Epidemiology and control of malaria and other arthropod born diseases

Malaria and other arthropod born diseases remain a serious public health problem affecting the lives and health of certain social groups when the two basic strategies to control fail due to : (1) the lack of effective chemoprophylaxis/chemotherapy or the rapid development of drug resistance of the infectious agents and (2) the ineffectiveness of pesticides or the arthropod vectors develop resistance to them. These situations enhances the need for the design and implementation of other alternatives for sustainable health programmes. The application of the epidemiological methods is essential not only for analyzing the relevant data for the understanding of the biological characteristics of the infectious agents, their reservoirs and vectors and the methods for their control, but also for the assessment of the human behaviour, the environmental, social and economic factors involved in disease transmission and the capacity of the health systems to implement interventions for both changes in human behaviour and environmental management to purpose guaranteed prevention and control of malaria and other arthropod born diseases with efficiency, efficacy and equity. This paper discuss the evolution of the malaria arthropod diseases programmes in the American Region and the perspectives for their integration into health promotion programs and emphasis is made in the need to establish solid basis in the decision-making process for the selection of intervention strategies to remove the risk factors determining the probability to get sick or die from ABDs. The implications of the general planning and the polices to be adopted in an area should be analyzed in the light of programme feasibility at the local level, in the multisectoral context specific social groups and taking in consideration the principles of stratification and equity

The gamma-crystallins and human cataracts: a puzzle made clearer.

Despite the fact that cataracts constitute the leading cause of blindness worldwide, the mechanisms of lens opacification remain unclear. We recently mapped the aculeiform cataract to the gamma-crystallin locus (CRYG) on chromosome 2q33-35, and mutational analysis of the CRYG-genes cluster identified the aculeiform-cataract mutation in exon 2 of gamma-crystallin D (CRYGD). This mutation occurred in a highly conserved amino acid and could be associated with an impaired folding of CRYGD. During our study, we observed that the previously reported Coppock-like-cataract mutation, the first human cataract mutation, in the pseudogene CRYGE represented a polymorphism seen in 23% of our control population. Further analysis of the original Coppock-like-cataract family identified a missense mutation in a highly conserved segment of exon 2 of CRYGC. These mutations were not seen in a large control population. There is no direct evidence, to date, that up-regulation of a pseudogene causes cataracts. To our knowledge, these findings are the first evidence of an involvement of CRYGC and support the role of CRYGD in human cataract formation.

Egg Structures of Anopheles fluminensis and Anopheles shannoni

Eggs of two species belonging to the Arribalzagia Series of the Laticorn Section of Anopheles (Anopheles) collected in Brazil are described from scanning electron micrographs. The An. fluminensis egg is long with shallow floats displaced far dorsally. The narrow deck region is overlain by a frill modified into prominent ridges that are nearly continuous to both ends of the egg. Slightly opened decks at both poles contain an average of four lobed tubercles. Polygonal, plastron-type chorionic cells cover the lateral and dorsal surfaces. The egg of An. shannoni is unique in possessing 22-27 fingerlike filaments that project with regular spacing from each of its massive floats. These filaments and their bases are highly perforated and are believed to trap air and support flotation of the egg with the dorsal surface up, contrary to the usual orientation for anophelines. The eggs are compared with those of related species bearing similar structures, notably An. fluminensis with An. mediopunctatus s.s and An. shannoni with An. peryassui

On Leishmania enriettii and Other Enigmatic Leishmania Species of the Neotropics

There are 20 named species of the genus Leishmania at present recognized in the New World, of which 14 are known to infect man. The present paper discusses the biological, biochemical and ecological features, where known, of six species which have not till now been found to cause human leishmaniasis; namely, Leishmania (Leishmania) enriettii, L. (L.) hertigi, L. (L.) deanei, L. (L.) aristidesi, L. (L.) forattinii and L. (Viannia) equatorensis. A protocol is suggested for attempts to discover the natural mammalian host(s) and sandfly vector of L. (L.) enriettii. Doubt is cast on the validity of the species L. herreri, described in Costa Rican sloths. Following the concensus of opinion that modern trypanosomatids derive from monogenetic intestinal flagellates of arthropods, phlebotomine sandflies are best regarded as the primary hosts of Leishmania species, with mammals acting as secondary hosts providing a source of parasites for these insects. There are probably natural barriers limiting the life-cycle of most leishmanial parasites to specific sandfly vectors

