edge application.
When you playback via the Test Player on the second edge application (or look at the Incoming Streams page), you'll see that it's pulling from the original edge application.

redpajama_set_name: RedPajamaStackExchange


text:
Q: Devise - openid + ldap So, I've been studying about Devise and I've really liked it, but one thing I didn't understand is, can you use multiple providers (e.g. ldap login + facebook/google/etc.)? So, what I want is:

*

*User - information connected to my website

*Linked provides - so, I want Users to be able to link their accounts to multiple providers.

For example, let's say we have user example_user. It has its facebook, google and ldap account linked to its account, so if it tries to login in with ldap, google or facebook account, it'll succeed and give me its instance of model User.
Sorry for my bad language, I'm quite bad at explaining my issue.
Thanks!
EDIT: I've resolved it by using omniauth.

A: maybe these three pointers will help:
http://wiki.phys.ethz.ch/readme/devise_with_ldap_for_authentication_in_rails_3
http://random-rails.blogspot.com/2010/07/ldap-authentication-with-devise.html
http://vimeo.com/13105005


Face it, you never get a do-over on a first impression. In a world saturated by media, you only have a short window to connect with your viewers. Good design doesn't need to be hard to be effective; I can help simplify and you can watch your business grow!
Magento, Drupal, Joomla, Zencart, Wordpress & more!
Mail Chimp, Constant Contact, etc.
Hi, I'm Christy Patton. I am a proud University of Utah alumna with a degree in Fine Arts. I've been lucky enough to have some fantastic marketing mentors over the years. In addition I have incredible drive to increase my skills and knowledge base in marketing and design. I've found that I like to have the answers and if I don't I find them.
I am a talented individual who possesses a broad range of skills including user interface design, web design, graphic design, writing and marketing with over 15 years of experience.
Want to see my work? Click here.
I just had to post how much I LOVE the new BC [Business Center] facelift. Thanks Christy!
Have you seen your PWS [Personal website] today? Demi changer and a jewelry changer! Thank you Christy!!! Thank you!!
If I could make the thumbs up bigger for this [Personal website redesign] link, I totally would!
Fill out the form and I'll get in touch with you right away!


text:
My private members motion addressing the humanitarian crisis of the Rohingya people in Myanmar
PRIVATE MEMBERS' BUSINESS
Notices 1
MS VAMVAKINOU: To move—That this House:
(1) notes that:
(a) Amnesty International has evidence that hundreds of Rohingya women, men and children have been killed since the escalation of a violent assault in Northern Arakan/Rakhine State, Myanmar, since 25 August 2017;
(b) the United Nations has estimated that since August 2017, over 589,000 Rohingyas have been forced to flee to refugee camps in Bangladesh;
(c) there are at least another 20,000 Rohingyas being detained at the borders;
(d) the United Nations Human Rights Council has witnessed accounts and heard testimonies of the Myanmar security force setting villages on fire and injuring, torturing, raping, killing and executing innocent victims; Page 6 of 12
(e) 214 villages have been destroyed through fire and will be taken over by the Myanmar Government because burnt land becomes government-managed land;
(f) the United Nations High Commissioner for Human Rights, Prince Zeid Ra'ad al-Hussein, has called these government attacks 'a textbook example of ethnic cleansing'; (g) approximately 600,000 people are still deadlocked inside Rakhine State with limited access to food, medical care or humanitarian assistance;
(h) despite the history of the Rohingya Muslims in the Rakhine region extending back the post-colonial era, this community has been denied citizenship and most basic government services under since 1982; and
(i) the treatment of Rohingya Muslims in the Rakhine region is an issue that deeply concerns the Australian community; and
(2) urges:
(a) the Government of Myanmar to:
(i) recommit to the pursuit of peace and national reconciliation; and
(ii) allow access to all parts of Rakhine State to allow for the provision of humanitarian aid;
(b) the Australian Minister for Foreign Affairs to:
(i) do everything in her power to help alleviate the suffering in Rakhine State;
(ii) lead the push for a strong United Nations General Assembly Resolution on the violence in Rakhine State, and
(iii) work to establish an independent United Nations investigation into human rights abuses in Myanmar; and
(c) the Australian Government to:
(i) support unimpeded humanitarian access to the Rohingya population;
(ii) maintain pressure on the Myanmar Government, particularly the military and security forces, by condemning the persecution, attacks, killings and human rights abuses of the Rohingyas; and
(iii) stand up for the moderate voices in Myanmar which are being widely suppressed by the threat of persecution by the Myanmar military.
(Notice given 23 October 2017.)


Tony and Brendan were super dooper!!! They showed up on time and did a quality job! Id trust these boys with anything! I don't know what they're getting paid but they definitely deserve a raise! Thanks again Safety King Air Duct Cleaning. I breath a lot easier now knowing that the poisons in my house are gone!!!


