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Highlights • Male infertility and adverse pregnancy outcomes are relevant human health problems. • Radiofrequency electromagnetic fields are widespread in the human environment. • A link between radiofrequency and adverse reproductive outcomes is controversial. • This is the protocol of WHO-funded systematic review and meta-analysis on this issue., Background Radiofrequency Electromagnetic Fields (RF-EMF) at environmental level have been reported to induce adverse effects on the male reproductive system and developing embryos. However, despite the number of experiments conducted since the 1970s, the diversity of testing approaches and exposure conditions, inconsistencies among results, and dosimetric flaws have not yet permitted a solid assessment of the relationship between RF-EMF exposure and such effects, warranting a more systematic and methodologically rigorous approach to the evaluation of available data. Objectives This study aims at evaluating the effects of RF-EMF exposure on male fertility and pregnancy outcomes by a systematic review (SR) of experimental studies, conducted in compliance with international guidelines. The evidence will be organized into three streams: 1) Studies evaluating the impact of RF-EMF on the male reproductive system of experimental mammals; 2) studies evaluating the impact of RF-EMF on human sperm exposed in vitro; 3) studies evaluating the impact of RF-EMF on adverse pregnancy, birth outcomes and delayed effects in experimental mammals exposed in utero. Study eligibility and criteria Eligible studies will include peer-reviewed articles reporting of original results about effects of controlled exposures to RF-EMF in the frequency range 100 kHz–300 GHz on the selected outcomes without any language or year-of-publication restrictions. Eligible studies will be retrieved by calibrated search strings applied to three electronic databases, PubMed, Scopus and EMF Portal and by manual search of the list of references of included papers and published reviews. Study appraisal and synthesis method The internal validity of the studies will be evaluated using the Risk of Bias (RoB) Rating Tool developed by National Toxicology Program/Office of Health Assessment and Translation (NTP/OHAT) integrated with input from the SYRCLE RoB tool. Given sufficient commensurate data, meta-analyses will be performed, otherwise narrative syntheses will be produced. Finally, the certainty of the effects of RF-EMF exposure on male fertility and pregnancy and birth outcomes will be established following GRADE. Funding The study is financially supported by the World Health Organization. Registration OSF Registration DOI https://doi.org/10.17605/OSF.IO/7MUS3; PROSPERO CRD42021227729, CRD42021227746.

Gaps in hepatitis C virus (HCV) testing, diagnosis, liver disease assessment and treatment uptake among people who inject drugs (PWID) persist. We aimed to describe the cascade of HCV care among PWID in Australia, prior to and following unrestricted access to direct-acting antiviral (DAA) treatment. Participants enrolled in an observational cohort study between 2014 and 2018 provided fingerstick whole-blood samples for dried blood spot, Xpert HCV Viral Load and venepuncture samples. Participants underwent transient elastography and clinical assessment by a nurse or general practitioner. Among 839 participants (mean age 43 years), 66% were male (n = 550), 64% (n = 537) injected drugs in the previous month, and 67% (n = 560) reported currently receiving opioid substitution therapy. Overall, 45% (n = 380) had detectable HCV RNA, of whom 23% (n = 86) received HCV treatment within 12 months of enrolment. HCV treatment uptake increased from 2% in the pre-DAA era to 38% in the DAA era. Significant liver fibrosis (F2-F4) was more common in participants with HCV infection (38%) than those without (19%). Age 50 years or older (aOR, 2.88; 95% CI, 1.18-7.04) and attending a clinical follow-up with nurse (aOR, 3.19; 95% CI, 1.61-6.32) or physician (aOR, 11.83; 95% CI, 4.89-28.59) were associated with HCV treatment uptake. Recent injection drug use and unstable housing were not associated with HCV treatment uptake. HCV treatment uptake among PWID has increased markedly in the DAA era. Evaluation of innovative and simplified models of care is required to further enhance treatment uptake.

Among people who inject drugs (PWIDs) the prevalence of tobacco smoking exceeds 80%; making smoking cessation intervention a priority for this population. This study aims to examine staff and client perspectives from a supervised injecting facility regarding: i) whether an organizational change intervention increased rates of smoking cessation care delivery (pre- to post-intervention); and ii) acceptability of the intervention.A pre-and-post intervention pilot study in a supervised injecting facility was conducted in Sydney, Australia between July 2014-December 2015. The intervention employed an organizational change approach and included six components. Cross-sectional samples of staff (pre n = 27, post n = 22) and clients (pre n = 202, post n = 202) completed online surveys pre and post intervention.From pre to post-intervention staff reported smoking cessation practices significantly increased for the provision of verbal advice (30% to 82%; p 0.001), offer of free or subsidized nicotine replacement therapy (30% to 91%; p 0.001), referral to a general practitioner (19% to 64%; p = 0.001), and follow-up to check on quit smoking progress (18.5% to 64%; p = 0.001). Significantly more clients reported receiving all smoking cessation strategies post-intervention. Over 85% of staff agreed that it was acceptable to address client smoking as part of usual care and 95% of clients agreed that it was acceptable to be asked by staff about their tobacco smoking.Increasing the provision of smoking cessation care using an organizational change approach is both feasible for staff and acceptable to staff and clients of supervised injecting facilities.

