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Electronic nicotine delivery systems (ENDS) are being developed as potentially reduced‐risk alternatives to the continued use of combustible tobacco products. Because of the widespread uptake of ENDS—in particular, e‐cigarettes—the biological effects, including the toxic potential, of their aerosols are under investigation. Preclinically, collection of such aerosols is a prerequisite for testing in submerged cell culture‐based in vitro assays; however, despite the growth in this research area, there is no apparent standardized collection method for this application. To this end, through an Institute for in vitro Sciences, Inc. workshop initiative, we surveyed the biomedical literature catalogued in PubMed® to map the types of methods hitherto used and reported publicly. From the 47 relevant publications retrieved, we identified seven distinct collection methods. Bubble‐through (with aqueous solvents) and Cambridge filter pad (CFP) (with polar solvents) collection were the most frequently cited methods (57% and 18%, respectively), while the five others (CFP + bubble‐through; condensation; cotton filters; settle‐upon; settle‐upon + dry) were cited less often (2–10%). Critically, the collected aerosol fractions were generally found to be only minimally characterized chemically, if at all. Furthermore, there was large heterogeneity among other experimental parameters (e.g., vaping regimen). Consequently, we recommend that more comprehensive research be conducted to identify the method(s) that produce the fraction(s) most representative of the native aerosol. We also endorse standardization of the aerosol generation process. These should be regarded as opportunities for increasing the value of in vitro assessments in relation to predicting effects on human health. Collection of e‐cigarette aerosols is a prerequisite to enable testing in submerged culture‐based in vitro assays; however, there is no standardized method for this. Thus, we surveyed the biomedical literature to map the types of published methods. Bubble‐through and Cambridge filter pad methods were most common, although there was heterogeneity among other parameters, and moreover, the resulting fractions were only minimally characterized. Comprehensive research is required to identify the method(s) that produce the fraction(s) most representative of the native aerosol. [ABSTRACT FROM AUTHOR]

The "delayed infection hypothesis" states that a paucity of infections in early childhood may lead to higher risks of childhood leukemia (CL), especially acute lymphoblastic leukemia (ALL). Using prospectively collected data from six population‐based birth cohorts we studied the association between birth order (a proxy for pathogen exposure) and CL. We explored whether other birth or parental characteristics modify this association. With 2.2 × 106 person‐years of follow‐up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards models, increasing birth order (continuous) was inversely associated with CL and ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77–0.99) and 0.85: (0.73–0.99), respectively. Being later‐born was associated with similarly reduced hazards of CL and ALL compared to being first‐born; HRs = 0.78: 95% CI: 0.58–1.05 and 0.73: 0.52–1.03, respectively. Successive birth orders were associated with decreased CL and ALL risks (P for trend 0.047 and 0.055, respectively). Multivariable adjustment somewhat attenuated the associations. We found statistically significant and borderline interactions between birth weight (p = 0.024) and paternal age (p = 0.067), respectively, in associations between being later‐born and CL, with the lowest risk observed for children born at <3 kg with fathers aged 35+ (HR = 0.18, 95% CI: 0.06–0.50). Our study strengthens the theory that increasing birth order confers protection against CL and ALL risks, but suggests that this association may be modified among subsets of children with different characteristics, notably advanced paternal age and lower birth weight. It is unclear whether these findings can be explained solely by infectious exposures. What's new? Can birth order affect childhood leukemia risk? Children with older siblings encounter more infectious pathogens than first‐born children, and fewer childhood infections might contribute to increased risk of childhood leukemia. Here, the authors studied birth order as a proxy for childhood infections. They conducted a prospective study and found that later‐born children had reduced risk of childhood leukemia compared with first‐borns. The effect was strongest in children with fathers age 30 or older, and in children with birth weight less than 3 kg. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer is a rare but leading cause of morbidity and mortality. Established risk factors, accounting for <10% of incidence, have been identified primarily from case-control studies. However, recall, selection and other potential biases impact interpretations particularly, for modest associations. A consortium of pregnancy and birth cohorts (I4C) was established to utilise prospective, pre-diagnostic exposure assessments and biological samples.Methods: Eligibility criteria, follow-up methods and identification of paediatric cancer cases are described for cohorts currently participating or planning future participation. Also described are exposure assessments, harmonisation methods, biological samples potentially available for I4C research, the role of the I4C data and biospecimen coordinating centres and statistical approaches used in the pooled analyses.Results: Currently, six cohorts recruited over six decades (1950s-2000s) contribute data on 388 120 mother-child pairs. Nine new cohorts from seven countries are anticipated to contribute data on 627 500 additional projected mother-child pairs within 5 years. Harmonised data currently includes over 20 "core" variables, with notable variability in mother/child characteristics within and across cohorts, reflecting in part, secular changes in pregnancy and birth characteristics over the decades.Conclusions: The I4C is the first cohort consortium to have published findings on paediatric cancer using harmonised variables across six pregnancy/birth cohorts. Projected increases in sample size, expanding sources of exposure data (eg, linkages to environmental and administrative databases), incorporation of biological measures to clarify exposures and underlying molecular mechanisms and forthcoming joint efforts to complement case-control studies offer the potential for breakthroughs in paediatric cancer aetiologic research. [ABSTRACT FROM AUTHOR]

