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Retinohypothalamic projections in the hamster and rat demonstrated using cholera toxin.

The organization of retinohypothalamic tract (RHT) projections in the rat and hamster was studied using anterograde transport of cholera toxin conjugated to HRP (CT-HRP). In both species the major RHT projections lead to the suprachiasmatic nuclei (SCN). This projection begins in the rostral SCN as a loose plexus in the hamster and a a dense aggregation of terminals along the chiasmal border in the rat. Through the remainder of the SCN there is a very dense terminal plexus in the ventral and lateral part of the nucleus with fewer terminals present medially. The RHT projection to the SCN is greater contralaterally in the rat whereas in the hamster the contralateral and ipsilateral projections are approximately equal. In addition to projections to the SCN, the RHT projects to the anterior hypothalamic area, the retrochiasmatic area and lateral hypothalamic area in both species. The anterior hypothalamic projections are more extensive in the hamster than in the rat and extend into the perifornical region, the dorsal hypothalamus and zona incerta. The SCN and anterior hypothalamic projections are continuous with a projection to the retrochiasmatic area and, in the hamster, with a projection extending into the subparaventricular zone with some axons and terminals continuing into the paraventricular nucleus. In contrast to these, the lateral hypothalamic projection in the rat is more extensive than in the hamster. Albino and pigmented rats show identical projections. In addition to the hypothalamic projections, there is in the hamster a small projection along the base of the telencephalon to the anterior amygdaloid area and cortical amygdaloid nucleus and a very sparse projection to the anterior thalamic nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The organization of serotonergic projections to cerebral cortex in primates: retrograde transport studies.

Retrograde axonal transport and immunocytochemical methods were utilized to determine the origin of serotonergic afferents to selected primary projection and association areas of cerebral cortex in macaque monkeys. After injections of Fast Blue or Diamidino Yellow in primary motor, somatosensory, or visual cortex, retrogradely labeled neurons are found in both the dorsal and median raphe nuclei. The sets of dorsal raphe neurons which innervate these cortical areas differ in their spatial distributions along the rostrocaudal axis of the brainstem; a coarse rostrocaudal topographic relationship is found between these groups of dorsal raphe neurons and their cortical targets. In contrast, neurons in the median raphe which innervate these primary projection areas are not differentially distributed along the rostrocaudal axis. However, in both the median and dorsal raphe nuclei, most neurons projecting to primary visual cortex are situated lateral to the cells which project to motor and somatosensory areas; many of these visually projecting neurons lie among the fascicles of the medial longitudinal fasciculus. For comparison with the serotonergic innervation of primary projection areas, the locations of raphe cells projecting to three areas of association cortex were examined: dorsolateral prefrontal cortex, area 5 and area 7b. Neurons projecting to each of these association areas are found throughout the dorsal and median raphe nuclei. Their distributions are similar to one another; however, more cells projecting to dorsolateral prefrontal cortex are in the rostral part of the dorsal raphe. The dorsal and median raphe neurons projecting to these association areas are intermingled with neurons projecting to motor and somatosensory cortex, but are medial to most of those projecting to visual cortex. Thus, separate cortical areas are innervated by different sets of raphe neurons; these sets partially overlap, yet differ in their rostrocaudal and mediolateral distributions. Ascending serotonergic projections to cerebral cortex form a widely distributed system which exhibits a highly intricate anatomic organization. The present observations support the hypothesis that the dorsal raphe nucleus is comprised of distinct sets of neurons whose output is distributed to multiple, interconnected cortical areas; these serotonergic projections may play a role in the coordination of excitability in functionally related areas of cortex. In contrast, the serotonergic projections arising from the median raphe appear to be more divergent and are likely to have a global influence on cortical activity. Since these individual raphe nuclei have different projection patterns, they are likely to have distinct functional roles.

Afferent Pathways↗

Projections of global mortality and burden of disease from 2002 to 2030.

