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This year we traveled to Wisconsin for Christmas, and it was the first year in quite a few that my brothers and I and my parents were all in the same place for Christmas! It was so good to see everyone and have that time together <3
My three youngest kiddos helped my mom decorate her tree (she promised to leave off the ornaments so they could assist – and this way there was no pressure for me to get out a tree and decorate, which was great, because I did not want to do it).
The next day was our extended family Christmas party, which included, of course, a game. My family is practically incapable of missing any opportunity for a competitive game.
We went bowling again 🙂
There was early morning art-making…
…and all-day-long snuggling with this girl <3
We've also outgrown my mother's house (by which I mean that me having 4 kids means that I have put us in a position of having outgrown my mother's house), so Danny and Sharon stayed at a hotel nearby, which wasn't always ideal (particularly when Danny came down with pneumonia later in the week and wanted nothing more than to sleep all day), but it did give us an opportunity to go swimming – and all of the kids thought that swimming with uncles who can turn into train engines or throw you high in the air was pretty awesome 🙂
One thing we've done a couple times now that I've loved is had a family book discussion. This year we read and discussed Casey Cep's Furious Hours: Murder, Fraud, and the Last Trial of Harper Lee. I always enjoy the opportunity to discuss books with other people, and our little family holiday book club has been a highlight for me.
I've always liked the idea of matching pajamas but hated the cost, but this year Miranda and I saw $5 matching fleece pants at Target, and that seemed like a good compromise. This was our Christmas morning photo (or 4 that Matt cropped together!).
We did our annual cookie decorating.
And of course there was a significant amount of game playing!
Everyone is really into Legos right now, and Atticus made several creations during our time in Wisconsin.
Miranda has been asking to get her ears pierced for a while now. Our stance on it has been that as long as you are old enough to care for your piercings appropriately, it is your body and your choice. However, as this is a "want" and not a "need," it is something you either have to pay for yourself or request as a gift. Danny and Sharon said they would take Miranda to get her ears pierced for her Christmas present (and doing so in Wisconsin actually requires less documentation and is cheaper – yay!), so one afternoon, Sharon, Miranda, and I went and got her ears pierced. She looks so grown up <3
On our last day, Matt and I took advantage of the Discovery World membership we bought last year, when we realized that it was cheaper to buy an annual membership than to pay for one visit for our family of six! The kids were going a bit stir crazy, so it was nice to get out and give them a chance to run around (and, of course, to learn!).
It was so good to have this time with family and celebrate together, and I'm already looking forward to the next time we can see everyone again – as is Miranda, who has been writing letters to each of our family members, one by one, lobbying for future visits!


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Columbia Bahama II Long Sleeve Sportshirt
Designed specifically for the needs of anglers, this lightweight, durable nylon shirt dries fast, with mesh-lined cape vents at the back shoulder to keep you cool and built-in UV protection. Omni-Shade UPF 30 provides maximum protection for long hours in the sun. Omni-Shade 100% nylon. Hidden vents at shoulders add bonus breathability. Buttons at upper arm to convert to a short sleeve. Quick dry. Relaxed fit. Imported.

subset: commoncrawl


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Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) show cardioprotective and renoprotective properties. cardioprotection and renoprotection for high-risk individuals. = 0.009), and losartan was connected with a 25% reduced occurrence of new-onset diabetes, a substantial cardiovascular risk factor. The cardiovascular protecting LY317615 effects were a lot more impressive inside a subanalysis of 1195 diabetics enrolled in the life span research.15 This analysis established the efficacy of the ARB over that of a -blocker in diabetics for cardiovascular protection, with a member of family threat of 0.76 for the principal endpoint of cardiovascular loss of life, heart stroke, or myocardial infarction, and only losartan (= 0.031). This cardiovascular protecting effect was demonstrated in actually higher risk individuals in the Morbidity and Mortality After Heart stroke, Eprosartan WEIGHED AGAINST Nitrendipine for Supplementary Prevention (MOSES) research. The MOSES research was the first ever to demonstrate superiority of the ARB more than a calcium mineral antagonist for LY317615 supplementary stroke avoidance.16 The ARB, eprosartan, was been shown to be more advanced than nitrendipine for the extra prevention of morbidity and mortality after stroke in 1352 evaluable high-risk hypertensive individuals with a brief history of the cerebral event within the prior 24 months, whilst having comparable reductions in blood circulation pressure. The amalgamated endpoint of mortality and everything cardiovascular and cerebrovascular occasions, including recurrent occasions, was reduced individuals treated with eprosartan versus nitrendipine (13.3 versus 16.7/100 patient-years; = 0.014). It is becoming clear within the last 2 decades that effective blockade from the RAAS confers essential benefits in individuals at risky for coronary disease. Previously, ACE inhibitors had been proven to confer focus on organ safety in individuals with hypertension and diabetes; recently, ARBs in huge medical trials have already been shown to decrease the threat of cardiovascular, renal, and neurological problems. ONTARGET solved the question concerning the potency of an ARB weighed LY317615 against an ACEI in high-risk individuals with coronary disease or diabetes mellitus without center failing,17 although there is still confusion on the medical implications of the results. In ONTARGET, telmisartan was been shown to be equal to ramipril in the occurrence of primary result of loss of life from cardiovascular causes, myocardial infarction, heart stroke, and hospitalization for center failure (Number 1).17 To underscore their similarities, the principal outcome happened in 16.5%, 16.7%, and 16.3% of individuals receiving ramipril alone, telmisartan alone, or their combination, respectively. The supplementary result in ONTARGET, loss of life from cardiovascular causes, myocardial infarction, or stroke, happened in 14.1%, 13.9%, and 14.1% of individuals receiving ramipril alone, LY317615 telmisartan alone, or their combination, respectively. The comparative risk percentage was 1.01 for the principal result and 0.99 for the secondary outcome with telmisartan versus ramipril, recommending similarities in the amount of cardioprotection provided by these providers individually and in combination over ramipril alone.17 Open up in another window Number 1 Assessment of telmisartan and ramipril for the relative threat of the principal and supplementary outcomes of ONTARGET (ONgoing Telmisartan Alone and in conjunction with Ramipril Global Endpoint Trial). The principal composite result was loss of life from cardiovascular causes, myocardial infarction, stroke, or hospitalization for center failure. The primary secondary result was loss of life from cardiovascular causes, myocardial infarction, or heart stroke. The value is perfect for the assessment using the noninferiority margins. Copyright ? 2008. Reproduced with authorization from ONTARGET Researchers; Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in individuals at risky for vascular occasions. 2008;358:1547C1559.17 Furthermore, data from ONTARGET usually do not support the usage of the mix of an ARB plus an ACEI.17 The relative risk ratios of combination therapy weighed against ramipril were 1.00 for the principal outcome and 0.99 for the secondary outcome. Blood circulation pressure reductions were very best in the mixture therapy group, with the average decrease at six weeks of 9.8/6.3 mmHg weighed against 6.4/4.3 mmHg for ramipril alone and 7.4/5.0 mmHg for telmisartan alone. Nevertheless, no relationship of risk decrease was shown in ONTARGET despite lower blood circulation pressure in the mixture group. Mixture therapy was also connected with a higher occurrence of adverse occasions. Just like ONTARGET, the Telmisartan Randomized Evaluation Research in aCE INtolerant topics with coronary disease (TRANSCEND) trial was carried out with a human population of individuals intolerant Rabbit Polyclonal to eNOS (phospho-Ser615) to ACEIs with founded coronary artery, peripheral vascular, or cerebrovascular disease, or diabetes with end-organ.
