Comparison of polysaccharide glycoconjugates as candidate vaccines to combat Clostridiodes (Clostridium) difficile.

Two known Clostridiodes (Clostridium) difficile surface antigens, a lipoteichoic acid (LTA) and a polysaccharide (PS-II) were isolated and purified in order to prepare glycoconjugate vaccines to the carrier protein human serum albumin utilising a reductive amination strategy. Mice and rabbits were immunized with a prime and two boost strategy and the resulting sera were examined for their ability to recognise the purified homologous antigens and subsequently killed whole cells of C. difficile strains and other Clostridia species. Immunisation derived antisera from rabbits and mice, recognised all strains of C. difficile vegetative cells examined, with generally similar titers from animals that received the LTA or the PS-II conjugates. Sera raised to the LTA conjugates were able to recognise other Clostridia species C. butyricum, C. bifermentans and C. subterminale whereas sera raised to the PS-II conjugates were not. These LTA and PS-II sera recognised live cells in an immunofluorescence assay and were also able to recognise the spore form of the bacterium. This study has confirmed that the LTA and PS-II polysaccharides are both highly conserved surface polymers of C. difficile that are easily accessible to the immune system and as such may have potential as vaccine antigens or as targets for therapeutics to combat C. difficile infection.

Analysis of the Daya Bay Reactor Antineutrino Flux Changes with Fuel Burnup.

We investigate the recent Daya Bay results on the changes in the antineutrino flux and spectrum with the burnup of the reactor fuel. We find that the discrepancy between current model predictions and the Daya Bay results can be traced to the original measured ^{235}U/^{239}Pu ratio of the fission ß spectra that were used as a base for the expected antineutrino fluxes. An analysis of the antineutrino spectra that is based on a summation over all fission fragment ß decays, using nuclear database input, explains all of the features seen in the Daya Bay evolution data. However, this summation method still allows for an anomaly. We conclude that there is currently not enough information to use the antineutrino flux changes to rule out the possible existence of sterile neutrinos.

Applications of nuclear physics.

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

Dissecting Reactor Antineutrino Flux Calculations.

Current predictions for the antineutrino yield and spectra from a nuclear reactor rely on the experimental electron spectra from ^{235}U, ^{239}Pu, ^{241}Pu and a numerical method to convert these aggregate electron spectra into their corresponding antineutrino ones. In the present work we investigate quantitatively some of the basic assumptions and approximations used in the conversion method, studying first the compatibility between two recent approaches for calculating electron and antineutrino spectra. We then explore different possibilities for the disagreement between the measured Daya Bay and the Huber-Mueller antineutrino spectra, including the ^{238}U contribution as well as the effective charge and the allowed shape assumption used in the conversion method. We observe that including a shape correction of about +6% MeV^{-1} in conversion calculations can better describe the Daya Bay spectrum. Because of a lack of experimental data, this correction cannot be ruled out, concluding that in order to confirm the existence of the reactor neutrino anomaly, or even quantify it, precisely measured electron spectra for about 50 relevant fission products are needed. With the advent of new rare ion facilities, the measurement of shape factors for these nuclides, for many of which precise beta intensity data from TAGS experiments already exist, would be highly desirable.

First characterization of immunogenic conjugates of Vi negative Salmonella Typhi O-specific polysaccharides with rEPA protein for vaccine development.

