text:
Early embryo development in a sequential versus single medium: a randomized study
Goedele Paternot1,
Sophie Debrock1,
Thomas M D'Hooghe1 &
Carl Spiessens1
The success of in vitro fertilization techniques is defined by multiple factors including embryo culture conditions, related to the composition of the culture medium. In view of the lack of solid scientific data and in view of the current general belief that sequential media are superior to single media, the aim of this randomized study was to compare the embryo quality in two types of culture media.
In this study, the embryo quality on day 3 was measured as primary outcome. In total, 147 patients younger than 36 years treated with IVF/ICSI during the first or second cycle were included in this study. Embryos were randomly cultured in a sequential (group A) or a single medium (group B) to compare the embryo quality on day 1, day 2 and day 3. The embryo quality was compared in both groups using a Chi-square test with a significance level of 0.05.
At day 1, the percentage of embryos with a cytoplasmic halo was higher in group B (46%) than in group A (32%). At day 2, number of blastomeres, degree of fragmentation and the percentage of unequally sized blastomeres were higher in group B than in group A. At day 3, a higher percentage of embryos had a higher number of blastomeres and unequally sized blastomeres in group B. The number of good quality embryos (GQE) was comparable in both groups. The embryo utilization rate was higher in group B (56%) compared to group A (49%).
Although, no significant difference in the number of GQE was found in both media, the utilization rate was significantly higher when the embryos were cultured in the single medium compared to the sequential medium. The results of this study have a possible positive effect on the cumulative cryo-augmented pregnancy rate.
Trial registration number
The success of in vitro fertilization techniques is defined by multiple factors including embryo culture conditions, related to the composition of the culture medium [1–3]. Currently, there is discussion about the ideal composition of culture media with two opposing views "back to nature" and "embryo free choice".
According to the "back to nature/need for sequential medium" principle, embryo culture media mimic in vivo conditions when the zygote moves from the fallopian tube to the uterus during early development [4–7]. In order to fulfill the needs of the embryo at each moment in development and to optimize the embryo quality, the sequential medium contains a different composition during different days of culture [5]. These "ideal" compositions are based on studies on animal models reporting a change of energy requirements as the in vitro culture of pre-implantation embryos evolves over time [8–10]. Moreover, molecules like EDTA, glutamine and some amino acids have been reported to have a variable effect on the embryo during development [4, 11–13].
According to the "embryo free choice/singe culture medium" paradigm, the embryo is cultured in a single medium which is constant and contains all the components needed during its development and the composition of this single medium does not change during embryo culture [8]. Proponents of this paradigm argue that there is no direct experimental evidence that sequential media are required for optimal embryo development [8].
It is not clear which type of culture media (sequential or single) is associated with the best quality of embryos on day 2, day 3 or day 5 or, more importantly, with the highest implantation rate per embryo transferred. No differences in embryo quality on day 3 and day 5 were found between a single medium and a sequential medium [14]. Optimal embryo quality has been reported after embryo culture in either a sequential [1, 15] or a single medium [16–18]. However, the quality of these studies was limited due to lack of randomization [1, 15], or, in case of randomization, due to the lack of a specific hypothesis with a power calculation [17, 18] or the failure to include a sufficient number of embryos [16]. It is not clear how the clinical implantation rate per embryo transferred is affected by embryo culture since only a few studies evaluated the difference in implantation rate with no significant advantage using one type of medium [1, 18]. The latter can be due to the fact that there are an insufficient number of embryos transferred.
In view of the lack of solid scientific data and in view of the hypothesis that sequential media are superior to single media, we carried out a prospective randomized study to evaluate the difference in embryo quality on day 1, day 2 and day 3 between a sequential media (Sydney IVF Cook, Queensland, Australia) and a single media (Gynemed, Lensahn, Germany).
A total of 178 patients, younger than 36 years, who entered their first or second IVF/ICSI cycle (each patient was included only once) between January 2008 and January 2009 at the Leuven University Fertility Centre, were informed about this prospective randomized study. The study was approved by the medical ethics committee of the University Hospitals Leuven (ML 4562). A total of 8 patients refused to participate. Patients were excluded when the cycle included biopsy for pre-implantation genetic diagnosis or if donor sperm/donor oocytes were used (table 1). A total of 170 patients were randomized, after informed consent, by a sealed envelope system. At random the embryos of the patient were cultured in a sequential medium (group A: Sydney IVF fertilization medium - Sydney IVF cleavage medium, Queensland, Australia) or in a single medium (group B: GM501 - GM 501, Gynemed, Lensahn, Germany) covered with mineral oil (Gynemed, Lensahn, Germany). In total, the dataset contained 85 patients in each group. Cycles with a failed fertilization (n = 7), an embryo transfer on day 2 (n = 13) or cryopreservation of all the fertilized oocytes on day 1 (n = 3) were eliminated (table 1). After this elimination step, group A contained 70 patients (419 embryos) and group B included 77 patients (583 embryos). In total, 28 patients entered their second cycle (group A: n = 12; group B: n = 16). An overview of patients and cycle characteristics are listed in table 2. The stimulation protocol used in our study is described in detail by Debrock et al. [19].
Table 1 Number of patients/cycles eligible, informed, excluded and included in the study
Table 2 Patients' and cycles characteristics of the study objects
IVF/ICSI procedure
During oocyte retrieval, the oocytes of patients of group A were kept in Sydney IVF Gamete buffer and those of patients of group B were placed in GM 501 Wash. After oocyte retrieval, oocytes were washed through 4 wells each containing 500 μl fertilization medium (group A: Sydney IVF fertilization medium, group B: GM501 culture) (37°C, pH: 7.25-7.35) under mineral oil. Spermatozoa used for the IVF procedure were prepared using standard density gradient procedures (Isolate, Irvine Scientific, USA). Sperm samples used for ICSI, including TESE samples(group A: n = 7; group B: n = 5), cryo samples (group A:n = 1; group B: n = 1) and samples with a low motility and/or low concentration (group A:n = 23; group B: n = 26), were diluted and were centrifuged two times during 10 minutes (300 g). During sperm preparation Sydney IVF Gamete Buffer and Fertilization medium were used in group A versus GM501 Wash buffer and culture medium in group B. Standard in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) procedures were performed 2-6 hours after oocyte retrieval. During the IVF procedure oocytes were inseminated with 200.000 progressively motile spermatozoa per well (0.5 ml). In case of an ICSI cycle, injected oocytes were incubated together in a 20 μl culture medium droplet under oil.
Embryo quality assessment
On day 1, 16 h-20 h after insemination/injection, oocytes were examined for the presence of two pronuclei. All fertilized oocytes were rinsed and transferred to individual 20 μl droplets cleavage medium (group A: IVF cleavage medium; group B: GM501 culture) and incubated under mineral oil in order to follow their further individual development. The computer system (FertiMorph, Image House, Copenhagen, Denmark) was used to record image sequences of the embryos on day 1, day 2 and day 3 of their development (submitted by Paternot et al. 2010).
At day 1: the size and position of the pronuclei and the presence of a cytoplasmic halo were evaluated. A total of 25 embryos were excluded from this evaluation since visible pronuclei were not seen at the moment of image recording. Twenty-four hours after ICSI and twenty-six hours after IVF, a number of embryos (n = 471, 172 embryos from group A and 299 embryos from group B) were additionally evaluated on day 1 for the of early cleavage. This additional analysis was not performed during weekends.
At day 2 (41 h-44 h after insemination/injection) and day 3 (66 h-71 h post-insemination/injection) all the embryos were scored for the number and the size of blastomeres (equal or unequal (> 25% difference in size)), the degree of fragmentation (0 = no fragmentation, 1 < 10%, 2 = 10-25%, 3 = 26-50%, 4 > 50%) the size (small or large) and the position (local or dispersed) of the fragments. In addition, on day 2 the presence of multinucleation and the orientation of the cleavage axes (when a four cell was available) were evaluated. Perpendicularly orientated cleavage axes were defined as normal orientated cleavage axes. An embryo at day 3 with 7,8 or 9 equally sized blastomeres was defined as a good quality embryo on day 3. At day 5 the blastocyst stage was evaluated based on the presence of the inner cell mass, the trophectoderm layer, the blastocoel and the degree of expansion as described by Gardner and Schoolcraft [20]. A blastocyst with a blastocoel completely filling the embryo, a tightly packed inner cell mass and a trophectoderm with many cells forming a cohesive epithelium was defined as a good quality blastocyst on day 5.
Embryo transfer and cryopreservation
After selection of the best embryo based on the morphological characteristics, embryo transfers were performed on day 3 or day 5. Regarding the Belgian legislation, single embryo transfers were performed when the patients entered for the first time an IVF/ICSI cycle. When they participated for the second time, the number of embryos transferred depended on the embryo quality. When a good quality embryo was available, a single embryo transfer was performed; in other cases two embryos were transferred. Embryos with at least 6 blastomeres, a degree of fragmentation less than 25% and equal sized blastomeres were cryopreserved on day 3. Embryos reaching the blastocyst stage (minimum expansion: early blastocyst; inner cell mass and trophectoderm layer: score A or B [20]) on day 5 were cryopreserved on day 5. Utilization rate was defined as the number of embryos available for cryopreservation and embryo transfer over the total number of embryos. Implantation was defined as the number of gestational sacs observed, divided by the number of embryos transferred [21].
The embryo quality on day 3 was measured as primary outcome. According to a power analysis, it was calculated that 395 embryos were needed in each group to detect a significant (reference value 35%) difference in embryo quality of 10%, at a statistical power of 0.80. The embryo quality was compared in both groups using a Chi-square test with a significance level of 0.05.
Fertilization rate
In total, 1645 oocytes were retrieved after pick-up with a mean number of 11.11 (± 5.31) oocytes per oocyte retrieval in group A and 11.26 (± 5.14) in group B. A total of 669 (86%) mature oocytes in group A and 788 (91%) mature oocytes in group B were inseminated on the day of oocyte retrieval. The fertilization rate was significantly higher in group B (74% (583/788)) compared to group A (63% (419/669)) (p < 0.001) (table 2) which could be due to a lower number of mature oocytes in group A. As a result, our dataset contained a total of 1002 embryos(419 embryos in group A and 583 embryos in group B) available for analysis, exceeding the number required (n = 395) according the above mentioned power analysis.
Embryo quality on day 1 (group A: n = 410; group B: n = 567)
A total of 25 embryos (group A: n = 9; group B: n = 16) were excluded for the evaluation of the characteristics on day 1 (as described in the Materials and Methods section). When compared to group A, embryos from group B had more embryos with a cytoplasmic halo (group B:46% (258/567) versus group A: 32% (132/410) (p < 0.0001)). Embryos from both groups were comparable for the other characteristics evaluated on day 1 (table 3).
Table 3 Morphological characteristics of the embryos evaluated on day 1 (Chi-square test)
There was a significant difference in the number of blastomeres, the degree of fragmentation and the size of blastomeres between both types of medium. The number of blastomeres was significantly higher in group B compared to group A (p = 0.0002). Significantly less embryos had 2 blastomeres (17% (100) versus 28% (119)) (p < 0.001) and significantly more embryos had at least 5 blastomeres (19% (110) versus 11% (45)) (p = 0.0004) on day 2 in group B (table 4).
Table 4 Morphological characteristics of the embryos on day 2 cultured in a sequential medium (group A) versus a single medium (group B) (Chi-square test)
In addition, more embryos had a degree of fragmentation higher than 50% (score 4) in group A (5% (22)) versus group B (3% (16)) (p = 0.0405). Finally, embryos of group A had significant more equally sized blastomeres (64% (270)) compared to the embryos of group B (50% (294)) (p < 0,0001) (table 4). No differences in both groups were seen in the evaluation of the position and the size of fragments, the presence of multinucleation or the orientation of the cleavage axes (table 4).
