The health and economic benefits of the global programme to eliminate lymphatic filariasis (2000-2014)

Background Lymphatic filariasis (LF), also known as elephantiasis, is a neglected tropical disease (NTD) targeted for elimination through a Global Programme to Eliminate LF (GPELF). Between 2000 and 2014, the GPELF has delivered 5.6 billion treatments to over 763 million people. Updating the estimated health and economic benefits of this significant achievement is important in justifying the resources and investment needed for eliminating LF. Method We combined previously established models to estimate the number of clinical manifestations and disability-adjusted life years (DALYs) averted from three benefit cohorts (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The economic savings associated with this disease prevention was then analysed in the context of prevented medical expenses incurred by LF clinical patients, potential income loss through lost-labour, and prevented costs to the health system to care for affected individuals. The indirect cost estimates were calculated using the human capital approach. A combination of four wage sources was used to estimate the fair market value of time for an agricultural worker with LF infection (to ensure a conservative estimate, the lowest wage value was used). Results We projected that due to the first 15 years of the GPELF 36 million clinical cases and 175 (116–250) million DALYs will potentially be averted. It was estimated that due to this notable health impact, 100.5 billion US Dollars will potentially be saved over the lifetimes of the benefit cohorts. This total amount results from summing the medical expenses incurred by LF patients (3 billion US Dollars), potential income loss (94 billion US Dollars), and costs to the health system (3.5 billion US Dollars) that were projected to be prevented. The results were subjected to sensitivity analysis and were most sensitive to the assumed percentage of work hours lost for those suffering from chronic disease (changing the total economic benefit between 69.30–150.7 billion US Dollars). Conclusions Despite the limitations of any such analysis, this study identifies substantial health and economic benefits that have resulted from the first 15 years of the GPELF, and it highlights the value and importance of continued investment in the GPELF.</p

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

Investment success in public health: an analysis of the cost-effectiveness and cost-benefit of the global programme to eliminate lymphatic filariasis

Background. It has been estimated that $154 million per year will be required during 2015–2020 to continue the Global Programme to Eliminate Lymphatic Filariasis (GPELF). In light of this, it is important to understand the program’s current value. Here, we evaluate the cost-effectiveness and cost-benefit of the preventive chemotherapy that was provided under the GPELF between 2000 and 2014. In addition, we also investigate the potential cost-effectiveness of hydrocele surgery. Methods. Our economic evaluation of preventive chemotherapy was based on previously published health and economic impact estimates (between 2000 and 2014). The delivery costs of treatment were estimated using a model developed by the World Health Organization. We also developed a model to investigate the number of disability-adjusted life years (DALYs) averted by a hydrocelectomy and identified the cost threshold under which it would be considered cost-effective. Results. The projected cost-effectiveness and cost-benefit of preventive chemotherapy were very promising, and this was robust over a wide range of costs and assumptions. When the economic value of the donated drugs was not included, the GPELF would be classed as highly cost-effective. We projected that a typical hydrocelectomy would be classed as highly cost-effective if the surgery cost less than$66 and cost-effective if less than $398 (based on the World Bank’s cost-effectiveness thresholds for low income countries). Conclusions. Both the preventive chemotherapy and hydrocele surgeries provided under the GPELF are incredibly cost-effective and offer a very good investment in public health

Monitoring Cognitive and Emotional Processes Through Pupil and Cardiac Response During Dynamic Versus Logical Task

The paper deals with the links between physiological measurements and cognitive and emotional functioning. As long as the operator is a key agent in charge of complex systems, the definition of metrics able to predict his performance is a great challenge. The measurement of the physiological state is a very promising way but a very acute comprehension is required; in particular few studies compare autonomous nervous system reactivity according to specific cognitive processes during task performance and task related psychological stress is often ignored. We compared physiological parameters recorded on 24 healthy subjects facing two neuropsychological tasks: a dynamic task that require problem solving in a world that continually evolves over time and a logical task representative of cognitive processes performed by operators facing everyday problem solving. Results showed that the mean pupil diameter change was higher during the dynamic task; conversely, the heart rate was more elevated during the logical task. Finally, the systolic blood pressure seemed to be strongly sensitive to psychological stress. A better taking into account of the precise influence of a given cognitive activity and both workload and related task-induced psychological stress during task performance is a promising way to better monitor operators in complex working situations to detect mental overload or pejorative stress factor of error