Purpose: Relapse prevention is an important goal in correctional settings. Although there is strong evidence for the effectiveness of certain treatment programs for juvenile offenders, those for adults lack such evidence. This study evaluated the effectiveness of a risk–need–responsivity (RNR)‐based intervention. Methods: A quasi‐experimental, observational study design and cox regression analysis were used to compare treated violent and sexual offenders (n = 171) with untreated offenders (n = 241). Results: Both groups were observed for an average of 7.9 years. Recidivism rates of treated offenders (11.7%, n = 20) were similar to those of control offenders (15.8%, n = 38; p = .25). When controlling for confounding variables, the hazard of recidivism in the treatment group was 5.2% lower than that in the control group. Subdividing the treatment group resulted in lower hazard ratios for offenders still in therapy when released and offenders cancelling therapy. However, none of the group differences was statistically significant. Conclusion: Our results show that control and RNR‐based treatment groups had comparable recidivism rates with a trend towards a positive treatment effect, especially for people in outpatient treatment. However, criminal history, age at the start of follow‐up, and actuarial risk of recidivism were significantly associated with recidivism. Future research needs to apply elaborate methodological approaches to detect robust treatment effects and consider different criteria of treatment effectiveness. Furthermore, the influence of prison climate, motivational factors, intervention quality, and factors supporting the success of outpatient treatment should be considered in future studies of larger offender samples. [ABSTRACT FROM AUTHOR]

Osseous-associated cervical spondylomyelopathy in dogs is characterized by both static and dynamic spinal cord compression; however, standard MRI methods only assess static compression. In humans with cervical spondylotic myelopathy, kinematic MRI is commonly used to diagnose dynamic spinal cord compressions. The purpose of this prospective, analytical study was to evaluate kinematic MRI as a method for characterizing the dynamic component of osseous-associated cervical spondylomyelopathy in dogs. We hypothesized that kinematic MRI would allow visualization of spinal cord compressions that were not identified with standard imaging. Twelve client-owned dogs with osseous-associated cervical spondylomyelopathy were enrolled. After standard MRI confirmed a diagnosis of osseous-associated cervical spondylomyelopathy, a positioning device was used to perform additional MRI sequences with the cervical vertebral column flexed and extended. Morphologic and morphometric (spinal cord height, intervertebral disc width, spinal cord width, vertebral canal height, and spinal cord area) assessments were recorded for images acquired with neutral, flexion, and extension imaging. A total of 25 compressions were seen with neutral positioning, while extension identified 32 compressions. There was a significant association between extension positioning and presence of a compressive lesion at C4-C5 ( p = 0.02). Extension was also associated with a change in the most severe site of compression in four out of 12 (33%) dogs. None of the patients deteriorated neurologically after kinematic imaging. We concluded that kinematic MRI is a feasible method for evaluating dogs with osseous-associated cervical spondylomyelopathy, and can reveal new compressions not seen with neutral positioning. [ABSTRACT FROM AUTHOR]

