A modified pseudolikelihood approach for analysis of longitudinal data

We consider the analysis of longitudinal data when the covariance function is modeled by additional parameters to the mean parameters. In general, inconsistent estimators of the covariance (variance/correlation) parameters will be produced when the "working" correlation matrix is misspecified, which may result in great loss of efficiency of the mean parameter estimators (albeit the consistency is preserved). We consider using different "Working" correlation models for the variance and the mean parameters. In particular, we find that an independence working model should be used for estimating the variance parameters to ensure their consistency in case the correlation structure is misspecified. The designated "working" correlation matrices should be used for estimating the mean and the correlation parameters to attain high efficiency for estimating the mean parameters. Simulation studies indicate that the proposed algorithm performs very well. We also applied different estimation procedures to a data set from a clinical trial for illustration.

Robust estimating functions and bias correction for longitudinal data analysis

Robust methods are useful in making reliable statistical inferences when there are small deviations from the model assumptions. The widely used method of the generalized estimating equations can be "robustified" by replacing the standardized residuals with the M-residuals. If the Pearson residuals are assumed to be unbiased from zero, parameter estimators from the robust approach are asymptotically biased when error distributions are not symmetric. We propose a distribution-free method for correcting this bias. Our extensive numerical studies show that the proposed method can reduce the bias substantially. Examples are given for illustration.

Effects of variance-function misspecification in analysis of longitudinal data

The approach of generalized estimating equations (GEE) is based on the framework of generalized linear models but allows for specification of a working matrix for modeling within-subject correlations. The variance is often assumed to be a known function of the mean. This article investigates the impacts of misspecifying the variance function on estimators of the mean parameters for quantitative responses. Our numerical studies indicate that (1) correct specification of the variance function can improve the estimation efficiency even if the correlation structure is misspecified; (2) misspecification of the variance function impacts much more on estimators for within-cluster covariates than for cluster-level covariates; and (3) if the variance function is misspecified, correct choice of the correlation structure may not necessarily improve estimation efficiency. We illustrate impacts of different variance functions using a real data set from cow growth.

Designs for phase I clinical trials with multiple courses of subjects at different doses

The goal of this article is to provide a new design framework and its corresponding estimation for phase I trials. Existing phase I designs assign each subject to one dose level based on responses from previous subjects. Yet it is possible that subjects with neither toxicity nor efficacy responses can be treated at higher dose levels, and their subsequent responses to higher doses will provide more information. In addition, for some trials, it might be possible to obtain multiple responses (repeated measures) from a subject at different dose levels. In this article, a nonparametric estimation method is developed for such studies. We also explore how the designs of multiple doses per subject can be implemented to improve design efficiency. The gain of efficiency from "single dose per subject" to "multiple doses per subject" is evaluated for several scenarios. Our numerical study shows that using "multiple doses per subject" and the proposed estimation method together increases the efficiency substantially.

Assessing the taxonomic status of dingoes Canis familiaris for conservation

1. The conservation status of the dingo Canis familiaris dingo is threatened by hybridization with the domestic dog C. familiaris familiaris. A practical method that can estimate the different levels of hybridization in the field is urgently required so that animals below a specific threshold of dingo ancestry (e.g. 1/4 or 1/2 dingoes) can reliably be identified and removed from dingo populations. 2. Skull morphology has been traditionally used to assess dingo purity, but this method does not discriminate between the different levels of dingo ancestry in hybrids. Furthermore, measurements can only be reliably taken from the skulls of dead animals. 3. Methods based on the analysis of variation in DNA are able to discriminate between the different levels of hybridization, but the validity of this method has been questioned because the materials currently used as a reference for dingoes are from captive animals of unproven genetic purity. The use of pre-European materials would improve the accuracy of this method, but suitable material has not been found in sufficient quantity to develop a reliable reference population. Furthermore, current methods based on DNA are impractical for the field-based discrimination of hybrids because samples require laboratory analysis. 4. Coat colour has also been used to estimate the extent of hybridization and is possibly the most practical method to apply in the field. However, this method may not be as powerful as genetic or morphological analyses because some hybrids (e.g. Australian cattle dog × dingo) are similar to dingoes in coat colour and body form. This problem may be alleviated by using additional visual characteristics such as the presence/absence of ticking and white markings.

