Numerical simulation of aerosol particle transport by oscillating flow in respiratory airways

Particle transport by oscillating flow in a tapered channel or in a tapered tube was computed from the complete equations of motion. These geometries represent a simplified model of the divergent flow field of the mammalian bronchial tree. The computed deformation profile of a line of particles, transported by the oscillatory motion, was compared with prior experimental results and analytical calculations. All three methods agree that there is transport in the divergent direction of the tube by an axial stream of steady drift in the core for moderately high frequency of oscillation (Womersley parameter in the range of 1 to 10). Bidirectional flow is established by an annular stream in the convergent direction, with no net flow on integral cycles of the oscillating fluid. At higher frequency, however, the steady stream transforms to a different shape in the tapered tube, with transport in the divergent direction nearer the walls of the tube, rather than in the core. Transport by the continuing streams with oscillatory ventilation of the respiratory tract should deliver medicinal aerosols of low intrinsic particle mobility to the peripheral regions of the lungs.     

Rapid repeat pregnancy and experiences of interpersonal violence among low-income adolescents

CONTEXT: Rapid repeat pregnancy (RRP) among adolescents, usually defined as pregnancy onset within 12-24 months of the previous pregnancy outcome, has frequently been the target of public health interventions, due to the exacerbation of negative consequences associated with recurrent adolescent pregnancy (and more specifically with childbearing). OBJECTIVE: To examine what, if any, relationship exists between RRP and the experience of interpersonal violence and abuse among low-income adolescents at one semi-urban health center. DESIGN: Case-control study using retrospective chart review. PARTICIPANTS AND SETTING: 100 women aged 13-21 who received prenatal care at one independent nonprofit health center that serves adolescents and their children from June 1994 through June 1996. MAIN OUTCOME MEASURES: Number and timing of pregnancies, occurrence of physical or sexual abuse; other psychosocial risk factors were evaluated. RESULTS: In this population, the experience of any form of physical or sexual violence during the study interval was associated with RRP within 12 months (p = 0.01, OR = 3.46) and 18 months (p = 0.013, OR = 4.29). Other previously reported predictors of RRP, including family stress, financial stress, and other environmental stressors did not reach statistical significance at either 12 months or 18 months in this sample. Of additional note, young women who experienced any form of abuse during the 12-month study interval were substantially more likely to miscarry than were their nonabused peers, and spontaneous abortion was also very strongly associated with RRP (p < 0.00001; OR = 22.6). CONCLUSIONS: The experience of interpersonal violence is correlated with rapid repeat pregnancy among low-income adolescents. This study strongly suggests a need for both extensive screening for partner and family violence among pregnant and postpartum adolescents, and follow-up safety planning support in combination with family planning interventions.     

The evaluation of the sensitivity and specificity of wrist examination findings for predicting fractures

Background

The aim of this study was to evaluate the sensitivity and specificity of physical examination findings and functional tests in adult acute wrist trauma patients who presented to the emergency department (ED) and to create a reliable and practical clinical decision rule for determining the necessity of radiography in wrist trauma.

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE epsilon4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-epsilon4 and 12 epsilon4 subjects. The epsilon4 group displayed greater activation than the non-epsilon4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE epsilon4-related deficiencies associated with verbal episodic memory encoding and consolidation.     

Neurocognitive impairment in middle-aged and older adults with bipolar disorder: comparison to schizophrenia and normal comparison subjects

BACKGROUND: The frequency, pattern, and correlates of neurocognitive impairment in older patients with bipolar disorder have received little study. We examined neurocognitive abilities in middle-aged and older adults with bipolar disorder to groups with schizophrenia or normal subjects, as well as the relation of neurocognition to clinical characteristics. METHOD: We administered a battery of neurocognitive and clinical measures to older (45-85 years) outpatients with bipolar disorder (n=67), schizophrenia (n=150), and normal comparison subjects (n=85). Within the bipolar group, we assessed the association between neurocognitive performance and psychiatric symptoms, quality of life, and medication status. RESULTS: The group with bipolar disorder differed on nearly all neuropsychological tests compared to normal subjects, with medium effect sizes. Bipolar patients as impaired as those with schizophrenia on half of the tests administered, and performed better on the remaining tests, with small effect sizes. Neurocognitive deficits in bipolar disorder group related to lower quality of life, but not to psychiatric symptom severity or duration of illness. LIMITATIONS: Samples were outpatients with mild-moderate symptoms, and findings may not generalize to acutely ill populations. We lacked data on illness history to examine the cumulative impact of psychopathology. CONCLUSIONS: Among clinically stable middle-aged and older outpatients, bipolar disorder was associated with substantial neurocognitive impairment, with a pattern that was somewhat distinct from that found in schizophrenia. Deficits in the bipolar group were not related to severity or duration of psychiatric symptoms, but were related to quality of life. Bipolar disorder often involve disabling and enduring cognitive impairments in older outpatients.     

