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Introduction: Benefits and harms of avoid the sent placement during IntraCorporeal Neobladder configuration are still debated. Our objective was to describe the step-by-step technique of Florence intracorporeal neobladder (FloRIN) configuration performed with stentless procedure focusing on perioperative and mid-term functional outcomes.Materials and methods: In this single institution prospective randomized 1:1 series all consecutive patients underwent Robot-Assisted Radical Cystectomy (RARC) and FloRIN reconfiguration from January 2021 to March 2021 were enrolled. Functional perioperative and mid-term outcomes were gathered. Postoperative complications were graded according to Clavien-Dindo classification and divided in early (<30 days from discharge) and delayed (>30 days).Results: Overall, 10 patients were included in the analysis. Of these, the 50.0% was treated with Stentless FloRIN. In terms of baseline features, no differences were recorded between the two groups. Median age was 65 and 66 years while median BMI was 27 and 25 in the stentless and in the stent group, respectively. Concerning intraoperative variables, no intraoperative complications as well as open conversion occurred among both groups. As regard introperative features, a shorter console time was associated with stentless procedure (331 min vs 365 min). In terms of perioperative outcomes, canalization and time to drainage removal didn’t differ between groups while length of hospital stay was significantly lower in stentless group 10 days versus 14 days. Early and delayed postoperative complication rate was not influenced by the ureteral management at a preliminary assessment with comparable rates of Clavien Dindo ⩾ 3a between the two groups. Mid-term functional outcomes did not differ between groups in terms of kidney function loss.Conclusions: FloRIN with Stentless technique showed functional and perioperative preliminary outcomes comparable with the standard ureteral management strategy. Further series with longer functional follow-up assessment will be needed to confirm our preliminary results.

Fostered by the top power conversion efficiencies (PCEs) of lab-scale devices, industrialization of perovskite solar cells is underway. Nevertheless, the intrinsically poor stability of these materials still represents a major concern. Herein, inspired by Nature, the use of β-carotene in perovskite solar cells is proposed to mimic its role as a protective pigment, as occurs in natural photosynthesis. Laser-mediated photostability (LMPS) assessment, Fourier-transform infrared spectra analysis acquired in attenuate total reflectance (ATR-FTIR), spectroscopy ellipsometry (SE), and time-resolved photoluminescence (TRPL) measurements under stress conditions prove that the inclusion of a thin β-carotene interlayer promotes a high improvement in the photostability of the perovskite films against photooxidation. Importantly, this is accompanied by an improvement of the solar cell PCE that approaches 20% efficiency with no hysteresis, which is among the highest values reported for a mixed halide (I-Br) perovskite with a band gap of 1.74 eV, relevant for coupling with silicon in tandem cells.

Multication and multianion hybrid perovskites are among the most attractive materials currently under investigation for tandem photovoltaic applications because of the possibility they offer to finely tune the band gap, thus allowing the coupling with other semiconductors. If mixing different ions in the perovskite compositions can, on one hand, give the possibility to create different useful materials with different properties, on the other hand it could be detrimental to the hybrid perovskite stability. The presence of different ions leads to the formation of different polytypes that could open new pathways for the degradation of the prepared films. In this work, we have investigated the role of different polytypes on the degradation and stability of mixed hybrid perovskites by in situ X-ray diffraction analyses. We found that the use of even a small amount of methylammonium cations opens a new route for the degradation of the perovskite film, triggering a more advanced degradation beyond the loss of the methylammonium cations. By in-situ analyses during focused thermal treatments, we unveil an interplay between the different polytypes triggered by temperature. In particular, we show how the 4H polytype of the formamidinium lead iodide (FAPbI3) is recovered with an annealing at 100 °C in N2that restores the 3C polytype. We propose the use of 1,3:2,4-bis-O-(4-methylbenzylidene) d-sorbitol (MDBS) additive as a remedy to increase the stability of the perovskite film even in the presence of the methylammonium cation by making the perovskite films more compact, thus reducing the surface/volume ratio.

