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This paper assumes that the effectiveness and efficiency of an integrated community system of care for HIV infected people may depend to a large extent on common perceptions of the objectives of such a system among three sets of actors—the patient, the professional care manager, and the continual care giver. It discusses a decision analytic inquiry into that concurrence on objectives. The conclusion is that within the community studied there is strong evidence of a significant lack of such common purpose.

Background: Mice lacking rod and cone photoreceptors ( rd/rd cl ) are still able to regulate a range of responses to light, including circadian photoentrainment, the pupillary light reflex, and suppression of pineal melatonin by light. These data are consistent with the presence of a novel inner-retinal photoreceptor mediating non-image-forming irradiance detection. Results: We have examined the nature and extent of intrinsic light sensitivity in rd/rd cl retinae by monitoring the effect of light stimulation (470 nm) on intracellular Ca 2+ via FURA-2 imaging. Using this approach, which does not rely on pharmacological or surgical isolation of ganglion cells from the rod and cone photoreceptors, we identified a population of light-sensitive neurons in the ganglion cell layer (GCL). Retinal illumination induced an increase of intracellular Ca 2+ in ∼2.7% of the neurons. The light-evoked Ca 2+ fluxes were dependent on the intensity and duration of the light stimulus. The light-responsive units formed an extensive network that could be uncoupled by application of the gap junction blocker carbenoxolone. Three types of light-evoked Ca 2+ influx were observed: sustained, transient, and repetitive, which are suggestive of distinct functional classes of GCL photoreceptors. Conclusions: Collectively, our data reveal a heterogeneous syncytium of intrinsically photosensitive neurons in the GCL coupled to a secondary population of light-driven cells, in the absence of rod and cone inputs.

Summary Studies in the 1930s demonstrated that birds possess photoreceptors that are located within the hypothalamus and regulate photoperiodic responses to day length [1, 2]. Most recently, photoperiod has been shown to alter the activity of the pars tuberalis to release thyrotrophin, which ultimately drives a reproductive response [3, 4]. Despite these significant findings, the cellular and molecular identity of the hypothalamic photoreceptors has remained a mystery. Action spectra implicated an opsin-based photopigment system [5], but further identification based on rod- or cone-opsin probes failed, suggesting the utilization of a novel opsin [6]. The vertebrate ancient ( VA ) opsin photopigments were isolated in 1997 [7, 8] but were thought to have a restricted taxonomic distribution, confined to the agnatha and teleost fish. Here, we report the isolation of VA opsin from chicken and show that the two isoforms spliced from this gene ( cVAL and cVA ) are capable of forming functional photopigments. Further, we show that VA opsin is expressed within a population of hypothalamic neurons with extensive projections to the median eminence. These results provide the most complete cellular and molecular description of a deep brain photoreceptor in any vertebrate and strongly implicate VA opsin in mediating the avian photoperiodic response.

Kainic (KA) and quisqualic (QA) acids have a potent depolarizing action on a variety of neurones of the central nervous system, including retinal horizontal cells. We now report the novel finding that at low concentrations (1-3 microM), these 'excitatory' amino acids hyperpolarize horizontal cells of the fish retina. We show that the hyperpolarizing effects of both KA and QA are reversed by the gamma-aminobutyric acid (GABA) antagonist bicuculline, whereas a second GABA antagonist, picrotoxin, reverses the effects of KA, but not of QA. Neither GABA antagonist influences horizontal cell depolarization by 50 microM KA or 50 microM QA, thus the excitatory (depolarizing and inhibitory (hyperpolarizing) effects of the amino acids involve independent mechanisms. We provide evidence that the hyperpolarizing effects are not mediated by the dopaminergic pathways associated with retinal horizontal cells.