Month: August 2018
The role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) procedures
The role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) procedures in the management of patients with gastrointestinal stromal tumor (GIST)-induced sarcomatosis that's refractory to tyrosine kinase inhibitors (TKI) isn't well described. for sufferers with disseminated GIST ought to be TKI therapy. Nevertheless, in sufferers with sarcomatosis from GIST, cytoreduction is highly recommended before developing TKI level of resistance. Development on TKI is normally connected with poor final results even after comprehensive cytoreduction. Gastrointestinal stromal tumor (GIST) buy 131438-79-4 gets the highest occurrence and prevalence of gastrointestinal system sarcomas, accounting for about five % of most mesenchymal tumors.1 However the mainstay of GIST treatment continues to be complete surgical resection, the introduction of tyrosine kinase inhibitors (TKIs) in 2002 has transformed GIST from a purely surgical disease to 1 where medical therapy significantly raises success. GISTs may bring about sarcomatosis that's chemotherapy-resistant, leaving individuals with few choices in the pre-TKI period. One medical option that is offered can be cytoreductive medical procedures with warmed intraperitoneal chemotherapy (CRS/HIPEC). This modality posesses long term recovery with morbidity prices approaching 40 %. Therefore, the part of medical procedures for metastatic GIST in the post-TKI period remains questionable.2 Recently, researchers possess described the positive effect of re-section in select individuals with metastatic GIST.3, 4 Frequently these research involve isolated peritoneal or liver metastases.5, 6 Individuals with peritoneal sarcomatosis stand for a little subset of individuals with metastasis and they are rarely analyzed as a distinctive cohort. The principal aim of this informative article was to look for the medical results of CRS/HIPEC methods on individuals with GIST-induced sarcomatosis. The supplementary objective was to define the effect of TKI level of resistance on overall success of individuals treated with CRS/HIPEC. Strategies That is a retrospective evaluation of the prospectively maintained data source of 1070 CRS/HIPEC methods performed from 1992 to 2012. Institutional Review Panel approval was acquired. Data highly relevant to our evaluation included histologic verification of sarcomatosis, demographics, Eastern Cooperative Oncology Group (ECOG) efficiency position, R position of resection, comorbidities, preoperative or postoperative usage of TKIs, level of peritoneal disease, morbidity, mortality, and success. Eligibility requirements for CRS/HIPEC had been histologic analysis of peritoneal dissemination and full recovery from prior systemic chemotherapy or rays remedies, resectable or resected major lesion, debulkable peritoneal disease, no extra-abdominal disease. CRS-HIPEC was carried out as previously referred to by our group.7 The amount of resection was judged from the surgeon and classified the following: R0 for complete macroscopic resection without proof involved margins on final buy 131438-79-4 pathology and R1 for complete macroscopic resection of gross tumor with positive microscopic margins on final pathology. Cytoreductions with residual macroscopic disease had been characterized as R2 and subdivided predicated on how big is residual disease (R2a 5 mm or much less, R2b 2 cm or much less, R2c higher than 2 cm). Chemoperfusion was performed at 40C with 40 mg mitomycin C with or without 10 to 30 mg mitoxantrone for 60 to 120 mins. All data had been gathered prospectively and analyzed retrospectively. Individuals were typically adopted with physical exam and computed tomography imaging every six months. We summarized individual features using means/regular deviations or medians/interquartile range for constant factors and frequencies for categorical factors. These descriptive figures were calculated general, by TKI anytime stage (yes/no), and by TKI preoperative development (yes/no) within TKI anytime point. Significant variations in these organizations were evaluated using Fishers precise check for categorical factors, evaluation of variance for about normal continuous factors, or Kruskal-Wallis check for non-normal constant variables. Time for you to loss of life or censorship was described from the day from the CRS/HIPEC towards the day of loss of life or last follow-up. We approximated median overall success (Operating-system), OS possibility, and 3-yr success possibility using Kaplan-Meier success estimators. To evaluate success with the pre-operative TKI position and TKI anytime point, we produced Kaplan-Meier success curves for every group and examined for significant distinctions in success using the log-rank check. For those sufferers who received several CRS/HIPEC, success was driven from the original method. All hypothesis lab tests performed had been two-sided and examined on the 0.05 significance level; statistical evaluation was performed in SAS Edition 9.3 (SAS Institute, Cary, NC). Outcomes 1000 seventy CRS/HIPEC techniques had EPLG6 been performed from 1992 to 2012, whereas 18 CRS/HIPEC techniques had been buy 131438-79-4 performed in 16 sufferers for GIST-induced sarcomatosis. Clinical features of.
Accumulating evidence shows that cancer could be envisioned like a signaling
Accumulating evidence shows that cancer could be envisioned like a signaling disease, where alterations in the mobile genome influence the expression and/or function of oncogenes and tumour suppressor genes. to hinder multiple, cross-talking pathways involved with growth and success control inside a logical, mechanism-based, style. These concepts could be usefully used, amongst others, to real estate agents that focus on two major sign transduction pathways: the main one initiated by epidermal development element receptor (EGFR) signaling and the main one converging on mitogen-activated proteins kinase (MAPK) activation. Right here we Dabigatran etexilate review the molecular systems of level of sensitivity/level of resistance to EGFR inhibitors, aswell as the explanation for merging them with additional targeted real estate agents, so that they can overcome level of resistance. In the next area of the paper, we review MAPK-targeted real estate agents, concentrating on their restorative potential in hematologic malignancies, and examine the leads for mixtures of MAPK inhibitors with cytotoxic real estate agents or other sign transduction-targeted real estate agents to acquire synergistic anti-tumour results. mutations in NSCLC confer level of resistance to erlotinib and gefitinib and, oddly enough, mutations in EGFR and appear to be mutually special (Pao et al., 2005b). 2.2. Activation of substitute TK receptors that bypass the pathway targeted by the precise agent Tumor cells often concurrently activate TK development element receptors of different family members, such as for example insulin-like growth element receptor-1 (IGF-1R), vascular endothelial development element receptors (VEGFRs), PDGFR (Panel and Jayson, 2005), and c-MET (hepatocyte development factor receptor), resulting in activation of redundant and frequently overlapping sign transduction pathways that effect multiple cell features (Samani et al., 2007; Takahashi et al., 1996; Morgillo and Lee, 2005). These receptors can preserve cell success by changing EGFR function. Specifically, signaling through the IGF-1R can be an essential alternative cell success pathway (Samani et al., 2007), that leads to EGFR inhibitor level of resistance. IGF-IR transduces indicators through insulin receptor substrate-1, which activates the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, and SHC, which activates the Ras/Raf/MAPK pathway. It really is generally decided that IGF-IR activation takes on a key part Itga2b in cell development, establishment and maintenance of a changed phenotype, cell success and differentiation. IGF-R1 and its own ligand insulin-like development element (IGF-1) are overexpressed in a number of malignancies and their signaling pathway can be altered in tumor cells (Nickerson et al., 2001; Samani et al., 2007). For example, GBM cells with obtained level of resistance to the EGFR-TKI AG1478, screen enhanced IGF-IR amounts and suffered signaling through the PI3K-AKT pathway The mixed focusing on of IGF-1R and EGFR significantly improved apoptosis and decreased the intrusive potential of the GBM resistant cells (Chakravarti et al., Dabigatran etexilate 2002). The relationship between IGF-1R activation and obtained level of resistance to EGFR blockade continues to be proven also for breasts and prostate tumor cell lines (Jones et al., 2004). MCF-7 breasts tumor cells with obtained level of resistance to tamoxifen also to gefitinib (MCF-7 TAM/TKI-R) show elevated degrees Dabigatran etexilate of IGF-IR, PKC and AKT, but no detectable basal phospho-EGFR activity. Treatment of the cells with the precise IGF-IR inhibitor AG1024 led to a significant development inhibition and in a lower life expectancy migratory capacity. Likewise, a gefitinib-resistant variant of androgen-independent human being prostate tumor cell range DU145 (DU145/TKI-R) activates improved signaling via the IGF-1R pathway (Jones et al., 2004). Significantly, IGF-1R overexpression inversely correlates with response to anti-HER2 MAb Trastuzumab in breasts tumor cells (Lu et al., 2005). Furthermore, a physical association between HER2 and IGF-IR continues to be within tamoxifen- and gefitinib-resistant MCF-7 cells (Balana et al., 2001). Likewise, a heterodimerization of EGFR and IGFR offers been reported as primary determinant of erlotinib level of resistance in NSCLC cell lines (Morgillo et al., 2006). 2.3. Individual or constitutive activation of intracellular molecular effectors downstream to the prospective proteins Activation of.
Sirtuins certainly are a category of phylogenetically conserved nicotinamide adenine dinucleotide-dependent
Sirtuins certainly are a category of phylogenetically conserved nicotinamide adenine dinucleotide-dependent deacetylases which have a firmly established function in aging. harm, or make cell loss of life, but are seldom tested because of their ability to trigger epigenetic changes, that may impact the behavior of the cell without straight changing 106266-06-2 manufacture the DNA series. Epigenetic changes have grown to be the concentrate of intense study so that they can understand the systems where they function. The Sir2 category of deacetylases is usually one course of proteins that settings some epigenetic procedures and, interestingly, continues to be implicated in increasing the longevity of many organisms. Right here the authors explain a book assay based on candida Sir2p function to display environmental chemicals for his or her capability to alter epigenetic silencing. From testing a relatively few brokers, the authors discovered that dihydrocoumarin, an all natural compound within (nice clover) that's synthetically manufactured and sometimes put into both meals and makeup products, disrupted epigenetic procedures in the candida Dihydrocoumarin 106266-06-2 manufacture also inhibited many human Sir2 family members deacetylases (SIRT1 and SIRT2) and, when put into cells in tradition, improved p53 tumor suppressor 106266-06-2 manufacture proteins acetylation and triggered elevated degrees of apoptosis. Today's study shows that humans face several environmental chemicals which may be categorized as epigenetic toxicants. Intro Members from the silent info regulator 2 category of genes encode extremely conserved nicotinamide adenine dinucleotide (NAD+)-reliant deacetylases within microorganisms from archaebacteria to eukaryotes [1]. In the candida Sir2p is usually a histone deacetylase necessary for heterochromatic silencing at telomeres, ribosomal DNA, and mating type loci [2]. The sirtuin category of deacetylases includes a strongly established part in ageing [3]. 106266-06-2 manufacture Improved activity, mediated either by overexpression or through sirtuin-activating substances, increases durability in [4], [5], and [5,6]. Conversely, deletion decreases life time in by 30% [7], and Sir2p inhibition by nicotinamide mimics this impact [8]. Seven obvious homologs of (SIRT1C7) can be found in human beings, with SIRT1 becoming the presumed Sir2p ortholog because of series similarity [1]. Even though human being sirtuin deacetylases possess a job in heterochromatin changes, they have primarily been recognized to have non-histone proteins focuses on [9]. SIRT1 continues to be recognized to deacetylate p53 [10] and a number of additional proteins associated with the apoptotic response [10C13]. The p53 tumor suppressor proteins is usually also known as the guardian from the genome because of its part in cell routine arrest, senescence, and apoptosis [14]. Lysine acetylation (K320, K373, K382) raises p53 balance [15,16], resulting in the transcriptional activation of DNA restoration, cell routine arrest, and proapoptotic genes. Because SIRT1-mediated p53 deacetylation reverses these results, inhibition of the deacetylation step is usually hypothesized to market p53 balance and boost apoptosis amounts. Apoptosis and p53 106266-06-2 manufacture stabilization accompany SIRT1 down-regulation [17], and SIRT1 inhibition by nicotinamide leads to p53 hyperacetylation pursuing DNA harm [10]. Furthermore, SIRT1?/? cells have already been identified to become more susceptible to eliminating from the genotoxic brokers cisplatin and Rabbit polyclonal to KCNV2 staurosporine [18], indicating that SIRT1 abrogation may enhance p53 function. SIRT1-deficient mice are found to possess developmental problems that tend due to improved tumor suppression with a hyperacetylated and steady p53 [19]. p53 activity seems to control an excellent balance between suitable tumor suppression resulting in malignancy avoidance and stem cell depletion resulting in cells senescence [20,21]. SIRT1 amounts these procedures. The breakthrough that resveratrol, a chemical substance found in burgandy or merlot wine and other food stuffs, increases life time in multiple microorganisms through a system that may involve the activation of Sir2p [4,5] shows that the dietary plan and environment may also.