We investigated the complex dielectric function of bromide perovskite single crystals (MAPbBr3, FAPbBr3and CsPbBr3) by spectroscopic ellipsometry from 1 to 5 eV in the 183–423 K temperature range and under a dry nitrogen environment. The temperature dependence of all critical points provided a benchmark for the interband electronic transition energies in the three bromide perovskites for a wide spectral range. We found that the number of transitions in CsPbBr3depends on the crystallographic phase, with the orthorhombic lattice showing an extra transition with respect to the tetragonal and the cubic phases. Through density functional theory calculations, we identified the changes in the electronic structure that accompany the tetragonal-to-orthorhombic transition, leading to splitting of the complex dielectric function along the aand bcrystallographic directions. We thereon used a similar experimental approach to study the robustness of bromide perovskites under humid air. We found that FAPbBr3and CsPbBr3remain unchanged up to 383 K, whereas MAPbBr3is irreversibly modified at 363 K. The degradation of MAPbBr3impacts its optical transitions and introduces a pregap absorption tail. Together with this, a dramatic damage of the surface is observed with the formation of reverse truncated pyramids accompanied by local worsening of the carrier extraction barrier in the remaining flat sample surface.

Phosphoinositol 3-kinases (PI3Ks) γ and δ are key enzymes in hematopoietic cells and have been seen as high-value targets for the treatment of diseases with inflammatory and immunomodulatory components since their discovery and the identification of their roles. In this Perspective we review progress in the application of inhibitors of PI3Kγ and δ to inflammatory and immunological conditions over the past 6 years. We consider progress in the understanding of the roles of PI3Kγ and PI3Kδ in immunology and inflammation, the experience from clinical trials where inhibitors have been tested, and what has been learned about the safety of their use. The extensive medicinal chemistry efforts to discover both isoform selective and dual PI3Kγδ inhibitors are analyzed and detailed. Developments in understanding the structural chemistry of the PI3K enzymes and the factors that govern isoform selectivity are discussed. The effects observed with the known inhibitor compounds in animal models are described.

Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1). Utilizing these cell lines, we have refined the previously published procedures to generate a new, higher throughput protocol suitable for drug discovery. Using paraffin-embedded sectioning and whole-mount immunostaining, we demonstrated that organoids grown in suspension culture express key markers of kidney biology (WT1, ECAD, LTL, nephrin) and vasculature (CD31) within renal cortical structures with microvilli, tight junctions and podocyte foot processes visualized by electron microscopy. Additionally, the organoids resemble the adult kidney transcriptomics profile, thereby strengthening the translatability of our in vitromodel. Thus, development of human nephron-like structures in vitrofills a major gap in our ability to assess the effect of potential treatment on key kidney structures, opening up a wide range of possibilities to improve clinical translation.

Diabetic nephropathy (DN) remains an unmet medical challenge as its prevalence is projected to continue to increase and specific medicines for treatment remain undeveloped. Activation of the immune system, in particular T-cells, is emerging as a possible mechanism underlying DN disease progression in humans and animal models. We hypothesized that inhibition of T-cell activation will ameliorate DN. Interaction of B7-1 (CD80) on the surface of antigen presenting cells with its binding partners, CTLA4 (CD152) and CD28 on T-cells, is essential for T-cell activation. In this study we used the soluble CTLA4-Fc fusion protein Abatacept to block cell surface B7-1, preventing the cellular interaction and inhibiting T-cell activation. When Abatacept was dosed in an animal model of diabetes-induced albuminuria, it reduced albuminuria in both prevention and intervention modes. The number of T-cells infiltrating the kidneys of DN animals correlated with the degree of albuminuria, and treatment with Abatacept reduced the number of renal T-cells. As B7-1 induction has been recently proposed to underlie podocyte damage in DN, Abatacept could be efficacious in DN by protecting podocytes. However, this does not appear to be the case as B7-1 was not expressed in 1) kidneys of DN animals; 2) stimulated human podocytes in culture; or 3) glomeruli of DN patients. We conclude that Abatacept ameliorates DN by blocking systemic T-cell activation and not by interacting with podocytes.

We report that R- and S-phenibut (β-phenyl-γ-aminobutyric acid) – derivatives of GABA – bind with an affinity of c.a.90μM to the gabapentin binding site in a competitive assay, a value comparable to that for previously claimed targets for this enantioermic molecule. This finding implied potential activity in neuropathic pain, this being one of the clinically validated indications for gabapentin.

Background: We report that R- and S-phenibut (ß-phenyl-?-aminobutyric acid) - derivatives of GABA - bind with an affinity of c.a.90 µM to the gabapentin binding site in a competitive assay, a value comparable to that for previously claimed targets for this enantioermic molecule. This finding implied potential activity in neuropathic pain, this being one of the clinically validated indications for gabapentin. Methods: The effect of phenibut on tactile allodynia was tested in a chronic constriction nerve injury (CCI) neuropathic pain model and against hypersensitivity following inflammation induced by inoculation using complete Freund’s adjuvant (CFA) model. Results: Indeed, a significant inhibitory effect on tactile allodynia was detected in rats in both employed chronic pain models with stronger and clearly dose dependent effect with R isomer. Conclusions: The results confirm activity in chronic pain models predicted from affinity for the gabapentin site and suggests, at least partially, that a2d-subunits of presynaptic voltage-gated calcium channels are involved in mediating this effect.

