Patient perspectives of using a web based intervention program for patients with type 2 diabetes and acute coronary syndrome

Introduction Research highlights patients with dual diagnoses of type 2 diabetes and acute coronary syndrome (ACS) have higher readmission rates and poorer health outcomes than patients with singular chronic conditions. Despite this, there is a lack of education programs targeted for this dual diagnosis population to improve self-management and decrease negative health outcomes. There is evidence to suggest that internet based interventions may improve health outcomes for patients with singular chronic conditions, however there is a need to develop an evidence base for ACS patients with comorbid diabetes. There is a growing awareness of the importance of a participatory model in developing effective online interventions. That is, internet interventions are more effective if end users’ perceptions of the intervention are incorporated in their final development prior to testing in large scale trials. Objectives This study investigated patients’ perspectives of the web-based intervention designed to promote self-management of the dual conditions in order to refine the intervention prior to clinical trial evaluation. Methods An interpretive approach with thematic analysis was used to obtain deeper understanding regarding participants’ experience when using web-application interventions for patients with ACS and type 2 diabetes. Semi-structured interviews were undertaken on a purposive sample of 30 patients meeting strict inclusion and exclusion criteria to obtain their perspectives on the program. Results Preliminary results indicate patients with dual diagnoses express more complex needs than those with a singular condition. Participants express a positive experience with the proposed internet intervention and emerging themes include that the web page is seen as easy to use and comforting as a support, in that patients know they are not alone. Further results will be reported as they become available. Conclusion The results indicate potential for patient acceptability of the newly developed internet intervention for patients with ACS and comorbid diabetes. Incorporation of patient perspectives into the final development of the intervention is likely to maximise successful outcomes of any future trials that utilise this intervention. Future quantitative evaluation of the effectiveness of the intervention is being planned.

Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refi nements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2∙4 billion and 1∙6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537∙6 million in 1990 to 764∙8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114∙87 per 1000 people to 110∙31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013. Interpretation Ageing of the world’s population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to nonfatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

Effect of antimony addition on the thermal and electrical-switching behavior of bulk Se-Te glasses

The thermal properties and electrical-switching behavior of semiconducting chalcogenide SbxSe55-xTe45 (2 <= x <= 9) glasses have been investigated by alternating differential scanning calorimetry and electrical-switching experiments, respectively. The addition of Sb is found to enhance the glass forming tendency and stability as revealed by the decrease in non-reversing enthalpy Delta H-nr. and an increase in the glass-transition width Delta T-g. Further, the glass-transition temperature of SbxSe55-xTe45 glasses, which is a measure of network connectivity, exhibits a subtle increase, suggesting a meager network growth with the addition of Sb. The crystallization temperature is also observed to increase with Sb content. The SbxSe55-xTe45 glasses (2 <= x <= 9) are found to exhibit memory type of electrical switching, which can be attributed to the polymeric nature of network and high devitrifying ability. The metallicity factor has been found to dominate over the network connectivity and rigidity in the compositional dependence of switching voltage. which shows a profound decrease with the addition of Sb.

Structure and Rheology of Cationic Molecular Hydrogels of Quinuclidine Grafted Bile Salts. Influence of the Ionic Strength and Counter-Ion type

Quinuclidine grafted cationic bile salts are forming salted hydrogels. An extensive investigation of the effect of the electrolyte and counterions on the gelation has been envisaged. The special interest of the quinuclidine grafted bile salt is due to its broader experimental range of gelation to study the effect of electrolyte. Rheological features of the hydrogels are typical of enthalpic networks exhibiting a scaling law of the elastic shear modulus with the concentration (scaling exponent 2.2) modeling cellular solids in which the bending modulus is the dominant parameter. The addition of monovalent salt (NaCl) favors the formation of gels in a first range (0.00117 g cm-3 (0.02 M) < TNaCl < 0.04675 g cm-3 (0.8 M)). At larger salt concentrations, the gels become more heterogeneous with nodal zones in the micron scale. Small-angle neutron scattering experiments have been used to characterize the rigid fibers ( ≈ 68 Å) and the nodal zones. Stress sweep and creeprecovery measurements are used to relate the lack of linear viscoelastic domain to a mechanism of disentanglement of the fibers from their associations into fagots. The electrostatic interactions can be screened by addition of salt to induce a progressive evolution toward flocculation. SEM, UV absorbance, and SAXS study of the Bragg peak at large Q-values complete the investigation.

