Improving primary care antimicrobial stewardship by implementing a peer audit and feedback intervention in Cape Town community healthcare centres.

BACKGROUND: The increasing prevalence of antibiotic resistance is a major threat to public health. Primary care, where 80% of antibiotics are consumed, is a pivotal setting to direct antimicrobial stewardship (AMS) efforts. However, the ideal model to improve antibiotic prescribing in primary care in low-resource settings is not known. OBJECTIVE: To implement a multidisciplinary audit and feedback AMS intervention with the aim to improve appropriate antibiotic prescribing at primary care level. METHODS: The intervention was implemented and monitored in 10 primary care centres of the Cape Town metropole between July 2017 and June 2019. The primary and secondary outcome measures were monthly adherence to a bundle of antibiotic quality process measures and monthly antibiotic consumption, respectively. Multidisciplinary audit and feedback meetings were initiated and integrated into facility clinical meetings. Two Excel tools were utilised to automatically calculate facility audit scores and consumption. Once a month, 10 antibiotic prescriptions were randomly selected for a peer review audit by the team. The prescriptions were audited for adherence to a bundle of seven antibiotic process measures using the standard treatment guidelines (STG) and Essential Medicines List (EML) as standard. Concurrently, primary care pharmacists monitored monthly antibiotic consumption by calculating defined daily doses (DDDs) per 100 prescriptions dispensed. Adherence and consumption feedback were regularly provided to the facilities. Learning collaboratives involving representative multidisciplinary teams were held twice-yearly. Pre-, baseline and post-intervention periods were defined as 6 months before, first 6 months and last 6 months of the study, respectively. RESULTS: The mean overall adherence increased from 19% (baseline) to 47% (post intervention) (p<0.001). Of the 2 077 prescriptions analysed, 33.7% had an antibiotic prescribed inappropriately. No diagnosis had been captured in patient notes, and the antibiotic chosen was not according to the STG and EML in 30.1% and 31.7% of cases, respectively. Seasonal variation was observed in prescribing adherence, with significantly lower adherence in winter and spring months (adjusted odds ratio 0.60). A reduction of 12.9 DDDs between the pre- and post-intervention periods (p=0.0084) was documented, which represented a 19.3% decrease in antibiotic consumption. CONCLUSION: The study demonstrated that peer reviewed audit and feedback is an effective AMS intervention to improve antibiotic prescribing in primary care in a low-resource setting. The intervention, utilising existing resources and involving multidisciplinary engagement, may be incorporated into existing quality improvement processes at facility level, to ensure sustainable change.

Antimicrobial stewardship in the Western Cape: A situational analysis of existing facility-level initiatives.

BACKGROUND: Antimicrobial resistance (AMR) is a growing problem worldwide. With the current occurrence of pan-resistant bacterial infections and a paucity of novel antimicrobials in development, the world has entered a post-antibiotic era, in which previously treatable, common infections can become fatal. Antimicrobial stewardship (AMS), defined as 'co-ordinated interventions to ensure appropriate and rational use of antimicrobials', aims to decrease rates of AMR. OBJECTIVES: To co-ordinate AMS in Western Cape Province. The National Department of Health (NDoH) has identified AMS as a key strategic objective, and the Western Cape has formed a provincial AMS committee. However, not much is known regarding current AMS activities in health facilities in the province. METHODS: A self-administered, email questionnaire was sent to specific staff at all district, regional and tertiary hospitals in the 6 health districts of the Western Cape - 47 facilities in total, of which 35 (74.4%) responded. Respondents included pharmacists, managers, doctors, nurses, infection prevention and control practitioners, as well as quality assurance practitioners. The number of facilities implementing AMS were determined, as well as the composition of AMS committees and the nature and frequency of team activities. Barriers to facility-level AMS were explored. Support and outreach activities were assessed, as well as facilities' needs and expectations of the provincial AMS committee. RESULTS: Approximately half of all responding hospitals (n=19; 54.3%) had active AMS committees. Double the proportion of metropolitan (83.3%) than rural facilities (39.1%) had committees. Stewardship activities included antimicrobial prescription chart reviews and audits, AMS ward rounds, antimicrobial restriction policies and training. Most committees included a pharmacist and an infection prevention and control practitioner. More than a third of hospitals (36.1%) did not review their antimicrobial consumption data on a regular basis. Just over half of the hospitals (n=18; 51.4%) did not review AMR patterns. CONCLUSIONS: Despite the need for effective AMS, there is limited information on AMS in South Africa. Most assistance is required in rural areas and smaller hospitals with low numbers of staff and greater numbers of transient rotating junior staff. Information management support, multidisciplinary teamwork and clinical governance are required to enable regular and ongoing AMS in facilities. Rural and smaller facilities require greater support to establish effectively functioning AMS committees.