BACKGROUND: Global and regional projections of mortality and burden of disease by cause for the years 2000, 2010, and 2030 were published by Murray and Lopez in 1996 as part of the Global Burden of Disease project. These projections, which are based on 1990 data, continue to be widely quoted, although they are substantially outdated; in particular, they substantially underestimated the spread of HIV/AIDS. To address the widespread demand for information on likely future trends in global health, and thereby to support international health policy and priority setting, we have prepared new projections of mortality and burden of disease to 2030 starting from World Health Organization estimates of mortality and burden of disease for 2002. This paper describes the methods, assumptions, input data, and results. METHODS AND FINDINGS: Relatively simple models were used to project future health trends under three scenarios-baseline, optimistic, and pessimistic-based largely on projections of economic and social development, and using the historically observed relationships of these with cause-specific mortality rates. Data inputs have been updated to take account of the greater availability of death registration data and the latest available projections for HIV/AIDS, income, human capital, tobacco smoking, body mass index, and other inputs. In all three scenarios there is a dramatic shift in the distribution of deaths from younger to older ages and from communicable, maternal, perinatal, and nutritional causes to noncommunicable disease causes. The risk of death for children younger than 5 y is projected to fall by nearly 50% in the baseline scenario between 2002 and 2030. The proportion of deaths due to noncommunicable disease is projected to rise from 59% in 2002 to 69% in 2030. Global HIV/AIDS deaths are projected to rise from 2.8 million in 2002 to 6.5 million in 2030 under the baseline scenario, which assumes coverage with antiretroviral drugs reaches 80% by 2012. Under the optimistic scenario, which also assumes increased prevention activity, HIV/AIDS deaths are projected to drop to 3.7 million in 2030. Total tobacco-attributable deaths are projected to rise from 5.4 million in 2005 to 6.4 million in 2015 and 8.3 million in 2030 under our baseline scenario. Tobacco is projected to kill 50% more people in 2015 than HIV/AIDS, and to be responsible for 10% of all deaths globally. The three leading causes of burden of disease in 2030 are projected to include HIV/AIDS, unipolar depressive disorders, and ischaemic heart disease in the baseline and pessimistic scenarios. Road traffic accidents are the fourth leading cause in the baseline scenario, and the third leading cause ahead of ischaemic heart disease in the optimistic scenario. Under the baseline scenario, HIV/AIDS becomes the leading cause of burden of disease in middle- and low-income countries by 2015. CONCLUSIONS: These projections represent a set of three visions of the future for population health, based on certain explicit assumptions. Despite the wide uncertainty ranges around future projections, they enable us to appreciate better the implications for health and health policy of currently observed trends, and the likely impact of fairly certain future trends, such as the ageing of the population, the continued spread of HIV/AIDS in many regions, and the continuation of the epidemiological transition in developing countries. The results depend strongly on the assumption that future mortality trends in poor countries will have a relationship to economic and social development similar to those that have occurred in the higher-income countries.

Acquired Immunodeficiency Syndrome↗

The distribution of pontine projection cells in visual and association cortex of the cat: an experimental study with horseradish peroxidase.

The projections from the visual and association areas of the cat's neocortex to the pons were investigated with horseradish peroxidase as retrograde tracer. Small injections were made into the pars basalis of the pons, along its entire rostrocaudal extent. The cortical areas considered were areas 17, 18, 19, 20, 21, and the lateral suprasylvian areas (LSA); the posterior (PMSA), and the anterior middle suprasylvian association area (AMSA), the anterior lateral association area (ALA) and the anterior suprasylvian association area (ASA). A pontine projection was found for all the areas investigated; however, areas differ in the relative strength of their projection, in their intraareal distribution of projection cells, and in the location of their projection zones within the pons. A low to moderate density of projection cells is seen in the areas 17, 18, 19, 20, 21, and in PMSA. The posterior part of LSA contains only a few projection cells, whereas in more anterior parts of LSA the density of projection cells is moderate to high. A relatively dense distribution of projection cells also appears in AMSA, ALA, and ASA. In those areas which are retinotopically organized (17, 18, 19, LSA) the representation of the center of gaze contains far fewer projection cells than the representation of peripheral vision. In the association areas the distribution of projection cells appears even. The projection zones from areas 17, 18, and 19 overlap with the zones from LSA in the anterior half of the basal pons. The projection zones from areas 20 and 21 and from ALA and ASA are located in the middle third and the projection zones from PMSA and AMSA spread throughout the entire rostrocaudal extent of the basal pons. Our findings indicate that efferent impulses from the visual cortical areas and from the association areas on the middle suprasylvian gyrus are relayed to the cerebellum exclusively via the basal pontine nuclei. The findings further suggest that the visual corticopontine projections carry a map of the visual field in which the cortical magnification factor is reduced.

Animals↗

Ascending projections to the mammillary nuclei in the rat: a study using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase.

Cells of origin of ascending afferents to the mammillary nuclei and the afferents' fields of termination within these nuclei were studied by using retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase in the rat. The pars compacta of the superior central nucleus projects bilaterally to the median region of the medial mammillary nucleus. The ventral tegmental nucleus projects ipsilaterally to the medial mammillary nucleus, except for its median region, in a topographic manner such that the rostrodorsolateral part of the ventral tegmental nucleus projects to the medial quadrant of the medial mammillary nucleus; the rostroventromedial part projects to the dorsal quadrant; the caudodorsolateral part projects to the ventral quadrant; and the caudoventromedial part projects to the lateral quadrant. These projection fields extend throughout the longitudinal axis of the medial mammillary nucleus, except for its most caudal region, to which only the dorsolateral part of the ventral tegmental nucleus projects. This nucleus also projects topographically to the ipsilateral dorsal premammillary nucleus; the rostral part of the ventral tegmental nucleus projects to the dorsal part of the dorsal premammillary nucleus, whereas the caudal part projects to the ventral part. The periaqueductal gray around the dorsal tegmental nucleus projects bilaterally to the supramammillary nucleus. The pars alpha of the pontine periaqueductal gray projects bilaterally to the peripheral part of the lateral mammillary nucleus, whereas the pars ventralis of the dorsal tegmental nucleus projects ipsilaterally to the lateral mammillary nucleus. The results show that the tegmentomammillary projections are organized in a gradient fashion, with the rostral to caudal position of cells of origin within the tegmental nuclei of Gudden being reflected by the medial to lateral position of fields of termination within the mammillary nuclei.

