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It is established that the human pathogen Legionella pneumophila becomes significantly augmented for infection of macrophages after intracellular growth in amoebae when compared to like-strains cultivated in laboratory media. Based on this observation, we reasoned that the most critical virulence determinants of L.p. are expressed by responding to stimuli generated by the protozoan host specifically; a process we term “protozoan-priming.” We sought to identify L.p. virulence factors that were required for replication in amoebae in order to highlight the genes necessary for production of the most infectious form of the bacterium. Using a transposon mutagenesis screen, we successfully identified 12 insertions that produced bacteria severely attenuated for growth in amoebae, while retaining a functional Dot/Icm type IVb secretion system. Seven of these insertion mutants were found dispensable for growth in macrophages, revealing attractive therapeutic targets that reside upstream of the pathogen-human interface. Two candidates identified, lpg0730 and lpg0122 were required for survival and replication in amoebae and macrophage host cells. Both genes are conserved among numerous important human pathogenic bacteria that can persist or replicate in amoebae. Each gene encodes a component of an ATP binding cassette (ABC) transport complex of unknown function. We demonstrate the lpg0730 ortholog in Francisella tularensis subsp. novicida to be essential for colonization of both protozoan and mammalian host cells, highlighting conserved survival mechanisms employed by bacteria that utilize protozoa as an environmental reservoir for replication.

The alternative sigma factor σE functions to maintain bacterial homeostasis and membrane integrity in response to extracytoplasmic stress by regulating thousands of genes both directly and indirectly. The transcriptional regulatory network governed by σE in Salmonella and E. coli has been examined using microarray, however a genome-wide analysis of σE-binding sites in Salmonella has not yet been reported. We infected macrophages with Salmonella Typhimurium over a select time course. Using chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq), 31 σE-binding sites were identified. Seventeen sites were new, which included outer membrane proteins, a quorum-sensing protein, a cell division factor, and a signal transduction modulator. The consensus sequence identified for σE in vivo binding was similar to the one previously reported, except for a conserved G and A between the -35 and -10 regions. One third of the σE-binding sites did not contain the consensus sequence, suggesting there may be alternative mechanisms by which σE modulates transcription. By dissecting direct and indirect modes of σE-mediated regulation, we found that σE activates gene expression through recognition of both canonical and reversed consensus sequence. New σE regulated genes (greA, luxS, ompA and ompX) are shown to be involved in heat shock and oxidative stress responses.

The alternative sigma factor σE functions to maintain bacterial homeostasis and membrane integrity in response to extracytoplasmic stress by regulating thousands of genes both directly and indirectly. The transcriptional regulatory network governed by σE in Salmonella and E. coli has been examined using microarray, however a genome-wide analysis of σE–binding sites in Salmonella has not yet been reported. We infected macrophages with Salmonella Typhimurium over a select time course. Using chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq), 31 σE–binding sites were identified. Seventeen sites were new, which included outer membrane proteins, a quorum-sensing protein, a cell division factor, and a signal transduction modulator. The consensus sequence identified for σE in vivo binding was similar to the one previously reported, except for a conserved G and A between the -35 and -10 regions. One third of the σE–binding sites did not contain the consensus sequence, suggesting there may be alternative mechanisms by which σE modulates transcription. By dissecting direct and indirect modes of σE-mediated regulation, we found that σE activates gene expression through recognition of both canonical and reversed consensus sequence. New σE regulated genes (greA, luxS, ompA and ompX) are shown to be involved in heat shock and oxidative stress responses. [ABSTRACT FROM AUTHOR]

The extracytoplasmic functioning sigma factor σE is known to play an essential role for Salmonella enterica serovar Typhimurium to survive and proliferate in macrophages and mice. However, its regulatory network is not well-characterized, especially during infection. Here we used microarray to identify genes regulated by σE in Salmonella grown in three conditions: a nutrient-rich condition and two others that mimic early and late intracellular infection. We found that in each condition σE regulated different sets of genes, and notably, several global regulators. When comparing nutrient-rich and infection-like conditions, large changes were observed in the expression of genes involved in Salmonella pathogenesis island (SPI)-1 type-three secretion system (TTSS), SPI-2 TTSS, protein synthesis, and stress responses. In total, the expression of 58% of Salmonella genes was affected by σE in at least one of the three conditions. An important finding is that σE up-regulates SPI-2 genes, which are essential for Salmonella intracellular survival, by up-regulating SPI-2 activator ssrB expression at the early stage of infection and down-regulating SPI-2 repressor hns expression at a later stage. Moreover, σE is capable of countering the silencing of H-NS, releasing the expression of SPI-2 genes. This connection between σE and SPI-2 genes, combined with the global regulatory effect of σE, may account for the lethality of rpoE-deficient Salmonella in murine infection. [ABSTRACT FROM AUTHOR]

