title: Preformulation and Formulation of Steroids and Assessment of an Electronically Modulated Intravaginal Device for Induced Calving or Oestrous synchronization of Cattle.

authors: Ismail, Ali Abdi

subjects: steroids

abstract: Drug delivery technology is currently advancing faster than at any time in biotechnology history. The challenge of drug delivery is to achieve a controlled release of therapeutic agents over an extended period. Controlled release potentially offers significant advantages over conventional dosage forms, by eliminating both under- and overdosing while maintaining a desired range of drug concentrations. An existing drug regimen for induced calving produces a declining blood profile that does not mimic the naturally occurring, gradually increasing, cortisol blood level around parturition effectively, causing animal health issues.  Likewise, while the existing progesterone controlled release systems for oestrous control successfully synchronise oestrus, it is however, associated with reduced fertility and as such other drugs have to be administered to improve the fertility during oestrus. Therefore, there is a need for a drug delivery system that is capable of delivering multiple drugs at various times and patterns. This research aimed to investigate, characterize, identify steroids with high absorption rates through vaginal mucosa and evaluate the potential of an electronic drug delivery system for the delivery of steroids for either the control of the bovine oestrous cycle or induced calving.
In order to identify steroids with high absorption rates across the vaginal mucosa, an in vitro permeation method was developed to screen selected steroids for their ability to permeate artificial and biological membranes. The steroids were pre-formulated to enhance their solubility and permeation through these membranes. Analytical UV and HPLC assays to characterise the pure and formulated steroidal compounds were also developed and validated. An assessment of an intravaginal Electronically Modulated Intravaginal Device (EMID) for the control of the bovine oestrous cycle or induced calving was carried out. Five different release assessment methods were investigated and critically evaluated in order to identify the most appropriate release assessment method for the EMID. These were: 1) the Drug Dissolution Test, 2) a weight loss method, 3) the dispensed weight method, 4) the determination of piston travel distance method, and 5) the rod expulsion from the EMID method. The methods investigated were critically evaluated in terms of ease of use and automation, reproducibility and cost/time savings. Optimisation of various components and construction materials of the EMID were also investigated. Animal trials were carried out using the original EMID (manufactured from polypropylene polymer) and modified inserts (manufactured from high density polyethylene polymer) to determine their retention rate in the animals. Accelerated stability testing of progesterone in suspension, oestradiol-17 tablets, cloprostenol as a powder blend and the driving mechanism of the EMID were examined.
The flux of the steroids was evaluated through poly-&-caprolactone and excised cow mucosa membranes using side-by-side permeation cells. 
Results indicated that progesterone followed by dexamethasone acetate and dexamethasone valerate showed higher permeability values through vaginal mucosa compared to dexamethasone or its other analogues. The weight loss method of the EMID proved to be an easy and appropriate method to measure the release rate from the EMID. A high density polyethylene polymer was identified as the most ideal body material for the insert compared to polypropylene body. Also double O-ring silicone, Elastollan WYO 1388-5 and solid silicone pistons were found to be amongst the best pistons tested and all performed well compared to other piston materials. There was a low retention rate with either the original EMID or the modified inserts. Further modification of retention wings of the EMID did not improve the retention rate, but a good blood profile response was obtained from cows treated with the complete EMID containing formulated progesterone. The formulations and driving mechanism were found to be stable under the tested conditions.  
Therefore, the EMID has potential for commercial application of induced calving or oestrous control per vaginum administration, reliant on improvement of its retention mechanism.

