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Strategic level analysis of the integrated behavior of lunar transportation and lunar surface systems architecture options is performed to assess the benefit, viability, affordability, and robustness of system design choices. This analysis employs both deterministic and probabilistic modeling techniques so that the extent of potential future uncertainties associated with each option are properly characterized. The results of these analyses are summarized in a predefined set of high-level Figures of Merit (FOMs) so as to provide senior NASA Constellation Program (CxP) and Exploration Systems Mission Directorate (ESMD) management with pertinent information to better inform strategic level decision making.

NASA s Constellation Program employs a strategic analysis methodology in providing an integrated analysis capability of Lunar exploration scenarios and to support strategic decision-making regarding those scenarios. The strategic analysis methodology integrates the assessment of the major contributors to strategic objective satisfaction performance, affordability, and risk and captures the linkages and feedbacks between all three components. Strategic analysis supports strategic decision making by senior management through comparable analysis of alternative strategies, provision of a consistent set of high level value metrics, and the enabling of cost-benefit analysis. The tools developed to implement the strategic analysis methodology are not element design and sizing tools. Rather, these models evaluate strategic performance using predefined elements, imported into a library from expert-driven design/sizing tools or expert analysis. Specific components of the strategic analysis tool set include scenario definition, requirements generation, mission manifesting, scenario lifecycle costing, crew time analysis, objective satisfaction benefit, risk analysis, and probabilistic evaluation. Results from all components of strategic analysis are evaluated a set of pre-defined figures of merit (FOMs). These FOMs capture the high-level strategic characteristics of all scenarios and facilitate direct comparison of options. The strategic analysis methodology that is described in this paper has previously been applied to the Space Shuttle and International Space Station Programs and is now being used to support the development of the baseline Constellation Program lunar architecture. This paper will present an overview of the strategic analysis methodology and will present sample results from the application of the strategic analysis methodology to the Constellation Program lunar architecture.

NASA's future human lunar campaign faces significant performance, cost, and risk challenges. These include: providing access to large portions of the lunar surface for expanded science and exploration opportunities within the performance constraints of the integrated transportation system; minimizing the annual cost of the lunar campaign; minimizing operational risk, including probability of loss of mission (PLOM) and probability of loss of crew (PLOC). Innovative lunar operations scenarios that address these challenges are potentially feasible based on the concept of dual, sequential missions utilizing a common crew and a single Ares I/crew exploration vehicle (CEV). Dual mission scenarios possible within the scope of baseline technology planning include outpost-based sortie missions, dual sortie missions, and enhanced outpost deployment. Additional mission scenarios are potentially possible with the development of advanced capabilities. These include expanded lunar abort modes and lander reusability options. Top-level benefits of these dual mission scenarios may be estimated by comparison with the Constellation Program reference two-mission-per-year lunar campaign. The primary performance benefit is substantially improved surface access and an increase in payload mass to the lunar surface for Mission B of the two-mission sequence. The cost benefit is the accomplishment of Mission B with a "single launch solution" because no Ares I launch is required. Compared with other single launch solutions that have been proposed, this option provides an additional cost benefit because it does not require the human rating of the Ares V. The PLOM for dual mission scenarios is significantly lower because Mission B does not require the successful launch of two launch vehicles and an orbital rendezvous in time for the translunar injection (TLI) window. Cumulative risk to the crew is lower because crew exposure to Earth launch risks and Earth entry risks is reduced versus comparable Constellation Program reference two-mission-per-year scenarios.

Human and simian immunodeficiency viruses (HIV and SIV) require a seven transmembrane chemokine (7TM) receptor in addition to CD4 for efficient entry into cells. CCR5 and CXCR4 act as major co-receptors for non-syncytium-inducing and syncytium-inducing strains respectively. We have examined the co-receptor requirement for HIV-1 infection of cells of macrophage lineage. Both CCR5 and CXCR4 can operate as functional co-receptors for infection in these cell types. Other co-receptors utilised by multi-co-receptor-using strains of HIV-1, including CCR3 and STRL33, were not used for macrophage infection. HIV-2 and SIV strains, however, can replicate in both peripheral blood mononuclear cells (PBMCs) and other primary cell types such as fibroblasts independently of CCR5 or CXCR4. HIV co-receptors, particularly CCR5, will be major targets for new therapeutics in this decade. We have therefore investigated different chemokines and derivatives that bind co-receptors for their capacity to inhibit HIV infection. These included derivatives of a CCR5 ligand, RANTES, with modified N-termini as well as Kaposi's sarcoma-associated herpesvirus-encoded chemokines that bind a wide range of co-receptors, including CCR5, CXCR4, CCR3 and CCR8, as well as the orphan 7TM receptors GPR1 and STRL33. One compound, aminooxypentane or AOP-RANTES, was a particularly potent inhibitor of HIV infection on PBMCs, macrophages and CCR5+ cell lines and demonstrated the great promise of therapeutic strategies aimed at CCR5.

