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We present panchromatic observations and modeling of calcium-strong supernovae (SNe) 2021gno in the star-forming host-galaxy NGC 4165 and 2021inl in the outskirts of elliptical galaxy NGC 4923, both monitored through the Young Supernova Experiment transient survey. The light curves of both, SNe show two peaks, the former peak being derived from shock cooling emission (SCE) and/or shock interaction with circumstellar material (CSM). The primary peak in SN 2021gno is coincident with luminous, rapidly decaying X-ray emission (L x = 5 × 1041 erg s−1) detected by Swift-XRT at δ t = 1 day after explosion, this observation being the second-ever detection of X-rays from a calcium-strong transient. We interpret the X-ray emission in the context of shock interaction with CSM that extends to r < 3 × 1014 cm. Based on X-ray modeling, we calculate a CSM mass M CSM = (0.3−1.6) × 10−3 M ⊙ and density n = (1−4) × 1010 cm−3. Radio nondetections indicate a low-density environment at larger radii (r > 1016 cm) and mass-loss rate of M ̇ < 10 − 4 M ⊙ yr−1. SCE modeling of both primary light-curve peaks indicates an extended-progenitor envelope mass M e = 0.02−0.05 M ⊙ and radius R e = 30−230 R ⊙. The explosion properties suggest progenitor systems containing either a low-mass massive star or a white dwarf (WD), the former being unlikely given the lack of local star formation. Furthermore, the environments of both SNe are consistent with low-mass hybrid He/C/O WD + C/O WD mergers.

We present the discovery of ASASSN-18jd (AT 2018bcb), a luminous optical/UV/X-ray transient located in the nucleus of the galaxy 2MASX J22434289--1659083 at $z=0.1192$. Over the year after discovery, Swift UVOT photometry shows the UV SED of the transient to be well modeled by a slowly shrinking blackbody with temperature $T \sim 2.5 \times 10^{4} \rm ~K$, a maximum observed luminosity of $L_\text{max} = 4.5^{+0.6}_{-0.3} \times 10^{44} \rm ~erg ~s^{-1}$, and a radiated energy of $E = 9.6^{+1.1}_{-0.6} \times 10^{51} \rm ~erg$. X-ray data from Swift XRT and XMM-Newton show a transient, variable X-ray flux with blackbody and power-law components that fade by nearly an order of magnitude over the following year. Optical spectra show strong, roughly constant broad Balmer emission as well as transient features attributable to He II, N III-V, O III, and coronal Fe. While ASASSN-18jd shares similarities with Tidal Disruption Events (TDEs), it is also similar to the newly-discovered nuclear transients seen in quiescent galaxies and faint Active Galactic Nuclei (AGNs)., 24 pages, 16 figures, 2 machine-readable tables (included as ancillary txt files)

We present photometric and spectroscopic data on three extragalactic luminous red novae (LRNe): AT 2018bwo, AT 2021afy, and AT 2021blu. AT 2018bwo was discovered in NGC 45 (at about 6.8 Mpc) a few weeks after the outburst onset. During the monitoring period, the transient reached a peak luminosity of 1040 erg s−1. AT 2021afy, hosted by UGC 10043 (∼49.2 Mpc), showed a double-peaked light curve, with the two peaks reaching a similar luminosity of 2.1(±0.6)×1041 erg s−1. Finally, for AT 2021blu in UGC 5829 (∼8.6 Mpc), the pre-outburst phase was well-monitored by several photometric surveys, and the object showed a slow luminosity rise before the outburst. The light curve of AT 2021blu was sampled with an unprecedented cadence until the object disappeared behind the Sun, and it was then recovered at late phases. The light curve of LRN AT 2021blu shows a double peak, with a prominent early maximum reaching a luminosity of 6.5 × 1040 erg s−1, which is half of that of AT 2021afy. The spectra of AT 2021afy and AT 2021blu display the expected evolution for LRNe: a blue continuum dominated by prominent Balmer lines in emission during the first peak, and a redder continuum consistent with that of a K-type star with narrow absorption metal lines during the second, broad maximum. The spectra of AT 2018bwo are markedly different, with a very red continuum dominated by broad molecular features in absorption. As these spectra closely resemble those of LRNe after the second peak, AT 2018bwo was probably discovered at the very late evolutionary stages. This would explain its fast evolution and the spectral properties compatible with that of an M-type star. From the analysis of deep frames of the LRN sites years before the outburst, and considerations of the light curves, the quiescent progenitor systems of the three LRNe were likely massive, with primaries ranging from about 13 M⊙ for AT 2018bwo, to 14−1+4 M⊙ for AT 2021blu, and over 40 M⊙ for AT 2021afy.