Some peptide analogs of Ac-CIYKYY (1) were synthesized by functional group
Some peptide analogs of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or introducing conformational constraints, to boost the inhibitory potency against active Src kinase. Ac-CIYKF(4-I)Y (15) exhibited (IC50 = 0.78 M) approximately 510-fold higher inhibitory potency than 1. As a result, the current presence of the 4-nitrophenylalanine or 4-iodophenylalanine at placement 5 is apparently optimal for producing the maximal inhibitory strength. Several factors, such as for example electronic ramifications of the useful groupings, conformation of peptides, and hydrogen bonding, could be involved in producing an optimum inhibition pattern with the peptides. The binding sites of peptides 2 and 15 filled with placement. Alternatively, these useful groups may connect to other useful BMS 378806 groups inside the peptide leading to the change from the conformation from the peptide. Molecular modeling research of energetically reduced structures of just one 1, 4, 18, 20, and 21 demonstrated the current presence of an intramolecular hydrogen bonding from the amino band of the K4 using the useful group in the medial side string of amino acidity residue at placement 5 in these peptides. The hydrogen bonding was disrupted by substitute of hydroxyl group with nitro (2), halogens (13C15), cyano (16), or azide (17), resulted in modification in the conformation from the peptide, and allowed the K4 aspect string amino group to stay free. Therefore, customized conformations and/or bonding connections BMS 378806 with the energetic site may describe the improved inhibitory strength for peptides 2 and 15. Additionally, c-Src can undergo conformational adjustments through the binding procedure to differentiate specific topographies for the interacting aspect chains from the peptide. X-ray crystallographic research of peptides 2 and 15 using the energetic c-Src must properly determine the binding settings of these substances. The system of inhibition by 2 was researched using adjustable concentrations of ATP as well as the inhibitor. The lineweaver story (Shape SCA12 2) demonstrated that substance 2 comes after a incomplete competitive inhibition design against ATP. Open up in another window Shape 2 Design of inhibition of c-Src by substance 2; LineweaverCBurk story of 1/V versus 1/ATP with differing focus of 2 displays incomplete competitive inhibition (Vm = 6.1 0.2 pmol/min, Kilometres = 63.1 4.2 M, Ki = 0.21 0.02 M, R2 = 0.996, AIC value = ?125.1). We've previously shown how the launch of conformational constraints boosts the binding affinities of pTyr-Glu-Glu-Ile (pYEEI), a conformationally versatile molecule, towards the Src SH2 site.18 Conformationally constrained derivatives of C1I2Y3K4Y5Y6 (22C32) had been synthesized (Figure 1) to determine if the presence from the constrained band in the peptide has any impact in improving the inhibitory strength of just one 1 (Desk 2). Desk 2 Inhibitory strength beliefs for the constrained peptide analogs of Ac-CIYKYY (22C32) against energetic Src. = 8.6 Hz), 7.50 (d, 2H, F5, = 8.6 Hz), 7.01 (d, 2H, Y6, = 8.4 Hz), 6.96 (d, 2H, 6.70, Y3, = 8.4 Hz), 6.66 (d, 2H, Y6, = 8.4 Hz), 6.58 (d, 2H, Y3, = 8.4 Hz), 4.70-4.60 (m, 1H, F5, NHC= 7.4 Hz), 0.67 (d, 3H, I2, CHC= 6.7 Hz). Synthesis of conformationally BMS 378806 constrained peptides (22C32) All conformationally constrained peptides had been synthesized with the solid-phase synthesis technique employing Fmoc structured chemistry as referred BMS 378806 to in the overall information section. The formation of conformationally constrained peptide 30 can be explained here on your behalf example. The syntheses of various other conformationally constrained peptides receive in the helping details section. Cys-Ile-cyclo[Phe-Lys]-Tyr-Tyr (Peptide 30): Linking the medial side string BMS 378806 of 4-aminophenylalanine at placement 3 aside string of K4 utilizing a succinic acidity linker (Structure 3) The set up from the linear peptide was performed by Fmoc solid-phase peptide synthesis technique and assembling Fmoc-Tyr(tBu)-OH, Fmoc-Lys(Dde)-OH, Fmoc-Phe(4-NO2)-OH, Fmoc-Ile-OH and Fmoc-Cys(Trt)-OH, respectively, on Fmoc-Tyr(tBu)-Wang resin (100.0 mg, 1.1 mmol/g) to produce 41. After capping with acetic anhydride, the nitro group in 41 was decreased to amino group with SnCl2.2H2O (2.70 g, 14.2 mmol) in DMF (6 mL) at area temperature by shaking for 24 h. The resin was gathered by purification and cleaned successively with DMF (50 mL), MeOH (50 mL), and DCM (50 mL) to cover 42. The free of charge amino band of the side string of phenylalanine at placement 3 was conjugated using the linker from the response with succinic anhydride (400 mg, 4.00 mmol) by shaking for 6 h. The.
The purpose of today's study was to judge the efficacy of
The purpose of today's study was to judge the efficacy of the potassium-competitive acid blocker (P-CAB), vonoprazan, for the maintenance therapy of healed reflux esophagitis (RE). maintenance therapy. The principal endpoint was to look for the percentage of sufferers who exhibited maintenance of healed RE refractory to PPIs pursuing 24 weeks of maintenance therapy with vonoprazan 10 mg once daily. Supplementary endpoints included evaluation from the percentage of sufferers with symptomatic non-relapse at 24 weeks. Maintenance therapy with vonoprazan 10 1092351-67-1 supplier mg once daily avoided relapse of esophageal mucosal breaks in 37/43 (86.0%) sufferers in 24 weeks. Nevertheless, the amount of sufferers with symptomatic relapse was 1 (1.9%) and 4 (7.7%) in 4 and eight weeks, respectively. A complete of 4 sufferers were withdrawn because of reduction to follow-up. By the end from the 24-week maintenance period, the symptomatic non-relapse price for acidity reflux-associated and dysmotility sign FSSG scores had been 86.5 and 80.8%, respectively. Furthermore, the symptomatic non-relapse price for reflux, abdominal discomfort, indigestion, diarrhea, and 1092351-67-1 supplier constipation GSRS ratings at 24 weeks had been 86.5, 80.8, 75.0, 71.2 and 76.9%, respectively. No significant adverse events had been reported through the research. The mean gastrin level was 1,059 pg/ml. To conclude, the outcomes of today's research indicate that vonoprazan 10 mg once daily works well for 24-week maintenance therapy of healed RE refractory to PPIs. disease, novel methods that allow even more sensitive recognition and analysis of GERD, as well as the amendment of endoscopic locating criteria based on the modified LA (LA) classification (2,3). The event of GERD symptoms, including acid reflux and acid reflux disorder, at least one time weekly may considerably influence the grade of existence (QoL) of individuals with GERD (4C7). Therefore, the medical practice recommendations for GERD founded by japan Culture of Gastroenterology emphasize the need for achieving complete quality of symptoms (1). GERD can be categorized into two classes: Non-erosive reflux disease (NERD) and erosive esophagitis (EE) (8). Proton pump inhibitors (PPIs) are suggested as the first-line treatment for GERD because they are powerful inhibitors of gastric acidity secretion (1,4). Nevertheless, a previous research reported that 40C50% of individuals with NERD and 6C15% of these with EE had been refractory to PPIs treatment (9). In a recently available multicenter prospective research from Japan, the endoscopic curing price of standard-dose PPIs was ~70% in individuals with reflux esophagitis (RE) of LA quality C and ~60% in individuals with RE of LA quality D (10). Because of these low 1092351-67-1 supplier curing rates, many individuals receiving the existing standard treatment aren't content with their gastrointestinal QoL (10). Vonoprazan can be a book potassium-competitive acidity blocker (P-CAB), section of a new course of gastric acid-suppressant 1092351-67-1 supplier real estate agents. Just like PPIs, P-CABs inhibit gastric H+,K+-adenosine triphosphatase (11). Nevertheless, unlike PPIs, P-CABs inhibit enzymes inside 1092351-67-1 supplier a K+-competitive and reversible way (11,12). Vonoprazan can be steady in gastric juice, includes a quick actions and its impact lasts for a long period (13C15). Vonoprazan goes through substantial metabolic eradication individually of CYP2C19 polymorphism (15). Consequently, the onset from the acid-inhibitory aftereffect of vonoprazan can be faster than that of esomeprazole in healthful Japanese adult male volunteers using the CYP2C19 intensive metabolizer genotype (15). Inside a stage 3 medical trial, the endoscopic curing price of RE pursuing treatment with vonoprazan 20 mg for eight weeks was 99% (16). Latest studies have exposed that vonoprazan 20 mg works well for most Japanese individuals with RE refractory to PPIs (17C19). Nevertheless, to the very best of our understanding no studies possess evaluated the JAG2 medical worth of maintenance therapy with vonoprazan 10 mg in individuals with RE. The purpose of the present research was to judge the effectiveness of vonoprazan 10 mg for maintenance therapy of healed RE refractory to PPIs. The principal goal was to look for the percentage of individuals who got maintenance of healed RE refractory to PPIs pursuing 24 weeks of maintenance therapy with vonoprazan 10 mg. The supplementary goal was to judge the percentage of individuals with symptomatic non-relapse at 24 weeks. Components and methods Research style This open-label, single-center, potential research was conducted in the Toyama City Medical center (Toyama, Japan) between March 2015 and January 2017.