The Negro River (Ancash-Peru): A unique case of water pollution, three environmental scenarios and an unresolved issue.

This paper is focused on the hydrogeochemical characterization of the Negro River along its course, as well as in the proposal of a functioning model for the contamination processes in order to establish potential cause-effect relationships between water quality, geology (ARD), mining activities (AMD) and the tectonic framework as transmission vector of acidity, metals and sulphates. The scenario shows a heavily-contaminated river compared to the unaffected regional background. By graphical and statistical treatments of physico-chemical data of Negro River and the unaffected values of regional background and other AMD/ARD representative rivers' it is possible to conclude that Antamina Mine, is not the cause of the Negro River contamination, without the need of isotopic tracers, but just through the inexistent concentrations of Cu, Bi and Mo found in the waters. In the proposed contamination model, climatic factors (glacial retreat) activate geological (ARD) processes. The tectonic scenario (faults) intervenes as a transport medium of the contamination flux from the sulphide oxidation surface in upper altitudes until the spring in lower altitudes. At the end, it is concluded that this contamination comes from the recent glacial retreat in areas near the Cordillera Blanca that has left massive amounts of sulphide materials exposed to weathering conditions, oxidizing naturally (ARD processes) and finally contributing to the contamination of the Negro River through faults. In this case, we would face an ARD process in the strict sense, which is the direct oxidation of sulphides outcropping in the upper part of the mountain with the generation of sulphates, the release of hydrogen ions and the consequent generation of acid and the dissolution of the metals. This ARD process would come from the glacial retreat, which, through the faults, transports contaminated water until the spring.

Antibiotic prescribing practice and adherence to guidelines in primary care in the Cape Town Metro District, South Africa.

BACKGROUND: Knowledge of antibiotic prescribing practice in primary care in South Africa is limited. As 80% of human antibiotic use is in primary care, this knowledge is important in view of the global problem of antibiotic resistance. OBJECTIVES: To assess antibiotic prescribing in primary care facilities in the Cape Town Metro District and compare it with current national guidelines, and to assess the reasons why prescriptions were not adherent to guidelines. METHODS: A retrospective medical record review was performed in April/May 2016. Records of all patients seen over 2 days in each of eight representative primary care facilities in the Cape Town Metro District were reviewed. The treatment of any patient who raised a new complaint on either of those days was recorded. Prophylactic antibiotic courses, tuberculosis treatment and patients with a non-infection diagnosis were excluded. Treatment was compared with the Standard Treatment Guidelines and Essential Medicines List for South Africa, Primary Healthcare Level, 2014 edition. RESULTS: Of 654 records included, 68.7% indicated that an antibiotic had been prescribed. Overall guideline adherence was 45.1%. Adherence differed significantly between facilities and according to the physiological system being treated, whether the prescription was for an adult or paediatric patient, and the antibiotic prescribed. Healthcare professional type and patient gender had no significant effect on adherence. The main reasons for non-adherence were an undocumented diagnosis (30.5%), antibiotic not required (21.6%), incorrect dose (12.9%), incorrect drug (11.5%), and incorrect duration of therapy (9.5%). CONCLUSIONS: This study demonstrates poor adherence to guidelines. Irrational use of antibiotics is associated with increased antibiotic resistance. There is an urgent need to improve antibiotic prescribing practice in primary care in the Cape Town Metro District.

Sofosbuvir and velpatasvir with or without voxilaprevir in direct-acting antiviral-naïve chronic hepatitis C: patient-reported outcomes from POLARIS 2 and 3.

BACKGROUND: Chronic hepatitis C infection leads to impairment of patient-reported outcomes (PROs). Treatment with direct-acting antiviral regimens results in short- and long-term improvement of these outcomes. AIM: To assess PROs in patients treated with a newly developed direct-acting antiviral, a fixed-dose combination of sofosbuvir/velpatasvir (SOF/VEL) with/without voxilaprevir (VOX). METHODS: The PRO data were collected from participants of POLARIS-2 and POLARIS-3 clinical trials (DAA-naïve, all HCV genotypes). Participants self-administered SF-36v2, FACIT-F, CLDQ-HCV and WPAI:SHP instruments at baseline, during treatment, and in follow-up. RESULTS: Of 1160 patients, 611 received SOF/VEL/VOX and 549 received SOF/VEL (52.8 ± 11.0 years, 55.9% male, 75.4% treatment-naïve, 33.9% cirrhotic). The sustained viral response at 12 weeks (SVR12) rates were 95%-98%. During treatment, improvements in most PRO scores were significant (all but one P < .01) and ranged from, on average, +2.3 to +15.0 points (on a 0-100 scale) by the end of treatment. These improvements were similar between SOF/VEL/VOX and SOF/VEL arms (all P > .05). After treatment discontinuation, patients treated with both regimens achieved significant and clinically meaningful PRO gains (+2.7 to +16.7 by post-treatment week 12, +3.9 to +20.1 by post-treatment week 24; all but one P < .001). Multivariate analysis showed that depression, anxiety and cirrhosis were the most consistent independent predictors of PRO impairment while no association of PROs with the treatment regimen choice was found (all P > .05). CONCLUSIONS: The pan-genotypic regimens with SOF/VEL with or without VOX not only have excellent efficacy and safety, but also significantly positively impact patients' experience both during treatment and after achieving sustained virologic response in DAA-naïve patients with HCV.

