Evaluation of the concept of pressure proof testing fuselage structures

The FAA and NASA have recently completed independent technical evaluations of the concept of pressure proof testing the fuselage of commercial transport airplanes. The results of these evaluations are summarized. The objectives of the evaluations were to establish the potential benefit of the pressure proof test, to quantify the most desirable proof test pressure, and to quantify the required proof test interval. The focus of the evaluations was on multiple-site cracks extending from adjacent rivet holes of a typical fuselage longitudinal lap splice joint. The FAA and NASA do not support pressure proof testing the fuselage of aging commercial transport aircraft. The argument against proof testing is as follows: (1) a single proof test does not insure an indefinite life; therefore, the proof test must be repeated at regular intervals; (2) for a proof factor of 1.33, the required proof test interval must be below 300 flights to account for uncertainties in the evaluation; (3) conducting the proof test at a proof factor of 1.5 would considerably exceed the fuselage design limit load; therefore, it is not consistent with accepted safe practices; and (4) better safety can be assured by implementing enhanced nondestructive inspection requirements, and adequate reliability can be achieved by an inspection interval several times longer than the proof test interval

Nipple-Sparing Mastectomy in 99 Patients With a Mean Follow-up of 5 Years

Background. The safety and practicality of nipple-sparing mastectomy (NSM) are controversial. Methods. Review of a large breast center's experience identified 99 women who underwent intended NSM with subareolar biopsy and breast reconstruction for primary breast cancer. Outcome was assessed by biopsy status, postoperative nipple necrosis or removal, cancer recurrence, and cancer-specific death. Results. NSM was attempted for invasive cancer (64 breasts, 24 with positive lymph nodes), noninvasive cancer (35 breasts), and/or contralateral prophylaxis (50 breasts). Twenty-two nipples (14%) were removed because of positive subareolar biopsy results (frozen or permanent section). Seven patients underwent a pre-NSM surgical delay procedure because of increased risk for nipple necrosis. Reconstruction used transverse rectus abdominis myocutaneous flaps (56 breasts), latissimus flaps with expander (35 breasts), or expander alone (58 breasts). Of 127 retained nipples, 8 (6%) became necrotic and 2 others (2%) were removed at patient request. There was no nipple necrosis when NSM was performed after a surgical delay procedure. At a mean follow-up of 60.2 months, all 3 patients with recurrence had biopsy-proven subareolar disease and had undergone nipple removal at original mastectomy. There were no deaths. Conclusions. Five-year recurrence rate is low when NSM margins (frozen section and permanent) are negative. Nipple necrosis can be minimized by incisions that maximize perfusion of surrounding skin and by avoiding long flaps. A premastectomy surgical delay procedure improves nipple survival in high-risk patients. NSM can be performed safely with all types of breast reconstruction

Alloimmunization in sickle cell disease: changing antibody specificities and association with chronic pain and decreased survival: Alloimmunization in SCD

Alloimmunization remains a significant complication of transfusion and has been associated with multiple factors, including inflammation, an important pathophysiologic mechanism in sickle cell disease (SCD). We explored whether alloimmunization is associated with disease severity in SCD

Provocation of ventricular tachycardia by an automatic implantable cardioverter defibrillator

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28495/1/0000292.pd

Adults with corrected oesophageal atresia: is oesophageal function associated with complaints and/or quality of life?

The aim of this study was to evaluate oesophageal function after correction of oesophageal atresia in adults, and to investigate the association between complaints, oesophageal function and quality of life (QoL). Twenty-five adults were included who participated in previous follow-up studies, during which complaints of dysphagia and gastro-oesophageal reflux (GOR), results of upper gastrointestinal endoscopy, oesophageal biopsies and QoL had been collected. Manometry was performed in 20 patients, 24 h pH-measurements were performed in 21 patients. pH-values (sample time 5 s) were calculated using criteria of Johnson and DeMeester. Associations were tested with ANOVA and χ2-tests. Ten patients (48%) reported complaints of dysphagia, seven (33%) of GOR. The amplitude of oesophageal contractions was low (<15 mmHg) in four patients (20%). pH-measurements showed pathological reflux in three patients (14%). Patients reporting dysphagia more often had disturbed motility (P = 0.011), and lower scores on the domains “general health perceptions” (SF-36) (P = 0.026), “standardised physical component” (SF-36) (P = 0.013), and “physical well-being” (GIQLI) (0.047). No other associations were found. This study shows a high percentage of oesophageal motility disturbances and a moderate percentage of GOR after correction of oesophageal atresia. Patients reporting dysphagia, whom more often had disturbed motility, seemed to be affected by these symptoms in their QoL

