Assessement of Malaria Transmission in an Area with Very Low Mosquito Density

The increase in world travel in recent years, especially to and from areas where vector-borne diseases are endemic, has resulted in a substantial rise in imported cases of those diseases. In particular, malaria is a cause of concern. In those countries at the edge of its distribution, it can be difficult to distinguish between autochthonous and imported cases. However, distinguishing between the two is important because of the different allocation of resources to combat the disease that each requires. In general, observation of the various stages of parasite development in wild-caught female mosquitoes is considered evidence of autochthonous transmission. Observation of oocysts in the mosquito mid-gut testifies that mosquitoes are susceptible to infection but conclusions cannot be reached about their ability to complete the transmission cycle. Perhaps the best indication of autochthonous transmission is microscopic observation of sporozoites in mosquito salivary glands, since this detects parasites ready to be inoculated (BELER et al., 1990). Detection of circumsporozoite protein (CSP)(BURKOT, WILLIAMS & SCHNEIDER, 1984) in dry mosquito thoraxes, by Enzyme Linked Immunosorbent Assay (ELISA) is also widely used to determine transmission, especially when large numbers of mosquitoes need to be processed. Such assays provide information about the parasite species infecting the mosquito (BURKOT & WIRTZ, 1986; WIRTZ et al., 1987; BELER et al., 1990).

Responsiveness of astrocytes in serum-free aggregate cultures to epidermal growth factor: dependence on the cell cycle and the epidermal growth factor concentration.

Serum-free aggregating cell cultures of fetal rat telencephalon treated with low doses (0.5 nM) of epidermal growth factor (EGF) showed a small, transient increase in DNA synthesis but no significant changes in total DNA and protein content. By contrast, treatment with high doses (13 nM) of EGF caused a marked stimulation of DNA synthesis as well as a net increase in DNA and protein content. The expression of the astrocyte-specific enzyme, glutamine synthetase, was greatly enhanced both at low and at high EGF concentrations. These results suggest that at low concentration EGF stimulates exclusively the differentiation of astrocytes, whereas at high concentration, EGF has also a mitogenic effect. Nonproliferating astrocytes in cultures treated with 0.4 microM 1-beta-D-arabinofuranosyl-cytosine were refractory to EGF treatment, indicating that their responsiveness to EGF is cell cycle-dependent. Binding studies using a crude membrane fraction of 5-day cultures showed a homogeneous population of EGF binding sites (Kd approximately equal to 2.6 nM). Specific EGF binding sites were found also in non-proliferating (and nonresponsive) cultures, although they showed slightly reduced affinity and binding capacity. This finding suggests that the cell cycle-dependent control of astroglial responsiveness to EGF does not occur at the receptor level. However, it was found that the specific EGF binding sites disappear with progressive cellular differentiation.

5-Azacytidine to Treat Acute Myeloid Leukemia In Elderly or Frail Patients: A Phase II Study (SAKK 30/07).

