The Effects of Mastery Criteria on Maintenance: A Replication With Most-to-Least Prompting.

Previous research has suggested that skills taught with a least-to-most prompting procedure to 80% and 90% accuracy did not always maintain high levels of performance maintenance. The present study replicates and extends previous research by evaluating the effects of various mastery criteria (i.e., 80%, 90%, and 100% accuracy across three consecutive sessions) on the maintenance of tacting skills taught with a most-to-least prompting procedure combined with a progressive time delay. Results of this study support previous research and further demonstrate that the highest levels of maintenance are achieved with 100% and 90% accuracy criteria for up to a month. For the 80% criterion, performance deteriorated during follow-up probes. Contrary to previous research suggesting a 90% criterion combined with least-to-most prompting procedures was not always sufficient for producing skill maintenance, the current study may provide preliminary support for the use of a 90% accuracy mastery criterion when combined with a most-to-least prompting procedure with a progressive time delay.

Mastery Criteria and Maintenance: a Descriptive Analysis of Applied Research Procedures.

Behavioral practitioners and researchers often define skill acquisition in terms of meeting specific mastery criteria. Only 2 studies have systematically evaluated the impact of any dimension of mastery criteria on skill maintenance. Recent survey data indicate practitioners often adopt lower criterion levels than are found to reliably produce maintenance. Data regarding the mastery criteria adopted by applied researchers are not currently available. This study provides a descriptive comparison of mastery criteria reported in behavior-analytic research with that utilized by practitioners. Results indicate researchers are more likely to adopt higher levels of accuracy across fewer observations, whereas practitioners are more likely to adopt lower levels of accuracy across more observations. Surprisingly, a large amount of research (a) lacks technological descriptions of the mastery criterion adopted and (b) does not include assessments of maintenance following acquisition. We discuss implications for interpretations within and across research studies.

Effect of concomitant vancomycin and piperacillin-tazobactam on frequency of acute kidney injury in pediatric patients.

PURPOSE: Results of a study of rates of acute kidney injury (AKI) in pediatric patients treated with vancomycin plus piperacillin-tazobactam or vancomycin plus alternative antipseudomonal ß-lactams (APBLs) are reported. METHODS: A retrospective, single-center cohort study was performed. Pediatric patients were included in the study cohort if they received combination therapy for at least 48 hours, had documented baseline and follow-up serum creatinine levels, and had a documented serum vancomycin trough concentration. The primary outcome was the frequency of AKI, defined as a 50% or greater increase in serum creatinine concentration from baseline or an increase of at least 0.5 mg/dL from baseline. The secondary outcome was time to AKI onset. RESULTS: A total of 474 patients were included. Among 100 patients who received vancomycin plus piperacillin-tazobactam, the rate of AKI was higher than the rate in the group treated with vancomycin plus alternative APBLs (27% versus 7%, p < 0.0001). The median time to AKI onset was shorter in the piperacillin-tazobactam group versus the alternative APBL group (3.8 versus 7.9 days, p = 0.0065). Patients who were administered piperacillin-tazobactam were almost 6 times as likely to develop AKI (odds ratio [OR], 5.955; 95% confidence interval [CI], 2.774-12.784), and patients who had a maximum vancomycin trough concentration greater than 20 mg/L were 7.5 times as likely to develop AKI (OR, 7.552; 95% CI, 3.625-15.734). CONCLUSION: Pediatric patients treated with concomitant vancomycin and piperacillin-tazobactam had a higher rate of AKI, with faster AKI onset, than those who received vancomycin in combination with other APBLs.

Group Procedures for Decreasing Problem Behavior Displayed by Detained Adolescents.

As one component of providing treatment in a residential facility, Brogan, Falligant, and Rapp decreased problem behavior by two groups of detained adolescents using group contingency procedures. The current series of studies evaluated the extent to which group procedures could be extended to other contexts within a residential facility. In Study 1, fixed-time delivery of attention by dormitory staff decreased problem behavior displayed by a group of five to 11 detained adolescents during free periods. In Study 2, rules from a therapist plus contingencies for following those rules increased appropriate line walking during specific transition periods. Subsequently, rules alone maintained appropriate line walking, however, direct training was required to produce appropriate line walking during other transitions. Measures of social validity indicated the procedures and outcomes in both studies were acceptable to facility personnel.

Adverse effects of pegaspargase in pediatric patients receiving doses greater than 3,750 IU.