Efficacious typhoid vaccines for young children will significantly reduce the disease burden in developing world. The Vi polysaccharide based conjugate vaccines (Vi-rEPA) against Salmonella Typhi Vi positive strains has shown high efficacy but may be ineffective against Vi negative S. Typhi. In this study, for the first time, we report the synthesis and evaluation of polysaccharide-protein conjugates of Vi negative S. Typhi as potential vaccine candidates. Four different conjugates were synthesized using recombinant exoprotein A of Pseudomonas aeruginosa (rEPA) and human serum albumin (HSA) as the carrier proteins, using either direct reductive amination or an intermediate linker molecule, adipic acid dihydrazide (ADH). Upon injection into mice, a significantly higher antibody titer was observed in mice administrated with conjugate-1 (OSP-HSA) (P=0.0001) and conjugate 2 (OSP-rEPA) (P≤0.0001) as compared to OSP alone. In contrast, the antibody titer elicited by conjugate 3 (OSPADH-HSA) and conjugate 4 (OSPADH-rEPA) were insignificant (P=0.1684 and P=0.3794, respectively). We conclude that reductive amination is the superior method to prepare the S. Typhi OSP glycoconjugate. Moreover, rEPA was a better carrier protein than HSA. Thus OSP-rEPA conjugate seems to be efficacious typhoid vaccines candidate, it may be evaluated further and recommended for the clinical trials.

Durability of carotid endarterectomy.

Carotid endarterectomy is the preferred treatment for patients with transient ischemic attacks and carotid stenosis. Although clinically these patients do well, the long-term fate of the operated carotid artery has not been well documented. To address this question, repeated noninvasive testing has been employed to follow our carotid endarterectomy patients since 1976. Supraorbital Doppler examination, oculoplethysmography-Kartchner, carotid phonoangiography and, later in this series, spectral analysis of the carotid Doppler velocities were performed after 193 endarterectomies. One hundred fifty-eight patients were initially tested within 3 months of operation, and 35 were initially tested 3 or more months after operation. Twenty-four arteries, four of which were symptomatic, had an initial abnormal test and are excluded from this study of carotid artery durability. Of the 169 patients with normal carotid tests, 36 had no further evaluation. Among the 133 patients who returned for serial testing from 1 to 60 months (mean 20 months), 115 carotid arteries continued to test normal at late follow-up but 18 subsequently developed test abnormalities. Ten had more than 75% stenosis, eight had 50% to 75% stenosis. Eight of these patients had contrast studies: three had normal findings; the five that had abnormal findings underwent reoperation. Interestingly, only two patients presented with symptoms appropriate to the abnormal test. The findings suggest that carotid endarterectomy is a reasonably durable operation. Recurrent stenosis was presumed or proven in 10% of 133 serially tested carotid arteries. This threat of restenosis makes long-term follow-up of these patients mandatory.

The effect of contralateral disease on carotid Doppler frequency.

Continuous-wave Doppler frequency analysis is one standard of noninvasive evaluation for stenotic carotid disease. Interpretation is most commonly based on frequency recorded at the site of stenosis. If flow velocity is increased because of contralateral disease, this criterion may overstate the degree of stenosis. To investigate this, three centers contributed 167 patients to a study of carotid Doppler frequency analysis. Each patient underwent bilateral carotid studies by a standard protocol with use of continuous-wave 5 MHz Doppler probe. There were 309 patent and 25 occluded internal carotids seen on subsequent angiographs. Each patient side was categorized by the severity of ipsilateral disease (less than 45%, 45% to 70%, 71% to 99%, occlusion) and then subgrouped by contralateral disease. For all carotid arteries, the optimal peak frequency to detect 45% or more stenosis was 5500 Hz, with an overall accuracy of 92.2%. Within the three classifications of ipsilateral stenosis, a trend was noted that related increasing peak frequency to greater degrees of contralateral disease. This was most apparent when the contralateral internal carotid artery was occluded. Of all false-positive errors, 43% were accounted for by this subset that represented 15% of the total population. For the 25 patients with occlusion opposite a stenosis, the 5500 Hz cutoff of Doppler peak frequency yielded only 76% accuracy; an ROC curve showed that a cutoff value of 8500 Hz improved overall accuracy to 92% for these patients. By applying two cutoff criteria--5500 Hz for those with patent contralateral internal carotids and 8500 Hz for those in whom a contralateral Doppler signal was not detected--the overall accuracy for all patients improved to 93.3%. It is concluded that contralateral occlusion affects Doppler peak frequency by increasing the velocity in the companion carotid artery, whereas severe contralateral stenosis did not result in a consistent pattern of increased velocity.