text:
Home / About / Contact & People / Hussein Keshani
Hussein Keshani
Creative Studies
Other Titles: Art History and Visual Culture Program Coordinator
Office: CCS 170
Email: hussein.keshani@ubc.ca
Graduate student supervisor
Sultanate, Mughal and Late-Mughal era (Nawwabi) visual culture; Digital Islamic Art History; Interpretation in Digital Media for Botanic Gardens and Museums
World Art History; Art Histories of the Islamic World & South Asia; Digital Humanities; World Literatures
Dr. Keshani initially studied architecture and design at the University of Manitoba, as well as urban planning. Troubled by the endemic Eurocentricism in his required art history coursework, he decided to pursue studies in art history with a focus on the Islamic World and South Asia at the University of Victoria (UVic), where he completed his MA thesis on the Delhi's Dargah of Nizamuddin and his PhD dissertation on Lucknow's Bara Imambara complex. He went on to complete postdoctoral fellowships at UVic, Stanford (IHUM), and MIT (AKPIA). He has been an invited to speak in the UK, Australia, and Algeria and has presented his scholarship at major international scholarly gatherings, which include the Association for Art History, Modern Language Association, College Art Association, and American Historical Association.
As a scholar and a teacher, Keshani's work crosses multiple disciplines including history, religious and gender studies, digital art history/humanities, world literature, interpretation and art and architectural history. His diverse research practices include, archival and museum research, fieldwork at architectural sites and botanic gardens, coding, and analytical renderings of architectural drawings and digital models.
ubc.academia.edu/HusseinKeshani
blogs.ubc.ca/darc
hkeshani.github.io/darc
github.com/hkeshani/darc
Bachelor of Environmental Studies, University of Manitoba, Master of Arts (Co-op), History in Art, University of Victoria, Doctor of Philosophy, History in Art, University of Victoria
The Evolving the Botanic Garden project. (forthcoming)
"A Collage of Projections: Exploring an Awadhi Miniature Painting's Pictorial Space Through 3D Modelling." Inside/Outside Islamic Art & Architecture: A Cartography of Boundaries in and of the Field. New York: Bloomsbury, 2019/20. (forthcoming)
"Doctrine and Design: Two Islamic Centres in Burnaby, Canada." BC Studies. No. 198 Summer 2018.
"Database Review of Archnet 2.0, A Resource for the Built Environments of Muslim Societies." Beyond Citations Project. June 18, 2018.
"Imāmbāra." In Encyclopaedia of Islam, THREE. Eds. Kate Fleet, Gudrun Krämer, Denis Matringe, John Nawas, Everett Rowson. 2018.
"Taj Mahal," Encyclopedia of Islam and the Muslim World (MacMillan Reference USA, Jan. 8, 2016 –Ebook; March 4, 2016 Print) pp. 1138-1140.
"The Writing on the Walls: Selections from the Twelver Shi`i Epigraphs of Lucknow's Husseinabad Imambara." In People of the Prophet's House: Art, Architecture and Shi'ism in the Islamic World. Ed. Fahmida Suleman. London: I.B. Taurus & British Museum, 2015. 115-125.
"Encounters with Digital Art History." Ars Orientalis, Vol 44., 2015
"Digitizing Islamic World Visual Cultural Heritage: Recolonizing or Decolonizing Cultural Memory, or Both?" Patrimoines du Maghreb à l'ère numérique Conference Proceedings. Eds. Samia Chergui and Bernadette Saou-Dufrêne eds., 2014.
"Towards Digital Islamic Art History" Journal of Art Historiography: Islamic Art History. Issue 2012. Eds. Moya Carey and Margaret Graves, University of Glasgow, 6-HK/1.
"Reading Visually: Can Art Historical Reading Approaches go Digital?" Scholarly and Research Communication 2012, vol 3, No 4 (2012).
"Architecture and Community," in Amyn B. Sajoo, ed., A Companion to Muslim Cultures, London: I.B. Tauris, 2012. 117-136.
"Theatres of Power and Piety: Architecture and Court Culture in Awadh, India." In Court Cultures in the Muslim World Seventh to Nineteenth Centuries. Eds. Albrecht Fuess and Jan-Peter Hartung. New York: Routledge, 2010. pp. 445-471.
"Engaging Islamic Views on Human-Animal Relations: Towards an Adab-centred Approach," Worldviews: Global Religions, Culture, and Ecology. Leiden: Brill, Volume 14, Number 1, 2010. pp. 6-25.
"Islamic Architecture." In The Islamic World. Ed. Andrew Rippin. London: Routledge, 2008. pp. 444-472.
"Islamic Art." In The Islamic World. Ed. Andrew Rippin. London: Routledge, 2008. pp. 421-443.
"Architecture and the Twelver Shi'a Tradition: The Great Imāmbārā complex of Lucknow." Muqarnas, vol. 23 (Nov.). Leiden: Brill, 2006. pp. 219-250. (Winner of the Margaret B. Sevcenko Prize in Islamic Art and Culture).
"The Abbasid Palace of Theophilus." al-Masaq: Islam and the Medieval Mediterranean. London: Carfax, 2004, vol. 16, No. 1, March 2004. pp. 75-91.
"Epigraphs, Scripture and Architecture in the Early Sultanate of Delhi." co-authored with Anthony Welch and Alexandra Bain. Muqarnas. Vol. 19, Leiden: Brill, 2002. pp. 12-43.
Selected Grants & Awards
SSHRC Insight, Co-Investigator, Botanic Gardens and the Politics of National and Transnational Environmental Governance, 2012-2021
National Endowment for Humanities-ODH Start-Up grant (Level II) (US), Co-Applicant, Evolving the Botanic Garden: Digital Environmental and Cultural Interpretation at the Edmonton Devonian Botanic Garden's new Islamic Garden, 2015
SSHRC, Partnership Development Grant, Evolving the Botanic Garden: Digital Environmental and Cultural Interpretation at the Edmonton Devonian Botanic Garden's new Islamic Garden, 2014-2017
SSHRC, Insight Development Grant, Model Images: Transforming Miniature Paintings into 3D Virtual Environments, 2012-2013
Internal Research Grant, UBC, The Gardens of Awadh: A Preliminary Study of the Mughal Garden Tradition in 18th and 19th C North India Funding, 2012
UBC Okanagan Grant for the Integration of Teaching and Research in Undergraduate Education, World History of Art Mashup (WHAM): Reimagining Art History Learning Tools, 2012
UBC Hampton Partnership Development Grant, Bloom: An Interpretive Program for Edmonton's Contemporary Islamic Garden, 2012
Martha Piper Research Fund, UBC, The "Medieval" Delhi Humanities Computing Research Collective, 2007
Beyond the Digitized Slide Library Summer Institute Participant Award, Getty Foundation and University of California, Los Angeles, July 28 –August 6, 2014
Teaching Award for Excellence & Innovation, Faculty of Creative & Critical Studies, UBCO, 2014
Marion Dean Ross Chapter, Society of Architectural Historians, Elisabeth Walton Potter Research Awards, Doctrine and Design in Islamic Centers of the Pacific Northwest, 2012
Margaret B. Sevcenko Prize in Islamic Art and Culture, Historians of Islamic Art, 2005/06
Introduction to Humanities Postdoctoral Fellowship, Stanford University, 2004
Aga Khan Program for Islamic Architecture at Harvard University and MIT Postdoctoral Fellowship, Strangers, Lovers, and Kin: Gender Roles and their Interplay with the Architecture of Awadh, 2004
Social Sciences and Humanities Research Council of Canada Postdoctoral Fellowship, Negotiating Presence: Architecture and Gender Relations in 18th C. Awadh, India, 2003
Graduate Supervisions
Nathalie Hager, From Nations to Networks: An Analysis of North American World Art History Discourse During the Transcultural Turn (PhD Candidate, in-process)
Chelsea Baumgartner, Queer Muslim Contemporary Artists: A Trans-Temporal Heuristic Model (PhD Candidate, in-process)
Undergraduate Honours Supervisions
Asia Li, Armstrong, Chinese Commemorative Memorial Report, 2017, FCCS Undergraduate Student Research Award
Lucas Glenn, Ellipsis, BFA Visual Arts Supervisor, 9/2013 – 4/2014 (Creative Studies Award 2013/14)
Dylan Ranney, BFA Visual Arts Supervisor, 9/2012 – 4/2013 (FCCS Visual Arts Prize, 2012/13)
Nadine Bradshaw, BFA Visual Arts Supervisor, 9/2012 – 4/2013 (DVC purchase Award, 2012/13)
Avery (Alanna) De Rousie, BFA Visual Arts Supervisor, 9/2011 – 4/2012
Barbara Morin, BFA Visual Arts Supervisor, 9/2009 – 4/2010
Jacqueline Karley, BFA Visual Arts Supervisor, 9/2008 – 4/2009