The purpose of our study was to quantitate the changes in axillary lymph node dissection ( ALND), frozen section ( FS), and the impact on costs after the publication of the American College of Surgeons Oncology Group ( ACOSOG) Z0011 trial. We compared axillary nodal management and cost data in breast cancer patients who met Z0011 criteria and were treated with lumpectomy and sentinel lymph nodes ( SLN) biopsy from 2007 to July 2013. Of 800 patients, 67 (13.5%) and 34 (12.5%) patients in the pre- and post-Z0011 era had 1-2 positive SLN. ALND decreased from 78% to 21% (p < 0.001) after publication of Z0011. The mean overall cost of SLN biopsy was $41,059 per patient, while SLN biopsy with completion ALND was $50,999 (p < 0.001). Intraoperative FS use decreased from 95% to 66% (p = 0.015). Omitting the FS decreased mean costs from $4,319 to $2,036. The application of Z0011 resulted in an overall mean cost savings of $571,653 from 2011 to July 2013. ACOSOG Z0011 significantly impacted axillary management resulting in a 20% reduction in the mean overall cost per patient by omitting ALND. In these patients, intraoperative FS analysis had poor sensitivity (56%) and doubled the cost of pathologic examination. Fewer ALND and intraoperative FS were performed after the publication of ACOSOG Z0011. Eliminating FS and ALND in patients who met Z0011 criteria, results in significant cost savings. [ABSTRACT FROM AUTHOR]

Background: Evidence relating childhood cancer to high birthweight is derived primarily from registry and case-control studies. We aimed to investigate this association, exploring the potential modifying roles of age at diagnosis and maternal anthropometrics, using prospectively collected data from the International Childhood Cancer Cohort Consortium.Methods: We pooled data on infant and parental characteristics and cancer incidence from six geographically and temporally diverse member cohorts [the Avon Longitudinal Study of Parents and Children (UK), the Collaborative Perinatal Project (USA), the Danish National Birth Cohort (Denmark), the Jerusalem Perinatal Study (Israel), the Norwegian Mother and Child Cohort Study (Norway), and the Tasmanian Infant Health Survey (Australia)]. Birthweight metrics included a continuous measure, deciles, and categories (≥ 4.0 vs. < 4.0 kilogram). Childhood cancer (377 cases diagnosed prior to age 15 years) risk was analysed by type (all sites, leukaemia, acute lymphoblastic leukaemia, and non-leukaemia) and age at diagnosis. We estimated hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models stratified by cohort.Results: A linear relationship was noted for each kilogram increment in birthweight adjusted for gender and gestational age for all cancers [HR = 1.26; 95% CI 1.02, 1.54]. Similar trends were observed for leukaemia. There were no significant interactions with maternal pre-pregnancy overweight or pregnancy weight gain. Birthweight ≥ 4.0 kg was associated with non-leukaemia cancer among children diagnosed at age ≥ 3 years [HR = 1.62; 95% CI 1.06, 2.46], but not at younger ages [HR = 0.7; 95% CI 0.45, 1.24, P for difference = 0.02].Conclusion: Childhood cancer incidence rises with increasing birthweight. In older children, cancers other than leukaemia are particularly related to high birthweight. Maternal adiposity, currently widespread, was not demonstrated to substantially modify these associations. Common factors underlying foetal growth and carcinogenesis need to be further explored. [ABSTRACT FROM AUTHOR]