Uncovering a role for micro-RNAs in sleep homeostasis and energy metabolism

Micro-RNAs (miRNAs) are key, post-transcriptional regulators of gene expression and have been implicated in almost every cellular process investigated thus far. However, their role in sleep, in particular the homeostatic aspect of sleep control, has received little attention. We here assessed the effects of sleep deprivation on the brain miRNA transcriptome in the mouse. Sleep deprivation affected miRNA expression in a brain-region specific manner. The forebrain expression of the miRNA miR-709 was affected the most and in situ analyses confirmed its robust increase throughout the brain, especially in the cerebral cortex and the hippocampus. The hippocampus was a major target of the sleep deprivation affecting 37 miRNAs compared to 52 in the whole forebrain. Moreover, independent from the sleep deprivation condition, miRNA expression was highly region-specific with 45% of all expressed miRNAs showing higher expression in hippocampus and 55% in cortex. Next we demonstrated that down-regulation of miRNAs in Com/c2o-expressing neurons of adult mice, through a conditional and inducible Dicer knockout mice model (cKO), results in an altered homeostatic response after sleep deprivation eight weeks following the tamoxifen-induced recombination. Dicer cKO mice showed a larger increase in the electro-encephalographic (EEG) marker of sleep pressure, EEG delta power, and a reduced Rapid Eye Movement sleep rebound, compared to controls, highlighting a functional role of miRNAs in sleep homeostasis. Beside a sleep phenotype, Dicer cKO mice developed an unexpected, severe obesity phenotype associated with hyperphagia and altered metabolism. Even more surprisingly, after reaching maximum body weight 5 weeks after tamoxifen injection, obese cKO mice spontaneously started losing weight as rapidly as it was gained. Brain transcriptome analyses in obese mice identified several obesity-related pathways (e.g. leptin, somatostatin, and nemo-like kinase signaling), as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin). A gene cluster with anti-correlated expression in the cerebral cortex of post-obese compared to obese mice was enriched for synaptic plasticity pathways. While other studies have identified a role for miRNAs in obesity, we here present a unique model that allows for the study of processes involved in reversing obesity. Moreover, our study identified the cortex as a brain area important for body weight homeostasis. Together, these observations strongly suggest a role for miRNAs in the maintenance of homeostatic processes in the mouse, and support the hypothesis of a tight relationship between sleep and metabolism at a molecular - Les micro-ARNS (miARNs) sont des régulateurs post-transcriptionnels de l'expression des gènes, impliqués dans la quasi-totalité des processus cellulaires. Cependant, leur rôle dans la régulation du sommeil, et en particulier dans le maintien de l'homéostasie du sommeil, n'a reçu que très peu d'attention jusqu'à présent. Dans cette étude, nous avons étudié les conséquences d'une privation de sommeil sur l'expression cérébrale des miARNs chez la souris, et observé des changements dans l'expression de nombreux miARNs. Dans le cerveau antérieur, miR-709 est le miARN le plus affecté par la perte de sommeil, en particulier dans le cortex cérébral et l'hippocampe. L'hippocampe est la région la plus touchée avec 37 miARNs changés comparés à 52 dans le cerveau entier. Par ailleurs, indépendamment de la privation de sommeil, certains miARNs sont spécifiquement enrichis dans certaines aires cérébrales, 45% des miARNs étant surexprimés dans l'hippocampe contre 55% dans le cortex. Dans une seconde étude, nous avons observé que la délétion de DICER, enzyme essentielle à la biosynthèse des miARNs, et la perte subséquente des miARNs dans les neurones exprimant la protéine CAMK2a altère la réponse homéostatique à une privation de sommeil, 8 semaines après l'induction de la recombinaison génétique par le tamoxifen. Les souris sans Dicer (cKO) ont une plus large augmentation de l'EEG delta power, le principal marqueur électro-encéphalographique du besoin de sommeil, comparée aux contrôles, ainsi qu'un rebond en sommeil paradoxal plus petit. De façon surprenante, les souris Dicer cKO développent une obésité rapide, sévère et transitoire, associée à de l'hyperphagie et une altération de leur métabolisme énergétique. Après avoir atteint un pic maximal d'obésité, les souris cKO entrent spontanément dans une période de perte de poids rapide. L'analyse du transcriptome cérébral des souris obèses nous a permis d'identifier des voies associées à l'obésité (leptine, somatostatine et nemo-like kinase), et à la prise alimentaire (Pmch, Neurotensin), tandis que celui des souris post-obèses a révélé un groupe de gènes liés à la plasticité synaptique. Au-delà des nombreux modèles d'obésité existant chez la souris, notre étude présente un modèle unique permettant d'étudier les mécanismes sous-jacent la perte de poids. De plus, nous avons mis en évidence un rôle important du cortex cérébral dans le maintien de la balance énergétique. En conclusion, toutes ces observations soutiennent l'idée que les miARNs sont des régulateurs cruciaux dans le maintien des processus homéostatiques et confortent l'hypothèse d'une étroite relation moléculaire entre le sommeil et le métabolisme.