The number of blastomeres of the embryos of group B was significantly higher compared to the embryos of group A (p < 0.0001). More embryos of group A (40% (169)) were evaluated with equally sized blastomeres compared to group B (30% (177)) (p = 0.0011) (table 5). For the other characteristics evaluated on day 3 no significant differences were found (table 5).
Table 5 Morphological characteristics of day 3 embryos cultured in both types of culture media (Chi-square test)
Embryo quality on day 5 (group A: n = 49; group B: n = 71)
No differences were found in the number of good quality blastocysts on day 5 between both groups (group A: 6% (3/49) versus group B: 6% (4/71)) (p = 0.1476).
Finally, the utilization rate was significantly higher in group B compared to group A (group B: 56% (326) versus group A: 49%(206)) (p = 0.0346) (table 5).
Implantation rate
No difference was found between the implantation rate of an embryo in the first (29% (33/113)) or second IVF/ICSI cycle (41% (14/34)) (p = 0.3572). Five patients had no embryo transfer due to a high risk of OHSS (Ovarium Hyper Stimulation Syndrome) (2 patients of group A; 3 patients of group B). The embryos of these patients were cryopreserved on day 3. In group A, 3 double embryo transfers were performed on day 3, 60 single embryos transfers on day 3 and 5 single blastocyst transfers on day 5. In group B, 2 double embryo transfers on day 3, 65 single embryo transfers on day 3 and 7 single blastocyst transfers on day 5 were performed. In total, 147 embryos were transferred (71 embryos in group A, 76 embryos in group B). The implantation rate was significantly higher in group B (group A 20% (14/71) (day 3 2 ET: n = 4/6; SET day 3: n = 9/60; SET day 5: n = 1/5)), group B 28% (21/76) (day 3 2 ET: n = 0/4; SET day 3: n = 18/65; SET day 5: n = 3/7)) (p = 0.032).
This study showed for the first time that on day 3 the number of good quality embryos was comparable but the utilisation rate was higher after culture in a single medium than after culture in a sequential medium. This is the first randomized study that evaluated a unique set of characteristics separately on day 1, day 2 and day 3 of embryo development.
When compared to embryos cultured in sequential medium, embryos cultured in single medium were observed to have more frequently a cytoplasmic halo on day 1. A cytoplasmic halo is a manifestation of a microtubule-mediated withdrawal of mitochondria and other cytoplasmic components to the perinuclear region. The presence of a cytoplasmic halo has been reported to positively correlate with embryo quality and pregnancy rates [22–24]. This could not be confirmed by our data since the embryo quality was comparable on day 3 among halo positive embryos and halo negative embryos. In literature, the presence of an early cleavage is shown to correlate with embryo quality [25, 26]. In our study no difference was found in the presence of an early cleavage between both types of culture media, possibly because our study was not powered to detect the difference in early cleavage rate between both groups or because such a difference does not exist.
When compared to embryos cultured in sequential medium, embryos cultured in single medium were observed to have a higher number of blastomeres on day 2 and day 3, suggesting that embryos develop faster in single medium than in sequential medium. This observation is in line with results reported by other investigators [17] in a different patient population (oocyte donors, mean age of recipients 40.06 ± 5.4 years). Ben-Yosef et al. compared two sequential media and reported a lower cleavage rate when embryos were cultured in the COOK IVF medium [27].
It is difficult to compare our results with those of other randomized studies with a similar design and aim [16, 18] because they were either underpowered [16] or power was not calculated [18]. Furthermore, a combination of embryo morphological characteristics was used in the embryo scoring system of these studies [16, 18] making it impossible to evaluate individual embryo characteristics. Nevertheless, both studies [16, 18] reported, like our study, no differences in the number of good quality embryos on day 3. Biggers and co-workers [14] reported also individual embryo characteristics and found no differences in the number of blastomeres and the degree of fragmentation on day 3 when embryos were cultured in a single or sequential medium.
Although no significant difference could be found in the number of good quality embryos on day 3, in our study the utilization rate was significantly higher for the embryos cultured in the single medium. The study of Macklon et al. [16] reported a similar characteristic on day 5, namely the blastulation rate, which was equal for both types of culture media.
In our study, no statistically solid conclusions can be made on the level of embryo development on day 5 nor on the level of implantation since our study was not powered to compare these outcome variables between both groups. Some studies [14] found no differences in the blastocyst development on day 5 after embryos were cultured in a sequential or single medium while others found a benefit when the embryos were cultured in a single medium [17]. Other studies showed no significant difference in the implantation rate of embryos cultured in a single or sequential medium [1, 16–18].
The fertilization rate was significantly higher in the single medium. This could be a possible explanation for the difference in embryo quality. Although in our study we cannot discriminate for the oocyte quality since this was not the scope of this study and therefore not included in the study design. Our observation that the embryo quality/embryo utilization rate was better after culture in single medium than in sequential medium lends some support to the "embryo free choice hypothesis and is in line with the conclusions from a recent review paper [8] failing to find strong evidence in the literature to promote the use of a sequential medium protocol based on biological reasons and proposing new studies to evaluate the impact of culture medium on the gene expression of the embryo.
In our study design, we did not compare embryo quality in different media using sibling oocytes, allowing each patient to serve as her own control. However, using sibling oocytes at the moment of fertilisation control can give a methodological problem. This is due to the fact that different types of culture media differ in osmolarity. Using sibling oocytes will result in extra stress to the embryos when the culture medium is changed after fertilization [14]. In this way, at the end of the study, the effect of the differences in osmolarity between available commercial media can also have an influence on the embryo quality which makes it difficult to make conclusions. However, using sibling oocytes, no differences were observed in embryo quality between single or sequential media in a previous paper [18].
In conclusion, this is the first randomized study comparing a unique set of embryo morphological characteristics on day 1, day 2 and day 3 between a sequential and a single medium. On day 3 the number of good quality embryos was comparable but the utilisation rate was higher after culture in a single medium than after culture in a sequential medium, with a possible positive effect on the cumulative cryo-augmented pregnancy rate. Additional randomized trials are needed to test the hypothesis that these data can be confirmed for embryos cultured up till day 5.
Aoki VW, Wilcox AL, Peterson CM, Parker-Jones K, Hatasaka HH, Gibson M, Huang I, Carell DT: Comparison of four media types during 3-day human IVF embryo culture. Reprod BioMed Online. 2005, 10: 600-606. 10.1016/S1472-6483(10)61667-7.
Hentemann M, Bertheussen K: New media for culture of blastocyst. Fertil Steril. 2009, 91: 878-883. 10.1016/j.fertnstert.2007.12.011.
Summers MC, Biggers JD: Chemically defined media and the culture of mammalian preimplantation embryos: historical perspective and current issues. Hum Reprod. 2003, 9: 557-582. 10.1093/humupd/dmg039.
Gardner DK, Lane M: Allevation of the '2-cell block' and development to the blastocyst of CFI mouse embryos: role of amino acids, EDTA and physical parameters. Hum Reprod. 1996, 11: 2703-2711.
Gardner DK, Lane M: Culture of viable human blastocysts in defined sequential serum-free media. Hum Reprod. 1998, 13: 148-159. 10.1093/humrep/13.12.3434.
Gardner DK, Lane M: Towards a single embryo transfer. Reprod BioMed Online. 2003, 6: 470-481. 10.1016/S1472-6483(10)62170-0.
Lane M, Gardner DK: Embryo culture medium: which is the best?. Best Res Clin Obstet Gyn. 2007, 21: 83-100. 10.1016/j.bpobgyn.2006.09.009.
Biggers JD, Summers MC: Choosing a culture medium: making informed choices. Fertil Steril. 2008, 90: 473-483. 10.1016/j.fertnstert.2008.08.010.
Gardner DK: Culture and selection of viable human blastocysts: a feasible proposition of human IVF. Hum Reprod update. 1997, 3: 367-382. 10.1093/humupd/3.4.367.
Pool TB: An update on embryo culture for human assisted reproductive technology: media, performance, and safety. Semin Reprod Med. 2002, 23: 309-318. 10.1055/s-2005-923388.
Gardner DK, Lane M: Amino acids and ammonium production regulate mouse embryo development in culture. Biol Reprod. 1993, 48: 377-385. 10.1095/biolreprod48.2.377.
Lane M, Gardner DK: Increase in postimplantation development of cultured mouse embryos by amino acids and induction of fetal retardation and encephaly by ammonium ions. J Reprod Fertil. 1994, 102: 305-312. 10.1530/jrf.0.1020305.
Gardner DK, Pool TB, Lane M: Embryo nutrition and energy metabolism and its relationship to embryo growth, differentiation, and viability. Semin Reprod Med. 2000, 18: 205-218. 10.1055/s-2000-12559.
Biggers J, Racowsky C: The development of fertilized human ova to the blastocyst stage in KSOM AA medium: is a two-step protocol necessary?. RBM Online. 2002, 5: 133-140.
Xella S, Marsella T, Tagliasacchi D, Giulini S, La Marca A, Tirelli A, Volpe A: Embryo quality and implantation rate in two different culture media: ISM1 versus Universal IVF Medium. Fertil Steril. 2010, 93 (6): 1859-63. 10.1016/j.fertnstert.2008.12.030.
Macklon NS, Pieters MHEC, Hassan MA, Jeucken PHM, Eijkemans MJC, Fauser BCJM: A prospective randomized comparison of sequential versus monoculture systems for in-vitro human blastocyst development. Hum Reprod. 2002, 17: 2700-2705. 10.1093/humrep/17.10.2700.
Sepulveda S, Garcia J, Arriagi E, Diaz J, Noriega-Portella L, Noriega-Hoces L: In vitro development and pregnancy outcome for human embryos cultured in either a single medium or in a sequential media system. Fertil Steril. 2009, 91: 1765-1770. 10.1016/j.fertnstert.2008.02.169.
Reed ML, Hamic A, Thompson DJ, Caperton CL: Continuous uninterrupted single medium culture without medium renewal versus sequential media culture: a sibling embryo study. Fertil Steril. 2009, 92: 1783-1789. 10.1016/j.fertnstert.2009.05.008.
Debrock S, Melotte C, Spiessens C, Peeraer K, Vanneste E, Meeuwis L, Meuleman C, Frijns JP, Vermeersch JR, D'Hooghe TM: Pre-implantation genetic screening for aneuploidy of embryos after in vitro fertilization in women aged at least 35 years: a prospective randomized trial. Fertil Steril. 2010, 93: 364-373. 10.1016/j.fertnstert.2008.10.072.
Gardner DK, Schoolcraft WB: vitro culture of the human blastocyst. Towards Reproductive Certainty: infertility and Genetics beyond 1999. Edited by: Jansen R, Mortimer D. 1999, Carnforth, UK: Parthenon Publishing, 378-388.
Zegers-Hochschild F, Adamson GD, de Mouzon J, Ishihara O, Mansour R, Nygren K, Sullivan E, van der Poel S: The international committee for monitoring assisted reproductive technology (ICMART) and the world health organisation (WHO) revised glossary on ART technology. Hum Reprod. 2009, 24: 2683-2687. 10.1093/humrep/dep343.
Bavister BD, Squirrell JM: Mitochondrial distribution and function in oocytes and early embryos. Hum Reprod. 2000, 15: 189-198. 10.1093/humrep/15.1.189.
Salumets A, Hydén-Granskog C, Suikkari AM, Tiitinen A, Tuuri T: The predictive value of pronuclear morphology of zygotes in the assessment of human embryo quality. Hum Reprod. 2001, 16: 2177-2181. 10.1093/humrep/16.10.2177.
Ebner T, Moser M, Sommergruber M, Gaiswinkler U, Wiesinger R, Puchner M, Tews G: Presence, but not type or degree of extension, of a cytoplasmic halo has a significant influence on preimplantation development and implantation behaviour. Hum Reprod. 2003, 18: 2406-2412. 10.1093/humrep/deg452.
Salumets A, Hydén-Granskog C, Mäkinen S, Suikkari AM, Tiitinen A, Tuuri T: Early cleavage predicts the viability of human embryos in elective single embryo transfer procedures. Hum Reprod. 2003, 18: 821-825. 10.1093/humrep/deg184.
Van Montfoort APA, Dumoulin JCM, Kester ADM, Evers JLH: Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers. Hum Reprod. 2004, 19: 2103-2108. 10.1093/humrep/deh385.
Ben-Yosef D, Amit A, Schwartz T, Cohen T, Mei-Raz N, Carmon A, Lessing JB, Yaron Y: Prospective randomized comparison of two embryo culture systems: P1 medium by Irvine Scientific and the COOK IVF medium. J Assist Reprod Genet. 2004, 21: 291-295. 10.1023/B:JARG.0000043702.35570.56.
Leuven University Fertility Centre, UZ Gasthuisberg, Campus Gasthuisberg, Herestraat 49, 3000, Leuven, Belgium
Goedele Paternot
, Sophie Debrock
, Thomas M D'Hooghe
& Carl Spiessens
Search for Goedele Paternot in:
Search for Sophie Debrock in:
Search for Thomas M D'Hooghe in:
Search for Carl Spiessens in:
Correspondence to Goedele Paternot.
GP and CS contribute to the paper by defining the design of the of the study, the analysis and the interpretation of the data. Both authors draft the paper and approved the final version. SD and TD interpreted the data and revised the paper critically for important intellectual content and approved the final version. All authors read and approved the final manuscript
Paternot, G., Debrock, S., D'Hooghe, T.M. et al. Early embryo development in a sequential versus single medium: a randomized study. Reprod Biol Endocrinol 8, 83 (2010) doi:10.1186/1477-7827-8-83
Oocyte Retrieval
Early Cleavage
Single Medium


