Author Correction: Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Efficient production of male Wolbachia-infected Aedes aegypti mosquitoes enables large-scale suppression of wild populations.

The range of the mosquito Aedes aegypti continues to expand, putting more than two billion people at risk of arboviral infection. The sterile insect technique (SIT) has been used to successfully combat agricultural pests at large scale, but not mosquitoes, mainly because of challenges with consistent production and distribution of high-quality male mosquitoes. We describe automated processes to rear and release millions of competitive, sterile male Wolbachia-infected mosquitoes, and use of these males in a large-scale suppression trial in Fresno County, California. In 2018, we released 14.4 million males across three replicate neighborhoods encompassing 293 hectares. At peak mosquito season, the number of female mosquitoes was 95.5% lower (95% CI, 93.6-96.9) in release areas compared to non-release areas, with the most geographically isolated neighborhood reaching a 99% reduction. This work demonstrates the high efficacy of mosquito SIT in an area ninefold larger than in previous similar trials, supporting the potential of this approach in public health and nuisance-mosquito eradication programs.

The Pathophysiology and Management of Taste Changes in Chronic Kidney Disease: A Review.

One of the most disabling, yet neglected, symptom of patients with chronic kidney disease (CKD) is alteration in taste. The purpose of this review is to examine the extent and content of research around this symptom in CKD with the goals of (1) identifying gaps in current research knowledge and (2) guiding future research. The review summarizes the basic anatomy and physiology of taste followed by analysis of the epidemiology, pathophysiology, and management strategies for taste changes in patients with CKD.

eHealth interventions for people with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with high morbidity and death, which increases as CKD progresses to end-stage kidney disease (ESKD). There has been increasing interest in developing innovative, effective and cost-efficient methods to engage with patient populations and improve health behaviours and outcomes. Worldwide there has been a tremendous increase in the use of technologies, with increasing interest in using eHealth interventions to improve patient access to relevant health information, enhance the quality of healthcare and encourage the adoption of healthy behaviours. OBJECTIVES: This review aims to evaluate the benefits and harms of using eHealth interventions to change health behaviours in people with CKD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 14 January 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs using an eHealth intervention to promote behaviour change in people with CKD were included. There were no restrictions on outcomes, language or publication type. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: We included 43 studies with 6617 participants that evaluated the impact of an eHealth intervention in people with CKD. Included studies were heterogeneous in terms of eHealth modalities employed, type of intervention, CKD population studied and outcomes assessed. The majority of studies (39 studies) were conducted in an adult population, with 16 studies (37%) conducted in those on dialysis, 11 studies (26%) in the pre-dialysis population, 15 studies (35%) in transplant recipients and 1 studies (2%) in transplant candidates We identified six different eHealth modalities including: Telehealth; mobile or tablet application; text or email messages; electronic monitors; internet/websites; and video or DVD. Three studies used a combination of eHealth interventions. Interventions were categorised into six types: educational; reminder systems; self-monitoring; behavioural counselling; clinical decision-aid; and mixed intervention types. We identified 98 outcomes, which were categorised into nine domains: blood pressure (9 studies); biochemical parameters (6 studies); clinical end-points (16 studies); dietary intake (3 studies); quality of life (9 studies); medication adherence (10 studies); behaviour (7 studies); physical activity (1 study); and cost-effectiveness (7 studies).Only three outcomes could be meta-analysed as there was substantial heterogeneity with respect to study population and eHealth modalities utilised. There was found to be a reduction in interdialytic weight gain of 0.13kg (4 studies, 335 participants: MD -0.13, 95% CI -0.28 to 0.01; I2 = 0%) and a reduction in dietary sodium intake of 197 mg/day (2 studies, 181 participants: MD -197, 95% CI -540.7 to 146.8; I2 = 0%). Both dietary sodium and fluid management outcomes were graded as being of low evidence due to high or unclear risk of bias and indirectness (interdialytic weight gain) and high or unclear risk of bias and imprecision (dietary sodium intake). Three studies reported death (2799 participants, 146 events), with 45 deaths/1000 cases compared to standard care of 61 deaths/1000 cases (RR 0.74, CI 0.53 to 1.03; P = 0.08). We are uncertain whether using eHealth interventions, in addition to usual care, impact on the number of deaths as the certainty of this evidence was graded as low due to high or unclear risk of bias, indirectness and imprecision. AUTHORS' CONCLUSIONS: eHealth interventions may improve the management of dietary sodium intake and fluid management. However, overall these data suggest that current evidence for the use of eHealth interventions in the CKD population is of low quality, with uncertain effects due to methodological limitations and heterogeneity of eHealth modalities and intervention types. Our review has highlighted the need for robust, high quality research that reports a core (minimum) data set to enable meaningful evaluation of the literature.