Ever since it was announced that Nobu was opening a hotel in Shoreditch we knew we would love it – so when we held an Eventprofslive event there last week they had a lot to live up to! And boy did they live up to our expectations!!
We started off the evening in the lobby bar with bubbles and a selection of bar snacks – OMG the yellowtail sashimi still dreaming of that now! The lobby bar has a super relaxing feel and makes a great first impression for your delegates as well as a great place for a late-night drink!
After chatting and consuming as much of that yellowtail sashimi as possible, we headed off to check out the bedrooms. The bedrooms and suites are all designed with a contemporary feel and would make your delegates feel right at home! Overall there are 150 bedrooms of which 7 are suites. The Miyabi Suite that we viewed has a fantastic private balcony, an amazing free standing bath in the bedroom and it was super handy that you can close off the bedroom from the living room so if needed meetings could take place in the living room of the suite.
The event spaces are located on the ground floor, it is a super flexible and versatile space. It can either be used as one room for up to 200 delegates or divided into 6 separate rooms. The space has fantastic natural day light with floor to ceiling windows and the space has a private entrance from the main hotel. Within the main restaurant, there are 2 private dining spaces – although separated by curtains from the main restaurant which is not an issue if your guests like to soak up the atmosphere but if they are having business conversations we would recommend using the spaces within the main event space for private dining. The highlight for the group was the main restaurant and bar which can be hired exclusively that even has its own terrace. It would be a fantastic space for a drinks and canapés reception. You can also have a semi-private area in the bar for a smaller drinks and canapés reception. Read more here for the event spaces.
We can guarantee that if you hold an event here that your delegates would be fed so well! The food was incredible, after seeing the spaces we headed off to the bar in the restaurant where we had our own area reserved. The food was incredible, highlights included the black cod and the prawn tempura…who am I kidding it was all a highlight! Can't wait to return!!
For further information reach out to Layla Jensen.


These very glamourous 10 denier lace top hold ups have a glossy appearance with a reinforced toe.
Can be worn in the evening or daytime wear.
The silicone bands in the lace will keep these hold ups in place.
88% Nylon, 12 % Eleastine.
You can pay in either British £, Euro's or USA $. Just select your currancy at the top of the page.
Credit and debit cards are processed by global payments - HSBC's online processing solution.
You can also pay by Paypal in any of the three currencies.
We do not keep any card details.
All UK orders are delivered by First class Royal Mail post. Orders are sent in plain packaging.
We are happy to exchange the goods or refund your money.
Just return the unopened goods in their original condition within 28 days of receipt.
If the goods have been opened, then we cannot exchange or refund any money as we are unable to resell the product for hygiene reasons.


Despite being in the Arabian desert, Dubai offers exciting water activities. From kayak or paddle boarding to extreme water sports like Jetpack or parasailing.
Enjoy kayaking or paddle boarding in the calm waters of Dubai.
- In cases of extreme weather, this tour may be cancelled. Your host will contact you directly.
- For Kayak, Paddle Boarding and Fly Boarding: Minimum age required is 16 years old. Min weight 45 kg, max 100 kg.
- For Jet Pack and Fly Fish: Minimum age required is 10 years old. Children above 10 years old must be accompanied by an adult.
- Participants should know how to swim.
Enjoy 30 minutes of fly boarding, the most amazing and extreme water sport activity. Fly like Iron-man above the water and perform some tricks including back-flip.
Enjoy 3 hours of diving at Dubai Jumeirah. Includes 30 minutes of briefing prior doing the dive.
Enjoy 60-minute of single Kayak down Dubai's calm water.
Enjoy a 60-minute Seabreacher experience. Sea Breacher is a highly sophisticated submersible watercraft, with a profile of an aggressive and mighty shark. You will get mesmerising vistas of both the surroundings and underwater and lifts you off up to 20 feet in the air and then dive you 7 feet beneath the serene waters. Maneuvered by an expert instructor, a Sea Breacher can accommodate up to two people.
Enjoy 30 min Jet Ski in Dubai Beach.
Enjoy a 30-minute jetpack ride. Be prepared to fly 20 to 30-feet above water with this extreme water activity and adrenaline-pumping Jetovator ride.
Enjoy a 15 minutes of Banana Boat Ride in Dubai Beach .
Enjoy a 15-minute fly fish ride, a large inflatable raft boat which moves with the swift pull off a speed boat.
Enjoya 15-minute Zup Boarding experience. Zup Boarding is new and fresh way to enjoy the thrill of surfing over the waves.
Enjoy a 30-minute Seabreacher experience. Sea Breacher is a highly sophisticated submersible watercraft, with a profile of an aggressive and mighty shark. You will get mesmerising vistas of both the surroundings and underwater and lifts you off up to 20 feet in the air and then dive you 7 feet beneath the serene waters. Maneuvered by an expert instructor, a Sea Breacher can accommodate up to two people.
Enjoy a 15-minute Seabreacher experience. Sea Breacher is a highly sophisticated submersible watercraft, with a profile of an aggressive and mighty shark. You will get mesmerising vistas of both the surroundings and underwater and lifts you off up to 20 feet in the air and then dive you 7 feet beneath the serene waters. Maneuvered by an expert instructor, a Sea Breacher can accommodate up to two people.
Enjoy 60 min Jet Ski in Dubai Beach.
Enjoy a 10-minute parasailing experience. Fly up 150 metres above the sea!
Enjoy 15 minutes of Donut Ride in Dubai Beach. Ride a round inflatable boat drawn by a speedboat or a personal watercraft along the beautiful shoreline of Dubai.