We present photometric and spectroscopic observations of Supernova 2020oi (SN 2020oi), a nearby ($\sim$17 Mpc) type-Ic supernova (SN Ic) within the grand-design spiral M100. We undertake a comprehensive analysis to characterize the evolution of SN 2020oi and constrain its progenitor system. We detect flux in excess of the fireball rise model $\delta t \approx 2.5$ days from the date of explosion in multi-band optical and UV photometry from the Las Cumbres Observatory and the Neil Gehrels Swift Observatory, respectively. The derived SN bolometric luminosity is consistent with an explosion with $M_{\rm ej} = 0.81 \pm 0.03 M_{\odot}$, $E_{k}= 0.79 \pm 0.09 \times 10^{51} \rm{erg} \rm{s}^{-1}$, and $M_{\rm Ni56} = 0.08 \pm 0.02 M_{\odot}$. Inspection of the event's decline reveals the highest $\Delta m_{15,\rm{bol}}$ reported for a stripped-envelope event to date. Modeling of optical spectra near event peak indicates a partially mixed ejecta comparable in composition to the ejecta observed in SN 1994I, while the earliest spectrum shows signatures of a possible interaction with material of a distinct composition surrounding the SN progenitor. Further, Hubble Space Telescope (HST) pre-explosion imaging reveals a stellar cluster coincident with the event. From the cluster photometry, we derive the mass and age of the SN progenitor using stellar evolution models implemented in the BPASS library. Our results indicate that SN 2020oi occurred in a binary system from a progenitor of mass $M_{\rm ZAMS} \approx 9.5 \pm 1.0 M_{\odot}$, corresponding to an age of $27 \pm 7$ Myr. SN 2020oi is the dimmest SN Ic event to date for which an early-time flux excess has been observed, and the first in which an early excess is unlikely to be associated with shock-cooling., Comment: 49 pages, 21 figures; accepted to ApJ

The detection of the optical transient AT2017gfo proved that binary neutron star mergers are progenitors of kilonovae (KNe). Using a combination of numerical-relativity and radiative-transfer simulations, the community has developed sophisticated models for these transients for a wide portion of the expected parameter space. Using these simulations and surrogate models made from them, it has been possible to perform Bayesian inference of the observed signals to infer properties of the ejected matter. It has been pointed out that combining inclination constraints derived from the KN with gravitational-wave measurements increases the accuracy with which binary parameters can be estimated, in particular breaking the distance-inclination degeneracy from gravitational wave inference. To avoid bias from the unknown ejecta geometry, constraints on the inclination angle for AT2017gfo should be insensitive to the employed models. In this work, we compare different assumptions about the ejecta and radiative reprocesses used by the community and we investigate their impact on the parameter inference. While most inferred parameters agree, we find disagreement between posteriors for the inclination angle for different geometries that have been used in the current literature. According to our study, the inclusion of reprocessing of the photons between different ejecta types improves the modeling fits to AT2017gfo and, in some cases, affects the inferred constraints. Our study motivates the inclusion of large ∼ 1-mag uncertainties in the KN models employed for Bayesian analysis to capture yet unknown systematics, especially when inferring inclination angles, although smaller uncertainties seem appropriate to capture model systematics for other intrinsic parameters. We can use this method to impose soft constraints on the ejecta geometry of the KN AT2017gfo.