Study Design Retrospective, chart review. Objectives The identification and management of pelvic obliquity in neuromuscular scoliosis can be difficult; therefore, appropriate evaluation of this pathology is important. Variations in presentation have resulted in various methods of measurement, without a consensus or gold standard measurement. This study is the evaluation of reliability of five methods commonly used to determine pelvic obliquity in the frontal plane. Summary of Background Data Previous studies have used five different methods (ie, the Maloney method, the O'Brien method, the Osebold method, the Allen and Ferguson method, and the Lindseth method) to determine pelvic obliquity in the frontal plane. Methods Radiographic images of 50 patients with neuromuscular scoliosis involving the pelvic girdle were identified and evaluated by a team of 5 raters. Each rater was instructed to apply five commonly used methods of measuring pelvic obliquity. The same raters were asked to rate the same radiographs again after a minimum of one month. The interobserver reliability was assessed using the intraclass correlation coefficient (ICC) and the intraobserver analysis was assessed using the Pearson correlation. A rating greater than 0.8 was considered excellent reliability. Results The Maloney method showing the highest interobserver reliability of ICC of 0.965 and 0.964. The Lindseth method had the lowest ICC, but all the methods were considered highly reliable by the rating classification system. The Maloney method also showed the highest intraobserver reliability, ranging from 0.845 to 0.962. The Allen and Ferguson method had the lowest intraobserver reliability. Conclusions Many of the methods tested had excellent reliability in this study, but our data suggest the Maloney method is the most reliable method of measuring pelvic obliquity on a frontal view radiograph. Level of Evidence Level III, retrospective, comparative study.

Introduction and designs Take-home naloxone (THN) interventions are an effective response to preventing overdose deaths, however uptake across Australia remains limited. This project designed, implemented and evaluated a model of care targeting opioid users attending alcohol and other drug (AOD) treatment, needle and syringe programs (NSP) and related health services targeting people who inject drugs. Design and methods Service providers, consumers and regulators collaboratively designed a THN brief intervention (ORTHN, Overdose Response with Take-Home Naloxone) involving client education and supply of naloxone in pre-filled syringes, delivered by nursing, allied health and NSP workers. ORTHN interventions were implemented in over 15 services across New South Wales, Australia. The evaluation included client knowledge, attitudes, substance use and overdose experiences immediately before and 3 months after ORTHN intervention in a subsample of participants. Results Six hundred and sixteen interventions were delivered, with 145 participants recruited to the research subsample, of whom 95 completed the three-month follow up. Overdose-related attitudes amongst participants improved following ORTHN, with no evidence of increased substance use or failure to implement other 'first responses' (e.g. calling an ambulance). Nine participants (10%) reversed an overdose using THN in the follow-up period. Participants identified a willingness to access THN from a range of services. While a minority (16%) indicated they were unwilling to pay for THN, the median price that participants were willing to pay was $AUD20 (IQR $10.40). Discussion and conclusions The ORTHN model of care for THN appears an effective way to disseminate THN to people who use opioids attending AOD, NSP and related health-care settings.

The primary catalysts for Financial Widgets Plus (FWP) to make such a monumental change were identified—the primary problem being centered on the ongoing and escalating costs over time of doing business with their current vendor. The benefits of their current DBMS being rock solid, dependable, and having served their needs effectively for many years, were revenue drivers going to be worth the risk to the company would be the next set of questions that would have to be answered.

When Vernon was first presented with the mandate to start researching alternative database solutions for Financial Widgets Plus (FWP) he saw a much larger opportunity at hand. Coming in to a new company that had a database department that consisted entirely of a group of what he termed as Reactive Database Administrators that had created and deployed an amalgamation of one off solutions and had never explored the concept of standardization, he realized that this was the best thing that could happen to not only Financial Widgets Plus, but also to the department that he was now heading up. Where others saw the migration to a new database solution as an opportunity to lower costs significantly and be done with what they perceived as a predatory vendor, Vernon saw this is an opportunity to fix many headaches and problems that had been plaguing the organization for quite some time.

Taking on such a monumental technology task as migrating to a different DBMS solution involves equally monumental risks, and the only way to mitigate those risks is through proper analysis, planning, testing, and implementation. Not to minimize other areas of technology, but migrating database solutions carries an extraordinary risk in comparison.