Background: Acute Myeloid Leukemia (AML) in the elderly is notoriously difficult to treat and has a low remission rate with very few long term survivors when using standard treatment approaches. Azacytidine, a hypomethylating agent, has been shown to induce remission and prolong survival in patients with myelodysplastic syndromes; studying this approach to patients with AML is therefore warranted. We present results of an ongoing phase II trial treating elderly or frail AML patients with Azacytidine. Methods: AML elderly or frail patients, and therefore unfit for an intensive chemotherapy regimens, with a WHO performance status 3 were considered for this trial. Trial therapy consisted of 100mg/m2 of Azacytidine injected subcutaneously on 5 consecutive days every 28 days up to 6 cycles, stopping at 6 months if no hematological improvement achieved, or earlier in the case of progression or complications. Treatment was continued beyond 6 months in responding patients. Trial therapy was considered uninteresting if the response rate (CR + PR) within 6 months of therapy initiation was 15% or less and promising if 34% or more. Using the exact single-stage phase II design by A'Hern with a 5% significance level and 90% power, 43 patients were required: If 10 or fewer achieved a response within 6 months the trial therapy should not be considered for further investigation in its current format for this indication and patient population. Results: Between September 2008 and January 2010, 45 evaluable patients across 10 Swiss centers were accrued with a median follow-up of 7 months (range: 0 - 13). 27 (60%) were male, median age was 74 (range: 55 - 86) years and 35 (78.8%) had performance status 0-1. Patients had been excluded from more intensive chemotherapy regimens because of age (n = 37) or due to comorbidities or patient refusal (n=8). Five patients had therapy related AML. Patients received a median of 3 (range: 1 - 10) cycles. Treatment was stopped for not achieving a response by the 6th cycle in 2 patients and earlier in 26 patients (for disease progression in 5, toxicity in 3, patient refusal in 2, recurrent infections in 1, and death in 8). Seventeen patients remain on therapy. The median time spent in the hospital was 12 days (1 - 30) in 24/38 patients hospitalized during the first treatment cycle and 13 days (2 - 28) in 15/31 patients hospitalized during subsequent cycles. Adverse events of grade III or higher most frequently reported were constitutional or hematologic, i.e. fatigue in 5, febrile neutropenia in 8, infections in 6, dyspnea in 6, anemia in 3, neutropenia in 12 and thrombocytopenia in 10, hemorrhage in 2 and retinal detachment in 5. Based on available data on 38 patients, CR/CRi or hematologic improvement or stable disease within 6 months of trial registration was observed in a proportion of patients. Final and mature data, determining whether the predefined proportion of responding patients has been reached or not, will be presented at the conference. Up to now there were a total of 26 deaths. Median overall survival time was 5.7 months (95% CI: 3.1, 8.7). Conclusions: The current results of this slightly modified Azacytidine schedule demonstrate a feasible new therapy option for elderly or frail AML patients in an outpatient setting with moderate, mainly hematologic toxicity.

A low-dose stimulation protocol using highly purified follicle-stimulating hormone can lead to high pregnancy rates in in vitro fertilization patients with polycystic ovaries who are at risk of a high ovarian response to gonadotropins.

OBJECTIVE: To study the benefits of a low-dose stimulation (LDS) protocol with purified urinary follicle-stimulating hormone in patients with polycystic ovaries who have presented previously with a very high ovarian response to a standard hMG stimulation. DESIGN: Cohort study. SETTING: Fertility center in a university hospital. PATIENT(S): Sixty-one patients involved in an IVF/ICSI program from January 1995 to December 1996. INTERVENTION(S): The patients were first stimulated with a standard protocol using hMG and presented with a very high ovarian response. These patients were then stimulated a second time using a low-dose protocol. Cryopreserved embryos were transferred in later artificial or natural cycles until to December 1999. MAIN OUTCOME MEASURE(S): Number of gonadotropin ampules; estradiol level on the day of ovulation induction; follicles, oocytes, and cryopreserved zygotes; fertilization, implantation, and pregnancy rates; and number of ovarian hyperstimulation syndromes (OHSS). RESULT(S): The number of ampules used, the estradiol level reached, and the number of oocytes obtained were significantly lower under the LDS than the standard protocol. High implantation (21.8%) and clinical pregnancy (38.4%) rates were obtained after LDS. The cumulated deliveries per cycle started and per patient were, respectively, 41.6% and 52.5%. Five patients suffered OHSS with the standard protocol, and none with the LDS. CONCLUSION(S): The LDS protocol offers a safe and efficient treatment for patients who present with echographic polycystic ovaries and are at risk of an excessive ovarian response to standard IVF stimulation protocols.

Radar analysis of the life cycle of mesoscale convective systems during the 10 June 2000 event

The 10 June 2000 event was the largest flash flood event that occurred in the Northeast of Spain in the late 20th century, both as regards its meteorological features and its considerable social impact. This paper focuses on analysis of the structures that produced the heavy rainfalls, especially from the point of view of meteorological radar. Due to the fact that this case is a good example of a Mediterranean flash flood event, a final objective of this paper is to undertake a description of the evolution of the rainfall structure that would be sufficiently clear to be understood at an interdisciplinary forum. Then, it could be useful not only to improve conceptual meteorological models, but also for application in downscaling models. The main precipitation structure was a Mesoscale Convective System (MCS) that crossed the region and that developed as a consequence of the merging of two previous squall lines. The paper analyses the main meteorological features that led to the development and triggering of the heavy rainfalls, with special emphasis on the features of this MCS, its life cycle and its dynamic features. To this end, 2-D and 3-D algorithms were applied to the imagery recorded over the complete life cycle of the structures, which lasted approximately 18 h. Mesoscale and synoptic information were also considered. Results show that it was an NS-MCS, quasi-stationary during its stage of maturity as a consequence of the formation of a convective train, the different displacement directions of the 2-D structures and the 3-D structures, including the propagation of new cells, and the slow movement of the convergence line associated with the Mediterranean mesoscale low.

