In praise of postgraduate career clinics: Translating health professionals' willingness to engagement.

AIM: To capture and retain healthcare staff in postgraduate courses relevant to individual career aspirations, service requirements and continuous practice development (CPD) within an English UK university. DESIGN: Two virtual career clinics for postgraduate practitioners to engage in CPD offers within the university. An online post-enrolment online survey to explore their experiences of engagement with the university. METHODS: Mixed: qualitative and quantitative methods. Engaging 10 participants attended the career clinics, and 42 participants with an online survey. RESULTS: The career clinics were well received by participants who mapped CPD requirements and individual career aspirations. The surveys exposed challenges with marketing and enrolment; however, these were mitigated with support. Four recommendations are presented within this paper applicable to the international postgraduate education of all health practitioners.

Gabapentin for spasticity and autonomic dysreflexia after severe spinal cord injury.

STUDY DESIGN: Using a complete transection spinal cord injury (SCI) model at the fourth thoracic vertebral level in adult rats, we evaluated whether blocking noxious stimuli below the injury diminishes abnormal somatic and autonomic motor reflexes, manifested in muscular spasticity and hypertensive autonomic dysreflexia, respectively. Gabapentin (GBP) is well tolerated and currently used to manage neuropathic pain in the SCI population; evidence suggests that it acts to decrease presynaptic glutamate release. As clinical evidence indicates that GBP may suppress muscular spasticity in the chronic SCI population, we hypothesized that preventing neurotransmission of noxious stimuli with GBP eliminates a critical physiological link to these distinct, debilitating SCI-induced secondary impairments. OBJECTIVES: Behavioural assessments of tail muscle spasticity and mean arterial blood pressure responses to noxious somatic and/or visceral stimulation were used to test the effects of GBP on these abnormal reflexes. SETTING: Lexington, Kentucky. METHODS: We used femoral artery catheterization and radio-telemetric approaches to monitor blood pressure alterations in response to noxious colorectal distension (CRD) weeks after complete SCI. RESULTS: At 2-3 weeks post-SCI, acute GBP administration (50 mg kg(-1), i.p.) significantly attenuated both autonomic dysreflexia and tail spasticity induced by noxious stimuli compared with saline-treated cohorts. CONCLUSION: These results show, for the first time, that a single-pharmacological intervention, GBP, can effectively attenuate the manifestation of both muscular spasticity and autonomic dysreflexia in response to noxious stimuli.

Atmospheric Carbon and Transport - America (ACT-America) Data Sets: Description, Management, and Delivery.

The ACT-America project is a NASA Earth Venture Suborbital-2 mission designed to study the transport and fluxes of greenhouse gases. The open and freely available ACT-America data sets provide airborne in situ measurements of atmospheric carbon dioxide, methane, trace gases, aerosols, clouds, and meteorological properties, airborne remote sensing measurements of aerosol backscatter, atmospheric boundary layer height and columnar content of atmospheric carbon dioxide, tower-based measurements, and modeled atmospheric mole fractions and regional carbon fluxes of greenhouse gases over the Central and Eastern United States. We conducted 121 research flights during five campaigns in four seasons during 2016-2019 over three regions of the US (Mid-Atlantic, Midwest and South) using two NASA research aircraft (B-200 and C-130). We performed three flight patterns (fair weather, frontal crossings, and OCO-2 underflights) and collected more than 1,140 h of airborne measurements via level-leg flights in the atmospheric boundary layer, lower, and upper free troposphere and vertical profiles spanning these altitudes. We also merged various airborne in situ measurements onto a common standard sampling interval, which brings coherence to the data, creates geolocated data products, and makes it much easier for the users to perform holistic analysis of the ACT-America data products. Here, we report on detailed information of data sets collected, the workflow for data sets including storage and processing of the quality controlled and quality assured harmonized observations, and their archival and formatting for users. Finally, we provide some important information on the dissemination of data products including metadata and highlights of applications of ACT-America data sets.

Influence of El Niño on atmospheric CO2 over the tropical Pacific Ocean: Findings from NASA's OCO-2 mission.

Spaceborne observations of carbon dioxide (CO2) from the Orbiting Carbon Observatory-2 are used to characterize the response of tropical atmospheric CO2 concentrations to the strong El Niño event of 2015-2016. Although correlations between the growth rate of atmospheric CO2 concentrations and the El Niño-Southern Oscillation are well known, the magnitude of the correlation and the timing of the responses of oceanic and terrestrial carbon cycle remain poorly constrained in space and time. We used space-based CO2 observations to confirm that the tropical Pacific Ocean does play an early and important role in modulating the changes in atmospheric CO2 concentrations during El Niño events-a phenomenon inferred but not previously observed because of insufficient high-density, broad-scale CO2 observations over the tropics.

