title: Secondary Blooming and Mottling in an Intravaginal Drug Release Product

authors: Waugh, Brendan Arthur

subjects: progesterone

abstract: This study was undertaken to determine the root cause of secondary blooming (surface progesterone) and mottling (translucent regions) in the CIDR insert.

A stability study on CIDR inserts found that the alternative supplier silicone (Dow Corning silicone is used in normal manufacture) did not exhibit either secondary blooming or mottling, in agreement with previous work. There was no difference in ‘in vitro’ drug release rate between CIDR inserts made from the two silicone feedstocks. This silicone was found to have a higher ratio of low molecular weight cyclic silicone compounds to straight chain silicone compounds (Measured through detected ion ratios in the leachate by ESMS). The exact relationship between blooming and secondary mottling and this discovery remains unknown.

Results from this research found that part B of the Dow Corning silicone was not responsible for causing secondary blooming and mottling in contrast to previous research. ESMS and GCMS results found that the Dow Corning part B had a more complex composition than of the samples from Dow Corning part A and alternative supplier silicone part A and part B.

It was found that addition of a silicone crosslinker into the Dow Corning silicone, increased mottling, but not secondary blooming. Increasing the mixing of progesterone and liquid silicone decreased mottling (via a static mixer), but did not increase surface progesterone.

The results from two studies into the packing of CIDR inserts immediately after manufacture were contradictory as one found a decrease in mottling from packing in line, while the other found no change in mottling. However there was no difference observed in surface progesterone levels between the packing conditions. Studies on the length of cure were also found to have no predictable effect on mottling.

Studies on arresting the cooling cured silicone above, between and below the melting points of the α and β progesterone polymorphs found that pausing cooling after cure at ~135 °C resulted in decreased secondary blooming and mottling, and that pausing after cure at ~125 °C exhibited less secondary blooming. Neither DSC nor XRD was able to determine a polymorphic bias in progesterone cooled by this cooling process (β progesterone polymorph was in all but one case (that had an added reduction in normal cooling rate)). Studies (XRD and DSC) on the cooling rate of progesterone found that only with very slow cooling rates was the α progesterone polymorph formed. XRD studies also revealed that the mottled regions of CIDR inserts exhibit the β progesterone polymorph, whereas the α progesterone polymorph was detected in non-mottled regions. The mottled regions were found to continue to exhibit the same polymorph after removal of surface progesterone, whereas the non-mottled regions gave no detectable XRD peak intensity.

The study found useful information to assist in the determination of the root cause of secondary blooming and mottling in CIDR inserts. However the root cause remains unknown.

text: Secondary Blooming and Mottling in an Intravaginal Drug Release Product This study was undertaken to determine the root cause of secondary blooming (surface progesterone) and mottling (translucent regions) in the CIDR insert.

A stability study on CIDR inserts found that the alternative supplier silicone (Dow Corning silicone is used in normal manufacture) did not exhibit either secondary blooming or mottling, in agreement with previous work. There was no difference in ‘in vitro’ drug release rate between CIDR inserts made from the two silicone feedstocks. This silicone was found to have a higher ratio of low molecular weight cyclic silicone compounds to straight chain silicone compounds (Measured through detected ion ratios in the leachate by ESMS). The exact relationship between blooming and secondary mottling and this discovery remains unknown.

Results from this research found that part B of the Dow Corning silicone was not responsible for causing secondary blooming and mottling in contrast to previous research. ESMS and GCMS results found that the Dow Corning part B had a more complex composition than of the samples from Dow Corning part A and alternative supplier silicone part A and part B.

It was found that addition of a silicone crosslinker into the Dow Corning silicone, increased mottling, but not secondary blooming. Increasing the mixing of progesterone and liquid silicone decreased mottling (via a static mixer), but did not increase surface progesterone.

The results from two studies into the packing of CIDR inserts immediately after manufacture were contradictory as one found a decrease in mottling from packing in line, while the other found no change in mottling. However there was no difference observed in surface progesterone levels between the packing conditions. Studies on the length of cure were also found to have no predictable effect on mottling.