text:
Perspective > Medscape Family Medicine > Cases in Deprescribing
Treating Depression in Primary Care: Are Biomarkers the Key?
Charles P. Vega, MD
Can a Lab Test Guide Antidepressant Therapy?
Which Drug When?
We need to identify and treat depression more effectively. But what is the best antidepressant? There really is no answer to that question.
Antidepressants are far more similar than different with regard to efficacy of treatment. Previous systemic reviews have found that citalopram and escitalopram have some significant improvements in depression scores compared with other antidepressants, but this difference is limited to the acute phase of treatment and is of questionable clinical relevance.[10,11] Similarly, venlafaxine has been demonstrated to be superior to SSRIs in terms of treatment response and remission in depression, and dropout rates from clinical trials are similar in comparing venlafaxine and SSRIs.[12]
However, in clinical practice, the individual response to antidepressant therapy may be quite variable, and no antidepressant medication clearly separates itself in terms of overall efficacy. One approach to choosing an antidepressant includes selecting therapy on the basis of a cluster of symptoms.
A recent review recommended SSRIs, such as citalopram, escitalopram, or sertraline, for patients with depression with features of anxiety, whereas such medications as venlafaxine should be avoided in these patients.[13] Depression with fatigue may respond better to a norepinephrine/dopamine reuptake inhibitor, such as bupropion, or such medications as venlafaxine or fluoxetine. Depression with insomnia might be best treated with mirtazapine or nefazodone. Finally, patients with depression with pain may respond best to tricyclic antidepressants or duloxetine.
A new symptom cluster to consider in depression is cognitive function. Cognition is often impaired among depressed patients and is associated with a poor response to medical treatment.[14] In two clinical trials, the relatively new antidepressant vortioxetine has been associated with improvements in not only depression scores, but also cognition scores.[15,16] Post hoc analysis suggested that most of the cognitive benefit associated with vortioxetine was independent of its antidepressive effect.
However, other well-considered reviews have raised serious questions about the effectiveness of using symptom clusters to choose an antidepressant, particularly with regard to anxiety and pain.[17]
Another important factor to consider in treatment choice is tolerability. The most common side effects among second-generation antidepressants include gastrointestinal effects, along with dizziness and sleep disturbance.[17] Sexual dysfunction may affect more than one half of patients receiving antidepressants. Bupropion and vortioxetine[18] are associated with lower rates of sexual dysfunction, whereas paroxetine is associated with higher rates.
Other adverse events to keep in mind when considering specific antidepressants vs comparator drugs include higher risk for weight gain with mirtazapine and paroxetine, higher incidence of diarrhea with sertraline, and increased risk for nausea and vomiting with venlafaxine.[17]
A Step in the Right Direction?
The lack of appropriate biomarkers has always hindered the identification and treatment of depression. Physicians prefer to order tests, interpret the results, and allow objective evidence to guide therapeutic choices. Depression is not so clear-cut. It takes some extra effort, but the benefit of a diligent approach in the diagnosis and management of depression can be outstanding.
Clinicians should familiarize themselves with multiple antidepressants to tailor treatment for individual patients. Treatment should be continued for at least 6 months after initiation, so assessing the side effect profile of antidepressant therapy is a good idea. There appears to be some value in using symptom clusters to predict the response to treatment, but it is far from perfect.
On the basis of the results of the current study, should CRP levels be routinely examined among depressed patients and tricyclic antidepressants prescribed to patients with evidence of inflammation? No and no. The promising results of this study need to be replicated in other trials. The decision to (re)apply tricyclic antidepressants more broadly in the treatment of depression is not to be taken lightly. Higher rates of adverse events with this drug class will result in more treatment discontinuation and nonadherence.
Nonetheless, as the healthcare community continues to wait for a groundbreaking change in depression management, innovative research regarding biomarkers may help to provide truly personalized care for depression.
Medscape Family Medicine © 2014 WebMD, LLC
Cite this: Charles P. Vega. Treating Depression in Primary Care: Are Biomarkers the Key? - Medscape - Nov 06, 2014.
Health Sciences Clinical Professor; Residency Program Director, Department of Family Medicine, UC Irvine School of Medicine, Irvine, California
Disclosure: Charles P. Vega, MD, has disclosed the following financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: McNeil Pharmaceuticals
Manage Email Alerts Manage Email Alerts
Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide
Depression in Docs Leads to Medical Errors and Vice Versa
Q&A: What Are We Doing About the Opioid Crisis?
Diseases & Conditions Depression
Diseases & Conditions Depression and Suicide
20021859039-overview
Diseases & Conditions Screening Tests for Depression
2001http://www.medscape.com/slideshow/2020-lifestyle-burnout-6012460
Depression and Suicide
Screening Tests for Depression
Pediatric Depression
Physician Suicide
Major Depressive Disorder: Disabling and Dangerous
How Is Antidepressant-Associated Sexual Dysfunction Managed?
Fatigue, Distress in Internal Medicine Residents Linked to Self-Perceived Medical Errors
'Convenient' Biomarker May Predict Antidepressant Response
Blood Test for Suicide Risk?
Elevated CRP Linked to Depression, Psychological Distress