Summary Background In bright light, mammals use a distinct photopigment (melanopsin) to measure irradiance for centrally mediated responses such as circadian entrainment. We aimed to determine whether the information generated by melanopsin is also used by the visual system as a signal for light adaptation. To this end, we compared retinal and thalamic responses to a range of artificial and natural visual stimuli presented using spectral compositions that either approximate the mouse’s experience of natural daylight (“daylight”) or are selectively depleted of wavelengths to which melanopsin is most sensitive (“mel-low”). Results We found reproducible and reversible changes in the flash electroretinogram between daylight and mel-low. Simultaneous recording in the dorsal lateral geniculate nucleus (dLGN) revealed that these reflect changes in feature selectivity of visual circuits in both temporal and spatial dimensions. A substantial fraction of units preferred finer spatial patterns in the daylight condition, while the population of direction-sensitive units became tuned to faster motion. The dLGN contained a richer, more reliable encoding of natural scenes in the daylight condition. These effects were absent in mice lacking melanopsin. Conclusions The feature selectivity of many neurons in the mouse dLGN is adjusted according to a melanopsin-dependent measure of environmental brightness. These changes originate, at least in part, within the retina. Melanopsin performs a role analogous to a photographer’s light meter, providing an independent measure of irradiance that determines optimal setting for visual circuits., Highlights • Adjustments in visual performance in daylight conditions are driven by melanopsin • Melanopsin adjusts visual feature selectivity in spatial and temporal dimensions • Melanopsin facilitates a richer and more reliable encoding of natural scenes, Allen et al. show that aspects of light adaptation rely on a measure of brightness provided by melanopsin, the retina’s most recently discovered photoreceptor. Recordings from the mouse thalamus show that melanopsin controls the types of visual features that excite single neurons, allowing a richer, more reliable representation of natural scenes.

The western-trained surgeon working in a mission hospital in a developing country finds that in spite of the heavy demands placed upon him the work can be most absorbing, challenging, and satisfying. Some impressions gained during 31/2 years working in the department of surgery of a mission hospital in Kathmandu, Nepal, are recorded. Particular reference is made to the striking differences in disease incidence, as brought out in a review of operative surgery for 1977.

We have studied the effects of naturally occurring metabolites of tryptophan, kynurenic and quinolinic acids, on the electrophysiological responses of retinal horizontal cells in the fish (Rutilus rutilus, the roach). Quinolinic acid usually hyperpolarizes the cells and reduces their light evoked responses (S-potentials) but on occasion, it causes a slight depolarization of the membrane potential. These actions are similar to those found with N-methyl-D-aspartate (NMDA) and our results are consistent with the proposal that it acts at NMDA binding sites. Kynurenic acid (greater than or equal to mM) invariably hyperpolarizes horizontal cells to their potassium Nernst equilibrium potential and, more significantly, blocks the depolarizing actions exerted on them by excitatory amino acids, such as kainic and quisqualic acids. We show that this action persists in the presence of the synaptic blocker, cobalt chloride, and thus is not mediated by chemical synaptic activity. Kynurenic acid does not reverse depolarization of horizontal cells by dopamine or gamma-aminobutyric acid, thus its inhibitory effects are selective to the actions of excitatory amino acids. Neither xanthurenic acid, a close structural analogue of kynurenic acid, nor quinolinic acid are effective in blocking depolarizations by excitatory amino acids.

Influenza virus M1 protein has been shown to inhibit viral RNA transcription, and in this study the epitopes on M1 critical for this function were localized. When a battery of 15 monoclonal anti-M1 antibodies were reacted with chemically cleaved fragments of M1 on a western blot, five distinct banding patterns were observed. A representative antibody was selected from each banding group, and its ability to reverse M1-effected transcription inhibition was measured. From these data, the sites on M1 critical for transcription inhibition were deduced. It appears now that the regions on M1 in the vicinity of amino acid residues #70 and #140 are critical for inhibition. Furthermore, by taking into account the hydropathicity and secondary structure, it is hypothesized that amino acids #70 and #140 are physically close together in the final three-dimensional conformation of M1 protein and that the residues in between form a loop and are thus removed from the functional site.

The Remote Orbital Servicing System (ROSS), a focal point for NASA research in automation and robotics, is discussed in terms of the role of man in such a system. In the supervisory control mode, the ROSS operator inputs high-level goals to a strategic (nonreal-time) planner which then passes the plan or series of actions to a tactical (real-time) planner which executes the plan. Using directed control, man makes more specific commands to perform strategic planning with or without the use of the automated strategic planner. Shared computer/manual control will require a multifunction interactive display. At the teleoperator control level, a hand controller is used to command the ROSS manipulator and end effectors.