The family invited us to stand a flag line at the funeral service and again for the interment service. Pete served in the U.S. Navy during WWII and was a member of the American Legion.
Riders will stage at Stephenville Funeral Home and prepare the flag line. When directed by the ride captain, the riders will take up positions on the flag line as the family and friends of Carpenters Mate 3rd Class J M Grundy arrive. After the service starts, the flags will be returned to the support vehicle, riders will then be debriefed and dismissed.


text:
package v1beta1

import (
	corev1 "k8s.io/api/core/v1"
	metav1 "k8s.io/apimachinery/pkg/apis/meta/v1"
)

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// DefaultPreemptionArgs holds arguments used to configure the
// DefaultPreemption plugin.
type DefaultPreemptionArgs struct {
	metav1.TypeMeta `json:",inline"`

	// MinCandidateNodesPercentage is the minimum number of candidates to
	// shortlist when dry running preemption as a percentage of number of nodes.
	// Must be in the range [0, 100]. Defaults to 10% of the cluster size if
	// unspecified.
	MinCandidateNodesPercentage *int32 `json:"minCandidateNodesPercentage,omitempty"`
	// MinCandidateNodesAbsolute is the absolute minimum number of candidates to
	// shortlist. The likely number of candidates enumerated for dry running
	// preemption is given by the formula:
	// numCandidates = max(numNodes * minCandidateNodesPercentage, minCandidateNodesAbsolute)
	// We say "likely" because there are other factors such as PDB violations
	// that play a role in the number of candidates shortlisted. Must be at least
	// 0 nodes. Defaults to 100 nodes if unspecified.
	MinCandidateNodesAbsolute *int32 `json:"minCandidateNodesAbsolute,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// InterPodAffinityArgs holds arguments used to configure the InterPodAffinity plugin.
type InterPodAffinityArgs struct {
	metav1.TypeMeta `json:",inline"`

	// HardPodAffinityWeight is the scoring weight for existing pods with a
	// matching hard affinity to the incoming pod.
	HardPodAffinityWeight *int32 `json:"hardPodAffinityWeight,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// NodeLabelArgs holds arguments used to configure the NodeLabel plugin.
//
// This plugin has been deprecated and is only configurable through the
// scheduler policy API and the v1beta1 component config API. It is recommended
// to use the NodeAffinity plugin instead.
type NodeLabelArgs struct {
	metav1.TypeMeta `json:",inline"`

	// PresentLabels should be present for the node to be considered a fit for hosting the pod
	// +listType=atomic
	PresentLabels []string `json:"presentLabels,omitempty"`
	// AbsentLabels should be absent for the node to be considered a fit for hosting the pod
	// +listType=atomic
	AbsentLabels []string `json:"absentLabels,omitempty"`
	// Nodes that have labels in the list will get a higher score.
	// +listType=atomic
	PresentLabelsPreference []string `json:"presentLabelsPreference,omitempty"`
	// Nodes that don't have labels in the list will get a higher score.
	// +listType=atomic
	AbsentLabelsPreference []string `json:"absentLabelsPreference,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// NodeResourcesFitArgs holds arguments used to configure the NodeResourcesFit plugin.
type NodeResourcesFitArgs struct {
	metav1.TypeMeta `json:",inline"`

	// IgnoredResources is the list of resources that NodeResources fit filter
	// should ignore. This doesn't apply to scoring.
	// +listType=atomic
	IgnoredResources []string `json:"ignoredResources,omitempty"`
	// IgnoredResourceGroups defines the list of resource groups that NodeResources fit filter should ignore.
	// e.g. if group is ["example.com"], it will ignore all resource names that begin
	// with "example.com", such as "example.com/aaa" and "example.com/bbb".
	// A resource group name can't contain '/'. This doesn't apply to scoring.
	// +listType=atomic
	IgnoredResourceGroups []string `json:"ignoredResourceGroups,omitempty"`

	// ScoringStrategy selects the node resource scoring strategy.
	// The default strategy is LeastAllocated with an equal "cpu" and "memory" weight.
	ScoringStrategy *ScoringStrategy `json:"scoringStrategy,omitempty"`
}

