Prevalence and risk factors associated with asymptomatic malaria among school children: repeated cross-sectional surveys of school children in two ecological zones in Ghana.

BACKGROUND: Asymptomatic Plasmodium infections significantly drive malaria transmission and impact control and elimination strategies, but are largely uncharacterized. We investigated the prevalence and risk factors of asymptomatic malaria infections to inform malaria control strategies in Ghana. METHOD: Five cross-sectional surveys were conducted at the end of the peak transmission season (August-September) on 4892 school children aged between 6 and 14 years in two distinct ecological settings in Ghana between 2013 and 2017. The study sites were Begoro (forest ecology) and Cape Coast (coastal ecology). The children were screened for malaria parasites by microscopic examination of Giemsa-stained thin and thick blood films. Hemoglobin levels were measured using the Hemocue HB analyzer. In addition, height was measured and the height-for-age z-scores estimated from the reference population defined by WHO to determine children who were stunted. Proportions of categorical and means of continuous variables were compared using Chi-square test and Student's t-test respectively, and multivariable logistic regression was done to assess risk factors associated with asymptomatic infections. RESULTS: The overall prevalence of asymptomatic malaria in the school children was higher in Begoro compared to Cape Coast (27% (95% CI: 17, 24%) vs. 24% (95% CI: 17, 24%), p value = 0.04). The study recorded three species of Plasmodium (Plasmodia falciparum, malariae, and ovale) in both sites. Plasmodium falciparum was the predominant species, accounting for about 85% of infections in both study sites. The asymptomatic school children were more likely to be anaemic (OR = 2.01, p value< 0.001) and stunted in growth (OR = 1.46, p value< 0.001). Males carried more asymptomatic infection than females (OR = 1.18, p value = 0.015). School children aged 12-14 years had more asymptomatic infections than those aged 6-8 years (OR = 1.28, p value = 0.005). CONCLUSION: There is a considerable burden of asymptomatic malaria in the two regions of Ghana, which is associated with males, older children, anaemia, and stunted growth in children, and may have implications for malaria control and elimination strategies in Ghana.

Embedded tin nanocrystals in silicon-an electrical characterization.

Tin nanocrystals embedded in a SiSn layer grown by molecular beam epitaxy on n-type Si are investigated by means of deep level transient spectroscopy. Two Sn related deep traps are observed, depending on the annealing temperature of the samples. A deep level at [Formula: see text] (Sn1) is observed for annealing temperatures up to [Formula: see text]C, whereas a level at [Formula: see text] (Sn2) appears for annealing temperatures above [Formula: see text]C. Scanning transmission electron microscopy shows the formation of Sn nanocrystals at [Formula: see text]C, which coincides with the appearance of Sn2. Sn1 is tentatively assigned to a Sn related precursor defect, which transforms upon annealing into either Sn nanocrystals or an interface defect located at the nanocrystal surface.

Effects of cognitive therapy versus interpersonal psychotherapy in patients with major depressive disorder: a systematic review of randomized clinical trials with meta-analyses and trial sequential analyses.

BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetime at tremendous suffering and cost. Cognitive therapy and interpersonal psychotherapy are treatment options, but their effects have only been limitedly compared in systematic reviews. METHOD: Using Cochrane systematic review methodology we compared the benefits and harm of cognitive therapy versus interpersonal psychotherapy for major depressive disorder. Trials were identified by searching the Cochrane Library's CENTRAL, Medline via PubMed, EMBASE, Psychlit, PsycInfo, and Science Citation Index Expanded until February 2010. Continuous outcome measures were assessed by mean difference and dichotomous outcomes by odds ratio. We conducted trial sequential analysis to control for random errors. RESULTS: We included seven trials randomizing 741 participants. All trials had high risk of bias. Meta-analysis of the four trials reporting data at cessation of treatment on the Hamilton Rating Scale for Depression showed no significant difference between the two interventions [mean difference -1.02, 95% confidence interval (CI) -2.35 to 0.32]. Meta-analysis of the five trials reporting data at cessation of treatment on the Beck Depression Inventory showed comparable results (mean difference -1.29, 95% CI -2.73 to 0.14). Trial sequential analysis indicated that more data are needed to definitively settle the question of a differential effect. None of the included trial reported on adverse events. CONCLUSIONS: Randomized trials with low risk of bias and low risk of random errors are needed, although the effects of cognitive therapy and interpersonal psychotherapy do not seem to differ significantly regarding depressive symptoms. Future trials should report on adverse events.