Pasteurella multocida Expresses Two Lipopolysaccharide Glycoforms Simultaneously, but Only a Single Form Is Required for Virulence: Identification of Two Acceptor-Specific Heptosyl I Transferases

Lipopolysaccharide (LPS) is a critical virulence determinant in Pasteurella multocida and a major antigen responsible for host protective immunity. In other mucosal pathogens, variation in LPS or lipooligosaccharide structure typically occurs in the outer core oligosaccharide regions due to phase variation. P. multocida elaborates a conserved oligosaccharide extension attached to two different, simultaneously expressed inner core structures, one containing a single phosphorylated 3-deoxy-D-manno-octulosonic acid (Kdo) residue and the other containing two Kdo residues. We demonstrate that two heptosyltransferases, HptA and HptB, add the first heptose molecule to the Kdo1 residue and that each exclusively recognizes different acceptor molecules. HptA is specific for the glycoform containing a single, phosphorylated Kdo residue (glycoform A), while HptB is specific for the glycoform containing two Kdo residues (glycoform B). In addition, KdkA was identified as a Kdo kinase, required for phosphorylation of the first Kdo molecule. Importantly, virulence data obtained from infected chickens showed that while wild-type P. multocida expresses both LPS glycoforms in vivo, bacterial mutants that produced only glycoform B were fully virulent, demonstrating for the first time that expression of a single LPS form is sufficient for P. multocida survival in vivo. We conclude that the ability of P. multocida to elaborate alternative inner core LPS structures is due to the simultaneous expression of two different heptosyltransferases that add the first heptose residue to the nascent LPS molecule and to the expression of both a bifunctional Kdo transferase and a Kdo kinase, which results in the initial assembly of two inner core structures.

Decoration of Pasteurella multocida lipopolysaccharide with phosphocholine is important for virulence

Phosphocholine (PCho) is an important substituent of surface structures expressed by a number of bacterial pathogens. Its role in virulence has been investigated in several species, in which it has been shown to play a role in bacterial adhesion to mucosal surfaces, in resistance to antimicrobial peptides, or in sensitivity to complement-mediated killing. The lipopolysaccharide (LPS) structure of Pasteurella multocida strain Pm70, whose genome sequence is known, has recently been determined and does not contain PCho. However, LPS structures from the closely related, virulent P. multocida strains VP161 and X-73 were shown to contain PCho on their terminal galactose sugar residues. To determine if PCho was involved in the virulence of P. multocida, we used subtractive hybridization of the VP161 genome against the Pm70 genome to identify a four-gene locus (designated pcgDABC) which we show is required for the addition of the PCho residues to LPS. The proteins predicted to be encoded by pcgABC showed identity to proteins involved in choline uptake, phosphorylation, and nucleotide sugar activation of PCho. We constructed a P. multocida VP161 pcgC mutant and demonstrated that this strain produces LPS that lacks PCho on the terminal galactose residues. This pcgC mutant displayed reduced in vivo growth in a chicken infection model and was more sensitive to the chicken antimicrobial peptide fowlicidin-1 than the wild-type P. multocida strain

Prevention of type 2 diabetes with lifestyle intervention - emphasis on dietary composition and identification of high-risk individuals