text: Preformulation and Formulation of Steroids and Assessment of an Electronically Modulated Intravaginal Device for Induced Calving or Oestrous synchronization of Cattle. Drug delivery technology is currently advancing faster than at any time in biotechnology history. The challenge of drug delivery is to achieve a controlled release of therapeutic agents over an extended period. Controlled release potentially offers significant advantages over conventional dosage forms, by eliminating both under- and overdosing while maintaining a desired range of drug concentrations. An existing drug regimen for induced calving produces a declining blood profile that does not mimic the naturally occurring, gradually increasing, cortisol blood level around parturition effectively, causing animal health issues.  Likewise, while the existing progesterone controlled release systems for oestrous control successfully synchronise oestrus, it is however, associated with reduced fertility and as such other drugs have to be administered to improve the fertility during oestrus. Therefore, there is a need for a drug delivery system that is capable of delivering multiple drugs at various times and patterns. This research aimed to investigate, characterize, identify steroids with high absorption rates through vaginal mucosa and evaluate the potential of an electronic drug delivery system for the delivery of steroids for either the control of the bovine oestrous cycle or induced calving.
In order to identify steroids with high absorption rates across the vaginal mucosa, an in vitro permeation method was developed to screen selected steroids for their ability to permeate artificial and biological membranes. The steroids were pre-formulated to enhance their solubility and permeation through these membranes. Analytical UV and HPLC assays to characterise the pure and formulated steroidal compounds were also developed and validated. An assessment of an intravaginal Electronically Modulated Intravaginal Device (EMID) for the control of the bovine oestrous cycle or induced calving was carried out. Five different release assessment methods were investigated and critically evaluated in order to identify the most appropriate release assessment method for the EMID. These were: 1) the Drug Dissolution Test, 2) a weight loss method, 3) the dispensed weight method, 4) the determination of piston travel distance method, and 5) the rod expulsion from the EMID method. The methods investigated were critically evaluated in terms of ease of use and automation, reproducibility and cost/time savings. Optimisation of various components and construction materials of the EMID were also investigated. Animal trials were carried out using the original EMID (manufactured from polypropylene polymer) and modified inserts (manufactured from high density polyethylene polymer) to determine their retention rate in the animals. Accelerated stability testing of progesterone in suspension, oestradiol-17 tablets, cloprostenol as a powder blend and the driving mechanism of the EMID were examined.
The flux of the steroids was evaluated through poly-&-caprolactone and excised cow mucosa membranes using side-by-side permeation cells. 
Results indicated that progesterone followed by dexamethasone acetate and dexamethasone valerate showed higher permeability values through vaginal mucosa compared to dexamethasone or its other analogues. The weight loss method of the EMID proved to be an easy and appropriate method to measure the release rate from the EMID. A high density polyethylene polymer was identified as the most ideal body material for the insert compared to polypropylene body. Also double O-ring silicone, Elastollan WYO 1388-5 and solid silicone pistons were found to be amongst the best pistons tested and all performed well compared to other piston materials. There was a low retention rate with either the original EMID or the modified inserts. Further modification of retention wings of the EMID did not improve the retention rate, but a good blood profile response was obtained from cows treated with the complete EMID containing formulated progesterone. The formulations and driving mechanism were found to be stable under the tested conditions.  
Therefore, the EMID has potential for commercial application of induced calving or oestrous control per vaginum administration, reliant on improvement of its retention mechanism.

year: 2007

title: Lost points of intervention in pathways to single adult homelessness in Hamilton, New Zealand

authors: McMinn, Carole Ann

subjects: Homeless

abstract: Homelessness is a serious problem in New Zealand, with many social, health, human rights, and economic ramifications. Despite a broad consensus in international literature about contributing factors which raise the risk of homelessness, many misconceptions still remain about which specific factors contribute to homelessness in New Zealand. This is in part because of limited research in this context. Many policy responses to homelessness in New Zealand focus on a person’s need for adequate housing as this is the prime presenting issue.  However, people often have complex existing background issues that also contributed, and these are equally important targets for policy responses to homelessness. 

Those who are single adults, without dependent children and homeless are often those found living in the most precarious circumstances. This cohort were the focus of this research. The objectives of this research were to determine pathways to single adult homelessness in Hamilton, New Zealand and to consider what other contributing factors and trigger events raised the risk of single adult homelessness. Robust objective quantitative and qualitative research into these contributors and triggers of homelessness is necessary to improve homelessness intervention. Further, recommendations about points of intervention were sought from those with the most knowledge about homelessness, those with lived experience. 

This research included structured questionnaires completed with 100 participants who were program participants engaged with a homeless service in Hamilton, New Zealand. Additional detailed qualitative narrative was collected by semi-structured interviews with 11 participants. One-on-one feedback interviews were conducted with six participants. A mixed method approach netted a rich and diverse body of data about single adult homelessness in Hamilton and provided for the collection of robust evidence about important points and means of intervention and prevention. 

Although everyone’s circumstances were unique, results revealed a series of commonly occurring disruptive events throughout participants’ lifetimes. A very high prevalence of adverse childhood events had resulted in an early exit from home for most participants, and time spent in state care. Instability in childhood had led to disruption, or exclusion, from schooling. Early disruption of social networks resulted in participants being isolated from natural familial and kinship support at critical points. Problematic substance use and mental health issues were common, often resulting in early institutionalization. These health and wellbeing issues had lifelong effects. 

Structural issues exacerbated circumstances for people. Participants lacked access to safe, affordable single-person private rental and public housing. Additionally, people experienced discrimination in their efforts to find housing. Participants had constrained incomes, most receiving welfare support, which further limited housing options in times of crisis. Many had high debt, particularly owed to government departments. Participants who sustained active relationships with government agencies and other organizations did not find these relationships to be a protective factor against homelessness. People sought the help of a homeless service because they felt they had nowhere else to turn. 

Participants’ recommendations provided important implications for policy responses to homelessness. A targeted reduction in family violence was advocated as a prevention opportunity.  Detecting, and supporting, those who have survived adverse childhood events was also seen as a critical point of intervention. Trauma-informed approaches to social sector support would help reduce negative assumptions and victim blaming. Social sectors were also described as needing to be supported to eliminate discrimination. 