Mung bean nuclease cleaves Plasmodium genomic DNA at sites before and after genes.

Mung bean nuclease was found to cut the genomic DNA of the malaria parasite Plasmodium at positions before and after genes but not within gene-coding regions. This cleavage, which had nearly the preciseness of a restriction nuclease, required controlled conditions in the presence of formamide. Southern blot analysis showed that the coding areas for Plasmodium actin, circumsporozoite protein, histidine-rich protein, ribosomal RNA's, and tubulin are each cleaved from genomic DNA to yield a single major band on an agarose gel. DNA sequence data on several clones of mung bean nuclease cleavage products containing the gene for the circumsporozoite protein of Plasmodium falciparum confirmed that cleavage sites are before and after genes. Recognition and cleavage of DNA did not seem to be related to any primary sequence but may be related to structural features of the DNA duplex that demarcate genes. Mung bean nuclease-cleaved DNA could be inserted directly into a lambda expression vector, yielding a representative but small gene bank of intact gene fragments.

Complete activation of Bax by a single site mutation.

Bax translocation from the cytosol to mitochondria culminates a key step by which this protein mediates cell death. Here, we identified two amino acids, L70 and D71, within the BH3 domain of Bax that play a critical role in regulating Bax's cytosolic vs mitochondrial distribution. Individual substitution of these amino acids with alanine resulted in Bax conformational change, oligomerization, localization to mitochondria and cell death. Further mutational analysis indicated that L70 interacts with T174, V177 and A178 of Bax's C-terminal hydrophobic segment, while the negative charge of D71 is required for maintaining Bax in its soluble monomeric state. In summary, we have identified a new regulatory site that controls Bax's subcellular distribution and activation.

Threshold response of benthic macrofauna integrity to metal contamination in West Greenland.

Sediment metal chemistry and benthic infauna surveys have been conducted over 33 years following a BACI protocol in relation to submarine tailings deposition (STD) from a lead-zinc mine in a western Greenland fjord system. We found clear predictable changes of benthic fauna composition in response to STD both temporally and spatially. Faunal re-colonization 15 years after mine closure, was slow and the impacted areas were still dominated by opportunistic species, although the most opportunistic ones (e.g. Capitella species) had decreased in importance. Concentration-response relations between sediment lead and faunal indices of benthic community integrity (e.g. the AMBI and DKI indices) indicated a threshold of ca. 200mg/kg, above which deterioration of faunal communities occurred. Above this threshold, diversity decreased dramatically and dominance of sensitive and indifferent species was substituted by tolerant or opportunistic species. Disposal of metal contaminated tailings may have long lasting effects on the biological system.

Localization of cap-binding protein in subcellular fractions of HeLa cells.

The 26,000-M(r) cap-binding protein was analyzed by a cross-linking assay in cell fractions from uninfected and poliovirus-infected HeLa cells. Cap-binding protein was found in the postribosomal supernatant (S-200) and in the ribosomal salt wash. The cap-binding protein in the S-200 had a sedimentation coefficient of 5 to 7S and lacked the ability to restore translation in extracts of poliovirus-infected cells.

Functional reconstitution of the angiotensin II type 2 receptor and G(i) activation.