Type 2 diabetes is an increasing, serious, and costly public health problem. The increase in the prevalence of the disease can mainly be attributed to changing lifestyles leading to physical inactivity, overweight, and obesity. These lifestyle-related risk factors offer also a possibility for preventive interventions. Until recently, proper evidence regarding the prevention of type 2 diabetes has been virtually missing. To be cost-effective, intensive interventions to prevent type 2 diabetes should be directed to people at an increased risk of the disease. The aim of this series of studies was to investigate whether type 2 diabetes can be prevented by lifestyle intervention in high-risk individuals, and to develop a practical method to identify individuals who are at high risk of type 2 diabetes and would benefit from such an intervention. To study the effect of lifestyle intervention on diabetes risk, we recruited 522 volunteer, middle-aged (aged 40 - 64 at baseline), overweight (body mass index > 25 kg/m2) men (n = 172) and women (n = 350) with impaired glucose tolerance to the Diabetes Prevention Study (DPS). The participants were randomly allocated either to the intensive lifestyle intervention group or the control group. The control group received general dietary and exercise advice at baseline, and had annual physician's examination. The participants in the intervention group received, in addition, individualised dietary counselling by a nutritionist. They were also offered circuit-type resistance training sessions and were advised to increase overall physical activity. The intervention goals were to reduce body weight (5% or more reduction from baseline weight), limit dietary fat (< 30% of total energy consumed) and saturated fat (< 10% of total energy consumed), and to increase dietary fibre intake (15 g / 1000 kcal or more) and physical activity (≥ 30 minutes/day). Diabetes status was assessed annually by a repeated 75 g oral glucose tolerance testing. First analysis on end-points was completed after a mean follow-up of 3.2 years, and the intervention phase was terminated after a mean duration of 3.9 years. After that, the study participants continued to visit the study clinics for the annual examinations, for a mean of 3 years. The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, mean weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 kg and 0.9 kg in the control group. Cardiovascular risk factors improved more in the intervention group. After a mean follow-up of 3.2 years, the risk of diabetes was reduced by 58% in the intervention group compared with the control group. The reduction in the incidence of diabetes was directly associated with achieved lifestyle goals. Furthermore, those who consumed moderate-fat, high-fibre diet achieved the largest weight reduction and, even after adjustment for weight reduction, the lowest diabetes risk during the intervention period. After discontinuation of the counselling, the differences in lifestyle variables between the groups still remained favourable for the intervention group. During the post-intervention follow-up period of 3 years, the risk of diabetes was still 36% lower among the former intervention group participants, compared with the former control group participants. To develop a simple screening tool to identify individuals who are at high risk of type 2 diabetes, follow-up data of two population-based cohorts of 35-64 year old men and women was used. The National FINRISK Study 1987 cohort (model development data) included 4435 subjects, with 182 new drug-treated cases of diabetes identified during ten years, and the FINRISK Study 1992 cohort (model validation data) included 4615 subjects, with 67 new cases of drug-treated diabetes during five years, ascertained using the Social Insurance Institution's Drug register. Baseline age, body mass index, waist circumference, history of antihypertensive drug treatment and high blood glucose, physical activity and daily consumption of fruits, berries or vegetables were selected into the risk score as categorical variables. In the 1987 cohort the optimal cut-off point of the risk score identified 78% of those who got diabetes during the follow-up (= sensitivity of the test) and 77% of those who remained free of diabetes (= specificity of the test). In the 1992 cohort the risk score performed equally well. The final Finnish Diabetes Risk Score (FINDRISC) form includes, in addition to the predictors of the model, a question about family history of diabetes and the age category of over 64 years. When applied to the DPS population, the baseline FINDRISC value was associated with diabetes risk among the control group participants only, indicating that the intensive lifestyle intervention given to the intervention group participants abolished the diabetes risk associated with baseline risk factors. In conclusion, the intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, body weight, and cardiovascular risk factors, and reduced diabetes risk. Furthermore, the effects of the intervention were sustained after the intervention was discontinued. The FINDRISC proved to be a simple, fast, inexpensive, non-invasive, and reliable tool to identify individuals at high risk of type 2 diabetes. The use of FINDRISC to identify high-risk subjects, followed by lifestyle intervention, provides a feasible scheme in preventing type 2 diabetes, which could be implemented in the primary health care system.

