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Background Neuronal cytoplasmic inclusions containing TAR DNA-binding protein 43 (TDP-43) are a neuropathological feature of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s Disease (AD). Emerging evidence also indicates that systemic inflammation may be a contributor to the pathology progression of these neurodegenerative diseases. Methods To investigate the role of systemic inflammation in the progression of neuronal TDP-43 pathology, AAV9 particles driven by the UCHL1 promoter were delivered to the frontal cortex of wild-type aged mice via intracranial injections to overexpress TDP-43 or green fluorescent protein (GFP) in corticospinal motor neurons. Animals were then subjected to a low-dose (500 μg/kg) intraperitoneal E. coli lipopolysaccharide (LPS) administration challenge for 2 weeks to mimic a chronically altered low-grade systemic inflammatory state. Mice were then subjected to neurobehavioral studies, followed by biochemical and immunohistochemical analyses of the brain tissue. Results In the present study, we report that elevated neuronal TDP-43 levels induced microglial and astrocytic activation in the cortex of injected mice followed by increased RANTES signaling. Moreover, overexpression of TDP-43 exerted abundant mouse immunoglobulin G (IgG), CD3, and CD4+ T cell infiltration as well as endothelial and pericyte activation suggesting increased blood-brain barrier permeability. The BBB permeability in TDP-43 overexpressing brains yielded the frontal cortex vulnerable to the systemic inflammatory response following LPS treatment, leading to marked neutrophil infiltration, neuronal loss, reduced synaptosome-associated protein 25 (SNAP-25) levels, and behavioral impairments in the radial arm water maze (RAWM) task. Conclusions These results reveal a novel role for TDP-43 in BBB permeability and leukocyte recruitment, indicating complex intermolecular interactions between an altered systemic inflammatory state and pathologically prone TDP-43 protein to promote disease progression.

TAR DNA-binding protein 43 (TDP-43) is a nuclear RNA/DNA binding protein involved in mRNA metabolism. Aberrant mislocalization to the cytoplasm and formation of phosphorylated/aggregated TDP-43 inclusions remains the hallmark pathology in a spectrum of neurodegenerative diseases, including frontotemporal disorders and Alzheimer's disease. Eukaryotic Translation Initiation Factor 5A undergoes a unique post-translation modification of lysine to hypusine (K50), which determines eIF5A binding partners. We used a sodium arsenite-induced cellular stress model to investigate the role of hypusinated eIF5A (eIF5AHypK50) in governing TDP-43 cytoplasmic mislocalization and accumulation in stress granule. Our proteomics and functional data provide evidence that eIF5A interacts with TDP-43 in a hypusine-dependent manner. Additionally, we showed that following stress TDP-43 interactions with eIF5AHypK50 were induced both in the cytoplasm and stress granules. Pharmacological reduction of hypusination or mutations of lysine residues within the hypusine loop decreased phosphorylated and insoluble TDP-43 levels. The proteomic and biochemical analysis also identified nuclear pore complex importins KPNA1/2, KPNB1, and RanGTP as interacting partners of eIF5AHypK50. These findings are the first to provide a novel pathway and potential therapeutic targets that require further investigation in models of TDP-43 proteinopathies.

Background Safety and efficacy of gemcitabine plus docetaxel (GD) and capecitabine plus docetaxel (CD) were compared in patients with metastatic breast cancer, where the alternate crossover monotherapy (GD→C or CD→G) was predetermined. Patients and methods Patients were randomly assigned to 3-week cycles of either gemcitabine 1000 mg/m2 on days 1 and 8 plus docetaxel 75 mg/m2 on day 1 or capecitabine 1000 mg/m2 twice daily on days 1–14 plus docetaxel 75 mg/m2 day 1. Upon progression, patients received crossover monotherapy. Primary end point was time to progression (TtP). Secondary end points evaluated overall response rate (ORR), overall survival (OS), and adverse events (AEs). Results Despite over-accrual of 475 patients, the trial matured with only 324 of 385 planned TtP events due to patient discontinuations. Human epidermal growth factor receptor 2 status was not captured in this study. More CD patients (28%) discontinued due to AEs than GD patients (18.0%, P = 0.009). TtP [hazard ratio (HR) = 1.101, 95% confidence interval (CI) 0.885–1.370, P = 0.387] and OS (HR = 1.031, 95% CI 0.830–1.280, P = 0.785) were not significantly different comparing GD and CD. ORR was not statistically different (P = 0.239) comparing GD (72 of 207, 34.8%) and CD (78 of 191, 40.8%). TtP, OS, and ORR were not significantly different comparing crossover groups. GD caused greater fatigue, hepatotoxicity, neutropenia, and thrombocytopenia but not febrile neutropenia; CD caused more hand–foot syndrome, gastrointestinal toxicity, and mucositis. Conclusions GD and CD produced similar efficacy and toxicity profiles consistent with prior clinical experience.