// PodTopologySpreadConstraintsDefaulting defines how to set default constraints
// for the PodTopologySpread plugin.
type PodTopologySpreadConstraintsDefaulting string

const (
	// SystemDefaulting instructs to use the kubernetes defined default.
	SystemDefaulting PodTopologySpreadConstraintsDefaulting = "System"
	// ListDefaulting instructs to use the config provided default.
	ListDefaulting PodTopologySpreadConstraintsDefaulting = "List"
)

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// PodTopologySpreadArgs holds arguments used to configure the PodTopologySpread plugin.
type PodTopologySpreadArgs struct {
	metav1.TypeMeta `json:",inline"`

	// DefaultConstraints defines topology spread constraints to be applied to
	// Pods that don't define any in `pod.spec.topologySpreadConstraints`.
	// `.defaultConstraints[*].labelSelectors` must be empty, as they are
	// deduced from the Pod's membership to Services, ReplicationControllers,
	// ReplicaSets or StatefulSets.
	// When not empty, .defaultingType must be "List".
	// +optional
	// +listType=atomic
	DefaultConstraints []corev1.TopologySpreadConstraint `json:"defaultConstraints,omitempty"`

	// DefaultingType determines how .defaultConstraints are deduced. Can be one
	// of "System" or "List".
	//
	// - "System": Use kubernetes defined constraints that spread Pods among
	//   Nodes and Zones.
	// - "List": Use constraints defined in .defaultConstraints.
	//
	// Defaults to "List" if feature gate DefaultPodTopologySpread is disabled
	// and to "System" if enabled.
	// +optional
	DefaultingType PodTopologySpreadConstraintsDefaulting `json:"defaultingType,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// RequestedToCapacityRatioArgs holds arguments used to configure RequestedToCapacityRatio plugin.
type RequestedToCapacityRatioArgs struct {
	metav1.TypeMeta `json:",inline"`

	// Points defining priority function shape
	// +listType=atomic
	Shape []UtilizationShapePoint `json:"shape"`
	// Resources to be managed
	// +listType=atomic
	Resources []ResourceSpec `json:"resources,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// NodeResourcesLeastAllocatedArgs holds arguments used to configure NodeResourcesLeastAllocated plugin.
type NodeResourcesLeastAllocatedArgs struct {
	metav1.TypeMeta `json:",inline"`

	// Resources to be managed, if no resource is provided, default resource set with both
	// the weight of "cpu" and "memory" set to "1" will be applied.
	// Resource with "0" weight will not accountable for the final score.
	// +listType=atomic
	Resources []ResourceSpec `json:"resources,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// NodeResourcesMostAllocatedArgs holds arguments used to configure NodeResourcesMostAllocated plugin.
type NodeResourcesMostAllocatedArgs struct {
	metav1.TypeMeta `json:",inline"`

	// Resources to be managed, if no resource is provided, default resource set with both
	// the weight of "cpu" and "memory" set to "1" will be applied.
	// Resource with "0" weight will not accountable for the final score.
	// +listType=atomic
	Resources []ResourceSpec `json:"resources,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// NodeResourcesBalancedAllocationArgs holds arguments used to configure NodeResourcesBalancedAllocation plugin.
type NodeResourcesBalancedAllocationArgs struct {
	metav1.TypeMeta `json:",inline"`

	// Resources to be managed, the default is "cpu" and "memory" if not specified.
	// +listType=map
	// +listMapKey=name
	Resources []ResourceSpec `json:"resources,omitempty"`
}

// UtilizationShapePoint represents single point of priority function shape.
type UtilizationShapePoint struct {
	// Utilization (x axis). Valid values are 0 to 100. Fully utilized node maps to 100.
	Utilization int32 `json:"utilization"`
	// Score assigned to given utilization (y axis). Valid values are 0 to 10.
	Score int32 `json:"score"`
}

// ResourceSpec represents a single resource.
type ResourceSpec struct {
	// Name of the resource.
	Name string `json:"name"`
	// Weight of the resource.
	Weight int64 `json:"weight,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// ServiceAffinityArgs holds arguments used to configure the ServiceAffinity plugin.
//
// This plugin has been deprecated and is only configurable through the
// scheduler policy API and the v1beta1 component config API. It is recommended
// to use the InterPodAffinity plugin instead.
type ServiceAffinityArgs struct {
	metav1.TypeMeta `json:",inline"`

	// AffinityLabels are homogeneous for pods that are scheduled to a node.
	// (i.e. it returns true IFF this pod can be added to this node such that all other pods in
	// the same service are running on nodes with the exact same values for Labels).
	// +listType=atomic
	AffinityLabels []string `json:"affinityLabels,omitempty"`
	// AntiAffinityLabelsPreference are the labels to consider for service anti affinity scoring.
	// +listType=atomic
	AntiAffinityLabelsPreference []string `json:"antiAffinityLabelsPreference,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// VolumeBindingArgs holds arguments used to configure the VolumeBinding plugin.
type VolumeBindingArgs struct {
	metav1.TypeMeta `json:",inline"`

	// BindTimeoutSeconds is the timeout in seconds in volume binding operation.
	// Value must be non-negative integer. The value zero indicates no waiting.
	// If this value is nil, the default value (600) will be used.
	BindTimeoutSeconds *int64 `json:"bindTimeoutSeconds,omitempty"`

	// Shape specifies the points defining the score function shape, which is
	// used to score nodes based on the utilization of statically provisioned
	// PVs. The utilization is calculated by dividing the total requested
	// storage of the pod by the total capacity of feasible PVs on each node.
	// Each point contains utilization (ranges from 0 to 100) and its
	// associated score (ranges from 0 to 10). You can turn the priority by
	// specifying different scores for different utilization numbers.
	// The default shape points are:
	// 1) 0 for 0 utilization
	// 2) 10 for 100 utilization
	// All points must be sorted in increasing order by utilization.
	// +featureGate=VolumeCapacityPriority
	// +optional
	// +listType=atomic
	Shape []UtilizationShapePoint `json:"shape,omitempty"`
}

// +k8s:deepcopy-gen:interfaces=k8s.io/apimachinery/pkg/runtime.Object

// NodeAffinityArgs holds arguments to configure the NodeAffinity plugin.
type NodeAffinityArgs struct {
	metav1.TypeMeta `json:",inline"`

	// AddedAffinity is applied to all Pods additionally to the NodeAffinity
	// specified in the PodSpec. That is, Nodes need to satisfy AddedAffinity
	// AND .spec.NodeAffinity. AddedAffinity is empty by default (all Nodes
	// match).
	// When AddedAffinity is used, some Pods with affinity requirements that match
	// a specific Node (such as Daemonset Pods) might remain unschedulable.
	// +optional
	AddedAffinity *corev1.NodeAffinity `json:"addedAffinity,omitempty"`
}

// ScoringStrategyType the type of scoring strategy used in NodeResourcesFit plugin.
type ScoringStrategyType string

const (
	// LeastAllocated strategy prioritizes nodes with least allcoated resources.
	LeastAllocated ScoringStrategyType = "LeastAllocated"
	// MostAllocated strategy prioritizes nodes with most allcoated resources.
	MostAllocated ScoringStrategyType = "MostAllocated"
	// RequestedToCapacityRatio strategy allows specifying a custom shape function
	// to score nodes based on the request to capacity ratio.
	RequestedToCapacityRatio ScoringStrategyType = "RequestedToCapacityRatio"
)

// ScoringStrategy define ScoringStrategyType for node resource plugin
type ScoringStrategy struct {
	// Type selects which strategy to run.
	Type ScoringStrategyType `json:"type,omitempty"`

	// Resources to consider when scoring.
	// The default resource set includes "cpu" and "memory" with an equal weight.
	// Allowed weights go from 1 to 100.
	// Weight defaults to 1 if not specified or explicitly set to 0.
	// +listType=map
	// +listMapKey=name
	Resources []ResourceSpec `json:"resources,omitempty"`

	// Arguments specific to RequestedToCapacityRatio strategy.
	RequestedToCapacityRatio *RequestedToCapacityRatioParam `json:"requestedToCapacityRatio,omitempty"`
}

// RequestedToCapacityRatioParam define RequestedToCapacityRatio parameters
type RequestedToCapacityRatioParam struct {
	// Shape is a list of points defining the scoring function shape.
	// +listType=atomic
	Shape []UtilizationShapePoint `json:"shape,omitempty"`
}

redpajama_set_name: RedPajamaGithub


On Saturday 23rd November 2013, the British Triathlon Federation hosted its annual awards dinner in Birmingham. Although Non Stanford and Jonathan Brownlee may have been the stars of the show, it was Dave who stole our hearts when he was announced as the Leigh Day British Triathlon Volunteer of the Year.
Dave has been involved in Triathlon for over 25 years. He is a founder member of this club and has organised our races every year since 1987. He is the driving force behind the UK's longest running triathlon series "The Hillingdon Triathlon Series". He is still the main organiser and volunteer for more than 30 races hosted by the club every year.
Please join us in congratulating a top man - Dave Wardle.