There are many drivers for change in the world of technology and business. We are going to look at a couple of those in the following chapters from the viewpoint of a fictional company that has come out with a new product while at the same time going through a licensing audit. These two catalysts caused the company, Financial Widgets Plus (FWP), to evaluate their current database solution and possible alternative solutions because the cost, along with the overhead of use, of the proprietary solution could no longer be supported or fiscally responsible. They needed a replacement that would propel their new platform into the forefront while allowing them to generate more revenue to drive and support growth.

Silicon-Carbide (SiC) device technology has generated much interest in recent years. With superior thermal performance, power ratings and potential switching frequencies over its Silicon (Si) counterpart, SiC offers a greater possibility for high powered switching applications in extreme environment. In particular, SiC Metal-Oxide-Semiconductor Field-Effect Transistors' (MOSFETs) maturing process technology has produced a plethora of commercially available power dense, low on-state resistance devices capable of switching at high frequencies. A novel hard-switched power processing unit (PPU) is implemented utilizing SiC power devices. Accelerated life data is captured and assessed in conjunction with a damage accumulation model of gate oxide and drain-source junction lifetime to evaluate potential system performance at high temperature environments.

Background Posterior spinal fusion (PSF) in children with cerebral palsy (CP) carries a high risk of complications and morbidity. The purpose of this study is to investigate the impact of using two attending surgeons on blood loss, operative time, and complications in this fragile population. Methods This was a prospective, matched cohort analysis of patients with CP who underwent PSF with two attending surgeons. These were matched with a control group that had a single-surgeon team, assisted by a senior resident or PA. The groups were compared using paired Student t tests and chi-square tests. Results 50 patients were included in the study (25 study and 25 matched controls), determined by our power analysis. There was no statistical difference in the mean age, preoperative major curve angle, major curve angle correction, or use of antifibrinolytics. The two-surgeon group decreased surgical time from 5.25 to 3.3 hours (p = .000002), and estimated blood loss from 1,238 to 865 mL (p = .009). The complication rate decreased from 33% to 8% (p=.034). Length of stay was also decreased from 6.5 days to 5.35 (p = .02). Conclusions Although confounding variables were present, this study demonstrates that the use of a two-surgeon team during spinal surgery for patients with cerebral palsy could have a role in reducing operative time, blood loss, complication rates, and hospital length of stay. Overall, these factors and any improved operating room efficiencies may lead to lasting improved patient outcomes. Level of Evidence Level III, retrospective, comparative study.

In this paper, inexpensive single-mode silica optical fibers were interrogated with Luna Innovations' optical backscatter reflectometer to perform distributed temperature measurements at temperatures up to 1000 °C. Measurements of the Rayleigh backscattered signal were taken continuously to determine the amount of light that is backscattered as a function of temperature and position along the length of the fiber. These data were post-processed to determine the spectral shift in the Rayleigh backscatter signature. The spectral shift data were then calibrated to a change in temperature. This paper determines an upper operational temperature limit of 650 °C for the distributed measurement technique based on Rayleigh backscatter using Corning's SMF-28e+ commercially available single-mode fiber.

The technique of placing an oblique screw in the terminal hole of a plate to increase screw pullout strength is widely taught in the operating room. The origin of this technique is unclear; however, it may have been used simply as a means to identify radiographs and misinterpreted to have some biomechanical benefit. The objective of this study was to measure the structural effect of oblique terminal screw placement (OTSP) during plate osteosynthesis. Foam blocks and limited contact dynamic compression plates and screws were used along with a custom fixture device. The terminal screw was placed in either an oblique (30-degree angle outward) or perpendicular fashion. A load was applied perpendicular to the plate in cantilever bending until failure. The oblique screw construct was significantly weaker than the perpendicular screw construct (399N vs. 465N, P < 0.001), independent of the block of material used. Post hoc analysis showed that the screw angle (P < 0.001) was a significant determinant of the load required to cause screw pullout. OTSP led to a decrease in pullout strength compared with a perpendicular screw in a deformable foam medium similar in density to osteoporotic bone. In patients with poor bone quality, OTSP may create a suboptimal fracture fixation construct.