text:
After losing job to pandemic, Missouri woman says landlord removed her front door over late rent
Zara Barker/KTVI
Posted: Dec 15, 2020 / 02:22 PM CST | Updated: Dec 15, 2020 / 02:22 PM CST
FENTON, Mo. (KTVI) — A Missouri woman said her landlord took off the front door to her apartment because she was two months late on rent and now an attorney with Legal Services of Eastern Missouri said that violates a state statute.
Hannah McGee said she lost her restaurant job due to COVID-19 and said she is two months late on paying her rent. That totals $1,000 owed to her landlord. She said she's lived in her same Fenton, Missouri apartment for three years without any issues and her mom has rented the apartment next door for the last 13 years.
Families struggle to pay bills during coronavirus pandemic
"He's always been a good landlord. I guess it just took one slip up," McGee said. "I've lived here without a problem, no incidents whatsoever, I've been on time every month, but since COVID happened, I lost my job, I was working in a restaurant."
Since the front door has been removed, McGee has put her closet doors in front of the space where the door used to be to try and trap heat inside.
"At night it gets definitely really cold, it's kind of unbearable without it," she said.
Her four-year-old daughter is spending the night at her grandmother's next door to stay warm at night.
Attorney Rob Swearingen said McGee's story is common. He said his law office is now getting calls at least once a day from tenants who are having their doors or locks taken off, being locked out, or having their utilities shut off.
"We try to call landlords and inform them that they're violating the law by illegally evicting people. You can only be evicted by a court order and with the sheriff present executing an eviction and right now that can't be done in St. Louis City and St. Louis County," Swearingen said. "The landlord needs to realize that the landlord has committed a tort and is liable for anything that happens to this tenant, its more than negligence, its intentional infliction of emotional distress, it's a violation of Missouri statutes and it's unlawful eviction."
Proposed Missouri bill to protect drivers if they hit protestors
When NewsNation affiliate KTVI arrived at the tenant's home Monday afternoon the landlord was there, but would not answer questions before driving off.
"I would never be able to do that to somebody, just make things even harder on them, especially with everything going on," McGee said.
She said it is difficult, but she is trying to keep a smile on her face for her daughter.
"My Christmas tree is right next to my door frame where there's no door, I don't know how we're going to open presents on Christmas like that," she added. "At least we have three walls. All I can do is find the humor in it and try to get by. I mean, a lot of people go through worse."
More Mid-South Stories
Police department fulfills young Arkansas man's wish to experience being a police officer
It was an exciting week for a young man in Arkansas who got his wish fulfilled as he became an honorary police officer.
Mid-South 8 hours ago
7th officer credited for saving lives before Nashville Christmas Day bombing
The brave officers are now known as the Nashville six, but NewsNation affiliate WKRN has since learned there was a 7th hero that day: officer David Snowden.
Mid-South 10 hours ago
Alabama man finds $300K worth of drugs in car bought from government auction
An Alabama family was in for an unwanted surprise when they opened the trunk of their newly purchased car. The deal they got at a government auction in Tennessee was full of heroin.
4-year-old Arkansas boy develops serious condition resulting from COVID-19
A 4-year-old Arkansas boy, who was hospitalized for COVID-19, is now battling a serious condition found in some children after they are exposed to coronavirus.
Elvis Presley's Graceland starting virtual tours
Elvis Presley's Graceland is now offering online tours for fans around the world, including those who can't travel to the Tennessee tourist attraction during the coronavirus pandemic.
Video: Game warden frees two interlocked deer by shooting antlers
Two game wardens with the Kansas Wildlife, Parks & Tourism were able to free two whitetail deer who were locked together.
Johnson & Johnson is on track to roll out its single-shot coronavirus vaccine in March, and expects to have clear data on how effective it is by the end of this month or early February, the U.S. healthcare company's chief scientific officer said.
Coronavirus Vaccine 1 day ago
Dolly Parton statue should be added to state Capitol grounds, Tennessee lawmaker says
A Tennessee state lawmaker introduced a bill Tuesday that would add a statue of Dolly Parton to the Capitol grounds in Nashville.
Mid-South 2 days ago
Arkansas governor on President Trump's impeachment and planned protests
NewsNation spoke with Gov. Asa Hutchinson (R-Arkansas) on Wednesday. He is a Republican and former federal prosecutor.


