Does value-based prioritization at working memory enhance long-term memory?

Research has demonstrated that individuals can direct their attention to valuable information in both working memory and long-term memory tasks with observable effects on performance. However, it is currently unclear whether prioritising an item for a working memory task automatically translates into a boost at long-term memory. This was examined in two experiments using relatively short (250 ms per item; Experiment 1) and longer (500 ms per item; Experiment 2) encoding times. Participants first completed a visual working memory task, in which they were presented with series of photographs of everyday objects. Following a brief delay (1,000 ms), they completed a four-alternative forced-choice test. Prior to encoding, participants were informed of the point values associated with each item. In some trials, the first item in the sequence was worth more points than the rest. In other trials, all items were equally valuable. After a filled delay, participants completed a surprise long-term memory task. At working memory, a value effect was reliably observed on recognition accuracy, along with some evidence of faster response times for high-value items. However, there was little consistent evidence of this effect automatically persisting into long-term memory. Thus, the benefits of attentional prioritization in working memory do not always translate into longer-term performance. More broadly, this provides further evidence that manipulations that enhance working memory performance do not necessarily enhance long-term memory.

The Living Donor Collective: A Scientific Registry for Living Donors.

In the setting of an overall decline in living organ donation and new questions about long-term safety, a better understanding of outcomes after living donation has become imperative. Adequate information on outcomes important to donors may take many years to ascertain and may be evident only by comparing large numbers of donors with suitable controls. Previous studies have been unable to fully answer critical questions, primarily due to lack of appropriate controls, inadequate sample size, and/or follow-up duration that is too short to allow detection of important risks attributable to donation. The Organ Procurement and Transplantation Network does not follow donors long term and has no prospective control group with which to compare postdonation outcomes. There is a need to establish a national living donor registry and to prospectively follow donors over their lifetimes. In addition, there is a need to better understand the reasons many potential donors who volunteer to donate do not donate and whether the reasons are justified. Therefore, the US Health Resources and Services Administration asked the Scientific Registry of Transplant Recipients to establish a national registry to address these important questions. Here, we discuss the efforts, challenges, and opportunities inherent in establishing the Living Donor Collective.

Consensus conference on best practices in live kidney donation: recommendations to optimize education, access, and care.

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

Is rapid organ recovery a good idea? An exploratory study of the public's knowledge and attitudes.

In 2006, the Institute of Medicine (IOM) recommended demonstration projects on uncontrolled donation after cardiac death or rapid organ recovery (ROR). To investigate what the public thinks about key ethical and policy questions associated with ROR, 70 African-American, Caucasian and Latino community members in St. Louis, MO, participated in focus groups and completed surveys, before and after being educated about ROR. Before the focus group, most participants believed mistakenly that they could donate organs following an unexpected cardiac arrest (76%). After the focus group, 84% would want to donate organs after unexpected cardiac arrest; 81% would support organ cooling to enable this. The public generally supported organ cooling without family consent if the individual had joined the donor registry, but were mixed in their opinions about what should be done if they were not on the registry. African-American and Latino participants expressed greater fears than Caucasians that if they consented to organ donation, physicians might do less to save their life; however, support for ROR was not significantly lower in these subgroups. Although this study is exploratory, public support for ROR was present. We recommend that adequate consent processes and safeguards be established to foster trust and support for ROR.

Differences in tolerance for health risk to the living donor among potential donors, recipients, and transplant professionals.

In organ donation, the donor, recipient, and transplant team must all accept potential health risks to the donor and any uncertainties. To gauge these risks, we surveyed general altruism and risk-taking behaviors in 112 potential donors, 111 potential recipients, and 51 transplant professionals. Next, participants indicated their risk thresholds for long-term donor hypertension, cardiovascular disease, and kidney failure that would stop them from pursuing living donation and their willingness to proceed when risks were uncertain. The three groups had similar general altruism and risk-taking behaviors. Potential donors were significantly more willing to accept greater long-term donor risks than potential recipients and transplant professionals. Moreover, these potential donors were significantly more likely to agree that living donation was acceptable when long-term donor risks were uncertain. Potential kidney donors readily accept high long-term risks, whereas potential recipients were the most averse to donor risk. Our study shows that transplant professionals facilitate the best decisions by appreciating the willingness of their patients to accept donor health risks along with their own risk tolerance.

Central sensitization as a result of surgical pain: investigation of the pre-emptive value of pethidine for ovariohysterectomy in the rat.