Transient or reversible proteinCprotein interactions are generally used to make sure
Transient or reversible proteinCprotein interactions are generally used to make sure effective targeting of signaling enzymes with their mobile substrates. field of expertise, osteoclast differentiation, cardiac valve advancement, and myocardial hypertrophy (29C32). The traditional method of preventing calcineurin-NFAT signaling is certainly to use the immunosuppressive substances cyclosporin A (CsA) and FK506, which, by means of CFD1 CsACcyclophilin or FK506CFKBP12 complexes, inhibit the enzymatic activity of calcineurin toward all its physiological substrates (33). Nevertheless, calcineurin employs a variety of targeting systems (1, 34C43) offering conceptually novel opportunities for disrupting calcineurin-substrate signaling. Specifically, a proteinCprotein relationship of calcineurin with NFAT-family protein controls the performance of NFAT dephosphorylation and in cells (1, 16, 44, 45). Right here, we recognize inhibitors of calcineurin-NFAT signaling that action ABT-492 as of this proteinCprotein get in touch with rather than on the calcineurin catalytic site. Components and Strategies Fluorescence Polarization Assay. Fluorescence measurements had been made on examples arrayed in 384-well plates through the use of an Analyst dish reader (Molecular Gadgets) to monitor the relationship ABT-492 between your catalytic area of individual calcineurin A (16) and an Oregon Green-labeled VIVIT peptide (OG-VIVIT). Find and and and data not really proven). We term these substances inhibitors of NFAT-calcineurin association (INCA). Three substances, INCA-1, INCA-2, and INCA-6, displaced VIVIT totally from calcineurin at low micromolar concentrations (Fig. 1and data not really proven). At least for INCA-5, INCA-7, INCA-12, and INCA-19, the plateau had not been due to limited aqueous solubility (data not really proven). Two plausible physical explanations are that inhibitors in the next group only partly occlude the VIVIT binding site, or these inhibitors bind to a close by site and alter the geometry from the VIVIT binding site. Additional analysis centered on INCA-1, INCA-2, and INCA-6 for their high affinities and their capability to displace the fluorescent probe totally from its binding site. To get insight in to the structure-activity interactions of ABT-492 INCA substances, we examined several structural analogues of the substances in competitive binding tests (Fig. 2). Oftentimes, the inhibitory performance was just marginally suffering from conservative adjustments in band substituents. Nevertheless, certain changes triggered moderate to dramatic deficits of potency. For instance, expansion from the band program of INCA-1 (INCA-1F), or reduced amount of the vicinal keto sets of INCA-1 to hydroxyl groupings or their substitute by halogen substituents (not really shown), led to inactive substances. Introduction of large substituents at R1 in INCA-2 (INCA-2L and INCA-2M) or of Cl at R5 (INCA-2F and INCA-2G) was harmful to binding. Total reduced amount of the quinonimine of INCA-2 (not really ABT-492 shown), reduced amount of the imino linkage with launch of the alkyl ether at R3 (INCA-2H ABT-492 and INCA-2K), or reduced amount of INCA-6 towards the hydroquinone or its dimethoxy derivative (INCA-6A and INCA-6B) triggered a pronounced reduction in or lack of inhibitory activity. Extension from the INCA-6 quinone band to a naphthoquinone (INCA-6C) abolished activity. Open up in another screen Fig. 2. Structure-activity romantic relationships for three groups of INCA substances. INCA-1 ((), (), and () positions of R2 in the current presence of 0 M (higher track) or 20 M (lower track) calcineurin. (in rather than proven). Pretreatment with INCA-6 led to a concentration-dependent blockade of NFAT dephosphorylation that was incomplete with 10 M INCA-6, almost filled with 20 M INCA-6, and total with 40 M INCA-6 (Fig. 4in and and in cells. The INCA substances we have discovered interfere selectively using the connections between calcineurin and its own substrate NFAT without stopping dephosphorylation of various other substrates. This substrate-selective enzyme inhibition represents a conceptual and useful progress over inhibition with CsA or FK506, which indiscriminately stop all signaling downstream of calcineurin. Current biochemical methods are increasingly effective at pinpointing the proteinCprotein connections that route intracellular signaling, and significant effort has been directed toward making extensive maps of proteinCprotein connections.
To be able to identify brand-new materials to take care of
To be able to identify brand-new materials to take care of Chagas disease through the severe phase with higher activity and lower toxicity compared to the reference drug benznidazole (Bz), two hydroxyphthalazine derivative chemical substances were ready and their trypanocidal effects against were evaluated by light microscopy through the dedication of IC50 values. inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity alongside the modest charges for the beginning components render this substance a proper molecule for the introduction of an inexpensive anti-Chagas agent. contamination is definately not innocuous, as around 30C40% of contaminated people develop debilitating and chronic disease, which contamination makes up about 20,000C50,000 fatalities each year (Tarleton and Curran, 2012). Presently, the available medicines used for the treating this contamination, Benznidazole (Bz) or nifurtimox, display limited restorative potential and so are associated with severe side effects, such as for example pores and skin rashes, leucopoenia, neurotoxicity, fever, articular and muscular discomfort, peripheral neuropathy, lymphadenopathy, agranulocytosis, and thrombocytopenic purpura (Wilkinson et?al., 2008; Urbina, 2010). Therefore, there can be an urgent dependence on the introduction of fresh anti-trypanosomal brokers with lower toxicity and higher activity, specifically for 64043-42-1 manufacture the chronic stage of the condition. To day, no vaccine continues to be created against (Dumonteil, 2009). Consequently, the seek out fresh focuses on for chemotherapy and vaccines is usually a major problem. Among the focuses on, the parasite antioxidant program offers attracted attention because of its uniqueness in the trypanosomatids. Considering this dependence on fresh drugs to fight parasites and taking into consideration the earlier experience our group offers with this sort of chemical substance constructions, the imidazole-based alkylaminophthalazine derivatives (Snchez-Moreno et?al., 2012). For the reason that event, we discovered that the monoalkylaminophthalazine had been the more vigorous constructions against the severe stage of Chagas disease and we also discovered that these were great inhibitors from the parasite particular enzyme Fe-SOD. Therefore, in today's function we considered learning the experience of two hydroxyphthalazine derivatives from the previous chosen compounds. In this specific, these were chemically change to add a hydroxyl group in the primary ring, this changes functionalized the molecule raising its solubility and in addition providing the molecule a less strenuous ability to potential modifications and intro of fresh groups. These substances are very interesting since their synthesis begins form inexpensive substrates as well as the procedures aren't Rabbit polyclonal to AnnexinVI very complicated generally in most from the cases. With this 64043-42-1 manufacture function, their anti-proliferative activity and unspecific mammalian cytotoxicity in the varieties considered had been evaluated activity 64043-42-1 manufacture demonstrated remarkable effects had been tested SN3 stress of IRHOD/CO/2008/SN3 was isolated from home that was gathered by centrifugation at 7000?g for 10?min?at 10?C according to (Cardoso and Soares, 2010). 2.4. Cell tradition and cytotoxicity assessments Vero cells (Flow) had been produced in RPMI and MEM (Gibco), supplemented with 10% iFBS and the task followed was as with Magn et?al. (2005). 2.5. activity assays, extracellular forms 2.5.1. Epimastigotes assay epimastigotes had been gathered in the exponential development stage and distributed in tradition trays (with 24 wells) at your final focus of 5??104 parasites/well. The consequences around the parasite development had been tested regarding to Olmo et?al. (2013). 2.5.2. Bloodstream trypomastigote forms assay Substances 1 and 2 had been also examined in bloodstream trypomastigotes of had been used seven days after disease. Blood was attained by cardiac puncture using 3.8% sodium citrate as an anticoagulant within a 7:3 blood:anticoagulant proportion. The parasitaemia in the contaminated mice was about 1??105 parasites/mL. The substances had been diluted in phosphate-buffered saline option (PBS) to provide a final focus 10, 25, and 50?M for every item. Aliquots (20?L) of every solution were mixed in lifestyle trays (96 wells) with 55?L of infected bloodstream containing the parasites in a focus of around 1??106 parasites/mL. Contaminated bloodstream with PBS, at the same concentrations as 64043-42-1 manufacture the merchandise, was utilized as control. The plates had been shaken for 10?min?at area temperature and held at 4?C for 24?h. Each option was analyzed microscopically (Olympus CX41) for parasite keeping track of using the Neubauer haemocytometric chamber (a dilution of just one 1:100 in PBS was essential to enter the.
