'Switch' catalysis: from monomer mixtures to sequence-controlled block copolymers.

A 'Switch' catalysis method is reviewed whereby a single catalyst is switched between ring-opening polymerization and ring-opening copolymerization cycles. It allows the efficient synthesis of block copolymers from mixtures of lactones, epoxides, anhydrides and carbon dioxide. In order to use and further develop such 'Switch' catalysis, it is important to understand how to monitor the catalysis and characterize the product block copolymers. Here, a step-by-step guide to both the catalysis and the identification of block copolymers is presented.This article is part of a discussion meeting issue 'Providing sustainable catalytic solutions for a rapidly changing world'.

Catalysts for CO2/epoxide ring-opening copolymerization.

This article summarizes and reviews recent progress in the development of catalysts for the ring-opening copolymerization of carbon dioxide and epoxides. The copolymerization is an interesting method to add value to carbon dioxide, including from waste sources, and to reduce pollution associated with commodity polymer manufacture. The selection of the catalyst is of critical importance to control the composition, properties and applications of the resultant polymers. This review highlights and exemplifies some key recent findings and hypotheses, in particular using examples drawn from our own research.

Carbon dioxide capture and utilization: using dinuclear catalysts to prepare polycarbonates.

The copolymerization of epoxides, including cyclohexene oxide and vinyl-cyclohexene oxide with carbon dioxide are presented. These processes are catalyzed using a homogeneous di-zinc complex that shows good activity and very high selectivities for polycarbonate polyol formation. The polymerizations are investigated in the presence of different amounts of exogenous reagents, including water, diols and diamines, as models for common contaminants in any carbon dioxide capture and utilization scenario.

Improving the solubility of pseudo-hydrophobic Alzheimer's Disease medicinal chemicals through co-crystal formulation.

Natural products are ligands and potential inhibitors of Alzheimer's disease (AD) tau. Dihydromyricetin (DHM) is a CNS active natural product. Despite having signature polyphenolic character, DHM is ostensibly hydrophobic owing to intermolecular hydrogen bonds that shield hydrophilic phenols. Our research shows DHM becomes ionized at near-neutral pH allowing formulation of salts with transformed solubility. The MicroED co-crystal structure with trolamine reveals DHM salts as metastable solids with unlocked hydrogen bonding and a thermodynamic bent to solubilize in water. All salt formulations show better inhibitory activity against AD tau than the non-salt form, with efficacies correlating to enhanced solubilities. These results underscore the role of structural chemistry in guiding selection of solubilizing agents for chemical formulation. We propose DHM salts are appropriate formulations for research as dietary supplements to promote healthy aging by combating protein misfolding. Additionally, DHM is a suitable lead for medicinal chemistry and possible development of CNS pharmaceuticals.

A new method of spike modelling and interval analysis.

Here we develop a new model of spike firing, based on the leaky integrate and fire model, modified to simulate afterpotentials. We also develop new analysis techniques, applying these to recorded and model generated data in order to make a comparative analysis and develop the model as a hypothesis for the functional components of the neuron. The model is based in this first instance on hypothalamic oxytocin neurons. We demonstrate how model parameters and cell properties relate to features observed in inter-spike intervals histograms, and the limits of these in being able to detect patterning features in spike recordings. A new technique, spike train analysis, is able to detect previously unobserved patterning, showing a dependence of spike intervals on previous firing activity. This effect is reproduced in the model by adding the small amplitude but long lasting after hyper-polarising potential (AHP). A fit measure based on log likelihood is used to compare model generated data to recorded spike intervals, taking account of interval dependence on previous activity. This measure is used with the simplex multiple parameter search algorithm to develop an automated method for fitting the model to recorded data.

Endoscopic sensing of alveolar pH.

Previously unobtainable measurements of alveolar pH were obtained using an endoscope-deployable optrode. The pH sensing was achieved using functionalized gold nanoshell sensors and surface enhanced Raman spectroscopy (SERS). The optrode consisted of an asymmetric dual-core optical fiber designed for spatially separating the optical pump delivery and signal collection, in order to circumvent the unwanted Raman signal generated within the fiber. Using this approach, we demonstrate a ~100-fold increase in SERS signal-to-fiber background ratio, and demonstrate multiple site pH sensing with a measurement accuracy of ± 0.07 pH units in the respiratory acini of an ex vivo ovine lung model. We also demonstrate that alveolar pH changes in response to ventilation.

Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the relative efficacy of an intensive cyclophosphamide, epirubicin, and fluorouracil (CEF) adjuvant chemotherapy regimen compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive breast cancer. PATIENTS AND METHODS: Premenopausal women with node-positive breast cancer were randomly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14; methotrexate 40 mg/m2 intravenously (i.v.) days 1 and 8; and fluorouracil 600 mg/m2 i.v. days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14; epirubicin 60 mg/m2 i.v. days 1 and 8; and fluorouracil 500 mg/m2 i.v. days 1 and 8. Each cycle was administered monthly for 6 months. Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy. RESULTS: The median follow-up was 59 months. One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients. The corresponding 5-year relapse-free survival rates were 53% and 63%, respectively (P = .009). One hundred seven CMF patients died compared with 85 CEF patients. The corresponding 5-year actuarial survival rates were 70% and 77%, respectively (P = .03). The rate of hospitalization for febrile neutropenia was 1.1% in the CMF group compared with 8.5% in the CEF group. There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group. Acute leukemia occurred in five patients in the CEF group. CONCLUSION: The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer.

Some epidemiological features of the human T-cell lymphotropic virus type I (HTLV-I) and ATL in Nigerians.

With a seroprevalence rate (SPR) of 6%-10% among healthy adult blood donors (ABD), Nigeria and other African locales represent an endemic zone for HTLV-I. We studied SPR in patients with leukaemia, lymphomas, solid tumours, and chronic disorders, as well as in groups of men and women with varying sexual lifestyles. Serum specimens were screened with ELISA and then confirmed with Western blot (WB). Sexual practices were investigated among volunteers of different sexual backgrounds by means of a questionnaire. Female prostitutes (FP) (13.0%) and patients with sexually transmitted diseases (STDP) (16.7%) had the highest SPR while a low rate occurred in religious celibate males (RCM) but not in religious celibate females (RCF) (11.8%). Heterosexual activity as well as geographical location of the place of birth constituted the most important risk factors for HTLV-I. HIV antibodies were demonstrable in none of the study subjects. ATL was associated with 100% SPR (4/4) while SPR in other clinical states were not different from normal. Western blot profile was rarely of strong poly band but more frequently of weak oligo band pattern with absent or weak p19 compared to p24. Only 18% of non Hodgkin's lymphoma in Ibadan, Nigeria was seropositive compared to 50% and > 60% in Japanese and Caribbean endemic zones respectively. The high SPR and aberrant WB profiles indicate reactivity to HTLV-I and to an HTLV-II-like activity, probably a new virus in the region. Excluding the aberrant WB profile, SPR based on HTLV-I-related profile was 3.8%-4.8% in ABD, 13% in FP, 10% in STDP, 1.9% in RCM, 0% in RCF, and 25% in ATL patients. The HTLV-II-related profile showed no such heterosexual association, but occurred in 75% of ATL patients. HTLV-I and probably and an HTLV-II-like virus appear to play a role in STD and lymphoma epidemiology in Nigeria.

Geographical distribution of acute lymphoblastic leukaemia subtypes: second report of the collaborative group study.

Childhood acute lymphoblastic leukemia (ALL) T and B precursor subtypes have been identified by standardised immunophenotyping in different geographic and ethnic settings. Comparison of the relative frequencies and estimated incidence rates of the major subtypes indicates very similar values, with the striking exception of black childhood populations in Africa in which there appears to be a significant and selective deficit in the incidence of the common (B-cell precursor) subset of ALL. There is suggestive evidence for a similar bias in ALL subtypes in South Africans of mixed ethnic origin and in Mapuche Indians from Chile. Several interpretations of these data are possible but the one favoured attributes these differences primarily to socio-economic factors and patterns of infection in infancy.

Effect of prenatal alcohol exposure on consumption of alcohol and alcohol-induced sleep time in mice.

An animal model was used to examine the effect of maternal alcohol administration on behaviors in the offspring which might predispose to alcoholism. Pregnant C3H mice were administered a liquid diet containing 28% ethanol-derived calories (EDC) from Gestation-Day 8 until parturition. Control animals were either pair-fed an isocaloric 0% EDC diet or received standard lab chow and water throughout pregnancy. Offspring were tested for sleep time following a challenge dose of 3.5 or 4.5 g/kg ethanol at 25 or 110 days of age or for consumption of 10% w/v ethanol in a two-bottle choice situation. The results demonstrated that prenatal exposure to alcohol did not affect alcohol-induced sleep time at either testing age or dose and that waking blood alcohol levels were similar across groups. Voluntary alcohol consumption, however, was higher in mice exposed to alcohol in utero during the initial week of testing but intake decreased to near control levels by the third week. Whether other alcohol-related behaviors are altered by prenatal alcohol exposure remains to be examined.

Development and use of virus-vectored immunocontraception.