Studies on arresting the cooling cured silicone above, between and below the melting points of the α and β progesterone polymorphs found that pausing cooling after cure at ~135 °C resulted in decreased secondary blooming and mottling, and that pausing after cure at ~125 °C exhibited less secondary blooming. Neither DSC nor XRD was able to determine a polymorphic bias in progesterone cooled by this cooling process (β progesterone polymorph was in all but one case (that had an added reduction in normal cooling rate)). Studies (XRD and DSC) on the cooling rate of progesterone found that only with very slow cooling rates was the α progesterone polymorph formed. XRD studies also revealed that the mottled regions of CIDR inserts exhibit the β progesterone polymorph, whereas the α progesterone polymorph was detected in non-mottled regions. The mottled regions were found to continue to exhibit the same polymorph after removal of surface progesterone, whereas the non-mottled regions gave no detectable XRD peak intensity.

The study found useful information to assist in the determination of the root cause of secondary blooming and mottling in CIDR inserts. However the root cause remains unknown.

year: 2006

title: Time-series and cross-sectional momentum investment strategies: International evidence

authors: Gao, Xiaojun

subjects: strategy

abstract: Numerous studies have found that profits that can be realised from following a momentum-based investment strategy of buying recent outperforming stocks (winners) and selling recent underperforming stocks (losers) (Jegadeesh & Titman, 1993, 2001). Momentum strategies have proved to be robust across time, countries and asset classes, leading Fama (1998) to observe that momentum remains the “premier unexplained anomaly”. The existence of the momentum abnormal returns continues to challenge the market efficiency theory.
The majority of momentum studies have investigated cross-sectional momentum strategies in which stocks are selected on the basis of their relative performances over some prior period. In a recent study, Moskowitz, Ooi, and Pedersen (2012) introduce a time-series momentum strategy which provides an alternative approach to security selection where stocks are chosen on the basis of their absolute performance over some prior period.
Although previous literature has evaluated momentum strategies in numerous markets settings, by far the bulk of these studies have concentrated on equity markets. Therefore, it is somewhat surprising that we are yet to see a comprehensive study that compares the two types of momentum strategies in this arena. The main objective of this study is to evaluate and compare the performances of the two momentum strategies in the security markets in order to examine validation of the market efficiency theory across international stock markets.
The study addresses the objective in three stages: before-transaction costs performance (raw returns), after-transaction costs performance (net returns) and after-transaction costsperformance adjusted for risks (risk-adjusted net returns). A further by-product of our research is that we utilise a large number of implementation alternatives for both momentum strategies and so provides an insight into the optimal way to implement both time-series and cross-sectional momentum strategies.
Before transaction cost (raw) return:
The first thing that has been found is that the time-series and cross-sectional momentum returns reduce as we increase the cut-offs used when choosing both winning and losing stocks and so increase the number of stocks in the momentum portfolios (i.e. including 32%, 60% and all stocks in either the winner or loser portfolios). The extension of the cut-offs from 32% to 100% results in a reduction in the returns on the momentum portfolios by approximately 50% on average based on the pooled data for the 24 markets. Having established this, we then use the 32% cut-offs over the remainder of our analysis.
The study finds that both time-series and cross-sectional momentum strategies produce significant positive outcomes under numerous implementations in the majority of developed stock markets with the major exceptions being Greece, Israel, Japan, Hong Kong, Portugal, Spain and the US. The time-series momentum strategy outperforms the cross-sectional momentum strategy under optimal implementations conditions in all markets and is statistically significant in half of these markets.
After transaction costs (net) returns, and risk-adjustment net returns:
We find that the transaction costs and standard risk explain most profitability of the time-series and cross-sectional momentum strategies. In terms of the Fama-French alpha determined using after-transaction costs return, about 6% on average of the implementations evaluated produce significant positive risk-adjusted net returns. There are absolutely no implementations that yield significant positive returns in Austria, France, Germany, Greece, Hong Kong, Israel, Japan, Norway, Portugal, Singapore, Spain and the US., while less than 5%of the implementations in Australia, Canada, and Ireland. The findings support that the market efficiency hypothesis still holds across the most markets in our sample and the existence of exploitable investment opportunities is rare.
The study particularly concentrates on the optimal implementations of both the time-series and cross-sectional momentum strategies across the 24 markets. Common characteristics of these optimal implementations for the risk-adjusted net returns are that they combine a formation and a holding period of between 15 and 18 months, a buy-and-hold portfolio construction policy and the use of either a market or inversed-volatility portfolio weighting scheme.
Based on the optimal implementation approach for each market, the overall performance of the two momentum strategies is eroded from 2.09% (raw return) to 1.34% (net return) and to 0.9% (Fama-French alpha) for the time-series momentum strategy, and from 1.43% (raw return) to 0.87% (net return) and finally to 0.51% (Fama-French alpha) for the cross-sectional momentum strategy. At each of the three steps along the way, this study finds that the time-series momentum strategy continues to outperform the cross-sectional momentum strategy; however the magnitude of the superior performance is diluted with an average difference from 0.66% (raw return) to 0.47% (net return) and to 0.39% (Fama-French alpha). In addition, the superior performance of the time-series momentum strategy relative to the cross-sectional momentum strategy comes during periods when the markets have been performing poorly but that this advantage also erodes as we proceed from raw returns to net returns to risk-adjusted net returns.
One possible explanation for the superiority of the time-series momentum strategy is that it forms portfolios of slightly smaller capitalization stocks with a greater spread in past performance between the winner and loser stocks. Both of these features suggest that thetime-series momentum strategy will outperform the cross-sectional momentum strategy. On the other hand, the transaction costs and risk from the time-series momentum strategy are higher than the costs from the cross-sectional momentum strategy which is largely a consequence of time-series momentum strategy selecting smaller and growth stocks, and generating a higher turnover over a market cycle, so it is not surprising that the outperformance of the time-series momentum strategy becomes smaller after adjusting for risk on an after-transaction costs basis.