Physical and Sensory Disability Strategy and Action Plan 2012-2015 (PDF 1.180KB)

A strategy to improve outcomes, services and support for people in Northern Ireland who have a physical, communication or sensory disability.

Hierarchy of Notch-Delta interactions promoting T cell lineage commitment and maturation.

Notch1 (N1) receptor signaling is essential and sufficient for T cell development, and recently developed in vitro culture systems point to members of the Delta family as being the physiological N1 ligands. We explored the ability of Delta1 (DL1) and DL4 to induce T cell lineage commitment and/or maturation in vitro and in vivo from bone marrow (BM) precursors conditionally gene targeted for N1 and/or N2. In vitro DL1 can trigger T cell lineage commitment via either N1 or N2. N1- or N2-mediated T cell lineage commitment can also occur in the spleen after short-term BM transplantation. However, N2-DL1-mediated signaling does not allow further T cell maturation beyond the CD25(+) stage due to a lack of T cell receptor beta expression. In contrast to DL1, DL4 induces and supports T cell commitment and maturation in vitro and in vivo exclusively via specific interaction with N1. Moreover, comparative binding studies show preferential interaction of DL4 with N1, whereas binding of DL1 to N1 is weak. Interestingly, preferential N1-DL4 binding reflects reduced dependence of this interaction on Lunatic fringe, a glycosyl transferase that generally enhances the avidity of Notch receptors for Delta ligands. Collectively, our results establish a hierarchy of Notch-Delta interactions in which N1-DL4 exhibits the greatest capacity to induce and support T cell development.

Innovation and absorptive capacity: What is the role of technological frontier?

This paper explores how absorptive capacity affects the innovative performance and productivity dynamics of Spanish firms. A firm’s efficiency levels are measured using two variables: the labour productivity and the Total Factor Productivity (TFP). The theoretical framework is based on the seminal contributions of Cohen and Levinthal (1989, 1990) regarding absorptive capacity; and the applied framework is based on the four-stage structural model proposed by Crépon, Duguet and Mairesse (1998) for setting the determinants of R&D, the effects of R&D activities on innovation outputs, and the impacts of innovation on firm productivity. The present study uses a twostage structural model. In the first stage, a probit estimation is used to investigate how the sources of R&D, the absorptive capacity and a vector of the firm’s individual features influence the firm’s likelihood of developing innovations in products or processes. In the second phase, a quantile regression is used to analyze the effect of R&D sources, absorptive capacity and firm characteristics on productivity. This method shows the elasticity of each exogenous variable on productivity according to the firms’ levels of efficiency, and thus allows us to distinguish between firms that are close to the technological frontier and those that are further away from it. We used extensive firm-level panel data from 5,575 firms for the 2004-2009 period. The results show that the internal absorptive capacity has a strong impact on the productivity of firms, whereas the role of external absorptive capacity differs according to nature of the each industry and according the distance of firms from the technological frontier. Key words: R&D sources, innovation strategies, absorptive capacity, technological distance, quantile regression.

New Strategic Direction for Alcohol and Drugs (2006-2011) (Online Publication)

Executive Summary and Strategy Document (May 2006) The New Strategic Direction has a set of overarching long-term aims to: • Provide accessible and effective treatment and support for people who are consuming alcohol and/or using drugs in a potentially hazardous, harmful or dependent way. • Reduce the level, breadth and depth of alcohol and drug-related harm to users, their families and/or their carers and the wider community. • Increase awareness on all aspects of alcohol and drug-related harm in all settings and for all age groups. • Integrate those policies which contribute to the reduction of alcohol and drug-related harm into all Government Department strategies. • Develop a competent skilled workforce across all sectors that can respond to the complexities of alcohol and drug use and misuse. • Promote opportunities for those under the age of 18 years to develop appropriate skills, attitudes and behaviours to enable them to resist societal pressures to drink alcohol and/or use illicit drugs, with a particular emphasis on those identified as potentially vulnerable. • Reduce the availability of illicit drugs in Northern Ireland åÊ