The Orbiting Carbon Observatory-2 early science investigations of regional carbon dioxide fluxes.

NASA's Orbiting Carbon Observatory-2 (OCO-2) mission was motivated by the need to diagnose how the increasing concentration of atmospheric carbon dioxide (CO2) is altering the productivity of the biosphere and the uptake of CO2 by the oceans. Launched on 2 July 2014, OCO-2 provides retrievals of the column-averaged CO2 dry-air mole fraction ([Formula: see text]) as well as the fluorescence from chlorophyll in terrestrial plants. The seasonal pattern of uptake by the terrestrial biosphere is recorded in fluorescence and the drawdown of [Formula: see text] during summer. Launched just before one of the most intense El Niños of the past century, OCO-2 measurements of [Formula: see text] and fluorescence record the impact of the large change in ocean temperature and rainfall on uptake and release of CO2 by the oceans and biosphere.

Inhibition of peptic activity by sucralfate.

It is known that antacids containing aluminum hydroxide inhibit peptic activity by raising intragastric pH and by adsorbing pepsin. Since sucralfate contains aluminum hydroxide moieties, the possibility that this drug might inhibit peptic activity by these same mechanisms was examined. Sucralfate was incubated at a concentration of 10 mg/ml with samples of human gastric juice having pH values between 1.5 and 4 for 30 minutes at 37 degrees C. The proteolytic activity of the supernatant was then determined at a pH of 2.2 against a bovine hemoglobin substrate. When the initial pH of the gastric juice sample was 1.5, sucralfate was converted to a viscous gel and the pH of the incubation mixture rose to 2.9. However, there was no decrease in the peptic activity of the supernatant. In contrast, when the pH of the gastric juice sample was more than 2, the drug remained in suspension, but there was a graded rise in pH to a maximum of 4.1 and a progressive decrease in peptic activity (determined at a pH of 2.2) to a nadir of 65 percent of the control value. However, because peptic activity declines rapidly at a pH of more than 3, peptic activity at the ambient pH of the samples was reduced to only 25 percent of the control value. The results indicate that at pH values of more than 2, sucralfate inhibits peptic activity by both adsorbing pepsin and buffering hydrogen ions.

Synthesis and antiviral evaluation of carbocyclic analogues of 2-amino-6-substituted-purine 3'-deoxyribofuranosides.

Carbocyclic analogues of 2-amino-6-substituted-purine 3'-deoxyribofuranosides were synthesized by beginning with (+/-)-(1 alpha,3 alpha,4 beta)-3-amino-4-hydroxycyclopentanemethanol and 2-amino-4,6-dichloropyrimidine. The route parallels the earlier syntheses of the corresponding ribofuranoside and 2'-deoxyribofuranoside analogues. The 2-amino-6-chloropurine, guanine, and 2,6-diaminopurine derivatives and the analogous 8-azapurines were prepared. The analogue (3'-CDG) of 3'-deoxyguanosine is active in vitro against a strain of type 1 herpes simplex virus (HSV-1) that induces thymidine kinase and is modestly active against a thymidine kinase inducing strain of type 2 HSV. 3'-CDG is not active against a strain of HSV-1 that lacks the thymidine kinase inducing capacity, whereas the carbocyclic analogue of 2-amino-6-chloropurine 3'-deoxyribofuranoside is active against that strain. The carbocyclic analogue of 2,6-diaminopurine 3'-deoxyribofuranoside displayed modest activity in vitro against influenza virus.

Synthesis and antiviral activity of the carbocyclic analogues of 5-ethyl-2'-deoxyuridine and of 5-ethynyl-2'-deoxyuridine.

The carbocyclic analogue of the antiviral agent 5-ethyl-2'-deoxyuridine (EDU) was synthesized by two routes. The pivotal step in the first route is the reaction of lithium dimethylcuprate with the carbocyclic analogue of 5-(bromomethyl)-2'-deoxyuridine dibenzoate (6). The second route is based on the synthesis of the carbocyclic analogue of 5-ethynyl-2'-deoxyuridine (12) by a coupling reaction catalyzed by bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide, a method reported recently (Robins and Barr) for the synthesis of the true nucleoside 5-ethynyl-2'-deoxyuridine (1b). The carbocyclic analogue of EDU inhibits the replication of type 1 and type 2 herpes simplex viruses in Vero cells. The carbocyclic analogue of 5-ethynyl-2'-deoxyuridine has modest activity against herpes simplex virus, types 1 and 2.