Five men have appeared in court charged in connection with a terror plot "to shoot, to kill, police officers or soldiers on the streets of London".
Tarik Hassane, Suhaib Majeed, Nyall Hamlett, and Momen Motasim, all from London, have been charged with intending to commit acts of terrorism.
A fifth man, Nathan Cuffy, 25, from London, faces firearms offences.
All five were remanded in custody until 27 October after the hearing at Westminster Magistrates' Court.
They will next appear at the Old Bailey.
They were charged following arrests in London over the last two weeks.
Prosecuting, Mark Dawson, told the court the case revolved around an alleged plot "to shoot, to kill, police officers or soldiers on the streets of London."
He said 21 details within the terror charge related to different individuals, but did not give specific details about which parts of the charge related to which accused.
The five men had appeared in the dock flanked by 12 police and security guards, said the BBC's Steve Swann, who was in court.
The Metropolitan Police said the men are accused of taking an oath of allegiance to the Islamic State (IS) militant group and arranging to buy a handgun equipped with a silencer and conducting "hostile reconnaissance" of a police station and Army barracks in London using Google Street View.
The terror charges also include allegations the four men set-up "methods of secret communications" and that they "entered into covert discussions".
They are accused of discussing the sourcing of a moped, along with where they could store the vehicle in Shepherd's Bush, west London.
The charges also allege the men conducted reconnaissance of Shepherd's Bush police station and White City Territorial Army barracks.
Police say the men are also accused of viewing and retaining images sent via Instagram of two Met Police officers and two Met police community support officers, and having "graphic images" of the beheading of Steven Sotloff.
Mr Sotloff, a US journalist, was killed by IS militants last month having been kidnapped in Syria in 2013.
Two other men, aged 20 and 21, arrested on 7 October on suspicion of being concerned in the commission, preparation or instigation of acts of terrorism were released without charge on Monday.
Another man, arrested on the same date, was released from custody earlier. Police say evidence was submitted to the Crown Prosecution Service, which advised it was "insufficient" to bring charges "at this time".
A woman, 19, has been released on police bail until next week pending further enquiries, police said.


We are looking for Support Workers to support individuals Cowley in Oxford with fantastic benefits.
You don't need experience as full training is given. We offer a great team environment and competitive pay rates. You will be friendly and approachable and support individuals to have a great life with excellent outcomes.
We are now offering free driving lessons if you join Dimensions!
For further information, please call James Milligan 07940 267556.


text:
Excellence in Industry Awards™ presented by The Greater Naples Chamber of Commerce, recognize Collier County businesses that exemplify innovation, economic diversification, and community enhancement. Sponsorship of this highly-regarded event ensures the Naples Chamber is able to fulfill its mission of making Naples the best place in America to live, work and visit.
Congratulations to our 2018 Winners!
Business Expansion: CID Design Group
CID Design Group, founded over 15 years ago, has grown from two to 38 employees.; 18 of those hired since January 2017. The interior design group has unique multifamily, hospitality and commercial projects in 35 states and over 65 cities. Annual revenues have grown from $1 million to over $15 million since 2014.
Company to Watch: Lenkbar, LLC.
Lenkbar LLC started operations in 2012 with three employees and an idea: to design and manufacture safe and innovative surgical instruments. It has grown to over 25 employees and is expanding into a 16,000 square foot state of the art facility.
Heart of the Community: Naples Zoo at Caribbean Gardens
For 99 years, the 43-acre Naples Zoo at Caribbean Gardens hosts over 350,000 guests each year. Constantly evolving and adapting, the Zoo seeks innovative ways to connect people with animals and nature to inspire them to respect, value and help conserve wildlife and the environment.
Pillar Award: Coastal Engineering Consultants, Inc.
Coastal Engineering Consultants, Inc. has been serving Southwest Florida for over 40 years. Its team of engineers, geologists, scientists and surveyors design workable alternatives to produce results that are in harmony with natural ecosystems. It encourages staff to get involved in the community and has served dozens of nonprofits over the last four decades.
YP of the Year: Alyssa Haney, First Florida Integrity Bank
Alyssa Haney has demonstrated ambition and a strong commitment to the community through her advancement at First Florida Integrity Bank and volunteer work for numerous organizations. A 2018 GAIN (Growing Associates in Naples™) graduate, she serves on the boards of the United Arts Council, Naples Players and Humane Society of Naples Pawfessionals.
Chairman's Award: John Passidomo
John Passidomo has served as a Chamber board member and chair of its Public Policy Committee for many years. His dedication to economic and workforce development is unmatched and he has been an integral part of shaping the mission of the Chamber as well as its governmental relations platform.
Welcome our Keynote Speaker CFO Alex Sink
Alex Sink served as Florida's Chief Financial Officer from 2007 to 2011. As one of four statewide elected officials, she was responsible for the state's treasury and accounting functions, served as a trustee for the state pension fund, directed the insurance consumer advocacy work along with serving as Chair of Florida Healthy Kids (S Chip program) among many other responsibilities. Prior to elected office, Alex had a 26-year career at Bank of America, where she was Florida President from 1993 to 2000.
Sink's previous public corporate board service includes Sykes Corporation, Raymond James Financial, and C1Bank. She currently serves on the board of Verger Capital, a private manager of endowment funds.
Her extensive nonprofit service includes serving as past board chair of United Way Suncoast, Leadership Florida, Take Stock in Children, Hillsborough Education Foundation, and The Nature Conservancy (Florida Chapter). She is a life trustee at Wake Forest University and is the incoming board chair of the Tampa Wave, a tech startup accelerator. Additionally, Alex serves on the United Way Worldwide Leadership Council, Junior Achievement Board, and Wake Forest University Baptist Medical Center Board.
For more information and sponsorship opportunities please contact Nikkie Dvorchak, VP of Events and Development at nikkie@napleschamber.org.
Download Sponsorship Packet

redpajama_set_name: RedPajamaCommonCrawl


text:
End captivity for whales and dolphins
Posted on September 11, 2015 November 1, 2017 by calvin
(Niagara Falls) – The governments of Ontario and Canada should take immediate action to ban whales and dolphins in captivity.
"We know that whales and dolphins are intelligent, emotional and social mammals," says Green Party of Ontario leader Mike Schreiner. "It's time to put the practice of using them for entertainment behind us."
Today, Mike Schreiner, leader of the Green Party of Ontario, visited Niagara Falls to support local federal candidates Steven Soos (Niagara Falls) and David Clow (Niagara Centre).
There is growing public support for ending the use of whales and dolphins for the purposes of entertainment.
"When these animals are put into captivity, their lifespan is greatly reduced," explained Soos. "The oldest known killer whale, aptly named Granny, is 103 years old. When in captivity, many killer whales die before they reach their 20's."
The Green Party of Ontario supports a ban on captivity of cetaceans (including whales and dolphins) and to create regulations for marine mammals to address the welfare and safety of grandfathered animals.
Federally, the Green Party of Canada supported Bill S-230, the Ending the Captivity of Whales and Dolphins Act, and will support similar legislation in the next parliament. The bill would amend Canada's animal cruelty laws to specifically prohibit whales and dolphins in captivity, while allowing for the rescue and rehabilitation of injured individuals. The bill also allows owners of currently captive whales and dolphins to retain those individuals, though not to breed them.
"Jobs at Marineland are important," added Schreiner. "I join David and Steven in urging Marineland to stop the practise of holding whales and dolphins in captivity, and refocus their business model on entertainment that does not harm these intelligent and highly social creatures."


text:
Q: Terminal not reporting resize properly I'm having a problem where when I resize my terminal, it doesn't seem to be reported properly and so none of the applications in it don't display properly. For example:
If I open a terminal, remote in to a server and open vim without resizing, vim will take up the entire screen as expected. If I then resize my terminal and open vim again (I'm using vim here as an example but it happens with any program or terminal output), it will still act as if the terminal is the original size.
Is there a way to force my terminal emulator to report this change in size to the remote server?
I'm connecting to AIX machines using Terminator 0.95 on RHEL 6.5, and the shell on the remote server is KSH, for reference.
Thanks!
Edit to answer the questions in the comment below:
echo $TERM gives xterm (I'm assuming this is what the default is in terminator, as I haven't changed it). I am logging in using rsh

A: I've tested Terminator (on Ubuntu) against an AIX machine using ssh and the terminal resize works correctly.
AIX reported $TERM as xterm.
It appears either rsh is not sending the proper control sequences when Terminator resizes the terminal, or rshd is not handling them properly at the AIX end (assumption, untested).
In any case, I recommend using ssh!

redpajama_set_name: RedPajamaStackExchange


text:
unset UCF_FORCE_CONFFOLD
export UCF_FORCE_CONFFNEW=YES
sudo ucf --purge /boot/grub/menu.lst
export DEBIAN_FRONTEND=noninteractive
sudo apt-add-repository -y ppa:ansible/ansible
sudo apt-get update
sudo apt-get -o Dpkg::Options::="--force-confnew" --force-yes -fuy dist-upgrade
sudo apt-get -y install openjdk-7-jre
sudo apt-get -y install awscli
sudo apt-get -y install python-setuptools
sudo apt-get -y install python-pip
sudo apt-get -y install ec2-api-tools
sudo apt-get -y install cloud-guest-utils
sudo apt-get -y install software-properties-common
sudo apt-get -y install python-configobj
sudo apt-get -y install git
sudo apt-get -y install ansible
sudo apt-get -y install facter
sudo apt-get -y upgrade
sudo pip install https://s3.amazonaws.com/cloudformation-examples/aws-cfn-bootstrap-latest.tar.gz
sudo pip install --upgrade boto
sudo pip install --upgrade boto3
sudo pip install --upgrade awscli
sudo wget -q -O /usr/local/bin/cli53 https://github.com/barnybug/cli53/releases/download/0.6.5/cli53-linux-amd64
sudo chmod a+x /usr/local/bin/cli53
sudo wget -q -O /usr/lib/apt/methods/s3 https://raw.githubusercontent.com/BashtonLtd/apt-transport-s3/master/s3
sudo chmod a+x /usr/lib/apt/methods/s3


We love food smoking, that's exactly why we have created this website! Our aim is to provide education about outdoor cooking to as many people as we can. We also sell the highest quality equipment, wood and rubs to help you with your smoking journey!
Food smoking is becoming the go to method for outdoor cooking, it makes the food much more succulant and flavourful giving a better taste than traditional BBQ methods. We do still love a good BBQ but food smoking is our go to.
Please do send us any questions you may have via our contact us page.