New Strategic Direction for Alcohol and Drugs (2006-2011) Executive Summary

Executive Summary and Strategy Document (May 2006) The New Strategic Direction has a set of overarching long-term aims to: • Provide accessible and effective treatment and support for people who are consuming alcohol and/or using drugs in a potentially hazardous, harmful or dependent way. • Reduce the level, breadth and depth of alcohol and drug-related harm to users, their families and/or their carers and the wider community. • Increase awareness on all aspects of alcohol and drug-related harm in all settings and for all age groups. • Integrate those policies which contribute to the reduction of alcohol and drug-related harm into all Government Department strategies. • Develop a competent skilled workforce across all sectors that can respond to the complexities of alcohol and drug use and misuse. • Promote opportunities for those under the age of 18 years to develop appropriate skills, attitudes and behaviours to enable them to resist societal pressures to drink alcohol and/or use illicit drugs, with a particular emphasis on those identified as potentially vulnerable. • Reduce the availability of illicit drugs in Northern Ireland

Effective Utilisation of Professional Skills of Nurses and Midwives

The Working Group recommends that the grade of Health Care Assistant/Maternity Health Care Assistant be introduced as a member of the healthcare team to assist and support the nursing and midwifery function. Chapter two of the report explores the complementary roles of health care assistants and nurses and midwives. Chapter three examines issues related to delegation and integration of the health care assistant to the care team. Chapter four makes recommendations related to the education and training of health care assistants. The Working Groupâ?Ts recommendations are underpinned by a comprehensive literature review Download the Report here

Research Strategy for Nursing and Midwifery in Ireland 2003-2008. Review of Attainments

The Research Strategy for Nursing and Midwifery in Ireland (Department of Health and Children, 2003) was a response to the Commission on Nursing’s (Government of Ireland, 1998: p114) suggestion that a national strategy be developed to guide and support the emerging need for the professions of nursing and midwifery to develop a research base as a fundamental to practice. The Commission itself had found a dearth of published Irish nursing and midwifery research (Government of Ireland, 1998; Condell, 1998) due to a lack of policy direction and funding availability. Download document here

Intergenic and external transcribed spacers of ribosomal RNA genes in lizard-infecting Leishmania: molecular structure and phylogenetic relationship to mammal-infecting Leishmania in the subgenus Leishmania (Leishmania)

To establish the relationships of the lizard- and mammal-infecting Leishmania, we characterized the intergenic spacer region of ribosomal RNA genes from L. tarentolae and L. hoogstraali. The organization of these regions is similar to those of other eukaryotes. The intergenic spacer region was approximately 4 kb in L. tarentolae and 5.5 kb in L. hoogstraali. The size difference was due to a greater number of 63-bp repetitive elements in the latter species. This region also contained another element, repeated twice, that had an inverted octanucleotide with the potential to form a stem-loop structure that could be involved in transcription termination or processing events. The ribosomal RNA gene localization showed a distinct pattern with one chromosomal band (2.2 Mb) for L. tarentolae and two (1.5 and 1.3 Mb) for L. hoogstraali. The study also showed sequence differences in the external transcribed region that could be used to distinguish lizard Leishmania from the mammalian Leishmania. The intergenic spacer region structure features found among Leishmania species indicated that lizard and mammalian Leishmania are closely related and support the inclusion of lizard-infecting species into the subgenus Sauroleishmania proposed by Saf'janova in 1982.

Performance of OptiMAL® in the diagnosis of Plasmodium vivax and Plasmodium falciparum infections in a malaria referral center in Colombia

Alternative, non-microscopic methods for the diagnosis of malaria have recently become available. Among these, rapid dipstick methods stand out. One such test, OptiMAL®, is based on the immunochromatographic detection of Plasmodium lactate dehydrogenase (pLDH) and has the capacity to detect and distinguish infections caused by P. falciparum and Plasmodium sp. This capacity is particularly important in countries where different species of Plasmodium co-exist. In this study we evaluated the performance of OptiMAL® in an urban referral center for malaria diagnosis. Two sets of patients were included: one (n = 112) having predetermined infections with P. falciparum or P. vivax and individuals with negative blood smears; and another consisting of all eligible consecutive patients (n = 80) consulting for diagnosis at the referral center during one month. The overall diagnostic efficiency of OptiMAL® for both sets of patients was 96.9%. Efficiency was higher for P. vivax (98.1%) than for P. falciparum (94.9%). These results corroborate the diagnostic utility of OptiMAL® in settings where P. vivax and P. falciparum co-exist and support its implementation where microscopic diagnosis is unavailable and in circumstances that exceed the capacity of the local microscopic diagnosis facility.

Evaluation of pilot initiatives undertaken in the North Eastern and South Eastern Health Boards on the provision of General Practitioner out-of-hours services in those areas

To assess the efficiency and effectiveness of the management, administrative and support structures for the General Practitioner out-of-hours pilot projects in the North Eastern and South Eastern Health Boards having regard to value for money and service enhancement considerations Download the Report here