Downregulated parafibromin expression is a promising marker for pathogenesis, invasion, metastasis and prognosis of gastric carcinomas

Parafibromin is a protein encoded by the hyperparathyroidism 2 oncosuppressor gene and its downregulated expression is involved in pathogenesis of parathyroid carcinomas. To clarify the roles of parafibromin expression in tumourigenesis and progression of gastric carcinomas, it was examined by immunohistochemistry (IHC) on tissue microarray containing gastric carcinomas (n = 508), adenomas (n = 45) and gastritis (n = 49) with a comparison of its expression with clinicopathological parametres of carcinomas. Gastric carcinoma cell lines (MKN28, AGS, MKN45, KATO-III and HGC-27) were studied for parafibromin expression by IHC and western blot. Parafibromin expression was localised in the nucleus of gastric epithelial cells, adenoma, carcinoma cells and cell lines. Its expression was gradually decreased from gastritis to gastric carcinoma, through gastric adenomas (p < 0.05) and inversely correlated with tumour size, depth of invasion, lymphatic invasion, lymph node metastasis and Union Internationale Contre le Cancer (UICC) staging (p < 0.05) but not with sex or venous invasion (p > 0.05). Parafibromin was strongly expressed in older carcinoma patients compared with younger ones (p < 0.05). There was stronger positivity of parafibromin in intestinal-type than diffuse-type carcinomas (p < 0.05). Univariate analysis indicated cumulative survival rate of patients with positive parafibromin expression to be higher than without its expression (p < 0.05). Multivariate analysis showed that age, tumour size, depth of invasion, lymphatic invasion, lymph node metastasis, UICC staging and Lauren’s classification but not sex, venous invasion or parafibromin expression were independent prognostic factors for carcinomas(p < 0.05). Downregulated parafibromin expression possibly contributed to pathogenesis, growth, invasion and metastasis of gastric carcinomas. It was considered as a promising marker to indicate the aggressive behaviours and prognosis of gastric carcinomas

Who mixes with whom among men who have sex with men? Implications for modelling the HIV epidemic in southern India

In India, the identity of men who have sex with men (MSM) is closely related to the role taken in anal sex (insertive, receptive or both), but little is known about sexual mixing between identity groups. Both role segregation (taking only the insertive or receptive role) and the extent of assortative (within-group) mixing are known to affect HIV epidemic size in other settings and populations. This study explores how different possible mixing scenarios, consistent with behavioural data collected in Bangalore, south India, affect both the HIV epidemic, and the impact of a targeted intervention. Deterministic models describing HIV transmission between three MSM identity groups (mostly insertive Panthis/Bisexuals, mostly receptive Kothis/Hijras and versatile Double Deckers), were parameterised with behavioural data from Bangalore. We extended previous models of MSM role segregation to allow each of the identity groups to have both insertive and receptive acts, in differing ratios, in line with field data. The models were used to explore four different mixing scenarios ranging from assortative (maximising within-group mixing) to disassortative (minimising within-group mixing). A simple model was used to obtain insights into the relationship between the degree of within-group mixing, R0 and equilibrium HIV prevalence under different mixing scenarios. A more complex, extended version of the model was used to compare the predicted HIV prevalence trends and impact of an HIV intervention when fitted to data from Bangalore. With the simple model, mixing scenarios with increased amounts of assortative (within-group) mixing tended to give rise to a higher R0 and increased the likelihood that an epidemic would occur. When the complex model was fit to HIV prevalence data, large differences in the level of assortative mixing were seen between the fits identified using different mixing scenarios, but little difference was projected in future HIV prevalence trends. An oral pre-exposure prophylaxis (PrEP) intervention was modelled, targeted at the different identity groups. For intervention strategies targeting the receptive or receptive and versatile MSM together, the overall impact was very similar for different mixing patterns. However, for PrEP scenarios targeting insertive or versatile MSM alone, the overall impact varied considerably for different mixing scenarios; more impact was achieved with greater levels of disassortative mixing