BACKGROUND: Increased toxicities have been identified with higher doses of pegaspargase (PEG-ASP) in adults. This has led to routine use of a dose cap of 3,750 IU for adult acute lymphoblastic leukemia (ALL) patients in most institutions. In pediatric ALL patients, PEG-ASP is not capped. There is concern at our institution that larger doses may result in increased rates of adverse effects and that increased monitoring may be warranted in pediatric patients receiving doses greater than 3,750 IU. The objective of this study is to quantify the difference in the rates of PEG-ASP-associated adverse events between pediatric patients who received doses greater than 3,750 IU and less than or equal to 3,750 IU. METHODS: Retrospective chart review of patients 1-21 years old with pre-B-cell ALL who received PEG-ASP between 2007 and 2014 at an academic medical center. RESULTS: Of 183 patients included in the analysis, 24 received PEG-ASP doses higher than 3,750 IU and 159 received doses less than or equal to 3,750 IU. The incidence of venous thromboembolism (VTE) was significantly higher for patients in the group that received more than 3,750 IU compared with those who received 3,750 IU or less (20.8 vs. 1.89%, respectively; P = 0.0011). The incidence of pancreatitis (P = 0.0306) and hyperglycemia (P = 0.0089) were also higher in the group that received more than 3,750 IU. CONCLUSIONS: PEG-ASP doses higher than 3,750 IU are associated with higher rates of VTE, pancreatitis, and hyperglycemia in pediatric patients with pre-B-cell ALL. Patients receiving more than 3,750 IU should have increased monitoring, and larger, multicenter trials are needed to determine if monitoring, VTE prophylaxis, and potential dose capping recommendations should be added to clinical trial protocols.

Vincristine toxicity with co-administration of fluconazole during induction therapy for pediatric acute lymphoblastic leukemia.

BACKGROUND: Antifungal prophylaxis is recommended for patients with acute lymphoblastic leukemia (ALL) during high-risk periods such as induction; however, increased vincristine toxicities have been reported with the co-administration of triazole antifungals. We sought to determine whether vincristine-associated toxicities are higher among children with ALL concurrently given fluconazole prophylaxis compared to no prophylaxis. PROCEDURE: Using a retrospective cohort design, we reviewed records of pediatric patients treated for newly diagnosed ALL from 2003 to 2013. Patients were classified by fluconazole exposure during induction. The development of vincristine-associated toxicity and vincristine dose adjustment were the primary outcomes evaluated. The adjusted risk difference (RD) for vincristine-related toxicity associated with triazole exposure was determined. RESULTS: We identified 197 patients meeting inclusion criteria for evaluation, 160 (81%) of whom received fluconazole prophylaxis. Among patients receiving fluconazole, 36/160 (22%) developed vincristine toxicity compared to 7/37 (19%) among those not receiving prophylaxis (RD: 3%, 95% confidence interval [CI] -11 to 18%). Adjusting for patient age and race, no statistically significant increased risk for vincristine-associated toxicity with fluconazole exposure was observed (RD 5%, 95% CI -8 to 17%). An increased risk for vincristine-associated toxicity was independently associated with age 10 years or older (RD 19%, 95% CI 4-34%). CONCLUSION: Co-administration of fluconazole during induction therapy for pediatric ALL does not significantly increase the risk for vincristine-associated toxicities; however, patients 10 years or older are at an increased risk for toxicity independent of fluconazole exposure. Prophylaxis with fluconazole during induction therapy for pediatric ALL, if warranted, appears to be a safe clinical practice.

Efficacy of fenbendazole and levamisole treatments in captive Houston toads (Bufo [Anaxyrus] houstonensis).

Effective disease monitoring and prevention is critical to the success of captive amphibian care. Nematodes, including the genera Rhabdias and Strongyloides, are known to contribute to mortality in captive amphibians and have been identified in the Houston Zoo's endangered Houston toad (Bufo [Anaxyrus] houstonensis) captive assurance colony. Five years of fecal data for the toad colony were compiled and analyzed in order to investigate the efficacy of two anthelminthic medications, fenbendazole (FBZ) and levamisole (LMS), which were used to control nematode infections. Both FBZ (dusted onto food items) and topical LMS (6.5 to 13.5 mg/kg) significantly reduced the number of nematode eggs, larvae, and adults observed by fecal parasitologic examination. There were no significant differences between treatments, and egg reappearance periods were difficult to compare as a result of low sample size. No adverse effects from either anthelminthic treatment were observed. Both topical LMS and oral FBZ appear to be safe and efficacious treatments for the reduction of the internal nematode burden in captive Houston toads.

Yuri gagarin is required for actin, tubulin and basal body functions in Drosophila spermatogenesis.