Serum glycodelin pattern during the menstrual cycle in healthy young women.

OBJECTIVE: Glycodelin (PP14) is produced by the epithelium of the endometrium and its determination in the serum is used for functional evaluation of this tissue. Given the complex regulation and the combined contraceptive and immunosuppressive roles of glycodelin, the current lack of normal values for its serum concentration in the physiological menstrual cycle, derived from a large sample number, is a problem. We have therefore established reference values from over 600 sera. DESIGN: Retrospective study using banked serum samples. SETTING: University hospital. METHODS: Measurement of blood samples daily or every second day during one full cycle. MAIN OUTCOME MEASURES: Serum concentrations of glycodelin and normal values for every such one- or two-day interval were calculated. Late luteal phase glycodelin levels were compared with ovarian hormones. Follicular phase levels were compared with stimulated cycles from patients undergoing in vitro fertilization. RESULTS: Glycodelin concentrations were low around ovulation. Highest levels were observed at the end of the luteal phase; the glycodelin serum peak was reached 6-8 days after the one for progesterone. Late luteal glycodelin levels correlated negatively with the body mass index and positively with the progesterone level earlier in the secretory (mid-luteal) phase in the same woman. No associations with other ovarian hormones were observed. Follicular phase glycodelin levels were higher in the spontaneous than in the in vitro fertilization cycles. CONCLUSIONS: Normal values taken at two- or one-day intervals demonstrate the very late appearance of high serum glycodelin levels during the physiological menstrual cycle and their correlation with progesterone occurring earlier in the cycle.

Frequency, characterisation and therapies of fatigue after stroke.

Post-stroke objective or subjective fatigue occurs in around 50% of patients and is frequent (30%) even after minor strokes. It can last more than one year after the event, and is characterised by a different quality from usual fatigue and good response to rest. Associated risk factors include age, single patients, female, disability, depression, attentional impairment and sometimes posterior strokes, but also inactivity, overweight, alcohol and sleep apnoea syndrome. There are few therapy studies, but treatment may include low-intensity training, cognitive therapy, treatment of associated depression, wakefulness-promoting agents like modafinil, correction of risk factors and adaptation of activities.

The activity of S.pombe DSC-1-like factor is cell cycle regulated and dependent on the activity of p34cdc2.

In the eukaryotic cell cycle, there are major control points in late G2 to determine the timing of the initiation of mitosis, and in late G1, regulating entry into S phase. In yeasts, this latter control is called start. Traverse of the start control and progression to S phase is accompanied by an increase in the expression of some of the genes whose products are required for DNA synthesis. In Saccharomyces cerevisiae, the coordinate expression of these genes in late G1 is dependent on a cis-acting sequence element called the MluI cell cycle box (MCB). A transcription factor called DSC-1 binds these elements and mediates cell cycle regulated transcription, though it is unclear whether this is by cell cycle-dependent changes in its activity. A DSC-1-like factor has also been identified in the fission yeast S.pombe. This is composed of at least the products of the cdc10 and sct1/res1 genes, and binds to the promoters of genes whose expression increases prior to S phase. We demonstrate that p85cdc10 is a nuclear protein and that the activity of the S.pombe DSC-1 factor varies through the cell cycle; it is high in cells that have passed start, decreases at the time of anaphase, remains low during the pre-start phase of G1 and increases at the time of the next S phase. We also show that the reactivation in late G1 is dependent on the G1 form of p34cdc2.