We present panchromatic observations and modeling of supernova (SN) 2020tlf, the first normal type II-P/L SN with confirmed precursor emission, as detected by the Young Supernova Experiment transient survey with the Pan-STARRS1 telescope. Pre-explosion emission was detected in $riz-$bands at 130 days prior to SN 2020tlf and persisted at relatively constant flux until first light. Soon after discovery, "flash" spectroscopy of SN 2020tlf revealed prominent narrow symmetric emission lines ($v_w < 300$ km s$^{-1}$) that resulted from the photo-ionization of unshocked circumstellar material (CSM) shedded in progenitor mass loss episodes in the final weeks to months before explosion. Surprisingly, this novel display of pre-SN emission and associated mass loss occurred in a RSG progenitor with ZAMS mass of only 10-12 M$_{\odot}$, as inferred from nebular spectra. Modeling of the light curve and multi-epoch spectra with the non-LTE radiative transfer code CMFGEN and radiation-hydrodynamical (RHD) code HERACLES suggests a dense CSM limited to $r \approx 10^{15}$ cm, and mass loss rate of $10^{-2}$ M$_{\odot}$ yr$^{-1}$. The subsequent luminous light-curve plateau and persistent blue excess indicates an extended progenitor, compatible with a RSG model with $R_{\star} = 1100$ R$_{\odot}$. Inferences from the limits on the shock-powered X-ray and radio luminosity are consistent with these conclusions and suggest a CSM density of $��< 2 \times 10^{-16}$ g cm$^{-3}$ for distances of $r \approx 5 \times 10^{15}$ cm, as well as a mass loss rate of $\dot M, 36 pages, 20 figures. Accepted for publication in ApJ

We present observations of ASASSN-19dj, a nearby tidal disruption event (TDE) discovered in the post-starburst galaxy KUG 0810+227 by the All-Sky Automated Survey for Supernovae (ASAS-SN) at a distance of d $\simeq98$ Mpc. We observed ASASSN-19dj from $-$21 to 392 d relative to peak ultraviolet (UV)/optical emission using high-cadence, multiwavelength spectroscopy and photometry. From the ASAS-SN $g$-band data, we determine that the TDE began to brighten on 2019 February 6.8 and for the first 16 d the rise was consistent with a flux $\propto t^2$ power-law. ASASSN-19dj peaked in the UV/optical on 2019 March 6.5 (MJD = 58548.5) at a bolometric luminosity of $L = (6.2 \pm 0.2) \times 10^{44} \text{ erg s}^{-1}$. Initially remaining roughly constant in X-rays and slowly fading in the UV/optical, the X-ray flux increased by over an order of magnitude $\sim$225 d after peak, resulting from the expansion of the X-ray emitting region. The late-time X-ray emission is well fitted by a blackbody with an effective radius of $\sim1 \times 10^{12} \text{ cm}$ and a temperature of $\sim6 \times 10^{5} \text{ K}$. The X-ray hardness ratio becomes softer after brightening and then returns to a harder state as the X-rays fade. Analysis of Catalina Real-Time Transient Survey images reveals a nuclear outburst roughly 14.5 yr earlier with a smooth decline and a luminosity of $L_V\geq1.4 \times 10^{43}$ erg s$^{-1}$, although the nature of the flare is unknown. ASASSN-19dj occurred in the most extreme post-starburst galaxy yet to host a TDE, with Lick H$\delta_{A}$ = $7.67\pm0.17$ \AA., Comment: Updated to match accepted MNRAS version