Additional measures were advocated to prevent formerly homeless individuals returning to homelessness.  This included support to facilitate access to a home (not a room), with comprehensive support to help people maintain this tenancy. Support to attend to background issues was also advocated. Facilitated access to work (where desired) was recommended as one mechanism to help reduce high levels of debt, particularly institutional debt. The absence of important familial and kinship networks to help provide support to access housing and other resources at critical points was a key factor participants identified as raising the risk of them becoming homeless. Therefore, alternative support mechanisms, such as homeless services like The People’s Project, were advocated.

text: Lost points of intervention in pathways to single adult homelessness in Hamilton, New Zealand Homelessness is a serious problem in New Zealand, with many social, health, human rights, and economic ramifications. Despite a broad consensus in international literature about contributing factors which raise the risk of homelessness, many misconceptions still remain about which specific factors contribute to homelessness in New Zealand. This is in part because of limited research in this context. Many policy responses to homelessness in New Zealand focus on a person’s need for adequate housing as this is the prime presenting issue.  However, people often have complex existing background issues that also contributed, and these are equally important targets for policy responses to homelessness. 

Those who are single adults, without dependent children and homeless are often those found living in the most precarious circumstances. This cohort were the focus of this research. The objectives of this research were to determine pathways to single adult homelessness in Hamilton, New Zealand and to consider what other contributing factors and trigger events raised the risk of single adult homelessness. Robust objective quantitative and qualitative research into these contributors and triggers of homelessness is necessary to improve homelessness intervention. Further, recommendations about points of intervention were sought from those with the most knowledge about homelessness, those with lived experience. 

This research included structured questionnaires completed with 100 participants who were program participants engaged with a homeless service in Hamilton, New Zealand. Additional detailed qualitative narrative was collected by semi-structured interviews with 11 participants. One-on-one feedback interviews were conducted with six participants. A mixed method approach netted a rich and diverse body of data about single adult homelessness in Hamilton and provided for the collection of robust evidence about important points and means of intervention and prevention. 

Although everyone’s circumstances were unique, results revealed a series of commonly occurring disruptive events throughout participants’ lifetimes. A very high prevalence of adverse childhood events had resulted in an early exit from home for most participants, and time spent in state care. Instability in childhood had led to disruption, or exclusion, from schooling. Early disruption of social networks resulted in participants being isolated from natural familial and kinship support at critical points. Problematic substance use and mental health issues were common, often resulting in early institutionalization. These health and wellbeing issues had lifelong effects. 

Structural issues exacerbated circumstances for people. Participants lacked access to safe, affordable single-person private rental and public housing. Additionally, people experienced discrimination in their efforts to find housing. Participants had constrained incomes, most receiving welfare support, which further limited housing options in times of crisis. Many had high debt, particularly owed to government departments. Participants who sustained active relationships with government agencies and other organizations did not find these relationships to be a protective factor against homelessness. People sought the help of a homeless service because they felt they had nowhere else to turn. 

Participants’ recommendations provided important implications for policy responses to homelessness. A targeted reduction in family violence was advocated as a prevention opportunity.  Detecting, and supporting, those who have survived adverse childhood events was also seen as a critical point of intervention. Trauma-informed approaches to social sector support would help reduce negative assumptions and victim blaming. Social sectors were also described as needing to be supported to eliminate discrimination. 

Additional measures were advocated to prevent formerly homeless individuals returning to homelessness.  This included support to facilitate access to a home (not a room), with comprehensive support to help people maintain this tenancy. Support to attend to background issues was also advocated. Facilitated access to work (where desired) was recommended as one mechanism to help reduce high levels of debt, particularly institutional debt. The absence of important familial and kinship networks to help provide support to access housing and other resources at critical points was a key factor participants identified as raising the risk of them becoming homeless. Therefore, alternative support mechanisms, such as homeless services like The People’s Project, were advocated.

year: 2021

title: Tauira Rangatahi Numeracy and Literacy Programme: Apps in Numeracy and Literacy Research

authors: Calder, Nigel Stuart

subjects: Youth Guarantee

abstract: A key aspect of tertiary education undertaken by Te Wananga o Aotearoa (TWoA) is re-establishing engagement and success in the rangatahi space through meeting the literacy and numeracy demands for programmes at levels 1–3. TWoA has Youth Guarantee programmes that deliver introductory Sport and Leisure and Contemporary Māori Arts programmes with embedded literacy and numeracy. The purpose of this research project was to investigate tauira rangatahi attitudes towards literacy and numeracy development through the application of appropriate cultural capital in conjunction with contemporary digital technologies. The research examined the influence of iPad apps on the beliefs and attitudes of Youth Guarantee tauira towards numeracy and literacy.

text: Tauira Rangatahi Numeracy and Literacy Programme: Apps in Numeracy and Literacy Research A key aspect of tertiary education undertaken by Te Wananga o Aotearoa (TWoA) is re-establishing engagement and success in the rangatahi space through meeting the literacy and numeracy demands for programmes at levels 1–3. TWoA has Youth Guarantee programmes that deliver introductory Sport and Leisure and Contemporary Māori Arts programmes with embedded literacy and numeracy. The purpose of this research project was to investigate tauira rangatahi attitudes towards literacy and numeracy development through the application of appropriate cultural capital in conjunction with contemporary digital technologies. The research examined the influence of iPad apps on the beliefs and attitudes of Youth Guarantee tauira towards numeracy and literacy.

year: 2014