Systematic review and pooled analysis of survival outcomes in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia who have undergone haematopoietic stem cell transplant.

OBJECTIVE: Information about the long-term survival impact of hematopoietic stem cell transplant (HSCT) in adults with relapsed/refractory B-cell acute lymphoblastic leukaemia is limited. The objective was to conduct a systematic review identifying studies reporting survival in HSCT-receiving patients and apply parametric analyses to predict long-term survival. MATERIALS AND METHODS: Twenty-five relevant studies were identified. Analyses were conducted in 10 studies (n=503; "global" analysis) reporting overall survival (OS) data as Kaplan-Meier curves or at patient level. Four studies (n=217; "subgroup" analysis) measured OS from the point of HSCT. Patient-level data were recreated from Kaplan-Meier curves and pooled, with six models tested for longer-term extrapolation. Additionally, a sensitivity analysis was undertaken involving removal of data from the oldest study cohort (recruited between 1981-1997) to determine if the year which patients received HSCT impacted survival compared to post-2009 data. RESULTS: Median OS and five-year survival probability were 11.4 months and 24.4% (95% CI, 20.5-28.5%) in the global analysis, and 12.0 months and 28.4% (95% CI, 22.1-34.9%) in the subgroup analysis. The generalised gamma and Gompertz models fit longer-term extrapolation criteria. The generalised gamma model predicted survival at 10.4% vs. 14.8% (15 years), 8.3% vs. 12.8% (20 years), and 6.9% vs. 11.4% (25 years) for the global and subgroup analysis, respectively. The Gompertz model predicted survival to plateau at 23% vs. 25.6% just before 10 years. The sensitivity analysis excluding older data found median survival increased two-fold (25.3 vs. 12 months). CONCLUSIONS: Results synthesize long-term evidence of outcomes for HSCT-receiving patients, providing a basis for treatment comparison. Risk of death is low beyond four years and newer data appears correlated with improved outcomes.

Cost-Effectiveness of Inotuzumab Ozogamicin Compared to Standard of Care Chemotherapy for Treating Relapsed or Refractory Acute Lymphoblastic Leukaemia Patients in Norway and Sweden.

OBJECTIVE: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA). MATERIALS AND METHODS: A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed. RESULTS: The base case deterministic ICERs for InO versus SoC were €16,219/quality-adjusted life years (QALY) in Sweden (probabilistic €19,415) and €44,405/QALY in Norway (probabilistic €47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were €74,061/QALY (probabilistic €77,484) and €59,391/QALY (probabilistic €63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC. CONCLUSIONS: InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.

Increased paediatric presentations of severe diabetic ketoacidosis in an Australian tertiary centre during the COVID-19 pandemic.

AIMS: To determine if the frequency of severe diabetic ketoacidosis at presentation of new-onset type 1 diabetes to an Australian tertiary centre increased during the initial period of restrictions resulting from the COVID-19 pandemic (March to May 2020). METHODS: Data were collected on presentations of newly diagnosed type 1 diabetes as well as on all paediatric presentations to the emergency department of a tertiary centre between 2015 and 2020. Data from the period of initial COVID restrictions in Australia (March to May 2020) were compared to the period March to May of the previous 5 years (pre-pandemic periods). RESULTS: The number of new diagnoses of type 1 diabetes was comparable in the pandemic period and pre-pandemic periods (11 in 2020 vs range 6-10 in 2015-2019). The frequency of severe diabetic ketoacidosis was significantly higher in the pandemic period compared to the pre-pandemic periods (45% vs 5%; P <0.003), odds ratio 16.7 (95% CI 2.0, 194.7). The overall frequency of diabetic ketoacidosis was also significantly higher during the pandemic period (73% vs 26%; P <0.007), odds ratio 7.5 (95% CI 1.7, 33.5). None of the individuals tested positive for COVID-19. Presentations of people aged <18 years to the emergency department decreased by 27% in the pandemic period compared to the average of the pre-pandemic periods (4799 vs 6550; range 6268 to 7131). CONCLUSIONS: A significant increase in the frequency of severe diabetic ketoacidosis at presentation of type 1 diabetes was observed during the initial period of COVID-19 restrictions. We hypothesize that concern about presenting to hospital during a pandemic led to a delay in diagnosis. These data have important implications for advocacy of seeking healthcare for non-pandemic-related conditions during a global pandemic.