On the basis of the patterns of conserved amino acid sequence, the angiotensin II type 2 (AT(2)) receptor belongs to the family of serpentine receptors, which relay signals from extracellular stimuli to heterotrimeric G proteins. However, the AT(2) receptor signal transduction mechanisms are poorly understood. We have measured AT(2)-triggered activation of purified heterotrimeric proteins in urea-extracted membranes from cultured COS-7 cells expressing the recombinant receptor. This procedure removes contaminating GTP-binding proteins without inactivating the serpentine receptor. Binding studies using [(125)I] angiotensin (Ang) II revealed a single binding site with a K(d)=0.45 and a capacity of 627 fmol/mg protein in the extracted membranes. The AT(2) receptor caused a rapid activation of alpha(i) and alpha(o) but not of alpha(q) and alpha(s), as measured by radioactive guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding. Activation required the presence of activated receptors, betagamma, and alpha subunits. As a first step aimed at developing an in vitro assay to examine AT(2) receptor pharmacology, we tested a battery of Ang II-related ligands for their ability to promote AT(1) or AT(2) receptor-catalyzed G(i) activation. Two proteolytic fragments of Ang II, Ang III and Ang1-7, also promoted activation of alpha(i) through the AT(2) receptor. Furthermore, we found that [Sar(1),Ala(8)]Ang II is an antagonist for both AT(1) and AT(2) receptors and that CPG42112 behaves as a partial agonist for the AT(2) receptor. In combination with previous observations, these results show that the AT(2) receptor is fully capable of activating G(i) and provides a new tool for exploring AT(2) receptor pharmacology and interactions with G-protein trimers.

Structure of the RNA-dependent RNA polymerase of poliovirus.

BACKGROUND: The central player in the replication of RNA viruses is the viral RNA-dependent RNA polymerase. The 53 kDa poliovirus polymerase, together with other viral and possibly host proteins, carries out viral RNA replication in the host cell cytoplasm. RNA-dependent RNA polymerases comprise a distinct category of polymerases that have limited sequence similarity to reverse transcriptases (RNA-dependent DNA polymerases) and perhaps also to DNA-dependent polymerases. Previously reported structures of RNA-dependent DNA polymerases, DNA-dependent DNA polymerases and a DNA-dependent RNA polymerase show that structural and evolutionary relationships exist between the different polymerase categories. RESULTS: We have determined the structure of the RNA-dependent RNA polymerase of poliovirus at 2.6 A resolution by X-ray crystallography. It has the same overall shape as other polymerases, commonly described by analogy to a right hand. The structures of the 'fingers' and 'thumb' subdomains of poliovirus polymerase differ from those of other polymerases, but the palm subdomain contains a core structure very similar to that of other polymerases. This conserved core structure is composed of four of the amino acid sequence motifs described for RNA-dependent polymerases. Structure-based alignments of these motifs has enabled us to modify and extend previous sequence and structural alignments so as to relate sequence conservation to function. Extensive regions of polymerase-polymerase interactions observed in the crystals suggest an unusual higher order structure that we believe is important for polymerase function. CONCLUSIONS: As a first example of a structure of an RNA-dependent RNA polymerase, the poliovirus polymerase structure provides for a better understanding of polymerase structure, function and evolution. In addition, it has yielded insights into an unusual higher order structure that may be critical for poliovirus polymerase function.

Effect of short-term prostacyclin administration on restenosis after percutaneous transluminal coronary angioplasty.

