Moderators and Predictors of Response After 36 Weeks of Treatment in the Treatment for Adolescents with Depression Study (TADS).

This study investigated pretreatment variables associated with depression severity in adolescents following maintenance treatment for major depressive disorder (MDD). Data was derived from the Treatment for Adolescents with Depression Study (TADS). Participants received one of three treatments: cognitive behavioral therapy (CBT), fluoxetine (FLX), or combined CBT and fluoxetine (COMB). Participants received 12 weeks of acute treatment, 6 weeks of consolidation treatment, and 18 weeks of maintenance treatment (N = 327, M age = 14.62 yrs). Outcome was measured by the Children's Depression Rating Scale-Revised. Results showed adolescents with shorter depressive episodes, better global functioning, less suicidal ideation, better health/social functioning, and greater expectancy of positive treatment response were more likely to have lower depression severity following 36 weeks of treatment, regardless of modality. Adolescents with lower initial depression demonstrated lower depression severity if treated with CBT. FLX was more effective in reducing depression severity in adolescents with severe baseline depression than for those with mild or moderate depression. Adolescents with higher family incomes were more likely to have lower depression severity if they received CBT only. In conclusion, adolescents with shorter depressive episodes, better health, social, and global functioning, less suicidal ideation, and greater expectancy for treatment at baseline respond equally well to CBT, fluoxetine, and combined treatment. Adolescents who are more severely depressed at baseline may have a better treatment response if they are treated with FLX; whereas adolescents of higher income are more likely to have a better response if they receive CBT only.

The effects of early- or mid-gestation nutrient restriction on bovine fetal pancreatic development.

Research on the effects of nutrient restriction in beef cows on fetal pancreatic development is limited. To address this, multiparous Angus-cross cows (n = 22) were fed either control (CON; to gain 1 kg/wk) or nutrient-restricted (NR; 0.55% NEm) diets based on NRC requirements. On d 30 of gestation, cows were blocked by body condition and randomly assigned to one of three nutritional regimes: CON fed from d 30 to 190 (n = 8), or NR/C (n = 7) or C/NR (n = 7) fed either the CON or NR diet from d 30 to 110 followed by CON or NR from d 110 to 190 of gestation. Cows were harvested on d 190 of gestation, and blood samples, fetal weights, and fetal tissue weights and samples were collected. Pancreas samples were embedded in paraffin and sectioned for standard immunohistochemistry procedures to quantify insulin-positive ß cells and number of apoptotic ß cells using TUNEL staining. Data were analyzed via ANOVA using the general linear model procedure of SAS. At harvest, empty carcass weights were decreased (P = 0.036) in fetuses of C/NR and NR/C fed dams compared to fetuses of CON fed dams. Pancreas weight was decreased (P = 0.028) in fetuses of C/NR fed dams compared to CON fetuses; however, fetuses of NR/C fed dams were not different (P > 0.05) from fetuses of CON fed dams. Maternal and fetal serum insulin concentrations were not different (P > 0.05) in NR/C fed compared to CON fed; however, concentrations of insulin were decreased (P = 0.036 and P = 0.40, respectively) in C/NR fed compared to CON fed. Beta cell number was decreased (P = 0.009) in fetuses of NR/C and C/NR fed dams compared to fetuses of CON fed dams. Percentage of apoptotic cells was increased (P < 0.0001) in fetuses of NR/C and C/NR fetuses than fetuses of CON fed dams. This evidence suggests that nutrient restriction either during early- or mid-gestation can negatively impact fetal pancreatic development. However, mid-gestational nutritional insult is potentially recovered by reacclimation to a diet that meets requirements of the dam, thus reducing negative outcomes in fetal offspring.

CDX2 promotes anchorage-independent growth by transcriptional repression of IGFBP-3.

CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. We have reported that CDX2 promotes tumorigenicity in a subset of human colorectal cancer cell lines. Here, we present evidence that CDX2 negatively regulates the well-documented growth inhibitor insulin-like growth factor binding protein-3 (IGFBP-3). Specifically, CDX2 binds to the IGFBP-3 gene promoter and can repress IGFBP-3 transcription, protein expression and secretion. Furthermore, inhibition of IGFBP-3 partially rescues the decreased anchorage-independent growth phenotype observed in CDX2 knockout cells. These data demonstrate for the first time that (1) CDX2 can function as a transcriptional repressor, and (2) one mechanism by which CDX2 promotes anchorage-independent growth is by transcriptional repression of IGFBP-3.