MYH9 and APOL1 are both associated with sickle cell disease nephropathy

Renal failure occurs in 5–18% of sickle cell disease (SCD) patients and is associated with early mortality. At risk SCD patients cannot be identified prior to the appearance of proteinuria and the pathobiology is not well understood. The MYH9 and APOL1 genes have been associated with risk for focal segmental glomerulosclerosis and end-stage renal disease in African Americans

Urinary Albumin Excretion is Associated with Pulmonary Hypertension in Sickle Cell Disease: Potential Role of Soluble Fms-Like Tyrosine Kinase-1

Pulmonary hypertension (PHT) is reported to be associated with measures of renal function in patients with sickle cell disease (SCD). The purpose of this exploratory study was to determine the relationship between albuminuria and both clinical and laboratory variables in SCD

Reduced selenium-binding protein 1 expression is associated with poor outcome in lung adenocarcinomas

The effects of selenium, an essential nutrient with anti-carcinogenic properties, are mediated by selenium-binding proteins. The protein expression status of human selenium-binding protein 1 (SBP1) in human tumours and the exact function of this protein are not known. In this study, quantitative two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used on 93 lung adenocarcinomas and ten uninvolved lung samples. Two likely isoforms of a 56 kD protein that showed a significantly decreased abundance in lung adenocarcinomas were observed. Tandem mass spectrometry and 2-D western blot analysis identified these two proteins as human SBP1. Tumour tissue microarrays were utilized to examine the cellular expression patterns of SBP1 using immunohistochemistry. The same tissue samples were examined for SBP1 mRNA expression using oligonucleotide microarrays. Two major SBP1 isoforms were detected, with an acidic isoform (457) being significantly down-regulated in lung adenocarcinomas compared with normal lung ( p = 0.02). Two additional more acidic SBP1 isoforms were only observed in normal lung. SBP1 protein isoforms and SBP1 mRNA levels were significantly decreased in poorly differentiated (versus moderately and well-differentiated), T2–T4 (versus T1), and bronchus-derived (versus bronchioloalveolar) tumours. Low levels of SBP1 protein (native form, 460) correlated significantly with poor survival ( p = 0.007). The lack of SBP1 expression was not due to gene deletion. Treatment of A549 lung adenocarcinoma cells with the methylation inhibitor 5-azacytidine did not affect expression of the SBP1 protein. Analysis of the tumour proliferation status using Ki-67 suggests that down-regulated expression of SBP1 may reflect increased cell proliferation and decreased differentiation in lung adenocarcinomas. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34487/1/1524_ftp.pd

Synthesis and Investigation of a Radioiodinated F3 Peptide Analog as a SPECT Tumor Imaging Radioligand

A radioiodinated derivative of the tumor-homing F3 peptide, (N-(2-{3-[125I]Iodobenzoyl}aminoethyl)maleimide-F3Cys peptide, [125I]IBMF3 was developed for investigation as a SPECT tumor imaging radioligand. For this purpose, we custom synthesized a modified F3 peptide analog (F3Cys) incorporating a C-terminal cysteine residue for site-specific attachment of a radioiodinated maleimide conjugating group. Initial proof-of-concept Fluorescence studies conducted with AlexaFluor 532 C5 maleimide-labeled F3Cys showed distinct membrane and nuclear localization of F3Cys in MDA-MB-435 cells. Additionally, F3Cys conjugated with NIR fluorochrome AlexaFluor 647 C2 maleimide demonstrated high tumor specific uptake in melanoma cancer MDA-MB-435 and lung cancer A549 xenografts in nude mice whereas a similarly labeled control peptide did not show any tumor uptake. These results were also confirmed by ex vivo tissue analysis. No-carrier-added [125I]IBMF3 was synthesized by a radioiododestannylation approach in 73% overall radiochemical yield. In vitro cell uptake studies conducted with [125I]IBMF3 displayed a 5-fold increase in its cell uptake at 4 h when compared to controls. SPECT imaging studies with [125I]IBMF3 in tumor bearing nude mice showed clear visualization of MDA-MB-435 xenografts on systemic administration. These studies demonstrate a potential utility of F3 peptide-based radioligands for tumor imaging with PET or SPECT techniques