The effect of short-term prostacyclin (PGI2) administration on the incidence of restenosis after coronary angioplasty was studied in a prospective single-blind randomized trial of 286 patients. Of the 270 patients in whom dilation was successful, 134 received prostacyclin and 136 received placebo. Intracoronary prostacyclin was administered before and after dilation and then intravenously for 48 h. The control group received intracoronary placebo infusions before and after dilation. All patients received aspirin and dipyridamole before and after angioplasty, at least until follow-up angiography. Follow-up angiograms were obtained in 93% of patients in whom angioplasty was successful. Restenosis of one or more lesions was present in 34 patients (27%) who were given prostacyclin compared with 40 patients (32%) in the control group (p = NS). Acute vessel closure and ventricular tachyarrhythmias were more common in the control group than in the patients who received prostacyclin (acute vessel closure occurred in 14 [10.3%] of 136 versus 4 [3.0%] of 134, respectively, p less than 0.01; ventricular tachyarrhythmias occurred in 5 [3.4%] of 147 versus 0 of 139 respectively, p less than 0.05). Short-term administration of prostacyclin did not significantly lower the risk of restenosis after coronary angioplasty.

Local hyperthermia, radiation therapy, and chemotherapy in patients with local-regional recurrence of breast carcinoma.

We retrospectively reviewed the response rate and the acute and long-term toxicity of combined treatment using radiation therapy, hyperthermia, and chemotherapy in 29 patients with locally or regionally recurrent or advanced adenocarcinoma of the breast who completed at least 4 of the 6 prescribed hyperthermia treatments as part of a Phase I-II trial. Thirty-nine separate hyperthermia treatment fields were evaluated. Cisplatin alone or cisplatin with etanidazole or bleomycin was delivered just prior to hyperthermia once weekly. Hyperthermia was delivered to a target minimum tumor temperature of 43 degrees C +/- 0.5 for 60 min. Following hyperthermia, a 400 cGy fraction of radiation was given. The radiation fraction size on other days was 200 cGy. Twenty-two fields had previously been irradiated and 17 fields had not. Prior chemotherapy had been given in 24 of 29 patients (83%) and hormonal therapy given in 21 (72%). The median follow-up time is 10 months; 16/29 patients (55%) have died of disease. The overall complete response rate for all fields was 53%. Response rate was not related to any clinical factor, radiation dose, microwave or ultrasound technique, type of chemotherapy, or tumor temperatures, but the number of patients in the study population was small. A statistically significant association between the likelihood of complications and the total radiation therapy dose (previous radiation and present radiation) was found. Persistent ulceration lasting greater than 1 month after completing treatment was seen in 67% of previously irradiated fields compared to 21% of fields that had not been previously treated (p = 0.015). Surgical wound repair was needed for 38% of fields with a history of prior irradiation versus 6% of those without prior treatment (p = 0.050). A statistically significant radiation therapy dose response was found for the likelihood of these complications. None of the hyperthermia temperature parameters studied correlated with an increased risk of complication. We conclude that the combination of radiation therapy, hyperthermia, and chemotherapy results in a high rate of complete response. However, in patients who have been treated with prior radiation therapy, this combination may be more locally toxic than treatment with hyperthermia and radiation therapy alone. The precise impact of chemotherapy on the therapeutic index of hyperthermia and radiation therapy remains to be determined in randomized clinical trials.

Radiosurgery for arteriovenous malformations of the brain using a standard linear accelerator: rationale and technique.

We have recently initiated a program for irradiating small, unresectable arteriovenous malformations (AVM's) in the brain. The treatments are delivered using a modified and carefully calibrated 6 MV linac. We are using high, single doses (15 to 25 Gy) with a goal of sclerosing the vessels and preventing hemorrhages. This technique, radiosurgery, is somewhat controversial in the radiotherapy community. Since the treatment is given in a single sitting, rather than in the more conventional pattern of multiple small daily fractions, there is some concern about late radiation damage to the normal brain tissue. However an extensive review of the literature leads us to the conclusion that if a technique is used that keeps the volume irradiated to high dose small, radiosurgery is a safe and efficacious treatment for small (less than 2.5 cm) AVM's. To decrease the risk of necrosis of normal brain tissue, it is important to confine the high dose region as tightly as possible to the target volume. Precise target localization and patient immobilization is achieved using a stereotactic head frame which is used during angiography, CT scanning, and during the radiation treatment. This minimizes the margin of safety that must be added to the target volume for errors in localization and set-up. The treatment is delivered using multiple noncoplanar arcs, with small, sharp edged X ray beams, and with the center of the AVM at isocenter. This produces a rapid dropoff of dose beyond the target volume. Early results in our first few patients are encouraging.