Diagnosis of peripheral occlusive disease: comparison of clinical evaluation and noninvasive laboratory.

One hundred and two patients with peripheral vascular disease were evaluated by the attending surgeon, residents and students, and the vascular laboratory prior to arteriography to test their ability to make a correct anatomic diagnosis. The attending surgeons made a correct anatomic diagnosis in 98 patients and were at least partially correct in the other four. Surgical housestaff and students were 62% totally correct, 35% partially correct, and 3% totally wrong. The vascular laboratory results were almost identical with the attending surgeon, but two patients could not be evaluated because of calcified arteries. The operation that was eventually performed was suggested initially by the laboratory and the attending surgeon in 98% of the patients.

Value of concomitant sympathectomy in aortoiliac reconstruction. Results of a prospective, randomized study.

The efficacy of concomitant lumbar sympathectomy in improving results of aortoiliac reconstruction was assessed by a prospective, randomized study of 51 patients undergoing operation for occlusive or aneurysmal disease. Sympathectomy was performed on 50 limbs, while 52 extremities served as controls. Sympathectomy resulted in a significant reduction in foot vascular resistance determined by plethysmography. However, the procedure had no effect on leg circulation, assessed by ankle/arm pressure indices determined by Doppler ultrasound. In the sympathectomy group, there were three early postoperative amputations for ischemia, despite patent grafts. In the control group, there was one late graft occlusion, caused by progressive atherosclerotic disease. Although sympathectomy may improve pedal circulation, the procedure does not appear to improve the results of aortoiliac reconstruction.

Value of segmental limb blood pressures in predicting results of aortofemoral bypass.

The efficacy of segmental limb blood pressure measurements, assessed noninvasively by Doppler ultrasound, in predicting the result of aortofemoral reconstruction was evaluated in fifty-two extremities with varying extent of aortoiliac and more distal arterial occlusive disease. Three prognostic correlates were analyzed: (1) preoperative proximal thigh/arm pressure index (TPI); (2) preoperative pressure gradient between adjacent leg segments (proximal thigh, above-knee, below-knee, and ankle), normally less than 30 mm Hg; and (3) early postoperative increase in the ankle/arm pressure index (API). After aortofemoral bypass, forty-one limbs (79 per cent) were asymptomatic or improved and eleven were unimproved. The mean TPI in extremities benefiting from aortofemoral bypass, 0.82 +/- 0.17 (+/-1SD) was significantly less than that of unimproved limbs, 1.01 +/- 0.09 (p less than 0.01). Aortofemoral bypass was beneficial in all twenty limbs with normal leg pressure gradients. Conversely, six of twenty-five legs with one abnormal gradient and five of seven with two abnormal gradients failed to improve. The postoperative increase in API was 0.1 or more in all forty-one improved extremities and was less than 0.1 in all eleven failures. Although eleven of thirty-two limbs (34 per cent) with arteriographic evidence of combined aortoiliac and subinguinal occlusive disease were not improved after proximal bypass, the result of operation could not be predicted from the angiographic pattern or severity of distal disease. Segmental limb blood pressures provide useful predictive indices of the efficacy of aortofemoral bypass and the potential need for more distal reconstruction in multisegmental disease.

Factors influencing morbidity of carotid endarterectomy without a shunt.

A retrospective analysis of 156 unshunted carotid endarterectomies in 124 patients indicates that at least three factors may influence the surgeon to consider using an indwelling shunt. Contralateral internal carotid artery occlusion, prolonged cross-clamp time, and possibly stump pressures less than 25 mm Hg torr were associated with increased rate of permanent neurologic deficit. Selective shunting would not be based on stump pressures less than 50 mm Hg torr, previous ipsilateral stroke, or abnormal intraoperative electroencephalogram.

Pneumatic compression devices for prophylaxis of deep venous thrombosis (DVT).

