The future of cognitive and behavioral therapies in the prevention and early management of psychosis: Opportunities and risks

Behavioral and cognitive interventions for people with psychosis have a long and distinguished history, although the evidence for their application to young people remains limited. We anticipate that the next decades will show substantial research into psychological intervention for this population. Important targets will include the management of environmental stressors, reduction of substance misuse, and promotion of early treatment. Psychological management of positive symptoms, depression, and suicidal behavior will continue to be critical objectives. Important secondary prevention goals will be the retention of cognitive functioning, vocational options, social skills, and social network support, including appropriate family support. We expect primary prevention to include both universal programs and interventions for adolescents at particularly high risk. Technical innovations will include increasing use of Internet-based intervention and behavior cueing devices. Pressures for intervention brevity will continue, as will problems with the systematic delivery of effective procedures.

Inhibitors of human immunodeficiency virus type 1 reverse transcriptase target distinct phases of early reverse transcription

Early HIV-1 reverse transcription can be separated into initiation and elongation phases. Here we show, using PCR analysis of negative-strand strong-stop DNA [(-)ssDNA] synthesis in intact virus, that different reverse transcriptase (RT) inhibitors affect distinct phases of early natural endogenous reverse transcription (NERT), The effects of nevirapine on NERT were consistent with a mechanism of action including both specific and nonspecific binding events. The nonspecific component of this inhibition targeted the elongation reaction, whereas the specific effect seemed principally to be directed at very early events (initiation or the initiation-elongation switch), In contrast, foscarnet and the nucleoside analog ddATP inhibited both early and late (-)ssDNA synthesis in a similar manner. We also examined compounds that targeted other viral proteins and found that Ro24-7429 (a Tat antagonist) and rosmarinic acid (an integrase inhibitor) also directly inhibited RT, Our results indicate that NERT can be used to identify and evaluate compounds that directly target the reverse transcription complex.

Does 'imprinting' with low prenatal vitamin D contribute to the risk of various adult disorders?

Hypovitaminosis D is a candidate risk-modifying factor for a diverse range of disorders apart from rickets and osteoporosis. Based on epidemiology, and on in vitro and animal experiment, vitamin D has been linked to multiple sclerosis, certain cancers (prostate, breast and colorectal), insulin-dependent diabetes mellitus and schizophrenia. I hypothesise that low pre- and perinatal vitamin D levels imprint on the functional characteristics of various tissues throughout the body, leaving the affected individual at increased risk of developing a range of adult-onset disorders. The hypothesis draws from recent advances in our understanding of the early origin of adult disease and proposes a 'critical window' during which vitamin D levels may have a persisting impact on adult health outcomes. Methods to test the hypothesis are outlined. If correct, the hypothesis has important implications for public health. Careful attention to maternal vitamin D status could translate into diverse improvements in health outcomes for the following generation. (C) 2001 Harcourt Publishers Ltd.

Optimal input states and feedback for interferometric phase estimation

We derive optimal N-photon two-mode input states for interferometric phase measurements. Under canonical measurements the phase variance scales as N-2 for these states, as compared to N-1 or N-1/2 for states considered bq previous authors. We prove, that it is not possible to realize the canonical measurement by counting photons in the outputs of the interferometer, even if an adjustable auxiliary phase shift is allowed in the interferometer. However. we introduce a feedback algorithm based on Bayesian inference to control this auxiliary phase shift. This makes the measurement close to a canonical one, with a phase variance scaling slightly above N-2. With no feedback, the best result (given that the phase to be measured is completely unknown) is a scaling of N-1. For optimal input states having up to four photons, our feedback scheme is the best possible one, but for higher photon numbers more complicated schemes perform marginally better.