Processing of mycotoxin contaminated waste streams through anaerobic digestion.

Food and feed stocks heavily contaminated with mycotoxins are rendered unfit for consumption and therefore discarded as waste. Due to the lack of guidelines and in accordance with the prudent avoidance principle, these waste streams are often incinerated. For better valorization, these streams could be used as input for anaerobic digestion. However, the degradation of multiple mycotoxins during anaerobic digestion and their effect on the methane production is currently unknown. In batch tests spiked with mycotoxins, aflatoxin B1, ochratoxin A, deoxynivalenol, zearalenone and T-2 toxin were degraded for more than 90%. For mesophile and thermophile digestion respectively, fumonisin B1 was degraded for 70% and 85%, and most ergot alkaloids for 64% and 98%. Neither biogas production, nor methane production were influenced by the presence of the mycotoxins. Subsequently, semi-continuous reactors fed with contaminated maize resulted in more than 99% degradation for all mycotoxins after 1.8 hydraulic retention time with stable biogas production and process parameters. This study shows that mycotoxin contaminated organic waste can be safely valorized to methane while the digestate is void of mycotoxin residues.

Antibiotic prescribing practice and adherence to guidelines in primary care in the Cape Town Metro District, South Africa

Background.Knowledge of antibiotic prescribing practice in primary care in South Africa is limited. As 80% of human antibiotic use is in primary care, this knowledge is important in view of the global problem of antibiotic resistance.Objectives. To assess antibiotic prescribing in primary care facilities in the Cape Town Metro District and compare it with current national guidelines, and to assess the reasons why prescriptions were not adherent to guidelines.Methods. A retrospective medical record review was performed in April/May 2016. Records of all patients seen over 2 days in each of eight representative primary care facilities in the Cape Town Metro District were reviewed. The treatment of any patient who raised a new complaint on either of those days was recorded. Prophylactic antibiotic courses, tuberculosis treatment and patients with a non-infection diagnosis were excluded. Treatment was compared with the Standard Treatment Guidelines and Essential Medicines List for South Africa, Primary Healthcare Level, 2014 edition.Results. Of 654 records included, 68.7% indicated that an antibiotic had been prescribed. Overall guideline adherence was 45.1%. Adherence differed significantly between facilities and according to the physiological system being treated, whether the prescription was for an adult or paediatric patient, and the antibiotic prescribed. Healthcare professional type and patient gender had no significant effect on adherence. The main reasons for non-adherence were an undocumented diagnosis (30.5%), antibiotic not required (21.6%), incorrect dose (12.9%), incorrect drug (11.5%), and incorrect duration of therapy (9.5%). Conclusions. This study demonstrates poor adherence to guidelines. Irrational use of antibiotics is associated with increased antibiotic resistance. There is an urgent need to improve antibiotic prescribing practice in primary care in the Cape Town Metro District

Herpes simplex hepatitis after liver transplantation: case report and literature review.

Herpes simplex virus (HSV) hepatitis is an uncommon cause of liver failure, but may have a dramatic outcome. We herein present a case report of a liver graft infection by HSV-1 associated with liver failure and encephalitis. A complete hospital chart review of the case and a literature search were undertaken. Literature review suggests that herpes simplex acute liver failure is rare and associated with a poor prognosis, even with early treatment. Novel diagnostic and preventive approaches need to be instituted.

Measles vaccination coverage in high-incidence areas of the Western Cape, following the mass vaccination campaign.