The aim of this study was to evaluate relative change over 17 years in clinical oral health outcomes inside and outside capital city areas of Australia.Using data from the National Oral Health Survey of Australia 1987-88 and the National Survey of Adult Oral Health 2004-06, relative trends in clinical oral health outcomes inside and outside capital city areas were measured by age and gender standardized changes in the percentage of edentate people and dentate adults with less than 21 teeth, in mean numbers of decayed, missing and filled teeth, and mean DMFT index.There were similar reductions inside and outside capital city areas in the percentage of edentate people (capital city 63.7%, outside capital city 60.7%) and dentate people with less than 21 teeth (52.5%, 50.1%), in the mean number of missing teeth (34.3%, 34.5%), filled teeth (0.0%, increase of 5.5%), and mean DMFT index (21.2%, 19.2%). The reduction in mean number of decayed teeth was greater in capital city areas (78.0%) than outside capital city areas (50.0%).Trends in four of the five clinical oral health outcomes demonstrated improvements in oral health that were of a similar magnitude inside and outside capital city areas of Australia.

An integrated flight propulsion control mode called Inlet Integration has been developed and will be flight demonstrated on an F-15 test aircraft in the Highly Integrated Digital Electronic Control (HIDEC) program. The HIDEC program is conducted by the NASA Ames/Dryden Flight Research Center. The development of the Inlet Integration mode is described in this paper, including the Inlet Integration concept, the control law, its implementation on the test bed aircraft, and the predicted performance benefits. The Inlet Integration system will increase excess thrust (thrustdrag) during supersonic operation. This improvement in aircraft performance is accomplished by utilizing a calculation of engine corrected airflow from the Digital Electronic Engine Control (DEEC) to improve the scheduling of the inlet ramp positions in real time. The improvement in scheduled ramp positions will result in increased inlet performance, hence aircraft performance, while maintaining stable inlet operation. Analyses have shown the Inlet Integration system can increase excess thrust by as much as 13 percent at Mach 2.3, 40,000 ft. This thrust increase will result in increased supersonic acceleration. Inlet integration has the additional feature of improving aircraft supportability by eliminating the need for replacing inlet controllers when higher thrust derivative engines are installed in the F-15.

An Enzyme Linked Immunosorbent Assay (ELISA) based on a monoclonal antibody, 3E1.2, was used to measure circulating Mammary Serum Antigen (MSA) in a study of 123 advanced breast cancer patients. Fifty two patients were monitored serially to investigate whether measurements of circulating MSA levels were of value in the management of advanced breast cancer patients on palliative therapy. Analysis of variance showed that circulating MSA levels at first presentation correlated with disease status both at initial presentation (p = 0.01) and also 4 months later (p = 0.003). At first presentation, the circulating MSA level also significantly correlated with the number of metastatic sites (p = 0.04), but this did not hold at 4 months. The circulating MSA levels did not at any time correlate with the type of treatment given nor age of the patient. We conclude that MSA might ultimately be useful in the management of advanced breast cancer patients as a prognostic marker for the course of the disease and for monitoring patient response to palliative hormonal therapy and chemotherapy.

Neural tube defects (NTD) are common findings in the 13q deletion syndrome, but the relationship between the 13q- syndrome and NTDs is poorly understood. We present a child with a 13q deletion and lumbosacral myelomeningocele. This was a boy with microcephaly, telecanthus, minor facial anomalies, and ambiguous genitalia. Cytogenetic and fluorescence in situ hybridization analysis showed a de novo 46,XY,del(13)(q33.2--qter) with no visible translocation. By using microsatellite markers, the deletion breakpoint was mapped to a 350-kb region between D13S274 and D13S1311 and was paternal in origin. An analysis of 13q deletions with NTDs, including the present case, suggests that a deletion in 13q33-34 is sufficient to cause an NTD. The deletions associated with NTDs are distal to and nonoverlapping with the previously defined critical region in 13q32 for the major malformation syndrome [Brown et al., 1999: Am J Hum Genet 57: 859-866]. Our analysis also suggests that one or more genes in 13q33-34 produces NTDs by haploinsufficiency.