Males of the genus Drosophila produce sperm of remarkable length. Investigation of giant sperm production in Drosophila melanogaster has demonstrated that specialized actin and microtubule structures play key roles. The gene yuri gagarin (yuri) encodes a novel protein previously identified through its role in gravitaxis. A male-sterile mutation of yuri has revealed roles for Yuri in the functions of the actin and tubulin structures of spermatogenesis. Yuri is a component of the motile actin cones that individualize the spermatids and is essential for their formation. Furthermore, Yuri is required for actin accumulation in the dense complex, a microtubule-rich structure on the sperm nuclei thought to strengthen the nuclei during elongation. In the yuri mutant, late clusters of syncytial nuclei are deformed and disorganized. The basal bodies are also mispositioned on the nuclei, and the association of a specialized structure, the centriolar adjunct (CA), with the basal body is lost. Some of these nuclear defects might underlie a further unexpected abnormality: sperm nuclei occasionally locate to the wrong ends of the spermatid cysts. The structure of the axonemes that grow out from the basal bodies is affected in the yuri mutant, suggesting a possible role for the CA in axoneme formation.

Challenges that opioid-dependent women present to the obstetric anaesthetist.

A retrospective casenote review was performed to identify anaesthetic challenges relevant to the opioid-dependent obstetric population. Medical records showed that of the 7,449 deliveries during a 24 month period, 85 women (1.1%) were taking regular opioids such as methadone and/or heroin. Of these 67 (79%) received anaesthetic services, ten of whom (11.7%) were referred antenatally. Forty opioid-dependent women (47%) received epidural analgesia in labour compared with the overall hospital rate of 38%. Twenty-three women (27%) delivered by caesarean section: five received general anaesthesia, five combined spinal anaesthesia, five spinal anaesthesia and eight epidural anaesthesia. Twenty opioid-dependent women (23.5%) had documented problems related to labour analgesia and 17 (74%) had problems with analgesia after caesarean section. A variety of postoperative analgesia methods were administered in addition to maintenance methadone. Fourteen patients (16.5%) had difficult intravenous access and seven "arrest" calls were documented. One anaesthetist was exposed to hepatitis C. This review demonstrates the demands placed on obstetric anaesthetic services by opioid-dependent women. Early antenatal referral for anaesthetic review is recommended.

Bcl-2 increases emptying of endoplasmic reticulum Ca2+ stores during photodynamic therapy-induced apoptosis.

Photodynamic therapy (PDT) is clinically approved for the treatment of several types of cancer as well as age-related macular degeneration, the leading cause of blindness in the elderly. PDT using the photosensitizer verteporfin has been previously shown to induce rapid apoptosis via a mitochondrial-caspase activation pathway. The impact of PDT on other cellular organelles such as the endoplasmic reticulum (ER) is undefined. The effect of PDT on intracellular Ca2+ ([Ca2+]i) in control and Bcl-2-overexpressing HeLa cells was assessed. A greater [Ca2+]i transient was observed for Bcl-2 overexpressing cells in response to PDT. The PDT-induced Ca2+ release was due to the emptying of Ca2+ from ER and possibly mitochondrial stores and was not due to an influx of Ca2+ from the medium. For Bcl-2-transfected cells, the release of Ca2+ was incomplete as determined by a further [Ca2+]i transient produced by the addition of the Ca2+ ionophore ionomycin after PDT. Furthermore, extrusion of Ca2+ was not hindered while ER-mediated sequestration of Ca2+ was impaired after PDT. Impairment of ER-mediated sequestration of Ca2+ may be due to the immediate caspase-independent depletion of sarco/endoplasmic reticulum Ca2+ ATPase-2 (SERCA2) that occurred in response to PDT in birth HeLa/Neo and Bcl-2 overexpressed HeLa cells. In summary, PDT induced the rapid degradation of SERCA2 and release of ER and mitochondrial Ca2+ stores. Although overexpression of Bcl-2 did not protect against SERCA2 degradation, it may influence the release of Ca2+ from ER and mitochondrial stores in PDT-treated cells.

Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive cancer patients.