The youngest of five siblings, Roger Wood grew up in Buckinghamshire, where his father was a rural GP. He qualified at a time when all students helped in the blitz. After war service …

Background Adoptive T cell therapy (ACT) has shown great promise in melanoma, with over 50 % response rate in patients where autologous tumor-reactive tumor-infiltrating lymphocytes (TIL) can be cultured and expanded. A major limitation of ACT is the inability to generate or expand autologous tumor-reactive TIL in 25–45 % of patients tested. Methods that successfully identify tumors that are not suitable for TIL generation by standard methods would eliminate the costs of fruitless expansion and enable these patients to receive alternate therapy immediately. Methods Multispectral fluorescent immunohistochemistry with a panel including CD3, CD8, FoxP3, CD163, PD-L1 was used to analyze the tumor microenvironment in 17 patients with melanoma among our 36-patient cohort to predict successful TIL generation. Additionally, we compared tumor fragments and enzymatic digestion of tumor samples for efficiency in generating tumor-reactive TIL. Results Tumor-reactive TIL were generated from 21/36 (58 %) of melanomas and for 12/13 (92 %) tumors where both enzymatic and fragment methods were compared. TIL generation was successful in 10/13 enzymatic preparations and in 10/13 fragment cultures; combination of both methods resulted in successful generation of autologous tumor-reactive TIL in 12/13 patients. In 17 patients for whom tissue blocks were available, IHC analysis identified that while the presence of CD8+ T cells alone was insufficient to predict successful TIL generation, the CD8+ to FoxP3+ ratio was predictive with a positive-predictive value (PPV) of 91 % and negative-predictive value (NPV) of 86 %. Incorporation of CD163+ macrophage numbers and CD8:PD-L1 ratio did not improve the PPV. However, the NPV could be improved to 100 % by including the ratio of CD8+:PD-L1+ expressing cells. Conclusion This is the first study to apply 7-color multispectral immunohistochemistry to analyze the immune environment of tumors from patients with melanoma. Assessment of the data using unsupervised hierarchical clustering identified tumors from which we were unable to generate TIL. If substantiated, this immune profile could be applied to select patients for TIL generation. Additionally, this biomarker profile may also indicate a pre-existing immune response, and serve as a predictive biomarker of patients who will respond to checkpoint blockade. We postulate that expanding the spectrum of inhibitory cells and molecules assessed using this technique could guide combination immunotherapy treatments and improve response rates. Electronic supplementary material The online version of this article (doi:10.1186/s40425-015-0091-z) contains supplementary material, which is available to authorized users.

To evaluate the association of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA), and scar in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Prospective cohort study within a randomized clinical trial.The 1185 CATT participants.Masked readers graded scar and GA on fundus photography and fluorescein angiography and graded SHRM on time-domain and spectral-domain (SD) optical coherence tomography (OCT) throughout 104 weeks. Measurements of SHRM height and width in the fovea, within the center 1 mm(2), or outside the center 1mm(2) were obtained on SD OCT images at 56 (n = 76) and 104 (n = 66) weeks.Presence of SHRM, as well as location and size, and associations with VA, scar, and GA.Among CATT participants, the percentage with SHRM at enrollment was 77%, decreasing to 68% at 4 weeks after treatment and to 54% at 104 weeks. At 104 weeks, scar was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved (64% vs. 31%; P0.0001). Among eyes with detailed evaluation of SHRM at weeks 56 (n = 76) and 104 (n = 66), mean VA letter score was 73.5 (standard error [SE], 2.8), 73.1 (SE, 3.4), 65.3 (SE, 3.5), and 63.9 (SE, 3.7) when SHRM was absent, present outside the central 1 mm(2), present within the central 1 mm(2) but not the foveal center, or present at the foveal center (P = 0.02), respectively. When SHRM was present, the median maximum height under the fovea, within the central 1 mm(2) including the fovea and anywhere within the scan, was 86 μm, 120 μm, and 122 μm, respectively. Visual acuity was decreased with greater SHRM height and width (P0.05).In eyes with neovascular age-related macular degeneration (AMD), SHRM is common and often persists after anti-vascular endothelial growth factor treatment. At 2 years, eyes with scar were more likely to have SHRM than other eyes. Greater SHRM dimensions were associated with worse VA. In eyes with neovascular AMD, SHRM is an important morphologic biomarker.

The paper will describe through case history evidence of high and ultra-high capacity drilled shaft foundations how an integrated approach to site characterisation and site specific geotechnical design method calibration through full scale instrumented load tests will deliver significantly increased reliability and reduced cost of deep foundations for large capital infrastructure projects. Recent advances in ultrahigh capacity load testing, in excess of 300 MN on a single shaft, when combined with comprehensive in situ strain and deflection monitoring, are allowing a new generation of large diameter foundations to be designed with confidence resulting in project benefits in terms of reduced construction times and cost. A case history from the US will be described to illustrate the key theme of the paper. The paper will also describe recent advances in the interpretation of strain gauge data obtained from underground concrete structures reviewing recently developed techniques for increasing confidence in the knowledge of section properties for the determination of load from such data. Improvements in the measurements of deflections particularly with respect to the provision of a stable reference datum will be examined. The paper will have direct application to all geotechnical engineers designing deep foundations helping to set the effective use of geomonitoring in the context of their primary responsibilities to manage ground risk into the twin desired project outcomes of increased certainty of outcome and value for money.