Isolation of a gene segment expressed by mature schizonts of Plasmodium knowlesi.

Fragments of Plasmodium knowlesi DNA, generated by mung bean nuclease digestion, were ligated into the lambda gt11 vector. This expression library was immunoscreened with a serum which inhibits invasion of erythrocytes by merozoites in vitro and whose primary specificity is directed against a Mr 140 000 merozoite surface antigen. One of the isolated clones contained a 125 base pair insert which hybridized to a 1.8 kilobase species of schizont RNA, indicating that this insert is part of a gene expressed during schizogony.

A new system for patient fixation in radiotherapy.

A new system for patient fixation in radiation treatment is described. The system consists of an airtight plastic bag with a contents of polysterol microspheres. A valve allows evacuation which results in a rigid close fitting cast. The system was compared with conventional foam cast fixation in 29 patients who were treated for carcinoma of the breast. The patients received radiation treatment over 22 fractions, and portal X-ray pictures were obtained at every second treatment. The portal films were compared with the stimulator radiographs and the variation in the position of the centre cross were measured in cranio-caudal and transversal direction as well as the rotation of the centre cross. The results showed that the daily reproducibility of the patient set-up was considerably improved by the new system, the centre cross deviation of the position of the actual radiation field to the centre cross of the intended field being less than 1 mm in 50% of the cases. The system is time-saving and cheap compared to conventional fixation systems.

Quantitation of serum tobramycin concentration using high-pressure liquid chromatography.

A high-pressure liquid chromatography method for the quantitative determination of tobramycin in serum is described. The antibiotic was separated from serum by chromatography on a silica gel column. The adsorbed antibiotic was derivatized with o-phthalaldehyde, and then eluted with isopropanol. The derivatized tobramycin was separated by reverse-phase chromatography and quantitated by fluorometry. Serum concentrations as low as 0.5 microgram/ml could be accurately measured. A linear response for serum samples containing tobramycin ranging from 0 to 20 microgram/ml was obtained. Other antibiotics, including various aminoglycosides, did not interfere with the tobramycin assay. Comparison with a standard microbiologic assay gave a correlation coefficient of 0.99. This chemical assay is sensitive, precise, specific, and can be performed in 30 minutes.

The influence of ionization chamber and phantom design on the measurement of lung dose in photon beams.

Lung dose correction factors, commonly defined as the ratios of ionization chamber readings in the heterogeneous and homogeneous phantoms, have been compared with those based on accurately determined doses. An analysis of stopping power values, Pwall values, and measurements in lunglike and waterlike materials showed that the wall material and thickness are not very critical in the determination of lung dose correction factors under conditions of electronic equilibrium. When lateral electronic equilibrium is not established due to the extended range of scattered electrons in the low density material, Prepl differs significantly from unity for ionization chambers with thick walls which do not match the lung material in density. An attempt has been made to characterize this effect as a function of photon energy, lung density, field size, and wall thickness.

A scanning-slit x-ray videoabsorptiometric technique for bone mineral measurement.

An x-ray videoabsorptiometric technique was developed for measurement of bone mineral content (BMC) in vivo. The principle utility of this technique is the precise measurement of commonly fractured bones, such as the femoral neck, that are difficult to measure by other techniques because of repositioning problems. Scanning slits reduce scattered radiation and improve linearity of measurements. Heavily filtered, high-kVp beams are used to minimize errors from beam hardening, and data renormalization is employed to compensate for spatial nonuniformities of the beam and detector. Linearity of measured BMC over the range 0.8 to 5 g/cm2 is very good (r = 0.998) and compares well to single- and dual-photon absorptiometry. A 1.6% change in measured BMC is observed for a 10% change (approximately 2 cm) in tissue thickness while a 10% change in marrow type causes a 0.6%-0.8% change in BMC. Manual repositioning of a femur phantom revealed a variation of 0.84% over ten measurements when femur values were referenced to standards. A computer repositioning algorithm provides much easier identification of the region for analysis and yields comparable variation (0.9%).