A pneumatic compression device was applied to 155 patients with a normal Doppler venous examination who underwent a general surgical procedure of at least 1 hr in duration. One hundred fifty-three patients had neither PE nor DVT clinically or by Doppler studies, one patient had a venographically proven DVT, and one patient had a clinical pulmonary embolism verified by lung scanning. Using clinical and Doppler criteria, the device was effective in the prophylaxis of thromboembolic complications.

The normal Doppler venous examination.

The clinical diagnosis of acute deep vein thrombosis (DVT) is but 50% accurate when compared to the results of contrast venography. This clinical inaccuracy had led to the dependence of the physician upon laboratory diagnosis. Whereas contrast venography is the gold standard of diagnosis, its expense, special equipment, personnel, and discomfort make it unsuitable for evaluating large numbers of patients. For this reason, numerous noninvasive tests utilizing plethysmographic and Doppler techniques have been developed to evaluate patients with suspected venous disease, and when expertly performed have a degree of accuracy of approximately 90%. This degree of accuracy coincides with the experience of our peripheral vascular laboratory using the Doppler venous examination. Based on these statistics, our current practice is to evaluate patients suspected of having DVT with a Doppler venous examination (Figure 1). If the test is abnormal or equivocal, contrast venography is usually obtained and anticoagulation recommended. Contrariwise, if the Doppler venous examination is normal, venography is not obtained, and anticoagulation treatment is not recommended. This practice should reduce the number of venograms in a patient population that is not at an increased risk of pulmonary embolism or repeated deep venous thrombosis. To evaluate the validity and safety of this practice, one hundred eighty-six patients with normal Doppler venous examinations in whom contrast venography was not obtained were evaluated and form the basis of this report.

Assessing potential risks from exposure to natural uranium in well water.

Over 50% of the wells in the Nambe region of northern New Mexico exceed the US Environmental Protection Agency's recommended drinking water standard of 20 microg l(-1) for 238U; the highest in the area was measured at 1,200 microg U l(-1). Uranium uptake was estimated in tomato (Lycopersicon esculentum), squash (Cucurbita pepo), lettuce (Lactuca scarriola), and radish (Raphanus sativus) irrigated with Nambe well water containing <1, 150, 500, and 1,200 microg U l(-1). Plant uptake and human dose and toxicity associated with ingestion of water and produce and inhalation of irrigated soil related to gardening activities were evaluated. Uranium concentration in plants increased linearly with increasing U concentration in irrigation water, particularly in lettuce and radish. The estimated total committed effective dose for 70 years of maximum continuous exposure, via the three pathways to well water containing 1,200 microg U l(-1), was 0.17 mSv with a corresponding kidney concentration of 0.8 microg U g(-1) kidney.

Prompt radiochemistry at the National Ignition Facility (invited).

Understanding mix in inertial confinement fusion (ICF) experiments at the National Ignition Facility requires the diagnosis of charged-particle reactions within an imploded target. Radiochemical diagnostics of these reactions are currently under study by scientists at Los Alamos and Lawrence Livermore National Laboratories. Measurement of these reactions requires assay of activated debris and tracer gases from the target. Presented below is an overview of the prompt radiochemistry diagnostic development efforts, including a discussion of the reactions of interest as well as the progress being made to collect and count activated material.

Population quality and sustainable development in Indonesia: notes on a framework for the discussion of policy issues.

PIP: A simple and far reaching framework is needed to indicate the interdisciplinary connections between issues of population, environment, society, and development. Policy makers must understand the holistic nature of these issues when they formulate programs and official proclamations. High population quality and sustainable development are the goals they are trying to achieve and only by drawing from various disciplines is this goal going to be achieved. State guidelines are the context in which issues from these different areas are discussed. Quality of life and sustainable development is a national objective and is a reflection of lifestyles and values of the people. The government knows that it must work in conjunction with its people in order to complete policy goals.^ieng

Cairo and the changing definition of population and development issues.