This guide particularly gives the information on India and Indian Industries and Companies in General.
How to get access to the Financial Times?
This page provides the latest news, comments, opinions by the experts, videos and full-text articles on the Global Economy, Indian Economy, Industry news across the Globe, company news under all Industries as well as Asian companies news.
To browse the information you need to register through your IIM-B mail ID.
Note: Already registered users can sign in through your registered Email Id and Password to browse the required information.
How to get access to the Economist?
This page primarily focuses on world events, politics and business, but it also runs regular sections on science and technology as well as books and the arts. The five main categories are Countries and Regions, Business, Finance and Economics, Science and Technology, and Other.
To browse the information, you need to log in through the below-mentioned log-in credentials.
How to get access to the Fortune International?
How to get access to the Forbes Asia?
Forbes International provides Business news and Financial news, Include technology, Stock market, Personal finance, Entrepreneurs and Leadership news.
How to get access to the Business Today?
Business Today Provide India Business News of BIZ Wrap, Stock Markets, Industries, Business news headlines, Financial, NSE, BSE, Sensex, Technology news and Case studies on business, Opinions of Entrepreneurs.
This page get an update on daily basis.
Just one click on the article for access.
How to get access to the Time?
How to get access to the Asia Money?
How to get access to the Asian Wall Street Journal?
Asian Wall Street Journal provides news and analysis of global business developments. It's covers Economy, Law, Politics, Industries, E-commerce, Commodities, Private equity, real-time economy, Economic forecasting news and Video's.
This Page gets an update on daily basis.


text:
Dragon Age: Inquisition on Sale for $45 from Amazon Today Only
News 12/1/2014 at 7:39 AM by Nick Puleo 0
Hack and slash.
It's Cyber Monday. But the reality is, there have been deals online for the past few weeks on everything from video games to tennis rackets. The holiday shopping season is a big one for retailers and consumers alike. Today's deal on Amazon though is on a recent release for a solid discount. You can snag Dragon Age: Inquisition on any platform for just $44.99.
If you read our review of the game last week, you know it's a solid sequel in the series and the deepest game in it as well. With a meaty campaign and a four player co-op mode that's equally as addictive you'll be getting a lot of value for your dollar.
The deal ends today or when Amazon's stock runs out, so get on it while you can!
Source: Amazon.com
dragon age inquisition
No More Dragon Age: Inquisition DLC on 360/PS3, but you Can Move Your Save
EA Launches New Origin Access Program
Dragon Age: Inquisition Half-Off This Week on Xbox One
Dragon Age Inquisition Gets Patch 1.03, Multiplayer Additions
Next Week's Dragon Age Inquisition Pre-Order Deals Dissected
Co-Op Release Alert for the Week of 11.16.2014
Amazon.com - $112.95