Relative migration rates and local adaptation in a mosquito-protozoan interaction.

Theory predicts that the direction of local adaptation depends on the relative migration rates of hosts and parasites. Here we measured relative migration rates and tested for local adaptation in the interaction between a tree hole mosquito (Ochlerotatus sierrensis) and a protozoan parasite (Lambornella clarki). We found strong support for the hypothesis that the host migrates more than its parasite. Hosts colonized artificial tree holes in the field at a much higher rate than the parasite. Field releases of the parasite demonstrated that it colonizes and persists in natural tree holes where it was previously absent, suggesting that parasite distribution is limited by its migratory ability. Although the host migrates more than its parasite, we found no evidence for local adaptation by hosts and some evidence for local adaptation by parasites. Other life history traits of the host and parasite may also influence patterns in local adaptation, particularly parasite virulence and host dormancy.

"On-demand" access to a multi-purpose collection of best practice standards.

On-demand" information has been chosen by clinicians as one of their preferred modes of interaction with computers when in need of information about evidence-based practices. However, most of the clinicians' information needs remain unmet, especially due to a lack of easy access to resources that are able to satisfy these needs in a timely manner. We present three scenarios indicating opportunities for a clinical information system to present interdisciplinary standards at the point-of-care. In each scenario, we highlight the importance of context of use and the opportunities offered by the clinical workflow for providing access to relevant "on-demand" information. We also present an XML model for structuring non-physician interdisciplinary standards, in an effort to fulfill the requirements exposed by the three scenarios.

Central role of hemocytes in Autographa californica M nucleopolyhedrovirus pathogenesis in Heliothis virescens and Helicoverpa zea.

Autographa californica M nucleopolyhedrovirus (AcMNPV) can infect and kill a wide range of larval lepidopteran hosts, but the dosage required to achieve mortal infection varies greatly. Using a reporter gene construct, we identified key differences between AcMNPV pathogenesis in Heliothis virescens and Helicoverpa zea, a fully permissive and a semipermissive host, respectively. Even though there was more than a 1,000-fold difference in the susceptibilities of these two species to mortal infection, there was no significant difference in their susceptibilities to primary infections in the midgut or secondary infections in the tracheal epidermis. Foci of infection within the tracheal epidermis of H. zea, however, were melanized and encapsulated by 48 h after oral inoculation, a host response not observed in H. virescens. Further, H. zea hemocytes, unlike those of H. virescens, were highly resistant to AcMNPV infection; reporter gene expression was observed only rarely even though virus was taken up readily, and nucleocapsids were transported to the nucleus. Collectively, these results demonstrated that hemocytes-by removing virus from the hemolymph instead of amplifying it and by participating in the encapsulation of infection foci-together with the host's melanization response, formed the basis of H. zea's resistance to fatal infection by AcMNPV.

8pter-p23 deletion is associated with racial differences in prostate cancer outcome.

Deletions of chromosome sequences mapping to the short arm of chromosome 8 have been observed frequently in a variety of human cancers. A small number of studies have suggested that the terminal portion of the short arm of chromosome 8, 8pter-p23, may be deleted independently of other portions of 8p in human tumors, and that deletion of the 8pter-p23 region may be correlated with poor prognosis. The aim of the present study was to physically define the minimal region of 8pter-p23 deletion and to define the frequency and prognostic significance of 8pter-p23 loss in human prostate tumors. DNA was purified from normal and tumor tissues of 45 radical prostatectomy specimens and amplified for 15 highly polymorphic microsatellite sequences, 13 spanning 8pter-p23 and 2 proximal 8p markers. Allelic loss of 8p sequences was observed in 28 of 45 (62%) tumors examined. Of these, approximately half (12 of 28; 43%) demonstrated independent loss of the 8pter-p23 region, with several tumors defining a 5-cM minimal region of deletion spanning D8S264-D8S1824-D8S1781-D8S262-D8S1798. When serum prostate-specific antigen was used as a surrogate end point marker for survival, 8pter-p23 loss was significantly associated with reduced disease-free progression (log-rank P = 0.0426). Moreover, loss of the 8pter-p23 region was significantly associated with poor survival for American Caucasian (log-rank P = 0.0024) but not African-American (log-rank P = 0.5832) prostate cancer patients. These studies suggest that independent deletion of 8pter-p23 is differentially associated with disease recurrence and poor outcome in American Caucasian but not African-American prostate cancer patients.