Measurements of dose distributions in small beams of 6 MV x-rays.

Dose distributions produced by small circular beams of 6 MV x-rays have been measured using ionisation chambers of small active volume. Specific quantities measured include tissue maximum ratios (TMR), total scatter correction factors (St), collimator scatter correction factors (Sc) and off-axis ratios (OAR). Field sizes ranged from 12.5 to 30 mm diameter, and were defined by machined auxiliary collimators with the movable jaws set for a 4 cm x 4 cm field size. Due to the lack of complete lateral electronic equilibrium for these small fields, the accuracy of the measurements was also investigated. This was accomplished by studying dose response as a function of detector size. Uncertainties of 2.5% were observed for the central axis dose in the 12.5 mm field when measuring with an ionisation chamber with a diameter of 3.5 mm. The total scatter correction factor exhibits a strong field size dependence for fields below 20 mm diameter, while the collimator scatter correction factor is constant and is defined by the setting of the movable jaws. Off-axis ratio measurements show larger dose gradients at the beam edges than those achieved with conventional collimator systems. Corrected profiles measured with an ionisation chamber are compared with measurements made with photographic film and LiF thermoluminescent dosemeters.

Rescue angioplasty during myocardial infarction has a beneficial effect on mortality: a tenable hypothesis.

HYPOTHESIS: Rescue percutaneous transluminal coronary angioplasty (PTCA) reduces mortality during myocardial infarction. OBJECTIVE: To determine if PTCA after failed thrombolytic therapy results in reduced mortality. DESIGN: Twenty-eight patients with a persistently occluded infarct artery following thrombolytic therapy more than 3 h after symptom onset were randomized to rescue PTCA (n = 16) or conservative treatment (n = 12) as part of a prospective randomized trial of reperfusion therapy during myocardial infarction in 184 patients. Hospital mortality was assessed in these groups as well as in the 177 patients with known infarct artery status after initial attempts at reperfusion. MAIN RESULTS: There was one death among the 16 patients in the rescue PTCA group versus four deaths in the 12 patients treated conservatively (P = 0.13). Moreover, the death in the rescue PTCA group occurred in one of three patients in whom the procedure failed. Mortality in the entire study group was 10.3% (19 of 184); 4.2% (six of 142) in patients in whom patency was achieved after thrombolysis and/or PTCA and 34.3% (12 of 35) in those in whom reperfusion was not achieved (P less than 0.001). In patients with anterior myocardial infarction, mortality was 6.7% (four of 60) in those with reperfusion and 47.1% (eight of 17) in those with a persistently occluded artery (P less than 0.001). In patients with inferior myocardial infarction, 2.4% (two of 82) with reperfusion and 22.2% (four of 18) with a persistently occluded artery died (P less than 0.01). CONCLUSIONS: Although the number of patients in the randomized groups was small, the trend toward a lower mortality after rescue PTCA supports the hypothesis that rescue PTCA may be beneficial. The mortality results in relation to presence or absence of reperfusion from the entire study population underscores the importance of achieving patency during myocardial infarction.

Implications of physical symmetries in adaptive image classifiers.

It is demonstrated that rotational invariance and reflection symmetry of image classifiers lead to a reduction in the number of free parameters in the classifier. When used in adaptive detectors, e.g. neural networks, this may be used to decrease the number of training samples necessary to learn a given classification task, or to improve generalization of the neural network. Notably, the symmetrization of the detector does not compromise the ability to distinguish objects that break the symmetry.