Fatigue shifts and scatters heart rate variability in elite endurance athletes

PURPOSE: This longitudinal study aimed at comparing heart rate variability (HRV) in elite athletes identified either in 'fatigue' or in 'no-fatigue' state in 'real life' conditions. METHODS: 57 elite Nordic-skiers were surveyed over 4 years. R-R intervals were recorded supine (SU) and standing (ST). A fatigue state was quoted with a validated questionnaire. A multilevel linear regression model was used to analyze relationships between heart rate (HR) and HRV descriptors [total spectral power (TP), power in low (LF) and high frequency (HF) ranges expressed in ms(2) and normalized units (nu)] and the status without and with fatigue. The variables not distributed normally were transformed by taking their common logarithm (log10). RESULTS: 172 trials were identified as in a 'fatigue' and 891 as in 'no-fatigue' state. All supine HR and HRV parameters (Beta+/-SE) were significantly different (P<0.0001) between 'fatigue' and 'no-fatigue': HRSU (+6.27+/-0.61 bpm), logTPSU (-0.36+/-0.04), logLFSU (-0.27+/-0.04), logHFSU (-0.46+/-0.05), logLF/HFSU (+0.19+/-0.03), HFSU(nu) (-9.55+/-1.33). Differences were also significant (P<0.0001) in standing: HRST (+8.83+/-0.89), logTPST (-0.28+/-0.03), logLFST (-0.29+/-0.03), logHFST (-0.32+/-0.04). Also, intra-individual variance of HRV parameters was larger (P<0.05) in the 'fatigue' state (logTPSU: 0.26 vs. 0.07, logLFSU: 0.28 vs. 0.11, logHFSU: 0.32 vs. 0.08, logTPST: 0.13 vs. 0.07, logLFST: 0.16 vs. 0.07, logHFST: 0.25 vs. 0.14). CONCLUSION: HRV was significantly lower in 'fatigue' vs. 'no-fatigue' but accompanied with larger intra-individual variance of HRV parameters in 'fatigue'. The broader intra-individual variance of HRV parameters might encompass different changes from no-fatigue state, possibly reflecting different fatigue-induced alterations of HRV pattern.

Investigation of Two Bridge Alternatives for Low Volume Roads - Phase II Volume 1 of 2 Concept 1: Steel Beam Precast Units, TR-410, 2000

This project continues the research which addresses the numerous bridge problems on the Iowa secondary road system. It is a continuation (Phase 2) of Project HR-382, in which two replacement alternatives (Concept 1: Steel Beam Precast Units and Concept 2: Modification of the Benton County Beam-in-Slab Bridge) were investigated. In previous research for concept 1, a precast unit bridge was developed through laboratory testing. The steel-beam precast unit bridge requires the fabrication of precast double-tee (PCDT) units, each consisting of two steel beams connected by a reinforced concrete deck. The weight of each PCDT unit is minimized by limiting the deck thickness to 4 in., which permits the units to be constructed off-site and then transported to the bridge site. The number of units required is a function of the width of bridge desired. Once the PCDT units are connected, a cast-in-place reinforced concrete deck is cast over the PCDT units and the bridge railing attached. Since the steel beam PCDT unit bridge design is intended primarily for use on low-volume roads, used steel beams can be utilized for a significant cost savings. In previous research for concept 2, an alternate shear connector (ASC) was developed and subjected to static loading. In this investigation, the ASC was subjected to cyclic loading in both pushout specimens and composite beam tests. Based on these tests, the fatigue strength of the ASC was determined to be significantly greater than that required in typical low volume road single span bridges. Based upon the construction and service load testing, the steel-beam precast unit bridge was successfully shown to be a viable low volume road bridge alternative. The construction process utilized standard methods resulting in a simple system that can be completed with a limited staff. Results from the service load tests indicated adequate strength for all legal loads. An inspection of the bridge one year after its construction revealed no change in the bridge's performance. Each of the systems previously described are relatively easy to construct. Use of the ASC rather than the welded studs significantly simplified the work, equipment, and materials required to develop composite action between the steel beams and the concrete deck.