Electronic travel aids are used for detecting obstacles, identifying services, and, generally, obtaining useful information from the surroundings, thus enabling a safe and effective exploitation of the environment. A drawback is unnatural codification, which may lead to usability concerns. This paper introduces a haptic device aimed to provide the user with information on the presence of obstacles inside the environment. The haptic interface is intended to reproduce the stimuli provided by a traditional white cane, without any contact with the environment. A prototype, implemented through a short cane with an embedded smart sensing strategy and an active handle, is presented. Twenty-five blindfolded normally sighted users participated to assess system performance in detecting obstacles and correctly conveying their position by the haptic interface. With respect to detecting obstacles and their positions, the average values of the sensitivity in the case of left, center, and right positioned obstacles are 0.735, 0.803, and 0.830, while the specificity values are 0.924, 0.835, and 0.827, respectively.

The aim of the present study was to describe the characteristics of repetitive self-injurious behaviour and related personality functioning as well as to explore the relationship between NSSI and alexithymia in a sample of NSSI adolescents (mean age= 16.1 yrs) within therapeutic communities. The results showed a representation of Cluster B personality features and personality disorders (e.g., borderline, narcissistic, antisocial). A significant association between NSSI behaviours and alexithymia was found. Additionally, the data supported the use of SWAP-200-A as an instrument for assessing personality functioning and personality pathology in adolescents who self-injure. Future research will be necessary to confirm these results.

Introduction/Purpose:Sleep is critical for health and plays a role in motor learning, which is an important component of post stroke rehabilitation. There is limited research on the impact of sleep on functional outcomes during the early stages of rehabilitation after stroke. The purpose of this study was to explore the associations between sleep parameters and functional recovery during inpatient rehabilitation in people with stroke.Methods:13 participants undergoing inpatient rehabilitation after stroke were recruited to participate. Function was measured at admission and discharge using GG Self Care and Mobility scales. Sleep parameters; sleep efficiency and wake after sleep onset (WASO); were determined from an ActiGraph wGT3X-BT activity monitor (AGAM), which participants wore for 5 days continuously upon admission. Associations between sleep parameters and function were determined using Pearson correlation coefficients.Results:Mean time since stroke was 15.5 (9.0) days, mean National Institutes of Stroke Scale score was 6.2 (4.1), mean age was 65.1 (12.1) years old, and 54% were women. There was a moderate association between sleep efficiency and change in GG mobility score; r=0.67 (p=0.012); and a moderate inverse association between WASO and change in GG mobility scores: r=-0.66 (p=0.013). There was not a significant association between change in GG self-care score and sleep parameters (p>=0.05).Discussion:Quality of sleep is associated with improvement in functional mobility during inpatient rehabilitation after stroke. Participants with better sleep efficiency and less time awake during the night after falling asleep during the first 5 days of their inpatient rehabilitation stay had greater improvement in functional mobility at discharge. Further research is needed to examine the complex relationships between sleep and recovery after stroke and to investigate possible interventions to promote better sleep during inpatient rehabilitation after stroke.

The author describes his relationship with his father and his family bakery Carlo's Bake Shop in Hoboken, New Jersey. He describes his visits at the bakery during childhood, his father's ambition of featuring his shop in a bridal magazine, and how he had to enter family business after death of his father. He narrates an incidence of how he learnt to make lobster tails from his father in a dream. He also describes how he expanded the business and started the television show "Cake Boss."

5-Hydroxytryptamine 6 (5-HT6) receptors are involved in learning and memory processes and are discussed as promising targets for the treatment of cognitive impairment in central nervous system disorders. A number of 5-HT6 antagonists are currently in the clinical development for schizophrenia and Alzheimer's disease (AD). There is some discrepancy regarding cognitive efficacy in subjects, and only limited data are available on the role of the 5-HT6 receptor in animal models of psychosis. The aim of this study was to investigate the efficacy of the selective 5-HT6 antagonists, Ro-4368554 (1–10 mgkg, intraperitoneally) and SB-258585 (3–30 mgkg, intraperitoneally), in animal models for schizophrenia and AD. Both compounds showed cognition-enhancing effects in object recognition, whereas only SB-258585 was able to prevent the scopolamine-induced deficit in the Morris water-maze test. Neither Ro-4368554 nor SB-258585 prevented scopolamine-induced impairment in contextual fear conditioning. Similarly, both compounds were ineffective on MK-801-induced deficits in contextual fear conditioning and spatial working memory. Ro-4368554, but not SB-258585 reversed the apomorphine-induced deficit in prepulse inhibition. Amphetamine-induced hyperlocomotion was not affected by either compound. Taken together, the overall efficacy of Ro-4368554 and SB-258585 in animal models for AD and schizophrenia is rather limited. These data show moderate efficacy in some models for AD but do not support the therapeutic potential of 5-HT6 antagonists for schizophrenia.