text: Time-series and cross-sectional momentum investment strategies: International evidence Numerous studies have found that profits that can be realised from following a momentum-based investment strategy of buying recent outperforming stocks (winners) and selling recent underperforming stocks (losers) (Jegadeesh & Titman, 1993, 2001). Momentum strategies have proved to be robust across time, countries and asset classes, leading Fama (1998) to observe that momentum remains the “premier unexplained anomaly”. The existence of the momentum abnormal returns continues to challenge the market efficiency theory.
The majority of momentum studies have investigated cross-sectional momentum strategies in which stocks are selected on the basis of their relative performances over some prior period. In a recent study, Moskowitz, Ooi, and Pedersen (2012) introduce a time-series momentum strategy which provides an alternative approach to security selection where stocks are chosen on the basis of their absolute performance over some prior period.
Although previous literature has evaluated momentum strategies in numerous markets settings, by far the bulk of these studies have concentrated on equity markets. Therefore, it is somewhat surprising that we are yet to see a comprehensive study that compares the two types of momentum strategies in this arena. The main objective of this study is to evaluate and compare the performances of the two momentum strategies in the security markets in order to examine validation of the market efficiency theory across international stock markets.
The study addresses the objective in three stages: before-transaction costs performance (raw returns), after-transaction costs performance (net returns) and after-transaction costsperformance adjusted for risks (risk-adjusted net returns). A further by-product of our research is that we utilise a large number of implementation alternatives for both momentum strategies and so provides an insight into the optimal way to implement both time-series and cross-sectional momentum strategies.
Before transaction cost (raw) return:
The first thing that has been found is that the time-series and cross-sectional momentum returns reduce as we increase the cut-offs used when choosing both winning and losing stocks and so increase the number of stocks in the momentum portfolios (i.e. including 32%, 60% and all stocks in either the winner or loser portfolios). The extension of the cut-offs from 32% to 100% results in a reduction in the returns on the momentum portfolios by approximately 50% on average based on the pooled data for the 24 markets. Having established this, we then use the 32% cut-offs over the remainder of our analysis.
The study finds that both time-series and cross-sectional momentum strategies produce significant positive outcomes under numerous implementations in the majority of developed stock markets with the major exceptions being Greece, Israel, Japan, Hong Kong, Portugal, Spain and the US. The time-series momentum strategy outperforms the cross-sectional momentum strategy under optimal implementations conditions in all markets and is statistically significant in half of these markets.
After transaction costs (net) returns, and risk-adjustment net returns:
We find that the transaction costs and standard risk explain most profitability of the time-series and cross-sectional momentum strategies. In terms of the Fama-French alpha determined using after-transaction costs return, about 6% on average of the implementations evaluated produce significant positive risk-adjusted net returns. There are absolutely no implementations that yield significant positive returns in Austria, France, Germany, Greece, Hong Kong, Israel, Japan, Norway, Portugal, Singapore, Spain and the US., while less than 5%of the implementations in Australia, Canada, and Ireland. The findings support that the market efficiency hypothesis still holds across the most markets in our sample and the existence of exploitable investment opportunities is rare.
The study particularly concentrates on the optimal implementations of both the time-series and cross-sectional momentum strategies across the 24 markets. Common characteristics of these optimal implementations for the risk-adjusted net returns are that they combine a formation and a holding period of between 15 and 18 months, a buy-and-hold portfolio construction policy and the use of either a market or inversed-volatility portfolio weighting scheme.
Based on the optimal implementation approach for each market, the overall performance of the two momentum strategies is eroded from 2.09% (raw return) to 1.34% (net return) and to 0.9% (Fama-French alpha) for the time-series momentum strategy, and from 1.43% (raw return) to 0.87% (net return) and finally to 0.51% (Fama-French alpha) for the cross-sectional momentum strategy. At each of the three steps along the way, this study finds that the time-series momentum strategy continues to outperform the cross-sectional momentum strategy; however the magnitude of the superior performance is diluted with an average difference from 0.66% (raw return) to 0.47% (net return) and to 0.39% (Fama-French alpha). In addition, the superior performance of the time-series momentum strategy relative to the cross-sectional momentum strategy comes during periods when the markets have been performing poorly but that this advantage also erodes as we proceed from raw returns to net returns to risk-adjusted net returns.
One possible explanation for the superiority of the time-series momentum strategy is that it forms portfolios of slightly smaller capitalization stocks with a greater spread in past performance between the winner and loser stocks. Both of these features suggest that thetime-series momentum strategy will outperform the cross-sectional momentum strategy. On the other hand, the transaction costs and risk from the time-series momentum strategy are higher than the costs from the cross-sectional momentum strategy which is largely a consequence of time-series momentum strategy selecting smaller and growth stocks, and generating a higher turnover over a market cycle, so it is not surprising that the outperformance of the time-series momentum strategy becomes smaller after adjusting for risk on an after-transaction costs basis.

