An alternative approach to produce versatile retinal organoids with accelerated ganglion cell development

Genetically complex ocular neuropathies, such as glaucoma, are a major cause of visual impairment worldwide. There is a growing need to generate suitable human representative in vitro and in vivo models, as there is no effective treatment available once damage has occured. Retinal organoids are increasingly being used for experimental gene therapy, stem cell replacement therapy and small molecule therapy. There are multiple protocols for the development of retinal organoids available, however, one potential drawback of the current methods is that the organoids can take between 6 weeks and 12 months on average to develop and mature, depending on the specific cell type wanted. Here, we describe and characterise a protocol focused on the generation of retinal ganglion cells within an accelerated four week timeframe without any external small molecules or growth factors. Subsequent long term cultures yield fully differentiated organoids displaying all major retinal cell types. RPE, Horizontal, Amacrine and Photoreceptors cells were generated using external factors to maintain lamination.</p

Влияние условий синтеза на размер наночастиц железа

Показана возможность получения наночастиц железа разного размера путем варьирования условий синтеза. Методами электронной микроскопии, ИК спектроскопии и электронной дифракции изучена их морфология и структура. Установлено, что при нанесении наночастиц железа на угольный носитель размер, распределение и строение частиц не меняется.Показана можливість отримання наночастинок заліза різного розміру шляхом варіювання умов синтезу. Методами електронної мікроскопії, ІЧ спектроскопії та електронної дифракції вивчено їх морфологію та структуру. Знайдено, що при нанесенні наночастинок заліза на носії розмір, розподіл та будова не змінюється.The preparation of monodisperse Fe nanoparticles of various sizes by varying synthesis conditions is reported. Nanoparticles have been studied by transmission electron microscopy, IR spectroscopy, and electron diffraction. It was shown that Fe nanoparticles do not change its size, distribution, and structure after impregnation of support

Cost and cost-eff ectiveness of newborn home visits: fi ndings from the Newhints cluster-randomised controlled trial in rural Ghana

Background Every year, 2·9 million newborn babies die worldwide. A meta-analysis of four cluster-randomised controlled trials estimated that home visits by trained community members in programme settings in Ghana and south Asia reduced neonatal mortality by 12% (95% CI 5–18). We aimed to estimate the costs and cost-eff ectiveness of newborn home visits in a programme setting. Methods We prospectively collected detailed cost data alongside the Newhints trial, which tested the eff ect of a homevisits intervention in seven districts in rural Ghana and showed a reduction of 8% (95% CI –12 to 25%) in neonatal mortality. The intervention consisted of a package of home visits to pregnant women and their babies in the fi rst week of life by community-based surveillance volunteers. We calculated incremental cost-eff ectiveness ratios (ICERs) with Monte Carlo simulation and one-way sensitivity analyses and characterised uncertainty with cost-eff ectiveness planes and cost-eff ectiveness acceptability curves. We then modelled the potential cost-eff ectiveness for baseline neonatal mortality rates of 20–60 deaths per 1000 livebirths with use of a meta-analysis of eff ectiveness estimates. Findings In the 49 zones randomly allocated to receive the Newhints intervention, a mean of 407 (SD 18) communitybased surveillance volunteers undertook home visits for 7848 pregnant women who gave birth to 7786 live babies in 2009. Annual economic cost of implementation was US$203 998, or$0·53 per person. In the base-case analysis, the Newhints intervention cost a mean of $10 343 (95$352 (95% CI 104 to –268) per discounted life-year saved, and had a 72% chance of being highly cost eff ective with respect to Ghana’s 2009 gross domestic product per person. Key determinants of cost-eff ectiveness were the discount rate, protective eff ectiveness, baseline neonatal mortality rate, and implementation costs. In the scenarios modelled with the meta-analysis results, the ICER increased from $127 per life-year saved at a neonatal mortality rate of 60 deaths per 1000 livebirths, to$379 per life-year saved at a rate of 20 deaths per 1000 livebirths. The strategy had at least a 99% probability of being highly cost eff ective for lower-middle-income countries in all neonatal mortality rate scenarios modelled, and at least a 95% probability of being highly cost eff ective for low-income countries at neonatal mortality rates of 30 or more deaths per 1000 livebirths. Interpretation Our fi ndings show that the seemingly modest mortality reductions achieved by a newborn home-visit strategy might in fact be cost eff ective. In Ghana, such strategies are also likely to be aff ordable. Our fi ndings support recommendations from WHO and UNICEF that low-income and middle-income countries implement newborn home visits

The seasonality of tuberculosis, sunlight, vitamin D, and household crowding.

BACKGROUND: Unlike other respiratory infections, tuberculosis diagnoses increase in summer. We performed an ecological analysis of this paradoxical seasonality in a Peruvian shantytown over 4 years. METHODS: Tuberculosis symptom-onset and diagnosis dates were recorded for 852 patients. Their tuberculosis-exposed cohabitants were tested for tuberculosis infection with the tuberculin skin test (n = 1389) and QuantiFERON assay (n = 576) and vitamin D concentrations (n = 195) quantified from randomly selected cohabitants. Crowding was calculated for all tuberculosis-affected households and daily sunlight records obtained. RESULTS: Fifty-seven percent of vitamin D measurements revealed deficiency (<50 nmol/L). Risk of deficiency was increased 2.0-fold by female sex (P < .001) and 1.4-fold by winter (P < .05). During the weeks following peak crowding and trough sunlight, there was a midwinter peak in vitamin D deficiency (P < .02). Peak vitamin D deficiency was followed 6 weeks later by a late-winter peak in tuberculin skin test positivity and 12 weeks after that by an early-summer peak in QuantiFERON positivity (both P < .04). Twelve weeks after peak QuantiFERON positivity, there was a midsummer peak in tuberculosis symptom onset (P < .05) followed after 3 weeks by a late-summer peak in tuberculosis diagnoses (P < .001). CONCLUSIONS: The intervals from midwinter peak crowding and trough sunlight to sequential peaks in vitamin D deficiency, tuberculosis infection, symptom onset, and diagnosis may explain the enigmatic late-summer peak in tuberculosis

Evaluating the implementation of community volunteer assessment and referral of sick babies: lessons learned from the Ghana Newhints home visits cluster randomized controlled trial.