This study investigates lightweight and efficient candidates for sound absorption to address the growing demand for sustainable and eco-friendly materials in noise attenuation. Juncus effusus (JE) is a natural fiber known for its unique three-dimensional network, providing a viable and sustainable filler for enhanced sound absorption in honeycomb panels. Microperforated-panel (MPP) honeycomb absorbers incorporating JE fillers were fabricated and designed, focusing on optimizing the absorber designs by varying JE filler densities, geometrical arrangements, and MPP parameters. At optimal filling densities, the MPP-type honeycomb structures filled with JE fibers achieved high noise reduction coefficients (NRC) of 0.5 and 0.7 at 20 mm and 50 mm thicknesses, respectively. Using an analytical model and an artificial neural network (ANN) model, the sound absorption characteristics of these absorbers were successfully predicted. This study demonstrates the potential of JE fibers in improving noise mitigation strategies across different industries, offering more sustainable and efficient solutions for construction and transportation.

In this study, solutions were prepared with fixed concentrations of hyaluronic acid (HA) but varied concentrations of poly (lactic-co-glycolic acid) (PLGA) to emphasize the effects of PLGA concentration and HA addition on solution properties and to further evaluate their electrospinning performance. The dependence of specific viscosity on PLGA concentration was studied to determine the concentration regimes and evaluate the critical concentration (C e ) for successful fiber generation. The C e of PLGA solutions is 12.07% compared to 10.09% for PLGA-HA solutions. Blending with HA results in a lower concentration dependence and better consistency to the theoretical scaling mechanisms due to the additional topological constrains, which thus result in more chain entanglements. Solutions in semi-dilute entangled regimes show the crossover of complex moduli, verifying the stable and reliable entanglement network. Higher concentrations and HA addition both led to lower crossover frequencies and, thus, a longer relaxation time. The effects of a higher PLGA concentration and HA addition on the surface tension were not evident. However, the HA addition significantly improved the solution conductivity up to three times in the pure PLGA solutions due to its polyelectrolyte nature. Defect-free and uniform nanofibers were generated from 35% to 40% of the PLGA-HA solutions, yet fibers with bead-on-string structures were produced from all studied pure PLGA solutions. Such solution characteristics and parametric correlations can provide predictive insights on tailoring the morphological characteristics of nanofibers for specific applications.

Equine-Assisted Services (EAS) gained a foothold in the healthcare industry as a unique modality addressing the physical, cognitive, and psychological health issues for people across the lifespan. These services require a team approach, with volunteer support playing a prominent role in service delivery. Volunteers are a precious resource for EAS programs and step into a variety of support roles, including preparation and handling. However, little is known about the horse-volunteer relationship or factors that influence their working relationships. Therefore, the purpose of this web-based survey was to characterize the volunteer experience and explore factors that may impact volunteers' ability to accurately identify equine behavior. A total of 240 volunteers from 25 Professional Association for Therapeutic Horsemanship, International (PATH, Intl.) Premier Accredited Centers participated in this survey. The results of the correlational analyses and a general linear model suggested certain volunteer characteristics can be linked to accurate identification of horse behaviors. Horse leaders (P < .001) and volunteers who help with adaptive riding (P = .048) or therapeutic driving (P = .031) sessions more accurately recognized behaviors than those who held other roles. Volunteers who had any amount of horse experience prior to volunteering correctly identified more behaviors than those who came with none. A qualitative content analysis showed that volunteers felt most unprepared when a horse exhibited a behavior they were not trained to handle, and volunteers indicated their preparation to assist in EAS could be improved with more general training and education related to equine behavior., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3., Aims: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19., Results: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC 50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls., Conclusions: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19's patients., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study investigated the production of phosphate glass fiber/polylactic acid (PGF/PLA) commingled yarns, textiles and composites for biomedical applications. The PGF volume contents of the composites investigated were 25% and 40%. Plain weave textiles with yarn counts of 10 warp/cm and 6 weft/cm were produced using a commercial weaving machine. An orthogonal array design (OAD) was employed as a statistical method to investigate the effects of compression molding parameters (processing temperature, preheating time, compression time, and pressure) on flexural strength and porosity of PGF/PLA textile composites. Processing temperature showed the most significant effect in achieving maximum laminate flexural strength and molecular weight of PLA. Processing models were developed using regression techniques to predict the laminate flexural strength and the molecular weight of PLA. Composites with fiber contents of 25 and 40 vol% produced using optimized processing conditions identified by the processing models, provided flexural strengths of 236 MPa and 293 MPa, respectively., (© 2020 Wiley Periodicals LLC.)