Targeted, structured text messaging to improve dietary and lifestyle behaviours for people on maintenance haemodialysis (KIDNEYTEXT): study protocol for a randomised controlled trial.

INTRODUCTION: Managing nutrition is critical for reducing morbidity and mortality in patients on haemodialysis but adherence to the complex dietary restrictions remains problematic. Innovative interventions to enhance the delivery of nutritional care are needed. The aim of this phase II trial is to evaluate the feasibility and effectiveness of a targeted mobile phone text messaging system to improve dietary and lifestyle behaviours in patients on long-term haemodialysis. METHODS AND ANALYSIS: Single-blinded randomised controlled trial with 6 months of follow-up in 130 patients on haemodialysis who will be randomised to either standard care or KIDNEYTEXT. The KIDNEYTEXT intervention group will receive three text messages per week for 6 months. The text messages provide customised dietary information and advice based on renal dietary guidelines and general healthy eating dietary guidelines, and motivation and support to improve behaviours. The primary outcome is feasibility including recruitment rate, drop-out rate, adherence to renal dietary recommendations, participant satisfaction and a process evaluation using semistructured interviews with a subset of purposively sampled participants. Secondary and exploratory outcomes include a range of clinical and behavioural outcomes and a healthcare utilisation cost analysis will be undertaken. ETHICS AND DISSEMINATION: The study has been approved by the Western Sydney Local Health District Human Research Ethics Committee-Westmead. Results will be presented at scientific meetings and published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12617001084370; Pre-results.

Experiences and Perspectives of Dietary Management Among Patients on Hemodialysis: An Interview Study.

OBJECTIVES: Diet and fluid management can reduce mortality, serious comorbidities, and debilitating symptoms in patients on hemodialysis, but restrictions may also be a major burden, and nonadherence remains high. We aimed to describe the perspectives and experiences of patients on hemodialysis regarding their dietary management to understand both facilitators and barriers to adherence and to identify strategies to improve care. DESIGN AND METHODS: Semi-structured interviews were conducted with 35 people on maintenance hemodialysis from six dialysis units in New South Wales, Australia. Transcripts were thematically analyzed using principles of grounded theory. RESULTS: We identified 5 major themes. Two themes reflect barriers to dietary change: exacerbating disruption (adding to treatment burden, contradicting healthy eating, confused by fragmented advice, conflicting cultural norms, changing appetite and palate, isolation from family and friends) and losing control (crises derailing discipline, frustrated by failure, combating bodily need for hydration). Three themes represent enablers for dietary change: attaining health benefits (avoiding medical catastrophes, enhancing benefits of dialysis, alleviating and managing symptoms, improving health), achieving treatment goals (building familiarity and acceptance, flexibility and moderation, taking personal responsibility), and succeeding withsupport (leaning on family for strength, trusting expert guidance, empowered with flexible and practical advice, relying on reminders and cues, motivation through shared experience). CONCLUSIONS: Patients on hemodialysis believe dietary control helps to reduce symptom burden and enhance general health and well-being, but competing medical and social issues coupled with contradictory and/or irrelevant dietary advice prevents them from implementing diet and fluid restrictions. Interventions involving collaborative multidisciplinary care including clinicians with dietetic expertise, and consistent information that addresses cultural and personal circumstances, may support adherence to dietary recommendations and improve outcomes.