Time domain science has undergone a revolution over the past decade, with tens of thousands of new supernovae (SNe) discovered each year. However, several observational domains, including SNe within days or hours of explosion and faint, red transients, are just beginning to be explored. Here, we present the Young Supernova Experiment (YSE), a novel optical time-domain survey on the Pan-STARRS telescopes. Our survey is designed to obtain well-sampled $griz$ light curves for thousands of transient events up to $z \approx 0.2$. This large sample of transients with 4-band light curves will lay the foundation for the Vera C. Rubin Observatory and the Nancy Grace Roman Space Telescope, providing a critical training set in similar filters and a well-calibrated low-redshift anchor of cosmologically useful SNe Ia to benefit dark energy science. As the name suggests, YSE complements and extends other ongoing time-domain surveys by discovering fast-rising SNe within a few hours to days of explosion. YSE is the only current four-band time-domain survey and is able to discover transients as faint $\sim$21.5 mag in $gri$ and $\sim$20.5 mag in $z$, depths that allow us to probe the earliest epochs of stellar explosions. YSE is currently observing approximately 750 square degrees of sky every three days and we plan to increase the area to 1500 square degrees in the near future. When operating at full capacity, survey simulations show that YSE will find $\sim$5000 new SNe per year and at least two SNe within three days of explosion per month. To date, YSE has discovered or observed 8.3% of the transient candidates reported to the International Astronomical Union in 2020. We present an overview of YSE, including science goals, survey characteristics and a summary of our transient discoveries to date., ApJ, in press; more information at https://yse.ucsc.edu/

The Foundation Supernova Survey aims to provide a large, high-fidelity, homogeneous, and precisely-calibrated low-redshift Type Ia supernova (SN Ia) sample for cosmology. The calibration of the current low-redshift SN sample is the largest component of systematic uncertainties for SN cosmology, and new data are necessary to make progress. We present the motivation, survey design, observation strategy, implementation, and first results for the Foundation Supernova Survey. We are using the Pan-STARRS telescope to obtain photometry for up to 800 SNe Ia at z < 0.1. This strategy has several unique advantages: (1) the Pan-STARRS system is a superbly calibrated telescopic system, (2) Pan-STARRS has observed 3/4 of the sky in grizy making future template observations unnecessary, (3) we have a well-tested data-reduction pipeline, and (4) we have observed ~3000 high-redshift SNe Ia on this system. Here we present our initial sample of 225 SN Ia griz light curves, of which 180 pass all criteria for inclusion in a cosmological sample. The Foundation Supernova Survey already contains more cosmologically useful SNe Ia than all other published low-redshift SN Ia samples combined. We expect that the systematic uncertainties for the Foundation Supernova Sample will be 2-3 times smaller than other low-redshift samples. We find that our cosmologically useful sample has an intrinsic scatter of 0.111 mag, smaller than other low-redshift samples. We perform detailed simulations showing that simply replacing the current low-redshift SN Ia sample with an equally sized Foundation sample will improve the precision on the dark energy equation-of-state parameter by 35%, and the dark energy figure-of-merit by 72%., MNRAS, accepted; 157 pages, but 139 pages are tables; 9 figures

Female yellow perch Perca flavescens exposed to three overwinter temperature regimes (4, 8 and 13° C) for 150 days spawned in markedly different proportions upon spring warming (37% of females in 4° C v. 64 and 91% in 8 and 13° C treatments, respectively), but exhibited no differences in fecundity, egg size or egg lipid content. Females held at 4° C also exhibited less within-clutch egg size variation than females held at 13° C. Moreover, eggs differed among temperature treatments in the overall proportions of 18 fatty acids, with the colder treatments resulting in potentially higher quality eggs containing more of the unsaturated fatty acids C16:1, C22:6-n3 and C18:2 cis. Female somatic condition also varied with temperature. Maternal somatic growth and protein content increased while lipid content decreased in 13° C compared to the colder treatments. There were, however, no differences among treatments in the fatty acid composition of maternal muscle. These results suggest that the temperatures experienced during winter may be less influential to P. flavescens egg size or number, which may exhibit relatively little plasticity in this species, but can alter both the number of females that spawn and the overall composition of eggs and maternal somatic tissues, which may have implications for future reproductive success.