Cardiopulmonary bypass is associated with substantial release of catecholamines and cortisol for 12 or more h. A technique was assessed that may mitigate the responses with continuous 12-h postoperative sedation using propofol.One hundred twenty-one patients having primary elective cardiopulmonary bypass graft (CABG) surgery were enrolled in a double-blind, randomized trial and anesthetized using a standardized sufentanil-midazolam regimen. When arriving at the intensive care unit (ICU), patients were randomly assigned to either group SC (standard care), in which intermittent bolus administration of midazolam and morphine were given as required to keep patients comfortable; or group CP (continuous propofol), in which 12 h of continuous postoperative infusion of propofol was titrated to keep patients deeply sedated. Serial perioperative measurements of plasma and urine cortisol, epinephrine, norepinephrine, and dopamine were obtained; heart rate and blood pressure were recorded continuously, and medication use, including requirements for opioids and vasoactive drugs, was recorded. Repeated-measures analysis was used to assess differences between study groups for plasma catecholamine and cortisol levels at each measurement time.In the control state-before the initiation of postoperative sedation in the ICU-no significant differences between study groups were observed for urine or plasma catecholamine or cortisol concentrations. During the ICU study period, for the first 6-8 h, significant differences were found between study groups SC and CP in plasma cortisol (SC = 28 +/- 15 mg/dl; CP = 19 +/- 12 mg/dl; estimated mean difference [EMD] = 9 mg/dl; P = 0.0004), plasma epinephrine (SC = 132 +/- 120 micrograms/ml; CP = 77 +/- 122 micrograms/ml; EMD = 69 micrograms/ml; P = 0.009), urine cortisol (SC = 216 +/- 313 micrograms/ml; CP = 93 +/- 129 micrograms/ml; EMD = 127 micrograms/ml; P = 0.007), urine dopamine (SC = 85 +/- 48 micrograms; CP = 52 +/- 43 micrograms; EMD = 32 micrograms; P = 0.002), urine epinephrine (SC = 7 +/- 8 micrograms; CP = 4 +/- 5 micrograms; EMD = 3 micrograms; P = 0.0009), and urine norepinephrine (SC = 24 +/- 14 mg; CP = 13 +/- 9 mg; EMD = 11 mg; P = 0.0004). Reductions in urine and plasma catecholamine and cortisol concentrations found for the CP group generally persisted during the 12-h propofol infusion period and then rapidly returned toward control (SC group) values after propofol was discontinued. Postoperative opioid use was reduced in the CP group (SC = 97%; CP = 49%; P = 0.001), as was the incidence of tachycardia (SC = 79%; CP = 60%; P = 0.04) and hypertension (SC = 58%; CP = 33%; P = 0.01), but the incidence of hypotension was increased (SC = 49%; CP = 81%; P = 0.001).Cardiopulmonary bypass graft surgery is associated with substantial increases in plasma and urine catecholamine and cortisol concentrations, which persist for 12 or more h. This hormonal response may be mitigated by a technique of intensive continuous 12-h postoperative sedation with propofol, which is associated with a decrease in tachycardia and hypertension and an increase in hypotension.

Considering that genetic variation linked to the beta S mutation may influence the clinical manifestations of sickle cell disease, we have analyzed the beta globin cluster haplotypes in 47 patients with this condition (33 SS homozygotes, one S/beta thal (0), and 13 SC) living in London (30 West Indian, 17 West African). Of the 80 chromosomes tested, 82.5% had the Benin haplotype and of the 13 C chromosomes tested, 85% had the Bantu-A4 haplotype. A minority of patients had Bantu or Senegal haplotypes, and in 5 patients we found new haplotypes called E, H and O which may have arisen through mutation or recombination. Because of the predominance of a single haplotype (Benin) nearly all our homozygous S patients were either homozygous or heterozygous for this haplotype. We concluded that the beta globin haplotype is unlikely to be an important determinant of the clinical severity in this patient population.