Purpose: To measure the CD8+T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule.Patients and Methods: Thirty HLA-A2–positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209–2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund’s adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry.Results: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+T cells specific for the g209–2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P < .0001). Eight patients (28%) exhibited peptide-specific CD8+T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b–treated patients also had significant increases in tetramer-binding cells (P < .0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P = .59).Conclusion: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results.

Objective: To study complications of vitrectomy surgery for full-thickness macular holes. Design: A multicentered, randomized, controlled clinical trial. Participants: Community and university-based ophthalmology clinics. Intervention: Standardized macular hole surgery versus observation. Main Outcome Measures: Assessment of anatomic and visual outcomes and determination of postoperative complications at 12 months after randomization. Results: Posterior segment complications were noted in 39 eyes (41%). The incidences of retinal pigment epithelium (RPE) alteration and retinal detachment (RD) were 33% and 11 %, respectively. One RD due to a giant retinal tear resulted in a visual acuity of light perception. Other complications included a reopening of the macular hole in 2 eyes (2%), cystoid macular edema in 1 eye (1%), a choroidal neovascular membrane in 1 eye (1%), and endophthalmitis in 1 eye (1%). Eyes with complications had significantly worse visual acuity outcomes as determined by the Early Treatment Diabetic Retinopathy Study, Word Reading, and Potential Acuity Meter charts ( P P = 0.07). Before surgery, the stage of the hole was related to postoperative RPE changes ( P P = 0.0002). Intraoperative trauma was related to the occurrence of these complications ( P P = 0.02 for RDs). Epiretinal membrane removal was related to RPE changes ( P = 0.02) but not RDs. Conclusions: The RPE alterations and RDs are common after macular hole surgery and result in significantly reduced postoperative visual acuity. The RPE changes may be related to surgical trauma or light toxicity. Further efforts to reduce complications associated with macular hole surgery are indicated.

An unknown aberrant flow in the right atrium observed on doppler with transesophageal echocardiogram (TEE) in a patient with prior coronary bypass. TEE revealed normal size left ventricle with severely dilated left atrium. There was moderate aortic regurgitation and moderate aortic stenosis noted. Patient was incidentally found to have an abnormal vascular communication noted to the right atrium. To further evaluate this finding, the patient underwent cardiac magnetic resonance angiography which revealed that the tubular structure noted on TEE was actually a graft that was abutting onto the coronary sinus, and the flow anomaly was really the graft coming up and running adjacent to the coronary sinus.

Background. Chemotherapy is most effective when applied during the biologically active stage of tumor cells. According to the authors' previous tumor marker kinetic study, methotrexate plus 5-fluorouracil (MF) was found to yield either a cytolytic effect in an MF-sensitive tumor cell population or a cytostatic effect in an MF-resistant population. In the latter, the suppressive effect was transient and the biologic activity resumed in one week after MF administration. Methods. Based on this marker kinetic study, an alternating chemotherapy program was designed to study its antitumor and side effects. Methotrexate (M) (200 mg/ m 2 ) and 5-fluorouracil (F) (500 mg/m 2 ) were administered intravenously on day 1 followed 24 hours later by leucovorin (L) (10 mg/m 2 orally every 6 hours for 6 doses). Cyclophosphamide (C) 300 (mg/m 2 ), doxorubicin (A) (50 mg/ m 2 ), and vincristine (V) (1 mg/m 2 ) were given on day 8. The MFL/CAV was given every 4 weeks. Results. Forty-nine patients with metastatic breast cancer were enrolled; 41 were eligible. There were 5 complete and 23 partial remissions, producing a total response rate of 68%. In 15 patients with liver metastases, the response rate was 73% and the median survival 13.7 months, results superior to those previously reported for this subgroup of patients. Side effects were manageable. Conclusions. This regimen, which can be given safely in an outpatient setting, yielded encouraging response and survival rates in patients with visceral-dominant disease with poor prognoses

Lowering total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels is widely recommended for the prevention of coronary heart disease (CHD) and for the management of patients with existing CHD. In most patients, dietary modification and drug therapy are often sufficient to lower LDL-C levels to within acceptable ranges as recommended by the National Cholesterol Education Program Guidelines. However, for some patients, particularly those with familial hypercholesterolemia (FH), additional therapy may be required to achieve desired cholesterol levels. In those patients for whom diet and maximum drug therapy are either ineffective or not tolerated, LDL-apheresis has been shown to be a safe and effective procedure. The Liposorber® LA-15 system is an LDL-apheresis system that selectively removes apolipoprotein B-containing lipoproteins, including LDL-C, very-low-density lipoprotein, and lipoprotein(a). In addition to its role in treating patients with FH, preliminary data also suggest that LDL-apheresis may be beneficial in the prevention of restenosis after percutaneous transluminal coronary angioplasty, the treatment of focal glomerular sclerosis, and the management of arteriosclerosis obliterans. The present paper discusses the main components of the Liposorber LA-15 system, the principles that underlie LDL-apheresis, and the clinical conditions in which the system has been used effectively.