Chemoradiation-Related Lymphopenia and Its Association with Survival in Patients with Squamous Cell Carcinoma of the Anal Canal

BackgroundAlthough treatment‐related lymphopenia (TRL) is common and associated with poorer survival in multiple solid malignancies, few data exist for anal cancer. We evaluated TRL and its association with survival in patients with anal cancer treated with chemoradiation (CRT).Materials and MethodsA retrospective analysis of 140 patients with nonmetastatic anal squamous cell carcinoma (SCC) treated with definitive CRT was performed. Total lymphocyte counts (TLC) at baseline and monthly intervals up to 12 months after initiating CRT were analyzed. Multivariable Cox regression analysis was performed to evaluate the association between overall survival (OS) and TRL, dichotomized by grade (G)4 TRL (<0.2k/μL) 2 months after initiating CRT. Kaplan‐Meier and log‐rank tests were used to compare OS between patients with versus without G4 TRL.ResultsMedian time of follow‐up was 55 months. Prior to CRT, 95% of patients had a normal TLC (>1k/μL). Two months after initiating CRT, there was a median of 71% reduction in TLC from baseline and 84% of patients had TRL: 11% G1, 31% G2, 34% G3, and 8% G4. On multivariable Cox model, G4 TRL at two months was associated with a 3.7‐fold increased risk of death. On log‐rank test, the 5‐year OS rate was 32% in the cohort with G4 TRL versus 86% in the cohort without G4 TRL.ConclusionTRL is common and may be another prognostic marker of OS in anal cancer patients treated with CRT. The association between TRL and OS suggests an important role of the host immunity in anal cancer outcomes.Implications for PracticeThis is the first detailed report demonstrating that standard chemoradiation (CRT) commonly results in treatment‐related lymphopenia (TRL), which may be associated with a poorer overall survival (OS) in patients with anal squamous cell carcinoma. The association between TRL and worse OS observed in this study supports the importance of host immunity in survival among patients with anal cancer. These findings encourage larger, prospective studies to further investigate TRL, its predictors, and its relationship with survival outcomes. Furthermore, the results of this study support ongoing efforts of clinical trials to investigate the potential role of immunotherapy in anal cancer.     

Arginase activity in alternatively activated macrophages protects PI3Kp110δ deficient mice from dextran sodium sulfate induced intestinal inflammation

Alternatively activated or M2 macrophages have been reported to protect mice from intestinal inflammation, but the mechanism of protection has not been elucidated. In this study, we demonstrate that mice deficient in the p110δ catalytic subunit activity of class I phosphatidylinositol 3‐kinase (PI3Kp110δ) have increased clinical disease activity and histological damage during dextran sodium sulfate (DSS) induced colitis. Increased disease severity in PI3Kp110δ‐deficient mice is dependent on professional phagocytes and correlates with reduced numbers of arginase I⁺ M2 macrophages in the colon and increased production of inflammatory nitric oxide. We further demonstrate that PI3Kp110δ‐deficient macrophages are defective in their ability to induce arginase I when skewed to an M2 phenotype with IL‐4. Importantly, adoptive transfer of IL‐4‐treated macrophages derived from WT mice, but not those from PI3Kp110δ‐deficient mice, protects mice during DSS‐induced colitis. Moreover, M2 macrophages mediated protection is lost when mice are cotreated with inhibitors that block arginase activity or during adoptive transfer of arginase I deficient M2 macrophages. Taken together, our data demonstrate that arginase I activity is required for M2 macrophages mediated protection during DSS‐induced colitis in PI3Kp110δ‐deficient mice.     

A p53 mutation in exon 5 associated with adenovirus transformation

The adenovirus type 5 (Ad5) 55-kDa E1B oncoprotein has been shown to form complexes with the p53 tumor suppressor protein. These complexes are thought to interfere with normal p53 activity and may be responsible for the paucity of p53 mutations in cells transformed by these viruses. This report describes an example of a p53 mutation in exon 5 in an Ad5-transformed cell line that exhibited less expression of E1B 55-kDa protein and a longer tumor-latency phenotype than another Ad5-transformed cell line expressing wild-type p53. The finding of a p53 mutation in an Ad5-transformed cell line is unusual, especially considering the current theory that p53-E1B interactions play an important role in adenovirus transformation. This mutation could represent an alternative method of inactivating p53 function in the absence of sufficient levels of E1B 55-kDa oncoprotein. © 1995 Wiley-Liss Inc.