The world's road to water scarcity: shortage and stress in the 20th century and pathways towards sustainability.

Water scarcity is a rapidly growing concern around the globe, but little is known about how it has developed over time. This study provides a first assessment of continuous sub-national trajectories of blue water consumption, renewable freshwater availability, and water scarcity for the entire 20th century. Water scarcity is analysed using the fundamental concepts of shortage (impacts due to low availability per capita) and stress (impacts due to high consumption relative to availability) which indicate difficulties in satisfying the needs of a population and overuse of resources respectively. While water consumption increased fourfold within the study period, the population under water scarcity increased from 0.24 billion (14% of global population) in the 1900s to 3.8 billion (58%) in the 2000s. Nearly all sub-national trajectories show an increasing trend in water scarcity. The concept of scarcity trajectory archetypes and shapes is introduced to characterize the historical development of water scarcity and suggest measures for alleviating water scarcity and increasing sustainability. Linking the scarcity trajectories to other datasets may help further deepen understanding of how trajectories relate to historical and future drivers, and hence help tackle these evolving challenges.

Analysis of late operations in transplant patients.

OBJECTIVE: The charts of 174 consecutive patients were analyzed for incidence, etiology, and outcome of late operations (1 month or more posttransplant) following liver (OLT), kidney (KT), or pancreas-kidney (SPK) transplantation. MATERIALS AND METHODS: Clinical and demographic data were analyzed by chi-square analysis and Fisher exact tests to compare subpopulations. All P values <.05 were considered statistically significant. RESULTS: Censured data revealed 155 patients who did not suffer death or organ loss within 30 days of transplant. Late operations were performed on 89 occasions in 57 patients (65% occurred within 1 year posttransplant) with 20 patients having two or more late operations. Of these 89 procedures, 40% were emergent, 37% were related to the transplant operation, 38% were related to the initial disease, and 73% were major interventions. Fifty-six procedures were performed by the transplant surgery team and all occurred in the same facility as the transplant. CONCLUSIONS: Transplant recipients have a high incidence (36%) of late operations, most within the first year and most related to either the transplant or the original disease. This heavy operative load is important in planning resource allocation. Oversight by and involvement of the transplantation service in these procedures may contribute to the favorable outcome of these operations.

Unequal representation of the temporal and nasal retina in an anomalous projection to the lateral thalamus.

Study of an anomalously regenerated, nontopographically organized retinal projection in the frog olfactory cortex revealed that the temporal retina is the main source of this projection, suggesting the existence of specific temporal fiber-directed attractant or trophic influences. In the present study, we examined the organization of an anomalous retinal projection that forms in the frog thalamus after ablation of the optic tectum. The projections from different sectors of the retina were studied by means of the anterograde transport of biotinylated dextran-amine (BDA) delivered to incisions made across the nerve fiber layer in frogs surviving ablation of the contralateral tectal hemisphere for 13-46 weeks. The projections from nasal retinal sectors were always lightly constructed in the aberrant terminal field, whereas their projections to the lateral geniculate complex remained reasonably strong. In contrast, the projections from temporal retinal sectors, though also weak initially, in time became robust and filled the aberrant field over most of its extent. The specific amplification of the temporal fiber projection now observed in two foreign targets provides further evidence for the existence of target-based, attractant/trophic molecules with functional specificity for temporal retinal fibers. That such agents can exist or be inducible in a foreign area would suggest that they belong to a family of molecules having natural biological activity in normal development or regeneration. However, the possibility that the augmented role of the temporal retina in these projections is a result of experience-based plasticity is also discussed.

Intraoperatively updated neuroimaging using brain modeling and sparse data.

OBJECTIVE: Image-guided neurosurgery incorporating preoperatively obtained imaging information is subject to spatial error resulting from intraoperative brain displacement and deformation. A strategy to update preoperative imaging using readily available intraoperative information has been developed and implemented. METHODS: Preoperative magnetic resonance imaging is used to generate a patient-specific three-dimensional finite element model of the brain by which deformation resulting from multiple surgical processes may be simulated. Sparse imaging data obtained subsequently, such as from digital cameras or ultrasound, are then used to prescribe the displacement of selected points within the model. Based on the model, interpolation to the resolution of preoperative imaging may then be performed. RESULTS: The algorithms for generation of the finite element model and for its subsequent deformation were successfully validated using a pig brain model. In these experiments, the method recovered 84% of the intraoperative shift resulting from surgically induced tissue motion. Preliminary clinical application in the operating room has demonstrated feasibility. CONCLUSION: A strategy by which intraoperative brain deformation may be accounted for has been developed, validated in an animal model, and demonstrated clinically.

Nuclear and cytoplasmic maturation of mouse oocytes after treatment with synthetic meiosis-activating sterol in vitro.