In 1986 the Sisters of Charity of the Incarnate Word, a multi-institutional system based in Houston, established specific mission objectives for all its healthcare facilities to meet the challenge of caring for the medically indigent in their communities. In response, St. Michael's Hospital, Texarkana, AR, established the Medical Indigent Committee to develop project proposals. To gain approval, proposals had to meet criteria established by the Sisters of Charity corporate office. These were consistency with mission, evidence of need, operational feasibility, and financial feasibility. The committee's first task was to collect information on the health status of the poor in its service area. Based on their findings, the committee decided to target the elderly and the very young for programs. After some brainstorming sessions, the committee developed three proposals: 1. Home Care Skills. 2. Pulmonary Rehabilitation Program. 3. Sick Child Clinic. By the end of 1986 the first two proposals were approved and funded; the Sick Child Clinic was not, because of operational concerns. The hospital offered the first Home Care Skills course in June 1987 and repeated it later that year. The 16-hour program proved so successful that the hospital is now considering having the class videotaped. The Pulmonary Rehabilitation Program began in May 1987. Although the hospital has not yet determined whether it has achieved its goal of reducing readmissions for poor patients with chronic obstructive pulmonary disease, program attendance exceeds that of other classes by more than 50 percent.

Chemically activated electroadhesive pads on spacecraft surface, allowing astronauts to maneuver or work in zero gravity environments

Triethylene thiophosphoramide (Thio-TEPA) as an adjuvant to radical mastectomy for the treatment of carcinoma of the breast has been shown to be effective in reducing tumour recurrences. In many centres radiotherapy is considered valuable in breast cancer treatment, and in the minds of many there has existed the question of the safety of giving triethylene thiophosphoramide, a radiomimetic drug, at the time of surgery to the patient destined to receive post-operative radiotherapy. Fears had been expressed that the additive effects of triethylene thiophosphoramide and radiotherapy would result in serious complications and preclude the use of this valuable drug.A total of 70 patients with breast cancer were treated by radical mastectomy and administration of triethylene thiophosphoramide. Most patients received postoperative radiotherapy. Results of this study showed that the benefit of adjuvant chemotherapy with triethylene thiophosphoramide need not be withheld and that the drug may be administered with safety to the patient with breast carcinoma for whom radical mastectomy and postoperative radiotherapy are planned.

Initial studies of the electroadhesive phenomenon are shown to indicate that electroadhesors are potentially usable as zero-g assistive devices for a range of intra- and extravehicular activities in space missions. These uses generally are related to astronaut and cargo maneuvering, worksite restraint, and tool and equipment tiedown.

Two lots of bivalent groups A and C meningococcal polysaccharides were evaluated in children 2-10 years old. Molecular weights of both the A and C polysaccharides were 100,000-300,000 in Lot S and >2,000,000 in Lot X. 68 children received a single dose of vaccine (34 Lot S, 34 Lot X) and 45 received 2 doses of vaccine 2 months apart (27 Lot S and 18 Lot X). Antibody responses were assessed by indirect immuno-fluorescence (FA) and by bactericidal activity (BA). Preimmunization FA titers of anti-A and anti-C were 5.9 and 6.7. One month post-primary, anti-A FA titers were 33.5 with Lot S and 134.1 with Lot X (p< .05); BA titers were 15 and 388 (p< .01). Significant anamnestic responses to A polysaccharide were not observed after either Lot S or Lot X. Anti-C FA titers one month post-primary were 32.0 after Lot S and 121.4 after Lot X (p< .05); BA titers were 45 and 697. Neither enhancement nor suppression of anti-C responses were seen after the second dose of vaccine with either lot. Protection of infants with vaccines similar in size to Lot S has been achieved against group A, but not group C meningococcal disease. The immunogenicity of large molecular weight vaccines similar to Lot X In infants is currently under investigation.