E-selectin ligands recognised by HECA452 induce drug resistance in myeloma, which is overcome by the E-selectin antagonist, GMI-1271.

Multiple myeloma (MM) is characterized by the clonal expansion and metastatic spread of malignant plasma cells to multiple sites in the bone marrow (BM). Recently, we implicated the sialyltransferase ST3Gal-6, an enzyme critical to the generation of E-selectin ligands, in MM BM homing and resistance to therapy. Since E-selectin is constitutively expressed in the BM microvasculature, we wished to establish the contribution of E-selectin ligands to MM biology. We report that functional E-selectin ligands are restricted to a minor subpopulation of MM cell lines which, upon expansion, demonstrate specific and robust interaction with recombinant E-selectin in vitro. Moreover, an increase in the mRNA levels of genes involved in the generation of E-selectin ligands was associated with inferior progression-free survival in the CoMMpass study. In vivo, E-selectin ligand-enriched cells induced a more aggressive disease and were completely insensitive to Bortezomib. Importantly, this resistance could be reverted by co-administration of GMI-1271, a specific glycomimetic antagonist of E-selectin. Finally, we report that E-selectin ligand-bearing cells are present in primary MM samples from BM and peripheral blood with a higher proportion seen in relapsed patients. This study provides a rationale for targeting E-selectin receptor/ligand interactions to overcome MM metastasis and chemoresistance.

The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Nanomorphology of polythiophene-fullerene bulk-heterojunction films investigated by structured illumination optical imaging and time-resolved confocal microscopy.

Structured illumination microscopy (SIM) and time-resolved confocal fluorescence microscopy are applied to investigate the nanomorphology of thin films comprising typical blends of the conjugated polymer, poly (3-hexylthiophene) (P3HT), and [6, 6]-phenyl C61-butyric acid methyl ester (PCBM), used for organic photovoltaic applications. SIM provides evidence for the presence of a thin emissive region around the crystalline regions of PCBM and at the tips of rod-like domains. The time-resolved measurements show that the emission surrounding the PCBM rods is longer lived than the bulk of the film. The two modes of microscopy provide complementary evidence indicating that electron-hole separation is inhibited between the polymer and the large PCBM-rich domains in these regions. We show here that structured illumination microscopy is a viable method of gaining additional information from these photovoltaic materials, despite their weak emission.

Multiphoton fluorescence lifetime imaging shows spatial segregation of secondary metabolites in Eucalyptus secretory cavities.

Multiphoton fluorescence lifetime imaging provides an excellent tool for imaging deep within plant tissues while providing a means to distinguish between fluorophores with high spatial and temporal resolution. Ideal candidates for the application of multiphoton fluorescence lifetime imaging to plants are the embedded secretory cavities found in numerous species because they house complex mixtures of secondary metabolites within extracellular lumina. Previous investigations of this type of structure have been restricted by the use of sectioned material resulting in the loss of lumen contents and often disorganization of the delicate secretory cells; thus it is not known if there is spatial segregation of secondary metabolites within these structures. In this paper, we apply multiphoton fluorescence lifetime imaging to investigate the spatial arrangement of metabolites within intact secretory cavities isolated from Eucalyptus polybractea R.T. Baker leaves. The secretory cavities of this species are abundant (up to 10 000 per leaf), large (up to 6 nL) and importantly house volatile essential oil rich in the monoterpene 1,8-cineole, together with an immiscible, non-volatile component comprised largely of autofluorescent oleuropeic acid glucose esters. We have been able to optically section into the lumina of secretory cavities to a depth of ∼80 µm, revealing a unique spatial organization of cavity metabolites whereby the non-volatile component forms a layer between the secretory cells lining the lumen and the essential oil. This finding could be indicative of a functional role of the non-volatile component in providing a protective region of low diffusivity between the secretory cells and potentially autotoxic essential oil.

Predicting tumour response to anti-HER1 therapy using medical imaging: a literature review and in vitro study of [18F]-FDG incorporation by breast cancer cells responding to cetuximab.