Virus-vectored immunocontraception (VVIC) is perceived to present biological risks, real or baseless, which create social and political constraints to deploying VVIC for managing vertebrate pests. Developing and deploying VVIC must be justified and address biological, social and political risks. Future needs for pest management will influence deployment of VVIC. Projections of human society and pest impact on agriculture and conservation suggest increasing need for cost-beneficial strategies. Best strategies are likely to integrate various methods, possibly including forms of VVIC. Processes identifying future pest impacts and roles for VVIC are shown using the rabbit in Australia. Present research developing VVIC aims to test physiological feasibility, to develop it for specific pests, and address aspects of ecological feasibility. Minimizing biological risks through choosing species-specific antigens and, if possible, viral vectors, is central and overseen by regulatory authorities. International collaborators study related valued species to develop protective strategies. Excellent science can withstand legal or public challenge to safe and cost-beneficial VVIC if aided by information needed by the public exposed to media distortion of scientific debate, complex argument and concepts of probability and risk. Sound science needs support from strategies for public processes to enable cost-beneficial management of vertebrate pests.

Comparing Bayesian neural network algorithms for classifying segmented outdoor images.

In this paper we investigate the Bayesian training of neural networks for region labelling of segmented outdoor scenes; the data are drawn from the Sowerby Image Database of British Aerospace. Neural networks are trained with two Bayesian methods, (i) the evidence framework of MacKay (1992a,b) and (ii) a Markov Chain Monte Carlo method due to Neal (1996). The performance of the two methods is compared to evaluating the empirical learning curves of neural networks trained with the two methods. We also investigate the use of the Automatic Relevance Determination method for input feature selection.

Health status of northern bobwhite quail (Colinus virginianus) in eastern Kansas.

The health status of wild northern bobwhite quail (Colinus virginianus) from Lyon County, Kansas, was evaluated by conducting comprehensive health assessments on 25 birds. Gross lesions indicative of avian pox, ulcerative enteritis, and quail bronchitis were not present. Serologic tests for antibodies to Salmonella pullorum, Salmonella gallinarum, Pasteurella multocida, Mycoplasma gallisepticum, Mycoplasma synoviae, and avian adenoviruses were all negative. Intestinal coccidia (Eimeria spp.) were found in 36% of the birds. Only three species of helminth parasites were found: Dispharynx nasuta in two birds, Cyrnea colini in one bird, and larval Physaloptera sp. in four birds. Arthropod parasites (ticks, lice, mites, and/or chiggers) were present on 96% of the birds examined. Compared with wild bobwhite populations in the southeastern United States, the diversity, prevalence, and intensities of microbial and parasitic agents were low.

Baylisascaris sp. found in a wild northern bobwhite (Colinus virginianus).

During a telemetry study conducted between 1993 and 1995 in east-central Kansas (USA) on northern bobwhite (Colinus virginianus) populations, a wild adult male quail was found with signs of disorientation and torticollis in August 1994 in Lyon County, Kansas. Based on histological and parasitological examination, it was determined that the bird was infected with larval nematodes of the genus Baylisascaris spp. This is the first known recorded case of Baylisascaris sp. in a wild game bird species.

Recent advances in chemotherapy of the lymphomas: a review.

A review of some of the developments over the last two decades in the field of chemotherapy of the lymphomas is provided. The evolution of the current treatment regimens through clinical trials is emphasized, and the need to develop a similar approach to cancer chemotherapy in African treatment centres is advocated. In view of their different natural histories, non-Hodgkin's lymphoma (NHL) of 'favourable' and 'unfavourable' histologic variants need to be treated differently. While the former type of NHL need only a non-myelosuppressive chemotherapy, the latter would benefit from intensive chemotherapy involving the use of adriamycin and cytosine arabinoside, which appear to have salutary effects in this form of NHL. Burkitt's and Hodgkin's lymphomas are both highly curable forms of cancer and indications are given in support of further improvement in their current chemotherapeutic management. As over 50% of adequately treated lymphoma patients are likely to experience prolonged survival, more attention is now being directed to factors contributory to their quality of life. Thus, some complications of chemotherapy and their prevention are reviewed.

Prospective studies on Hodgkin's disease in Ibadan--a preliminary report.