Afferent Pathways↗

Anatomical investigation of projections to the basis pontis from posterior parietal association cortices in rhesus monkey.

The projections to the basis pontis from cytoarchitectonically defined subregions of the superior (SPL) and inferior (IPL) parietal lobules were investigated in 14 rhesus monkeys by using the anterograde tracing techniques of autoradiography and horseradish peroxidase histochemistry. The results of our study confirm and complement available information regarding the parietopontine projections. The projections are found in clusters distributed in lamellae approximately concentric to the peduncle. They are directed most heavily towards the peripeduncular and lateral nuclei of the pons. There are also lesser, but nevertheless substantial projections to other nuclei including the intrapeduncular, ventral, dorsolateral, extreme dorsolateral, and dorsal nuclei. The dorsomedial, paramedian, and NRTP nuclei receive only minor projections. The SPL projections are relatively widespread with respect to the more focussed IPL projections. The IPL projections are, in general, situated more laterally and at more rostral levels of the pontine nuclei than are those of the SPL. The sulcal cortex of the SPL (area PEa) favors the dorsolateral, extreme dorsolateral, and ventral nuclei compared to the light projections to these nuclei from the convexity of the SPL. The sulcal cortex of the IPL, area POa, differs from the gyral cortex in favoring the ventral and extreme dorsolateral nuclei. The rostral IPL differs from the caudal IPL in that the intrapeduncular nucleus receives projections only from rostral regions, while the lateral nucleus receives projections preferentially from caudal regions. The pontine projections from the medial SPL, area PGm, are unique in the parietal lobe in that they include the paramedian nucleus. Projections arising from multimodal regions located caudally in the SPL (areas PEa and PGm) and IPL (areas PG and Opt) are more strongly represented and more laterally placed within the pontine nuclei than projections arising from more rostral, unimodal, posterior parietal regions. The heavy projections to the pontine nuclei from the posterior parietal cortex, and particularly from those caudal parietal regions that have prominent associative and limbic connections, seem to suggest that the corticopontocerebellar pathways permit a cerebellar contribution not only to the coordination of movement, but also to the modulation and integration of higher function.

Animals↗

Organization of striatopallidal, striatonigral, and nigrostriatal projections in the macaque.

The topographic organization of neostriatal connections was investigated by axonal transport of horseradish peroxidase, tritiated amino acids, or mixtures of both injected into the neostriatum of macaque monkeys. Striatal projections to pallidum and substantia nigra and the origin of projections to striatum from cerebral cortex and substantia nigra were examined. All striatal injections gave rise to projections to external and internal pallidum and to substantia nigra. Injections in caudate nucleus and in putamen both gave rise to substantial projections to pallidum and to substantia nigra, and the ratio of pallidal and nigral projections was generally similar. The striatopallidal projection showed prominent arborizations at right angles to the striatofugal pathway traversing the pallidum, forming in this manner terminal fields consisting of multiple bands or discs within a broad segment of the pallidum. Thus separate but neighboring regions of striatum appeared to have overlapping pallidal projection territories. In broad terms, rostral striatum projects to rostral pallidum, caudal striatum to caudal pallidum, and dorsal and ventral striatum, respectively, to dorsal and ventral pallidum. Inner (medial) and outer (lateral) putamen showed only subtle differences in pallidal projection patterns. The striatonigral projection from each injected area of striatum formed a longitudinal band extending over the entire length of the substantia nigra, with scattered, dense terminal fields occupying portions of pars compacta as well as pars reticularis. Rostral striatum projected to medial nigra and caudal striatum to lateral nigra. Terminal fields from ventral striatum were located somewhat more dorsally in the substantia nigra than those from dorsal striatum. Neighboring but separate regions of striatum appeared to have overlapping nigral projection territories, especially in caudal nigra. The nigrostriatal neurons projecting to an injected area of striatum generally were located in the same longitudinal band of the substantia nigra as the corresponding striatonigral projection. Labeled pars compacta neurons were often surrounded by a dense, labeled striatonigral terminal field, suggesting the existence of a striato-nigrostriatal loop. The rostromedial pars compacta contained labeled neuronal cell bodies in most cases, suggesting a widely divergent projection to striatum from this cell group. A slight tendency for preferential cell labeling rostrally in nigra with rostral striatal injection and caudally in nigra with caudal injections was noted. The preferred relationship of lateral nigra with caudal striatum and medial nigra with rostral striatum has implications for clinical expression of Parkinson's disease, which may vary with differential involvement of different nigral cell groups along the medial to lateral axis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Efferent projections from the periventricular and medial parvicellular subnuclei of the hypothalamic paraventricular nucleus to circumventricular organs of the rat: a Phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study.