The terminal genes of Drosophila specify non-segmented regions of the larval body that are derived from the anterior and posterior regions of the early embryo. Terminal class genes include both maternal-effect loci (typified by the receptor tyrosine kinase torso) that encode components of a signal transduction cascade and zygotic genes (e.g. tailless and huckebein) that are transcribed at the poles of the embryo in response to the local activation of the pathway. We have characterized a zygotic gene, bowel, that was identified as a zinc finger homolog of the pair-rule segmentation gene odd-skipped. bowel transcripts are initially expressed at both poles of the blastoderm embryo and in a single cephalic stripe. This pattern depends upon torso and tailless activity, but is not affected in huckebein mutants. We isolated and sequenced five mutations that affect the bowel protein, including a nonsense mutation upstream of the zinc fingers and a missense mutation in a putative zinc-chelating residue. bowel mutants die as late embryos with defects in terminal derivatives including the hindgut and proventriculus. Our results indicate that the developmental roles of odd-skipped and bowel have diverged substantially, and that bowel represents a new member of the terminal hierarchy that acts downstream of tailless and mediates a subset of tailless functions in the posterior of the embryo.

Vegetative State (VS) implies significant issues. The aim of the MORFEO study is to identify the most relevant complications in VS patients and to supply clinicians and policy-makers with data derived from the analysis of a cohort of patients treated in a dedicated long-term facility setting.A cohort of 22 VS patients treated between 2003 and 2007 were enrolled and followed up for 1 year. The information recorded were: Disability Rating Scale (DRS), Levels of Cognitive Functioning (LCF), pressure sores, nutritional status, neurological complications, articular complications (passive range of motion-ROM), deep-vein thrombosis and infections. The Kolmogorov-Smirnov test was used to verify the normal distribution of the variables. The indicators of complications were analysed with the Friedman test (continuous variables) and with the Cochran Q test (dichotomous variables).DRS and LCF values showed no significant variation. The number of pressure sores decreased. The nutritional status remained satisfying. The ROM worsened in lower limb joints; a trend (p = ns) towards an improved range was observed in shoulders and elbows. Fifteen infections were recorded.The data that proved significant suggest a minimum set of quality-of-care indicators in VS patients: pressure sores follow-up, nutritional status, ROM and incidence of infections.

Purpose-The purpose of this paper is to demonstrate the pro-active nature of the New Zealand Intensive Medicines Monitoring Programme (IMMP) and make an assessment of its effectiveness in postmarketing drug safety evaluation.Methods-The IMMP undertakes prospective observational cohort studies of selected new drugs. Patient cohorts are established from prescription data received from dispensing pharmacists nationwide. Adverse events are reported by doctors on prescription follow-up questionnaires or as spontaneous reports. The method of signal generation is reviewed with particular emphasis on the review of individual event reports and their relationship to the medicine. Signals reported over the last 10 years are assessed for timeliness in advising the regulatory authority.Results-Mean cohort size is 10,964 patients and the mean study period for each drug was 58 months. A total of 153 signals were recorded from 11 drugs with 132 (86%) being notified to the regulatory authority prior to any publication in the literature. The use of 'incidents' in controlling for reporting bias is illustrated and examples are given of data on safety in pregnancy and lactation, the assessment of deaths, reassurance with drug scares, risk comparison and signal validation studies.Conclusion-PEM type methodology is effective and cost-efficient in pro-active safety surveillance even with limited resources. Copyright (c) 2000 John WileySons, Ltd.

odd-skipped (odd) is one of eight known pair-rule genes that establish portions of alternating segments during Drosophila embryogenesis; odd mutant embryos exhibit pattern defects in anterior regions of odd-numbered segments. P element transposon tagging was used to clone 25 kb of DNA from the odd genomic region. Molecular analysis of phenotypic revertants confirmed that the P element used to tag the locus was responsible for the corresponding odd mutation, and significant structural changes were identified in two additional odd mutants. Several cDNA clones derived from a 2.2 kb embryonic transcript were isolated and the longest was sequenced. The predicted odd protein of 392 amino acids is highly basic and contains four tandem Cys-Cys/His-His zinc finger repeats, consistent with a presumed function for odd as a DNA binding protein and transcriptional regulator. In situ hybridization analysis indicated that odd transcripts accumulate in a dynamic pattern during early embryogenesis, with two temporally distinct modes of expression. The first mode results in a 'pair-rule' pattern of seven stripes at the blastoderm stage, representing the expected double segment periodicity. During gastrulation, the seven primary stripes are supplemented by secondary stripes which appear in alternate segments, resulting in the equivalent labeling of every segment in the extended germ band. Similar double to single segment transitions have now been reported for four of the six pair-rule genes analyzed.

