title: Outcomes from colonoscopy following referral from New Zealand general practice: a retrospective analysis

authors: Lawrenson, Ross

subjects: Science & Technology

abstract: Background: New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. 
Methods: This study is a retrospective analysis of e-referral data for patients aged 30–70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015–31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. 
Results: 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value < 0.001). Females (p value < 0.001), non-Māori (p value < 0.001), and patients with a high suspicion of cancer (HSCan) label originating from their GP were more likely to have a colonoscopy, while the odds ratio of Māori having a colonoscopy was 0.66 (95% CI 0.60–0.73). The odds ratio of a CRC diagnosis following colonoscopy was 1.67 (95% CI 1.35–2.07) for men compared to women, and 2.34 (95% CI 1.70–3.22) for those with a GP HSCan label. Of the 585 patients referred with a GP HSCan, 423 (72.3%) were reprioritised by the hospital and 55 patients had their diagnosis unnecessarily delayed. 
Conclusions: If a GP refers a patient with an HSCan, and the patient receives a colonoscopy, then the likelihood of having CRC is almost 15.0%. This would suggest that these patients should be routinely prioritised without further triage by the hospital. Further research is needed to understand why Māori are less likely to receive a colonoscopy following referral from general practice.

text: Outcomes from colonoscopy following referral from New Zealand general practice: a retrospective analysis Background: New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. 
Methods: This study is a retrospective analysis of e-referral data for patients aged 30–70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015–31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. 
Results: 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value < 0.001). Females (p value < 0.001), non-Māori (p value < 0.001), and patients with a high suspicion of cancer (HSCan) label originating from their GP were more likely to have a colonoscopy, while the odds ratio of Māori having a colonoscopy was 0.66 (95% CI 0.60–0.73). The odds ratio of a CRC diagnosis following colonoscopy was 1.67 (95% CI 1.35–2.07) for men compared to women, and 2.34 (95% CI 1.70–3.22) for those with a GP HSCan label. Of the 585 patients referred with a GP HSCan, 423 (72.3%) were reprioritised by the hospital and 55 patients had their diagnosis unnecessarily delayed. 
Conclusions: If a GP refers a patient with an HSCan, and the patient receives a colonoscopy, then the likelihood of having CRC is almost 15.0%. This would suggest that these patients should be routinely prioritised without further triage by the hospital. Further research is needed to understand why Māori are less likely to receive a colonoscopy following referral from general practice.

year: 2021-12-15

title: Bilingual Education in Aotearoa/New Zealand

authors: Hill, Richard Kenneth

subjects: Maori medium

abstract: Bilingual education in the context of New Zealand is now over 30 years old. The two largest linguistic minority groups involved in this type of education – the Indigenous Māori and Pasifika peoples of Samoan, Tongan, Cook Islands and Niuean and Tokelauan backgrounds – have made many gains but have struggled in a national context where minority languages have low status. Māori bilingual programs are well established and have made a significant contribution towards reducing Māori language shift that in the 1970s looked to be beyond regeneration. Pasifika bilingual education by contrast is not widely available and not well resourced by the New Zealand government. Both forms continue to need support and a renewed focus at local and national levels.

This chapter provides an overview of past development of Māori and Pasifika bilingual education and present progress. For Māori, the issues relate primarily to how to boost language regeneration, particularly between the generations. Gaining greater support for immersion programs and further strengthening bilingual education pedagogies, particularly relating to achieving biliteracy objectives, are key. In the context of Pasifika, extending government and local support would not only safeguard the languages but has the potential to counteract long-established patterns of low Pasifika student achievement in mainstream/English-medium schooling contexts. Finally, the future of both forms of bilingual education can be safeguarded if they are encompassed within a national languages policy that ensures minority language development in the predominantly English monolingual national context of New Zealand.

text: Bilingual Education in Aotearoa/New Zealand Bilingual education in the context of New Zealand is now over 30 years old. The two largest linguistic minority groups involved in this type of education – the Indigenous Māori and Pasifika peoples of Samoan, Tongan, Cook Islands and Niuean and Tokelauan backgrounds – have made many gains but have struggled in a national context where minority languages have low status. Māori bilingual programs are well established and have made a significant contribution towards reducing Māori language shift that in the 1970s looked to be beyond regeneration. Pasifika bilingual education by contrast is not widely available and not well resourced by the New Zealand government. Both forms continue to need support and a renewed focus at local and national levels.

This chapter provides an overview of past development of Māori and Pasifika bilingual education and present progress. For Māori, the issues relate primarily to how to boost language regeneration, particularly between the generations. Gaining greater support for immersion programs and further strengthening bilingual education pedagogies, particularly relating to achieving biliteracy objectives, are key. In the context of Pasifika, extending government and local support would not only safeguard the languages but has the potential to counteract long-established patterns of low Pasifika student achievement in mainstream/English-medium schooling contexts. Finally, the future of both forms of bilingual education can be safeguarded if they are encompassed within a national languages policy that ensures minority language development in the predominantly English monolingual national context of New Zealand.