The heterogeneous hypothalamic paraventricular nucleus (PVN) is intimately involved in the regulation of several homeostatic functions. These regulations might, at least partly, be mediated via neuronal projections from the PVN to circumventricular organs outside the blood-brain barrier. To study the efferent projections of the medial and periventricular parvicellular subnuclei of the PVN with particular emphasis on the projections to the circumventricular organs, anterograde tracing with Phaseolus vulgaris leucoagglutinin (PHA-L) was applied. Three major efferent pathways and one minor one coursed from the medial and periventricular parvicellular subnuclei to the circumventricular organs. The major fiber projections included a rostral, a lateral, and a dorsocaudal projection tract, whereas the minor projection coursed ventrally. Fibers of the rostral projection were followed to the preoptic area and along the fornix to the subfornical organ. Single fibers originating from this projection coursed further rostrally to the organum vasculosum laminae terminalis. The lateral projection equivalent to the hypothalamo-pituitary tract passed through the lateral hypothalamic area to the median eminence, and nerve terminals were observed throughout the rostrocaudal extent of this structure. A few fibers of this bundle continued into the infundibular stalk and some terminated in the posterior pituitary lobe. Few fibers of the lateral projection descended to caudal pontine levels, where they reached descending fibers of the dorsocaudal projection. The dorsocaudal projection was essentially restricted to midline structures. Along the midline, fibers were followed from the hypothalamus either dorsally through the thalamus to the dorsal part of the third ventricle or caudally alongside the ventricular wall to the mesencephalic periaqueductal grey. The density of fibers decreased along the caudal direction of the neuraxis. The dorsal part of this projection gave rise to terminals in the deep pineal gland and pineal stalk, whereas the caudal part of this projection sent terminating fibers into the area postrema. The minor ventrally directed projection could be followed through the periventricular region to the rostral part of the median eminence. The number of terminals in the circumventricular organs varied. Within the median eminence, a high density of afferents was observed in the entire rostrocaudal extent of the external zone, whereas a low density of fibers was seen in the internal zone. A medium density of afferents was observed in the organum vasculosum laminae terminalis, whereas a relative low density of nerve terminals was observed in the posterior pituitary, the deep pineal gland, the subfornical organ, and the area postrema.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Direct projections from the anterior thalamic nuclei to the retrohippocampal region in the rat.

The present study examined the areal and laminar distribution of direct projections from the anterior thalamic nuclei to the retrohippocampal region in the rat, with anterograde transport of Phaseolus vulgaris-leucoagglutinin. The anteromedial nucleus (AM) projects to the temporal subiculum, medial entorhinal area, perirhinal area, and caudomedial part of the lateral entorhinal area. The interanteromedial nucleus (IAM) projects to the perirhinal area and the caudolateral part of the lateral entorhinal area. Furthermore, both the AM and IAM project to the temporal area 2, occipital area 1, and lateral occipital area 2. The projections from the AM and IAM to these retrohippocampal and neocortical regions terminate mainly in deep layers. The anteroventral nucleus (AV) projects to the subicular complex with a complex topographic organization. The most rostral part of the AV projects to layers I and III of the ventral presubiculum, the pyramidal cell layer of the temporal subiculum, and deep layers of the parasubiculum and medial entorhinal area. At the midrostrocaudal level of the AV, the lateral and the dorsal quadrants of the AV project, respectively, to layers I and III and to layers I and IV-VI of the ventral presubiculum, whereas the ventral and the medial quadrants project, respectively, to layers I and III and to layers I and IV-VI of the dorsal presubiculum. Furthermore, the lateral and dorsal quadrants project to the pyramidal cell layer of the temporal subiculum, whereas the ventral and medial quadrants project more septally. At the caudal third level of the AV, the dorsolateral part projects to layers I and III of the presubiculum with a patchy pattern and to the pyramidal cell layer of the septal subiculum. The anterodorsal nucleus projects mainly to deep layers of the presubiculum, parasubiculum, and entorhinal area. The results show that each subdivision of the anterior thalamic nuclei projects to a distinct field in the retrohippocampal region. This suggests that each of these projections may have a distinct modulatory influence upon the activity of retrohippocampal neurons that play important roles in limbic functioning such as memory and learning processes.

Animals↗

Measuring biotechnology employees' ethical attitudes towards a controversial transgenic cattle project: the ethical valance matrix.

