The effect of NOM characteristics and membrane type on microfiltration performance

Efforts to understand and predict the role of different organic fractions in the fouling of low-pressure membranes are presented. Preliminary experiments with an experimental apparatus that incorporates automatic backwashing and filtration over several days has shown that microfiltration of the hydrophilic fractions leads to rapid flux decline and the formation of a cake or gel layer, while the hydrophobic fractions show a steady flux decline and no obvious formation of a gel or cake layer. The addition of calcium to the weakly hydrophobic acid (WHA) fraction led to the formation of a gel layer from associations between components of the WHA. The dominant foulants were found to be the neutral and charged hydrophilic compounds, with hydrophobic and small pore size membranes being the most readily fouled. The findings suggest that surface analyses such as FTIR will preferentially identify hydrophilic compounds as the main foulants, as these components form a gel layer on the surface while the hydrophobic compounds adsorb within the membrane pores. Furthermore, coagulation pre-treatment is also likely to reduce fouling by reducing pore constriction rather than the formation of a gel layer, as coagulants remove the hydrophobic compounds to a large extent and very little of the hydrophilic neutral components

To Disclose or Not to Disclose: The Dilemma of the School Counselor

Symposiuim on Education La

Community-based first aid: a program report on the intersection of community-based participatory research and first aid education in a remote Canadian Aboriginal community

Community-based first aid training is the collaborative development of locally relevant emergency response training. The Sachigo Lake Wilderness Emergency Response Education Initiative was developed, delivered, and evaluated through two intensive five-day first aid courses. Sachigo Lake First Nation is a remote aboriginal community of 450 people in northern Ontario, Canada with no local paramedical services. These courses were developed in collaboration with the community, with a goal of building community capacity to respond to medical emergencies. Issue. Most first aid training programs rely on standardized curriculum developed for urban & rural contexts with established emergency response systems. Delivering effective community-based first aid training in remote aboriginal communities required specific adaptations to conventional first aid educational content and pedagogy. Lessons Learned. Three key lessons emerged during this program that used collaborative principles to adapt conventional first aid concepts and curriculum. (1) 15 Standard algorithmic approaches may not be relevant nor appropriate. Relationships between course participants and the people they help are relevant and important. Curriculum must be attentive to existing informal and formal emergency response systems. These lessons may be instructive for the development of other programs in similar settings

Development of a Pain Management Protocol for a Paediatric Ward in the Gambia, West Africa

Despite recent advances in our understanding of paediatric pain and its management, pain continues to be undertreated globally, particularly in children and in low income countries. This article describes the development of a paediatric analgesia and sedation protocol, tailored to the specific setting of the Medical Research Council (MRC) paediatric ward in the Gambia, West Africa. An iterative process was used throughout development, with inputs from the medical literature, local providers, and pain experts, incorporated to ensure a safe, effective, and locally appropriate protocol. We demonstrate that evidence-based published guidelines, can and should be adapted to allow for optimal pain management given the resources and capabilities of specific health care settings. It is hoped that the process and protocol described here, will not only help to improve care on the MRC ward, but serve as an example to others working toward improving pain management in similar health care settings

Genotypic and phenotypic analyses reveal distinct population structures and ecotypes for sugar beet-associated Pseudomonas in Oxford and Auckland

Fluorescent pseudomonads represent one of the largest groups of bacteria inhabiting the surfaces of plants, but their genetic composition in planta is poorly understood. Here, we examined the population structure and diversity of fluorescent pseudomonads isolated from sugar beet grown at two geographic locations (Oxford, United Kingdom and Auckland, New Zealand). To seek evidence for niche adaptation, bacteria were sampled from three types of leaves (immature, mature, and senescent) and then characterized using a combination of genotypic and phenotypic analysis. We first performed multilocus sequence analysis (MLSA) of three housekeeping genes (gapA, gltA, and acnB) in a total of 152 isolates (96 from Oxford, 56 from Auckland). The concatenated sequences were grouped into 81 sequence types and 22 distinct operational taxonomic units (OTUs). Significant levels of recombination were detected, particularly for the Oxford isolates (rate of recombination to mutation (r/m) = 5.23 for the whole population). Subsequent ancestral analysis performed in STRUCTURE found evidence of six ancestral populations, and their distributions significantly differed between Oxford and Auckland. Next, their ability to grow on 95 carbon sources was assessed using the Biolog™ GN2 microtiter plates. A distance matrix was generated from the raw growth data (A660) and subjected to multidimensional scaling (MDS) analysis. There was a significant correlation between substrate utilization profiles and MLSA genotypes. Both phenotypic and genotypic analyses indicated presence of a geographic structure for strains from Oxford and Auckland. Significant differences were also detected for MLSA genotypes between strains isolated from immature versus mature/senescent leaves. The fluorescent pseudomonads thus showed an ecotypic population structure, suggestive of adaptation to both geographic conditions and local plant niches

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro

Operational Implementation of the Healthy Communities Study How Communities Shape Children’s Health

The Healthy Communities Study (HCS) is examining how characteristics of community programs and policies targeting childhood obesity are related to childhood diet, physical activity, and obesity outcomes. The study involves selected districts and public schools in 130 communities; families recruited through schools; and data collected at the community, school, household, and child levels. Data collection took place in two waves—Wave 1 in Spring 2012 and Wave 2 from 2013 to 2015—with analysis to be completed by August 2016. This paper describes operational elements of the HCS, including recruitment activities, field operations, training of data collectors, human subjects protection, and quality assurance and quality control procedures. Experienced trainers oversaw and conducted all training, including training of: (1) district and school recruitment staff; (2) telephone interviewers for household screening and recruitment; (3) field data collectors for conducting household data collection; and (4) community liaisons for conducting key informant interviews, document abstraction, and community observations. The study team developed quality assurance and quality control procedures that were implemented for all aspects of the study. Planning and operationalizing a study of this complexity and magnitude, with multiple functional teams, required frequent communication and strong collaboration among all study partners to ensure timely and effective decision making

A Highly Stable Blood Meal Alternative for Rearing \u3cem\u3eAedes\u3c/em\u3e and \u3cem\u3eAnopheles\u3c/em\u3e Mosquitoes

We investigated alternatives to whole blood for blood feeding of mosquitoes with a focus on improved stability and compatibility with mass rearing programs. In contrast to whole blood, an artificial blood diet of ATP-supplemented plasma was effective in maintaining mosquito populations and was compatible with storage for extended periods refrigerated, frozen, and as a lyophilized powder. The plasma ATP diet supported rearing of both Anopheles and Aedes mosquitoes. It was also effective in rearing Wolbachia-infected Aedes mosquitoes, suggesting compatibility with vector control efforts

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Tafenoquine for Weekly Prophylaxis against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e

Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase (G6PD) function. A randomized, doubleblind, placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum. The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage. Relative to the placebo, all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection: for 25 mg/week, protective efficacy was 32% (95% confidence interval [CI], 20%–43%); for 50 mg/week, 84% (95% CI, 75%–91%); for 100 mg/week, 87% (95% CI, 78%–93%); and for 200 mg/week, 86% (95% CI, 76%–92%). The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection (protective efficacy, 86%; 95% CI, 72%–93%). There was little difference between study groups in the adverse events reported, and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters. Tafenoquine dosages of 50, 100, and 200 mg/week were safe, well tolerated, and effective against P. falciparum infection in this study population