Investigation of Two Bridge Alternatives for Low Volume Roads - Phase II Volume 2 of 2, Concept 2: Beam in Slab Bridge, TR-410, 2000

This project continues the research which addresses the numerous bridge problems on the Iowa secondary road system. It is a continuation (Phase 2) of Project HR-382, in which two replacement alternatives (Concept 1: Steel Beam Precast Units and Concept 2: Modification of the Benton County Beam-in-Slab Bridge) were investigated. In previous research for concept 1, a precast unit bridge was developed through laboratory testing. The steel-beam precast unit bridge requires the fabrication of precast double-tee (PCDT) units, each consisting of two steel beams connected by a reinforced concrete deck. The weight of each PCDT unit is minimized by limiting the deck thickness to 4 in., which permits the units to be constructed off-site and then transported to the bridge site. The number of units required is a function of the width of bridge desired. Once the PCDT units are connected, a cast-in-place reinforced concrete deck is cast over the PCDT units and the bridge railing attached. Since the steel beam PCDT unit bridge design is intended primarily for use on low-volume roads, used steel beams can be utilized for a significant cost savings. In previous research for concept 2, an alternate shear connector (ASC) was developed and subjected to static loading. In this investigation, the ASC was subjected to cyclic loading in both pushout specimens and composite beam tests. Based on these tests, the fatigue strength of the ASC was determined to be significantly greater than that required in typical low volume road single span bridges. Based upon the construction and service load testing, the steel-beam precast unit bridge was successfully shown to be a viable low volume road bridge alternative. The construction process utilized standard methods resulting in a simple system that can be completed with a limited staff. Results from the service load tests indicated adequate strength for all legal loads. An inspection of the bridge one year after its construction revealed no change in the bridge's performance. Each of the systems previously described are relatively easy to construct. Use of the ASC rather than the welded studs significantly simplified the work, equipment, and materials required to develop composite action between the steel beams and the concrete deck.

Low temperature impact on photosynthetic parameters of coffee genotypes

The objective of this work was to evaluate photoprotective mechanisms related to low positive temperatures in Coffea canephora (Conilon clones 02 and 153) and C. arabica ('Catucaí' IPR 102) genotypes, involved in cold temperature tolerance. To accomplish this, one-year-old plants were successively submitted to: temperature decrease of 0.5ºC day-1, from 25/20ºC to 13/8ºC; a three-day chilling cycle at 13/4ºC; and a recovery period of 14 days (25/20ºC). During the experiment, leaf gas exchange, chlorophyll a fluorescence and leaf photosynthetic pigment content were evaluated. Total activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and ribulose-5-phosphate kinase (Ru5PK) were quantified to measure the activity of photosynthesis key enzymes. All genotypes showed low temperature sensitivity, but displayed diverse cold impact and recovery capabilities regarding the photosynthetic-related parameters studied. Catucaí IPR 102 cultivar showed better ability to cope with cold stress than the Conilon clones, especially Conilon 02, and had full recovery of leaf gas exchange, fluorescence parameters, enzymatic activity, and higher contents of the photoprotective pigments zeaxanthin and lutein.

Association of poorly controlled diabetes with low serum leptin in morbid obesity.

OBJECTIVES: Leptin may be involved in the regulation of body weight, food intake, and energy expenditure. In view of a possible link between leptin concentrations and diabetes that has been suggested in obese rodents, we investigated the potential relationship between serum leptin concentrations and hyperglycaemia in French patients with morbid obesity. SUBJECTS: Fasting leptin concentrations were measured in 241 morbidly obese patients with various degrees of glucose tolerance in a cross-sectional study. RESULTS: Fasting serum leptin concentrations did not differ between normoglycaemia (NG, 61.5 +/- 24.0 ng/ml) and glucose intolerant morbidly obese subjects (IGT, 56.5 +/- 18.5 ng/ml) and were slightly lower in those with controlled diabetes (55.1 +/- 30.3 ng/ml, P = 0.06 when compared to NG subjects). In contrast, leptin concentrations were 30% lower in patients with poorly controlled diabetes (43.0 +/- 22.2 ng/ml, P = 0.001 vs NG subjects). Leptin concentrations were negatively correlated with fasting glucose in all groups combined (p = -0.24, P = 0.0001) and particularly in NIDDM subjects (p = 0.31, P = 0.0054). Although leptin concentrations were higher in women than in men, similar significant correlation with fasting glucose was found when females were analyzed separately. A positive correlation was found with BMI (p = 0.25, P = 0.0001) in all groups. Multivariate analysis revealed that fasting glucose was independently associated with serum leptin concentrations (F = 12.5, P = 0.0005). Sex, age, BMI, waist/hip ratio, fasting glucose and insulin, total cholesterol and triglycerides, tested in the model, explained 42% of the leptin variability in this population. CONCLUSIONS: Poorly controlled diabetes was accompanied by a significant reduction of serum leptin concentrations in morbidly obese subjects. We suggest that a relative leptin deficiency (lower than expected for the BMI) associated with insulin deficiency in this population might contribute to a vicious cycle maintaining (or even worsening) obesity itself and/or its metabolic complications.

