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The graded Hedgehog (Hh) signal is transduced by the transmembrane Smoothened (Smo) proteins in both vertebrates and invertebrates. In Drosophila, associations between Smo and the Fused (Fu)/Costal-2 (Cos2)/Cubitus Interruptus (Ci) cytoplasmic complex lead to pathway activation, but it remains unclear how the cytoplasmic complex responds to and transduces different levels of Hh signaling. We show here that, within the Hh gradient field, low- and high-magnitude Smo activations control differentially the phosphorylation of Cos2 on two distinct serines. We also provide evidence that these phosphorylations depend on the Fu kinase activity and lead to a shift of Cos2 distribution from the cytoplasm to the plasma membrane. Moreover, the distinct Cos2 phosphorylation states mediate differential Hh signaling magnitude, suggesting that phosphorylation and relocation of Cos2 to the plasma membrane facilitate high-level Hh signaling through the control of Ci nuclear translocation and transcriptional activity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: Cognitive-existential group therapy (CEGT) was developed to improve mood and mental attitude toward cancer in women with early-stage breast cancer receiving adjuvant chemotherapy. Given the debate about group therapy's association with increased survival in women with metastatic breast cancer, we were curious to check its effect at a much earlier stage in the cancer journey., Patients and Methods: We randomly assigned 303 women with early-stage breast cancer who were receiving adjuvant chemotherapy to either 20 sessions of weekly group therapy plus three relaxation classes (n = 154) or to a control condition of three relaxation classes alone (n = 149). The primary outcome was survival., Results: CEGT did not extend survival; the median survival time was 81.9 months (95% CI, 64.8 to 99.0 months) in the group-therapy women and 85.5 months (95% CI, 67.5 to 103.6 months) in the control arm. The hazard ratio for death was 1.35 (95% CI, 0.76 to 2.39; P = .31). In contrast, histology and axillary lymph node status were significant predictors of survival. Low-grade histology yielded a hazard ratio of 0.342 (95% CI, 0.17 to 0.69), and axillary lymph node-negative status yielded a hazard ratio of 0.397 (95% CI, 0.20 to 0.78)., Conclusion: CEGT does not prolong survival in women with early-stage breast cancer.

Background: We conducted a randomised, controlled trial of cognitive-existential group therapy (CEGT) for women with early stage breast cancer receiving adjuvant chemotherapy with the aim of improving mood and mental attitude to cancer., Methods: Women were randomised to 20 sessions of weekly group therapy plus 3 relaxation classes or to a control arm receiving 3 relaxation classes. Assessments, independently done at baseline, 6 and 12 months, included a structured psychiatric interview and validated questionnaires covering mood, attitudes to cancer, family relationships, and satisfaction with therapy., Results: Three hundred and three of 491 (62%) eligible patients participated over 3 years. Distress was high pre-intervention: 10% were diagnosed as suffering from major depression, 27% from minor depression and 9% from anxiety disorders. On an intention-to-treat analysis, there was a trend for those receiving group therapy (n=154) to have reduced anxiety (p=0.05, 2-sided) compared to controls (n=149). Women in group therapy also showed a trend towards improved family functioning compared to controls (p=0.07, 2-sided). The women in the groups reported greater satisfaction with their therapy (p<0.001, 2-sided), appreciating the support and citing better coping, self-growth and increased knowledge about cancer and its treatment. They valued the CEGT therapy. Overall effect size for the group intervention was small (d=0.25), with cancer recurrence having a deleterious effect in three of the 19 therapy groups. Psychologists as a discipline achieved a moderate mean effect size (d=0.52)., Conclusion: CEGT is a useful adjuvant psychological therapy for women with early stage breast cancer. Interaction effects between group members and therapists are relevant to outcome. Group-as-a-whole effects are powerful, but the training and experience of the therapist is especially critical to an efficacious outcome., (Copyright 2003 John Wiley & Sons, Ltd.)