text:
How Not To Fail At Kickstarter
James Poulos Contributor
Political theory and strategy that works for American humans
For those about to crowdfund....
I have a rock and roll band. It's called Black Hi-Lighter. Right now, we're halfway through a rite of passage: the Kickstarter campaign.
The first rule of how not to fail at Kickstarter is: Please pledge your support!
Or, in other words, start shameless.
Ours is a simple goal: $3500 to put our new record on vinyl, today's platinum standard of musical credibility and relevance. (Plus, it's just prettier to look at and use.) But Kickstarter, of course, lets you set a fundraising goal much, much higher than that. The second rule of how not to fail at Kickstarter is: Learn from the winners.
That's why I've asked two musicians and two filmmakers -- all of whom launched and completed successful, substantial Kickstarter campaigns -- to share their lessons learned. For extra infotainment value, I've broken out their comments into the categories that imbue me with the most dread.
I've Overshared And I Can't Get Up
"Most of your funding will come from your existing crowd," says Kim Boekbinder. That's why, straight out of the gate, you're at automatic risk of oversharing. "It doesn't matter how noble, worthy, or amazing your project is," she says. "It probably won't go viral and no amount of nagging celebrities to tweet about it will help. Use your crowd, even if that's just 50 of your friends for now."
You'll need to keep them amused, and not in a grim way. "The balancing act between going unnoticed and flooding feeds is a tough one," Brendan MacLean cautions, "especially on launch day."
The trick is in the pitch, so finding legitimate reasons to post is vital: celebrate daily milestones, alert people to individual rewards or publicly thank a backer for a donation. Of course the best way to avoid becoming a social media eye-sore is by having others post on your behalf -- get pledgers in the habit of sharing your updates and take the time to personally thank them for that too. Crowdfunding projects run very much like any advertising campaign: too much exposure and people detest you, too little and you're invisible.
According to Braxton Pope, the issue is simple: you have to "try to artfully conceal your flagrant narcissism." In a culture as "self-promotional" as ours," the "true difficulty" is "how you can differentiate your self promotion from everyone else's and make people actually care. The best way to do this," he says, "is to devise a project that has creative merit and to inject some levity into the proceedings."
I'm Panicking Over My Trendline
Because the internet is awesome, it's awesome at telling you what you know you don't want to know. At sites like Kicktraq.com, your Kickstarter fate is plotted out in real time, complete with nerve-wracking trendlines you can use to freak out over how awful your friends are, how nobody understands your genius, and how little access you really have to rich, famous benefactors. "It is very strenuous to reach out to people and hear no most of the time," admits Luciana Faulhaber, "but the one yes makes up for it." The trick is not to lose your cool when your drip feed of yeses momentarily dries up.
"All crowd funding projects run on a "U" shaped graph," Brendan says. "It starts with a bang as your family and friends excitedly pitch in" -- and "as it ends, procrastinators dive in at the last minute to lend a hand." That means you should expect to hit Peak Panic in your campaign's "midsection." Some days," says Brendan, you're "lucky to make $50 and sometimes nothing at all." To cope, he released a halfway mark reward in the form of a new single. "I was able to refresh the message of my campaign," to "prove my project was still buzzing and worth getting behind."
Of course, for those of you with a low enough risk tolerance -- or who have taken on a high enough level of risk -- the waves of panic may be more or less constant. For Braxton, "the stress kicks in once you go live and doesn't really relent until you are basically assured you are going to get to the finish line.' His preferred coping mechanism: "a fully stocked liquor shelf and adequate mixers."
One thing to keep in mind, Kim suggests, is that "there's nothing like the rush of a successful Kickstarter campaign. It feels like winning the lottery, but a lottery you worked for." Channeled into the discipline of engaging your supporters and would-be supporters like the important humans they are, that frantic Kickstarter energy can turn into something constructive. "Make all emails, messages, and phone calls personal," Luciana says; "people are more likely to engage and help when they feel personally accountable." Likewise, make yourself accountable for commensurate gratitude. "You really can't get your project of the ground without their help. Make sure they know that." Locking into a routine encourages a positive feedback loop -- especially for your own benefit, when that mid-stretch lag does arrive:
Be persistent. We are all busy and most people genuinely forget to check the kickstarter page or when you remind them they might not be home so remind them again. But also be mindful of those who choose not to partake. It hurts, specially when you have supported their work buying tickets to their shows, taking your friends to do the same. But in the end people are who they will be all you can do is not hold a grudge and know when your project is funded you'll be happy they are not part of it.
I Failed Before I Even Started
Here's a horrible thought: What if you baked failure into your Kickstarter cake, and no matter how well you execute, you're doomed from the start for some unnoticed reason? It turns out there are some fatal Kickstarter mistakes. And though some might be project-specific, the biggest nonstarter is the simplest of all: presentation.
Give your audience "an inept, dull or shoddy introductory video," Braxton says, and you might as well stop before you start hitting them up for cash. "People underestimate the power of a short entertaining pitch video," Brendan warns. "A long overly earnest speech about how you're 'passionate about music' really puts the audience to sleep. The other thing that will really run your project into the ground is complaining. It's worth remembering how lucky you are to get any money whatsoever. I've seen artists whinge that their fans aren't giving more early in a campaign. That's a real turnoff."
Naturally, the wrong attitude will fail you before you begin -- even if you succeeded once before. "I know people who had successful campaigns," Kim recalls, "who vowed never to crowdfund again because they promised too much, didn't budget costs well, and resented becoming a mail order business rather than an artist."
Post-partum depression? Only, says Braxton, "if you don't make your goal." But what about total exhaustion? That scary morning-after feeling? It's all possible. "Shipping costs way more than you think it does," Kim continues. "Did you budget for shipping supplies? Envelopes? Printer ink? An assistant to help you?" When the fog of fundraising lifts, you don't want to find yourself underequipped on the battlefield.
If you do, you're likely to find yourself too wiped out to compensate. Says Brendan: "the day my campaign ended I feel like I'd passed a kidney stone. After making myself sick worrying about how I was running the campaign I was pretty relieved to see the clock run down to 0:00." A moment's rest is well-earned, but your supporters aren't expecting you to take the first flight to St. Maarten. Post-Kickstarter, Brendan says, "my only concern now is making sure people are confident their money is being well spent." Yep -- more work. Congratulations, you got what you asked for.
And for the musicians out there, the morning after can turn into the rest of your life -- not in a bad way, either. Two years ago, Kim started pre-selling shows on Kickstarter. "There are now several websites that offer that service," she explains, "but at the time I was the first artist to do it." Kim's favorite way to crowdfund is with her monthly subscription service, which delivers the goods to fans who sign up for monthly payments. By monetizing "exclusive access to my creative process," Kim has figured out how to "eat, pay rent," and not "go crazy" -- hooking up her audience with "new songs, demoes, live recordings, webcasts, journals," and more.
"Suddenly having a stable income was life changing," she says. And the whole idea that Kickstarter can supply musicians and other creatives with a stable income? That's pretty life-changing too.
James Poulos
James Poulos writes about political news, focusing on our choices for liberty and our options for reform. He's a columnist at The Daily Beast, the host of the Free Radic...


An award-winning tax firm offering tax preparation services, financial planning, and consultancy to personal and business clients of a variety of sizes. With the company generating a profit margin of 80 percent, this business is expected to see substantial growth, and is a lucrative investment. Buy in, so you can cash out!