Management of waste from carbon fibre composites has become a significant societal issue as the application of composite grows across many industries. In this study, carbon fibres (CF) were successfully recovered from cured carbon fibre/epoxy (CF/EP) prepreg under microwave pyrolysis at 450, 550 and 650 °C followed by oxidation of any residual char. The recovered fibres were investigated for their tensile properties, surface morphologies and the elements/functional groups presented on the surface. The chemical compositions of gaseous and oil pyrolysis products were also analysed. The microwave pyrolysis effectively pyrolyzed the epoxy (EP) resin. Char residue remained on the fibre surface and the amount of char reduced as the pyrolysis temperature increased. Compared to virgin fibres, the recovered fibre suffered from a strength reduction by less than 20%, and this reduction could be mitigated by reducing the pyrolysis temperature. The surface of recovered fibre remained clean and smooth, while the profile of elements and functional groups at the surface were similar to those of virgin fibres. The main gaseous products were CO, H 2 , CO 2 and CH 4, whilst the liquid product stream included phenolic and aromatic compounds.

Hybrid composites composed of bio-based thin-ply carbon fibre prepreg and flame-retardant mats (E20MI) have been produced to investigate the effects of laminate design on their fire protection performance and mechanical properties. These flame-retardant mats rely primarily on expandable graphite, mineral wool and glass fibre to generate a thermal barrier that releases incombustible gasses and protects the underlying material. A flame retardant (FR) mat is incorporated into the carbon fibre bio-based polymeric laminate and the relationship between the fire protection properties and mechanical properties is investigated. Hybrid composite laminates containing FR mats either at the exterior surfaces or embedded 2-plies deep have been tested by the limited oxygen index (LOI), vertical burning test and cone calorimetry. The addition of the surface or embedded E20MI flame retardant mats resulted in an improvement from a base line of 33.1% to 47.5% and 45.8%, respectively. All laminates passed the vertical burning test standard of FAR 25.853. Cone calorimeter data revealed an increase in the time to ignition (TTI) for the hybrid composites containing the FR mat, while the peak of heat release rate (PHRR) and total heat release (TTR) were greatly reduced. Furthermore, the maximum average rate of heat emission (MARHE) values indicated that both composites with flame retardant mats had achieved the requirements of EN 45545-2. However, the tensile strengths of laminates with surface or embedded flame-retardant mats were reduced from 1215.94 MPa to 885.92 MPa and 975.48 MPa, respectively. Similarly, the bending strength was reduced from 836.41 MPa to 767.03 MPa and 811.36 MPa, respectively.

Composites of biodegradable phosphate glass fiber and polylactic acid (PGF/PLA) show potential for bone tissue engineering scaffolds, due to their ability to release Ca, P, and Mg during degradation, thus promoting the bone repair. Nevertheless, glass degradation tends to acidify the surrounding aqueous environment, which may adversely affect the viability and bone-forming activities of osteoblasts. In this work, MgO was investigated as a neutralizing agent. Porous network-phase gyroid scaffolds were additive-manufactured using four different materials: PLA, MgO/PLA, PGF/PLA, and (MgO + PGF)/PLA. The addition of PGF enhanced compressive properties of scaffolds, and the resultant scaffolds were comparably strong and stiff with human trabecular bone. While the degradation of PGF/PLA composite induced considerable acidity in degradation media and intensified the degradation of PGF in return, the degradation media of (MgO + PGF)/PLA maintained a neutral pH close to a physiological environment. The experiment results indicated the possible mechanism of MgO as the neutralizing agent: the local acidity was buffered as the MgO reacted with the acidic degradation products thereby inhibiting the degradation of PGF from being intensified in an acidic environment. The (MgO + PGF)/PLA composite scaffold appears to be a candidate for bone tissue engineering.