Synthetically produced meiosis-activating sterol, a sterol originally derived from follicular fluid (FF-MAS), induces meiotic maturation of mouse oocytes in vitro. We therefore compared FF-MAS-induced maturation of naked mouse oocytes arrested in prophase I by either hypoxanthine (Hx) or forskolin (Fo) with spontaneous maturation of naked oocytes. FF-MAS-treated oocytes overcame the meiotic block by Hx or Fo, although germinal vesicle breakdown was delayed by 11 h and 7 h, respectively. We also investigated the influence of FF-MAS on chromosome, microtubule, and ultrastructural dynamics in Hx-cultured oocytes by immunocytochemistry and electron microscopy. Similarly to spontaneously matured oocytes, chromosomes became aligned, a barrel-shaped spindle formed, and overall organelle distribution was normal in FF-MAS-matured oocytes. The number of small cytoplasmic asters was elevated in FF-MAS-treated oocytes. Although the number of cortical granules (CGs) was similar to that in spontaneously matured oocytes, the overall distance between CGs and oolemma was increased in the FF-MAS group. These observations suggest that the initiation of meiotic maturation in FF-MAS-treated oocytes in the presence of high cAMP levels leads to a delayed but otherwise normal nuclear maturation. FF-MAS appears to improve oocyte quality by supporting microtubule assembly and by delaying CG release, which is known to contribute to reduced fertilization.

Model-updated image guidance: initial clinical experiences with gravity-induced brain deformation.

Image-guided neurosurgery relies on accurate registration of the patient, the preoperative image series, and the surgical instruments in the same coordinate space. Recent clinical reports have documented the magnitude of gravity-induced brain deformation in the operating room and suggest these levels of tissue motion may compromise the integrity of such systems. We are investigating a model-based strategy which exploits the wealth of readily-available preoperative information in conjunction with intraoperatively acquired data to construct and drive a three dimensional (3-D) computational model which estimates volumetric displacements in order to update the neuronavigational image set. Using model calculations, the preoperative image database can be deformed to generate a more accurate representation of the surgical focus during an operation. In this paper, we present a preliminary study of four patients that experienced substantial brain deformation from gravity and correlate cortical shift measurements with model predictions. Additionally, we illustrate our image deforming algorithm and demonstrate that preoperative image resolution is maintained. Results over the four cases show that the brain shifted, on average, 5.7 mm in the direction of gravity and that model predictions could reduce this misregistration error to an average of 1.2 mm.

Updated neuroimaging using intraoperative brain modeling and sparse data.

A strategy to update preoperative imaging for image-guided surgery using readily available intraoperative information has been developed and implemented. A patient-specific three-dimensional finite element model of the brain is generated from preoperative MRI and used to simulate deformation resulting from multiple surgical processes. Intraoperatively obtained sparse imaging data, such as from digital cameras or ultrasonography, is then used to prescribe the displacement of selected points within the model. Interpolation to the resolution of preoperative imaging may then be performed based upon the model. The algorithms for generation of the finite element model and for its subsequent deformation have been successfully validated using a pig brain model, and preliminary clinical application in the operating room has demonstrated feasibility.

Biotinylated dextran amine and biocytin hydrochloride are useful tracers for the study of retinal projections in the frog.

Anatomical study of the topographic organization of retinal projections requires a tracer capable of resolving fine morphological detail and permitting analysis of the projection from either the whole retina or selected areas. To obtain a permanent record of the experiments and to have access to ultrastructural data, it is preferable for the tracer to be compatible with both brightfield microscopy and electron microscopy. Biotinylated dextran amine and biocytin hydrochloride, as employed in the present experiments, meet these needs exceptionally well for anterograde tracing studies on the frog visual system. Both tracers labeled axons and terminal arbors more prominently than comparable material studied by the widely used methods of anterograde fiber-filling with horseradish peroxidase or cobalt. When used to trace the projections from small sectors of retina, the finest unmyelinated fibers in layers A, C and E of the frog optic tectum and their synaptic boutons were made readily visible by the new tracers.

Antiserum inhibition of propagating viruses.

The design and implementation of controlled environments to continuously culture and evolve viruses provides a means to track how their populations respond to natural and designed anti-viral agents. We have previously demonstrated how the growth of viruses in spreading plaques enables detection and characterization of their evolutionary dynamics. Using plaques of phage T7 growing on E. coli as a model system, we observe here that velocities of propagation can be readily controlled by the level of anti-viral antiserum incorporated into the propagation medium. Further, we develop a simple analytic expression for the radial velocity of propagation in terms of the microscopic rates of viral amplification, Fickian diffusion of the virions and their neutralization by antiserum. Our analysis captures the essential dependence of propagation velocity on antiserum concentration. This study provides an ex vivo foundation for exploring how medically relevant viruses escape suppression by the immune system.

A compartment-based, asymmetric representation of the retina in an induced projection to the olfactory cortex.