text:
Florida should support statehood for Puerto Rico | Column
"Brazen partisanship stands in the way and threatens to deny equality to the U.S. citizens of Puerto Rico," writes attorney Jose Cabrera
The U.S. citizens of Puerto Rico demanded statehood on Election Day, a message that resonates with over 1.2 million Puerto Ricans living in Florida. Facing a yes-or-no vote on statehood, an absolute majority of 52 percent voted "Yes".
Attorney José A. Cabrera, a U.S. Army veteran, is chair of the Puerto Rico Star Project, a nonprofit organization that advocates statehood for Puerto Rico. [ HERIBERTO HERNANDEZ | Courtesy of Jose Cabrera ]
And yet, turning the people's mandate into an admission process remains a challenge. Brazen partisanship stands in the way and threatens to deny equality to the U.S. citizens of Puerto Rico. It doesn't have to be that way.
Puerto Rican statehood should be a bipartisan matter because the islands' political status is an American problem. Over 3 million U.S. citizens, including nearly 90,000 veterans, reside in a territory devoid of basic American rights, such as the right to vote for president and equal treatment under the law.
However, Congress will not act unless stateside Americans demand action from their elected representatives. Florida has led the way in this effort. The state has a large concentration of Puerto Ricans, a population that overwhelmingly supports statehood. These Puerto Ricans have experienced the contrast between having their rights as U.S. citizens denied in Puerto Rico and fully enjoying those rights as residents of a state. That contrast, and the thought of their disenfranchised loved ones back in Puerto Rico, inspire their strong support for equality.
Florida-based Puerto Ricans are also finely attuned to how their elected representatives align themselves with the statehood cause. Politicians on both sides of the aisle have consequently taken proactive stances. Florida's elected representatives know that, instead of overturning the Insular Cases in the U.S. Supreme Court, or amending the Constitution, admitting Puerto Rico is the simplest way of resolving the islands' dilemma.
For the Republicans, Sen. Marco Rubio has long supported statehood, a posture that garnered him a lopsided victory during the 2016 Puerto Rico Republican primary. Sen. Rick Scott also embraced statehood, both as governor and senator. On the Democratic side, Rep. Darren Soto introduced H. Res. 1113 to call on Congress to act if voters chose statehood during the November 3 referendum. Twelve members of Florida's delegation co-sponsored the resolution, including Rep. Stephanie Murphy, who eloquently argued for Congress to respect the will of the people of Puerto Rico.
Although Puerto Rico faces considerable work ahead to achieve statehood, the support of fellow citizens in the mainland will be critical to ensure that the statehood mandate is respected. In this regard, the people of Florida and their elected representatives have shown other states how to work together.
Now the task at hand is to remain steadfast in that endeavor. The people of Puerto Rico are counting on you to continue leading the way.
Attorney José A. Cabrera, a U.S. Army veteran, is chair of the Puerto Rico Star Project, a nonprofit organization that advocates statehood for Puerto Rico.
Up next:Put the brakes on Florida's new toll road project | Letters


LadyBug loves sharing cupcakes with her Daddy...even though she knows she's really not supposed to have them!!
It always tastes better when they give us a lick or two from their own cupcakes, right?!
Yum Yum. Those cupcakes sure look delicious! LadyBug is lucky to have a dad that shares.
Cute cute cute! Yum I want one! Hope you're all having a great Sunday!
Why is it that everything we aren't supposed to have is always so good? A question for both the humans and the pups!
why is it that daddy's always seem to give in to things like this easier than moms do?
Daddys are pushovers! Those cupcakes look yummy!
Oh my gosh, I really want one of those cupcakes right now! You're a lucky dog!
Oh there is nothin better than somethin sweet from the Pawrents fingers!
I would beg too !!
Well I would say that Ladybug has the right idea!


When Cara is made redundant and unable to find another job in journalism, she takes on a seasonal position on a cruise ship with Billie, her best friend's girlfriend. Billie isn't her type at all, but as the two grow closer during their time at sea, Cara finds herself torn between loyalty toward her friend Dan and her growing feelings for the beautiful and flirtatious Billie, who might very well be the best thing that's ever happened to her. What do you do when the only thing you want is the one thing you can't have?
Lily, a heartbroken editor from London, has just learned the hard way that love is unpredictable. After finding her fiancee entangled with another woman, she travels to Bali to recover from her failed relationship. River is a womanizing artist with a troubled past and serious commitment issues. She traded a successful career in L.A. for a quiet, anonymous life in Bali where she works as a tour guide on weekends. After the two meet on an excursion led by River, Lily is shocked to find herself curiously drawn to her new friend. Lily has never been involved with a woman before but she can't seem to get the charming and persuasive blonde out of her head.
Alexis thought her life contained everything she wanted, until her partner of five years drops a bombshell on her. Catherine is an accomplished neurosurgeon looking for a fresh start in a new city. A chance meeting between the two imprints the doctor in Alexis's mind, with thoughts of Catherine pushing to the forefront months after they meet. When life places the pair in the same city, Alexis is unable to deny her attraction to Catherine. As the pair become closer, Alexis finds herself falling for Catherine, despite knowing that her feelings will never be reciprocated.
Sophie Scott is a privileged but hard working London girl who's had just about enough of her mother's obsessive attempts to set her up with an eligible bachelor. She has no interest in dating and has never been in love.
I absolutely loved Beyond the Skyline. The description of Hong Kong is marvellous, I might use this book as a guide if I ever want to visit there again, the chemistry between the main characters is very real. That both women are gorgeous is maybe unrealistic but doesn't hurt the story. I do have a weakness for coming out stories, so also in that way it's just my favourite kind.
The narrator is one of the best I've heard recently. I'm very critical about narrators, but Jessica Jeffries is perfect, at least she is for his book. I didn't have any driving to do and I kept finding moments to get back to this book and listen further.
This was a cute little love story mixed with a tease of coming out. I saw it coming between the two characters, early on of course, it was plain as day! The coming out piece was a little bit down played but I suspect that wasn't the main point so it didn't need to be in the forefront. The characters had plenty of chemistry and and we're very likable. Overall, the book was pretty good, I loved the energy and enthusiasm of the narrator throughout the book. She brought the experience of seeing new places to life, found myself wanting plan my own trip. Def worth the listen/read!
This was a cute story, I probably will not use it as a tour book in Hong Kong as someone wrote, but I enjoyed it. It was well written, I like the characters, the story line was somewhat predictable but most of them are, right?
I loved the narration, Jessica Jeffries did an excellent job, with the accent of Chinese people and any other non English speakers.
just loved this story and the narrator. One of my favorites. I spent time in Hong Kong and it filed me with memories of my time there.
I loved Beyond the Skyline. Sophie and Mel are great characters. This is a workplace romance. The setting in Hong Kong certainly adds spice to the story. Jessica Jeffries does an excellent job with the narration.