Oxidative stress is currently considered a mediator of cell death in several neurodegenerative diseases. Notably, it may play an important role in the degeneration of dopamine neurons of the substantia nigra in Parkinson’s disease. We examined the effect of a strong oxidant, the herbicide paraquat, on cell distress using native and neuronal pheochromocytoma PC12 cells. Paraquat administration for 8 hours induced a significant cellular death in both native and in neuronal PC12 cells. Since the anti-oxidant properties of estrogens may promote neuroprotectionin vitroandin vivo, we then investigated the ability of estradiol stereoisomers, 17α-estradiol and 17β-estradiol, to rescue PC12 cells submitted to paraquat-induced oxidative stress. Our results show a protective effect of both estradiol stereoisomers in neuronal PC12 cells treated with paraquat, whereas this effect could not be observed in native PC12 cells. We also demonstrate that estrogen receptor β protein expression is modulated by paraquat administration in native PC12 cells, while paraquat does not change estrogen receptor β expression in neuronal PC12 cells. Paraquat also decreases estrogen receptor α in neuronal PC12 cells, thus suggesting new routes for paraquat to collapse cellular metabolism. Besides, the oxidation of dihydrodhodamine-123 into fluorescent rhodamine in the presence of paraquat but not in presence of paraquat and 17α-estradiol or 17β-estradiol,sustain a possible direct scavenging role of both estradiol stereoisomers.

Abstract: Oxidative stress has been recently considered as a mediator of nerve cell death in several neurodegenerative diseases. We studied the effect of the parkinsonism-inducing toxine 1-methyl-4-phenyl-pyridine (MPP+) on several parameters of cell distress using native and neuronal PC12 cells. Then, since estrogens have been reported to prevent neuronal degeneration caused by oxidative damage, we investigated the ability of 17β-estradiol (E2); two Ginkgo biloba extracts, EGb 761 and Cp 202; as well as two flavonoids, quercetin and kaempferol, to rescue PC12 cells submitted to MPP+-induced oxidative stress. Our results consistently show that both Ginkgo biloba extracts could prevent cell death in native and neuronal PC12 cells, while in neuronal PC12 cells also quercetin and E2 could reverse MPP+ neurotoxic effet. Western blot analysis demonstrated that MPP+ injuries might modulate dopamine transporter (DAT) protein expression but not estrogen receptor β (ERβ) protein expression. EGb 761 and Cp 202 also modulate DAT and ERβ protein expression in neuronal cells. From these studies, we outline the importance of testing estrogen-like plant-derived molecules as potent antioxidants and examine their effect on protein expression.

D-myo-inositol 1,2,3,4,5,6-hexakisphosphate (InsP6), one of the most abundant inositol phosphates within cells, has been proposed to play a key role in vesicle trafficking and receptor compartmentalization. In the present study, we used in vitro receptor autoradiography, subcellular fractionation, and immunoblotting to investigate its effects on α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors. Qualitative and quantitative analysis of ³H-AMPA binding indicated that incubation of frozen-thawed brain sections with InsP6 at 35°C enhanced AMPA receptor binding in several brain regions, with maximal increases in the hippocampus and cerebellum. Moreover, saturation kinetics demonstrated that InsP6-induced augmentation of AMPA binding was due to an increment in the maximal number of AMPA binding sites. At the immunological level, Western blots performed on crude mitochondrial/synaptic (P2) fractions revealed that InsP6 (but not InsP5 and InsP3) treatment increased glutamate receptor (GluR)1 and GluR2 subunits of AMPA receptors, an effect that was associated with concomitant reductions in microsomal (P3) fractions. Interestingly, the InsP6-induced modulation of AMPA receptor binding was blocked at room temperature, and pretreatment with heparin also dampered its action on both AMPA receptor binding and GluR subunits. These effects of InsP6 appear to be specific to AMPA receptors, as neither ³H-glutamate binding to NMDA receptors nor levels of NR1 and NR2A subunits in P2 and P3 fractions were affected. Taken together, our data strongly suggest that InsP6 specifically regulates AMPA receptor distribution, possibly through a clathrin-dependent process. Hippocampus 2001;11:673–682. © 2001 Wiley-Liss, Inc.