Inpatient hospital care and its costs among type 1 diabetic patients in Finland : a nationwide longitudinal study

Background. In Finland, the incidence of type 1 diabetes mellitus (T1DM) is the highest in the world, and it continues to increase steadily. No effective preventative interventions exist either for individuals at high risk or for the population as a whole. In addition to problems with daily lifelong insulin replacement therapy, T1DM patients with long-lasting disease suffer from various diabetes related complications. The complications can lead to severe impairments and reductions in functional capacity and quality of life and in the worst case they can be fatal. Longitudinal studies on the costs of T1DM are extremely rare, especially in Finland. Typically, in these studies, distinctions between the various types of diabetes have not been made, and costs have not been calculated separately for the sexes. Aims. The aim of this study was to describe inpatient hospital care and costs of inpatient care in a cohort of 5,166 T1DM patients by sex during 1973-1998 in Finland. Inpatient care and costs of care due to T1DM without complications, due to T1DM with complications and due to other causes were calculated separately. Material and Methods. The study population consisted of all Finnish T1DM patients diagnosed before the age of 18 years between January 1st in 1965 and December 31st in 1979 and derived from the Finnish population based T1DM register (N=5,120 in 1979 and N=4,701 in 1997). Data on hospitalisations were obtained from the Finnish Hospital Discharge Register. Results. In the early stages of T1DM, the majority of the use of inpatient care was due to the treatment of T1DM without complications. There were enormous increases in the use of inpatient care for certain complications when T1DM lasted longer (from 9.5 years to 16.5 years). For women, the yearly number of bed-days for renal complications increased 4.8-fold, for peripheral vascular disease 4.3-fold and for ophthalmic complications 2.5-fold. For men, the corresponding increases were as follows: 5-fold, 6.9-fold and 2.5-fold. The yearly bed-days for glaucoma increased 8-fold, nephropathy 7-fold and microangiopathy 6-fold in the total population. During these 7 years, the yearly numbers of bed-days for T1DM without complications dropped dramatically. The length of stay in inpatient care decreased notably, but hospital visits became more frequent when the length of duration of T1DM increased from 9.5 years to 16.5 years. The costs of treatments due to complications increased when T1DM lasted longer. Costs due to inpatient care of complications in the cohort 2.5-folded as duration of T1DM increased from 9.5 years to 16.5 years, while the total costs of inpatient care in the cohort dropped by 22% due to an 80% decrease in the costs of care of T1DM without complications. Treating complications of female patients was more expensive than treating complications of men when T1DM had lasted 9.5 years; the mean annual costs for inpatient care of a female diabetic (any cause) were 1,642 , and the yearly costs of care of complications were 237 . The corresponding yearly mean costs for a male patient were 1,198 and 167 . Treating complications of female patients was more expensive than that of male patients also when the duration of diabetes was 16.5 years, although the difference in average annual costs between sexes was somewhat smaller. Conclusions. In the early phases of T1DM, the treatment of T1DM without complications causes a considerable amount of hospital bed-days. The use of inpatient care due to complications of T1DM strongly increases with ageing of patients. The economic burden of inpatient care of T1DM is substantial.

Type 1 and type 2 diabetes among young adults in Finland : Incidence and perinatal exposures