Co-infection of Manduca sexta larvae with polydnavirus from Cotesia congregata increases susceptibility to fatal infection by Autographa californica M Nucleopolyhedrovirus.

We investigated pathogenesis of Autographa californica M Nucleopolyhedrovirus in the semipermissive host, Manduca sexta, using a lacZ recombinant virus (AcMNPV-hsp70/lacZ) to track the temporal progression of infection. Results from time course studies monitoring infections initiated orally in fourth instars demonstrated that primary infection of midgut columnar cells began at 3 h post inoculation (hpi). We observed secondary infections in midgut-associated tracheae as early as 9 hpi, showing that the early events of pathogenesis in M. sexta are similar to those of permissive noctuid larvae. In M. sexta, however, unlike in permissive hosts, hemocytes rapidly surrounded infected tracheal cells and formed capsules. Subsequently, baculovirus infections failed to spread and ultimately were cleared, suggesting that a cellular immune response had been triggered. To assess the effects of immunosuppression on baculovirus-induced disease, we compared the outcome of infections in immunocompetent hosts with those that were immunocompromised either by parasitization with the braconid, Cotesia congregata, or by injection of the parasitoid's polydnavirus. During the first 9 days after inoculation, parasitized and polydnavirus-inoculated M. sexta larvae died more quickly and at higher levels than nonparasitized and sham-injected controls, suggesting that the cellular immune response was a factor in conferring resistance to fatal infection by AcMNPV-hsp70/lacZ.

Multiple nucleocapsid packaging of Autographa californica nucleopolyhedrovirus accelerates the onset of systemic infection in Trichoplusia ni.

Among the nucleopolyhedroviruses (Baculoviridae), the occlusion-derived virus (ODV), which initiates infection in host insects, may contain only a single nucleocapsid per virion (the SNPVs) or one to many nucleocapsids per virion (the MNPVs), but the significance of this difference is unclear. To gain insight into the biological relevance of these different packaging strategies, we compared pathogenesis induced by ODV fractions enriched for multiple nucleocapsids (ODV-M) or single nucleocapsids (ODV-S) of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) containing a beta-galactosidase reporter gene. In time course experiments wherein newly molted fourth-instar Trichoplusia ni were challenged with doses of ODV-S or ODV-M that yielded the same final mortality ( approximately 70%), we characterized viral foci as either being restricted to the midgut or involving tracheal cells (the secondary target tissue, indicative of systemic infection). We found that while the timing of primary infection by ODV-S and ODV-M was similar, ODV-S established significantly more primary midgut cell foci than ODV-M, but ODV-M infected tracheal cells at twice the rate of ODV-S. The more efficient establishment of tracheal infections by ODV-M decreased the probability that infections were lost by midgut cell sloughing, explaining why higher numbers of primary infections established by ODV-S within larvae were needed to achieve the same final mortality. These results showed that the multiple nucleocapsid packaging strategy of AcMNPV accelerates the onset of irreversible systemic infections and may indicate why MNPVs have wider individual host ranges than SNPVs.

AcMNPV pathogenesis and developmental resistance in fifth instar Heliothis virescens.