D‐myo‐inositol 1,2,3,4,5,6‐hexakisphosphate (InsP6), one of the most abundant inositol phosphates within cells, has been proposed to play a key role in vesicle trafficking and receptor compartmentalization. In the present study, we used in vitro receptor autoradiography, subcellular fractionation, and immunoblotting to investigate its effects on α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) and N‐methyl‐D‐aspartate (NMDA) receptors. Qualitative and quantitative analysis of 3H‐AMPA binding indicated that incubation of frozen‐thawed brain sections with InsP6 at 35°C enhanced AMPA receptor binding in several brain regions, with maximal increases in the hippocampus and cerebellum. Moreover, saturation kinetics demonstrated that InsP6‐induced augmentation of AMPA binding was due to an increment in the maximal number of AMPA binding sites. At the immunological level, Western blots performed on crude mitochondrial/synaptic (P2) fractions revealed that InsP6 (but not InsP5 and InsP3) treatment increased glutamate receptor (GluR)1 and GluR2 subunits of AMPA receptors, an effect that was associated with concomitant reductions in microsomal (P3) fractions. Interestingly, the InsP6‐induced modulation of AMPA receptor binding was blocked at room temperature, and pretreatment with heparin also dampered its action on both AMPA receptor binding and GluR subunits. These effects of InsP6 appear to be specific to AMPA receptors, as neither 3H‐glutamate binding to NMDA receptors nor levels of NR1 and NR2A subunits in P2 and P3 fractions were affected. Taken together, our data strongly suggest that InsP6 specifically regulates AMPA receptor distribution, possibly through a clathrin‐dependent process. Hippocampus 2001;11:673–682. © 2001 Wiley‐Liss, Inc.

Various forms of synaptic plasticity in the brain have been proposed to result from modifications in the properties of glutamate receptors by calcium‐dependent mechanisms. In the present study, changes in glutamate receptors elicited by calcium treatment of previously frozen mouse brain sections were evaluated by qualitative as well as quantitative analysis of tritiated ligand binding to both α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) and N‐methyl‐D‐aspartate (NMDA) glutamate receptor subtypes. Quantitative analysis revealed that 3H‐AMPA binding was reduced in a dose‐dependent manner by calcium in the cerebral cortex and striatum formations. However, an opposite change in AMPA receptor properties was observed in the hippocampus, as calcium generated an increase of AMPA binding in all hippocampal fields. Analysis of the saturation kinetics of 3H‐AMPA binding showed that the calcium‐induced augmentation of AMPA binding in the stratum radiatum of the CA1region was due to an alteration in the maximal number of sites, while the reduction of binding elicited by calcium in the cortex appeared to be due to modified AMPA receptor affinity. Calcium‐induced downregulation of AMPA receptor affinity in the cortex and striatum was affected by baicalein, a selective inhibitor of the lipoxygenase pathways of arachidonic acid metabolism, whereas the same inhibitor did not modify calcium‐mediated upregulation of receptor number in the CA1region of the hippocampus. On the other hand, the effect of calcium appeared to be specific for the AMPA receptor, as the same treatment did not affect glutamate binding to the NMDA glutamate receptor subtype. Our results suggest the possibility that, depending on the brain regions, calcium ions may generate opposite modulation of AMPA receptor properties. Because the regulation of AMPA receptors by calcium‐dependent enzymes has been implicated in synaptic plasticity, our results suggest that regional variations in the effect of calcium on AMPA binding account for differential plasticity at glutamatergic synapses. Hippocampus 2000;10:645–653. © 2000 Wiley‐Liss, Inc.