Cetuximab, an anti-HER1 (EGFR) antibody, is currently under trial for the treatment of breast cancer. HER1 expression is not necessarily a predictor of response to cetuximab as mutant components of the pathways activated by HER1 which include PI3K/Akt can lead to resistance. Techniques that monitor events downstream of HER1 are more likely to provide an accurate measure of the efficacy of an anti-HER1 treatment. Glucose metabolism has been shown to be strongly influenced by the state of activation of PI3K/Akt. Here, the association between [18F]-FDG incorporation in breast cancer cells during response to cetuximab is investigated. The study also reviews the development of medical imaging probes that target HER1 The sensitivity to cetuximab of three breast tumour cell lines, SKBr3, MDA-MB-453 and MDA-MB-468, expressing HER1 at low and high levels, are determined using an MTT assay over a six-day period and a clonogenic assay carried out after seven- and 10-day exposures. Incorporation of FDG by cells treated with growth inhibitory doses of cetuximab were carried out after 4 hand two, four and six days of treatment. Glucose transport (rate of uptake of the non-metabolisable analogue [3H]o-methyl-D-glucose), hexokinase activity and lactate production were measured on cells treated with inhibitory doses of cetuximab for six days. The IC50, dose for MDA-MB-468 cells and the IC10 (maximum achievable inhibition) doses for MDA-MB-543 and SKBr3 treated with cetuximab for six days were 2.6, 5 and 148 microg/mL, respectively. Incorporation of FDG by SKBr3 and MDA-MB-453 cells was found to be decreased by MDA-MB468 cells using IC50, and IC20, doses of cetuximab for six days. Lactate production was found to be increased by MDA-MB-468 cells responding to cetuximab. Incorporation of FDG at the tumour cell level is modulated by treatment with growth inhibitory doses of cetuximab in cells sensitive to cetuximab due to modulation of HK activity.

AFLPs support deep relationships among darters (Percidae: Etheostomatinae) consistent with morphological hypotheses.

Recent attention has focused on the efficacy of amplified fragment length polymorphisms (AFLPs) for resolving deep evolutionary relationships. Here we show that AFLPs provide resolution of deep relationships within the family Percidae that are more consistent with previous morphological hypotheses than are relationships proposed by previous molecular analyses. Despite in silico predictions, we were able to resolve relatively ancient divergences, estimated at >25 MA. We show that the most distantly related species share the fewest fragments, but suggest that large data sets and extensive taxon sampling are sufficient to overcome this obstacle of the AFLP technique for deep divergences. We compare genetic distances estimated from mitochondrial DNA with those from AFLPs and contrast traditional PAUP(*) Nei-Li AFLP genetic distances with a recently proposed method utilizing the Dice equation with constraining nucleotides.

[F]fluoro-2-deoxy-d-glucose incorporation by mcf-7 breast tumour cells in vitro is modulated by treatment with tamoxifen, Doxorubicin, and docetaxel: relationship to chemotherapy-induced changes in ATP content, hexokinase activity, and glucose transport.

Breast tumours responding to chemotherapy exhibit decreased [(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) incorporation. Underlying mechanisms of these changes is poorly understood. Here, in MCF-7 cells, responding to chemotherapy drugs commonly utilised in the treatment of breast cancer, [(18)F]FDG incorporation and several pivotal factors associated with [(18)F]FDG incorporation investigated. Methods. IC50 and subclinical doxorubicin, docetaxel, and tamoxifen doses determined using MTT assay. [(18)F]FDG incorporation by cells treated with IC50 drug doses for 48 hours and 72 hours were determined and FDG dephosphorylation estimated by measuring loss of 18F from [(18)F]FDG-preincubated cells (pulse-chase). Glucose transport determined by measuring initial uptake rate of non-metabolised glucose analogue omethylglucose; hexokinase activity and ATP content measured in cell homogenates; Cell cycle distribution determined using flow cytometry of propidium iodide stained nuclei. Results. [(18)F]FDG incorporation and ATP content decreased in cells after 72 hours treatment with IC50 doses of tamoxifen, doxorubicin, and docetaxel compared with untreated controls. Decreased glucose transport and/or hexokinase activity accompanied decreased [(18)F]FDG incorporation by MCF-7 cells treated with tamoxifen or doxorubicin but not docetaxel. Conclusions. Tumour cell [(18)F]FDG incorporation along with ATP content decreased by treatment with tamoxifen, doxorubicin and docetaxel paralleling clinical observations for solid tumours. Effect of each treatment on glucose transport and hexokinase activity was chemotherapy-drug dependent.