Perspectives of healthcare providers on the nutritional management of patients on haemodialysis in Australia: an interview study.

OBJECTIVE: To describe the perspectives of healthcare providers on the nutritional management of patients on haemodialysis, which may inform strategies for improving patient-centred nutritional care. DESIGN: Face-to-face semistructured interviews were conducted until data saturation, and thematic analysis based on principles of grounded theory. SETTING: 21 haemodialysis centres across Australia. PARTICIPANTS: 42 haemodialysis clinicians (nephrologists and nephrology trainees (15), nurses (12) and dietitians (15)) were purposively sampled to obtain a range of demographic characteristics and clinical experiences. RESULTS: Six themes were identified: responding to changing clinical status (individualising strategies to patient needs, prioritising acute events, adapting guidelines), integrating patient circumstances (assimilating life priorities, access and affordability), delineating specialty roles in collaborative structures (shared and cohesive care, pivotal role of dietary expertise, facilitating access to nutritional care, perpetuating conflicting advice and patient confusion, devaluing nutritional specialty), empowerment for behaviour change (enabling comprehension of complexities, building autonomy and ownership, developing self-efficacy through engagement, tailoring self-management strategies), initiating and sustaining motivation (encountering motivational hurdles, empathy for confronting life changes, fostering non-judgemental relationships, emphasising symptomatic and tangible benefits, harnessing support networks), and organisational and staffing barriers (staffing shortfalls, readdressing system inefficiencies). CONCLUSIONS: Organisational support with collaborative multidisciplinary teams and individualised patient care were seen as necessary for developing positive patient-clinician relationships, delivering consistent nutrition advice, and building and sustaining patient motivation to enable change in dietary behaviour. Improving service delivery and developing and delivering targeted, multifaceted self-management interventions may enhance current nutritional management of patients on haemodialysis.

Use of rhodamine B to mark the body and seminal fluid of male Aedes aegypti for mark-release-recapture experiments and estimating efficacy of sterile male releases.

BACKGROUND: Recent interest in male-based sterile insect technique (SIT) and incompatible insect technique (IIT) to control Aedes aegypti and Aedes albopictus populations has revealed the need for an economical, rapid diagnostic tool for determining dispersion and mating success of sterilized males in the wild. Previous reports from other insects indicated rhodamine B, a thiol-reactive fluorescent dye, administered via sugar-feeding can be used to stain the body tissue and seminal fluid of insects. Here, we report on the adaptation of this technique for male Ae. aegypti to allow for rapid assessment of competitiveness (mating success) during field releases. METHODOLOGY/PRINCIPLE FINDINGS: Marking was achieved by feeding males on 0.1, 0.2, 0.4 or 0.8% rhodamine B (w/v) in 50% honey solutions during free flight. All concentrations produced >95% transfer to females and successful body marking after 4 days of feeding, with 0.4 and 0.8% solutions producing the longest-lasting body marking. Importantly, rhodamine B marking had no effect on male mating competitiveness and proof-of-principle field releases demonstrated successful transfer of marked seminal fluid to females under field conditions and recapture of marked males. CONCLUSIONS/SIGNIFICANCE: These results reveal rhodamine B to be a potentially useful evaluation method for male-based SIT/IIT control strategies as well as a viable body marking technique for male-based mark-release-recapture experiments without the negative side-effects of traditional marking methods. As a standalone method for use in mating competitiveness assays, rhodamine B marking is less expensive than PCR (e.g. paternity analysis) and stable isotope semen labelling methods and less time-consuming than female fertility assays used to assess competitiveness of sterilised males.