To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy.Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated.One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated.Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.

A 7-year-old German Shepherd dog was referred for evaluation of severe nonregenerative anemia (PCV, 10%; reticulocyte fraction, 0.2%). Cytologic examination of a bone marrow aspirate indicated erythroid predominance and dyserythropoiesis, and a diagnosis of myelodysplastic syndrome (MDS) with erythroid predominance was made. The dog was given a single blood transfusion and was treated with prednisone and recombinant human erythropoietin (EPO). Eight weeks later, anemia had resolved. The dog remained clinically normal 30 months after treatment, with a PCV of 45%. Results suggest that EPO may be useful in the treatment of dogs with MDS with erythroid predominance or erythroleukemia. Additional studies are required to confirm the benefit of EPO to manage MDS-associated anemia in dogs.

Normal operation of the University of Washington’s ram accelerator involves the use of a perforated tube to vent gases from the light gas gun into an evacuated tank before the projectile enters the ram accelerator tubes. Because there is residual air in the launch tube and gases from the gun that blow by the obturator, a shock is generated and reflects between the moving projectile/obturator and the entrance diaphragm. The vent tube perforations relieve the resulting pressure rise, such that it does not become significant until after the projectile has passed the vent section. Experiments were performed to determine the feasibility of eliminating the venting process. It was found, as expected, that the pressure increase from the shock reflections was much higher for ventless operation than for vented operation and in some cases prevented initiation of the ram acceleration process. The effect of increasing residual launch tube pressure on the starting process of the ram accelerator was also investigated. It was found that for initial gun launch tube pressures of 21 kPa or less, successful starting of the ram accelerator was possible at a fill pressure of 5.0 MPa.

To assess our patients' knowledge of glaucoma and to measure the effect of a brief education program on their understanding of glaucoma.Patients attending glaucoma clinics at a university and a Veterans' Affairs hospital were randomized into two groups: "exposed" and "unexposed" to a simple education program of a video and brochures. Glaucoma knowledge was assessed twice by an oral questionnaire, at 2 weeks and 6 months after randomization plus or minus education.Younger patients and those with more years of formal schooling knew more about glaucoma. Two weeks after the education program, the exposed group performed significantly better than did the unexposed group. Analysis of the results showed benefit from both brochures and video. This effect of education was not seen at retesting 6 months later.Older patients and those with less formal education know less about glaucoma. A brief, simple education program can significantly improve levels of knowledge about glaucoma, even in a relatively well-informed population. However, patient education must be repeated to maintain a useful effect.

This study aimed to estimate the prevalence of dental anxiety and examine its associations among a representative sample of Australians aged 18 and over. A random sub-sample of participants in a national dental telephone interview survey completed a follow-up postal questionnaire (response rate 85.2 per cent) which included Corah's Dental Anxiety Scale (DAS). The prevalence of dental anxiety (defined by a DAS score of 13 or more) in the sample was 14.9 per cent, with overall severity represented by the mean score of 9.04 (sd, 3.45). The prevalence and severity of dental anxiety were greater among women than men, and in the 35-44 age group. High-anxiety individuals reported more deferring of dental care, and more frequently reported an episodic dental visiting pattern. Although there were no differences in dental anxiety by self-reported dental status, individuals who reported impact from their oral conditions had higher dental anxiety. These associations with social impacts and deferment of care indicate that dental anxiety may be an important dental public health problem in Australia.

Data on the mobility of dental patients are scarce. The aim of this study was to investigate movement among dentists of a representative sample of the Australian public. A postal questionnaire was completed by a random subsample of 1,010 participants in the 1995 National Dental Telephone Interview Survey. The response rate was 85.2 per cent. Approximately one-third of the 885 dentate respondents reported attending a different dentist to that attended two years previously; this was substantially higher (over half) among those whose last visit was not in the private sector. Most (81.8 per cent) of those who had changed dentist had done so for reasons which were beyond the immediate control of the dental profession, but 15.2 per cent had changed because they were unhappy with the care provided by the previous dentist, and 3.0 per cent had changed because the previous dentist was too expensive. Perceived freedom to change dentist was greater among individuals who used the private sector, spoke English in the home, and who were not holders of health cards. The findings of this study indicate that the Australian public manifests a moderate degree of movement among dental providers, and that such movement is greater among users of public-sector dental services.