Climate change is a major threat to public health worldwide. Conversely, well-designed action to mitigate climate change offers numerous opportunities to improve health and equity. Despite this, comprehensive climate action has not been forthcoming within New Zealand. The media plays an important role in shaping public opinion and support for policy change. Previous literature has suggested that certain types of framing may be more effective than others at encouraging support for climate action and policy. This includes positive, personally relevant framing, as well as key journalistic tools which appear counter-intuitive, such as an increase in human interest stories and 'sensationalist' framing. We undertook a qualitative thematic analysis of climate change and health media coverage in two online New Zealand news outlets to understand how the issue was framed, and how it may be framed more effectively to encourage climate action. We compared the framing used by journalists in mainstream media outlet the New Zealand Herald Online (NZHO) with that of contributors to independent news repository site Scoop. Content in both outlets emphasized the threat unchecked climate change poses to health, which overshadowed the positive health opportunities of climate action. The NZHO was more prone to negative framing, and more likely to favour stories which could be sensationalized and were international in scope. We considered the possible effectiveness of the framing we found for attracting greater media attention and encouraging support for climate action and policy., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This work presents manufacturing, processing and characterisation of the phosphate glass fibre (PGF) products for biomedical applications, including multifilament PGF strands, yarns and textiles, and PGF textile composites. The multifilament production of PGF strands was achieved using a 50-nozzle bushing. PGF yarns, with a linear density of 87 tex, a twist angle of 14° and a tensile strength of 0.29 N/tex, were produced by combining 8 fibre strands using the ring-spinning method. PGF textiles, with a width of 15 mm and a thickness of 0.36 mm, were prepared using an inkle loom. The maximum flexural strength and modulus of unidirectional (UD) composites with a fibre volume fraction of ~17% were 262 ± 11 MPa and 10.4 ± 0.2 GPa, respectively. PGF textile composites with a fibre volume fraction of ~21% exhibited mechanical properties of 176 ± 13 MPa for flexural strength and 8.6 ± 0.6 GPa for flexural modulus. Despite the UD and textile composites having almost an equivalent amount of fibres in the 0 direction, the crimp of the yarns was found to contribute to the significantly lower flexural properties of the textile composites in comparison with the unidirectional (UD) composites. Additionally, the processing conditions such as processing temperature and time were found to have a strong effect on the mechanical properties of the resultant composite products. The number-average molecular weight of PLA was also found to reduce by 13% and 19% after the production of PLA films and PLA plates, respectively, in comparison with the as-received PLA pellets., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Anxiety and depression are common comorbidities in people diagnosed with chronic obstructive pulmonary disease (COPD). Despite concomitant psychological symptomatology being reported in 22-48% of people with COPD, most literature focuses on identifying the risk factors for anxiety or depression separately. Therefore, our objective was to determine whether there is an association between people living with concomitant anxiety and depression and sociodemographic risk factors in people and living with COPD., Methods: This was a cross-sectional study of 242 people living with COPD. Symptomatology of anxiety and depression were assessed using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI-II). Univariate and multivariable logistic regression models were used to test the association between symptomatology and demographic predictor variables. Odds ratios and 95% confidence intervals were derived., Results: Of the 242 people included, 48.8% (n = 118) had no symptoms of anxiety or depression and 33.5%% (n = 81) had symptomatology for both. Multivariable modelling suggested younger age, having a carer, having a previous psychological medical history, having a higher number of comorbidities and poorer quality of life were associated with concomitant anxiety and depression compared to those without symptomatology., Conclusion: Further work should be done to build upon our results which adds to the limited literature surrounding risk factors for concomitant psychological symptomatology to facilitate future discussion surrounding reducing these detrimental comorbidities in people with COPD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: While in school, girls require an environment that is supportive of menstrual hygiene management (MHM) in order to ensure regular school attendance and participation. Little is known about schoolgirls access to and practice of MHM in rural Zambia. This study explores girls' experiences of MHM in rural schools of Zambia from the perspectives of schoolgirls, schoolboys and community and school-based adults key to MHM for schoolgirls., Methods: In July and August 2015, we conducted this qualitative exploratory study in six rural schools of Mumbwa and Rufunsa districts of Zambia. Twelve in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among girls ages 14-18 who had begun menstruating. Two FGDs with boys ages 14-18 and 25 key informant interviews were also conducted with teachers, female guardians and traditional leaders to provide the context within which schoolgirls practice MHM., Results: Most girls reported learning about menstruation only at menarche and did not know the physiological basis of menstruation. They reported MHM-related challenges, including: use of non-absorbent and uncomfortable menstrual cloth and inadequate provision of sanitary materials, water, hygiene and sanitation facilities (WASH) in schools. In particular, toilets did not have soap and water or doors and locks for privacy and had a bad odor. Girls' school attendance and participation in physical activities was compromised when menstruating due to fear of teasing (especially by boys) and embarrassment from menstrual leakage. Boys said they could tell when girls were menstruating by the smell and their behaviour, for instance, moving less and isolating themselves from their peers. Girls complained of friction burns on their inner thighs during their long journey to school due to chaffing of wet non-absorbent material used to make menstrual cloth. Girls preferred to dispose used menstrual materials in pit latrines and not waste bins for fear that they could be retrieved for witchcraft against them. Though traditional leaders and female guardians played a pivotal role in teaching girls MHM, they have not resolved challenges to MHM among schoolgirls., Conclusion: When menstruating, schoolgirls in rural Zambia would rather stay home than be uncomfortable, inactive and embarrassed due to inadequate MHM facilities at school. A friendly and supportive MHM environment that provides education, absorbent sanitary materials and adequate WASH facilities is essential to providing equal opportunity for all girls.