What is the relationship between biotechnology employees' beliefs about the moral outcomes of a controversial transgenic research project and their attitudes of acceptance towards the project? To answer this question, employees (n=466) of a New Zealand company, AgResearch Ltd., were surveyed regarding a project to create transgenic cattle containing a synthetic copy of the human myelin basic protein gene (hMBP). Although diversity existed amongst employees' attitudes of acceptance, they were generally: in favor of the project, believed that it should be allowed to proceed to completion, and that it is acceptable to use transgenic cattle to produce medicines for humans. These three items were aggregated to form a project acceptance score. Scales were developed to measure respondents' beliefs about the moral outcomes of the project for identified stakeholders in terms of the four principles of common morality (benefit, non-harm, justice, and autonomy). These data were statistically aggregated into an Ethical Valence Matrix fo the project. The respondents' project Ethical Valence Scores correlated significantly with their project acceptance scores (r=0.64, p<0.001), accounting for 41% of the variance in respondents' acceptance attitudes. Of the four principles, non-harm had the strongest correlation with attitude to the project (r=0.59), followed by benefit and justice (both r=0.54), then autonomy (r=0.44). These results indicate that beliefs about the moral outcomes of a research project, in terms of the four principles approach, are strongly related to, and may be significant determinants of, attitudes to the research project. This suggests that, for employees of a biotechnology organization, ethical reasoning could be a central mechanism for the evaluation of the acceptability of a project. We propose that the Ethical Valence Matrix may be used as a tool to measure ethical attitudes towards controversial issues, providing a metric for comparison of perceived ethical consequences for multiple stakeholder groups and for the evaluation and comparison of the ethical consequences of competing alternative issues or projects. The tool could be used to measure both public and special interest groups' ethical attitudes and results used for the development of socially responsible policy or by science organizations as a democratizing decision aid to selection amongst projects competing for scarce research funds.

Agriculture↗

The postnatal development of retinocollicular projections in normal hamsters and in hamsters following neonatal monocular enucleation: a horseradish peroxidase tracing study.

The pattern of distribution of the retinal projections to the superior colliculus (SC) has been studied in developing normal hamsters and in hamsters following unilateral eye enucleation at birth, using the anterograde horseradish peroxidase (HRP) method. The results show that in normal hamsters the contralateral retinocollicular projection has already reached the caudal pole of the SC on the day of birth, and covered the entire SC by day 1. The ipsilateral retinocollicular projection is distributed only to the rostrolateral portion of the SC on day 0, but has covered the entire area of the SC on day 1. The innervation of the SC by the ipsilateral projection increases gradually until it reaches its maximum density on day 3 or day 4. Beginning on day 6, the density of the ipsilateral projection decreases markedly except in areas where there is a distinct clumping of retinal fibers. The normal adult pattern, which consists of dense clumps of ipsilateral retinal projections in the rostral half of the SC and a sparse ipsilateral retinal projection distributing in almost the entire extent of the SC, is established on day 10. In animals in which one eye was removed on the day of birth, the ipsilateral projection is observed in the rostral two-thirds of the SC on day 1, and innervates the entire extent of the colliculus on day 2. On day 3 or day 4, this projection is denser than that found in normal animals of the same age. The SC remains heavily innervated by ipsilateral fibers on and after day 6. The abnormal adult pattern, which consists of dense ipsilateral retinal projections in most parts of the SC, is observed on day 10. The anomalous ipsilateral retinocollicular projection which develops in eye-enucleated animals suggests that there is a competitive interaction between fibers from the two eyes during development which is critical in shaping the normal adult pattern of the ipsilateral retinocollicular projection. The early development of the contralateral projection is in advance of the ipsilateral projection, and removal of the contralateral fibers by eye enucleation at birth seems to result in a further delay in the development of the ipsilateral projection. This suggests that in the hamster the contralateral fibers may play a role in guiding the ipsilateral fibers to reach their target region.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Different pontine projections to the two sides of the cerebellum.

This study analyzed the projections of the basilar pontine nuclei (BPN) and of the nucleus reticularis tegmenti pontis (NRTP) to the two sides of the cerebellum in the rat. It showed that the two sides of the cerebellar cortex were innervated by different percentages of BPN (about 82% of the cells project to the contralateral cortex and 18% to the ipsilateral) and NRTP cells (some 60% project to the contralateral cortex and 40% to the ipsilateral). In comparison to projections traced to the cortex, only a few fibers were traced to the nuclei of the same animals. Most of the projections of the BPN to the cerebellar nuclei were traced to the lateralis and posterior interpositus nucleus of the contralateral side (95%), while a few were traced to homologous nuclei of the ipsilateral side (5%). Thus, the BPN principally control the activity of the contralateral cerebellum, with a much less important control over the activity of the ipsilateral cerebellum. Vice versa, the NRTP, which project to the lateralis, interpositus, and medialis nuclei of the two sides, with percentages (64% contra- and 36% ipsilateral) similar to those reported for the projections to the cortex, is more concerned in the bilateral control of the cerebellum, although with a moderate contralateral prevalence. The fact that projections of the BPN were principally traced to the contralateral nuclei, from which the efferent projection fibers from the cerebellum originate, suggests that the BPN are principally involved in the motor control of the contralateral body. Conversely, the bilateral projections of the NRTP to the cerebellar nuclei suggest that the NRTP is mainly involved in bilateral motor activities. The comparison of the projections to the cortex and nuclei of the cerebellum of single animals supports the co-existence of coupled (i.e., projections to the cortex and the corresponding nuclei) and uncoupled (i.e., projections to the cortex but not to the nuclei) projection patterns, from both the BPN and the NRTP. These features of the pontocerebellar projections open new vistas on the functional architecture of this pathway.