PIP: This article discusses a few intellectual and ideological developments during the 1980s and 1990s which impacted on the goals articulated at the UN International Conference on Population and Development and in its Plan of Action (POA). A major shift occurred between the Bucharest Plan of 1974 and the 1994 POA. The economic view was improved by an emphasis on the ecological, human rights, and nongovernmental organization (NGO) participatory views. The Bucharest Plan promoted the institutionalization of integrated population and development programs. The Cairo POA offered little guidance in how to institutionalize integrated approaches. The main Cairo strategy was radical in promoting the empowerment of women as a means to slow population growth. This strategy will require changes in existing power relations in society, at home, and in traditional morality. Consensus among 180 governments is a powerful statement of support for social change agents and undermines the "moral legitimacy" of those who resist. Scientific understanding of the links between population and development have improved over 20 years. However, political priorities have shifted, demographics have changed, goals for development have risen, and more viewpoints must be accounted for. Agreement on definitions of the problem and solutions will be difficult. Economic, ecological, and other perspectives have evolved into a more complex and conflicting understanding of interrelationships. A brief description of changes in perspectives is given for economic, ecological, human rights, and NGO views.^ieng

Non-invasive evaluation of patients with extracranial to intracranial bypass.

In selected patients with cerebrovascular insufficiency, an extracranial-intracranial bypass is indicated to increase cerebral blood flow. To assess the effect of this operation upon routine non-invasive testing, 15 patients had oculoplethysmography, carotid phonoangiography and Doppler testing. None of those with a preoperative abnormality were changed after surgery, despite angiographically proven anastomotic patency. Whereas non-invasive tests may correctly identify severe internal carotid stenosis, use of these modalities in their routine form does not predict extracranial-intracranial bypass patency.

Neutrino-12C scattering in the Ab initio shell model with a realistic three-body interaction.

We investigate cross sections for neutrino-12C exclusive scattering and for muon capture on 12C using wave functions obtained in the ab initio no-core shell model. In our parameter-free calculations with basis spaces up to the 6 variant Planck's over 2pi Omega we show that realistic nucleon-nucleon interactions, like, e.g., the CD-Bonn, underpredict the experimental cross sections by more than a factor of 2. By including a realistic three-body interaction, Tucson-Melbourne TM'(99), the cross sections are enhanced significantly and a much better agreement with experiment is achieved. At the same time, the TM'(99) interaction improves the calculated level ordering in 12C. The comparison between the CD-Bonn and the three-body calculations provides strong confirmation for the need to include a realistic three-body interaction to account for the spin-orbit strength in p-shell nuclei.

Carotid endarterectomy without a shunt: the control series.

Nine hundred forty carotid endarterectomies were performed without the use of a temporary indwelling shunt. Six patients (0.6%) died, all from stroke; 17 other patients (1.8%) had another stroke, and 21 patients (2.2%) had temporary neurologic symptoms. Complete x-ray films detailing the opposite internal carotid artery and carotid artery back pressure were available for 783 operations. Correlation of stroke to back pressure, status of the contralateral internal carotid artery, preoperative neurologic deficit, and carotid clamp time was examined. Statistical analysis demonstrated significantly increased neurologic complications only if the systolic carotid back pressure was less than or equal to 50 mm Hg or the contralateral internal carotid artery was occluded. Analysis to determine if these factors were dependently related showed that when both a contralateral carotid occlusion and a carotid back pressure of less than or equal to 50 mm Hg coexisted (82 patients), the rate of permanent deficit was 11.0% compared with 2.8% when either factor was singly present and 0.9% when neither factor was present. No statistical difference exists between the group with only a single factor and those with neither factor. When a temporary shunt is not used during carotid endarterectomy, the risk of neurologic complication is increased if both a contralateral internal carotid artery occlusion and a carotid back pressure of less than or equal to 50 mm Hg coexist. The use of a shunt in this patient population may be beneficial.