Maximising the contribution of native-range studies towards the identification and prioritisation of weed biocontrol agents

Effective study in the native range to identify potential agents underpins all efforts in classical biological control of weeds. Good agents that demonstrate both a high degree of host specificity and the potential to be damaging are a very limited resource and must therefore be carefully studied and considered. The overseas component is often operationally difficult and expensive but can contribute considerably more than a list of herbivores attacking a particular target. While the principles underlying this foreign component have been understood for some time, recently developed technologies and methods can make very significant contributions to foreign studies. Molecular and genetic characterisations of both target weed and agent organism can be increasingly employed to more accurately define the identity and phylogeny of them. Climate matching and modelling software is now available and can be utilised to better select agents for particular regions of concern. Relational databases can store collection information for analysis and future enquiry while quantification of sampling effort, employment of statistical survey methods and analysis by techniques such as rarefaction curves contribute to efficient and effective searching. Obtaining good and timely identifications for discovered agent organisms is perhaps the most serious issue confronting the modern explorer. The diminishing numbers of specialist taxonomists employed at the major museums while international and national protocols demand higher standards of identity exacerbates the issue. Genetic barcoding may provide a very useful tool to overcome this problem. Native-range work also offers under-exploited opportunities for contributing towards predicting safety, abundance and efficacy of potential agents in their target environment.

Risk Minimizing Option Pricing in a Semi-Markov Modulated Market

We address risk minimizing option pricing in a semi-Markov modulated market where the floating interest rate depends on a finite state semi-Markov process. The growth rate and the volatility of the stock also depend on the semi-Markov process. Using the Föllmer–Schweizer decomposition we find the locally risk minimizing price for European options and the corresponding hedging strategy. We develop suitable numerical methods for computing option prices.

Studies of Solids and Surfaces by Auger Electron Spectroscopy

Although the applications of Auger electron spectroscopy in surface analysis have by far outweighed its use as a tool to investigate electron states of solids and surfaces, there are a variety of situations where Auger spectroscopy provides unique information. Apart from the chemical shifts, Auger intensities are useful in determining the number of d-electron states in transition metal systems. Auger spectroscopy is a good probe to investigate the surface oxidation of metals. In addition to the intra-atomic Auger transitions, inter-atomic transitions observed in oxides and other systems reveal the nature of electron states of surfaces. Charge-transfer and hybridization effects in alloys are also usefully studied by Auger spectroscopy. Auger electron spectroscopy has not been a popular technique to investigate adsorption of molecules on surfaces, but the technique is useful to obtain fingerprints of surface species.

Using catch rate data for simple cost-effective quota setting in the Australian spanner crab (Ranina ranina) fishery.

For many fisheries, there is a need to develop appropriate indicators, methodologies, and rules for sustainably harvesting marine resources. Complexities of scientific and financial factors often prevent addressing these, but new methodologies offer significant improvements on current and historical approaches. The Australian spanner crab fishery is used to demonstrate this. Between 1999 and 2006, an empirical management procedure using linear regression of fishery catch rates was used to set the annual total allowable catch (quota). A 6-year increasing trend in catch rates revealed shortcomings in the methodology, with a 68% increase in quota calculated for the 2007 fishing year. This large quota increase was prevented by management decision rules. A revised empirical management procedure was developed subsequently, and it achieved a better balance between responsiveness and stability. Simulations identified precautionary harvest and catch rate baselines to set quotas that ensured sustainable crab biomass and favourable performance for management and industry. The management procedure was simple to follow, cost-effective, robust to strong trends and changes in catch rates, and adaptable for use in many fisheries. Application of such “tried-and-tested” empirical systems will allow improved management of both data-limited and data-rich fisheries.

