The dynamics and control of the in-orbit SCOLE configuration

The study of the dynamics of the Spacecraft Control Laboratory Experiment (SCOLE) is extended to emphasize the synthesis of control laws for both the linearized system as well as the large amplitude slewing maneuvers required to rapidly reorient the antenna line of sight. For control of the system through small amplitude displacements from the nominal equilibrium position LQR techniques are used to develop the control laws. Pontryagin's maximum principle is applied to minimize the time required for the slewing of a general rigid spacecraft system. The minimum slewing time is calculated based on a quasi-linearization algorithm for the resulting two point boundary value problem. The effect of delay in the control input on the stability of a continuously acting controller (designed without considering the delay) is studied analytically for a second order plant. System instability can result even for delays which are only a small fraction of the natural period of motion

Issues in modeling and controlling the SCOLE configuration

The parametric study of the in-plane Spacecraft Control Laboratory Experiment (SCOLE) system, the Floquet Stability Analysis, and three dimensional formulations of the SCOLE system dynamics are examined. Control issues are discussed, such as: control of large structures with delayed input in continuous time; control with delayed input in discrete time; control law design for SCOLE using Linear Quadratic Gaussian (LQC)/TRR technique; and optimal torque control for SCOLE slewing maneuvers

Impact of a malaria intervention package in schools on Plasmodium infection, anaemia and cognitive function in schoolchildren in Mali: a pragmatic cluster-randomised trial.

BACKGROUND: School-aged children are rarely targeted by malaria control programmes, yet the prevalence of Plasmodium infection in primary school children often exceeds that seen in younger children and could affect haemoglobin concentration and school performance. METHODS: A cluster-randomised trial was carried out in 80 primary schools in southern Mali to evaluate the impact of a school-based malaria intervention package. Intervention schools received two interventions sequentially: (1) teacher-led participatory malaria prevention education, combined with distribution of long-lasting insecticidal nets (LLINs), followed 7 months later at the end of the transmission season by (2) mass delivery of artesunate and sulfadoxine-pyrimethamine administered by teachers, termed intermittent parasite clearance in schools (IPCs). Control schools received LLINs as part of the national universal net distribution programme. The impact of the interventions on malaria and anaemia was evaluated over 20 months using cross-sectional surveys in a random subset of 38 schools(all classes), with a range of cognitive measures (sustained attention, visual search, numeracy, vocabulary and writing) assessed in a longitudinal cohort of children aged 9-12 years in all 80 schools. RESULTS: Delivery of a single round of IPCs was associated with dramatic reductions in malaria parasitaemia (OR 0.005, 95% CI 0.002 to 0.011, p<0.001) and gametocyte carriage (OR 0.02, 95% CI 0.00 to 0.17, p<0.001) in intervention compared with control schools. This effect was sustained for 6 months until the beginning of the next transmission season. IPCs was also associated with a significant decrease in anaemia (OR 0.56, 95% CI 0.40 to 0.78, p=0.001), and increase in sustained attention (difference +0.23, 95% CI 0.10 to 0.36, p<0.001). There was no evidence of impact on other cognitive measures. CONCLUSION: The combination of malaria prevention education, LLINs and IPCs can reduce anaemia and improve sustained attention of school children in areas of highly seasonal transmission. These findings highlight the impact of asymptomatic malaria infection on cognitive performance in schoolchildren and the benefit of IPCs in reducing this burden. Additionally, malaria control in schools can help diminish the infectious reservoir that sustains Plasmodium transmission

Seasonal malaria vaccination: protocol of a phase 3 trial of seasonal vaccination with the RTS,S/AS01E vaccine, seasonal malaria chemoprevention and the combination of vaccination and chemoprevention.