The New Zealand Intensive Medicines Monitoring Programme which has been in operation for 20 years is described. The methodology is reviewed in detail and illustrated in the results. Some of the principles of early postmarketing surveillance and advantages and problems associated with the IMMP are discussed. The methodology is based on establishing cohorts of patients and the aggregation of adverse events from a combination of prescription follow-up (PFU) and intensified spontaneous reporting. In signal detection particular emphasis is placed on provisional 'causality' assessment and a study of the events thought not to be reactions (incidents) and in addition, their use in controlling for reporting bias particularly in respect of reaction rates and the identification of risk factors. With the small population base, cohorts are built up more slowly, but the longer duration of observation has advantages. Monitoring has been completed for 20 drugs with an average cohort size of 10,511 patients and a mean monitoring period of 55 months. The use of duplicate prescriptions with PFU achieved much higher reporting rates than IMMP spontaneous reporting. Information on deaths was best obtained from questionnaires on reasons for cessation of therapy which also provided data on efficacy.

The NMDA subtype of glutamate receptor plays an important role in the molecular mechanisms of learning, memory and excitotoxicity. NMDA receptors are highly permeable to calcium, which can lead to the activation of the calcium-dependent protease, calpain. In the present study, the ability of calpain to modulate NMDA receptor function through direct proteolytic digestion of the individual NMDA receptor subunits was examined. HEK293t cells were cotransfected with the NR1a/2A, NR1a/2B or NR1a/2C receptor combinations. Cellular homogenates of these receptor combinations were prepared and digested by purified calpain I in vitro. All three NR2 subunits could be proteolyzed by calpain I while no actin or NR1a cleavage was observed. Based on immunoblot analysis, calpain cleavage of NR2A, NR2B and NR2C subunits was limited to their C-terminal region. In vitro calpain digestion of fusion protein constructs containing the C-terminal region of NR2A yielded two cleavage sites at amino acids 1279 and 1330. Although it has been suggested that calpain cleavage of the NMDA receptor may act as a negative feedback mechanism, the current findings demonstrated that calpain cleavage did not alter [(125)I]MK801 binding and that receptors truncated to the identified cleavage sites had peak intracellular calcium levels, (45)Ca uptake rates and basal electrophysiological properties similar to wild type.

Profound alterations in the function of GABA occur over the course of postnatal development. Changes in GABA(A) receptor expression are thought to contribute to these differences in GABAergic function, but how subunit changes correlate with receptor function in individual developing neurons has not been defined precisely. In the current study, we correlate expression of 14 different GABA(A) receptor subunit mRNAs with changes in the pharmacological properties of the receptor in individual hippocampal dentate granule cells over the course of postnatal development in rat. We demonstrate significant developmental differences in GABA(A) receptor subunit mRNA expression, including greater than two-fold lower expression of alpha1-, alpha4- and gamma2-subunit mRNAs and 10-fold higher expression of alpha5-mRNA in immature compared with adult neurons. These differences correlate both with regional changes in subunit protein level and with alterations in GABA(A) receptor function in immature dentate granule cells, including two-fold higher blockade by zinc and three-fold lower augmentation by type-I benzodiazepine site modulators. Further, we find an inverse correlation between changes in GABA(A) receptor zinc sensitivity and abundance of vesicular zinc in dentate gyrus during postnatal development. These findings suggest that developmental differences in subunit expression contribute to alterations in GABA(A) receptor function during postnatal development.