Various forms of synaptic plasticity in the brain have been proposed to result from modifications in the properties of glutamate receptors by calcium-dependent mechanisms. In the present study, changes in glutamate receptors elicited by calcium treatment of previously frozen mouse brain sections were evaluated by qualitative as well as quantitative analysis of tritiated ligand binding to both α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptor subtypes. Quantitative analysis revealed that ³H-AMPA binding was reduced in a dose-dependent manner by calcium in the cerebral cortex and striatum formations. However, an opposite change in AMPA receptor properties was observed in the hippocampus, as calcium generated an increase of AMPA binding in all hippocampal fields. Analysis of the saturation kinetics of ³H-AMPA binding showed that the calcium-induced augmentation of AMPA binding in the stratum radiatum of the CA1 region was due to an alteration in the maximal number of sites, while the reduction of binding elicited by calcium in the cortex appeared to be due to modified AMPA receptor affinity. Calcium-induced downregulation of AMPA receptor affinity in the cortex and striatum was affected by baicalein, a selective inhibitor of the lipoxygenase pathways of arachidonic acid metabolism, whereas the same inhibitor did not modify calcium-mediated upregulation of receptor number in the CA1 region of the hippocampus. On the other hand, the effect of calcium appeared to be specific for the AMPA receptor, as the same treatment did not affect glutamate binding to the NMDA glutamate receptor subtype. Our results suggest the possibility that, depending on the brain regions, calcium ions may generate opposite modulation of AMPA receptor properties. Because the regulation of AMPA receptors by calcium-dependent enzymes has been implicated in synaptic plasticity, our results suggest that regional variations in the effect of calcium on AMPA binding account for differential plasticity at glutamatergic synapses. Hippocampus 2000;10:645–653. © 2000 Wiley-Liss, Inc.

A subaerially exposed coral reef records a period of marine conditions following earliest Holocene transgression into the technically active, subsea level Enriquillo Valley, Dominican Republic. Field mapping, detailed leveling of reef elevations, and I4C dating of fossil corals and mollusks reveal the following chronology of reef development in an unusual geologic and tectonic environment: (1) earliest Holocene ($$9760 \pm 100$$yr B.P.) marine transgression and growth of oysters on an alluvial fan surface approximately 33 m below sea level (BSL); (2) colonization of reef corals at approximately 34 m BSL on the oyster shell deposits ($$8990 \pm 60$$yr B.P.); (3) middle Holocene development of a typical Caribbean fringing reef in a protected environment ($$6200 \pm 80$$to $$4760 \pm 90$$yr B.P.); (4) late Holocene sedimentation over the reef with fossil bivalves ($$5710 \pm 90$$to $$2820 \pm 40$$yr B.P.) that record a gradual change from marine to brackish water that accompanied growth of shoreline thrombolitic stromatolites near present sea level; and (5) subsequent evaporation of Lake Enriquillo to its present level (March 1983) of 41.5 m BSL. The mid-Holocene reef crest corals (stage 3 above) are about 2 m higher than corals of similar age reported for reefs elsewhere in the Caribbean and western Atlantic. Apparent uplift is attributed to either deformation along thrust faults bounding the valley or underestimation of paleosea levels by previous reef studies in the Caribbean and western Atlantic. The Enriquillo Valley probably contains a record of post-glacial sea level rise extending more than 10,000 yr B.P. It may also contain a record of other sea level transgressions that invaded the valley in late Quaternary time. It is possible that this record could be recovered by drilling or coring the lake sediments.

Zusammenfassung Die jungpleistozänen Glazialformationen in der Páramo de La Culata-Region, der nördlichen Zentralanden Venezuelas, enthalten: 1. Ablagerungsformationen: Moränen und fluvio-glaziale Ablagerungen (Terrassenkonglomerate); 2. Glazialskulpturformationen: Glazialtäler, Kare, Home und schroffe Felsgrate; und 3. Erosionsformationen: Gletscherschrammen und Furchen, Gletscherschliff, Rundhöcker und Wahlrückenformen, und erratische Blöcke. Es wurden zwei Hauptmoränenniveaus gefunden, ein älteres Niveau in 2600 m Höhe und ein jüngeres zwischen 3000 und 3500 m. Dieser Altersunterschied entspricht einer stärkeren Verwitterung, Erosion und Vegetationsdecke in dem niederen Niveau, verglichen mit dem höheren. Radiokohlenstoffdatierungen und ein Vergleich und eine Korrelation dieser Glazialformationen mit denen in anliegenden Regionen, gibt Anhalt zur Behauptung, daß das niedere Moränenniveau (2600 m) wahrscheinlich durch den Hauptgletschervorstoß der Spät-Wisconsin-Eiszeit entstand. Das Hauptmoränenniveau (3000 bis 3500 m) wurde wahrscheinlich durch den jüngsten (letzten) Wisconsin-Gletschervorstoß produziert. Die jungpleistozäne Schneegrenze lag ungefähr 1200 m unter der heutigen Schneegrenze (also in ungefähr 3500 m Höhe).