Through detailed strategies and sophisticated analysis, the Humphrey automated visual field analyzer attempts to indicate if visual field loss is artefactual. Can these measures be outwitted by malingerers?The author investigated the ease with which motivated individuals (such as are malingerers) could simulate visual field defects consistent with organic neurologic disease on the Humphrey visual field analyzer. Visual field test results were analyzed for characteristic features and compared with visual field tests from patients with documented pituitary tumors.Volunteers, given only broad suggestions as to the visual field they were to simulate, produced consistent, convincing, neurologic-type field defects, according to textbook descriptions of such fields. These plotted fields were only distinguishable from genuine pituitary tumor Humphrey field tests, in that they more convincingly fitted the classic descriptions of visual fields seen with chiasmal compression.The author concludes that single routine Humphrey visual field tests do not show malingerers. An incidental finding of this study was the extent to which Humphrey visual fields from patients with genuine neurologic disease contain field defects with characteristics different from those of the (kinetic) visual field test appearances described in the textbooks.

A presumptive clinical diagnosis of cytomegalovirus (CMV) retinitis was made in two patients presenting with atypical ophthalmologic findings. The diagnosis was confirmed by finding specific CMV DNA sequences in sampled vitreous fluid using a polymerase chain reaction (PCR) based assay. Neither of these patients yielded CMV on culture or PCR of peripheral blood leucocytes, nor was CMV present in tears or urine of either patient. Serum antibody titres were stable and did not help in establishing the diagnosis. This report suggests that CMV retinitis can occur in the absence of disseminated CMV disease.

The Dual Engine Performance Seeking Control (PSC) flight/propulsion optimization program has been developed and will be flown during the second quarter of 1993. Previously, only single engine optimization was possible due to the limited capability of the on-board computer. The implementation of Dual Engine PSC has been made possible with the addition of a new state-of-the-art, higher throughput computer. As a result, the single engine PSC performance improvements already flown will be demonstrated on both engines, simultaneously. Dual Engine PSC will make it possible to directly compare aircraft performance with and without the improvements generated by PSC. With the additional thrust achieved with PSC, significant improvements in acceleration times and time to climb will be possible. PSC is also able to reduce deceleration time from supersonic speeds. This paper traces the history of the PSC program, describes the basic components of PSC, discusses the development and implementation of Dual Engine PSC including additions to the code, and presents predictions of the impact of Dual Engine PSC on aircraft performance.

1000 Background: GD and CD are efficacious in patients (pts) with MBC. This study compared safety and efficacy of GD and CD induction regimens, where the alternate, single-agent, crossover therapy (GD to C or CD to G) was predetermined. Primary endpoint was time to progressive disease (TTP). Secondary endpoints included toxicities, overall response (ORR), and overall survival (OS). Methods: This multicenter, open-label, phase III study enrolled MBC pts with possible prior anthracycline therapy, adjuvant or neoadjuvant taxane therapy, but no taxane therapy for MBC ≤6 months prior to entry. Enrollment of 442 pts (221 per arm) was planned with 385 progressions required to achieve 80% power for a 2-month observed difference in median TTP between arms. Pts were randomized to: GD: G 1,000mg/m2 Days 1, 8 plus D 75 mg/m2 Day 1, q21 days; or CD: C 1,000 mg/m2 BID, Days 1–14 plus D 75 mg/m2 Day 1, q 21 days. Upon disease progression, pts were given crossover C or G at doses and schedules identical to induction. ORR was assessed by RECIST. Results: Demographics of 472 enrolled pts were balanced between arms; 57% had prior anthracycline. GD caused greater myelosuppression than CD, but without greater febrile neutropenia. Gastrointestinal toxicities, mucositis, and hand-foot syndrome were greater with CD. More pts in the CD arm (n=61, 26.2%) versus the GD arm (n=41, 17.2%) discontinued due to toxicity (p=0.023). ORR, TTP, and OS were not significantly different comparing GD and CD. However, ORR and TTP were significantly greater for the GD to C crossover monotherapy compared to CD to G. Post-hoc analysis of crossover pts showed that the TTP sum from induction through crossover was 6.1 months greater for GD to C. Conclusions: GD and CD had similar efficacy with toxicity profiles consistent with prior clinical experience. Results suggest that the GD to C crossover sequence may provide a clinical benefit over CD to G. [Table: see text] [Table: see text]