text:
Former Unficyp soldiers with Cyprus in their blood
By Annette Chrysostomou November 20, 2016 November 21, 2016 5 41
Winter walking tour of the long-term visitors
By Annette Chrysostomou
First, they came here for soldiering. Now, they come every year for a holiday, a very long holiday indeed.
A group of retired Swedes and Norwegians, many of whom had once served in the UN peacekeeping force in Cyprus (Unficyp), visit Larnaca every winter. Some stay for two months, others up to six months. But altogether they enjoy a very active social life. They play boules three times a week at the beach, organise weekly bus trips to the mountains where they go for walks around the villages, and 35 to 40 play darts at a local pub on Wednesdays.
Much of this is organised by 70-year-old Jan Mernelius who first came to Cyprus when he served in the Swedish UN battalion in Famagusta in 1974 and 1975. Now retired, he has been living in Larnaca for the past five years.
Swedish Unficyp soldiers in 1974
Most of the other retirees stay only over the winter months, but usually there are roughly two groups, those who come from October until November or Christmas, and those who stay between January and April.
"They come and go. I can never be sure who or how many will turn up at the next event," the retired UN veteran said.
He guesses there are around 70 permanent residents and 60 who come and go. "I want more to join," Mernelius explained, "we take care of each other and call each other when we need help."
Those who come for a few months, rent apartments in and around Larnaca.
Larnaca is a popular choice because it is near the airport and the visitors want a lively place. As Mernelius explained the popular summer tourist centres like Ayia Napa and Protaras are almost dead in winter.
"People think we only want the sun. That is not true, we want an adventure, something to do," Mernelius said.
Hence the organised walks and the rest of the activities. Not to forget about the pub, which is the Old Country Pub, complete with a flag of the Swedish UN contingent.
His friend, 76-year-old Ove Kristofferson, is another retired Swedish national. He has spent the last ten winters in Larnaca and agrees on the importance of the shared activities.
Jan Mernelius
"I play tennis twice a week and go to the gym," he said. "On Thursdays we go for walks, and on Wednesdays to the pub."
Would he come here if this support group didn't exist? "Yes, though it wouldn't be the same. The people are nice, and the weather is perfect. In Sweden there is lots of snow in winter. Here [in Larnaca] you can do something every day."
Although not all the long-stay visitors served in Unficyp, many of them did.
In 2014, 125 Swedish UN veterans returned to Cyprus for a reunion, 40 years after they witnessed the invasion of the island in the summer of 1974. Now they are planning another one, on an even bigger scale, in 2019. Already invitations have been sent, 500 cards and 200 text messages, and more than 200 people are expected to attend.
Sweden was one of the first troop-contributing countries to Unficyp. Between 1964 and 1993, a total of 27,981 Swedish military and police officers served in Cyprus.
At its height, the Swedish contingent that took over responsibility for Famagusta district had a strength of 240 military personnel and police officers. Mernelius was based in the Carl Gustav camp in Famagusta which has a long history. Once known as Karaolos camp, it had first been used as a detention camp for Jewish refugees attempting to jump the British blockade of Palestine after WW2. The barracks were not in a particularly good condition in 1974.
"But they were a roof on our heads and we had a church and a hospital," said Mernelius.
Old Country Pub, complete with a flag of the Swedish UN contingent
Before the invasion many of the soldiers were stationed at many hotspots around the island in groups of seven. They would see to it that Greek and Turkish Cypriots would keep the peace. For example, Mernelius recalls, there was a line right in the middle of a road, and members of the UN had to see that the Greek Cypriots didn't cross it from one side and the Turkish Cypriot on the other to prevent potential fights. They would also help the civil police out, for examples when traffic accidents happened.
One of many new duties of the Swedish peacekeepers in the wake of the invasion was to feed and take care of animals at farms, left behind by their fleeing Greek Cypriot owners.
They also set up and manned new observation posts in Famagusta district and acted as mediators between the opposing forces.
During the invasion, Unficyp numbers swelled to over 4,400 with soldiers from Austria, the UK, Canada, Finland, Denmark and Sweden. The force is now around 860 although Sweden no longer takes part.
Cyprus ProblemSwedenUNFICYPShare0
Federal structure would barely change our daily lives
A son's long fight for justice
Annette Chrysostomou
Will new Greek Premier change anything?


The Journal of Information Technology and Laptop Science (JITeCS) is a peer-reviewed open access journal revealed by College of Computer Science, Universitas Brawijaya (UB), Indonesia. Digital life іѕ bоth рublіс and permanent. Evеrуthіng wе dо оnlіnе сrеаtеѕ dіgіtаl footprints that mіgrаtе аnd persist. Sоmеthіng thаt hарреnѕ оn thе spur оf the mоmеnt – a funnу рісturе, аn аngrу put up – саn rеѕurfасе уеаrѕ lаtеr. And if we aren't саrеful, оur rерutаtіоnѕ саn bе harmed. Alѕо, a nasty digital footprint can affect оur future livelihood. Cоllеgеѕ nоw are сhесkіng thе ѕосіаl media роѕtіngѕ оf роtеntіаl students, аnd еmрlоуеrѕ аrе dоіng thе ѕаmе fоr applicants. That's why іt іѕ сruсіаl thаt Dad or mum Pаrtnеrѕhір Sеrvісе (PPS) and fogeys wоrk together tо ensure thаt our ѕtudеntѕ аrе gооd dіgіtаl сіtіzеnѕ.
Mr. Y has created each of the files in the first 9 weeks folder of this staff. By the end of July, his account with the district has been robotically deleted. His workforce comes back to school in August to search out the first 9 weeks folder containing all of their mutual work is completely empty. Seems, Mr. Y owned all the information within regardless that all the group contributed to them. Except the technology department can restore his files and switch possession, they are gone without end.
This post mortem methodology really helps the group celebrate wins of working collectively as workforce, in addition to helps the staff focus on enhancing together, where everyone has a voice. It is also a fantastic indicator for the leadership team on the well being of the core of their business and the place management ought to spend effort. Effort may include replacing core applied sciences if they aren't working, or finding key expertise to enhance data or simply ensure their crew is staffed appropriately.
When it is time to review a document, Voice Dream Writer includes some very thoughtful options for modifying. The app consists of two customizable proof studying modes that use text-to-speech to help with the enhancing process. The first is designed to assist writers edit the content of their document. On this mode words are read back using textual content-to-speech sound natural and easy: as they might when reading a e book with Voice Dream Reader. This allows writers to concentrate on the content material and group of their doc.
At the moment, we require a Knowledge Privacy Addendum (DPA) from every vendor that we contract with to purchase software program. Moreover, we quickly will probably be asking lecturers to watch this video , vet, and checklist free click-through applications that they are utilizing in their lecture rooms. Centralized vetting would imply that this responsibility would shift to district personnel. Recap is a cross platform app that allows academics to create courses and handle college students and set them reflection questions that they'll reply to utilizing video on their laptop webcam or sensible phone from their own residence.