Bronchodilators are a central therapy for symptom relief in respiratory diseases such as chronic obstructive pulmonary disease ( COPD) and asthma, with inhaled β2-adrenoceptor agonists and anticholinergics being the primary treatments available. The present studies evaluated the in vivo pharmacology of (R)-6-[[3-[[4-[5-[[2-Hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino]pent-1-ynyl]phenyl]carbamoyl]phenyl]sulfonyl]-4-[(3-methoxyphenyl)amino]-8-methylquinoline-3-carboxamide ( GS-5759), a novel bifunctional compound with both phosphodiesterase 4 ( PDE4) inhibitor and long-acting β2-adrenoceptor agonist ( LABA) activity, which has been optimized for inhalation delivery. GS-5759 dose-dependently inhibited pulmonary neutrophilia in a lipopolysaccharide ( LPS) aerosol challenge model of inflammation in rats with an ED50 ≤ 10 μg/kg. GS-5759 was also a potent bronchodilator with an ED50 of 0.09 μg/kg in guinea pigs and 3.4 μg/kg in dogs after methylcholine ( MCh) and ragweed challenges respectively. In cynomolgus monkeys, GS-5759 was dosed as a fine-particle dry powder and was efficacious in the same dose range in both MCh and LPS challenge models, with an ED50 = 70 μg/kg for bronchodilation and ED50 = 4.9 μg/kg for inhibition of LPS-induced pulmonary neutrophilia. In models to determine therapeutic index (T.I.), efficacy for bronchodilation was evaluated against increased heart rate and GS-5759 had a T.I. of 700 in guinea pigs and >31 in dogs. In a ferret model of emesis, no emesis was seen at doses several orders of magnitude greater than the ED50 observed in the rat LPS inflammation model. GS-5759 is a bifunctional molecule developed for the treatment of COPD, which has both bronchodilator and anti-inflammatory activity and has the potential for combination as a triple therapy with a second compound, within a single inhalation device. [ABSTRACT FROM AUTHOR]

This discussion of the goals and methods of teaching biblical literature is an edited transcription of a panel recorded at the 2010 Society for Biblical Literature conference. The panelists were asked to reflect on William Placher's recently published theological commentary on Mark as an example or test case of how one might use a biblical commentary as a classroom resource. Karl Barth wrote that insofar as their usefulness to pastors goes, most modern commentaries are 'no commentary at all, but merely the first step toward a commentary.' What value might commentaries have for our students, whether future pastors or undergraduates in the liberal arts? While the panel consisted of teachers of undergraduates as well as theological students, the emphasis of the presentations and subsequent discussion focused mostly on theological formation. [ABSTRACT FROM AUTHOR]

The ascertainment of serum free light chain (sFLC) levels has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. For patients with amyloidosis and those with oligo-secretory or non-secretory multiple myeloma (MM), serial measurement of sFLC has also been shown to be valuable in monitoring disease status. However, in patients with a measureable, intact monoclonal protein by immunofixation (M protein), the serial measurement of sFLC remains undefined and is currently not recommended in professional guidelines. Herein, we provide data comparing sFLC with M protein as biomarkers of response in newly diagnosed patients with MM undergoing induction therapy with the novel agents thalidomide, lenalidomide and/or bortezomib. We show that although M protein appears to outperform sFLC comparatively over the course of induction therapy, the addition of FLC to M protein further informs the characterization of residual disease status post-induction. Moreover, sFLC at the time of stem cell mobilization appears to hold prognostic power for survival endpoints following high-dose chemotherapy/autologous stem cell transplant (HDC/SCT). These findings suggest potentially novel roles for sFLC in patients with MM with an intact M protein receiving novel agent-based induction strategies followed by HDC/SCT. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