Animals↗

Healthy city projects in developing countries: the first evaluation.

The 'healthy city' concept has only recently been adopted in developing countries. From 1995 to 1999, the World Health Organization (WHO), Geneva, supported healthy city projects (HCPs) in Cox's Bazar (Bangladesh), Dar es Salaam (Tanzania), Fayoum (Egypt), Managua (Nicaragua) and Quetta (Pakistan). The authors evaluated four of these projects, representing the first major evaluation of HCPs in developing countries. Methods used were stakeholder analysis, workshops, document analysis and interviews with 102 managers/implementers and 103 intended beneficiaries. Municipal health plan development (one of the main components of the healthy city strategy) in these cities was limited, which is a similar finding to evaluations of HCPs in Europe. The main activities selected by the projects were awareness raising and environmental improvements, particularly solid waste disposal. Two of the cities effectively used the 'settings' approach of the healthy city concept, whereby places such as markets and schools are targeted. The evaluation found that stakeholder involvement varied in relation to: (i) the level of knowledge of the project; (ii) the project office location; (iii) the project management structure; and (iv) type of activities (ranging from low stakeholder involvement in capital-intensive infrastructure projects, to high in some settings-type activities). There was evidence to suggest that understanding of environment-health links was increased across stakeholders. There was limited political commitment to the healthy city projects, perhaps due to the fact that most of the municipalities had not requested the projects. Consequently, the projects had little influence on written/expressed municipal policies. Some of the projects mobilized considerable resources, and most projects achieved effective intersectoral collaboration. WHO support enabled the project coordinators to network at national and international levels, and the capacity of these individuals (although not necessarily their institutions) was increased by the project. The average annual running cost of the projects was approximately 132,000 US dollars per city, which is close to the costs of the only other HCP for which a cost analysis has been undertaken, Bangkok (115,000 US dollars per year) Recommendations for these and other HCPs are provided.

Community Health Planning↗

Birth dates of retinal ganglion cells giving rise to the crossed and uncrossed optic projections in the mouse.

In the mouse, as in most mammals, the crossed optic projections originate from the entire extent of the retina, whereas ganglion cells giving rise to the uncrossed (ipsilateral) projection are restricted to the temporal and ventral retina. The nasal border of this bilaterally projecting region in the retina corresponds to the midline of the visual field. Here the birth dates of ipsilaterally and contralaterally projecting ganglion cells were determined by combining tritiated thymidine labelling in the embryo with horseradish peroxidase tracings from the optic tract in the adult. Contralaterally projecting ganglion cells were found to be generated from embryonic day E11 to about E19 in a crude concentric fashion with the oldest cells in central and youngest ones in peripheral retina. Ipsilaterally projecting cells were born from E11 to E16, that is, during the earlier part of the period in which the contralateral projection was born. At the earliest time of ganglion cell generation (E11-12) ipsi- and contralaterally projecting cells were born within separate retinal regions, with the future midline representation forming the border between the two zones. This distinction became lost after E13, when both ipsi- and contralaterally projecting cells were born in the bilaterally projecting region. Hence at E11-12 the retina was found to have a bipartite organization that may allow the specification of the two maps of opposite topographical polarity in which the crossed and uncrossed projections are organized. Since in the adult retina this bipartite organization is preserved only in the large ganglion cells that project to the lateral geniculate nucleus, and since large ganglion cells are known to be the earliest ones formed in the mouse, these cells may be the ones that establish the early and bilateral projections of the retina. The conclusion that the bilateral projection system in the retina reflects an early developmental programme, and not the result of competition between the two eyes at later stages, was reinforced by observing a practically normal retinal origin of ipsilateral projections in mice which had only one normal eye from the earliest stages of eye development.

Animals↗

Projections of the trapezoid body and the superior olivary complex of the Kangaroo rat (Dipodomys merriami).