year: 2017

title: Inhibition of ERK and GSK3 signalling pathways promotes development and expression of pluripotent markers in bovine blastocysts

authors: Harris, Daina

subjects: bovine

abstract: Embryo-derived pluripotent stem cells (ePSCs) naturally derive from different founder tissues, namely the early and late epiblast, that vary in their cellular characteristics. Recent evidence in mice suggests these sources of starting material correspond with two states of pluripotency referred to as ‘naïve’ and ‘primed’, respectively. Pluripotency is defined as the ability of a cell to give rise to any foetal or subsequent adult cell type. Naïve and primed ePSCs have different fundamental properties and only naïve cells can give rise to all cell types of an animal, including functional gametes (Nichols & Smith 2009). Until recently, naïve ePSCs (also known as embryonic stem cell or ESCs) were only available in mouse. After almost 30 years, the first non-mouse ESCs were derived in rat using a combination of specific inhibitors that block the FGF-ERK differentiation pathway and simultaneously maintain self-renewal through inhibition of GSK3 (Buehr et al. 2008; Ying et al. 2008). The three inhibitor combination, or 3i, included inhibitors of the FGF receptor (PD173074), downstream ERK activity (PD0325901) and the GSK3 pathway (CHIR99021). The dual inhibition of PD0325901 and CHIR99021, termed 2i, was found to be effective for ESC culture; therefore the requirement for PD173074 became dispensable. If pluripotent mechanisms are conserved between species, we hypothesise that these inhibitors would aid the derivation of naïve ESCs in livestock species i.e. cattle.

The aim of this study was to assess the effects of these inhibitors on the developing bovine embryo. We hypothesised that the use of the inhibitors in culture medium would enhance the pluripotent characteristics of blastocysts for subsequent ESC culture. To test this idea we cultured in vitro fertilised bovine embryos in the presence of the inhibitors to initially assess the effect on embryo development. To assess embryo quality, blastocysts were analysed to evaluate the total number of cell nuclei. Additionally, mRNA and protein analyses were undertaken to characterise the expression of core pluripotent genes and assess if the inhibitors had an effect on their expression.

We found that culturing bovine embryos in either 3i or 2i did not influence the total number of embryos that progressed to the blastocyst stage. A significant decrease was observed in the proportion of early vs. late stage blastocysts in 2i, which suggested acceleration in the rate of development. In 2i medium, the number of cell nuclei in D7 blastocysts was significantly increased in both the inner cell mass (ICM) and the outer trophectoderm (TE). Additionally, embryos cultured in 2i showed a >2-fold increase in NANOG, a transcription factor at the core of the pluripotency network. The ICM-specific pluripotency marker SOX2 was also up-regulated in the presence of 2i. Both these genes were found to be significantly enriched in the ICM of bovine blastocysts. Overall, we conclude that bovine blastocysts differ from mouse in their response to 2i signal inhibition and molecular control of pluripotency.

text: Inhibition of ERK and GSK3 signalling pathways promotes development and expression of pluripotent markers in bovine blastocysts Embryo-derived pluripotent stem cells (ePSCs) naturally derive from different founder tissues, namely the early and late epiblast, that vary in their cellular characteristics. Recent evidence in mice suggests these sources of starting material correspond with two states of pluripotency referred to as ‘naïve’ and ‘primed’, respectively. Pluripotency is defined as the ability of a cell to give rise to any foetal or subsequent adult cell type. Naïve and primed ePSCs have different fundamental properties and only naïve cells can give rise to all cell types of an animal, including functional gametes (Nichols & Smith 2009). Until recently, naïve ePSCs (also known as embryonic stem cell or ESCs) were only available in mouse. After almost 30 years, the first non-mouse ESCs were derived in rat using a combination of specific inhibitors that block the FGF-ERK differentiation pathway and simultaneously maintain self-renewal through inhibition of GSK3 (Buehr et al. 2008; Ying et al. 2008). The three inhibitor combination, or 3i, included inhibitors of the FGF receptor (PD173074), downstream ERK activity (PD0325901) and the GSK3 pathway (CHIR99021). The dual inhibition of PD0325901 and CHIR99021, termed 2i, was found to be effective for ESC culture; therefore the requirement for PD173074 became dispensable. If pluripotent mechanisms are conserved between species, we hypothesise that these inhibitors would aid the derivation of naïve ESCs in livestock species i.e. cattle.

The aim of this study was to assess the effects of these inhibitors on the developing bovine embryo. We hypothesised that the use of the inhibitors in culture medium would enhance the pluripotent characteristics of blastocysts for subsequent ESC culture. To test this idea we cultured in vitro fertilised bovine embryos in the presence of the inhibitors to initially assess the effect on embryo development. To assess embryo quality, blastocysts were analysed to evaluate the total number of cell nuclei. Additionally, mRNA and protein analyses were undertaken to characterise the expression of core pluripotent genes and assess if the inhibitors had an effect on their expression.

We found that culturing bovine embryos in either 3i or 2i did not influence the total number of embryos that progressed to the blastocyst stage. A significant decrease was observed in the proportion of early vs. late stage blastocysts in 2i, which suggested acceleration in the rate of development. In 2i medium, the number of cell nuclei in D7 blastocysts was significantly increased in both the inner cell mass (ICM) and the outer trophectoderm (TE). Additionally, embryos cultured in 2i showed a >2-fold increase in NANOG, a transcription factor at the core of the pluripotency network. The ICM-specific pluripotency marker SOX2 was also up-regulated in the presence of 2i. Both these genes were found to be significantly enriched in the ICM of bovine blastocysts. Overall, we conclude that bovine blastocysts differ from mouse in their response to 2i signal inhibition and molecular control of pluripotency.

year: 2012