We evaluated the impact of busulfan dose intensity in patients undergoing reduced toxicity/intensity conditioning allogeneic transplantation in a multicenter retrospective study of 112 consecutive patients. Seventy-five patients were conditioned with busulfan (0.8 mg/kg/dose IV × 8 doses), fludarabine (30 mg/m2/day, days −7 to −3), and 6 mg/kg of ATG [reduced intensity conditioning (RIC) group], while 37 patients received a more-intense conditioning with busulfan (130 mg/m2/day IV, days −6 to −3), fludarabine (40 mg/m2/day, days −6 to −3) and 6 mg/kg of ATG [reduced toxicity conditioning (RTC) group]. At baseline both groups were matched for median age, unrelated donor allografts, and human leukocyte antigen-mismatched allografts. More patients in RIC group had high-risk disease, and higher median comorbidity index. There were no graft rejections. Median time to neutrophil (17 days vs. 15 days; p = 0.003) and platelet engraftment (16 days vs. 11 days; p < 0.001) was significantly longer in the RIC group. RTC group had significantly more bacterial (62.2% vs. 32%; p = 0.004) and fungal infections (13.5% vs. 1.3% p = 0.01). For RIC and RTC groups rates of grades II-IV acute GVHD (34% vs. 40%; p-value = 0.54), and chronic GVHD (45% vs. 57%; p-value = 0.30) were not significantly different. In similar order at 1 year the cumulative-incidence of non-relapse mortality (NRM; 12% vs. 21%; p-value = 0.21) and relapse rates (38% vs. 39%; p = 0.96) were not significantly different. Patients in RIC and RTC groups had similar 1-year overall survival (61% vs. 50%, p = 0.11) and progression-free survival (50% vs. 36%, p-value = 0.39). Our data suggest that the merits of higher busulfan dose intensity in the context of fludarabine/busulfan-based RTC may be offset by higher early morbidity. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The long-term follow-up is presented for 317 patients with acute myeloid leukaemia who underwent human leucocyte antigen-identical sibling marrow transplants between 1984 and 1995 following preparation with busulfan 16 mg/kg and cyclophosphamide 120 mg/kg. Among the 142 (45%) who were alive and leukaemia-free 3 years following transplantation, the leukaemia-free survival at 15 years was 72·8%. The cumulative incidence of late (>3 years beyond transplant) non-relapse mortality at 15 years was 12·9% and of late relapse was 16·5%. None of the variables considered (including age, disease stage, and graft- versus-host disease) were predictive of late failure. [ABSTRACT FROM AUTHOR]

1. Chronic wounds, especially in diabetics, represent a serious threat to human health. 2. Correcting a compromised state of tissue oxygenation by the administration of supplemental O2 is known to benefit wound healing. Beyond its role as a nutrient and antibiotic, O2 supports wound healing by driving redox signaling. 3. Hyperbaric oxygen (HBO) therapy is widely used and approved by Center for Medicare and Medicaid Services to treat specific ulcerations. The current literature supports the notion that approaches to topically oxygenate wounds may be productive. 4. Here, we present the results of two simultaneous studies testing the effects of HBO and portable topical oxygen (TO) therapies. These two therapeutic approaches have several contrasting features. 5. In total, 1854 patients were screened in outpatient wound clinics for non-randomized enrolments into the HBO ( n = 32; 31% diabetic) and TO ( n = 25; 52% diabetic) studies. 6. Under the conditions of the present study, HBO treatment seemed to benefit some wounds while not benefiting others. Overall, HBO did not result in statistically significant improvements in wound size in the given population over the time monitored in the present study. 7. However, TO significantly improved wound size. Among the three O2-sensitive genes ( VEGF, TGFb1 and COL1A1) studied in wound edge tissue biopsies, TO treatment was associated with higher VEGF165 expression in healing wounds. Expression of the other genes mentioned was not affected by TO. There was no significant change in the expression levels of any of genes studied in patients in the HBO study. This establishes a link between VEGF gene expression and healing outcome for TO therapy. 8. Taken together, the present study provides evidence demonstrating that TO treatment benefits wound healing in patients suffering from chronic wounds. Treatment with TO is associated with an induction of VEGF expression in wound edge tissue and an improvement in wound size. [ABSTRACT FROM AUTHOR]

The article discusses a study about the relation between hyperglycemia and hospital mortality in patients with acute myeloid leukemia (AML). Under the study, hospitalization, glucose exposure and outcomes of 283 adult patients were analyzed. Results show that hyperglycemia during a patient's hospitalization leads to an increase in hospital mortality. It adds that sepsis does not play a main role for the negative impacts of hyperglycemia on hospital mortality.

The article investigates the convergent validity of individual clinical task interviews suggested by Jean Piaget and Barbel Inhelder associated with the group tests of cognitive development. These tests were constructed to evaluate the acquisition of cognitive abilities. The three group tests raw scores combined with the raw scores of the concrete-formal task interviews will come up with the Pearson product-moment correlations. It includes the Reasoning Test, Logical Reasoning Test, and Classroom Test of Formal Operations. It was revealed that Reasoning test indicates lower cognitive levels of subjects compared to logical Reasoning Test and Classroom Test of Formal Operations.