There has been much controversy about the impact of the health sector and the infant food industry on breast-feeding behavior. This study links causal factors to breast-feeding decisions, using a longitudinal survey of more than 3,000 Filipino mother-infant pairs. Most factors decreasing the likelihood that mothers will breast-feed seem to be related to family economics. Delivery in a private hospital, urban residence, high income, absence of spouse, and having worked for wages affect adversely the initiation of breast-feeding. Formula advertising and distribution of samples appear to have relatively little impact on feeding decisions.

A 56-year-old female underwent treatment with leucovorin and 5-fluorouracil for extensive metastatic moderately differentiated transitional cell carcinoma (TCC) of the renal pelvis. This resulted in a complete response for 20 + months. This combination has not been reported before in TCCs of the urinary tract and requires further exploration. (Aust NZ J Med 1991; 21: 244–245.)

An adaptive, integrated flight/propulsion control algorithm called Performance Seeking Control (PSC) has been developed to optimize total aircraft performance during steady-state engine operation. The multimode algorithm will minimize fuel consumption at cruise conditions; maximize excess thrust (thrust minus drag) during aircraft accelerations, climbs, and dashes; and extend engine life by reducing Fan Turbine Inlet Temperature (FTIT) when the extended life mode is engaged. On-board models of the inlet, engine, and nozzle are optimized to compute a set of control trims, which are then applied as increments to the nominal engine and inlet control schedules. The on-board engine model is continually updated to match the operating characteristics of the actual engine cycle through the use of a Kalman filter, which accounts for anomalous engine operation. The PSC algorithm will be flight demonstrated on an F-15 test aircraft under the direction of the NASA Ames/Dryden Flight Research Facility. This paper discusses the PSC design strategy, describes the control algorithm, and presents results from high-fidelity, nonlinear aircraft/engine simulations. Simulation results indicate that thrust increases as high as 15 percent and specific fuel consumption reductions up to 3 percent are realizable by the PSC system.

Blood from 1497 women who were either non-pregnant, pregnant at all stages of gestation, lactating after parturition, postmenopausal, or who had benign breast lumps, primary breast cancer or advanced breast cancer were tested for their peripheral blood mammary serum antigen (MSA), using the 3E1.2 monoclonal antibody (MoAb) in an inhibition enzyme linked immunosorbent assay test system. The study aimed to establish normal ranges for comparison with MSA levels in breast cancer and benign breast disease. Compared with normal premenopausal women, which included women measured 8-10 times throughout their menstrual cycle, circulating MSA levels were significantly elevated throughout pregnancy (P less than 0.0001), in postmenopausal women (P less than 0.05), in women with primary breast cancer (P less than 0.05) and women with advanced (metastatic) breast cancer (P less than 0.0001). As a group, the 30 women with benign breast disease did not demonstrate significantly different MSA level from normal. However, 3% of the group did have levels above the 'cut off' for normal (400 IU/mL). Analysis of the normal premenopausal women according to age, parity and stage of the menstrual cycle and during lactation showed that these parameters did not affect MSA levels. It is concluded that the test is potentially valuable in the detection of metastatic but not primary breast cancer, and the effects of pregnancy and postmenopausal status on the circulating MSA levels need to be considered in the interpretation of MSA measurements.

The NASA Ames-Dryden Flight Research Facility is sponsoring a flight research program designated Highly Integrated Digital Electronic Control (HIDEC), whose purpose is to develop integrated flight-propulsion control modes and evaluate their benefits in flight on the NASA F-15 test aircraft. The Adaptive Engine Control System (ADECS I) is one phase of the HIDEC program. ADECS I involves uptrimming the P&W Engine Model Derivative (EMD) PW1128 engines to operate at higher engine pressure ratios (EPR) and produce more thrust. In a follow-on phase, called ADECS II, a constant thrust mode will be developed which will significantly reduce turbine operating temperatures and improve thrust specific fuel consumption. A Performance Seeking Control mode is scheduled to be developed. This mode features an onboard model of the engine that will be updated to reflect actual engine performance, accounting for deterioration and manufacturing differences. The onboard engine model, together with inlet and nozzle models, are used to determine optimum control settings for the engine, inlet, and nozzle that will maximize thrust at power settings of intermediate and above and minimize fuel flow at cruise. The HIDEC program phases are described in this paper with particular emphasis on the ADECS I system and its expected performance benefits. The ADECS II and Performance Seeking Control concepts and the plans for implementing these modes in a flight demonstration test aircraft are also described. The potential pay-offs for these HIDEC modes as well as other integrated control modes are also discussed.