New pollen records from White Lake in the Southern High Plains and from Friesenhahn Cave on the southeastern Edwards Plateau of Texas indicate that the glacial-age vegetation of the southern Great Plains was a grassland. The High Plains was a treeless Artemisiagrassland and the Edwards Plateau, at the south edge of the Great Plains, was a grassland with pinyon pines and deciduous trees in canyons and riparian habitats. The glacial-age grasslands differ from modern shortgrass and tallgrass prairies and may have no modern analog. The dominance of prairie vegetation during the last glacial maximum is compatible with late Pleistocene mammalian faunas and late-glacial grassland pollen records from the region. Earlier interpretations of a pine-spruce forest on the High Plains were based on pollen assemblages that are here shown to have been altered by postdepositional deterioration, resulting in differential preservation of conifer pollen grains. Accordingly, the "Tahoka Pluvial" and other "climatic episodes" defined by High Plains pollen records are abandoned.

Haploxylon pine(s) and Artemisiadominated the initial vegetation in front of the receding Okanogan Lobe until ca. 10,000 yr B.P., as revealed by two pollen records in north-central Washington. After 10,000 yr B.P. the macroclimate became warmer throughout the Okanogan drainage as diploxylon pines and Artemisiaincreased. The Mount Mazama eruption at ca. 6700 yr B.P. is recorded as two stratigraphically separate and petrographically distinct tephra units at Bonaparte Meadows. While there are apparent short-term changes in the vegetation coincident with the ashfall(s), Artemisiacontinues to dominate the Okanogan Valley until ca. 5000 yr B.P. By 4700 yr B.P. the modern vegetation, dominated by Pseudotsuga menziesii, had become established around Bonaparte Meadows.

Pollen records in the Kootenai and Fisher River drainages in western Montana reveal a fivezone sequence of Holocene vegetation change. Deposition of Glacier Peak Ash-Layer G (ca. 10,540 ± 660 yr B.P.) in the lowermost sediments (clay intermixed with pebbles) at Tepee Lake gives a minimum date for the initiation of sedimentation. Initial vegetation on the newly deglaciated terrain was dominated by Pinus(probably white bark pine) with small amounts of Gramineae, Piceaand Abies, reflecting a relatively cool, moist macroclimate. Two vegetation units appear to contribute to Pollen Zone II (ca. 11,000–7100 yr B.P.): arboreal communities with pines, along with Pseudotsugaor Larix, or both, and treeless vegetation dominated by Artemisia. Pollen Zone II represents an overall warmer macroclimate than occurred upon ice withdrawal. After ca. 7100 yr B.P. (Pollen Zone III) diploxylon pines became a major pollen contributor near both Tepee Lake and McKillop Creek Pond, indicating an expansion of xerophytic forest ( P. contortaand P. ponderosa) along with an increase in the prominence of Pseudotsuga menziesiior Larix occidentalis, or both. Artemisiabriefly expanded coverage near Tepee Lake concomitant with the Mazama ashfall ca. 6700 yr B.P. A short-term climatic trend with more available water began after ca. 4000 yr B.P. as Abies(probably A. grandis) along with Picea engelmanniibecame a more regular component of the forest surrounding both sites. Emergence of the modern macroclimate is indicated primarily with the first regular appearance of Tsuga heterophyllain the pollen record by ca. 2700 yr B.P., synchronous with the development of western hemlock forest within the same latitudes in northern Idaho and northeastern Washington.

Three Pleistocene glaciations and two Holocene Neoglacial advances occurred on volcano Ajusco in central Mexico. Lateral moraines of the oldest glaciation, the Marqués, above 3250 m are made of light-gray indurated till and are extensively modified by erosion. Below 3200 m the till is dark red, decomposed, and buried beneath volcanic colluvium and tephra. Very strongly to strongly developed soil profiles (Inceptisols) have formed in the Marqués till and in overlying colluvia and tephra. Large sharp-crested moraines of the second glaciation, the Santo Tomás, above 3300 m are composed of pale-brown firm till and are somewhat eroded by gullies. Below 3250 m the till is light reddish brown, cemented, and weathered. Less-strongly developed soil profiles (Inceptisols) have formed in the Santo Tomás till and in overlying colluvia and tephra. Narrow-crested moraines of yellowish-brown loose till of the third glaciation, the Albergue, are uneroded. Weakly developed soil profiles (Inceptisols) in the Albergue till have black ash in the upper horizon. Two small Neoglacial moraines of yellowish-brown bouldery till on the cirque floor of the largest valley support weakly developed soil profiles with only A and Cox horizons and no ash in the upper soil horizons. Radiocarbon dating of organic matter of the B horizons developed in tills, volcanic ash, and colluvial volcanic sand includes ages for both the soil-organic residue and the humic-acid fraction, with differences from 140 to 660 yr. The dating provides minimum ages of about 27,000 yr for the Marqués glaciation and about 25,000 yr for the Santo Tomás glaciation. Dates for the overlying tephra indicate a complex volcanic history for at least another 15,000 yr. Comparison of the Ajusco glacial sequence with that on Iztaccíhuatl to the east suggests that the Marqués and Santo Tomás glaciations may be equivalent to the Diamantes glaciation First and Second advances, the Albergue to the Alcalican glaciations, and the Neoglacial to the Ayolotepito advances.