Background: While numerous theoretical and conceptual models suggest social evaluation anxiety would likely influence performance in simulation-based learning environments, there has been surprisingly little research to investigate the extent to which this is true., Methods: Final-year Bachelor of Science (Nursing) students (N=70) were randomly assigned to complete one of three clinically identical simulation-based scenarios designed to elicit varying levels of social evaluation anxiety by manipulating the number of other people present with the student during the simulation (1, 2 or 3 others). Rises in acute stress were measured via continuous heart-rate and salivary cortisol. Performance scores were derived from the average of two independent raters' using a structured clinical checklist (/16)., Results: Statistically different increases were found within the first minute of the simulation between those students with one versus three other people in the room (+4.13 vs. +14.01beats-per-minute respectively, p=0.01) and salivary cortisol measures suggested significantly different changes in anxiety between these groups (-0.05 vs. +0.11μg/dL respectively, p=0.02). Independent assessments suggested students with only one other person accompanying them in the simulation significantly outperformed those accompanied by three others (12.95 vs. 10.67 respectively, p=0.03)., Discussion: Students accompanied by greater numbers during simulations experienced measurably greater anxiety and measurably poorer performances. These results demonstrate the ability to manipulate social evaluation anxiety within high-fidelity simulation training of undergraduates in order to help students better acclimatise to stressful events prior to practising in real clinical settings., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The objective of this study was to investigate the discriminant validity of commonly used depression and anxiety screening tools in order to determine the most suitable tool for patients with chronic obstructive pulmonary disease (COPD). COPD patients (n = 56) completed the Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI-II) and Beck Anxiety Inventory (BAI). These scores were compared to confirmed clinical diagnoses of depression and anxiety using the Mini Neuropsychiatric Interview. HADS depression subscale (HADS-D) sensitivity/specificity was 78/81%; BDI-II 89/77%; HADS anxiety subscale (HADS-A) 71/81%; and BAI 89/62%. HADS-D sensitivity/specificity was improved (100/83%) with the removal of Q4 'I feel as if I am slowed down' and adjusted cut-off (≥5). Removal of BDI-II Q21 'Loss of interest in sex' with adjusted cut-off ≥12 resulted in similar improvement (100/79%). No problematic items were identified for HADS-A or BAI. Previously reported low sensitivity/specificity of the HADS for COPD patients was not replicated. Furthermore, simple modifications of the HADS-D markedly improved sensitivity/specificity for depression.BDI-II, HADS-A and BAI produced acceptable sensitivity/specificity unmodified. Pending further research for COPD patients we recommend continued use of the HADS-A with standard cut-off (≥8) and removal of Q4 of the HADS-D with lower cut-off ≥5., (© The Author(s) 2016.)