A World Health Organization (WHO)/United Nations Children's Fund (UNICEF) (2009) joint statement recommended home visits by community-based agents as a strategy to improve newborn survival, based on promising results from Asia. This article presents detailed evaluation of community volunteer assessment and referral implemented within the Ghana Newhints home visits cluster-Randomized Controlled Trial (RCT). It highlights the lessons learned to inform implementation/scale-up of this model in similar settings. The evaluation used a conceptual framework adopted for increasing access to care for sick newborns and involves three main steps, each with a specific goal and key requirements to achieving this. These steps are: sick newborns are identified within communities and referred; families comply with referrals and referred babies receive appropriate management at health facilities. Evaluation data included interviews with 4006 recently delivered mothers; records on 759 directly observed volunteer assessments and 52 validation of supervisors' assessments; newborn care quality assessment in 86 health facilities and in-depth interviews (IDIs) with 55 mothers, 21 volunteers and 15 health professionals. Assessment accuracy of volunteers against supervisors and physician was assessed using Kappa (agreement coefficient). IDIs were analysed by generating and indexing into themes, and exploring relationships between themes and their contextual interpretations. This evaluation demonstrated that identifying, understanding and implementing the key requirements for success in each step of volunteer assessment and referrals was pivotal to success. In Newhints, volunteers (CBSVs) were trusted by families, their visits were acceptable and they engaged mothers/families in decisions, resulting in unprecedented 86% referral compliance and increased (55-77%) care seeking for sick newborns. Poor facility care quality, characterized by poor health worker attitudes, limited the mortality reduction. The important implication for future implementation of home visits in similar settings is that, with 100% specificity but 80% sensitivity of referral decisions, volunteers might miss some danger signs but if successful implementation must translate into mortality reductions, concurrent improvement in facility newborn care quality is imperative

Quality of newborn care: a health facility assessment in rural Ghana using survey, vignette and surveillance data

Peer reviewe

Configuring Balanced Scorecards for Measuring Health System Performance: Evidence from 5 Years' Evaluation in Afghanistan

Anbrasi Edward and colleagues report the results of a balanced scorecard performance system used to examine 29 key performance indicators over a 5-year period in Afghanistan, between 2004 and 2008

Comparing health system performance assessment and management approaches in the Netherlands and Ontario, Canada

BACKGROUND: Given the proliferation and the growing complexity of performance measurement initiatives in many health systems, the Netherlands and Ontario, Canada expressed interests in cross-national comparisons in an effort to promote knowledge transfer and best practise. To support this cross-national learning, a study was undertaken to compare health system performance approaches in The Netherlands with Ontario, Canada. METHODS: We explored the performance assessment framework and system of each constituency, the embeddedness of performance data in management and policy processes, and the interrelationships between the frameworks. Methods used included analysing governmental strategic planning and policy documents, literature and internet searches, comparative descriptive tables, and schematics. Data collection and analysis took place in Ontario and The Netherlands. A workshop to validate and discuss the findings was conducted in Toronto, adding important insights to the study. RESULTS: Both Ontario and The Netherlands conceive health system performance within supportive frameworks. However they differ in their assessment approaches. Ontario's Scorecard links performance measurement with strategy, aimed at health system integration. The Dutch Health Care Performance Report (Zorgbalans) does not explicitly link performance with strategy, and focuses on the technical quality of healthcare by measuring dimensions of quality, access, and cost against healthcare needs. A backbone 'five diamond' framework maps both frameworks and articulates the interrelations and overlap between their goals, themes, dimensions and indicators. The workshop yielded more contextual insights and further validated the comparative values of each constituency's performance assessment system. CONCLUSION: To compare the health system performance approaches between The Netherlands and Ontario, Canada, several important conceptual and contextual issues must be addressed, before even attempting any future content comparisons and benchmarking. Such issues would lend relevant interpretational credibility to international comparative assessments of the two health systems

The Dutch Consumer Quality Index: an example of stakeholder involvement in indicator development

Background: Like in several other Western countries, in the Dutch health care system regulated competition has been introduced. In order to make this work, comparable information is required about the performance of health care providers in terms of effectiveness, safety and patient experiences. Without further coordination, external actors will all try to force health care providers to be transparent. For health care providers this might result in a situation in which they have to deliver data for several sets of indicators, defined by different actors. Therefore, in the Netherlands an effort is made to define national sets of performance indicators and related measuring instruments. In this article, the following questions are addressed, using patient experiences as an example: - When and how are stakeholders involved in the development of indicators and instruments that measure the patients' experiences with health care providers? - Does this involvement lead to indicators and instruments that match stakeholders' information needs? Discussion: The Dutch experiences show that it is possible to implement national indicator sets and to reach consensus about what needs to be measured. Preliminary evaluations show that for health care providers and health insurers the benefits of standardization outweigh the possible loss of tailor-made information. However, it has also become clear that particular attention should be given to the participation of patient/consumer organisations. Summary: Stakeholder involvement is complex and time-consuming. However, it is the only way to balance the information needs of all the parties that ask for and benefit from transparency, without frustrating the health care system.