Carbocyclic analogues of 5'-amino-5'-deoxy- and 3'-amino-3'-deoxythymidines.

The carbocyclic analogue of 5'-amino-5'-deoxythymidine was synthesized from the carbocyclic analogue of 2,5'-O-anhydrothymidine acetate. The carbocyclic analogues of 3'-amino-3'-deoxythymidine and of 1-(3'-amino-2',3'-di-deoxylyxofuranosyl)thymine (an all-cis structure) were synthesized from the carbocyclic analogues of 5'-O-trityl-2,3'-O-anhydrothymidine and 5'-O-trityl-3'-O-(methylsulfonyl)thymidine, respectively. The carbocyclic analogue of 5'-amino-5'-deoxythymidine inhibited cytopathogenic effects (CPE) induced by a TK+ strain of type 1 herpes simplex virus replicating in L929 (mouse connective tissue) cells, but it did not inhibit CPE in Vero cells. In contrast, the all-cis-3'-azido-3'-deoxythymidine analogue demonstrated modest inhibition of CPE in Vero cells, but not in L929 cells.

Carbocyclic analogues of 5-substituted uracil nucleosides: synthesis and antiviral activity.

Carbocyclic analogues of 3'-deoxyuridines, 3'-deoxyuridines, and uridines with substituents at position 5 of the uracil moiety were prepared by direct halogenation (5-bromo and 5-iodo groups) and by displacement of the 5-bromo group by amino and substituted-amino groups. The analogue of 5-(hydroxymethyl)uridine was prepared via reaction of the isopropylidene derivative of the uridine analogue with paraformaldehyde. The carbocyclic analogues of thymidine and of 5-bromo-, 5-iodo-, and 5-(methylamino)-2'-deoxyuridine were highly active in vitro against herpes simplex virus, types 1 and 2. The corresponding analogues of 5-substituted 3'-deoxyuridines and of 5-substituted uridines were not active in this assay.

Resolution of racemic carbocyclic analogues of purine nucleosides through the action of adenosine deaminase. Antiviral activity of the carbocyclic 2'-deoxyguanosine enantiomers.

The action of adenosine deaminase on racemic carbocyclic analogues of 6-aminopurine nucleosides was investigated. When either racemic carbocyclic adenosine [(+/-)-C-Ado] or the racemic carbocyclic analogue [(+/-)-C-2,6-DAP-2'-dR] of 2,6-diaminopurine 2'-deoxyribofuranoside was incubated with this enzyme, approximately half of the material was deaminated rapidly. From the resulting solution, the D isomers of the deaminated carbocyclic analogues (D-carbocyclic inosine, D-C-Ino, or D-carbocyclic 2'-deoxyguanosine, D-2'-CDG) and the L isomers of the undeaminated carbocyclic analogues were isolated. At higher concentrations of the enzyme, deamination of L-C-Ado and L-C-2,6-DAP-2'-dR proceeded slowly, thus also making the other enantiomers accessible. In tests in vitro against herpes simplex virus, types 1 and 2, D-2'-CDG was as active and potent as (+/-)-2'-CDG, whereas L-2'-CDG displayed only modest activity. In contrast to the previously reported high activity and potency of (+/-)-C-2,6-DAP-2'-dR against these two viruses, L-C-2,6-DAP-2'-dR was inactive.

Synthesis and antiviral activity of carbocyclic analogues of 2'-deoxyribofuranosides of 2-amino-6-substituted-purines and of 2-amino-6-substituted-8-azapurines.

(+/-)-(1 alpha, 2 beta, 4 alpha)-4-[(2,5-Diamino-6-chloro-4-pyrimidinyl) amino]-2-hydroxycyclopentanemethanol (9) was synthesized by beginning with 2-amino-4,6-dichloropyrimidine and (+/-)-1 alpha, 2 beta, 4 alpha)-4-amino-2-hydroxycyclopentanemethanol, preparing the 5-[(4-chlorophenyl)azo] derivative of the resulting pyrimidine, and reducing the azo derivative. The carbocyclic analogue of 2-amino-6-chloropurine 2'-deoxyribofuranoside (10) was prepared from 9 and triethyl orthoformate, and the analogous 8-azapurine (11) was obtained by diazotizing 9. From 10 or 11, the carbocyclic analogues of 2'-deoxyguanosine, 2'-deoxythioguanosine, 2,6-diaminopurine 2'-deoxyribofuranoside, 2'-deoxy-8-azaguanosine, and 2,6-diamino-8-azapurine 2'-deoxyribofuranoside were prepared. All of these 2'-deoxyribofuranoside analogues were active against herpes simplex virus (types 1 and 2) replicating in cells in culture; some demonstrated potent activity.