This study aimed to examine the incidence of young adult-onset T1DM and T2DM among Finns, and to explore the possible risk factors for young adult-onset T1DM and T2DM that occur during the perinatal period and childhood. In the studies I-II, the incidence of diabetes was examined among 15-39-year-old Finns during the years 1992-2001. Information on the new diagnoses of diabetes was collected from four sources: standardized national reports filled in by diabetes nurses, the Hospital Discharge Register, the Drug Reimbursement Register, and the Drug Prescription Register. The type of diabetes was assigned using information obtained from these four data sources. The incidence of T1DM was 18 per 100,000/year, and there was a clear male predominance in the incidence of T1DM. The incidence of T1DM increased on average 3.9% per year during 1992-2001. The incidence of T2DM was 13 per 100,000/year, and it displayed an increase of 4.3% per year. In the studies III-V, the effects of perinatal exposures and childhood growth on the risk for young adult-onset T1DM and T2DM were explored in a case-control setting. Individuals diagnosed with T1DM (n=1,388) and T2DM (n=1,121) during the period 1992-1996 were chosen as the diabetes cases for the study, and two controls were chosen for each case from the National Population Register. Data on the study subjects parents and siblings was obtained from the National Population Register. The study subjects original birth records and child welfare clinic records were traced nationwide. The risk for young adult-onset T2DM was the lowest among the offspring of mothers aged about 30 years, whereas the risk for T2DM increased towards younger and older maternal ages. Birth orders second to fourth were found protective of T2DM. In addition, the risk for T2DM was observed to decrease with increasing birth weight until 4.2 kg, after which the risk began to increase. A high body mass index (BMI) at the BMI rebound between ages 3-11 years substantially increased the risk for T2DM, and the excess weight gain in individuals diagnosed with T2DM began in early childhood. Maternal age, birth order, or body size at birth had no effect on the risk for young adult-onset T1DM. Instead, individuals with T1DM were observed to have a higher maximum BMI before the age of 3 than their control subjects. In conclusion, the increasing trend in the development of both T1DM and T2DM among young Finnish adults is alarming. The high risk for T1DM among the Finnish population extends to at least 40 years of age, and at least 200-300 young Finnish adults are diagnosed with T2DM every year. Growth during the fetal period and childhood notably affects the risk for T2DM. T2DM prevention should also target childhood obesity. Rapid growth during the first years of life may be a risk factor for late-onset T1DM.

Statistical analysis of the associations of hereditary factors with the risk of Type 1 diabetes and Diabetic Nephropathy based on the familial data collected through ascertaiment from population-based registers

In genetic epidemiology, population-based disease registries are commonly used to collect genotype or other risk factor information concerning affected subjects and their relatives. This work presents two new approaches for the statistical inference of ascertained data: a conditional and full likelihood approaches for the disease with variable age at onset phenotype using familial data obtained from population-based registry of incident cases. The aim is to obtain statistically reliable estimates of the general population parameters. The statistical analysis of familial data with variable age at onset becomes more complicated when some of the study subjects are non-susceptible, that is to say these subjects never get the disease. A statistical model for a variable age at onset with long-term survivors is proposed for studies of familial aggregation, using latent variable approach, as well as for prospective studies of genetic association studies with candidate genes. In addition, we explore the possibility of a genetic explanation of the observed increase in the incidence of Type 1 diabetes (T1D) in Finland in recent decades and the hypothesis of non-Mendelian transmission of T1D associated genes. Both classical and Bayesian statistical inference were used in the modelling and estimation. Despite the fact that this work contains five studies with different statistical models, they all concern data obtained from nationwide registries of T1D and genetics of T1D. In the analyses of T1D data, non-Mendelian transmission of T1D susceptibility alleles was not observed. In addition, non-Mendelian transmission of T1D susceptibility genes did not make a plausible explanation for the increase in T1D incidence in Finland. Instead, the Human Leucocyte Antigen associations with T1D were confirmed in the population-based analysis, which combines T1D registry information, reference sample of healthy subjects and birth cohort information of the Finnish population. Finally, a substantial familial variation in the susceptibility of T1D nephropathy was observed. The presented studies show the benefits of sophisticated statistical modelling to explore risk factors for complex diseases.

Michael Reactions of the Anions generated by the Metal-Ammonia Reduction of Benzoic Acids.

A novel method for the construction of carboncarbon bonds is described in which anions obtained by the metal-ammonia reduction of benzoic acid and its derivatives undergo ready Michael reaction with methyl crotonate to give the addition products.