A preliminary report of a prospective study of Hodgkin's disease (HD) is provided, based on clinical and laboratory findings on 21 patients seen between July 1978 and December 1979 at the University College Hospital (UCH), Ibadan. Staging procedure was minimized to relatively simple surgical procedures like lymphangiography and percutaneous biopsy. Staging laparotomy was performed only in one case. Female patients were significantly older than males (P less than 0.05). Patients with lymphadenopathy were significantly older than those without (P less than 0.05), while those with systemic symptoms were significantly younger than those without. Eighteen (86%) of the patients presented with stage IV disease while 12 (57%) had the unfavourable histologic "mixed cellularity' or "lymphocyte depleted' variants. Systemic symptoms were present in 16 (76%) of patients. Fifty-three % of adequately treated patients showed poor response to chemotherapy. The prognosis of HD in Ibadan is on the whole unfavourable. A delineation of the prognostic factors is indicated.

Neoplastic diseases of the haemopoietic system in Ibadan: preliminary report of a prospective study.

The clinical and epidemiological features of haemopoietic malignancies in Ibadan have been evaluated in this preliminary analysis on findings on 113 patients seen at the University College Hospital, Ibadan, Nigeria, from July 1978 to June 1981. Twenty-seven patients had acute myelogenous (AML), twenty-two acute lymphoblastic (ALL), thirty-one chronic myelocytic (AML), thirty-one chronic lymphocytic leukaemia (CLL), two had polycythaemia rubra vera (PRV) and one myelofibrosis (MF). Incidence rates (IR) of 0.9 X 10(-5) and 1.9 X 10(-5) were estimated for acute leukemia (AL) and all leukemia subtypes respectively. Chloroma occurred frequently in association with AML especially in childhood, and CLL in elderly patients (greater than 50 years) and ALL appeared to manifest unusually aggressive features in spite of apparently adequate chemotherapy. Some of these clinical and epidemiological features suggest deviant biology of some haemopoietic malignancies in Ibadan.

Management of malignant lymphoproliferative disorders of the nervous system.

The frequency of involvement of the nervous system (NS) among 266 patients seen at the University College Hospital (UCH), Ibadan, with a diagnosis of malignant lymphoproliferative diseases (MLPD) was determined. Only one of these patients who had a solitary spinal-cord involvement by Hodgkin's disease (HD) was considered to have primary lymphoma of NS. In all other cases, NS was only secondarily involved by MLPD. This was most commonly observed in association with Burkitt's lymphoma and occurred in 49.3 and 67% of such patients who were previously untreated or previously treated, respectively. Nervous system (NS) involvement at presentation was much less commonly observed in non-Hodgkin's (NHL), HD and acute lymphoblastic leukaemia (ALL) at the rate of 6.7, 4.4 and 0% respectively of previously untreated patients. The NS was the site of relapse in 63.6, 43, 12.5 and 0% in BL, ALL, NHL and HD, respectively. Intra-cranial NS disease was identified as a poor prognostic feature as this was associated with a reduction of the probability of prolonged survival from 48% to less than 20% among patients with intra-cranial and/or extra-cranial disease in BL. Management of MLPD with high rate of NS involvement should include effective delivery of chemotherapy into CFS, both by direct injection intrathecally and through filtration across the blood-brain barrier following high-dose intravenous injection of agents like methotrexate or cytosine arabinoside.

Continuous in-vitro cultivation of Plasmodium falciparum in Ibadan: solutions to scientific and logistical problems.

The technique of continuous in-vitro cultivation of Plasmodium falciparum has not been widely applied in malaria-endemic areas, due to scientific as well as purely logistical problems. Methods for solving or coping with these problems are described. They have already proved effective for over 4 years. The parasites harvested have been satisfactory, as judged by reproducible logarithmic growth curves and normal morphology in Leishman-stained smears as well as phase-contrast microscopy of wet-preparations. They have also been successfully used as antigen sources in the malarial fluorescent-antibody test and to investigate enhanced platelet aggregation in experimental malaria.

Haemolytic anaemia associated with Nigerian barbecued meat (red suya).

Five cases of haemolytic anaemia occurring in male Nigerians following the ingestion of spiced barbecued meat (suya) are described. Although suya is a popular food item in various parts of Nigeria, all five patients described in this report had consumed a special brand, called red suya, purchased from vendors at a popular road junction between the cities of Lagos and Ibadan. Ingestion of the culprit suya sample was followed within 24 h by malaise and fever, while passage of dark-coloured urine and jaundice followed 1-3 days thereafter. Glucose-6-phosphate dehydrogenase (G6PD) deficiency was demonstrated by a fluorescent screening test in all cases, while the enzyme phenotype was shown to be GdA- in all four cases studied by starch-gel electrophoresis, thus suggesting that G6PD deficiency was a predisposing factor in the cases reported in this series. The haemolytic disease was self-limiting and full recovery followed in all cases. In view of the markedly circumscribed range from where the patients originated, the culprit agent responsible for the haemolytic disease is believed to be a recently introduced food additive that is probably accessible only to a limited number of suya vendors.