Carbocyclic analogues of 5-halocytosine nucleosides.

Carbocyclic analogues of 5-halocytosine nucleosides were prepared by direct halogenation of the carbocyclic analogues of cytidine, 2'-deoxycytidine, 3'-deoxycytidine, or ara-C. The 5-chloro and 5-bromo derivatives of the cytidine (carbodine) and of the 2'-deoxycytidine analogues and the 5-iodo derivatives of all four of the cytosine nucleoside analogues were prepared. All of the C-5-halocytosine nucleosides, as well as the parent C-cytosine nucleosides, were tested against a strain of herpes simplex virus type 1 (HSV-1) that induces thymidine kinase in host cells. Carbodine, 5-bromocarbodine, C-2'-deoxycytidine, C-5-bromo-2'-deoxycytidine, the four C-5-iodocytosine nucleosides, and C-ara-C inhibited replication of this strain of HSV-1 in cultured cells. Most of these compounds were tested also against the type 2 virus (HSV-2) in vitro and were active. The greatest activity observed was exerted by C-5-iodo-2'-deoxycytidine in inhibiting replication of HSV-1 in L929 cells. In tests against these DNA viruses, carbodine, a ribofuranoside analogue that had been shown previously to be highly active against human influenza A virus in vitro, was the most active compound against HSV-2 and one of the most active compounds against HSV-1 in Vero cells. 5-Bromocarbodine was active against influenza virus, but it was less active than carbodine.

The risk of seizure recurrence after a first unprovoked afebrile seizure in childhood: an extended follow-up.

OBJECTIVE: To assess the long-term recurrence risks after a first unprovoked seizure in childhood. METHODS: In a prospective study, 407 children who presented with a first unprovoked seizure were then followed for a mean of 6.3 years from the time of first seizure. RESULTS: One hundred seventy-one children (42%) experienced subsequent seizures. The cumulative risk of seizure recurrence was 29%, 37%, 42%, and 44% at 1, 2, 5, and 8 years, respectively. The median time to recurrence was 5.7 months, with 53% of recurrences occurring within 6 months, 69% within 1 year, and 88% within 2 years. Only 5 recurrences (3%) occurred after 5 years. On multivariable analysis, risk factors for seizure recurrence included a remote symptomatic etiology, an abnormal electroencephalogram (EEG), a seizure occurring while asleep, a history of prior febrile seizures, and Todd's paresis. In cryptogenic cases, the risk factors were an abnormal EEG and an initial seizure during sleep. In remote symptomatic cases, risk factors were a history of prior febrile seizures and age of onset younger than 3 years. Risk factors for late recurrences (after 2 years) were etiology, an abnormal EEG, and prior febrile seizures in the overall group and an abnormal EEG in the cryptogenic group. These are similar to the risk factors for early recurrence. CONCLUSIONS: The majority of children with a first unprovoked seizure will not have recurrences. Children with cryptogenic first seizures and a normal EEG whose initial seizure occurs while awake have a particularly favorable prognosis, with a 5-year recurrence risk of only 21%. Late recurrences do occur but are uncommon.

Radionuclide bone-scan abnormalities in leprosy: case reports.

Radionuclide bone scans were performed on two patients with leprosy. The resulting scan patterns simulated hypertrophic osteoarthropathy and diffuse arthritis, findings entirely consistent with the primary disease process.

Development of acuity in a primate model of human infantile unilateral aphakia.

We are studying infant rhesus monkeys that have been reared under various conditions of deprivation to model infantile unilateral aphakia. Grating acuity was assessed in these monkeys from birth to approximately 1 year of age using the quick acuity card procedure. We found that an uncorrected aphakic eye develops little or no pattern vision. Undercorrection or near point optical correction of an aphakic eye with an extended-wear contact lens coupled with continuous occlusion of the opposite eye sometimes results in normal development of acuity in the aphakic eye but does so only at the cost of loss of vision in the occluded eye. Fifty percent partial occlusion coupled with near-point correction of the aphakic eye results in similar development of acuity for both eyes during the time tested. Monkeys wearing near-point correction in the aphakic eye and without any occlusion of the other eye show surprisingly good residual acuities in their aphakic eyes. Based on these results we conclude that aphakic eyes should be treated by providing them with an optical correction, and that occlusion of the opposite eye should be used cautiously.