Glass micropipettes filled with 2 M sodium cyanide were used to physiologically locate and iontophoretically damage the nucleus of the trapezoid body (NTB), the medial superior olive (MSO), and the lateral superior olive (LSO). Mechanical lesions were made in the trapezoid body as it leaves the cochlear nuclei. After a 3- to 10-day survival time the projections and terminal degeneration were traced with the Fink-Heimer and Nauta-Gygax stains. The ventral cochlear nucleus (VCN) projects via the trapezoid body to ipsilateral LSO, ipsilateral preolivary nuclei, ipsilateral lateral and a contralateral medial dendritic fields of MSO, and contralateral NTB; there is also a small ipsilateral projection to the ventral nucleus of the lateral lemniscus (VNLL) and the central nucleus of the inferior colliculus (CNIC). Some trapezoid body fibers ascend via the contralateral lateral lemniscus to VNLL, DNLL (dorsal nucleus of the lateral lemniscus), and CNIC. There is no projection from the ventral cochlear nucleus to the ipsilateral NTB and contralateral preolivary nuclei. All portions of NTB project ipsilaterally to LSO (ventral NTB to dorsomedial LSO, dorsal NTB to ventral LSO) and to the retro-olivary nucleus. In two animals with NTB lesions there is also degeneration in the ventromedial portion of the ipsilateral facial nucleus. NTB projects contralaterally by way of the stria of Monakow to the pyramidal and molecular cell layers of the dorsal cochlear nucleus (DCN). The NTB does not project ipsilaterally to MSO, preolivary nuclei, VNLL, DNLL and CNIC. Contralaterally there are no projections to any of the nuclei of the auditory pathway except the DCN. Most MSO projections are ipsilateral. The densest goes by way of the lateral lemniscus to the lateral aspect of the ipsilateral CNIC, terminating throughout its dorsoventral axis. MSO also projects bilaterally to the pyramidal and molecular cell layers of dorsal cochlear nucleus (DCN), and ipsilaterally to the ventral portion of the motor nucleus of V and to the facial nucleus. MSO does not project ipsilaterally to the LSO, NTB, preolivary, VCN and retro-olivary nuclei. On the contralateral side, all structures except the DCN are free of projection patterns from axons originating in the MSO. LSO projects bilaterally to the central and ventral portions of CNIC and to the nuclei of the lateral lemnisci, and ipsilaterally to the large and small spherical cell areas of anterior ventral cochlear nucleus (AVCN) and to all portions of DCN. The LSO does not project ipsilaterally to the NTB, MSO, preolivary and retro-olivary nuclei. On the side opposite, this nucleus does not project to NTB, MSO, retro-olive, VCN, preolivary and LSO. For all lesions regardless of the site, there is no degeneration found rostral to the CNIC. The medial geniculate body or other structures in the diencephalon or cortex are free of any fields of terminal degeneration.

Animals↗

The net effects of the Project NetWork return-to-work case management experiment on participant earnings, benefit receipt, and other outcomes.

The Social Security Administration (SSA) initiated Project NetWork in 1991 to test case management as a means of promoting employment among persons with disabilities. The demonstration, which targeted Social Security Disability Insurance (DI) beneficiaries and Supplemental Security Income (SSI) applicants and recipients, offered intensive outreach, work-incentive waivers, and case management/referral services. Participation in Project NetWork was voluntary. Volunteers were randomly assigned to the "treatment" group or the "control" group. Those assigned to the treatment group met individually with a case or referral manager who arranged for rehabilitation and employment services, helped clients develop an individual employment plan, and provided direct employment counseling services. Volunteers assigned to the control group could not receive services from Project NetWork but remained eligible for any employment assistance already available in their communities. For both treatment and control groups, the demonstration waived specific DI and SSI program rules considered to be work disincentives. The experimental impact study thus measures the incremental effects of case and referral management services. The eight demonstration sites were successful in implementing the experimental design roughly as planned. Project NetWork staff were able to recruit large numbers of participants and to provide rehabilitation and employment services on a substantial scale. Most of the sites easily reached their enrollment targets and were able to attract volunteers with demographic characteristics similar to those of the entire SSI and DI caseload and a broad range of moderate and severe disabilities. However, by many measures, volunteers were generally more "work-ready" than project eligible in the demonstration areas who did not volunteer to receive NetWork services. Project NetWork case management increased average annual earnings by $220 per year over the first 2 years following random assignment. This statistically significant impact, an approximate 11-percent increase in earnings, is based on administrative data on earnings. For about 70 percent of sample members, a third year of followup data was available. For this limited sample, the estimated effect of Project NetWork on annual earnings declined to roughly zero in the third followup year. The findings suggest that the increase in earnings may have been short-lived and may have disappeared by the time Project NetWork services ended. Project NetWork did not reduce reliance on SSI or DI benefits by statistically significant amounts over the 30-42 month followup period. The services provided by Project NetWork thus did not reduce overall SSI and DI caseloads or benefits by substantial amounts, especially given that only about 5 percent of the eligible caseload volunteered to participate in Project NetWork. Project NetWork produced modest net benefits to persons with disabilities and net costs to taxpayers. Persons with disabilities gained mainly because the increases in their earnings easily outweighed the small (if any) reduction in average SSI and DI benefits. For SSA and the federal government as a whole, the costs of Project NetWork were not sufficiently offset by increases in tax receipts resulting from increased earnings or reductions in average SSI and DI benefits. The modest net benefits of Project NetWork to persons with disabilities are encouraging. How such benefits of an experimental intervention should be weighed against costs of taxpayers depends on value judgments of policymakers. Because different case management projects involve different kinds of services, these results cannot be directly generalized to other case management interventions. They are nevertheless instructive for planning new initiatives. Combining case and referral management services with various other interventions, such as longer term financial support for work or altered provider incentives, could produc

Adolescent↗

Long-range global population projections, as assessed in 1980.