Phase sensitive pumping and coherence of superposition states

The continuous parametric pumping of a superconducting lossy QED cavity supporting a field prepared initially as a superposition of coherent states is discussed. In contrast to classical pumping, we verify that the phase sensitivity of the parametric pumping makes the asymptotic behaviour of the cavity field state strongly dependent on the phase theta of the coherent state \ alpha > = \ alpha \e(i theta)>. Here we consider theta = pi /4, -pi /4 and we analyse the evolution of the purity of the superposition states with the help of the linear entropy and fidelity functions. We also analyse the decoherence process quantitatively through the Wigner function, for both states, verifying that the decay is slightly modified when compared to the free decoherence case: for theta = -pi /4 the process is accelerated while for theta = pi /4 it is delayed.

Early rise in blood pressure following administration of adrenocorticotropic hormone-[1-24] in humans

1. An elevation in blood pressure has been consistently observed 24 h after adrenocorticotropic hormone (ACTH) administration and is caused by increased ACTH-stimulated cortisol secretion, in association with increased cardiac output. The aim of the present study was to investigate the previously undefined time of onset of this increase in blood pressure in normal humans. 2. Ten normal healthy volunteers received 250 mug ACTH-[1-24], in 500 mL normal saline, infused at a constant rate over 8 h. Six subjects also received a placebo infusion (normal saline only). Blood pressure, heart rate and cortisol levels were determined hourly. Adrenocorticotropic hormone (ACTH-[1-24] plus native ACTH) was measured at 0, 1, 7 and 8 h. 3. Infusion of ACTH-[1-24] produced maximal secretion rates of cortisol, resulting in a mean peak plasma level of 985 +/- 46 nmol/L at 8 h. In response, blood pressure and heart rate rose significantly by 2 h and remained generally elevated for the duration of the infusion. 4. The early onset of haemodynamic responses is consistent with classical steroid receptor-mediated genomic mechanisms, but could be due non-genomic mechanisms. 5. The cardiovascular consequences of therapeutic use of ACTH are well recognized. This results of the present study suggest that even diagnostic administration of ACTH, delivered over a few hours, may raise blood pressure.

Rapid transplacental infection with bovine pestivirus following intranasal inoculation of ewes in early pregnancy

Despite the importance of congenital viral infections in both veterinary and human medicine, only limited experimental work has been carried out to elucidate the mechanisms involved in transplacental virus infections. To further an understanding of fetal infection with pestiviruses, the distribution of bovine pestivirus in the uterine and fetal tissues of ewes in early pregnancy, following a natural route of infection, was investigated. On the 18th day of pregnancy, nine ewes were inoculated by the intranasal route with 1 X 10(5) 50% tissue culture infective doses of an Australian isolate of noncytopathic bovine pestivirus (bovine viral diarrhea virus genotype 1). All ewes were ovariohysterectomized at approximately 100 hours postinfection. Samples from the reproductive tract and conceptus were examined histologically and tested for bovine pestivirus by nested reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry and for interferon-tau mRNA expression by nonnested RT-PCR. Although no histopathologic changes were observed in the maternal or fetal tissues, virus was detected in the reproductive tract of all nine ewes and in all of the conceptuses examined. Al; the time of surgery, only two of the nine ewes were demonstrably viremic. This study demonstrates that bovine pestivirus can spread from a natural site of infection to the ovine fetus within 4 days in the absence of maternal immunity and despite the presence of interferon expression in the reproductive tract.

Development of educational policy and early intervention for learning difficulties in Australia: In the case of Queensland