Background: Introduction of new vaccines in low- and lower middle-income countries has accelerated since Gavi, the Vaccine Alliance was established in 2000. This study sought to (i) estimate the costs of introducing pneumococcal conjugate vaccine, rotavirus vaccine and a second dose of measles vaccine in Zambia; and (ii) assess affordability of the new vaccines in relation to Gavi's co-financing and eligibility policies., Methods: Data on 'one-time' costs of cold storage expansions, training and social mobilisation were collected from the government and development partners. A detailed economic cost study of routine immunisation based on a representative sample of 51 health facilities provided information on labour and vaccine transport costs. Gavi co-financing payments and immunisation programme costs were projected until 2022 when Zambia is expected to transition from Gavi support. The ability of Zambia to self-finance both new and traditional vaccines was assessed by comparing these with projected government health expenditures., Results: 'One-time' costs of introducing the three vaccines amounted to US$ 0.28 per capita. The new vaccines increased annual immunisation programme costs by 38%, resulting in economic cost per fully immunised child of US$ 102. Co-financing payments on average increased by 10% during 2008-2017, but must increase 49% annually between 2017 and 2022. In 2014, the government spent approximately 6% of its health expenditures on immunisation. Assuming no real budget increases, immunisation would account for around 10% in 2022. Vaccines represented 1% of government, non-personnel expenditures for health in 2014, and would be 6% in 2022, assuming no real budget increases., Conclusion: While the introduction of new vaccines is justified by expected positive health impacts, long-term affordability will be challenging in light of the current economic climate in Zambia. The government needs to both allocate more resources to the health sector and seek efficiency gains within service provision., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Programme for the Awareness and Elimination of Diarrhoea (PAED) was a pilot comprehensive diarrhoea prevention and control programme aimed to reduce post-neonatal, all-cause under-five mortality by 15 % in Lusaka Province. Interventions included introduction of the rotavirus vaccine, improved clinical case management of diarrhoea, and a comprehensive community prevention and advocacy campaign on hand washing with soap, exclusive breastfeeding up to 6 months of age, and the use of ORS and Zinc. This study aimed to assess the impact of PAED on under-5 mortality., Methods: The study was a pre-post evaluation design. The Demographic and Health Survey style population-based two-stage approach was used to collect data at the beginning of the intervention and 3 years following the start of intervention implementation in Lusaka province. The primary outcome of interest was an all-cause, post-neonatal under-five mortality rate defined as the probability of dying after the 28th day and before the fifth birthday among children aged 1-59 months. The Kaplan-Meier time to event analysis was used to estimate the probability of death; multiplying this probability by 1000 to yield the post-neonatal mortality rate. Survival-time inverse probability weighting model was used to estimate Average Treatment Effect (ATE)., Results: The percentage of children under age 5 who had diarrhoea in the last 2 weeks preceding the survey declined from 15.8 % (95 % CI: 15.2 %, 16.4 %) in 2012 to 12.7 % (95 % CI: 12.3 %, 13.2 %) in 2015. Over the same period, mortality in post-neonatal children under 5 years of age declined by 34 %, from an estimated rate of 29 deaths per 1000 live births (95 % CI: (26, 32) death per 1000 live births) to 19 deaths per 1000 live births (95 % CI: (16, 21) death per 1000 live births). When every child in the population of children aged 1-59 months is exposed to the intervention, the average time-to-death was estimated to be about 8 months more than when no child is exposed (ATE = 7.9; 95 % CI: 4.4,11.5; P < 0.001)., Conclusion: Well-packaged diarrhoea preventive and treatment interventions delivered at the clinic and community-level could potentially reduce probability of death among children aged 1-59 months.