Towards detecting the HER-2 receptor and metabolic changes induced by HER-2-targeted therapies using medical imaging.

HER-2/neu (a receptor for human epidermal growth factor) is involved in cell survival, proliferation, angiogenesis and invasiveness. It is overexpressed in about 25% of breast cancers. Overexpression of HER-2 is associated with response to the anti-HER-2 antibody trastuzumab (herceptin). However, HER-2 expression can be heterogeneous within the primary tumour and can also exhibit discordant expression between a primary tumour and its metastases, bringing into question the practice of HER-2 screening to determine whether a patient is a candidate for trastuzumab using material obtained only from the primary tumour. Medical imaging modalities using HER-2-targeted tracers (or contrast agents) facilitate a global approach to the determination of HER-2 expression across all detectable tumour lesions, and could provide a more reliable indication of the patient's likely response to trastuzumab treatment. Here, I review the development and pre-clinical (and occasional clinical) assessment of HER-2-targeted tracers. I discuss studies in which established imaging tracers, such as (11)C-choline, have been used to determine response to trastuzumab in a range of medical imaging modalities, including positron emission tomography (PET), single photon emission tomography (SPECT), MRI and optical imaging.

Biomarkers of in vivo fertility in sperm and seminal plasma of fertile stallions.

The global proteome of sperm and seminal plasma of fertile stallions was investigated to determine whether associations with relative in vivo fertility exist. Seven stallions at stud in a commercial breeding station were collected throughout the breeding season and bred to a total of 164 mares to determine conception rates. On three occasions during the breeding season, raw semen was obtained from a regular collection for proteomic analysis using two-dimensional electrophoresis and also assessed for routine semen quality end points. First cycle conception rate was negatively related to ejaculate volume (r = -0.43, P = 0.05) and total IGF1 content (ng) per ejaculate (r = -0.58, P = 0.006), whereas overall pregnancy rate was positively related to sperm concentration (r = 0.56, P = 0.01). The abundance of three proteins known to be involved in carbohydrate metabolism in sperm was positively related to fertility. Furthermore, the abundance of four seminal plasma proteins were identified as being negatively related to fertility; these were identified as kallikrein-1E2 (KLK2), clusterin, and seminal plasma proteins 1 (SP1) and 2 (SP2). Abundance of cysteine-rich secretory protein 3 (CRISP3) was positively related to first cycle conception rate (r = 0.495, P = 0.027) and may provide a good marker of fertility. Based on stepwise regression analysis, clusterin and SP1 in seminal plasma together with sperm citrate synthase were predictive of fertility (r = 0.77, P < 0.0001). This study identified proteins within sperm and seminal plasma that could serve as biomarkers of semen quality and fertility in stallions.

Navigating transdermal diffusion with multiphoton fluorescence lifetime imaging.

We demonstrate the potential of fluorescence lifetime imaging by time-correlated single-photon counting as a method for monitoring the transdermal diffusion pathway and diffusion rate of pharmaceuticals in human skin. The current application relies on observing subtle changes in the fluorescence lifetime of the intrinsic fluorophores present in the intracellular region between corneocytes of the stratum corneum. We have comprehensively characterized the measured fluorescence lifetimes from intracorneocyte junctions in three skin section types (dermatomed skin, epidermal membranes and stratum corneum) revealing statistically significant differences of the short lifetime component between each of the types, which we attribute to the sample preparation and imaging method. We show using epidermal membrane sections that application of a drug/solvent formulation consisting of ethinyl estradiol and spectroscopic grade ethanol to the surface gives rise to a slight but statistically significant shortening of the fluorescence lifetime of the long-lived emitting species present in the sample, from approximately 2.8 ns to 2.5 ns. The method may be useful for future studies where the kinetics and pathways of a variety of applied formulations could be investigated.

Cost-sharing strategies combining targeted public subsidies with private-sector delivery achieve high bednet coverage and reduced malaria transmission in Kilombero Valley, southern Tanzania.