Reynolds-number criteria are developed for acceptable variations in Space Shuttle Orbiter entry trajectories for use in computational aeroheating analyses. The criteria determine if an existing computational fluid dynamics solution for a particular trajectory can be extrapolated to a different trajectory. The criteria development begins by estimating uncertainties for seventeen types of computational aeroheating data, such as boundary layer thickness, at exact trajectory conditions. For each type of datum, the allowable uncertainty contribution due to trajectory variation is set to be half of the value of the estimated exact-trajectory uncertainty. Then, for the twelve highest-priority datum types, Reynolds-number relations between trajectory variation and output uncertainty are determined. From these relations the criteria are established for the maximum allowable trajectory variations. The most restrictive criterion allows a 25% variation in Reynolds number at constant Mach number between trajectories.

Pressure loads on a protruding gap filler during an Orbiter reentry are investigated to evaluate the likelihood of extraction due to pressure loads, and to ascertain how much bending will be induced by re-entry pressure loads. Oblique shock wave theory is utilized to develop a representation of the pressure loads induced on a gap filler for the ISSHVFW trajectory, representative of a heavy weight ISS return. A free body diagram is utilized to react the forces induced by the pressure forces. Preliminary results developed using these methods demonstrate that pressure loads, alone, are not likely causes of gap filler extraction during reentry. Assessment of the amount a gap filler will bend over is presented. Implications of gap filler bending during re-entry include possible mitigation of early boundary layer transition concerns, uncertainty in ground based measurement of protruding gap fillers from historical Orbiter flight history, and uncertainty in the use of Orbiter gap fillers for boundary layer prediction calibration. Authors will be added to the author list as appropriate.

To compare baseline characteristics, treatment frequency, visual acuity (VA), and morphologic outcomes of eyes with50% of the lesion composed of blood (B50 group) versus all other eyes (Other group) enrolled in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT).Prospective cohort study within a multicenter randomized clinical trial.CATT patients with neovascular age-related macular degeneration (AMD).Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different dosing regimens over a 2-year period. Reading center graders evaluated baseline and follow-up morphology in color fundus photographs, fluorescein angiography (FA), and optical coherence tomography (OCT). Masked examiners tested VA.Morphologic features and VA at 1 and 2 years.The B50 group consisted of 84 of 1185 (7.1%) patients enrolled in CATT. Baseline lesion characteristics differed between groups. In the B50 group, choroidal neovascularization size was smaller (0.73 vs 1.83 disc areas [DA]; P0.001), total lesion size was greater (4.55 vs 2.31 DA; P0.001), total retinal thickness was greater (524 vs 455 μm; P = 0.02), and mean VA was worse (56.0 vs 60.9 letters; P = 0.002). Increases in mean VA were similar in the B50 and Other groups at 1 year (+9.3 vs +7.2 letters; P = 0.22) and at 2 years (9.0 vs 6.1 letters; P = 0.17). Eyes treated PRN received a similar number of injections in the 2 groups (12.2 vs 13.4; P = 0.27). Mean lesion size in the B50 group decreased by 1.2 DA at both 1 and 2 years (primarily owing to resolution of hemorrhage) and increased in the Other group by 0.33 DA at 1 year and 0.91 DA at 2 years (P 0.001). Leakage on FA and fluid on OCT were similar between groups at 1 and 2 years.In CATT, the B50 group had a visual prognosis similar to the Other group. Lesion size decreased markedly through 2 years. Eyes like those enrolled in CATT with neovascular AMD lesions composed of50% blood can be managed similarly to those with less or no blood.

Background Centers have expanded indications for robotic mitral valve repairs to include complex pathologic features. We studied our results after robotic mitral valve repair for anterior leaflet or bileaflet prolapse. Methods Data were collected contemporaneously on 289 patients operated on from May 2000 to September 2006. Every patient underwent preoperative transesophageal echocardiography. Follow-up consisted of serial echocardiograms, clinic visits, and phone conversations with patients and their physicians. Results A total of 66 patients (anterior leaflet, n=14; and bileaflet, n=52) were identified. Mean age was 52.6 ± 7.1 years, and 57 (86%) patients had New York Heart Association functional class II or III symptoms. Cardiopulmonary bypass and cross-clamp times were 171 ± 52 and 132 ± 39 minutes, respectively. The 30-day and late mortality rates were 3% (n = 2) for each time point. There were no device-related or perfusion-related complications or sternotomy conversions. Complications included 2 strokes (3%), 2 bleeding reexplorations (3%), and 10 pleural effusions requiring intervention (15%). The length of hospital stay for surviving patients was 5 ± 3 days, and time to extubation averaged 9.5 ± 13 hours. A total of 6 (9%) patients required valve reoperation. Mean follow-up was 795 ± 495 days, and echocardiographic mitral regurgitation (n = 60) was none or trace (n = 35, 58.3%), mild (n = 19, 31.6%), moderate (n = 2, 3.3%), and severe (n = 4, 6.7%). Conclusions Robotic mitral valve repair for anterior leaflet and bileaflet prolapse is feasible and safe. Outcomes and degree of late mitral regurgitation are similar to series using conventional techniques. Long-term follow-up is required to formally address the efficacy of robotic repair techniques.