INTRODUCTION: Seasonal malaria chemoprevention (SMC), with sulphadoxine-pyrimethamine plus amodiaquine (SP+AQ) is effective but does not provide complete protection against clinical malaria. The RTS,S/AS01E malaria vaccine provides a high level of protection shortly after vaccination, but this wanes rapidly. Such a vaccine could be an alternative or additive to SMC. This trial aims to determine whether seasonal vaccination with RTS,S/AS01E vaccine could be an alternative to SMC and whether a combination of the two interventions would provide added benefits. METHODS AND ANALYSIS: This is an individually randomised, double-blind, placebo-controlled trial. 5920 children aged 5-17 months were enrolled in April 2017 in Mali and Burkina Faso. Children in group 1 received three priming doses of RTS,S/AS01E vaccine before the start of the 2017 malaria transmission season and a booster dose at the beginning of two subsequent transmission seasons. In addition, they received SMC SP+AQ placebo on four occasions each year. Children in group 2 received three doses of rabies vaccine in year 1 and hepatitis A vaccine in years 2 and 3 together with four cycles of SMC SP+AQ each year. Children in group 3 received RTS,S/AS01E vaccine and four courses of SMC SP+AQ. Incidence of clinical malaria is determined by case detection at health facilities. Weekly active surveillance for malaria is undertaken in a randomly selected subset of children. The prevalence of malaria is measured in surveys at the end of each transmission season. The primary endpoint is the incidence of clinical malaria confirmed by a positive blood film with a minimum parasite density of 5000 /µL. Primary analysis will be by modified intention to treat defined as children who have received the first dose of the malaria or control vaccine. ETHICS AND DISSEMINATION: The protocol was approved by the national ethics committees of Mali and Burkina Faso and the London School of Hygiene and Tropical Medicine. The results will be presented to all stakeholders and published in open access journals. TRIAL REGISTRATION NUMBER: NCT03143218; Pre-results

Evaluation of seasonal malaria chemoprevention in two areas of intense seasonal malaria transmission: Secondary analysis of a household-randomised, placebo-controlled trial in Houndé District, Burkina Faso and Bougouni District, Mali.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is now widely deployed in the Sahel, including several countries that are major contributors to the global burden of malaria. Consequently, it is important to understand whether SMC continues to provide a high level of protection and how SMC might be improved. SMC was evaluated using data from a large, household-randomised trial in Houndé, Burkina Faso and Bougouni, Mali. METHODS AND FINDINGS: The parent trial evaluated monthly SMC plus either azithromycin (AZ) or placebo, administered as directly observed therapy 4 times per year between August and November (2014-2016). In July 2014, 19,578 children aged 3-59 months were randomised by household to study group. Children who remained within the age range 3-59 months in August each year, plus children born into study households or who moved into the study area, received study drugs in 2015 and 2016. These analyses focus on the approximately 10,000 children (5,000 per country) under observation each year in the SMC plus placebo group. Despite high coverage and high adherence to SMC, the incidence of hospitalisations or deaths due to malaria and uncomplicated clinical malaria remained high in the study areas (overall incidence rates 12.5 [95% confidence interval (CI): 11.2, 14.1] and 871.1 [95% CI: 852.3, 890.6] cases per 1,000 person-years, respectively) and peaked in July each year, before SMC delivery began in August. The incidence rate ratio comparing SMC within the past 28 days with SMC more than 35 days ago-adjusted for age, country, and household clustering-was 0.13 (95% CI: 0.08, 0.20), P < 0.001 for malaria hospitalisations and deaths from malaria and 0.21 (95% CI 0.20, 0.23), P < 0.001 for uncomplicated malaria, indicating protective efficacy of 87.4% (95% CI: 79.6%, 92.2%) and 78.3% (95% CI: 76.8%, 79.6%), respectively. The prevalence of malaria parasitaemia at weekly surveys during the rainy season and at the end of the transmission season was several times higher in children who missed the SMC course preceding the survey contact, and the smallest prevalence ratio observed was 2.98 (95% CI: 1.95, 4.54), P < 0.001. The frequency of molecular markers of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) resistance did not increase markedly over the study period either amongst study children or amongst school-age children resident in the study areas. After 3 years of SMC deployment, the day 28 PCR-unadjusted adequate clinical and parasitological response rate of the SP + AQ regimen in children with asymptomatic malaria was 98.3% (95% CI: 88.6%, 99.8%) in Burkina Faso and 96.1% (95% CI: 91.5%, 98.2%) in Mali. Key limitations of this study are the potential overdiagnosis of uncomplicated malaria by rapid diagnostic tests and the potential for residual confounding from factors related to adherence to the monthly SMC schedule. CONCLUSION: Despite strong evidence that SMC is providing a high level of protection, the burden of malaria remains substantial in the 2 study areas. These results emphasise the need for continuing support of SMC programmes. A fifth monthly SMC course is needed to adequately cover the whole transmission season in the study areas and in settings with similar epidemiology. TRIAL REGISTRATION: The AZ-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT02211729