Developing and implementing an integrated delirium prevention system of care:a theory driven, participatory research study

Background: Delirium is a common complication for older people in hospital. Evidence suggests that delirium incidence in hospital may be reduced by about a third through a multi-component intervention targeted at known modifiable risk factors. We describe the research design and conceptual framework underpinning it that informed the development of a novel delirium prevention system of care for acute hospital wards. Particular focus of the study was on developing an implementation process aimed at embedding practice change within routine care delivery. Methods: We adopted a participatory action research approach involving staff, volunteers, and patient and carer representatives in three northern NHS Trusts in England. We employed Normalization Process Theory to explore knowledge and ward practices on delirium and delirium prevention. We established a Development Team in each Trust comprising senior and frontline staff from selected wards, and others with a potential role or interest in delirium prevention. Data collection included facilitated workshops, relevant documents/records, qualitative one-to-one interviews and focus groups with multiple stakeholders and observation of ward practices. We used grounded theory strategies in analysing and synthesising data. Results: Awareness of delirium was variable among staff with no attention on delirium prevention at any level; delirium prevention was typically neither understood nor perceived as meaningful. The busy, chaotic and challenging ward life rhythm focused primarily on diagnostics, clinical observations and treatment. Ward practices pertinent to delirium prevention were undertaken inconsistently. Staff welcomed the possibility of volunteers being engaged in delirium prevention work, but existing systems for volunteer support were viewed as a barrier. Our evolving conception of an integrated model of delirium prevention presented major implementation challenges flowing from minimal understanding of delirium prevention and securing engagement of volunteers alongside practice change. The resulting Prevention of Delirium (POD) Programme combines a multi-component delirium prevention and implementation process, incorporating systems and mechanisms to introduce and embed delirium prevention into routine ward practices. Conclusions: Although our substantive interest was in delirium prevention, the conceptual and methodological strategies pursued have implications for implementing and sustaining practice and service improvements more broadly

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

Validation of the diabetes, hypertension and hyperlipidemia (DHL) knowledge instrument in Malaysia

BACKGROUND: Patient's knowledge on diabetes, hypertension and hyperlipidaemia and its medications can be used as one of the outcome measures to assess the effectiveness of educational intervention. To date, no such instrument has been validated in Malaysia. Therefore, the aim of this study was to evaluate the validity and reliability of the Diabetes, Hypertension and Hyperlipidemia (DHL) knowledge instrument for assessing the knowledge of patients with type 2 diabetes in Malaysia. METHODS: A 28-item instrument which comprised of 5 domains: diabetes, hypertension, hyperlipidemia, medications and general issues was designed and tested. One point was given for every correct answer, whilst zero was given for incorrect answers. Scores ranged from 0 to 28, which were then converted into percentage. This was administered to 77 patients with type 2 diabetes in a tertiary hospital, who were on medication(s) for diabetes and who could understand English (patient group), and to 40 pharmacists (professional group). The DHL knowledge instrument was administered again to the patient group after one month. Excluded were patients less than 18 years old. RESULTS: Flesch reading ease was 60, which is satisfactory, while the mean difficulty factor(SD) was 0.74(0.21), indicating that DHL knowledge instrument was moderately easy. Internal consistency of the instrument was good, with Cronbach's alpha = 0.791. The test-retest scores showed no significant difference for 26 out of the 28 items, indicating that the questionnaire has achieved stable reliability. The overall mean(SD) knowledge scores was significantly different between the patient and professional groups 74.35(14.88) versus 93.84(6.47), p < 0.001. This means that the DHL knowledge instrument could differentiate the knowledge levels of participants. The DHL knowledge instrument shows similar psychometric properties as other validated questionnaires. CONCLUSIONS: The DHL knowledge instrument shows good promise to be adopted as an instrument for assessing diabetic patients' knowledge concerning their disease conditions and medications in Malaysia