Autographa californica M nucleopolyhedrovirus carrying a lacZ reporter gene was used to study pathogenesis and developmental resistance in fifth instar Heliothis virescens. Compared to fourth instar larvae, the progression of infection proceeded much more slowly in fifth instar larvae, and developmental resistance in orally inoculated larvae was much more sudden and severe. The resistance occurred within the first 6 h of the fifth instar and was partially relieved by the optical brightener M2R. Inclusion of M2R in oral inocula not only increased mortality levels, but also increased both the percentages of insects expressing lacZ and the numbers of foci 24 h after infection. This early developmental resistance was not observed in insects infected intrahemocoelically, indicating that it was mediated by the midgut and/or the tracheal system servicing the midgut. Another less severe resistance was encountered in insects intrahemocoelically infected 36 to 48 h postmolt. This later resistance was partially relieved by methoprene indicating that it was, in part, hormonally mediated. Fifth instar insects fatally infected prior to 12 h postmolt never pupated, but pupation increasingly occurred in insects fatally infected 12 to 48 h postmolt. This pattern of larval/pupal death was consistent with viral inactivation of the ecdysone commitment peak.

Patient sources of information and decision factors in selecting cosmetic surgeons.

This paper presents the results of an exploratory study designed to examine influential information sources and decision factors in the selection of plastic surgeons for cosmetic versus medical procedures. Physician referrals were found to be the most influential sources of information for both groups. Word-of-mouth and magazine and newspaper articles were also important information sources for cosmetic patients. Primary selection factors were significantly different between groups, with board certification the most influential for cosmetic patients and recommendation by physician most influential for medical patients.

Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North Central Cancer Treatment Group study.

PURPOSE: Megestrol acetate has been reported to improve appetite and quality of life and to decrease nausea and vomiting in patients with cancer anorexia/cachexia. The present trial was formulated to evaluate the impact of megestrol acetate on quality of life, toxicity, response, and survival in individuals with extensive-stage small-cell lung cancer who received concomitant chemotherapy. PATIENTS AND METHODS: Patients were randomized to receive megestrol acetate 800 mg/d orally or placebo. In addition, all patients were scheduled to receive a maximum of four cycles of cisplatin and etoposide chemotherapy. Quality of life was self-assessed at entry onto study, with every cycle of chemotherapy, and 4 months thereafter with a linear visual analog scale. Toxicity was evaluated by patient questionnaire and investigator reports. RESULTS: A total of 243 eligible patients were randomized. Those who received megestrol acetate had increased nonfluid weight gain (P = .004) and significantly less nausea (P = .0002) and vomiting (P = .02). Significant thromboembolic phenomena occurred more often in patients who received megestrol acetate versus placebo (9% v 2%, P = .01). Patients who received megestrol acetate had more edema (30% v 20%, P = .002), an inferior response rate to chemotherapy (68% v 80%, P = .03), and a trend for inferior survival duration (median, 8.2 v 10.0 months, P = .49). These findings may have been influenced by a poorer quality of life of the megestrol acetate group at study initiation. There were no significant changes in quality of life scores over time between either of the study arms. CONCLUSION: Megestrol acetate cannot be routinely recommended for all patients with small-cell lung cancer at the time of chemotherapy initiation. Rather, its therapeutic ratio may be more favorable for patients with problematic cancer anorexia/cachexia.

Regulatory factors affecting larval mosquito populations in container and pool habitats: implications for biological control.

Empirical studies have shown that populations of larval mosquitoes developing in ground pools are subjected to different mortality factors than populations developing in water-filled containers. In general, larvae in ground pools are limited by natural enemies whereas those in containers are limited by resource availability. Containers also are typically smaller than ground pools and lack appreciable internal primary productivity. These physical and biological features have significant implications for successful implementation of biological control agents. Island biogeography theory suggests that container habitats will support smaller populations of fewer species compared to ground pools, implying that it may be more difficult to establish natural enemies in container habitats. The lack of primary productivity within containers may limit the number of trophic levels and reduce the likelihood of establishing and maintaining predator populations. Most importantly, larval mosquito populations in containers are regulated by competitive interactions, and mortality from natural enemies is likely to be compensatory. These habitat and population characteristics, combined with difficulties in locating and treating containers, suggest that successful control of ground pool mosquitoes using biological control agents is more feasible.

Comparative pathogenesis of Autographa californica M nuclear polyhedrosis virus in larvae of Trichoplusia ni and Heliothis virescens.