The development of central hypersensitivity as a result of a routine surgical procedure, midline ovariohysterectomy, was investigated in rats using the paw pressure test (PPT) and tail-flick latency (TFL) tests of spinal reflex activity. In addition, the modulating effect of pre-emptive versus post-operative administration of pethidine (a short-acting pure mu-opioid agonist) on the development of central hypersensitivity was studied. Initial experiments indicated that pethidine (15 mg/kg, i.m.) gave sub-maximal increases in thresholds for 60 min, and also that the administration of an anaesthetic did not unduly prolong the action of pethidine. Subsequently, 24 female Wistar rats were allocated to 1 of 4 treatment protocols: (1) anaesthesia without analgesics; (2) anaesthesia and surgery (midline ovariohysterectomy) without analgesics; (3) anaesthesia and surgery with pre-operative administration of pethidine; (4) anaesthesia and surgery with post-operative administration of pethidine. Thirty-five minutes after the end of anaesthesia thermal and mechanical nociceptive thresholds were measured at stepwise increasing intervals for 480 min. Changes were expressed as percentage changes from baseline (PPT) or deviation from expected values (TFL). Area under the threshold versus time response curves (AUCs) were also calculated for the following time sectors: 30-90, 90-150, 150-270, 270-390 and 390-510 min post-anaesthetic. Results of the TFL testing did not indicate the development of any significant hyperalgesia in any groups, but the results of the PPT did. In the time sectors 150-270 and 270-390 min post-anaesthetic, the AUCs in rats subjected to anaesthesia and surgery with either post-operative administration of pethidine or surgery with no analgesic drug administration, were significantly lower than the AUCs in rats given analgesics pre-operatively or those subjected to general anaesthesia alone (P < 0.01), Mann-Whitney). In summary, it appears that pethidine, in this protocol, prevented the development of surgically induced hyperalgesia when it was given pre-emptively.

Analgesic effects of intrathecally-applied alpha 2-adrenoceptor agonists in conscious, unrestrained sheep.

Intrathecal injections of small volumes of the alpha 2-adrenoceptor agonists, xylazine and clonidine, into the cervical region of the spinal cord of conscious unrestrained sheep produced a dose-dependent analgesia of the forelimbs as measured using a mechanical pressure device. Intravenous injection of the alpha 2-adrenoceptor antagonist, idazoxan completely abolished the analgesic effects of the intrathecally applied alpha 2-adrenoceptor agonists. Subsequent studies using [3H] clonidine injected at a similar dose and volume via the intrathecal catheters, indicated that the volume of drug used, 100 microliter, gave a localisation of the drug limited to about five vertebral segments around the catheter tip.

The development of tolerance to ketamine in rats and the significance of hepatic metabolism.

1. A decrease in sleeping time in rats pretreated with ten daily doses of ketamine compared to controls is shown. 2. This decrease in sleeping time is associated with a more rapid decrease in circulating and brain levels of ketamine and its N-demethylated metabolite and higher levels of the subsequent oxidation metabolite in the pretreated animals. 3. Metabolism of ketamine to its N-demethylated metabolite by liver homogenates in vitro was more rapid when the livers were obtained from ketamine pretreated rats. 4. Microsomal preparations from rat liver were capable of metabolizing ketamine to its N-demethylated metabolite and this metabolite to the subsequent oxidation metabolite in vitro. The Vmax and Km for the first reaction calculated from loss of substrate were 433 mol mg-1 protein h-1 and 0.133 mM respectively and 199 nmol mg-1 protein h-1 and 0.121 mM for the second reaction. 5. The results indicate that tolerance to ketamine in rats is associated with increased hepatic metabolism which can also be demonstrated in vitro in liver homogenates.

Investigation of the antinociceptive activity of buprenorphine in sheep.

1. Buprenorphine given intravenously (6 micrograms kg-1) was examined for its antinociceptive activity in unrestrained sheep using devices to measure thermal and mechanical thresholds. 2. The plasma levels of buprenorphine following intravenous injection over the time period of the antinociceptive testing were measured using a radioimmunoassay. 3. Buprenorphine produced a clear antinociceptive effect lasting for up to three and a half hours when measured by the thermal threshold test, but no detectable antinociception in the mechanical test. 4. The plasma levels of buprenorphine indicated that the drug was rapidly distributed in a manner not dissimilar to that reported in man, although individual animals showed a wide variation in some parameters. 5. When plasma levels of the drug were high (less than 700 pg ml-1) during the first sixty minutes, no antinociceptive activity in the thermal test could be detected, which may be due to the slow receptor kinetics shown by this drug.

The spinal antinociceptive activity of the alpha 2-adrenoceptor agonist, xylazine in sheep.