Summary.-Serumsialyl transferase (SST) wasmeasuredin49female patients withadvancedbreastcancerand60femalecontrols. Themean SSTlevel was significantly raised in patients with advanced breast cancer. There wasno correlation between specific sites, ornumbersof sites of metastatic disease and SSTlevels. The patients withadvanced breast cancerwere all treatedwithchemotherapy;in 13/21 respondersthere was a significant fall in SSTand in 2 responders a significant rise in SST.The6 patients whodied after onecourseof chemotherapyhada significantly higher meanSSTthan those surviving longer. SST appearsto lack sufficient specificity tobeof practical value as a markerof response in patients with breast cancer treated bychemotherapy, though constant measurement of changes in SST maybe of usein monitoring drug response. Raised SSTat the commencement of chemotherapymay signify poor prognosis.THE GLYCOSYL TRANSFERASES are a groupofenzymesinvolvedin glycoprotein synthesis; they catalyseadditionof specific

A series of low-volume spray treatments were conducted to study the contact and residual effect of two concentrations of the insecticide phosphamidon to fourth instar spruce budworm, Choristoneura fumiferana (Clem.), on balsam fir, Abies balsamea (L.) Mill, and red spruce, Picea rubens Sarg. Treatment of sprayed larvae on sprayed trees, unsprayed larvae on sprayed trees, and sprayed larvae on unsprayed trees, resulted in two principal conclusions: (a) Higher concentrations of phosphamidon (1% versus 0.5% active) accelerated mortality in all instances and (b) no statistical difference (P = 0.1%) was found in the final mortalities between treatments in which only the foliage was treated and where both larvae and foliage were treated with phosphamidon.

This paper contains a study of the solubility of copper and its oxides in supercritical steam which was undertaken because of difficulties experienced with copper deposition in the high-pressure turbine of the Ohio Power Company’s Philo 6 supercritical steam-generating cycle. This study shows that copper has appreciable solubility in superheated supercritical steam. The extent of solubility is apparently a function of the oxidation state of the metal, with the highest state of oxidation (CuO) showing the greatest solubility. A slightly increased solubility was effected by increasing pH values from ∼7.5 to ∼9.5 with ammonia. It is also shown that copper solubility is principally a function of pressure over the narrow temperature range tested (900–1150 F) probably because this parameter has the greatest effect on specific volume.

Twenty-seven patients with advanced ovarian cancer were treated with a total of 80 courses of cis-dichlorodiammine platinum (II) (cisplatin). The doses in three courses were less than 50 mg/m2, in 64 courses they were 50 mg/m2, and in eight courses they were 100 mg/m2. In addition, five courses of low-dose daily treatment (20 mg/m2 for five days) were administered. Twelve patients received cisplatin alone, 12 received cisplatin and cyclophosphamide (750 mg/m2), and three patients received cisplatin with other drugs. There were eight responders (33%) in the 24 evaluable patients. Renal toxicity occurred in four patients, ototoxicity in four, and leucopenia (which was life-threatening in one patient) occurred in 16 patients (white cell count less than 3.0 X 10(9)/L). There were two early drug-related deaths. The median survival of patients who responded to cisplatin treatment was longer than 30 weeks compared with nine weeks for non-responders.

An integrated flight propulsion control mode called Adaptive Engine Control System (ADECS) has been developed and flight demonstrated on an F-15 test aircraft in the Highly Integrated Digital Electronic Control (HIDEC) Program, sponsored by the NASA Ames/Dryden Flight Research Center. The ADECS system provides additional engine thrust by increasing engine pressure ratio (EPR) at intermediate and afterburning power. The amount of EPR uptrim is modulated based on a unique predictor scheme for angle-of-attack and sideslip angle thus ensuring adequate fan stall margin for the engine. These predicted angles are derived from fight control and inertial navigation information. The ADECS mode demonstrated substantial improvements in aircraft and engine performance in the flight evaluation program, even with only one engine incorporating EPR uptrim. Highlights were a 16% rate of climb increase, a 14% reduction in time to climb, and a 15% reduction in time to accelerate. Significant EPR uptrim capability was demonstrated with angles-of-attack up to 20 degrees.