Background The quantity of inosine monophosphate dehydrogenase (IMPDH), a pivotal enzyme
Background The quantity of inosine monophosphate dehydrogenase (IMPDH), a pivotal enzyme for the biosynthesis from the guanosine tri-phosphate (GTP), is generally increased in tumor cells. apoptotic-resistant tumor cells. Launch An increase price in malignancies after body organ transplantation may be the toll to cover allograft long-term success as well as the post-transplant lymphoproliferation disorders (PTLD) represent the main reason behind cancer-related mortality in kidney transplant recipients [1]. Mycophenolate mofetil (MMF) can be an immunosuppressive agent trusted in transplantation the energetic compound which, mycophenolic acidity (MPA), depletes the intracellular pool of GTP through the inhibition from the inosine monophosphate dehydrogenase (IMPDH). IMPDH is SVIL available often over-expressed in tumor cells, rendering it an attractive focus on for the era of anti-tumoral agencies [2]. Recently it's been noticed a propensity toward a lesser threat of malignancy in the MMF versus non-MMF provided transplanted sufferers [3] and MPA was endowed with an antitumoral actions within an experimental within a tumor development model [4]. Cell loss of life plays an important function in the homeostasis of tissue and organs and enables the reduction of contaminated or changed cells. Up to now, three types of main cell death have already been defined: apoptotis (type I), autophagic cell loss of life (type II) and necrosis (type III) [5]. Level of resistance to apoptosis takes place during tumorigenesis and points out tumor relapse pursuing chemotherapeutic treatment. To evade apoptosis, tumor cells make use of various mechanisms, several which have not really however been characterized. For example, chronic myeloid leukemia (CML) is certainly seen as a the expression of the chimeric BCR-ABL oncoprotein in hematopoietic precursor cells [6] which behaves being a potent inhibitor of apoptosis [7]. Cancers cells from Chronic Lymphocytic Leukemia (CLL) may also be reported to show a common default in apoptosis [8]. Furthermore, 80% to 90% of the reduced quality follicular non-Hodgkin lymphomas withstand to apoptosis through the over-expression of Bcl-2 a powerful inhibitor from the mitochondrion-dependent apoptotic indication [9]. Cdc42 is certainly a 1058137-23-7 key aspect linking intracellular and extracellular indicators 1058137-23-7 to the business from the actin cytoskeleton network [10]. This little GTPase is one of the Rho-GTPase family members. Herein, we confirmed the pivotal function of Cdc42 to transmit the MPA-mediated necrotic indication. Furthermore, we explored whether this recently characterized necrotic indication distributed common signaling hubs with several apoptotic pathways by evaluating the cytotoxic actions of MPA on different tumor cells exhibiting level of resistance to apoptosis. Components and Strategies Ethics declaration All clinical analysis has been carried out based on the concepts indicated in the Declaration of Helsinki. Bloodstream was sampled from individuals identified as having B-CLL after created consent was from every individual. This research was authorized by institutional review table at the Center Hospitalier Universitaire de Bordeaux. Individuals All CLL individuals had been Binet stage 1058137-23-7 A. Using Ficoll parting and removal of monocytes by adherence, the purified B-lymphocytes ( 85% from the isolated cells had been CD19+Compact disc5+ B lymphocytes) had been maintained inside a RPMI moderate supplemented with 8% human being serum. Cells The lymphoblastoid B-cell lines Dab-1, the leukemic T-cell lines CEM and Jurkat as well as the chemotherapy-resistant cells had been grown up in RPMI 1640 supplemented with 8% v/v heat-inactivated FCS and 2 mM L-glutamine at 37C within a humidified atmosphere filled with 5% CO2. PBLs (peripheral bloodstream lymphocytes) from healthful donors had been isolated 1058137-23-7 by Ficoll gradient centrifugation just as defined previously [11]. Doxorubicin-resistant Jurkat and CEM cells had been produced by treatment with stepwise upsurge in the focus of doxorubicin and clones had been isolated with the restricting dilution method. Era of Bcl-2 over-expressing Jurkat cells was defined somewhere else [12]. Reagents Guanosine, adenosine, ribavirin, mycophenolic acidity, latrunculin A and cytochalasin D had been bought from Sigma (St Louis, MO, USA). Soluble Compact disc95L was produced in the lab [13]. Nilotinib (AMN-107) was attained by Dr Mahon F.X. from Novartis Pharma AG. The anti-Bcl-2 mAb as well as the anti-CD95 mAb (clone DX2) had been bought from Pharmingen (BD Biosciences, NORTH PARK, CA, USA). Killer Path.
UDP-glucuronosyltransferase (UGT) isozymes catalyze cleansing of numerous chemical substance toxins within
UDP-glucuronosyltransferase (UGT) isozymes catalyze cleansing of numerous chemical substance toxins within our daily diet plan and environment by conjugation to glucuronic acidity. protein reside within 11.4 ? of every other. Furthermore, mutation of three PKC sites in each UGT isozyme showed that T73A/G and T202A/G triggered null activity, whereas S432G-UGT1A7 triggered a major change of its pH-8.5 optimum to 6.4 with new substrate selections, including 17-estradiol. S432G-UGT1A10 exhibited a pH change without substrate modifications. PKC participation was confirmed with the demo that PKC overexpression improved activity of UGT1A7 however, not of its S432 mutant as well as the transformation of 17-[14C]estradiol by S432G-UGT1A7 however, not by UGT1A7. In keeping with these observations, treatment of UGT1A7-transfected cells with PKC-specific inhibitor peptide or general PKC inhibitors elevated 17-estradiol catalysis between 5- and 11-flip, with parallel reduces in phosphoserine-432. Right here, we survey a system regarding PKC-mediated phosphorylation of UGT in a way that phosphoserine/threonine regulates substrate specificity in response to chemical substance exposures, which perhaps confers survival advantage. genes result in lethal hyperbilirubinemic Crigler-Najjar disease (3) also to dangerous tissue degrees of the widely used analgesic acetaminophen (Tylenol) in rats (4). The actual fact a 97-59-6 IC50 limited variety of UGT isozymes facilitate excretion of the multitude of structurally different chemical substances suggests a system progressed to confer versatility with an isozyme to metabolicly process multiple poisons. Because UGTs are destined to membranes from the endoplasmic reticulum (ER) that trigger difficulties connected with purification and structural characterization, the molecular system controlling detoxification offers, until now, continued to be unresolved. Following the fast down-regulation of UGT activity in human being digestive tract cells treated with the normal condiment curcumin and calphostin-C (5, 6), referred to as an over-all kinase (7) and PKC inhibitor (8), respectively, we wanted to determine whether: (Glucuronidation Using Different Acceptor Substrates. The 97-59-6 IC50 glucuronidation assay, referred to in refs. 6 and 9, utilized 100 g of mobile proteins. Buffers for the pH curves and item control and quantitation are referred to in refs. 9 and 10. Response mixtures had been incubated for 2-4 h at 37C (5). Traditional western Blot Evaluation of UGT-Transfected COS-1 Cells. All transfections utilized pSVL-based UGTcDNAs in COS-1 cells, that have been incubated for 72 h; cells had been incubated for 60 h for UGT radiolabeling as well as the PKC-overexpression research. Cells had been neglected or treated with curcumin or calphostin-C; similar cellular proteins was solved in SDS-10%/Web page and Western-blotted with anti-UGT1 (6). All tests showing PKC proteins, except the cross-linking test, had been immunocomplexed with anti-UGT (common end) and stuck with protein-A-Sepharose (coimmunoprecipitation) before Traditional western blotting with different antibodies. To look for the phosphorylation position of placement 432 in UGT1A7, UGT1A10, and their mutants, 97-59-6 IC50 microsomes had been ready from transfected COS-1, solubilized, and immunocomplexed with anti-UGT (6). Duplicate examples had been solved by SDS/12% Web page and Western-blotted with anti-UGT1 and anti-phosphoserine (4A9, Calbiochem). Membranes had been obstructed with 5% BSA/0.1% Tween 20 in 25 mM Tris/137 mM NaCl, pH 7.5 (TBS), washed in TBS-Tween 20, and subjected to antibody-horseradish peroxidase conjugate for visualization (6). After treatment of UGT1A7-transfected cells with PKC-specific inhibitor peptide or general PKC inhibitors, cells had been cross-linked with 11.4-? spacer-arm disuccinimidyl suberate (DSS) (Pierce), based on Rabbit Polyclonal to CAMKK2 the manufacturer's process. Cells had been solubilized and solved in 4-15% gradient SDS/Web page before Traditional western blotting as defined above. Labeling of UGTs with [33P]Orthophosphate. Sixty hours after transfection with UGT1A7, UGT1A10, or their triple PKC-sites mutants, cells had been conditioned (6) before contact with 5.0 mCi (1 Ci = 37 GBq) of [33P]orthophosphate per ml of medium for 8 h 97-59-6 IC50 with or without calphostin-C within the last hour. Equivalent solubilized cellular proteins (11, 12) was immunocomplexed with anti-UGT to create duplicate gels, prepared, and solved in SDS/Web page. One gel was Western-blotted with anti-UGT (12); the various other was set and subjected to x-ray film (6). Parallel unlabeled civilizations had been examined for glucuronidation. Inhibition of UGT in LS180 and UGT-Transfected COS-1 Cells Treated with PKC-Specific Translocation-Inhibitor Peptide. Confluent LS180 or UGT1A7-transfected cells had been treated with Antennapedia-conjugated PKC-specific peptide (KAI Pharmaceuticals, South SAN FRANCISCO 97-59-6 IC50 BAY AREA, CA) produced from the unique area V1 of PKC, its scrambled control,.


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Between this, White Denim's "I Start To Run" and Yeasayer's "Ambling Alp" videos, we are not going anywhere near Arizona in the foreseeable future. Some of us have family there, but it looks like a meth Terrordome in some of this footage. Oh wait, someone just informed us that these videos are not real. Sorry AZ, you remain totally sane. But "Marlene" is crazy and will be on Lightspeed's new album, Life Is Sweet! Nice To Meet You, come next February.
December 03, 2009


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In the real estate sector, perhaps more than any other, one of the best marketing actions you can perform is leveraging your existing Customer Relationship. Having loyal customers and strong relationships is essential for boosting your sales and lead generation. But how can this be achieved?
Optimise your Customer Relationship
1- Work in a structured way, and store all your data in the same place
Having multiple sources of leads is both a blessing and a curse. The entire real estate system is based on potential customers being able to get in touch easily with real estate agents in charge of selling or renting properties (houses, apartments, offices, boats, etc.). Of course, they do this through different channels. One of the most efficient ways to consolidate all this data in one place, and to be able to access it from anywhere, at any time, whether in the office or on the go via a smartphone or a tablet, is to have a CRM solution for real estate. How many potential customers did you miss simply by not answering them in time, or by forgetting their search criteria? The answer to this problem is a CRM solution!