1. The intrathecal administration of xylazine (100 micrograms), via a chronic indwelling, cervical intrathecal catheter, produced a marked elevation of the mechanical nociceptive thresholds in the sheep. This antinociceptive effect was abolished by the prior intrathecal administration of the alpha 2-adrenoceptor antagonist, idazoxan. 2. The intrathecal administration of the selective alpha 2-antagonists, idazoxan (100 micrograms) and RX811059 (33 micrograms), significantly attenuated the antinociceptive activity of intravenous xylazine, with a 60-65% reduction in the area under the antinociceptive curve. The intrathecal administration of the antagonists alone had no significant effect on nociceptive thresholds. 3. Examination of the distribution of tritiated idazoxan (25 microCi in 100 microliters) indicated that the site of action of the drug was limited to the cervical spinal cord after intrathecal administration. 4. These studies demonstrate that a significant proportion of the antinociceptive effect of systemically administered xylazine is mediated by spinal alpha 2-adrenoceptors.

3'-Azido-3'-deoxythymidine inhibition of human lymphocyte cytolytic function in vitro.

Despite administration of 3'-azido-3'-deoxythymidine (AZT, Zidovudine) to seriously immunocompromised patients, little has been reported regarding effects of AZT on specific immune functions. This study analyzed the in vitro effect of AZT on normal human lymphocyte cytolytic activity. AZT at concentrations up to 100 microM had no effect when added directly to cytotoxicity assays with lymphocyte effector cells and natural killer (NK)-sensitive or NK-resistant target cells. In contrast, addition of AZT to lymphocytes cultured for 4-10 days with interleukin-2 (IL-2) prior to cytotoxicity assays produced a concentration- and time-dependent inhibition; this effect was not mimicked by acyclovir or ganciclovir. Lymphocyte cell numbers and viability were not reduced in parallel to inhibition of cytolytic activity by AZT. Furthermore, AZT inhibition of IL-2-dependent cytolytic activity was not correlated with alterations in lymphocyte cell surface phenotypes by flow cytometry, and lymphocyte culture supernatant levels of interferon-gamma were not reduced by AZT. These results suggest that AZT may selectively inhibit human lymphocyte functions and thus may have implications for long-term therapeutic administration of AZT in chronic immunodeficiency states.

Urinary and faecal Escherichia coli O-sero-groups in symptomatic urinary-tract infection and asymptomatic bacteriuria.

The degree of correspondence between urinary and faecal Escherichia coli O-groups has been assessed in non-pregnant women with symptomatic urinary-tract infection or asymptomatic bacteriuria. In 20 of 26 patients with symptomatic urinary tract infection E. coli of the same O-groups as that of the urinary infecting strain was also present in the patient's faecal flora of only five of 25 patients with asymptomatic bacteriuria. This finding indicates that the majority of episodes of symptomatic urinary tract infection in non-pregnant women are not preceded by a significant period of asymptomatic bacteriuria. E. coli O6 showed correspondence between urinary and faecal isolates more frequently than did other O-groups, but it had a relatively low prevalence in the faecal flora of patients with urinary-tract infection caused by E. coli of other O-groups. This finding lends support to previous suggestions that E. coli O6 may be especially pathogenic for the urinary tract.

A technique for recording from spinal neurones in awake sheep.

A technique is described for implanting a chamber on 1 or 2 vertebrae of the spinal column of the sheep. This chamber protrudes permanently through the dorsal skin of the back and is covered by a light bandage. Between recording sessions the chamber houses an inner cap sealing the hole that gives access to the cord. During recording sessions this cap is removed and a miniature manipulator inserted instead. This manipulator can accept a motor drive that holds a glass-coated tungsten microelectrode. The drive has a hole through which an arthroscope tube can be passed so that insertion of the electrode can be performed under visual control. Extracellular recordings have been made of single spinal neurones for up to 4 h in animals that are drug-free, untrained and only lightly restrained. Recording sessions can be repeated on a daily basis for several weeks until the dura and/or arachnoid becomes too thickened to permit electrode penetrations. Animals remain healthy and their behaviour remains normal throughout this time.

Behavioural analysis of changes in nociceptive thresholds produced by remoxipride in sheep and rats.