A Continuous Span Aluminum Girder Concrete Deck Bridge - Part 2 of 2: Fatigue Tests of Aluminum Girders, Final Report, 1997

In 1957, the Iowa State Highway Commission, with financial assistance from the aluminum industry, constructed a 220-ft (67-m) long, four-span continuous, aluminum girder bridge to carry traffic on Clive Road (86th Street) over Interstate 80 near Des Moines, Iowa. The bridge had four, welded I-shape girders that were fabricated in pairs with welded diaphragms between an exterior and an interior girder. The interior diaphragms between the girder pairs were bolted to girder brackets. A composite, reinforced concrete deck served as the roadway surface. The bridge, which had performed successfully for about 35 years of service, was removed in the fall of 1993 to make way for an interchange at the same location. Prior to the bridge demolition, load tests were conducted to monitor girder and diaphragm bending strains and deflections in the northern end span. Fatigue testing of the aluminum girders that were removed from the end spans were conducted by applying constant-amplitude, cyclic loads. These tests established the fatigue strength of an existing, welded, flange-splice detail and added, welded, flange-cover plates and horizontal web plate attachment details. This part, Part 2, of the final report focuses on the fatigue tests of the aluminum girder sections that were removed from the bridge and on the analysis of the experimental data to establish the fatigue strength of full-size specimens. Seventeen fatigue fractures that were classified as Category E weld details developed in the seven girder test specimens. Linear regression analyses of the fatigue test results established both nominal and experimental stress-range versus load cycle relationships (SN curves) for the fatigue strength of fillet-welded connections. The nominal strength SN curve obtained by this research essentially matched the SN curve for Category E aluminum weldments given in the AASHTO LRFD specifications. All of the Category E fatigue fractures that developed in the girder test specimens satisfied the allowable SN relationship specified by the fatigue provisions of the Aluminum Association. The lower-bound strength line that was set at two standard deviations below the least squares regression line through the fatigue fracture data points related well with the Aluminum Association SN curve. The results from the experimental tests of this research have provided additional information regarding behavioral characteristics of full-size, aluminum members and have confirmed that aluminum has the strength properties needed for highway bridge girders.

Constant and variable amplitude fatigue strength of high strength steel welds treated with ultrasonic impact treatment

Hitsattujen rakenteiden väsymiskestävyyttä pystytään parantamaan jälkikäsittelymenetelmillä, joistayksi, ultraäänikäsittely muokkaa hitsin geometriaa ja aiheuttaa puristusjäännösjännitystilan. Tässä tutkimuksessa verrataan kokeellisesti kuormaa kantamattoman hitsatun ja ui -käsitellyn rivan väsymislujuutta toisiinsa. Tutkimusohjelmaan kuuluu kahta teräslajia ja sekä vakio - että vaihtuva - amplitudista kuormitusta. Ultraäänikäsittelyllä saavutetaan väsymiskestoiän parantuminen vakio - ja vaihtuva - amplitudisella kuormituksella. Perusaineen lujuudella ei ole merkittää vaikutusta väsymislujuuteen kun liitos on hitsatussa tilassa. Tällöin väsymiskestävyyden määrää hitsin rajaviivan jännityskeskittymä. Ultraäänikäsitellyn hitsatunliitoksen väsymiskestävyys on suurempi korkeamman lujuuden omaavilla teräksillä. Tästä syystä korkealujuuksisten terästen käyttö ultraäänikäsiteltynä väsyttävästi kuormitetuissa kevytrakenteissa on perusteltua.