Latitudinal and seasonal effects on growth of the Australian eastern king prawn (Melicertus plebejus)

The growth of the Australian eastern king prawn (Melicertus plebejus) is understood in greater detail by quantifying the latitudinal effect. The latitudinal effect is the change in the species’ growth rate during migration. Mark–recapture data (N = 1635, latitude 22.21°S–34.00°S) presents northerly movement of the eastern king prawn, with New South Wales prawns showing substantial average movement of 140 km (standard deviation: 176 km) north. A generalized von Bertalanffy growth model framework is used to incorporate the latitudinal effect together with the canonical seasonal effect. Applying this method to eastern king prawn mark–recapture data guarantees consistent estimates for the latitudinal and seasonal effects. For M. plebejus, it was found that growth rate peaks on 25 and 29 January for males and females, respectively; is at a minimum on 27 and 31 July, respectively; and that the shape parameter, k (per year), changes by –0.0236 and –0.0556 every 1 degree of latitude south increase for males and females, respectively.

Kinetics of resinification of furfuryl alcohol in aqueous solution

Kinetic information on the resinification of furfuryl alcohol has been derived from the rate of increase of color intensity measured with a photoelectric colorimeter, the resinification being carried out isothermally in Clark-Lubs aqueous buffer solutions in the pH range of 1.0-2.2. The activation energy for polymerization is found to increase exponentially with pH. The time required for emulsification (which is quickly followed by separation of resin layer) to occur in an aqueous solution of furfuryl alcohol also increases exponentially with pH, but it decreases exponentially with temperature. This is described quantitatively by a single expression.

SPECT-aided diagnostics and genetic risk factors in Parkinson's disease

Hypokinesia, rigidity, tremor, and postural instability are the cardinal symptoms of Parkinson s disease (PD). Since these symptoms are not specific to PD the diagnosis may be uncertain in early PD. Etiology and pathogenesis of PD remain unclear. There is no neuroprotective therapy. Genetic findings are expected to reveal metabolic routes in PD pathogenesis and thereby eventually lead to therapeutic innovations. In this thesis, we first aimed to study the usefulness and accuracy of 123I-b-CIT SPECT in the diagnosis of PD in a consecutive clinic-based material including various movement disorders. We subsequently a genetic project to identify genetic risk factors for sporadic PD using a candidate gene approach in a case-control setting including 147 sporadic PD patients and 137 spouse controls. Dopamine transporter imaging by 123I-b-CIT SPECT could distinguish PD from essential tremor, drug-induced parkinsonism, dystonia and psychogenic parkinsonism. However, b-CIT uptake in Parkinson plus syndromes (PSP and multiple system atrophy) and dementia with Lewy bodies was not significantly different from PD. 123I-b-CIT SPECT could not reliably differentiate PD from vascular parkinsonism. 123I-b-CIT SPECT was 100% sensitive and specific in the diagnosis of PD in patients younger than 55 years but less specific in older patients, due to differential distribution of the above conditions in the younger and older age groups. 123I-b-CIT SPECT correlated with symptoms and detected bilateral nigrostriatal defect in patients whose PD was still in unilateral stage. Thus, in addition to as a differential diagnostic aid, 123I-b-CIT SPECT may be used to detect PD early, even pre-symptomatically in at-risk individuals. 123I-b-CIT SPECT was used to aid in the collection of patients to the genetic studies. In the genetic part of this thesis we found an association between PD and a polymorphic CAG-repeat in POLG1 gene encoding the catalytic subunit of mitochondrial polymerase gamma. The CAG-repeat encodes a polyglutamine tract (polyQ), the two most common lengths of which are 10Q (86-90%) and 11Q. In our Finnish material, the rarer non-10Q or non-11Q length variants (6Q-9Q, 12Q-14Q, 4R+9Q) were more frequent in patients than in spouse controls (10% vs. 3.5 %, p=0.003), or population controls (p=0.001). Therefore, we performed a replication study in 652 North American PD patients and 292 controls. Non-10/11Q alleles were more common in the US PD patients compared to the controls but the difference did not reach statistical significance (p=0.07). This larger data suggested our original definition of variant length allele might need reconsideration. Most previous studies on phenotypic effects of POLG1 polyQ have defined 10Q as the only normal allele. Non-10Q alleles were significantly more common in patients compared to the controls (17.3% vs. 12.3 %, p= 0.005). This association between non-10Q length variants and PD remained significant when compared to a larger set of 1541 literature controls (p=0.00005). In conclusion, POLG1 polyQ alleles other than 10Q may predispose to PD. We did not find association between PD and parkin or DJ-1, genes underlying autosomal recessive parkinsonism. The functional Val158Met polymorphism, which affects the catalytic effect of COMT enzyme, and another coding polymorphism in COMT were not associated with PD in our patient material. The APOE e2/3/4 polymorphism modifies risk for Alzheimer s disease and prognosis of for example brain trauma. APOE promoter and enhancer polymorphisms 219G/T and +113G/C, and APOE e3 haplotypes, have also been shown to modify the risk of Alzheimer s disease but not reported in PD. No association was found between PD and APOE e2/3/4 polymorphism, the promoter or enhancer polymorphisms, or the e3 haplotypes.