The ability to accurately determine the number of syringe needle penetration holes through the rubber stoppers in pharmaceutical vials and rubber septa in intravenous (i.v.) line and bag ports has been a critical factor in a number of forensic cases involving the thefts of controlled substances or suspected homicide by lethal injection. In the early 1990s, the microscopy and microanalysis group of the U.S. Food and Drug Administration's Forensic Chemistry Center (FCC) developed and implemented a method (unpublished) to locate needle punctures in rubber pharmaceutical vial stoppers. In 1996, as part of a multiple homicide investigation, the Indiana State Police Laboratory (ISPL) contacted the FCC for information on a method to identify and count syringe needle punctures through rubber stoppers in pharmaceutical vials. In a joint project and investigation using the FCC's needle hole location method and applying a method of puncture site mapping developed by the ISPL, a systematic method was developed to locate, identify, count, and map syringe punctures in rubber bottle stoppers or i.v. bag ports using microscopic analysis. The method requires documentation of punctures on both sides of the rubber stoppers and microscopic analysis of each suspect puncture site. The final result of an analysis using the method is a detailed diagram of puncture holes on both sides of a questioned stopper and a record of the minimum number of puncture holes through a stopper.

Two different oxidation treatments, ozonation and electroflocculation, were experimented on a pilot scale to test their efficiency in removing polluting substances from wastewaters of textile industries. Both pilot plants used reproduced very closely a full-scale treatment in order to obtain indications about the feasibility of a transfer on industrial scale. By means of ozone treatment very high colour removal (95-99%) was achieved and treated waters were reused satisfactorily in dyeing even with light colours. This evidence despite the fact that the chemical oxygen demand of treated waters was still in a range (75-120 mg/l, a decrease up to 60%) that was usually considered to be too high for recycling purposes, especially for dyeing light colours. Treating plants working at the above-mentioned conditions should guarantee low operating costs. A biological pre-treatment and a sand filtration are absolutely essential. The transfer on industrial scale of the treatment is currently under development under an already financed European project. Electrochemical treatment showed to be very efficient in removing colour (80-100%) and chemical oxygen demand (70-90%). Moreover, a sensible decrease of chloride and sulphate ions was detected. Removal of flocculated material (post-treatment) must be, however, perfected in order to establish a correct costs-to-benefits ratio and therefore, propose an implementation of the technique on an industrial scale.

As part of a suspected homicide investigation, a sampling of the gastric contents from the victim was forwarded to the U.S. Food and Drug Administration's Forensic Chemistry Center (FCC) for analysis of specific, selected components. The victim was known to have consumed string mozzarella cheese, as a snack, less than 24 h before his disappearance and the subsequent discovery of the body. The investigation sought to confirm or dismiss speculation the victim may have been fed a meal or eaten additional food prior to his death. Analysis of the stomach contents involved examination by stereoscopic light microscopy (SLM) and isolation, processing, and analysis of suspect materials by scanning electron microscopy (SEM). Several wax-like, off-white to cream-colored objects were noted by SLM examination and removed from the gastric contents. Through a series of fixation, sectioning, drying, and coating steps, these objects were prepared for analysis by SEM. Comparison of the suspect material with laboratory control string mozzarella cheese showed excellent correlation between the analyzed samples, confirming the suspect material from the stomach contents as string mozzarella cheese.

Product tampering, as detailed by the Federal Anti-Tampering Act of 1983 (1), is a felony punishable by both fine and imprisonment. The rationale for product tampering ranges from pranks and attention seeking acts to extortion, terrorism, and homicide. One such case submitted for analysis involved four medical syringes found in a supermarket and suspected of being used to tamper with various products. One of the syringes was found piercing a pear while the other three syringes were found with needles exposed in other parts of the supermarket. Microscopic analysis was used to collect residue from the syringe barrels and the pear. A multidiscipline approach involving SLM, PLM, including microchemical analysis, FTIR, and GC/MS analyses, performed on the residual liquid found in the syringe barrels and in the suspect pear, confirmed the presence of cocaine. This multidisciplinary approach is often necessary when there is a possible health risk to the public and rapid response is important. With this approach, it was quickly determined which drugs or poisons were used in this tampering.