text:
HomeNewsWhich Is The Strongest Predisposing Factor For Asthma
Which Is The Strongest Predisposing Factor For Asthma
Why Is Asthma An Important Public Health Issue
The Risk Factors for Development of Asthma and Food Allergies
The negative impact on asthmatics from direct or second-hand smoke is significant.
The incidence of asthma has been increasing in the last few decades in the developed world,especially amongst children. Asthma is now a serious chronic condition in Ontario and in Canada.Asthma impacts the quality of life of those affected with the disease, as well as their families.According to the 1996-97 National Population Health Survey, more than 2.2 million Canadians hadbeen diagnosed with asthma by a physician at some time in their lives . The same survey found that approximately 10 per cent ofCanadian children and five per cent of adults had asthma at the time of the survey .
The prevalence of asthma in Canadian children aged 0-14 years increased from 141,000 childrenin 1978/79, to 167,000 children in 1983/84, and then to 672,000 children in 1994/95. This is adramatic increase from 2.5 per cent to 11.2 per cent of children under 14 years, over a periodof 18 years.
Asthma is also becoming more prevalent among low-income adults over the age of 35 years. It is notclear at this time whether that higher prevalence can be attributed to lifestyle , residential status, occupation or other factors.
Yet, despite these statistics, 35 per cent of people with asthma were regularly exposed to smoke inside their home. Thus, it is evident that a change in attitudes and behaviors around smoking is especially important for asthma sufferers.
* age standardized to 1991 population
Which Condition Is Associated With The Highest Rate Of Comorbidity With Depression
The most prevalent comorbidities are anxiety disorders,8 substance use disorders9 and other depressive disorders. Epidemiologic studies have shown that the prevalence of at least one lifetime anxiety disorder was 59% in patients with lifetime MDD,10 while the prevalence of substance use disorders in MDD was 14%./span>
Read Also: Do Inhalers Make You Gain Weight
Prevalence And Symptoms Of Multi
Multi-symptom asthma was detected in 2.0% of the population. No significant differences were found by age, while it was significantly more common among females than males . Subjects with multi-symptom asthma comprised 24.4% of subjects with physician-diagnosed asthma. All investigated symptoms were more common among multi-symptom asthmatics compared with nonasthmatics, while all symptoms except allergic rhinitis were more common compared with subjects with other asthma .
Who's Strategy For Prevention And Control Of Asthma
WHO recognizes that asthma is of major public health importance. The Organization plays a role in coordinating international efforts against the disease. The aim of its strategy is to support Member States in their efforts to reduce the toll of disease, disability and premature death related to asthma.
Can Asthma Get Worse As You Age
With age, the immune system's response to inflammation becomes blunted, making it harder to fight off infections that can trigger asthma exacerbations. Other biological changes, notably shifts in patterns of inflammation, may reduce older patients' response to inhaled corticosteroids that need to be taken daily./span>
Updating Prior To Publication
In order to update the review prior to publication, we undertook forward citation on all included studies . Pursuing references from included studies is an efficient approach to updating systematic reviews as it is unlikely that relevant papers will have been published without citing at least one of the included studies.
You May Like: Does Weight Gain Make Asthma Worse
Reducing The Burden Of Asthma
Asthma cannot be cured, but good management with inhaled medications can control the disease and enable people with asthma to enjoy a normal, active life.
There are two main types of inhaler:
bronchodilators , that open the air passages and relieve symptoms and
steroids , that reduce inflammation in the air passages. This improves asthma symptoms and reduces the risk of severe asthma attacks and death.
People with asthma may need to use their inhaler every day. Their treatment will depend on the frequency of symptoms and the different types of inhalers available.
It can be difficult to coordinate breathing using an inhaler especially for children and during emergency situations. Using a spacer device makes it easier to use an aerosol inhaler and helps the medicine to reach the lungs more effectively. A spacer is a plastic container with a mouthpiece or mask at one end, and a hole for the inhaler in the other. A homemade spacer, made from a 500-ml plastic bottle, can be as effective as a commercially-manufactured inhaler.
Access to inhalers is a problem in many countries. In 2019, only half of people with asthma had access to a bronchodilator and less than one in five had access to a steroid inhaler in public primary health-care facilities in low-income countries .
Breastfeeding And The Risk Of Asthma
Risk Factors for Asthma – John R. Balmes MD
Publications on asthma and breastfeeding were sought from the MEDLINE database for the period 1 Jan. 2000 to 31 Jan. 2003 by searching for publications that contained both of these terms anywhere in their title, abstract or MESH subject headings. We retrieved 27 citations, of which 10 were primary studies that had collected and analyzed information on the independent association of breastfeeding and asthma. Publications pertinent to this area that appeared through to December 2004 were reviewed, but they contained insufficient data to modify the recommendations.
Current evidence
A meta-analysis of prospective studies examining the relation between breastfeeding and asthma reviewed the literature up to 1999. Among the 41 studies reviewed, 12 comprised more than 8000 children whose average age was 4.1 years. Overall, breastfeeding had a protective effect with respect to diagnosed asthma and recurrent wheeze among children with an atopic predisposition . Of interest, the benefit was less pronounced in studies where participants were followed past the age of 2 years. Since the end of 1999, several more studies have examined this association among children < 6 years of age at follow-up, using either prospective or cross-sectional, designs. The results are quite similar to those reported in the meta-analysis breastfeeding appears to be protective against wheezing syndromes early in life in similar populations.
Don't Miss: Does Smoking Weed Help Asthma
The Economic Burden Of Asthma :
1. Costs to the Health Care System
An estimate of the total cost of asthma in Canada in 1990 is between $504 million and $648 million.Sixty-one per cent of all asthma costs were direct costs such as in-patient care,emergency visits, physician services, nursing services, and drugs. Drug costs were by far the singlelargest component of direct costs , followed by hospital in-patient care and physician services . Indirect costs accounted for $197.7 million and includedthose costs related to travelling, absence from school, disability, and premature deaths. Illness-related disability was the largest contributor to indirect costs , followed by absence from school and premature deaths .
Health Canada data on the economic burden of illness in 1993 for Chronic/Bronchitis/ Emphysema/Asthma combined, reports direct costs of $1.3 billion and indirect costs of approximately $3 billion,for a total cost of $4.3 billion. This more recent cost data does not show the costs of asthma alone,but reveals that the economic burden of these respiratory diseases is a substantial one.
2. Costs to Individuals and Families
Global Alliance Against Chronic Respiratory Diseases:
The Global Alliance against Chronic Respiratory Diseases is part of WHOâs global work to prevent and control asthma. GARD is a voluntary alliance of internationally-recognized organizations, institutions and agencies from a range of countries working towards a common goal of improving global lung health. Its vision is to make the right to breathe freely a reality for all. GARD promotes an integrated approach that capitalizes upon synergies of chronic respiratory diseases with other chronic diseases. GARD focuses specifically on the needs of low and middle income countries and vulnerable populations. The Global Initiative for Asthma , which was formed in 1992 by WHO and the US-based National Heart, Lung and Blood Institute, is part of GARD, as is the Global Initiative on Allergic Rhinitis and its impact on Asthma , in which WHO is a participant. WHOâs Practical Approach to Lung Health , which is a strategy designed to help primary health care workers better manage respiratory symptoms, is used in GARDâs implementation strategy.
Read Also: Can Albuterol Cause Dizziness
Real Life Data On Incidence And Risk Factors Of Severe Asthma Exacerbations In Children In Primary Care
25% of children with a severe asthma exacerbation will experience another exacerbation within 1 year.
4 out of 1000 children with treated asthma will experience a severe exacerbation per follow-up year.
The risk of severe asthma exacerbations is the highest in spring and fall.
A previous asthma exacerbation is the strongest risk factor for subsequent asthma exacerbations.
What Are The Risk Factors Associated With Asthma
Asthma also affects the quality of life of the families of individuals with asthma
The exact cause of asthma is not known, but it appears to be the result of a complex interaction ofthe following two groups of factors :
1) Predisposing Factors :
Atopy – Atopy is a greater tendency to have allergic reactions to environmental allergens. This appears to be the strongest identifiable predisposing factor for asthma.
Gender – Young boys appear to develop asthma more often than do young girls, probably as a resultof their smaller airways. This imbalance reverses with age however, and by the time girls reachadulthood, it is adult women who more often develop asthma than men.
Genetics – Asthma is more common in families where at least one parent has asthma. This link is even stronger when it is the mother who has asthma.
Solid Food at an Early Age – Although the research is somewhat conflicting, there are indications that children who are breast-fed seem to have a lower risk of developing asthma.
2) Triggers :
Allergens can include pets, dust mites, cockroach allergen, moulds, pollen, foods and additives.
Triggers are factors that exacerbate asthma. They are exposures to causal factors that have alreadysensitized a person's airways. Triggers may be irritants, allergens or viral infections. Some asthmatics may react only to one trigger, others may react to several. Also, an individual's triggers may change over time.
Two triggers, in particular, are worthy of further discussion :
Family History Of Asthma
Blame Mom or Dad or both for your asthma. Your inherited genetic makeup predisposes you to having asthma. In fact, it's thought that three-fifths of all asthma cases are hereditary. According to a CDC report, if a person has a parent with asthma, they are three to six times more likely to develop asthma than someone who does not have a parent with asthma.
Comparisons To Other Studies
Comparisons with other studies should be interpreted with caution due to varying definitions of disease. The prevalence of current eczema in our study was 13.5 %. Earlier studies addressing eczema in adults have found similar magnitudes of prevalence with 11.6 % in Sweden , 8.1 % in Italy , 14.3 % in Denmark , 11.5 % in Colombia and 10.210.7 % in the United States . Earlier studies of rhinitis have mainly focused on either allergic rhinitis or symptoms of chronic rhinosinusitis. Our definition of current rhinitis included subjects with either allergic rhinitis or other chronic nasal symptoms. The observed prevalence of current rhinitis in our study was 42.8 %. This high prevalence of rhinitis may seem remarkable however, another recent study in Sweden found that the prevalence of rhinitis symptoms was 51 % . Further, 28.1 % in our study reported use of medication against rhinitis in the last year. Allergic rhinitis has also seen a significant increase in prevalence during the last thirty years . The prevalence in Italy has been estimated at 26 % and in southern Finland it has exceeded 40 % .
Af And Multiple Risk Factors
The AF was highest for a family history of allergy, which explained 37.1% of the multi-symptom asthma in the study population . In addition, a family history of asthma , female sex , and occupational exposure to gas, dust or fumes were important explanations for multi-symptom asthma. When the AF for occupational exposure to gas, dust or fumes was calculated for males and females separately, the AF for males was 35.3% and for females was 12.5%, reflecting the fact that 56.0% of the males and 24.4% of the females were exposed at work.
Attributable fractions for multi-symptom asthma.
An obvious additive risk effect on OR was seen when analysing the joint effect of family history, occupational exposure and current smoking. Using nonsmoking subjects with no family history of asthma or allergy and no occupational exposure to gas, dust or fumes as a reference, the OR for multi-symptom asthma for subjects with a history of both asthma and allergy, and occupational exposure and/or current smoking was 10.5 .
The effect of interaction between family history, smoking status and occupational exposure on the odds ratios for multi-symptom asthma. : OR 1 whiskers: 95% CI.
Environmental Factors And Asthma
Depression as a Risk Factor for the Development of Asthma in Adults
Indoor air pollution such as cigarette smoke, mold, and noxious fumes from household cleaners and paints can cause allergic reactions and asthma. Environmental factors such as pollution, sulfur dioxide, nitrogen oxide, ozone, cold temperatures, and high humidity are all known to trigger asthma in susceptible individuals. In fact, asthma symptoms and hospital admissions are greatly increased during periods of heavy air pollution. Ozone is the major destructive ingredient in smog. It causes coughing, shortness of breath, and even chest pain — and can boost the susceptibility to infection. Sulfur dioxide, another component of smog, also irritates the airways and constricts the air passages, resulting in asthma attacks.
Gas stoves are the primary source of indoor nitrogen dioxide, a common indoor pollutant. Studies show that people who cook with gas are more likely to have wheezing, breathlessness, asthma attacks, and hay fever than those who cook with other methods. It is estimated that more than half of the households in the U.S. use gas stoves.
Weather changes can also result in asthma attacks in some people. For instance, cold air causes airway congestion and an increase in mucus production. Increases in humidity may also cause breathing difficulty in a certain population.
You May Like: Reduce Asthma Symptoms
Implications For Parents And Clinical Practice
Our findings suggest that it is possible to identify the high-risk child with asthma. The factors associated with moderately or greatly increased risk are easily identifiable in routine practice. For example: a history of acute attacks, persistent troublesome symptoms, frequency of prescription requests and comorbid atopic/allergic conditions are recommended components of regular reviews, and knowledge of the social context is a core component of family medicine practice.
Identifying that their child is at-risk enables parents to take decisions about modifying risk, such as reducing exposure to ETS, and reconsidering the necessity for controller treatment against their concern about harms of regular medication. Clinicians alerted to the at-risk child can target care, specifically instituting evidence-based management to reduce risk.
Greatly Or Moderately/greatly Increased Risk Of Attacks
Previous attacks
Previous attacks were consistently associated with a greatly increased risk of future attacks . Due to the consistency of findings and quality of the studies the Panel was highly confident in this assessment .
Poor control and/or persistent symptoms
Ten studies had at least one significant result demonstrating that poor control or persistent symptoms identified a child at moderately/greatly increased risk of future attacks . The exception was a small , short duration cohort study of moderate quality which showed no association. The Panel was highly confident in this assessment. Persistent symptoms of any severity were associated with greater risk.
Poor access to healthcare
Five studies examined access to healthcare defined by insurance status. Four demonstrated that poor access to healthcare was associated with a moderately/greatly increased risk of attacks. A small cohort study of moderate quality demonstrated no increased risk in children with or without Medicaid . The Panel was moderately confident in this assessment. The studies were all US based with participants from deprived inner-city populations: one study controlled for ethnicity and poverty.
You May Like: What Happens If Eosinophil Count Is High
Slightly Increased Risk Of Attacks
ETS exposure
Five studies found at least one positive association between ETS exposure and asthma attacks. One high-quality cross-sectional study highlighted that the association between cotinine levels and risk of attack was lost when parent report was used to estimate ETS. Of note, the three negative studies relied on parental report. The Panel was highly confident that ETS exposure was associated with a slightly increased risk of asthma attack .
Younger age
All six of the studies that examined the effect of age on risk of asthma attacks found that younger children were more likely to have an attack. The ORs ranged from 0.8 to 1.0 the Panel was highly confident of this.
Overweight/obesity
Four studies showed a significant, though small association between overweight or obesity and increased risk of attacks. The Panel was highly confident that there was a slightly increased risk of an attack in overweight or obese children.
Low parental education
All four studies, including one large, high-quality cross-sectional study, showed slightly increased risk of attacks in children of families with low parental education level . The Panel was moderately confident in this assessment.
Previous articleAre There Steroids In Asthma Inhalers
Next articleWhere Does Asthma Occur In The Body
How To Treat Asthma Attack Naturally
Is Asthma A Primary Secondary Or Tertiary Disease
How Do You Know If You Have Sports Induced Asthma


Warning: Page using Template:Infobox person with unknown parameter "1 = 250px" (this message is shown only in preview).
He was born on March 30, 1944 in Chihota communal area , Marondera East. He studied Genetics in Czechoslovakia and Medicine at the University of Lund, Sweden (1964).
He became an active politician during the Second Chimurenga in the 1960s when he was granted a scholarship to study in Sweden as he had been expelled at a local Rhodesian school. He was a college student at the University of Lund when he became Zanu- PF's representative in Sweden. In 1979 while in Sweden, he used his position as Secretary General of the National Students Union to facilitate Herbert Chitepo's visit to Europe. His war credentials, knowledge and considerable education facilitated him to be appointed Minister of Lands, Resettlement and Rural Development at independence in 1980. He had been elected Mashonaland Central Member of Parliament in the same year. Since independence, he has held many government posts from being Minister of Health (1984–88), Minister of Mines from 2000 to 2001.
Sekeramayi won the House of Assembly seat from Marondera East Constituency, in Mashonaland East Province, as the Zanu-PF candidate in the March 2005 parliamentary election. According to official results he defeated Movement for Democratic Change (MDC) candidate Iain Kay with 19,912 votes against Kay's 10,066 votes; this victory was questioned on the grounds that the total number of votes was said to exceed voter turnout.
In the Zanu-PF primaries for the March 2008 parliamentary election, Sekeramayi again sought the party's nomination as its candidate for the House of Assembly seat from Marondera East, but was defeated. He was instead nominated as ZANU-PF's candidate for the Senate from Marondera-Hwedza in Mashonaland East. Sekeramayi won this seat according to official results, receiving 24,571 votes against 17,370 for Jane Chifamba of the MDC-Tsvangirai faction and 6,994 for Molai Penelope of the MDC-Mutambara faction.
Zanu- (PF)Secretary for National Security.
Energy Mutodi claimed that Mnangagwa was poisoned by then Defence Minister Sekeramayi and David Parirenyatwa who were in the helicopter with him. In an interview with the Financial Times , Mnangagwa claimed he knew people who administered the poison which almost claimed his life.
One of his sons Floyd Sekeramayi was banned from practicing law in Canada following allegations that he sexually assaulted nurses at a Canadian hospital.
↑ David Blair, "Mugabe 'conjures up' winning votes", Daily Telegraph (United Kingdom), 8 April 2005.
↑ Spiwe Ncube, "Zanu (PF) heavyweights lose primary polls", zimdaily.com, 6 February 2008.
↑ Lebo Nkatazo, "Makoni humiliated as Zanu PF rejects his bid for MP", newzimbabwe.com, 5 February 2008.
Please visit the following to contribute to the profile of Sydney Sekeramayi.