BACKGROUND: Cost-sharing schemes incorporating modest targeted subsidies have promoted insecticide-treated nets (ITNs) for malaria prevention in the Kilombero Valley, southern Tanzania, since 1996. Here we evaluate resulting changes in bednet coverage and malaria transmission. METHODS: Bednets were sold through local agents at fixed prices representing a 34% subsidy relative to full delivery cost. A further targeted subsidy of 15% was provided to vulnerable groups through discount vouchers delivered through antenatal clinics and regular immunizations. Continuous entomological surveys (2,376 trap nights) were conducted from October 2001 to September 2003 in 25 randomly-selected population clusters of a demographic surveillance system which monitored net coverage. RESULTS: Mean net usage of 75% (11,982/16,086) across all age groups was achieved but now-obsolete technologies available at the time resulted in low insecticide treatment rates. Malaria transmission remained intense but was substantially reduced: Compared with an exceptionally high historical mean EIR of 1481, even non-users of nets were protected (EIR [fold reduction] = 349 infectious bites per person per year [x4]), while the average resident (244 [x6]), users of typical nets (210 [x7]) and users of insecticidal nets (105 [x14]) enjoyed increasing benefits. CONCLUSION: Despite low net treatment levels, community-level protection was equivalent to the personal protection of an ITN. Greater gains for net users and non-users are predicted if more expensive long-lasting ITN technologies can be similarly promoted with correspondingly augmented subsidies. Cost sharing strategies represent an important option for national programmes lacking adequate financing to fully subsidize comprehensive ITN coverage.

[18F]2-fluoro-2-deoxy-D-glucose incorporation by AGS gastric adenocarcinoma cells in vitro during response to epirubicin, cisplatin and 5-fluorouracil.

Decreased tumour [(18)F]2-fluoro-2-deoxy-D-glucose ((18)FDG) incorporation is related to response however its significance at the cell level in gastro-oesophageal cancer and how it relates to cell death is unknown. Here human gastric adenocarcinoma (AGS) cells were treated with lethal dose 10 and 50 (LD(10) and LD(50)), determined by using the MTT assay, of the three drugs, epirubicin, 5-fluorouracil and cisplatin, commonly used in the treatment of patients with gastro-oesophageal cancer. (18)FDG incorporation was determined after 48 and 72 h of treatment with each drug and related to drug-induced changes in glucose transport, hexokinase activity, cell cycle distribution and annexin V-PE binding (a measure of apoptosis). Treatment of cells for 48 and 72 h with LD(50) doses of cisplatin resulted in reductions in (18)FDG incorporation of 27 and 25% respectively and of 5-fluorouracil reduced (18)FDG incorporation by 34 and 33% respectively: epirubicin treatment reduced incorporation by 30 and 69% respectively. Cells that had been treated for 72 h with each drug were incubated in drug-free media for a further 6 days to determine their ability to recover. Comparison of the ability to recover from the chemotherapy agent, with (18)FDG incorporation before the recovery period allowed an assessment of the predictive ability of (18)FDG incorporation. Cells treated with either 5-fluorouracil or cisplatin demonstrated recovery on removal of the drug. In contrast, cells treated with epirubicin did not recover corresponding with the greatest 72 h treatment decrease in (18)FDG incorporation. In contrast to adherent cells treated with cisplatin or 5-fluorouracil, adherent epirubicin-treated cells also exhibited very high levels of apoptosis. Glucose transport was decreased after each treatment whilst hexokinase activity was only decreased after 72 h of treatment with each drug. There was no consistent relationship observed between (18)FDG incorporation and cell cycle distribution. Our results show that at the tumour cell level in gastric tumour cells, decreased (18)FDG incorporation and glucose transport, accompanies therapeutic growth inhibition. (18)FDG incorporation is particularly diminished in cells exhibiting apoptosis.

[Prevalence, genetic diversity and multiplicity of Plasmodium falciparum infection in school children in central Cote d'Ivoire]. / Prevalence, diversité antigénique et multiplicité d'infections de Plasmodium falciparum en milieu scolaire au centre de la Côte d'Ivoire.