Desflurane, a coronary vasodilator, may induce myocardial ischemia in patients with coronary artery disease. To determine whether desflurane is safe to administer to the at-risk patient population (with known coronary artery disease), we compared the incidence and characteristics of perioperative myocardial ischemia in 200 patients undergoing coronary artery bypass graft (CABG) surgery randomly assigned to receive desflurane (thiopental adjuvant) versus sufentanil anesthesia. Under conditions of hemodynamic control, perioperative ischemia was assessed using continuous echocardiography (precordial: during induction; transesophageal: during surgery) and Holter electrocardiography (ECG); hemodynamics (including pulmonary artery pressure) were measured continuously. Hemodynamic results: During induction, no significant changes in hemodynamics occurred in the sufentanil group, while in the desflurane group, heart rate, systemic and pulmonary arterial pressure increased and stroke volume decreased significantly. During the intraoperative period, the incidence of hemodynamic variations was low in both anesthetic groups; however, the prebypass incidence of tachycardia (greater than 120% of preoperative baseline heart rate) was greater in the desflurane group (4 +/- 7% of total time monitored) than in the sufentanil group (1 +/- 6%) (P = 0.0003). Similarly, the incidence of prebypass hypotension (less than 80% of preoperative baseline systolic arterial blood pressure) was greater in the desflurane group (21 +/- 14%) than in the sufentanil group (15 +/- 16%) (P = 0.01). ECG results: Preoperatively, 15% (28/191) of patients developed ECG ischemia, with no difference between patients who received desflurane, 13% (12/96) or sufentanil, 16% (16/95) (P = 0.6). During anesthetic induction, 9% (9/99) of patients who received desflurane developed ECG ischemia, compared with 0% (0/98) who received sufentanil (P = 0.007). During the prebypass period, 5% (10/197) of patients developed ECG ischemia, with no difference between patients who received desflurane, 7% (7/99) or sufentanil, 3% (3/98) (P = 0.3). Postbypass, 12% (24/194) of patients developed ECG ischemic changes, with no difference between patients who received desflurane, 13% (13/97) or sufentanil, 11% (11/96) (P = 0.9). Echocardiographic results: The incidence of precordial echocardiographic ischemia during anesthetic induction was 13% (5/39) in the desflurane group versus 0% (0/29) in the sufentanil group (P = 0.1). Moderate to severe transesophageal echocardiographic (TEE) ischemic episodes occurred in 12% (21/175) of patients during prebypass, with no significant difference between the desflurane group, 16% (15/91) and the sufentanil group, 7% (6/84) (P = 0.09). TEE ischemic episodes occurred in 27% (49/178) of patients during the postbypass period, with no difference between the desflurane, 29% (27/92) and sufentanil, 25% (22/86) groups (P = 0.7).(ABSTRACT TRUNCATED AT 400 WORDS)

Symptomatic ventricular coaptation, or the slit ventricle syndrome, is frequently described and recognized as a clinical entity in the pediatric population. It is characterized by symptoms of shunt failure (i.e., ataxia, obtundation, nausea, vomiting, lethargy, irritability, and complaints of headache) and the CT findings of ventricular coaptation (slit-like ventricles). This study of twenty-two children with this syndrome reflects the variety of possible clinical presentations, and the variety of available treatment modalities. Multiple therapeutic approaches were required in seven of the patients. This illustrates not only an evolving treatment regimen, but also that a single treatment modality is not universally effective. Six patients needed only occasional symptomatic support. Blockage and/or removal of the shunt system was the definitive therapy in six patients, pressure augmentation in nine patients, and subtemporal craniectomy in one. This article outlines the theoretical pathophysiology, and a scheme for the management of patients with this syndrome.

Clinical manifestations, findings, management and outcome of a series of 177 cases with tumours of the limbic and paralimbic systems are presented. There was no operative mortality. Postoperatively 95% of them had no or only minor neurological deficits. Most of them were able to resume work. Pre-operatively 77% of the patients had epilepsy, but 84% became seizure-free after tumour removal. All 77 cases with malignant tumours died within 1-5 years. In the past many neurosurgeons were reluctant to attempt complete tumour removal in these areas. This series demonstrates the efficacy of highly skilled microneurosurgery.

240 patients with tumours of the limbic and paralimbic areas are presented. The following tumour growth patterns have been observed: they remain isolated to areas within the allocortex; they spread throughout allocortical regions; they spread from allocortical to mesocortical zones. With the exception of advanced malignant tumours there seems to be a tendency for tumours to spare the adjacent neocortical and medial structures. The tumours can be approached and extirpated using the trans-Sylvian approach and microneurosurgical technique. 56% have been histologically benign. 60% were below 40 years of age. Seizures were the leading manifestation (77%). In 95% the postoperative results were good. There was no peri-operative mortality.

The purpose of this study was to evaluate the need for separate Hb screening criteria according to race by evaluating the Hb response to a therapeutic trial of iron in 1-yr-old infants. Among the 1128 infants who were screened, a significantly larger percentage of blacks (37%) than Caucasians (22%) had a Hb less than 11.5 g/dl. However, when these screen-positive infants were treated with oral iron for 3 months, the percentage who had a greater than or equal to g/dl response was similar in blacks (38%) and Caucasians (35%). Our results indicated that a slight but significant inherent tendency to lower Hb values among the black infants was counter-balanced by a substantially higher prevalence of iron deficiency anemia. These findings are in favor of using uniform Hb screening criteria in similar populations.