'S e bhideo aithriseach a th' ann am 'Passing Places - Na Fìor Eileanan Siar', a chaidh a choimiseanadh le Ionad Ealain Taigh Chearsabhagh ann an Uibhist a Tuath. Chaidh fhilmeadh le còrr is 100 duine bho na h-Eileanan an Iar anns a' bhliadhna 2000, bho Cheann Bharraigh gu Rubha Robhanais.
Anna Chàimbeul a' cruinneachadh nan caorach air latha geamhraidh.


Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m 2 to less than 15, at which point the patient is said to have end-stage kidney disease (ESKD).
Treatment with an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), which dilates the arteriole exiting the glomerulus, thus reducing the blood pressure within the glomerular capillaries, which may slow (but not stop) progression of the disease.
Their main uses are in the treatment of hypertension (high blood pressure), diabetic nephropathy (kidney damage due to diabetes) and congestive heart failure.
Protein loss in the urine due to damage to the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) and result in the nephrotic syndrome. The status of DN may be monitored by measuring two values: the amount of protein in the urine - proteinuria; and a blood test called the serum creatinine.
Protein loss in the urine due to damage to the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) and result in the nephrotic syndrome.
Affected individuals with end-stage kidney disease often require hemodialysis and eventually kidney transplantation to replace the failed kidney function.
This is done in patients with diabetes mellitus type 1, in whom the diabetes is due to destruction of the beta cells of the pancreas and in whom the diabetes has caused renal failure (diabetic nephropathy).
The pathophysiology of the glomerulus in DN can best be understood by considering the three involved cells as a unit: the endothelial cell, the podocyte, and the mesangial cell.
The expansion of mesangial matrix is one characteristic of diabetic nephropathy although it also involves other cells in interaction including podocytes and endothelial cells.
These changes damage the kidney's glomeruli (networks of tiny blood vessels), which leads to the hallmark feature of albumin in the urine (called albuminuria).
Examples are diabetic kidney disease, glomerulonephritis, and IgA nephropathy.
Another relevant factor is diabetes-induced hypoxia, which is an aggravating factor, since it increases interstitial fibrosis, partly by the induction of the synthesis of TGF-β and vascular endothelial growth factor (VEGF), which is mediated by hypoxia-inducing factor-1.
Microalbuminuria (between 30 and 300 mg/24h, mg/l of urine or µg/mg of creatinine ) can be a forerunner of diabetic nephropathy. The term albuminuria is now preferred in Nephrology since there is not a "small albumin" (microalbuminuria) or a "big albumin" (macroalbuminuria). A1 represents normal to mildly increased urinary albumin/creatinine ratio (0 mg/g or < 3 mg/mmmol); A2 represents moderately increased urinary albumin/creatinine ratio (30–300 mg/g or 3–30 mg/mmmol, previously known as microalbuminuria); and A3 reflects severely increased urinary albumin/creatinine ratio >300 mg/g or > 30 mg/mmol).
Initially, there is constriction of the efferent arterioles and dilation of afferent arterioles, with resulting glomerular capillary hypertension and hyperfiltration; this gradually changes to hypofiltration over time.
Concurrently, there are changes within the glomerulus itself: these include a thickening of the basement membrane, a widening of the slit membranes of the podocytes, an increase in the number of mesangial cells, and an increase in mesangial matrix.
The status of DN may be monitored by measuring two values: the amount of protein in the urine - proteinuria; and a blood test called the serum creatinine.
Three classes of diabetes medications – GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors – are also thought to slow the progression of diabetic nephropathy.


Italy was wonderful, beautiful, art-filled, exciting, and endlessly interesting. There's so much to tell, and it's difficult to even know where to start. I'll be posting lots of photos and notes about the trip over the coming weeks, but I'm guessing a lot of you are wondering if I actually did any sketching while I was over there.
Since the purpose of this trip was to see Italy at a slower pace and have time to do lots of sketching, I had high hopes of coming home with a sketchbook brimming with beautiful finished pages filled with watercolor sketches and travel journaling.
I started off with a bang on Day 1. After tasting our first Italian cappuccino at a coffee shop in town, we sat outside and sketched the gelateria across the street. It was a lot of fun painting on site, and I worked quickly to splash on the watercolor after doing my drawing with a brown watercolor pencil. The text was added later, and the page was complete!
In the hours and days that followed, I found myself wanting to get more and more of my experiences down on paper, but there simply wasn't enough time to paint it all. Around every corner there was an ancient building with weathered shutters just begging to be drawn, or a beautiful wrought iron balcony with trailing vines against warm golden stucco walls. There were castles and vineyards and olive groves everywhere we turned - so much to draw in a limited amount of time!
There are pages like this next one, where I was having so much fun painting that I totally neglected to finish the right side of the lower sketch. See the area where the distant mountain is missing?
I generally had a loose idea of a plan for the page layout in my head when I began sketching on a page. Other times, I slapped something down in the excitement of the moment, then later tried to figure out how to bring the page together with a title, text, borders, or bands of color which could be added later.
I journaled every evening, writing about all the interesting places we'd seen and people we met. I worked on inking the penciled-in text on the flight home when I had eight hours with nothing to do. Reading over all of our adventures was a great way to end the trip.
I'll be working on finishing up my Italy sketchbook as time allows this spring and summer, and I'll be sure to share it with you. I'd love to be in my studio working on it all day every day, but spring is a busy time of year, with planting and mulching and mowing to tend to, plus my sewing business. I know it might take awhile to complete all seventy journal pages, but that's okay. I'm looking forward to reliving those good times and wonderful places as I draw and paint my way from Venice to Tuscany to Cinque Terre on the pages of my sketchbook.


Sheez! You reminded me to get mine, just done it. Inv to Wick with bike £6.35...with a rail card. Good value! We're going to pass each other around Compton Martin / Cheddar.
Tee hee hee. I finished a LEJOG last summer during storm Hector. Downwind from Bettyhill to Lands End. Tee hee hee. And I have big ears so they helped out as sails. Got into JOG so early the surly hotelier said I was an hour early to check in so sent me away. Didn't matter, went for a coffee.
There are a chain of stores called Co-op (Cooperative) and they do a Meal Deal (a sandwich / wrap, crisps/sweets, fizzy drink). This does me, and once I "Meal Deal'ed" the entire journey (the Scottish Co-ops are called something slightly different), and I almost managed it.
Thanks for getting back Brucey, I appreciate your help.
I'm going to look at a Stevens San Remo tomorrow, does anyone know anything about these bikes???
I just felt the luxuries of life mattered more to me now.
Careful, that luxuriously silk lined coffin might become enticing as well.
Actually that's quite enticing; i used to be a Goth.
Sheeez Spinners, you're in a glass half empty mood today!
charliepolecat wrote: I didn't think there was an age limit for staying in YHA's or do you mean you were just too geographically old anyway for hostels ?
Spinners wrote: Tackling those steep Cornish hills right at the end? Ouch!
..but by then I should be at my fittest???? What do you reckon??
FasterFerret wrote: Does your GPS have an option to reverse the wind also?
Hang on, is there something I should know?


text:
Home Communication Page 3
Vanderbloemen Group - January 29, 2023
Charles Stone - January 28, 2023
What Then Do You Say, Lord?
Communication Dr. O'Shea Lowery - November 28, 2022 0
Sandy was a young lady who had given her life over to Christ and was living for Him in mighty ways. However, she often...
Message Angst
Communication Carey Nieuwhof - November 28, 2022 0
Almost every preacher who has been charged with the responsibility to communicate the message of God's Word can tell you this story. Message prep...
How Our Team Is "mission Ready"
Communication Vanderbloemen Group - November 26, 2022 0
There's a saying in the Marines that we love to try and mirror as we serve you: "Mission Ready." We are fully focused on you;...
Communication Joseph Lalonde - November 24, 2022 0
Diversity in the workplace is becoming increasingly important as businesses strive to create a better work environment for their employees. A diverse team is...
4 Church Frustrations That Can Get the Best of You (but Don't Have To.)
Communication Dan Reiland - November 13, 2022 0
Frustrations are common in the church, just as in any organization. However, the way we see them and how we handle them can be...
We've Led the Way
Vanderbloemen was born out of a holy discontent. William spent the first leg of his career as a Senior Pastor of churches of all sizes....
Tips for Managers: 8 Ways to Be a Better Leader at Work
Leadership is more than just giving orders and being the boss. To be an effective leader, you need to be able to motivate and...
3 Simple, High-potential Things Most Churches Miss In Their Digital Strategy
Communication Carey Nieuwhof - November 9, 2022 0
As a church leader, you probably struggle with social media, streaming services, and online ministry. There are a million suggestions on what to do online,...
Five (seemingly) Well-intending Sentences That Are Hurting the Church
Communication Thom Rainer - November 6, 2022 0
Have you ever received a backhanded compliment? Just beneath the veneer of a compliment lies a stinging insult. It may not register at first,...
5 Steps to Take to Improve People Management Skills
Communication Joseph Lalonde - November 5, 2022 0
Whether you are starting your career as a manager or you are looking to develop in a position, there is always something to learn....