Nutrition in Renal Supportive Care: Patient-driven and flexible.

Renal Supportive Care is an alternative treatment pathway in advanced chronic kidney disease that is being increasingly adopted, particularly in the elderly. Renal Supportive Care uses principles of palliative care and has been developed to enhance the care for dialysis patients with a high symptom burden and those being managed on a non-dialysis pathway. Nutrition management is often an under-recognized component of care and can play an important role in improving patients' quality of life to reduce symptom burden, support physical function and independence and provide appropriate counselling to patients and their families to ensure the goals of Renal Supportive Care are met. Nutrition interventions need to target patient and treatment goals, with frequent monitoring to ensure patient needs are being met. This review outlines available literature on this topic and suggests some practical ways in which nutrition can be enhanced for these patients.

Genetic control of Aedes aegypti: data-driven modelling to assess the effect of releasing different life stages and the potential for long-term suppression.

BACKGROUND: Control of the world's most important vector-borne viral disease, dengue, is a high priority. A lack of vaccines or effective vector control methods means that novel solutions to disease control are essential. The release of male insects carrying a dominant lethal (RIDL) is one such approach that could be employed to control Aedes aegypti. To maximise the potential of RIDL control, optimum release strategies for transgenic mosquitoes are needed. The use of field data to parameterise models allowing comparisons of the release of different life-stages is presented together with recommendations for effective long-term suppression of a wild Ae. aegypti population. METHODS: A compartmental, deterministic model was designed and fitted to data from large-scale pupal mark release recapture (MRR) field experiments to determine the dynamics of a pupal release. Pulsed releases of adults, pupae or a combination of the two were simulated. The relative ability of different release methods to suppress a simulated wild population was examined and methods to maintain long-term suppression of a population explored. RESULTS: The pupal model produced a good fit to field data from pupal MRR experiments. Simulations using this model indicated that adult-only releases outperform pupal-only or combined releases when releases are frequent. When releases were less frequent pupal-only or combined releases were a more effective method of distributing the insects. The rate at which pupae eclose and emerge from release devices had a large influence on the relative efficacy of pupal releases. The combined release approach allows long-term suppression to be maintained with smaller low-frequency releases than adult- or pupal-only release methods. CONCLUSIONS: Maximising the public health benefits of RIDL-based vector control will involve optimising all stages of the control programme. The release strategy can profoundly affect the outcome of a control effort. Adult-only, pupal-only and combined releases all have relative advantages in certain situations. This study successfully integrates field data with mathematical models to provide insight into which release strategies are best suited to different scenarios. Recommendations on effective approaches to achieve long-term suppression of a wild population using combined releases of adults and pupae are provided.

A high-yielding CHO transient system: coexpression of genes encoding EBNA-1 and GS enhances transient protein expression.

An efficient rapid protein expression system is crucial to support early drug development. Transient gene expression is an effective route, and to facilitate the use of the same host cells as for subsequent stable cell line development, we have created a high-yielding Chinese hamster ovary (CHO) transient expression system. Suspension-adapted CHO-K1 host cells were engineered to express the gene encoding Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) with and without the coexpression of the gene for glutamine synthetase (GS). Analysis of the transfectants indicated that coexpression of EBNA-1 and GS enhanced transient expression of a recombinant antibody from a plasmid carrying an OriP DNA element compared to EBNA-1-only transfectants. This was confirmed with the retransfection of an EBNA-1-only cell line with a GS gene. The retransfected cell lines showed an increase in transient expression when compared with that of the EBNA-1-only parent. The transient expression process for the best CHO transient cell line was further developed to enhance protein expression and improve scalability by optimizing the transfection conditions and the cell culture process. This resulted in a scalable CHO transient expression system that is capable of expressing 2 g/L of recombinant proteins such as antibodies. This system can now rapidly provide gram amounts of recombinant antibody to supply preclinical development studies that has comparable product quality to antibody produced from a stably transfected CHO cell line.