Geographical and temporal distribution of human giardiasis in Ontario, Canada

BACKGROUND: Giardia is the most frequently identified intestinal parasite in North America. Although information on geographical distribution of giardiasis is critical in identifying communities at high risk, little has been done in this area. Therefore, the objective of this study was to investigate the geographical and temporal distribution of human giardiasis in Ontario in order to identify possible high risk areas and seasons. Two spatial scales of analyses and two disease measures were used with a view to identifying the best of each in assessing geographical patterns of giardiasis in Ontario. Global Moran's I and Moran Local Indicators of Spatial Associations were used to test for evidence of global and local spatial clustering, respectively. RESULTS: There were seasonal patterns with summer peaks and a significant (P < 0.001) decreasing temporal trend. Significant (P < 0.05) global spatial clustering of high rates was observed at the Census Sub-division spatial scale but not at the Census Division scale. The Census Sub-division scale was a better scale of analyses but required spatial empirical Bayesian smoothing of the rates. A number of areas with significant local clustering of giardiasis rates were identified. CONCLUSIONS: The study identified spatial and temporal patterns in giardiasis distribution. This information is important in guiding decisions on disease control strategies. The study also showed that there is benefit in performing spatial analyses at more than one spatial scale to assess geographical patterns in disease distribution and that smoothing of disease rates for mapping in small areas enhances visualization of spatial patterns

The scope of coverage under the Rotterdam Rules - Unimodal and multimodal aspects

U radu se proučavaju, raščlanjuju i interpretiraju sve relevantne odredbe o polju primjene Roterdamskih pravila. Analizira se njihovo opće polje primjene, govori se o ugovorima, prijevozima te subjektima prijevoznih poslova na koje se Roterdamska pravila primjenjuju. Proučavaju se i specifične odredbe o posebnim isključenjima. Tumači se u kojem opsegu Roterdamska pravila pokrivaju multimodalni prijevoz te se govori o multimodalnosti kao obilježju suvremenog prijevoza i unifikaciji multimodalnog prijevoza. Pomno se ulazi u sadržaj i doseg odredbi kojima se propisuju uvjeti koji moraju biti ispunjeni da bi odredbe druge međunarodne prijevozne konvencije imale prednost u odnosu na odredbe Roterdamskih pravila. Nastoji se ukazati i na razlike u pogledu njezinog polja primjene i polja primjene međunarodnih konvencija koje su na snazi, a kojima se uređuje prijevoz stvari morem. Odredbe o polju primjene iznimno su važne i zadiru u bit nove konvencije, njezinu koncepciju, temeljna načela i ciljeve novog pravnog uređenja koje Konvencija propisuje. Najvažnije novine polja primjene Roterdamskih pravila u odnosu na međunarodne konvencije koje su na snazi, a koje uređuju prijevoz stvari morem jesu proširenje polja primjene na prijevoze “od vrata do vrata” i novo uređenje prijevoznih isprava. Cilj rada je skrenuti pažnju na polje primjene kao važno pitanje koje utječe na recepciju Roterdamskih pravila i istaknuti ona rješenja koja se najviše kritiziraju i za koja se osnovano može pretpostaviti da predstavljaju zapreku za njihovu recepciju.This paper considers the application of provisions of the United Nations Convention on Contracts for the International Carriage of Goods Wholly or Partly by Sea (the Rotterdam Rules). The scope of coverage issues go to the heart of the new Convention. This article highlights the major topics relating to the scope of coverage. All aspects of this key issue are examined here: the general scope of application; criteria that must be satisfied for the Convention to be applied; types of transactions that the Convention might govern; application to certain parties. Some of these questions have been particularly controversial. Moreover, this paper addresses the circumstances under which the Rotterdam Rules give way to other conventions. The author discusses issues that may arise from the fact that the Convention will cover both the inward and the outward carriage. It further considers specific exclusions from the Convention. Differences between the Rotterdam Rules and the international legislation in force are pointed out. One of the most significant changes introduced by the Rotterdam Rules to the existing law is the expansion of its scope of coverage to include the door-to-door transport. The Convention covers both the inbound and the outbound international shipments to or from a Contracting State. The Convention applies to contracts in both the liner and the non-liner trades, but not to charterparties and other contracts for the use of a ship or of any space thereon. Volume contract, to which the Convention applies, may provide for greater or lesser obligations and liabilities than those imposed by the Rotterdam Rules

The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone

BACKGROUND: A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. METHODS: In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. RESULTS: The overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. CONCLUSIONS: The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. TRIAL REGISTRATION: The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218