The Columbia accident on February 1, 2003 began an unprecedented level of effort within the hypersonic aerothermodynamic community to support the Space Shuttle Program. During the approximately six month time frame of the primary Columbia Accident Investigation Board activity, many technical disciplines were involved in a concerted effort to reconstruct the last moments of the Columbia and her crew, and understand the critical events that led to that loss. Significant contributions to the CAIB activity were made by the hypersonic aerothermodynamic community(REF CAIB) in understanding the re-entry environments that led to the propagation of an ascent foam induced wing leading edge damage to a subsequent breech of the wing spar of Columbia, and the subsequent breakup of the vehicle. A core of the NASA hypersonic aerothermodynamics team that was involved in the CAIB investigation has been combined with the United Space Alliance and Boeing Orbiter engineering team in order to position the Space Shuttle Program with a process to perform in-flight Thermal Protection System damage assessments. This damage assessment process is now part of the baselined plan for Shuttle support, and is a direct out-growth of the Columbia accident and NASAs response. Multiple re-entry aeroheating tools are involved in this damage assessment process, many of which have been developed during the Return To Flight activity. In addition, because these aeroheating tools are part of an overall damage assessment process that also involves the thermal and stress analyses community, in addition to a much broader mission support team, an integrated process for performing the damage assessment activities has been developed by the Space Shuttle Program and the Orbiter engineering community. Several subsets of activity in the Orbiter aeroheating communities support to the Return To Flight effort have been described in previous publications (CFD?, Cavity Heating? Any BLT? Grid Generation?). This work will provide a description of the integrated process utilized to perform Orbiter tile damage assessment, and in particular will seek to provide a description of the integrated aeroheating tools utilized to perform these assessments. Individual aeroheating tools will be described which provide the nominal re-entry heating environment characterization for the Orbiter, the heating environments for tile damage, heating effects due to exposed Thermal Protection System substrates, the application of Computational Fluid Dynamics for the description of tile cavity heating, and boundary layer transition prediction. This paper is meant to provide an overall view of the integrated aeroheating assessment process for tile damage assessment as one of a sequence of papers on the development of the boundary layer transition prediction capability in support of Space Shuttle Return To Flight efforts.

Imaging the synchrotron source profile onto the entrance slit of a monochromator provides a stable and reproducible energy calibration which is independent of the absolute position and drift of the electron beam. Potential electron-beam motions occurring during a fill result in a loss of flux through the beamline. We have implemented two independent beam position monitors which can be used as sensors to steer the vertical entrance mirror in order to maintain a maximum flux through a spherical grating varied line-spacing monochromator beamline. The system consists of a slotted plate photodiode which intercepts 2 mrad of synchrotron radiation next to the entrance mirror and a detector utilizing the photocurrents generated at the jaws of the entrance-slit assembly. Both monitors have a wide linear response range with a vertical position resolution of μ m. The combination of two independent beam position monitors allows an easy check on the mechanical and thermal stability of the entrance optical system as well as on the reproducibility and long-term fluctuations of the electron-beam source during user shifts. We will discuss the performance of the optical beam-position-monitor system and its implementation as a sensor in a closed-loop feedback system to maintain maximum flux through the beamline.

Home health agencies constantly seek ways to improve patient care as part of their performance improvement program. This includes revising and updating agency policies and procedures. Changing care processes, such as administering intravenous medications, requires input from pharmacy and nursing staff as well as administration. The authors describe how one agency used this process while adopting the i.v. push method of administering certain antibiotics to home care patients.