An evaluation was made of 278 healthy-appearing 1-year-old infants who were tested for iron deficiency to determine the relative frequency of adverse side effects attributable to oral iron treatment. After obtaining parental informed consent, laboratory tests of iron status were performed on venous blood and infants with hemoglobin level greater than 10.5 g/dL were randomly chosen to receive 1.2 mL of ferrous sulfate (FeSO4) drops (about 3 mg of iron per kilogram per day) or equal volume of placebo for 3 months. After 3 months of treatment, infants were to return to the clinic for repeat blood testing, compliance estimation, and evaluation for possible adverse side effects. There was no significant difference (P greater than .50) in the frequency of vomiting, diarrhea, or fussiness in iron-treated infants (6%) compared with placebo-treated infants (9%). Constipation was slightly more frequently reported (P = .03) in placebo-treated infants (9%) than in iron-treated infants (1%). Compliance with therapy was confirmed in 179 completely evaluated infants by the lack of remaining medication at 3 months, the higher incidence (P less than .0001) of dark stools reported among iron-treated infants, and the changes in laboratory tests of iron status. No parents reported dark stools as an adverse effect of therapy. It is concluded that once daily, moderate-dose FeSO4 therapy given to fasting 1-year-old infants results in no more gastrointestinal side effects than placebo therapy.

Iron deficiency is a common problem in otherwise healthy children and in children with systemic disease. We have reviewed the pathophysiology, laboratory diagnosis, and systemic effects of iron deficiency. We have emphasized that routine screening procedures do not efficiently predict those otherwise healthy children who will demonstrate a therapeutic response to iron. Furthermore, in patients with certain systemic diseases the diagnosis of iron deficiency is complicated by the inflammatory process and the response to a therapeutic trial of oral iron is often blunted. Since the potential adverse effects of iron deficiency may be extensive, a therapeutic trial of iron is indicated to establish the diagnosis of iron deficiency if the index of suspicion is high and laboratory results are equivocal.

Since infants with malignant osteopetrosis often die from infection at an early age, we studied several aspects of host defense in five such infants. No consistent abnormality was found in cellular or humoral immunity. Monocyte cellular chemotaxis and phagocytosis were normal in four tested infants. However, all four of these infants had decreased intracellular bacterial killing by monocytes. Neutrophil function tests in five infants showed that two had defective bacterial phagocytosis and four had reduced cellular chemotaxis, decreased nitroblue tetrazolium reduction, and decreased intracellular bacterial killing. The severity of the decreased bactericidal capacity of granulocytes did not correlate with the number of circulating immature granulocytes. Our data suggest that abnormal function of circulating monocytes and granulocytes may contribute to impaired host resistance to infection. We postulate that this defect may reflect a more generalized inherited abnormality of phagocytic cells and perhaps osteoclasts that plays a role in the pathogenesis of infantile osteopetrosis.

Iron supplements are commonly administered to infants in order to prevent iron deficiency. We wished to determine whether iron administration could compromise zinc nutrition as might be suspected from previous studies. Measures of iron nutrition, serum zinc, and serum copper were measured before and after randomization of 291 healthy 1-yr-old infants to a 3 mo course of placebo or iron treatment (30 mg iron as ferrous sulfate given before a meal). There was no significant difference in serum zinc or copper in the two groups before or after treatment; thus iron administration did not result in any evidence of zinc deficiency in a healthy, well-nourished group of T-yr-old infants.

CASE-history data are presented on 12 women who have carried in their skeletons for many years toxicologically interesting burdens of the radioisotopes Ra226 (radium, or Ra) and Ra228 (mesothorium, or MsTh). This is one of a series of reports from these laboratories on a continuing study of Ra and MsTh toxicity to human beings. The most recent previous publication of data obtained in this project, aside from annual progress reports, appeared in 1952.1 The effects of long continued skeletal irradiation in human beings have thus far been observed in significant detail only in persons occupationally or medically exposed to Ra . . .

Purified human rhinovirus type 14 has been subjected to acid and alkaline degradation and the effects of hydrogen ions on particle morphology and infectivity are being studied. Considerable morphological degradation of the capsid occurred by pH 5.5. Breakdown may be by loss of discrete capsomere groups accompanied by release of the viral genome in the form of a ribonucleoprotein strand. Examination of virions prepared for electron microscopy by the “critical point” procedure which results in essentially 3 dimensional specimens confirms this finding. Under alkaline conditions there is very little loss of infectivity up to pH 9.8. There is a precipitous loss in infectivity at around pH 10.9 accompanied by complete break up of viral capsid morphology.

Haemoglobin H disease is described in successive generations of 2 Filipino families. The condition was asymptomatic. The inheritance pattern of haemoglobin H disease in these families appeared to be like that described for Thais.