2- Stay in touch with your customers
Smooth and fluid communication is the key to a good Customer Relationship. Even when your buyers or tenants have found the property of their dreams, keep in touch with them. Of course, do not bombard them with promotional emails. Rather send them personalized messages every now and again. Something along the lines of: "Hi Peter, it's already been a year since you got the keys to your house. How are those barbecues going?". This way, the customer will remember you and, in due course, will contact you again to buy a larger house, recommend you to a friend, etc. It's a great way to improve customer experience, while building customer loyalty.
Save time and focus on your customers
3- Automate tasks and processes
By using a CRM solution for real estate, you can easily automate certain commercial, administrative and financial tasks, and share news with the entire network of agents, all with just a click! You can also set up automatic notifications whenever there are changes to your ads. Has the price of a house gone down? An automatic email is sent to customers who are looking for this type of property. Convenient, responsive and very business-oriented.
4- Be reactive, optimise your request management
Habitat du Nord, one of the major players of social housing in France, uses an Efficy CRM in a powerful way. It is used by their Customer Service department to centralise all customer requests, whether commercial, technical or social. It also enables the company to manage their dealings with suppliers and improve relations with tenants. What's more, Habitat du Nord's CRM solution is interfaced via sensors with connected objects (elevators or collective heating), and so provides real-time information should a problem arise.
5- Communicate with your teams
It is easy to feel overwhelmed by marketing information, customer data, multiple promotions, mass email campaigns, price changes and all the other aspects involved in real estate. With a CRM solution, your teams can work from a unified and centralized information system, and in real time.
CRM: a must for real estate!
Of course, there are many other advantages to using a CRM solution for real estate that we would be happy to present to you (get your demo!). By way of conclusion, here's what a real estate agent working with a CRM solution thinks of it: "It's pure gold for your Customer Relationship".
Learn more:
CRM meaning. What is CRM?
Increase Your Customer Retention with a CRM
The 6 customer service techniques that make for happy customers


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Pet Friendly Indoor Plants
Browse our range of Pet Friendly Indoor Plants. These lush indoor plants are safe for your beloved pets. Each an every one of them effortlessly enriches rooms with exotic and modern style, all while cleaning the air you breathe and fulfilling your body and mind. Watching them grow is an absolute treat, we promise you won't regret buying one.
Buy Plants that are Friendly to your Pets
We understand that nothing can come between you and your pets, so we made a range of Pet Friendly Plants for you to enjoy. These exotic indoor plants are superb for ornamentation, turning drab spaces into urban jungles and refreshing the air by removing harmful toxins. Breathe new life into your home with this delightful range.
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Caring for our Indoor Plants is easy. Simply place them in a room without central heating and make sure they get their preferred light level. Let the top 1 inch of soil dry between waterings, mist the leaves every so often, and make sure the soil isn't waterlogged.
Order our Pet Friendly Plants now. You can even add a personalised card if you're sending it as a gift. We'll handle the gift-wrapping and delivery.


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European Broadcasting Union Future Leaders Programme, Virtual, April 2020
INMA Virtual World Congress, May 2020
Google News Labs Argentina Webinar, June 2020 (virtual)
European Media Management Association 'EMMA Talk', June 2020 (virtual)
Hamburg Media School Digital Journalism Fellowship, June 2020 (virtual)
Newsrewired, London, June 2020 (virtual)
Forum Journalism and Media, Vienna, September 2020 (virtual)
DPG Media Campusfest, Antwerp, September 2020
BDVZ German Publishers Association Annual Conference, September 2020 (virtual)
FIPP Virtual World Congress, September 2020
Executive School, University of St Gallen, Compliance Management Day, October 2020 (virtual)
EBU New Radio Radio Day, October 2020 (virtual)
IMNA Webinar, November 2020 (virtual)
Future Media Conference, Polish Press Agency, Warsaw, December 2020 (virtual)
BBC Product Group, Salford, February 2019
SXSW, Austin Texas, March 2019
CEO and Editor in Chief Forum, Oxford, April 2019
Perugia Journalism Festival, Italy, April 2019
PPA Festival for Magazine Media, London, May 2019
Austria Newspaper Association, June. 2019
PSI Public Service Broadcasters International Conference, Helsinki, September 2019
Public Service Heads of News Forum, Oxford 2019
European Broadcasting Union Radio Days, Rome, October 2019
Leading Newsroom Change, Reuters Institute, Oxford, November 2019
Society of Editors Conference, London, 2019
Media Perspectives Amsterdam, November 2018
Digital Editors Network Leadership Event, BBC London, November 2018
Helsinki Media Day, Finland, November 2018
Leading Newsroom Change, Reuters Institute Oxford University, November 2018
Korean Press Foundation Journalism Conference, Seoul, October 2018
'Managing Transformation' Media Innovation Day, Vienna, October 2018
Public Service News Forum, Reuters Institute Oxford University, September 2018
Launch of UK Government and Communication Service 'Accelerate' Digital Transformation, 10 Downing Street, London, September 2018
INMA World Congress of News Media, Washington DC, June 4-5, 2018
Norwegian Media Industry and Association of Norwegian Editors, Bergen, 2 May, 2018
Finnish Conference of Media and Communication Research, Finland, April 27, 2018
CEO and Editor in Chief Forum, Reuters Institute, Oxford University, 20 April, 2018
Perugia Journalism Festival, Perugia, 11-15 April, 2018
Global Editors' Network Masterclass, Lisbon, 12 March, 2018
Oxford Perspectives, Reuters Institute, Oxford University, 21-25 February, 2018
EBU Digital Transition Workshop, European Broadcasting Union, Brussels, 5 February, 2018
'Envisioning the Newsroom in 2020'. Oxford Perspectives, Reuters Institute, Oxford, 24 November 2017.
'Going Digital. A Roadmap for Organisational Transformation'. Launch of Reuters Institute, Oxford University and Google Report. London. 23 November 2017.
'Digital Transformation. The Organisational Challenges'. In-company presentation at NRK. Oslo, 13 September 2017.
FIPP World Congress. London, 9-11 October, 2017.
Bonnier Grid. Stockholm, 4-5 August, 2017.
GEN (Global Editors Network) Summit. Vienna, 21-23 June, 2017.
Perspectives on Media Innovation Conference. Elche, Spain, 9 June, 2017.
Media24 Leadership Event. Cape Town, 4-5 May, 2017.
FIPP Digital Innovators Summit. Berlin, 20-21 March, 2017.
'Leadership Priorities for Innovation'. Oxford Editor-in-Chief and CEO Forum, Oxford, April 2016.
'How Pureplays Innovate'. Digital Innovators' Summit Berlin, 21/22 March 2016
'Mobile News Summit'. WAN IFRA. Chair and moderation. Hamburg 6 October 2015
'Leadership and Innovation'. Public Broadcasters International Conference Munich 2015. Panel.
'How not to be Disrupted'. Prisa Group Conference on 'Digital Transformation in the Media Sector'. Madrid, July 2015.
'Leading in a Disrupted Industry'. FIPP Worldwide Magazine Media Association Executive Programme. Said Business School, Oxford University, July 2015 (and 2014).
'The Good, the Bad and The Ugly – What does the Future hold for the Media?'. Keynote at Digital Disruption and the Media Conference. Royal Library, Stockholm, June 2015.
'Innovation in Digital News – Why are some digital news organisations more successful than others?' Oxford Editor-in-Chief and CEO Forum, Oxford, April 2015.
'Digital Media Strategies' Two-Day Conference. Chair, London, March 2015.
'Innovation in News Organisations'. Nordic PSB Executive Seminar on 'The New News Environment', Reuters Institute, Oxford University, February 2015.


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Students, Athletes, Parents and Coaches,
It is another year in the books for Delta's Lacrosse academy and what a year it has been. We have seen many changes in the structure, location and activity of our academy this year so, for posterity's sake, let us recount the past ten months: first, we started our year on the field at Dougald Morrison where we rehearsed some of our fundamental skills, then we competed at our Annual tournament on the island, we lived the last few months of Sportstown as it closed down and moved to learn about the fundamentals of weight lifting in Delta's gym. Last, we even had the opportunity to get in the box and start rehearsing some of our box lacrosse skills for this year's season.
Indeed, it has been a long ten months that has tested our athletes' ability, fitness, resolve and resiliency and as coaches, we are pleased to see growth in all of these areas. Through it all, however, there have been a few stand-out athletes that, in the coaches opinions, have continued push themselves to "be better" from September through to June. So, without further ado, I present to you the Delta Lacrosse Academy's Athlete of the Year:
Anneke Cunningham
As a grade eight student, Anneke surprised the coaching staff this year with her tenacity. Anneke has been a relentless competitor all year. She has taken every opportunity to make herself better in each drill and she has learned from her mistakes to make several huge improvements in her skills.
But it is not her tenacity or her overall improvement that have lead the coaching staff to this conclusion. What make Anneke one of the Academy's Athletes of the Year is her winning attitude. Anneke will work for a win. She does not give up, does not shy away, and will not back down from a challenge. Anneke is the type of Athlete that all coaches want on their teams because she demands more of herself than she ever asks of anybody else. She is a team player whose primary focus is success and it is obvious for those that play and work with her that failure is not an option. Excellent work Anneke.
Jared Moloci
Known to his teammates as Molōsh, this smiley grade 10 kid has been a pillar of commitment from the first week of September through to last week. Jared has been one of the Academy's most focused, consistent and durable athletes. He is consistently the person that the coaches can count on to give his best effort and he is consistently the athlete that pushes his teammates to "be better."