Displacing the optic nerve into the telencephalon in adult Rana pipiens induces a projection to olfactory cortex. We have examined the topographic organization of this projection anatomically by injecting a mixture of biotin dextran (BDA) with 3H-amino acids into the affected eye immediately after making cuts across defined sectors of the nerve fiber layer to trace the complementary patterns of anterograde migration of BDA and 3H label in the cut and intact retinal axons, respectively. Fibers from the temporal side of the optic disc terminated in an oblique band along the posterior two-thirds or more of the ectopic projection field. In contrast, fibers arising in the nasal retina terminated in a parallel strip occupying the anterior one-third or less of the field. Varying the location of the cuts within each hemiretina did not reveal any further organization along the nasotemporal or dorsoventral axes of the retina. The retinal location of the cells involved in this projection was further studied with injections of wheat germ agglutinin conjugated to horseradish peroxidase into the olfactory cortex. Ganglion cells labeled by retrograde transport were found throughout the retina, but they were much more numerous on the temporal side, having a mean spatial density 3.7-7.4 times greater in the temporal hemiretina, whereas the overall ganglion cell density (labeled plus unlabeled) was roughly the same in the two halves of the retina. These data provide an example of a permanent projection in which the overall representation of the retina, though nontopological, is polarized in one axis (nasotemporal) and, therefore, compartmentally organized.

Concentration and storage of biotin in the amphibian brain.

Prominent displays of endogenous biotin reactivity can be observed at specific locations in histochemical preparations of the forebrain and midbrain in the northern leopard frog (Rana pipiens) and common American toad (Bufo americanus). At the light microscopic level, the biotin reactivity appears in clusters of darkly stained puncta of either spherical or rodlike shape in the olfactory cortex, nucleus isthmi, and hypothalamus. With the electron microscope, the biotin reactive spheres are identified as neuronal varicosities and synaptic boutons and the rods as short segments of axons. Appropriate controls demonstrate that the punctate biotin-reactive structures are sites of concentration of biotin or a biotin analog in the processes of certain neurons. These data represent the first observation on the selective concentration of a vitamin in vertebrate neurons and suggest that biotin may have specialized functions in anatomically delimited areas of the central nervous system. Localization of the densest concentration of the biotin-reactive puncta in the dorsolateral prominence of the olfactory cortex may have relevance to the functional organization of the olfactory system. The distributions of biotin-reactive puncta were observed in laboratory-housed frogs and in wild toads captured in the summer months but were sparse or absent in batches of commercially obtained frogs examined immediately upon arrival in the laboratory. Systemic administration of biotin or biocytin hydrochloride did not alter the appearance or numbers of the biotin-reactive structures either in newly received or laboratory-housed frogs. These findings suggest that the capacity of the biotin-storage mechanism in the amphibian brain may be set by environmental factors and may be readily saturable from natural dietary or enteric sources.

A double-blind, placebo-controlled study of the effect of imipramine on TRH-induced urinary urgency in healthy men.

We studied the effect of imipramine (IMI) on thyroid releasing hormone (TRH)-induced urinary urgency as a way of investigating the mechanism of the beneficial effect of IMI on enuresis. In a double-blind study, 12 normal, healthy men between 21 and 39 yr of age ranked their urge to urinate at 30-sec intervals following IV injection of TRH (500 micrograms) or saline. The subjects then were randomly assigned to either IMI (1 mg/kg) or placebo groups for 10 days, and the procedure was repeated. Compared to saline, TRH produced a significant elevation in urinary urgency in all subjects. IMI did not significantly blunt TRH-induced urinary urgency. Thus, the mechanism by which IMI affects enuresis is likely not mediated at the level of the urinary urgency induced by TRH.

Hypercalcemia and reversible renal failure in heavy-chain disease.

We have reported a case of gamma heavy-chain disease associated with hypercalcemia and reversible renal failure. After combined chemotherapy the patient remains well after 21 months of follow-up, and serum calcium levels remain in the normal range. This case supports the notion of Kyle et al that heavy-chain disease may present a diverse picture, and documents the first use of aggressive combination chemotherapy in the management of associated moderately severe hypercalcemia and hypercalcemic renal failure.

Tobramycin sulfate elimination in premature infants.

The elimination pharmacokinetics of tobramycin sulfate was studied in 25 newborn infants of birth weight 0.7 to 4.7 kg during 31 treatment episodes. The peak serum concentrations after a 2.5 mg/kg dose were usually within the therapeutic range of 5 to 10 micrograms/ml; however, the serum predose trough values were elevated above the theoretical safe limit of 2 micrograms/ml. Because of the prolonged serum elimination half-lives, a calculated extended dosage interval, sometimes greater than 24 hours, was necessary to obtain a predose trough of less than or equal to 2 micrograms/ml. The serum elimination half-lives inversely correlated with gestational age, extrauterine age, birth weight, and creatinine clearance. The very low ratio of tobramycin renal clearance to creatinine renal clearance was virtually constant and indicated a probable tubular reabsorption of tobramycin. A general dosage schedule based on birth weight was derived from the data. An alternative formula was derived to enable prediction of the tobramycin elimination half-life based on a combination of birth weight, gestational age, and extrauterine age for an infant younger than 7 days of age.