We compared early viral pathogenesis and dose-mortality relationships for larvae of two highly susceptible hosts, Trichoplusia ni and Heliothis virescens, using a construct of AcMNPV containing the lacZ reporter gene. Larvae were inoculated either as newly molted fourth instars (4(0)) or 15 hr after the molt (4(15)). In 4(0)-inoculated larvae, first lacZ expression was detected in the midgut epithelium of T. ni at 4 hr postinoculation (hpi) compared to 18 hpi in H. virescens, and systemic infections were initiated from tracheole cells servicing the midgut epithelia beginning at 12 and 20 hpi, respectively. The longer viral tenure within the midgut and the slower progression of systemic infections within H. virescens ultimately contributed to its longer time to death. For 4(0)-inoculated H. virescens, proportions of lacZ-expressing larvae increased from 18 hpi until the onset of the molt to the fifth instar at 36 hpi; at this time point, the proportion of signaling insects equaled the final larval mortality. Viral infections within the midgut epithelium of H. virescens were lost during the molt to the fifth instar. Dose-mortality relationships suggested that the peritrophic membrane provided little protection from AcMNPV infections for either species.

Primary infection of insect tracheae by Autographa californica M nuclear polyhedrosis virus.

Previously we found that Autographa californica M nuclear polyhedrosis virus infections initiated in the midguts of insect hosts are disseminated within the hosts via tracheae, elements composing the insect respiratory system. Herein we report that infection of tracheae also can be initiated directly via the spiracles, exterior openings of the tracheal system to the atmosphere. Infections were initiated both by direct application of viral inoculum to the spiracles and by aerosol. Infections established by both these methods appeared to advance much more rapidly than infections established by the oral route, and a host highly refractory to infection orally was easily susceptible to direct tracheal infection. These findings are important for continuing efforts to improve the use of baculoviruses as pest control agents; they also establish the possibility that direct tracheal infection via aerosol may facilitate horizontal transmission of baculoviruses during natural epizootics.

The insect tracheal system: a conduit for the systemic spread of Autographa californica M nuclear polyhedrosis virus.

Baculoviruses establish systemic infections within susceptible insect hosts, even though host tissues are surrounded by basal laminae, extracellular matrices that exclude particles smaller than these viruses. Using a recombinant Autographa californica M nuclear polyhedrosis virus containing a lacZ reporter gene under the control of a constitutive promoter, we followed the progression of infection in Trichoplusia ni larvae. We discovered that infection of the larval insect tracheal system (and not hemocytes, as thought previously) provides the major conduit for this virus to pass through basal laminae and to spread throughout the host. Tracheal epidermal cells, the only known cellular components of the tracheal system, share a common lymph system. Locally these cells contact one another by interdigitating cytoplasmic extensions called epidermal feet. These two features of the tracheal system are likely to facilitate the rapid systemic spread of the virus. The findings reported here have major implications for the fields of insect pathology and biological control and usher in an important consideration regarding host-range factors.

Habitat overflow, a source of larval mortality for Aedes sierrensis (Diptera: Culicidae).

In laboratory and field tests, larvae of the western tree hole mosquito, Aedes sierrensis (Ludlow), were flushed by rainfall from both glass containers and natural tree holes. After 7 d and an accumulated rainfall of 7.9 cm (3.1 in), between 0 and 327 Ae. sierrensis immatures were recovered in collection devices placed below four natural tree holes. Habitat overflow affected all larval stages and may be an important, but overlooked, density-independent source of larval mortality for mosquitoes developing in some water-filled containers.

Correlation of Aedes sierrensis captures at human sentinels with CO2-baited Fay-Prince and duplex cone traps.

The efficiency of the duplex cone and Fay-Prince traps for monitoring adult male and female Aedes sierrensis was evaluated at 3 field sites in California. The numbers of females captured by both types of traps were significantly correlated with human sentinel collections. The Fay-Prince trap captured more Ae. sierrensis females than the duplex cone trap and was a better tool for estimating female activity levels. There was no significant correlation between the number of males captured in Fay-Prince traps and at humans. Male numbers in duplex cone trap collections explained only 27% of the variation in the number of males collected at sentinels, suggesting that neither trap is a robust tool for estimating male activity around humans.