The antinociceptive potential of remoxipride was investigated in sheep and rats with concurrent motor function assessments. Previous studies of sheep given intravenous remoxipride have revealed increases in mechanical nociceptive thresholds. Here, further investigation in sheep demonstrated elevated thermal nociceptive thresholds with no effect on subjectively assessed sedation or motor impairment scores. However, in rats, the dose of remoxipride (100 mg/kg i.p.) required to produce nociceptive thresholds similar to those elicited by morphine (30 mg/kg i.p.), itself reduced rotarod performance. Medetomidine (200 micrograms/kg i.p.) evoked sedation without influencing rotarod performance or antinociception. The antinociceptive, motor deficit and cataleptogenic actions of remoxipride were similar to those induced by two other dopamine antagonists, haloperidol (5 mg/kg) and raclopride (16 mg/kg i.p). Tocainide (100 mg/kg i.p.) induced thermal antinociception with normal rotarod performance and no catalepsy suggesting that Na+ channel blockade by remoxipride is not responsible for the changes in nociceptive thresholds. This study emphasizes the importance of motor function assessment during acute antinociceptive testing.

Investigation into the antinociceptive potential of remoxipride administered intrathecally in sheep.

Systemic administration of remoxipride, a dopamine (D2) antagonist, to sheep has previously been shown to generate an antinociceptive action without producing a significant motor impairment. The present study examined whether a spinal locus of action was responsible for this action of remoxipride. Remoxipride (17.7 mg) administered intrathecally via chronically indwelling catheters produced a greatly variable but significant (p<0.05) increase in nociceptive thresholds as judged by a focused mechanical stimulus (blunt pin) applied to the forelimb of four sheep. However, this dose of remoxipride induced a marked forelimb motor impairment as judged by a subjective visual analogue scoring system. Conversely, intrathecal xylazine (100 and 200 microg), an alpha-adrenergic agonist with antinociceptive properties, did not produce forelimb weakness although the higher dose (200 microg) produced significant sedation. In vitro autoradiography was performed on cervical spinal cord sections taken from sheep. Remoxipride displaced [3H] YM-09151-2, a selective D2 antagonist, from densely-labelled areas in the superficial layer of the dorsal horn, lamina X and ventral horn. Even though there are possible anatomical substrates within the spinal cord for both an antinociceptive and motor disturbance action of remoxipride, the behavioural data suggest that the spinal cord is unlikely to be the primary site of antinociceptive action for systemically-administered doses of remoxipride.

Chronic intrathecal catheterization in the sheep.

This paper describes a relatively simple and noninvasive method for the chronic implantation of intrathecal catheters in the sheep. The technique has been carried out on 17 occasions in nine sheep, with 60% of attempted catheterizations producing a correctly positioned, functional catheter. The placement and integrity of the catheters were confirmed by radiography using a contrast medium. Correctly placed catheters have been maintained for up to 16 months without problems.

Psychosocial development in adulthood: a 22-year sequential study.

Data supporting the notion of adult personality stability are challenged by the present findings, in which developmental change was demonstrated using the Eriksonian-stage-based Inventory of Psychosocial Development (IPD; Constantinople, 1969). A sequential design over the ages 20-42 was used on 2 cohorts of college students and alumni originally tested in 1966 and 1976-1977 (ns in 1988 = 99 and 83, respectively), and a 3rd cohort of college students in 1988-1989 (n = 292). Results of longitudinal, cross-sectional, and sequential analyses challenged ideas about personality stability, with evidence of increasingly favorable resolutions of the early Eriksonian psychosocial stages up through the oldest age studied. There was evidence of a trend over the past decade toward less favorable resolution of ego integrity versus despair. The findings were interpreted in terms of developmental change processes during the adult years interacting with culturally based environmental effects on psychosocial development.

Evaluation of the actions and use of alphaxolone/alphadolone (CT1341) in sheep.

CT1341 (alphaxolone/alphadolone) (Saffan; Glaxo) at various dose rates was investigated for use as an intravenous anaesthetic agent in sheep and it was found that at least 1.65 mg/kg was required to induce anaesthesia. In an experimental group of animals the effect of CT1341 2.2 mg/kg, on PaO2, PaCO2, paH and mean arterial blood pressure was measured. The drug caused a mild respiratory acidosis accompanied by a slight decrease in PaCO2 tensions. Mean arterial blood pressure decreased by 50 per cent, 30 seconds after injection but this fall lasted for only 10 minutes. Prior administration of either atropine sulphate or mepyramine maleate failed to modify this hypotensive effect. Injection of the vehicle, Cremophor EL, alone had no effect on mean arterial blood pressure. Intracerebroventricular administration of CT1341 while producing anaesthesia failed to produce any hypotension. The drug was used for the induction of anaesthesia in 19 sheep. A mean dose of 3.0 mg/kg was found to be most useful clinically. In a further three sheep an infusion of a dilute solution (0.234 mg/kg per minute) was used to maintain anaesthesia. The most notable clinical feature in sheep was the fast, complete recovery. It is concluded that this agent is an extremely useful drug for the induction and maintenance of anaesthesia in sheep.