Although epilepsy is fundamentally a circuit phenomenon, the most basic manifestation of the hyperexcitability characteristic of epilepsy must be evident at the level of a single neuron. Furthermore, in the future, manipulations of surviving neurons within the epileptic focus will constitute one of the best therapeutic targets for intervention to cure this devastating disease. Therefore, the more that can be learned about epileptogenic alterations in this population of surviving focal neurons, the more potential avenues for therapeutic intervention will emerge. This chapter has summarized one aspect of postsynaptic neuronal function that undergoes dramatic alterations in the epileptic brain: the properties of inhibitory neurotransmitter (i.e., GABA) receptors in surviving focal neurons. GABARs in these neurons undergo significant alterations in their function and pharmacology, which appear to be mediated, at least in part, by alterations in the transcriptional production of GABAR subunits. These GABAR alterations fulfill many of the requirements for an epileptogenic mechanism: they are consistent with the hyperexcitability characteristic of epilepsy; the changes develop prior to the onset of recurrent spontaneous seizures; and the elevated zinc sensitivity of epileptic GABARs combined with epilepsy-associated mossy fiber sprouting (a zinc "delivery mechanism") can account for the existence of a prolonged latent period. Although GABAR alterations in DGCs of the epileptic hippocampus may be consistent with hyperexcitability and therefore contribute to epileptogenesis, many other processes undoubtedly also contribute, including (but not limited to) neuronal loss, circuit rearrangements, alterations in other membrane proteins, and birth of new neurons. Assuming any single change is both necessary and sufficient to fully account for epilepsy is undoubtedly an oversimplification. The initial precipitating events associated with the subsequent development of epilepsy are often traumatic events and associated with changes in many processes in widespread areas of the brain. Some of these processes may contribute to excitability changes, some may resist the development of epilepsy, and some may be unrelated to epileptogenesis. Characterizing the critical processes initiated during epileptogenesis remains an important and challenging research endeavor for the foreseeable future.

This chapter reviews two main aspects of the basic mechanisms of status epilepticus--acute factors, which are important in inducing status epilepticus in an in vitro brain slice model of status epilepticus, and the acute and chronic epileptogenic consequences of status epilepticus. Status epilepticus is difficult to produce in vitro in normal extracellular medium. This suggests that seizure-terminating mechanisms are normally quite robust. To produce long- duration, self-sustained epileptic discharges in vitro, we have found it necessary to include reciprocally connected entorhinal cortex with our hippocampal slices. Doing so closes the normal excitatory limbic loop in the brain. We found incorporation of the full loop in our brain-slice preparations necessary to bring about epileptic discharges of long duration that fit the definition of status epilepticus. Reentrant activation from distant sites may be necessary for maintenance of status epilepticus-like activity of long duration. Similar requirements may exist for generalized tonic-clonic status epilepticus discharges, but as yet no data support or refute this hypothesis. There are both acute and chronic consequences of an episode of status epilepticus. Acute consequences are alterations in membrane potential and membrane properties of hippocampal pyramidal cells accompanied by alterations in neurotransmitter-activated conductances and receptor expression. Some of these acute alterations in receptor and transmembrane iongradient associated with status epilepticus may be critically involved in the development of drug resistance during the late stages of status epilepticus. Long-term consequences of status epilepticus in the limbic system include alterations in patterns of expression of neurotransmitter receptors and in the function of excitatory and inhibitory synapses, cell loss, and circuit rearrangements within the limbic system. An episode of status epilepticus that involves the limbic system clearly elicits brain damage, at least among adult animals. This brain damage can contribute to the development of epilepsy, or a condition of recurrent, spontaneous seizures. Conversely, development of an epileptic condition enhances the susceptibility of the limbic system to trigger status epilepticus discharges.

The frequency with which agranulocytosis was associated with mianserin in New Zealand was calculated, by two methods, from spontaneous reports to the Intensive Medicines Monitoring Programme (IMMP)--one gave a frequency of 1 in 1354 (95% CI 1 in 3145 to 1 in 685) and the other gave a rate of 1 in 1743 (95% CI 1 in 2895 to 1 in 1116). There were 3 deaths. Age and dose seemed to be related to occurrence of agranulocytosis. The frequency of the complication seemed to be higher than that reported for other countries, perhaps because higher doses were prescribed in New Zealand but also perhaps because of a selection bias in surveys elsewhere. The occurrence of agranulocytosis with mianserin in New Zealand is higher than that of white-cell dyscrasias reported with use of chloramphenicol, phenylbutazone, and oxyphenbutazone, and although the case-fatality rate of agranulocytosis is lower with mianserin than with the other drugs, the overall mortality rate may be higher.