As coaches, it is sometimes hard for us believe that Molōsh is a student in grade ten. Sometimes his calm collected demeanor is more befitting of a college student. What's more, his work ethic is reflective of a man driven toward that college atmosphere. Molōsh is on the field before most of his teammates, and is leaving the field long after the bus has departed. He is one of our Athletes of the year because he is always trying to improve his skill through individual practice and, in drills and games, is regularly the top competitor on the floor. When it comes to Lacrosse, it is safe to say that Jared Moloci lives the mantra "be better." All the coaches agree that it was a privilege working with you Jared.
Student athletes, thank you all for an excellent school year. We look forward to working with many of you next year.
To our graduating players, Congratulations.
Tristan Butler, Kyle Durec, Cody Hoegg, Victor Robichaud and Curtis Tyson, may your journey through life find you fulfilled and may your celebrations to come be joyful and safe.
Coach Campbell
Coach Neumann &
Coach Hannah


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Laptop Repair – Troubleshooting and Maintenance
Whether you have a Toshiba, an Apple, or any other brand name of the laptop, it is in your best interest to have laptop repair Toronto services available when you need them. Your local One Stop Shop for all kinds of Laptop Repair Toronto/ GTA.
Some of the most common repairs they may need are laptop battery replacement, laptop screen repair, and laptop keyboard repair. While some laptops can typically be repaired fairly easily, other laptops require extensive technical skill and experience.
One of the most popular types of laptop repair Toronto companies can provide is laptop keyboard repair. If your laptop has become slightly unstable while in use, or you find that the screen is coming off at an alarming rate, then your laptop may require a laptop memory upgrade. This upgrade will allow your laptop to work much faster and provide you with enhanced performance. In addition, your laptop may also need to have a laptop battery replacement.
Sometimes, your laptop will experience an unfortunate accident. It may be dropped, stolen, or otherwise damaged, and now you need to determine how you're going to fix your laptop issues. Perhaps your laptop needs a simple memory upgrade, or maybe you've completely lost your monitor. No matter what happened to your laptop, there is a Toronto computer repair company that will provide you with the service you need.
One of the most frustrating laptop problems that a laptop repair company in Toronto can help with is laptop overheating problems. Many people end up having to replace their laptop batteries simply because they were not careful enough when dealing with laptop overheating problems. There are many simple steps you can take to reduce the temperature of your laptop generates in order to prevent laptop overheating problems.
If your laptop has fallen on the ground and been badly damaged, you most likely need a laptop hinge repair Toronto service. Laptop hinges are not something that most people think about when they first purchase laptops, but they can easily become damaged.
The weight of a laptop can often cause it to become extremely difficult to open and close. In addition, the weight of a laptop can often cause the screen to become cracked and broken. For these reasons, you should consider a laptop repair Toronto service as soon as possible.
Another common problem is a problematic mother board. Most likely, your laptop repair technician will suggest the motherboard laptop repair Toronto you need. Motherboards have become a common problem among new laptop models, simply because of the way that many new motherboards are produced today.
Unfortunately, many older motherboards contain defects that can prevent your computer from operating properly. A qualified Toronto computer technician can easily identify the problem with your motherboard and ensure that it is repaired so that you can get back online quickly.


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#AANAM – Greater Exposure to Ocrevus Means Less Risk of Disability Progression in MS Patients, Study Contends
Higher exposure to Ocrevus (ocrelizumab) is associated with greater immune B-cell depletion in the blood, and lessened risk of disability progression in patients with relapsing multiple sclerosis (MS) and primary progressive disease (PPMS), according to new research.
The study supporting that finding, "Pharmacokinetics, Pharmacodynamics and Exposure-Response Analyses of Ocrelizumab in Patients With Multiple Sclerosis," was presented at the 2019 American Academy of Neurology (AAN) Annual Meeting, held in Philadelphia May 4–10. The data were presented by Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco (UCSF).
Ocrevus is an approved treatment marketed by Genentech for patients with relapsing MS and those with PPMS. The therapy is a humanized monoclonal antibody that targets specific immune cells — CD20+ B-cells — and is administered intravenously (600 mg every six months).
In the study, researchers used Phase 2 and 3 clinical trial data to characterize Ocrevus's pharmacokinetics — its absorption, distribution, metabolism, and excretion in the body — and pharmacodynamics (how the body responds to the therapy).
The team also analyzed exposure-response associations in terms of clinical effectiveness — as assessed through the annualized relapse rate, and 12- and 24-week confirmed disability progression (CDP) — and safety, namely the associated serious adverse side effects, serious infections, and infusion-related reactions.
Researchers created a model accounting for time-dependent Ocrevus' clearance and patients' body weight, which accurately described the treatment's pharmacokinetics in 941 patients with relapsing MS and 482 with PPMS. Exposure to the therapy was 26% higher in patients with relapsing MS under 60 kilograms (kg), and 21% lower in those above 90 kg of body weight versus a 75 kg reference patient.
The data further showed that depletion of B-cells — targeted by Ocrevus — correlated with the extent of exposure to the therapy. Although the reduction in relapses was found to be independent of exposure in patients with relapsing MS.
Ocrevus also reduced lesions, assessed through magnetic resonance imaging (MRI), to nearly undetectable levels in relapsing MS and PPMS patients.
"Greater B-cell depletion is observed with higher Ocrevus exposure," Hauser said, while noting that the "annualized relapse rate and MRI [magnetic resonance imaging] outcomes were not exposure-dependent."
Results also showed that greater decreases in the risk of 12- and 24-week CDP were associated with higher exposure to Ocrevus in patients with relapsing MS and PPMS, when compared to Rebif (interferon beta-1a, marketed by EMD Serono) and placebo, respectively.
"Lower rates of disability progression were associated with higher ocrelizumab exposure and lower median B-cell levels prior to the next infusion," Hauser said.
Regarding safety, all safety parameters were similar across patients with different exposure to Ocrevus, suggesting that higher exposure does not seem to increase the likelihood of adverse side effects.
Overall, based on the results, Hauser concluded that "higher Ocrevus exposure and greater B-cell depletion may be important for the control of disability progression," he said.
In an AAN-related Genentech press release, Hauser emphasized: "These are the first data to show that higher Ocrevus exposure is associated with greater control of disability progression without impacting safety. These analyses … create a compelling case for initiating therapy early in the disease course, and provide important information that clinicians can use to inform treatment decisions."
Also, the fact researchers saw more pronounced effects in patients with higher Ocrevus exposure could indicate "that the current approved dose is closer to the lower part of the dose-response curve," the team noted, suggesting that greater responses could be seen with higher Ocrevus doses.
However, Hideki Garren, MD, PhD, global head of MS and neuroimmunology at Genentech, is cautious about the idea of "higher dosing, more benefits."
"It's important to remember that the most well-characterized dose … is the [approved] 600 milligram dose — 600 mg every six months. In other words, we think that is enough to reduce lesions, reduce relapses, and reduce disability progression. We'll certainly look into this data and explore more, but what physicians should follow is the well-characterized and proven dose," Garren said in an interview with Multiple Sclerosis News Today.
Referring to Hauser's presentation, Garren emphasized that the data show MS patients "need a robust B-cell suppression to see [Ocrevus effect in] disability progression, and again, disability progression, we believe, underlines all forms of MS," Garren said.
Of note, six of the researchers involved in the study presented at the AAN meeting are affiliated with Roche, which owns Genentech.


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Simon, it's a great blog. I enjoy reading it and am in awe of how prolific you are compared to my efforts. It was your blog that inspired me to start my Grumpy Dad site. Your number 10 was one of my favourites and I shared it with my network. Cheers Nathan
10,000 hits and top 10 posts
I started blogging just under 6 months ago, in that time I have published 136 posts and managed to get over 10,000 hits so I wondered which posts got the most hits. There was a couple of surprises in there.
Here's the Top 10
1. Is it powered by coal and steam? – The irony of the intel ad
This was the first surprise. I thought it was just me that saw irony in the suggestion that coal and steam was old technology when we are still using the same technology after 100 years. It's amazing how many hits I get from a google search for the term 'powered by coal and seam ad'.
2. Wind turbines in buildings – is venturi the answer?
I get quite a few hits to this one from people searching for 'invelox scam". I don't know what the score is but there is comment on the post claiming its a scam!
3. Green ratings survey what's the point – Survey Results
A good number of hits for this one during the first few weeks of the post but not much after that. I think it had a good level of interest as it was topical during Green Cities.
4. The most efficient air conditioning system is one that's turned off
Quite pleased about getting a number 4 for this one, it's a post about how often we turn the air conditioning off in our Sydney office. It got shared a fair bit on linkedin as well.
5. Water footprint showers versus red meat, which would you choose?
A personal mission of mine is to provide data to allow people to make informed sustainable decisions, one of those was to highlight the difference in water consumption between water saving shower heads and a reduction in red meat.
6. China coal, mind the gap and future global energy use
I was trying to counter some of the "look how bad they are, please don't look at us" coverage in the media at the time. Classic case of 'people in glasshouses shouldn't throw stones".
7. Every architect should have one of these
I was in Hassell's sydney office recently in a meeting room with a 3D printer chugging away in the room next to us, which was cool, but what every architect should have is a Filabot which turns waste plastic into the filament that the 3D printers need – now that's awesome.
8. Tri Harder Part 1 – Electricity generation carbon intensity
This was the first post in a series on trigeneration in Australia, it caused a few stirs and generated a series of seminars in Sydney and Melbourne. It's still a hot topic.
9. Green Cities – calculating the value of trees
This one was cool, a study from the US put a dollar value on trees in cities. We should place a greater value on our ecological system and then maybe we would protect it more.
10. What we eat in a week – photos from around the world
Not just the amount of food, but the difference in the type of food was a real eye opener on this post. What was also amusing was seeing it appear on The Project on TV three days after the post. I found it after a client found it, just shows how slow TV is compared to the internet.