Twenty-seven patients with advanced ovarian cancer were treated with a total of 80 courses of cis-dichlorodiammine platinum (II) (cisplatin). The doses in three courses were less than 50 mg/m2, in 64 courses they were 50 mg/m2, and in eight courses they were 100 mg/m2. In addition, five courses of low-dose daily treatment (20 mg/m2 for five days) were administered. Twelve patients received cisplatin alone, 12 received cisplatin and cyclophosphamide (750 mg/m2), and three patients received cisplatin with other drugs. There were eight responders (33%) in the 24 evaluable patients. Renal toxicity occurred in four patients, ototoxicity in four, and leucopenia (which was life-threatening in one patient) occurred in 16 patients (white cell count less than 3.0 X 10(9)/L). There were two early drug-related deaths. The median survival of patients who responded to cisplatin treatment was longer than 30 weeks compared with nine weeks for non-responders.

The project-management system developed for NASA's participation in the X-29A aircraft development program is characterized from a theoretical perspective, as an example of a system appropriate to advanced, highly integrated technology projects. System-control theory is applied to the analysis of classical project-management techniques and structures, which are found to be of closed-loop multivariable type; and the effects of increasing project complexity and integration are evaluated. The importance of information flow, sampling frequency, information holding, and delays is stressed. The X-29A system is developed in four stages: establishment of overall objectives and requirements, determination of information processes (block diagrams) definition of personnel functional roles and relationships, and development of a detailed work-breakdown structure. The resulting system is shown to require a greater information flow to management than conventional methods. Sample block diagrams are provided.

Out of 1300 patients referred to a medical oncology unit, there were 87 with metastatic cancer in whom a primary tumour site was not evident from the history and after physical examination and chest radiography had been carried out. An analysis of the investigations performed in these patients and their results showed that in only eight of the 87 patients did non-surgical investigations at presentation determine the primary site. In two patients it was identified by diagnostic laparotomy, and in a further 13 clinical follow-up led to recognition of the primary tumour site before death. Few investigations should be performed in patients in whom the primary site is known since they have a low yield, and in our population identifying the primary tumour did not improve the outcome or alter management. Treatable tumours should be excluded, and this may be done in most cases by simple blood tests, particularly those measuring acid phosphatase activity and other tumour markers.

Digital flight control systems are popular for their flexibility, reliability, and power; however, their use sometimes results in deficient handling qualities, including pilot-induced oscillation (PIO), which can require extensive redesign of the control system. When redesign is not immediately possible, temporary solutions, such as the PIO suppression (PIOS) filter developed for the Space Shuttle, have been proposed. To determine the effectiveness of such PIOS filters on more conventional, high-performance aircraft, three experiments were performed using the NASA F-8 digital fly-by-wire and USAF/Calspan NT-33 variable-stability aircraft. Two types of PIOS filters were evaluated, using high-gain, precision tasks (close formation, probe-and-drogue refueling, and precision touch-and-go landing) with a time delay or a first-order lag added to make the aircraft prone to PIO. Various configurations of the PIOS filter were evaluated in the flight programs, and most of the PIOS filter configurations reduced the occurrence of PIOs and improved the handling qualities of the PIO-prone aircraft. These experiments also confirmed the influence of high-gain tasks and excessive control system time delay in evoking pilot-induced oscillations.

Summary Metastases of basal cell carcinoma are very uncommon. Only 10 reported cases have been treated with cytotoxic chemotherapy, and no good responses have been documented. The case is presented of a 54-year-old male who had several basal cell carcinomas (BCCs) removed surgically and who, 12 years after his first presentation, developed respiratory symptoms related to metastatic pulmonary BCCs. These failed to respond to initial chemotherapy with methotrexate, bleomycin, and vincristine, but regressed when treated with cyclophosphamide and cis-diamine dichloroplatinum.

A modification to the CEC 21–110 mass spectrometer that permits the utilization of a stable programmable magnet power supply to allow rapid scanning with minimum reset time under either manual or computer control is described.