Gender, Politics and Democratisation in Cameroon

Gender perceptions, religious belief systems, and political thought have excluded women from politics, for ages, around the world. Combining feminist and modernisation theorists in my theoretical framework, I examine the trends in patriarchal Europe and I highlight the gender-sensitive model of the Nordic countries. Retracing local gender patterns from precolonial to postcolonial eras in sub-Saharan Africa, I explore the links between perceptions, needs, resources, education and women's political participation in Cameroon. Democratisation is supposed to open up political participation, to grant equal opportunities to all adults. One ironic feature of the liberalisation process in Cameroon has been the decrease of women in parliamentarian representation (14% in 1988, 6% in 1992, 5% in 1997 and 10% in 2002). What social, cultural and institutional mechanisms produced this paradoxical outcome, the exclusion of half the population? The gender complementarity of the indigenous context has been lost to male prevalence privileged by education, church, law, employment, economy and politics in the public sphere; most women are marginalised in the private sphere. Nation building and development have failed; ethnicism and individualism are growing. Some hope lies in the growing civil society. From two surveys and 21 focus groups across Cameroon, in 2000 and 2002, some significant results of the processed empirical data reveal low electoral registration (34.5% women and 65.9% men), contrasted by the willingness to run for municipal elections (33.3 % women and 45.2% men). The co-existence of customary and statutory laws, the corrupt political system and fraudulent practices, contribute to the marginalisation of women and men who are interested in politics. A large majority of female respondents consider female politicians more trustworthy and capable than their male counterparts; they even foresee the appointment of a female Prime Minister. The Nordic countries have institutionalised gender equality in their legislation, policies and practices. France has improved women's political inclusion with the parity laws; Rwanda is another model of women's representation, thanks to its post-conflict constitution. From my analysis, Cameroonian institutions, men and more so women, may learn and borrow from these experiences, in order to design and implement a sustainable and gender-balanced democracy. Keywords: democratisation, politics, gender equality, feminism, citizenship, Cameroon, Nordic countries, Finland, France, United Kingdom, quotas, societal social psychology.

Oxygen chemistry in copper oxides: evidence for O− species

Core-level spectroscopic studies suggest that cuprates nominally supposed to contain Cu3+ions are likely to have the excess positive charge on oxygen instead, giving rise to O-type species (oxygen holes)

Orbital evolution studies of two HMXB pulsars

High mass X-ray binary (H M X B) pulsars are of two types, persistent and transient. 4U 1538-52 is a persistent HMXB whose orbit was previously measured to be circular but the RXTE observations revealed an eccentric orbit. We observed this system with RXTE-PCA in August 2003 and our timing analysis supports the eccentric orbit of the system. However, we do not find any evidence for orbital evolution. Rotational and tidal interactions between the stars of a closed binary system result in apsidal motion which can be measured in systems with eccentric orbit. 4U0115+63 is a Be-transient HMXB whose eccentric orbit was well-determined during its 1978 outburst. We report preliminary results from analysis of data obtained during the 1999 outburst of this source with the RXTE-PCA.