It's been an interesting and challenging six months, I wonder what will happen over the next 6 months.


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This is a long-term, ongoing review of my Fujifilm FinePix F200EXR 12MP Super CCD digital camera, which I purchased on Wednesday, April 08, 2009 (just for the record).
To view and download full-resolution samples and test photos taken with my F200, visit Fuji F200 Full-Sized Photos.
Flash at close distances
The F200 has the amazing ability to throttle flash output for correct exposure even when photographing subjects at macro distances.
At the camera shop where I was contemplating between buying the deep red Canon Powershot A480 or the F200, this exceptional performance by the F200 was one of the deciding factors that pushed me to get the F200 in the end. The A480 simply washed out the macro photo with its internal flash.
Today, outside the house, I saw a Lynx Spider resting on a leaf. One side of the leaf was fully lit by the strong morning sun, while the part of the leaf the Lynx rested on was in the shadows. I just made sure FORCED FLASH was turned on, and got the camera as close to the bug as possible. The F200 was in EXR Auto mode, and it quickly primed its internal settings to Macro Mode when it detected that the subject it was focusing on was within the macro range.
Click to view the full-resolution, unedited version (12 MP, 3.9 MB, ISO 200, f/9, 1/100 sec):
I'd say the F200 does macro fill-flash exceedingly well.
Higher ISO performance
The F200 earns very high marks in my books for being able to produce natural-looking photos, even when taken at high ISO values of ISO800 and higher.
This is especially true when the EXR S/N (Signal to Noise, Low Noise priority) mode is utilized.
The resolution drops to 6 MP in this mode, but this is a far better option than having a noisy, mottled, 12 MP image.
Fuji seems to have made sure that images shot at high ISO values retain beautiful tonality and colors, and just enough detail to make for a printable A4 (8" x 10") photo.
The image of a colorful jumping spider was taken in the shade, and the F200 automatically activated Macro Mode and S/N EXR modes, and bumped the ISO up to ISO800.
Click to view the full-resolution, unedited version (6 MP, 2.5 MB, ISO 800, f/3.3, 1/75 sec):
Here's a 100% crop of just the spider. Notice how nicely detail, color and tonality are captured.


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After three long years the wait is finally over and a new KXM record is coming in the form of Scatterbrain, due out on March 17 via Rat Pak Records. This is a band like no other with a musical pedigree that simply can't be touched. George Lynch (guitar), Ray Luzier (drums), and dUg Pinnick (bass, vocals) have once again crafted something truly amazing, and if you don't know who any of these men are stop reading now and hit yourself over the head with the nearest blunt instrument. I sat down with dUg recently to discuss the new album as well as what's going on with KING'S X and a bunch of other projects he's involved in. Have a look:
Amps: You were the first interview I ever did, at Trees Dallas, in May of 2013. I was so nervous and you made me feel totally at ease. And incidentally, THAT is where you first told me about KXM, but at that point you said you guys were a group working on a record, no name yet.
dUg: Ah, we named ourselves right before we put the debut out. We couldn't think of anything so we said, "Let's just use our initials."
Amps: That record was one of the best of 2014, Hell one of the best of the last few years!
dUg: Oh, thank you! That's awesome. Don't stop, I love it (laughs).
Amps: If it's possible you may have topped it with Scatterbrain, and the debut was a perfect 10/10 for me.
dUg: I hope so. I hope we keep moving forward and not just rehash, you know?
Amps: Was the songwriting approach the same this time around?
dUg: Yeah, we just jammed everything out like last time. We did it very quickly. I think we've been playing for so long and doing this for so long it doesn't take long for us to come up with riffs and parts. Some bands it may take them a year to record one song, not us.
Amps: One of my favorites so far is definitely "Not a Single Word," and "Noises In the Sky" is incredibly well put-together, too. What are some of yours?
dUg: It's like looking at yourself in the mirror. Some days I like what I see, some days I don't (laughs). I don't know, I really, really like for everyone else to decide their favorites, because I really can't tell you which ones are my favorites. When I'm a part of something, once it's complete I don't go back and listen to it. I mean, I play a record many, many times before it comes out, but once it's released I'll probably never play it again. That's what I do. I play the shit out of it until the day it's released, and then after it's out there's nothing you can do. It's there, and it's time to start writing some new tunes, and I don't look back.
Amps: I know you're a very busy guy. How many projects do you have going now? It's hard to keep track of you, you're everywhere.
dUg: I have a side project called GRINDER BLUES, a blues band with Jabo and Scott Bihlman and it's a blues rock band in the style of ZZ TOP'S Tres Hombres tuned down to C and B. It's really hardcore blues, but tuned down low. I'm getting ready to fly to Indiana to finish up the vocals on Grinder Blues II. I have a Jimi Hendrix tribute record coming out as soon as we get the KXM record out. I took a couple guys in the studio with me and we decided to do some Hendrix covers and try to replicate them as close to the record as we could. It was a lot of fun, and that'll be out pretty soon. It's called Often Imitated, never Duplicated.
Amps: The three of you in KXM have a lot going on all year, but do you think we'll see some KXM live dates anytime soon?
dUg: Not with KXM. Ray's on tour with KORN for a year so there's nothing we can do. But KING'S X is doing some shows. We're going to Europe in a few months, and we're talking about doing a new record, too. So that'll be coming up as well.
Amps: Really?? I was just gonna ask!
dUg: Yep. I'm excited. It's been almost ten years since we put one out, so we'll see what we can come up with (laughs).
Amps: The last one XV, and Gretchen Goes to Nebraska are two of my favorites, and permanent fixtures in my phone at work.
dUg: That's awesome man, oh wow!
Amps: I saw you twice on the XV tour, once with EXTREME, and once with BLACK WATER RISING. Awesome shows!
dUg: Those were some great nights, man.
Amps: Since your hernia operation and Jerry's (Gaskill, drums) heart problems how is everyone's health these days? All good?
dUg: Oh, we're all fine. Yeah, it's been years since all that stuff happened, so we're ready to go!
Amps: You've got so many irons in the fire, what's next? Are you gonna start flying into burning buildings and save people Superman-style? The dUg Pinnick-machine never seems to stop.
dUg: (Laughs) well, Bruce Franklin (guitar) from TROUBLE and I, we did a record with our band SUPERSHINE. He sent me a bunch of tracks to sing and play bass to, so that'll be coming down the road as well. I'm gonna keep going until I can't go.
Amps: Is there anything else you like to do, or is it all music all the time?
dUg: I actually don't have any free time. And I don't want any because if I'm not making music with some kind of project, I'm on social media trying to keep my career up, you know? I don't do anything else. At my age I just wanna make as much music as I can before I'm gone.
Amps: When the listener gets this KXM album in their greedy little hands what do you hope they take away from it after they finish the last song?
dUg: I hope they say it's the greatest record they've ever heard (chuckles). I mean that's what we all really want. What I expect is that hopefully the people that loved the first album love the next one and they'll pass it on so more people will come to the party. Yeah, everything I do I always hope will become the greatest thing anybody's ever heard. Not that I think it is, because the way I look at it is you gotta get the people to hear what you're doing, and if enough of them hear it they'll like it, you know?
Amps: What would you like to say to all the fans of your music out there in the world?
dUg: Thank you for all your support. It's made a world of difference in everything that I've done in my life and that I am. Don"t give up your dreams. Just keep doing what you're doing and don't let anybody tell you not to.
It feels like A&GS has come full circle with this one. Nearly four years after sitting down with my first ever interview, dUg Pinnick, it was great to talk to him again and be reminded of what a nice and humble guy he is. And to also have my mind blown by how much this man works, works, and works! Scatterbrain from KXM comes out March 17, so be sure to grab your copy that day…NO EXCUSES!!


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Companies, organizations and entities of every size, across industries and geographies put the theme of work/life balance at the top of their Human Recourses agenda. Companies over the last decade have increasingly spent time and resources to understand what their staff and employees need and to map those needs with the needs of the companies in the effort of increasing productivity at work and their corporate image in a world where focus is high on recruiting and more importantly retaining scares top talent. Professional services companies are front and center in the battle for talent and are pursuing and promoting HR policies that support the work/life balance agenda.
The new generation of professionals no longer perceives success in their professional life as the most important source of satisfaction and personal happiness. This generation assigns a lot of weight to the second element in their definition of success and that element is having a successful personal life.
This is the tricky part in my opinion. What is the definition of a successful personal life? Is the definition the same for all? If we consider just a couple variables that might factor into the definition of a successful and happy personal life such as gender, different age group and geographies, we will find that it hard, no, in fact difficult to find a single formula to fit all.
Having said that, the question that comes to mind, is the promise of a work/life balance and the fulfillment of this promise the sole responsibility of companies; or does some of that responsibility fall upon the shoulders of the staff and employees themselves?
In my opinion, companies have an enormous responsibility and play a major part in the fulfillment of the promise but individuals have an equally vital role in the process. While companies are required to encourage, support and promote work/life balance through developing and implementing HR policies in this regard, it is the individuals that need to decide on what works for them and what is their personal preference or definition of a successful work/life balance depending on the stage of their lives they are at, their character and their vision of where they want to be in the near and far future, on a professional and personal basis. Once an individual is confident with the choice he/she has made, the policies and procedures that companies should have established should be able to support reasonable work/life balance decisions of its staff.
Needless to say that what works for an individual is not a constant and that is why, individuals should not be afraid to shift or tip the balance in either direction depending on the circumstances surrounding them and is best for their wellbeing, professionally and personally.
Equally important is that we as individuals are aware that our choices do not come without consequences that we need to ready to accept and manage to achieve the promise of work/life balance that best serves our personal and professional aspirations and goals.
Ask yourself this, have you achieved your work/life balance promise?
By Nada Maalouf, partner, Audit, Deloitte Middle East