This paper aims to describe the historical outline and current development of the educational policy for students with learning difficulties in Australia, focusing especially on the state of Queensland. In order to develop educational policy of learning difficulities at the state level, the concept of learning difficulities had been discussed until the middle of the 1970's. Receiving the submissions which argued strongly against a diagnostically-oriented definition of learning disabilities, the Select Comittee concluded that there was much conceptual confusion regarding the definition and cause of learining difficulties that might take many years to resolve. Despite that it was recongnised that action was needed to assist children by looking at their "total learning environmerit", and recommended the development of an educational policy for students with learning difficulties. During 1980's, support teachers for students with learning difficulties were employed in many schools. Scince the early 1980's support teachers have been making their efforts in regular classrooms rather than in the resource rooms. Their roles have been to help students with learning difficulties using effective and specific skills, and to consult with the regular classroom teacher in solving the problems related to learning difficulties in regular classes. Currently, the support system for students with learning difficulties has been employed to organize a more systematic and broader approach in Queensland based on the accountability of schools. In the context of enphasizing literacy and numeracy, a systematic whole school approach and particular programs, such as the Year 2 Diagnostic Net and Reading Recovery, have been introduced into the educational system for early identification and early intervention.

Timing and magnitude of peak height velocity and peak tissue velocities for early, average, and late maturing boys and girls

Height, weight, and tissue accrual were determined in 60 male and 53 female adolescents measured annually over six years using standard anthropometry and dual-energy X-ray absorptiometry (DXA). Annual velocities were derived, and the ages and magnitudes of peak height and peak tissue velocities were determined using a cubic spline fit to individual data. Individuals were rank ordered on the basis of sex and age at peak height velocity (PHV) and then divided into quartiles: early (lowest quartile), average (middle two quartiles), and late (highest quartile) maturers. Sex- and maturity-related comparisons in ages and magnitudes of peak height and peak tissue velocities were made. Males reached peak velocities significantly later than females for all tissues and had significantly greater magnitudes at peak. The age at PHV was negatively correlated with the magnitude of PHV in both sexes. At a similar maturity point (age at PHV) there were no differences in weight or fat mass among maturity groups in both sexes. Late maturing males, however, accrued more bone mineral and lean mass and were taller at the age of PHV compared to early maturers. Thus, maturational status (early, average, or late maturity) as indicated by age at PHV is inversely related to the magnitude and late maturers for weight and fat mass in boys and girls. Am. J. Hum. Biol. 13:1-8, 2001. (C) 2001 Wiley-Liss, Inc.

Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites - In vivo assessment using phospho-specific antibodies

Recent studies have provided evidence that breast cancer susceptibility gene products (Brca1 and Brca2) suppress cancer, at least in part, by participating in DNA damage signaling and DNA repair. Brca1 is hyperphosphorylated in response to DNA damage and co-localizes with Rad51, a protein involved in homologous-recombination, and Nbs1.Mre11.Rad50, a complex required for both homologous-recombination and nonhomologous end joining repair of damaged DNA. Here, we report that there is a qualitative difference in the phosphorylation states of Brca1 between ionizing radiation (IR) and UV radiation. Brca1 is phosphorylated at Ser-1423 and Ser-1524 after IR and W; however, Ser-1387 is specifically phosphorylated after IR, and Ser-1457 is predominantly phosphorylated after W. These results suggest that different types of DNA-damaging agents might signal to Brca1 in different ways. We also provide evidence that the rapid phosphorylation of Brca1 at Ser-1423 and Ser-1524 after IR (but not after W) is largely ataxia telangiectasia mutated (ATM) kinase-dependent. The overexpression of catalytically inactive ATM and Rad3 related (ATR) kinase inhibited the UV-induced phosphorylation of Brca1 at these sites, indicating that ATR controls Brca1 phosphorylation in vivo after the exposure of cells to UV light. Moreover, ATR associates with Brca1; ATR and Brca1 foci co-localize both in cells synchronized in S phase and after exposure of cells to DNA-damaging agents. ATR can itself phosphorylate the region of Brca1 phosphorylated by ATM (Ser-Gln cluster in the C terminus of Brca1, amino acids 1241-1530), However, there are additional uncharacterized ATR phosphorylation site(s) between residues 521 and 757 of Brca1, Taken together, our results support a model in which ATM and ATR act in parallel but somewhat overlapping pathways of DNA damage signaling but respond primarily to different types of DNA lesion.