Depot medroxyprogesterone acetate or oral contraception in postpartum adolescents.

OBJECTIVE: To compare rates of method continuation and repeat pregnancy among postpartum adolescents selecting depot medroxyprogesterone acetate or oral contraceptives (OCs). METHODS: A retrospective study of 161 adolescents aged 19 years and younger who gave birth at an urban teaching hospital between May 1, 1994, and April 30, 1995, returned to the hospital's family planning clinic within 14 weeks of delivery and chose depot medroxyprogesterone acetate (n=111, 69%), or OC (n=50, 31%) as their postpartum contraceptive method. Most subjects were black (99%), single (97%), and on medical assistance (85%). Data were gathered 12-18 months postpartum (mean+/-standard deviation [SD] 14.5+/-1.6 months) by telephone interview and medical record review. The main outcome measures were method continuation and repeat pregnancy. RESULTS: The mean (+/-SD) age at delivery was 17.8+/-1.4 years. Variables differentiating subjects selecting depot medroxyprogesterone acetate or OC included multiparity (34% versus 12%, P < .05), mean age at first pregnancy (15.9 versus 16.6 years, P < .05), and mean age at first delivery (16.1 versus 16.9 years, P < .05). The survival curves for depot medroxyprogesterone acetate and OC continuation differed significantly (median duration of use 8.1 versus 5.4 months, respectively), but the continuation rates at 12 months were similar (34% versus 32%). The survival curves for repeat pregnancy among subjects selecting depot medroxyprogesterone acetate differed significantly from curves of those choosing OC, with repeat pregnancy rates of 15% and 36% by 15 months. Postpartum selection of OC was the only variable entering a Cox regression model designed to predict repeat pregnancy (relative risk 3.0, 95% confidence interval 1.4, 6.7). CONCLUSION: Adolescent mothers choosing depot medroxyprogesterone acetate or OC immediately postpartum face similarly high rates of method discontinuation and repeat pregnancy within 1 year.

Neuroimaging abnormalities in children with an apparent first unprovoked seizure.

OBJECTIVE: To determine the incidence and type of neuroimaging abnormalities in children presenting with a first seizure. METHODS: In a prospective observational study, 411 children with a first afebrile seizure were seen between 1983 and 1992. Imaging studies were performed in 218 (53%). For this analysis we examined the most sensitive neuroimaging study performed which included 159 computed tomography scans and 59 magnetic resonance imagings (MRI). RESULTS: Four children were found to have lesions requiring intervention (brain tumor in two, neurocysticercosis in two). The remaining 407 were enrolled in a follow-up study of children with a first unprovoked seizure. After a mean follow-up of >10 years, none have developed clinical evidence of a tumor. In these 411 children, 45 (21%) of 218 imaging studies were abnormal. The most common abnormalities were focal encephalomalacia (n=16) and cerebral dysgenesis (n=11). Although children with partial seizures were more likely to be imaged (64%) than children with generalized seizures (43%) (P<0.001), the fraction of abnormal imaging studies was similar in both groups. Six children with a normal neurological examination who were initially classified as cryptogenic were subsequently found to have errors of cerebral migration on MRI. The incidence of lesions requiring acute intervention in children presenting with a first seizure is low. A significant proportion will have neuroimaging abnormalities particularly on MRI. CONCLUSIONS: Neuroimaging should be considered in any child with a first seizure who does not have an idiopathic form of epilepsy.

The development of stereoacuity in infant rhesus monkeys.

The emergence of stereopsis at 3-4 months postnatal in human infants is striking and has led to speculation that its rapid onset and subsequent development must be due to a dramatic reorganization of the brain. Stereopsis has never been measured in infant monkeys, but previous studies have demonstrated that many other visual functions develop four times faster in infant monkeys than in humans. We made longitudinal assessments of stereoacuity in 11 infant rhesus monkeys. A forced-choice preferential-looking technique was used to present random-dot stereograms during testing. By 8 weeks after birth, all of the monkeys were responding to at least coarse levels of disparity (1760" [seconds]), and by 13 weeks of age, all were responding to the relatively fine level of 88" disparity. Age of onset for stereopsis in monkeys was at about one-quarter the age when it occurs in humans, as expected. However, subsequent development proceeded at a similar absolute rate in monkeys and humans. The findings are discussed relative to the neural mechanisms which might be responsible for the differing rates of development.