Background: Diarrhea is the third leading cause of child death in Zambia. Up to one-third of diarrhea cases resulting in hospitalization and/or death are caused by vaccine-preventable rotavirus. In January 2012, Zambia initiated a pilot introduction of the Rotarix live, oral rotavirus vaccine in all public health facilities in Lusaka Province., Methods: Between July 2012 and October 2013, we conducted a case-control study at 6 public sector sites to estimate rotavirus vaccine effectiveness (VE) in age-eligible children presenting with diarrhea. We computed the odds of having received at least 1 dose of Rotarix among children whose stool was positive for rotavirus antigen (cases) and children whose stool was negative (controls). We adjusted the resulting odds ratio (OR) for patient age, calendar month of presentation, and clinical site, and expressed VE as (1 - adjusted OR) × 100., Results: A total of 91 rotavirus-positive cases and 298 rotavirus-negative controls who had under-5 card-confirmed vaccination status and were ≥6 months of age were included in the case-control analysis. Among rotavirus-positive children who were age-eligible to be vaccinated, 20% were hospitalized. Against rotavirus diarrhea of all severity, the adjusted 2-dose VE was 26% (95% confidence interval [CI], -30% to 58%) among children ≥6 months of age. VE against hospitalized children ≥6 months of age was 56% (95% CI, -34% to 86%)., Conclusions: We observed a higher point estimate for VE against increased severity of illness compared with milder disease, but were not powered to detect a low level of VE against milder disease., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Simulation-based education (SBE) has seen a dramatic uptake in health professions education over the last decade. SBE offers learning opportunities that are difficult to access by other methods. Competent faculty is seen as key to high quality SBE. In 2011, in response to a significant national healthcare issue--the need to enhance the quality and scale of SBE--a group of Australian universities was commissioned to develop a national training program--Australian Simulation Educator and Technician Training (AusSETT) Program. This paper reports the evaluation of this large-scale initiative., Methods: The AusSETT Program adopted a train-the-trainer model, which offered up to three days of workshops and between four and eight hours of e-learning. The Program was offered across all professions in all states and territories. Three hundred and three participants attended workshops with 230 also completing e-learning modules. Topics included: foundational learning theory; orientation to diverse simulation modalities; briefing; and debriefing. A layered objectives-oriented evaluation strategy was adopted with multiple stakeholders (participants, external experts), methods of data collection (end of module evaluations, workshop observer reports and individual interviews) and at multiple data points (immediate and two months later). Descriptive statistics were used to analyse numerical data while textual data (written comments and transcripts of interviews) underwent content or thematic analysis., Results: For each module, between 45 and 254 participants completed evaluations. The content and educational methods were rated highly with items exceeding the pre-established standard. In written evaluations, participants identified strengths (e.g. high quality facilitation, breadth and depth of content) and areas for development (e.g. electronic portfolio, learning management system) of the Program. Interviews with participants suggested the Program had positively impacted their educational practices. Observers reported a high quality educational experience for participants with alignment of content and methods with perceived participant needs., Conclusions: The AusSETT Program is a significant and enduring learning resource. The development of a national training program to support a competent simulation workforce is feasible. The Program objectives were largely met. Although there are limitations with the study design (e.g. self-report), there are strengths such as exploring the impact two months later. The evaluation of the Program informs the next phase of the national strategy for simulation educators and technicians with respect to content and processes, strengths and areas for development.

d-Glucosamine derivatives bearing latent O4 functionality provide modified H/HS-type disaccharide donors for a final stage capping approach enabling introduction of conjugation-suitable, non-reducing terminal functionality to biologically important glycosaminoglycan oligosaccharides. Application to the synthesis of the first O4-terminus modified synthetic LMWH decasaccharide and an HS-like dodecasaccharide is reported.

The extracytoplasmic functioning sigma factor σ(E) is known to play an essential role for Salmonella enterica serovar Typhimurium to survive and proliferate in macrophages and mice. However, its regulatory network is not well-characterized, especially during infection. Here we used microarray to identify genes regulated by σ(E) in Salmonella grown in three conditions: a nutrient-rich condition and two others that mimic early and late intracellular infection. We found that in each condition σ(E) regulated different sets of genes, and notably, several global regulators. When comparing nutrient-rich and infection-like conditions, large changes were observed in the expression of genes involved in Salmonella pathogenesis island (SPI)-1 type-three secretion system (TTSS), SPI-2 TTSS, protein synthesis, and stress responses. In total, the expression of 58% of Salmonella genes was affected by σ(E) in at least one of the three conditions. An important finding is that σ(E) up-regulates SPI-2 genes, which are essential for Salmonella intracellular survival, by up-regulating SPI-2 activator ssrB expression at the early stage of infection and down-regulating SPI-2 repressor hns expression at a later stage. Moreover, σ(E) is capable of countering the silencing of H-NS, releasing the expression of SPI-2 genes. This connection between σ(E) and SPI-2 genes, combined with the global regulatory effect of σ(E), may account for the lethality of rpoE-deficient Salmonella in murine infection.