Molecular biology of progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1)

Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited disorder characterized by age of onset at 6-15 years, stimulus-sensitive myoclonus, tonic-clonic epileptic seizures and a progressive course. Mutations in the cystatin B (CSTB) gene underlie EPM1. The most common mutation underlying EPM1 is a dodecamer repeat expansion in the promoter region of CSTB. In addition, nine other mutations have been identified. CSTB, a cysteine protease inhibitor, is a ubiquitously expressed inhibitor of cathepsins, but its physiological function is unknown. The purpose of this study was to investigate CSTB gene expression and CSTB protein function in normal and pathological conditions. The basal CSTB promoter was mapped and characterized using different promoter-luciferase gene constructs. The binding activity of transcription factors to one ARE half, five Sp1 and four AP1 sites in the CSTB promoter was demonstrated. The CSTB promoter activity was clearly decreased using a CSTB promoter with "premutation" repeat expansions and in individuals with alike expansions. The expression of CSTB mRNA and protein was markedly reduced in patient cells. The endogenous CSTB protein localized to the nucleus, cytoplasm and lysosomes, and in differentiated cells merely to the cytoplasm. This suggests that the subcellular distribution of CSTB is dependent on the differentation status of the cells. The proteins representing patient missense mutations failed to associate with lysosomes, implying the importance of the lysosomal association for the proper physiological function of CSTB. Several alternatively spliced CSTB isoforms were identified. Of these CSTB2 was widely expressed with very low levels whereas the other alternatively spliced forms seemed to have limited tissue expression. In patients CSTB2 expression was reduced similarly to that of CSTB. The physiological relevance of CSTB alternative splicing remains unknown. The mouse Cstb transcript was shown to be present in all embryonic stages and adult tissues examined. The expression was highest at embryonic day 7 and in thymus, as well as in postnatal brain in the cortex, caudate putamen, thalamus, hippocampus, and in the Purkinje cell layer of the cerebellum. Our data implies that CSTB expression is tightly temporally and spatially regulated. The data presented in my thesis lay the basis for further understanding of the role of CSTB in health and disease.

Germinating the seeds of three species of Pimelea sect. Epallage (Thymelaeaceae)1

Pimelea trichostachya Lindl., P. simplex F.Muell. and P. elongata Threlfall frequently cause pimelea poisoning of cattle. Fresh seeds of these species, belonging to sect. Epallage (Endl.) Benth. of Pimelea Gaertn. (Thymelaeaceae) are strongly dormant for years when in laboratory storage. Common methods of stimulating germination, such as scarification, dry heat and cold stratification, did not remove much of the dormancy. ‘Smoke water’ stimulated some germination but its effect was unpredictable and many seedlings then grew aberrantly. Exposure of imbibed seeds to gibberellic acid greatly and reliably improved the germination of all three species. However, the manner of application and the concentration of gibberellic acid used had to be appropriate or many young seedlings grew abnormally or died suddenly, limiting successful plant establishment rates. The dormancy type involved is non-deep Type 2 physiological. Ten days of good moisture, in addition to gibberellic acid exposure, is required before appreciable laboratory germination occurs at optimal temperatures. Thus, the mechanism by which gibberellic acid stimulates good germination does not appear to be the same as that which primes seeds for the rapid and prolific germination often seen under natural conditions in arid Australia. Seeds of P. simplex subsp. continua (J.M.Black) Threlfall proved most difficult to germinate and those of P. elongata the easiest.

Electrical transport in Bi doped n-type amorphous semiconductors (GeSe3.5)100-xBix at high pressure

Electrical transport in Bi doped amorphous semiconductors (GeSe3.5)100-xBix (x=0,4,10) is studied in a Bridgman anvil system up to a pressure of 90 kbar and down to 77 K. A pressure induced continuous transition from an amorphous semiconductor to a metal-like solid is observed in GeSe3.5. The addition of Bi disturbs significantly the behaviour of resistivity with pressure. The results are discussed in the light of molecular cluster model for GeySe1-y proposed by Phillips.