A study was carried out in the village of Taabo, located in the vicinity of a large man-made lake in central Côte d'Ivoire. The objectives were (i) to determine the level of prevalence, genetic diversity and multiplicity of Plasmodiumfakiparum infection in schoolchildren and (ii) to compare the diagnostic performance of light microscopy and polymerase chain reaction (PCR). A total of 424 schoolchildren ranging in age from 5 to 15 years underwent diagnostic testing using both light microscopy of blood smears and PCR. Multiplicity of P. falciparum infection was investigated in 196 children (46.2%). The prevalence of malaria was 54.7% based on light microscopy and 83.9% based on PCR. Genotyping based on polymorphism in the length of the restriction fragment of the gene encoding the merozoite surface protein-2 (msp2) showed that 86.5% of cases involved multiple infection with a geometric mean of 3.87 genotypes per positive child. There was a strong positive correlation between multipcity of infection and parasite density in the 56-year old age group. A total of 50 genotypes including six observed for the first time were identified and classified into families with similar-sized sequence groups: 26 x FC27 (52%) and 24 x 3D7 (48%). In comparison with PCR, the sensitivity and specificity of light microscopy for diagnosis of P. falciparum was 81.3% and 88.2% respectively. Data are discussed in the light of similar studies carried out in sub-Saharan Africa and elsewhere. These findings can serve as a basis for monitoring the longterm effect of major water resource management projects on the prevalence, genetic diversity and multiplicity of P. falciparum infection.

Prevalence; diversite antigenique et multiplicite d'infections de Plasmodium falciparum en milieu scolaire au centre de la Cote d'Ivoire

Une etude a ete conduite a Taabo - village; localite rurale du centre de la Cote d'Ivoire; situee a proximite d'un gra n d lac artificiel. Les objectifs etaient (i) de determiner le taux d'endemicite du paludisme; la diversite antigenique et la multiplicite des infections a Plasmodium falciparum au sein d'ecoliers; et (ii) de comparer la performance du diagnostic microscopique a celle de la reaction de polymerisation en chaine (PCR). Au total; 424 eleves ages de 5 a 15 ans ont eu des examens de sang au microscope et par PCR. La multiplicite d'infection a porte sur 196 (46;2) d'entre eux. L'indice plasmodique detecte au micro s c o p e est de 54;7et de 83;9par PCR. Les typages genotypiques determines par le polymorphisme des longueurs de fragments de restriction du gene respon sable des proteines de surface-2 du mero zoite (m s p 2); ont revele 86;5de cas d'infections multipes; avec une moyenne geometrique de 3;87 genotypes par individu positif. Une correlation positive significative a ete obtenue entre a multiplicite et les densites parasitaires au sein du groupe d'age 5-6 ans. 50 genotypes dont six observes pour la premiere fois ont ete denombres puis classes en familles de tailles similaires FC27 (n=26 ; 52) et 3D7 (n=24 ; 48). Compare a la PCR; la microscopie a montre une sensibilite et une specificite respectivement de 81;3et 88;2. Nos donnees sont discutees au regard d'etudes similaires en Afrique sub-saharienne et ailleurs; et peuvent servir de base a long terme pour l'evaluation d'impact des grands amenagements d'eau sur la prevalence; la diversite antigenique et la multiplicite des infections a P. fal c i p a ru m

Code of practice for food handler activities.

BACKGROUND: The food industry regulates various aspects of food handler activities, according to legislation and customer expectations. The purpose of this paper is to provide a code of practice which delineates a set of working standards for food handler hygiene, handwashing, use of protective equipment, wearing of jewellery and body piercing. METHODS: The code was developed by a working group of occupational physicians with expertise in both food manufacturing and retail, using a risk assessment approach. Views were also obtained from other occupational physicians working within the food industry and the relevant regulatory bodies. The final version of the code (available in full as Supplementary data in Occupational Medicine Online) therefore represents a broad consensus of opinion. CONCLUSION: The code of practice represents a set of minimum standards for food handler suitability and activities, based on a practical assessment of risk, for application in food businesses. It aims to provide useful working advice to food businesses of all sizes.

Human serum transferrin cobalt complex: stability and cellular uptake of cobalt.

Transferrin (Tf) receptor expression is up-regulated on tumour cells. The human serum iron transport protein transferrin (Tf) can bind to many metals including gallium and cobalt. Cobalt has a positron-emitting isotope with a half-life of 18 h and would thus be a useful isotope for imaging purposes. This study has examined the stability of the Co-Tf in the presence of serum and albumin and the uptake of radioactive Co from Co-Tf by tumour cells. Dialysis of 57Co-Tf with serum or with apo-Tf resulted in loss of most 57Co from the complex. The time course of Co uptake from cells incubated with Co-Tf showed an initial rapid association with cells, then a slower rate of accumulation, that is, a similar uptake profile to that of iron. Competition and displacement experiments showed that uptake specifically occurred by interaction with Tf receptors.