background Because the majority of breast masses in males are benign and need not be excised if asymptomatic, we studied the combination of physical examination (PE) and fine needle aspiration (FNA), with or without mammography, as a diagnostic alternative to routine surgical biopsy of these lesions. methods A diagnostic test study and cost-effectiveness analysis was performed in three participating multidisciplinary breast clinics, involving a consecutive sample of 51 males with unilateral breast masses. Each lesion was tested with both PE and FNA; 13 were also studied with mammography, and each test was scored as benign or suspicious. Lesions for which all tests were benign were followed up clinically (mean 19 months). Lesions for which any test was suspicious were excised. results All tests were benign in 38 cases. No cancers developed at the index sites during follow-up of these lesions, including 8 excisional biopsies done for symptoms (negative predictive value and specificity 100%). Open biopsy confirmed malignancy in all 6 cases for which all tests were suspicious (positive predictive value and sensitivity 100%). In all 7 cases where the tests were not in agreement, open biopsy was benign. In these cases FNA (2 false positives) proved more accurate than PE (5 false positives). Mammography added no additional diagnostic information to the combination of PE and FNA. Compared with routine open biopsy, the combination of PE and FNA avoided surgical biopsy in 30 of the 51 lesions, and was associated with an average decrease in charges of up to $510 per case. conclusions The combination of PE and FNA for the evaluation of breast masses in males is diagnostically accurate and results in a reduction in patient charges compared with routine open biopsy.

Tumor-associated antigens have been identified on a variety of human neoplasms. Each of these antigens may be able to serve as a target for an immune response, the result of which would be elimination of the tumor cell. An essential component of this immune response is the presentation of antigen to potential effector cells. This can be accomplished via host professional antigen-presenting cells (APC), such as dendritic cells, or via the tumor itself. The lack of information about tumor-associated antigens and their apparent lack of immunogenicity in vivo complicate the induction of immune responses against breast cancers. We have undertaken the effort to increase the antigen-presenting cell (APC) function of a breast cancer line that expresses at least one tumor-associated antigen, Her2/neu. The her2/neu gene encodes a 185-kd transmembrane tyrosine kinase receptor that shares homology with the epidermal growth factor receptor. Previous studies indicated that Her2/neu was overexpressed by 20–30% of breast and ovarian tumors and its overexpression has been associated with a poor prognosis [1, 2], Studies have also suggested that Her2/neu can also function as a tumor-associated antigen. Cytotoxic T lymphocytes (CTL) isolated from ovarian tumors specifically recognizes Her2/neu-derived peptides and can kill Her2/neu+ tumors but not Her2/neu- tumors [3, 4]. Antibodies to Her2/neu can be found in the sera of patients with metastatic breast cancer but not in control subjects [5,6]. In addition, rats immunized with Her2/neu peptides developed CD4+ T cell immune responses as well as antibody responses [7] and mice immunized with Her2/neu peptides developed Her2/neu-specific tumor immunity [8].

A plane grating monochromator (PGM) has recently been completed and installed on an undulator port at the Synchrotron Radiation Center (SRC). The beamline is designed to be a high resolution, high throughput beamline with an energy range of 8 to 245 eV. Initial results show the undulator is performing very well and agreeing closely with theoretical predictions. The undulator and monochromator can be scanned together throughout the energy range using software on the beamline computer. Undulator scans are routinely performed during the morning shift and the small effects this induces on the storage ring are being further minimized. Monochromator scanning is achieved by rotating the plane mirror and rotating and translating the grating. An advanced control system maintains sub-arcsecond resolution for the rotations. Flux and resolution tests have shown that the grating performs poorly. A new laminar profile grating will be installed soon.

Recently, it was recognized that an immune response develops along one of two major pathways. One leads to a destructive immune response (type 1), while the alternative leads to a nondestructive immune response (type 2). Our studies in animal models suggest that therapeutic vaccines induce a tumor-specific type 1 immune response while ineffective vaccines induce a type 2 response. These results have led us to examine the immune response in sentinel lymph nodes draining tumor vaccines of patients entered onto clinical trials for melanoma, breast and renal cell cancer.

This paper evaluates the long range economic benefits of first generation and advanced fuel cells in the future generation capacity plans of a representative electric utility system. The economic benefits of fuel cells' unique characteristics are separately quantified and the relationships between market penetration, fuel price, and capital cost are analyzed. Reliability, production cost, and optimum generation mix methods commonly used for generation planning in utilities were used for this study.

The case histories of three women with verrucous carcinoma of the vagina are presented. Verrucous carcinoma, in the female genital tract as elsewhere, is a relentlessly growing, destructive, but generally nonmetastasizing neoplasm of stratified squamous epithelium with a characteristic gross and microscopic appearance. It should be recognized and segregated from the usual type of squamous carcinoma so that appropriate therapy can be administered. Surgical excision is the treatment of choice. Radiotherapy is usually contraindicated. Two of the patients described here were treated by surgery alone with good results. The other received radiation only and died within a year with persistent disease.

In discussing Mr. Schwartz’s paper, I shoud ld like to keep in mind Mr. Nef’s remarks about the creative role that commerce has played in culture.1 I think we should realize it is not only the visual arts, or music, or literature that can contribute to international understanding, but also business itself. Business shares many of the aspects of art. Particularly today, as we all know, as business institutions become more complex, they need to be organized. Organizing matters of business resembles organizing the materials of a work of art. We business men are faced with the same old struggle as the artist, between form and content.

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