year: 2012

title: Ethnicity and deliberate self-injury: A review of the literature

authors: Wilson, Cate

subjects: Maori

abstract: Deliberate self-injury is a significant social problem affecting youth in New Zealand. Rates of
hospitalisation for youth (aged 15 to 19) from deliberate self-injury approximate 225 per
100,000. It appears that the rates for Maori and women are significantly higher. From 1987 to
1993, an average of 488 Maori women per 100 000 population have been hospitalised each
year (Ministry of Health: Manatu Hauora, 1996). This paper draws upon both local and
international literature to examine factors underlying this ethnic disparity.
There is a wealth of literature examining risk factors underlying suicidal behaviour as a whole.
Deliberate self-injury is usually assumed to be an adjunct of youth suicide; prevention
strategies are conflated. This paper argues that this assumption is untenable, and in particular,
that prevention strategies designed for youth suicide are problematic in terms of deliberate selfinjury.
While prevention strategies are based upon studies that do not differentiate between
these groups, results will be compromised.

text: Ethnicity and deliberate self-injury: A review of the literature Deliberate self-injury is a significant social problem affecting youth in New Zealand. Rates of
hospitalisation for youth (aged 15 to 19) from deliberate self-injury approximate 225 per
100,000. It appears that the rates for Maori and women are significantly higher. From 1987 to
1993, an average of 488 Maori women per 100 000 population have been hospitalised each
year (Ministry of Health: Manatu Hauora, 1996). This paper draws upon both local and
international literature to examine factors underlying this ethnic disparity.
There is a wealth of literature examining risk factors underlying suicidal behaviour as a whole.
Deliberate self-injury is usually assumed to be an adjunct of youth suicide; prevention
strategies are conflated. This paper argues that this assumption is untenable, and in particular,
that prevention strategies designed for youth suicide are problematic in terms of deliberate selfinjury.
While prevention strategies are based upon studies that do not differentiate between
these groups, results will be compromised.

year: 1999