PURPOSE: Radiation therapy is an important treatment modality for oncology patients. DNA sequence variants have so far been identified in only a few genes in radiosensitive cancer patients. Patients known to be clinically radiosensitive were tested for mutation of a gene involved in DNA double-strand break repair and sister chromatid cohesion--hHR21. METHODS AND MATERIALS: Clinically radiation-sensitive patients were accrued to the study after giving informed consent. Blood samples were obtained and lymphoblastoid cell lines established. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed to amplify the hHR21 gene, and the DNA product was sequenced to identify any genetic abnormalities. Northern blot analysis, cell survival, and growth assays were performed on control cells and cells with hHR21 variants, and a restriction digest assay was developed to screen for carriers of a detected gene variant. RESULTS: The DNA sequence of the hHR21 gene was determined in 19 radiation-sensitive cancer patients. In 6 of the 19 patients, a thymidine (T) to cytosine (C) transition was detected at position 1440 of the hHR21 open reading frame (T1440C). This variant did not alter the amino acid sequence and was likely to be a polymorphism. One patient with a particularly severe radiation reaction had a second sequence variant immediately adjacent to the first. This was a guanine (G) to adenine (A) transition (G1441A), resulting in a change of the amino acid sequence (glycine --> arginine) in a portion of the protein conserved in evolution. This suggests that this DNA alteration may be biologically significant. Restriction digest with the HpaII enzyme confirmed the presence of both sequence variants on the same allele. CONCLUSIONS: We describe the first two DNA sequence variants ever found in the hHR21 gene, in patients with clinical radiation hypersensitivity. Although no direct evidence for the involvement of hHR21 alterations in the radiosensitivity of the cancer patients examined has been demonstrated, the possibility exists that homozygous mutations or other mutations of this gene could contribute to radiosensitivity. A simple test is described that could be applied to screening for these variants in relevant populations.

Mitochondrial release of apoptosis-inducing factor and cytochrome c during smooth muscle cell apoptosis.

Photodynamic therapy (PDT) is under investigation for the treatment of intimal hyperplastia in conditions such as atherosclerosis and restenosis. Although smooth muscle cells (SMCs) may be a key target for treatment, the effects of PDT on these cells are poorly characterized. In the present study, apoptosis was induced in primary human aortic SMCs by the combination of the photosensitizer verteporfin and visible light. After PDT, an increase in mitochondrial cytochrome c (cyt c) and apoptosis-inducing factor (AIF) levels were detected in the cytosol immediately and their levels increased steadily up to 2 hours. Cytosolic levels of the pro-apoptotic Bcl-2 family member Bax decreased reciprocally throughout this period, but this change did not occur before cyt c release. Confocal microscopy revealed a diffuse staining pattern of cyt c within apoptotic cells as compared to a distinct mitochondrial staining in normal cells. AIF translocated from mitochondria to the nucleus during the progression of apoptosis. After cyt c release, caspase-9 and caspase-3 processing was visible by 1 hour and caspase-6, -7, and -8 processing was apparent by 2 hours after PDT. In summary, these results demonstrate for the first time the cellular redistribution of mitochondrial AIF during SMC apoptosis, as well as the early release of cyt c and the subsequent activation of multiple caspases during PDT-induced SMC apoptosis.

Is reduced dermatoglyphic a-b ridge count a reliable marker of developmental impairment in schizophrenia?

BACKGROUND: Finger and hand prints are formed during the late first and second trimester of foetal development, after which they remain unchanged. Their expression may be influenced by both genetic and environmental factors. Some studies have suggested that a reduced total finger ridge count (TFRC) and, in particular, a reduce total a-b ridge count (TABRC), may be associated with schizophrenia. AIM: To study these two variables in a large, ethnically homogenous sample and to compare our findings with those of other recent studies. METHOD: Finger and hand prints of 150 people with DSM-III-R schizophrenia were compared with those of 92 healthy controls. RESULTS: Patients had a reduced mean TABRC (P = 0.03) compared with controls. There was a significant (P=0.02) linear trend for lower TABRC and increasing incidence of schizophrenia (ORlineartrend = 1.3; 95%CI1.1-1.7), implying a continuous increase in the risk for schizophrenia with reduction in TABRC. No significant difference between groups was observed for TFRC. CONCLUSION: These results provide further evidence that dermatoglyphic abnormalities exist in at least some patients with schizophrenia and that the a-b ridge count may be a marker of disruption, probably environmental, that occurs when the developing brain may also be particularly vulnerable to such insult. These findings support the concept that some cases of schizophrenia may be due to adverse intrauterine events.

Small cell carcinoma of the vagina.

A case of localized small cell neuroendocrine carcinoma of the vagina is reported. The patient was treated with concurrent chemoradiation with significant toxicity but obtained a complete response. Thirteen months after therapy the patient developed distant metastasis and died shortly thereafter. Review of the literature found that patients treated with local therapy alone had a shorter survival and died of systemic disease. As with small cell neuroendocrine carcinomas arising from other sites, systemic relapse remains an important issue that warrants combination therapies, although in pelvic sites this may be associated with an increase in side-effects.