Hydraulic and biotic impacts on neutralisation of high-pH waters

The management of alkaline (pH 11–12.5) leachate is an important issue associated with the conditioning, afteruse or disposal of steel slags. Passive in-gassing of atmospheric CO₂ is a low cost option for reducing Ca(OH)₂ alkalinity, as Ca(OH)₂ is neutralised by carbonic acid to produce CaCO₃. The relative effectiveness of such treatment can be affected by both the system geometry (i.e. stepped cascades versus settlement ponds) and biological colonization. Sterilized mesocosm experiments run over periods of 20 days showed that, due to more water mixing and enhanced CO₂ dissolution at the weirs, the cascade systems (pH 11.2 → 9.6) are more effective than settlement ponds (pH 11.2 → 11.0) for lowering leachate alkalinity in all the tested conditions. The presence of an active microbial biofilm resulted in significantly more pH reduction in ponds (pH 11.2 → 9.5), but had a small impact on the cascade systems (pH 11.2 → 9.4). The pH variation in biofilm colonized systems shows a diurnal cycle of 1 to 1.5 pH units due to CO₂ uptake and release associated with respiration and photosynthesis. The results demonstrate that, where gradient permits, aeration via stepped cascades are the best option for neutralisation of steel slag leachates, and where feasible, the development of biofilm communities can also help reduce alkalinity

Diagnostic hysteroscopy and saline infusion sonography in the diagnosis of intrauterine abnormalities: an assessment of patient preference

This study was conducted to assess whether women would prefer to undergo saline infusion sonography (SIS) or office hysteroscopy for the investigation of the uterine cavity. In a randomised controlled trial, 100 patients underwent SIS or office hysteroscopy for assessing patients' pain scores. After the investigation, 92 of them were asked to fill out an anonymous questionnaire addressing their preference regarding the method of evaluation and treatment of the uterine cavity. A control group, consisting of 50 women who never underwent SIS or office hysteroscopy, was also asked to complete an identical questionnaire. The questionnaire was completed by 113 women (83.7%). Twenty-four (21.2%) women would opt for SIS, whereas 52 (46.0%) would opt for office hysteroscopy, and 37 (32.7%) had no preference. If therapy would be necessary, 48.7% of the women would opt for an outpatient treatment, whereas 33.0% of the women would prefer treatment under general anaesthesia. Despite the fact that SIS is less painful, the majority of the women prefer office hysteroscopy. Additionally, therapy in an outpatient setting is preferred to a day case setting

A Randomized Controlled Pilot Trial of Azithromycin or Artesunate Added to Sulfadoxine-Pyrimethamine as Treatment for Malaria in Pregnant Women

New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance. We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi.This was a randomized open-label clinical trial, conducted at two rural health centers in Blantyre district, Malawi. A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and randomly allocated to 3 treatment groups: sulfadoxine-pyrimethamine (SP; 3 tablets, 500 mg sulfadoxine and 25 mg pyrimethamine per tablet); SP plus azithromycin (1 g/dayx2 days); or SP plus artesunate (200 mg/dayx3 days). Women received two doses administered at least 4 weeks apart. Heteroduplex tracking assays were performed to distinguish recrudescence from new infections. Main outcome measures were incidence of adverse outcomes, parasite and fever clearance times and recrudescence rates. All treatment regimens were well tolerated. Two women vomited soon after ingesting azithromycin. The parasite clearance time was significantly faster in the SP-artesunate group. Recrudescent episodes of malaria were less frequent with SP-azithromycin [Hazard Ratio 0.19 (95% confidence interval 0.06 to 0.63)] and SP-artesunate [Hazard Ratio 0.25 (95% confidence interval 0.10 to 0.65)] compared with SP monotherapy. With one exception (an abortion in the SP-azithromycin group), all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes. Because of the small sample size, the effect on birth outcomes, maternal malaria or maternal anemia could not be evaluated.Both SP-artesunate and SP-azithromycin appeared to be safe, well tolerated and efficacious for the treatment of malaria during pregnancy. A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes.ClinialTrials.gov NCT00287300

Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Scale and the Origins of Structural Change

Structural change involves a broad set of trends: (i) sectoral reallocations, (ii) rich movements of productive activities between home and market, and (iii) an increase in the scale of productive units. After extending these facts, we develop a model to explain them within a unified framework. The crucial distinction between manufacturing, services, and home production is the scale of the productive unit. Scale technologies give rise to industrialization and the marketization of previously home produced activities. The rise of mass consumption leads to an expansion of manufacturing, but a reversal of the marketization process for service industries. Finally, the later growth in the scale of services leads to a decline in industry and a rise in services