Hager Pond, a mire in northern Idaho, reveals at least five pollen zones since sediments formed after the last recession of continental ice (>9500 yr BP). Zone I (>9500-8300 yr BP) consists mainly of diploxylon pine, plus low percentages of Abies, Artemisia, and Picea. SEM examination of conifer pollen at selected levels in the zone reveals that Pinus albicaulis, P. monticola, and P. contortaare present in unknown proportions. The zone resembles modern pollen spectra from the Abies lasiocarpa-P. albicaulisassociation found locally today only at high elevation. Presence of whitebark pine indicates a cooler, moister climate than at present, but one which was rapidly replaced in Zone II (8300-7600 yr BP) by warmer, drier conditions as inferred by prominence of grass with diploxylon pine. Zone III (7600-3000 yr BP) was probably dominated by Pseudotsuga menziesii, plus diploxylon pine and prominent Artemisiaand denotes a change in vegetation but continuation of the warmer drier conditions. Beginning at approximately 3000 yr BP Picea engelmannii, Abies lasiocarpa, and/or A. grandisand diploxylon pine were dominants and the inferred climate became cooler and moister concomitant with Neoglaciation. The modern climatic climax (Zone V), with Tsuga heterophyllaas dominant, has emerged in approximately the last 1500 yr.

TEPHRA falls from Mount Mazama1,2, on the site of the present Crater Lake caldera in Oregon, form the most extensive Holocene marker horizon in the Pacific North-west of the US and the adjacent part of Canada. Ash has been found east to Saskatchewan, south to Nevada, north to central British Columbia and on the Pacific Ocean floor3–6. Although the Mazama ash unit has been radiometrically dated repeatedly in the past 25 years (its age was one of the first determined by Arnold and Libby7), problems remain about the nature of the ashfall(s) and the radiometric control for the event(s). For example, the ash shows a degree of pertrographic variation that is not attributable only to gravity sorting away from the source. Also the spread of bracketing or included dates for tephra from 6,600 to ∼7,000 BP, using charcoal or non-calcareous sediments, is wider than expected for a single Holocene event8–10. Taken together, these facts suggest multiple Holocene eruptions of Mount Mazama. Substantial evidence of repeated or multiple eruptions is seen in the two unit sequence of Mazama ash in the C horizons of some soils and in peat bogs in Oregon. The ranges of radiocarbon dates under either the upper or the lower ash layers at several of these sites are significantly different, suggesting that three ash layers may occur11. Near Stillwater, Nevada, at least three ash units can be attributed to Mazama, the lowest of which is petrographically distinct from Mazama ash found elsewhere4. We report here the first demonstration that Mount Mazama erupted at least twice within a 200-yr span in the Holocene.

The aim of this work was to investigate the use of TLD-100 detectors in the field of relative dosimetry in proton eye facilities. These dosemeters, of different sizes, were used to measure transverse and longitudinal distributions of 62 MeV unmodulated proton beams at INFN-LNS in Catania. Comparison with other detectors, such as ionisation chambers, GAF and radiographic film, is extensively discussed.

A palaeomagnetic investigation of Carbon-14-dated marsh and near-shore lacustrine sediments deposited between about 25 000–5000 yr bp at Tlapacoya, Mexico, reveals normal polarity of the geomagnetic field in all samples measured. At one site, anomalous palaeomagnetic directions in a mud unit dated about 14 500 yr bp raised the possibility of a geomagnetic excursion, but subsequent work at six additional sites in the unit revealed no abnormal directions. Thus the anomalous directions are most likely not a true reflection of geomagnetic field behaviour, although no specific alternative explanation is entirely convincing. The preliminary Tlapacoya data of anomalous directions have been cited by others as positive evidence for an excursion. We strongly recommend it no longer be considered as such.