In this paper we will describe recent advances in the development of optical systems for future space infrared telescope and interferometer applications which will operate at very low or cryogenic temperatures (T≤77K) with emphasis on beryllium and silicon carbide optics. New material formulations and advanced processing and manufacturing techniques are enabling the development of large, very low mass, high performance cryogenic optics. The design, manufacturing and cryogenic testing of several recently developed mirrors and optical assemblies will be discussed.

The terminal genes of Drosophila specify non-segmented regions of the larval body that are derived from the anterior and posterior regions of the early embryo. Terminal class genes include both maternal-effect loci (typified by the receptor tyrosine kinase torso) that encode components of a signal transduction cascade and zygotic genes (e.g. tailless and huckebein) that are transcribed at the poles of the embryo in response to the local activation of the pathway. We have characterized a zygotic gene, bowel, that was identified as a zinc finger homolog of the pair-rule segmentation gene odd-skipped. bowel transcripts are initially expressed at both poles of the blastoderm embryo and in a single cephalic stripe. This pattern depends upon torso and tailless activity, but is not affected in huckebein mutants. We isolated and sequenced five mutations that affect the bowel protein, including a nonsense mutation upstream of the zinc fingers and a missense mutation in a putative zinc-chelating residue. bowel mutants die as late embryos with defects in terminal derivatives including the hindgut and proventriculus. Our results indicate that the developmental roles of odd-skipped and bowel have diverged substantially, and that bowel represents a new member of the terminal hierarchy that acts downstream of tailless and mediates a subset of tailless functions in the posterior of the embryo.

We reviewed medical records of inborn babies of30 gestational weeks who died before hospital discharge to identify the cause of death and age at death. We compared all surfactant-treated babies born during the first 19 months of our experience in a phase III trial of exogenous surfactant prophylaxis of respiratory distress syndrome with all untreated babies born during the 19 months immediately preceding the surfactant trial. The two groups were virtually identical in birth weight and gestational age. Mortality in all gestational age groups declined by half after the initiation of surfactant treatment. The mean age at death did not change significantly. Cases of early or late mortality did not change between the two periods. Exogenous surfactant prophylaxis does not significantly prolong the lives of extremely premature babies who are destined to die before hospital discharge.

To review reports of angiooedema and urticaria associated with angiotensin converting enzyme inhibitors (ACEI) in the New Zealand Centre for Adverse Reactions Monitoring and Intensive Medicines Monitoring Programme (IMMP) database.Adverse reaction reports describing angiooedema and/or urticaria between April 1981 and December 1994 were examined. Captopril, enalapril and lisinopril were intensively monitored on the IMMP during this period.Of a total of 116 reports there were 68 reports of angiooedema and 37 of urticaria alone and 11 where angiooedema and urticaria occurred in the same patient. The total number of patients is unknown, but cohorts of patients on captopril, enalapril and lisinopril in the IMMP were 16342, 25686 and 11235, totalling 53263 patients. There were 63 reports of angiooedema/urticaria in patients monitored on the IMMP, giving a reported rate of 1.2/1000 (0.9-1.5). Forty seven reactions occurred between 3 weeks and 4 years after commencement of therapy. Severe angiooedema occurred in 9 patients with early-onset angiooedema and 6 with late-onset angiooedema. There were no deaths. Seventeen patients had up to 12 episodes before diagnosis. Angiooedema/ urticaria occurred without gender preference. Although a dose relationship was not apparent, 3 patients developed angiooedema or urticaria after an increase in dose.Although reactions are more common shortly after initiation of ACEI therapy, late onset reactions may be less well recognised. Clinicians should be reminded, and ACEI data sheets should emphasise, that onset may be delayed for weeks or months, that patients may have multiple episodes with long symptom free intervals, and that angiooedema may occur with or without urticaria.