UN medium range projections prepared in the 1980 assessment projected the population of individual countries up to the year 2025. The long range projections discussed here were prepared by projecting the population of 8 major world regions from 2025-2100. The purpose of the projection was to observe the implications of the changes from the 1978 assessment made in the 1980 medium range projections on the long range projections of the world's populations. As in previous projections, high, medium, and low variants were prepared in which fertility is assumed to be constant at the replacement level but at different times in the future. In addition, these projections contain 2 variants not previously prepared--namely, the growth and decline variants, in which the ultimate net reproduction rate is 1.05 and 0.95, respectively. In all the variants, expectation of life at birth is assumed to reach 75 years for males and 80 for females. According to the current medium variant projection, the earth's population will become stationary after 2095 at 10.2 billion persons, compared with a total of 10.5 billion projected in the 1978 assessment. The lower projection is largely attributable to a recent decline in the growth rate of several countries in South Asia which was greater than previously assumed. When the world population becomes stationary, both crude birth and death rates would be about 13/1000. In the decline variant, total population would peak at 7.7 billion in 2055, then decline gradually to 7.2 billion in 2100. The total population as projected by the growth variant would equal 14.9 billion in 2100 and would still be growing slowly. Between 1980 and 2050, 95% of the world's growth will occur in the currently less developed regions. Their share of total population will increase from 75-85% during that period. The age structure in all regions is expected to converge to 1 in which the median age is 39 years, the proportion both below age 15 and above age 64 is about 19% each, and the dependency ratio is about 60. A precise degree of accuracy cannot be specified, but the argument is made that the actual future population of the world is very likely to fall within the range of the projection variants and probably not far from the medium variant.

Africa↗

Ascending projections of the brain stem reticular formation in a nonmammalian vertebrate (the lizard Varanus exanthematicus), with notes on the afferent connections of the forebrain.

In the present study an attempt has been made to analyze the ascending reticular projections in the lizard Varanus exanthematicus by means of the horseradish peroxidase (HRP) technique. Reticular projections ascending to the telencephalon were found to arise in the mesencephalon, but not caudal to the mesorhombencephalic border. HRP injections into the dorsal thalamus have demonstrated retrogradely labeled cells in the mesencephalic reticular formation, particularly at the level of the oculomotor nerve and in the medial magnocellular zone of the rhombencephalic reticular formation, predominantly rostrally. HRP infiltrations at the mesodiencephalic border damaged most of the fibers passing beyond this junction, resulting in the uptake of HRP by the damaged axons and subsequent labeling of the cell bodies or origin of ascending reticular projections to the diencephalon and telencephalon. From a comparison of cell-labeling patterns in cases of HRP injections of, respectively, the dorsal thalamus and the mesodiencephalic border, it seems likely that the nucleus reticularis medius and more sparsely the nucleus reticularis inferior project to ventral diencephalic structures (ventral thalamus and hypothalamus), whereas the midbrain reticular formation and the rostral parts of the rhombencephalic reticular formation (nuclei reticulares isthmi and superior) project to both the dorsal thalamus and more ventral diencephalic structures. Projections arising throughout the rhombencephalic reticular formation, but predominantly in the nucleus reticularis inferior, were found to ascend to the midbrain reticular formation. The present experimental data in the lizard Varanus exanthematicus are comparable to the findings in mammals, with the exception of the reticulo-oculomotor pathways which have not been analyzed so far in reptiles. In addition to the aforementioned ascending reticular projections, the present study has demonstrated projections ascending from monoamine cell groups, various diencephalic structures, as well as from neuronal groups involved in somatosensory, auditory, and gustatory systems. Projections were found from the locus coeruleus and the nucleus raphes superior to the telencephalon, as well as from the substantia nigra and the presumable reptilian homologue of the mammalian ventral tegmental area to the basal forebrain and the dorsal thalamus. Bilateral projections were demonstrated from the principal trigeminal nucleus to the telencephalon, reminiscent of the quintofrontal tract of birds. Ascending projections to the diencephalon were found to originate bilaterally in the descending trigeminal nucleus and the dorsal funicular nucleus. Auditory projections to the midbrain arise bilaterally in the superior olivary complex and in the cochlear nuclear complex. Finally, the ascending gustatory pathway arising in the nucleus of the solitary tract was found to project to the "parabrachial region," which in its turn has extensive projections to the forebrain.

Afferent Pathways↗