BACKGROUND: Despite significant advances in measles control, large epidemics occurred in many African countries in 2009 - 2011, including South Africa. South Africa's control strategy includes mass vaccination campaigns about every 4 years, the last of which was conducted nationally in April 2010 and coincided with the epidemic. AIM: A community survey was conducted in the Western Cape to assess measles vaccination coverage attained by routine and campaign services, in children aged 6 months to 59 months at the time of the mass campaign, from high-incidence areas. METHODS: Households were consecutively sampled in high-incidence areas identified using measles epidemic surveillance data. A caregiver history of campaign vaccination and routine vaccination status from the child's Road to Health card were collected. Pre- and post-campaign immunity was estimated by analytical methods. RESULTS: Of 8 332 households visited, there was no response at 3 435 (41.2%); 95.1% (1 711/1 800) of eligible households participated; and 91.2% (1 448/1 587; 95% confidence interval 86 - 94%) of children received a campaign vaccination. Before the campaign, 33.0% (103/312) of 9 - 17-month-olds had not received a measles vaccination, and this was reduced to 4.5% (14/312) after the campaign. Of the 1 587 children, 61.5% were estimated to have measles immunity before the campaign, and this increased to 94.0% after the campaign. DISCUSSION: Routine services had failed to achieve adequate herd immunity in areas with suspected highly mobile populations. Mass campaigns in such areas in the Western Cape significantly increased coverage. Extra vigilance is required to monitor and sustain adequate coverage in these areas.

Long term administration of LMWH - pharmacodynamic parameters under therapeutic or prophylactic regimen of enoxaparin or tinzaparin in neurological rehabilitation patients.

We investigated anti-FXa- and anti-FIIa-activity, thrombin generation (ETP), tissue factor pathway inhibitor (TFPI) - and D-dimer in patients exhibiting high bleeding risk in early neurological rehabilitation over 2 months in an observational study. Blood of 64 patients under LMWH administration due to therapeutic (cohort 1 [tinzaparin 90 IE/kg BID, N = 18] and 2 [enoxaparin 100 IE/kg BID; N = 15]) or prophylactic (cohort 3 [tinzaparin 4500 IE; N = 16] and 4 [enoxaparin 4000 IE; N = 15]) indication was drawn before and 4h after injection on day 7 (V1) and 2 months (follow up [V2]). Although the dose in cohort 1 and 2 was similar (median 7000 IE BID), a-FXa-activity was significantly larger under enoxaparin than under tinzaparin (e.g. median at V2: 0.70 IU/ml vs. 0.33 IU/ml). Also, prophylactic enoxaparin exhibited larger a-FXa-activity than tinzaparin (e.g. median at V2: 0.37 IU/ml vs. 0.22 IU/ml). The a-FXa/a-FIIa-ratio in plasma samples at 4h p.a. was about 4 (tinzaparin) and 8 (enoxaparin), respectively. No differences were seen for TFPI and ETP between cohort 1 and 2 or between cohort 3 and 4. D-dimer levels decreased significantly between V1 (e.g. cohort 4 median 1940 ng/ml) and V2 (median 652 ng/ml). Minimal bleeding events occurred in 6 patients (2 under tinzaparin, 4 under enoxaparin) and were associated with significantly higher anti-FXa-activity. In conclusion, although marked differences between tinzaparin and enoxaparin based on anti-FXa-activity were seen, markers of in vivo biological activity such as TFPI and D-dimer were not different. Furthermore, BID tinzaparin is a feasible option for therapeutic anticoagulation in patients with high bleeding risk.

Usefulness of a novel Caco-2 cell perfusion system II. Characterization of monolayer properties and peptidase activity.

In this study, the enzymatic activity and the influence of support filters and extracellular matrix proteins on the differentiation of Caco-2 cells grown in a perfusion system (Minucells and MinutissueTM) were examined and compared to traditional culturing approaches. Differences were observed regarding the differentiation of Caco-2 cells using the traditional approach and perfusion system such that the cell monolayers grown in a perfusion system showed a significant increase in dipeptidase activities (18.20 +/- 0.43nmol x min(-1) x cm(-2)) compared to the cells cultivated using the 21-day protocol (9.45 +/- 0.50 nmol x min(-1) x cm(-2)). The peptidase activity of Caco-2 cells was strikingly inhibited when Matrigel extracellular protein was used for coating polycarbonate support filters. While the enzymatic activities of the cell monolayers differentiated in the perfusion system were up-regulated, the transepithelial electrical resistance values of the cell monolayers (171 +/- 52 and 251 +/- 62 omega x cm2 for polycarbonate and polyester, respectively) decreased compared to the traditional Snapwell inserts (644 +/- 119 omega x cm2). The results suggested that the perfusion systems were useful permeability models which reduce workload, resources and manpower needed to obtain useful Caco-2 monolayers. In addition, the approach offers an efficient tool for long-term culturing of highly differentiated Caco-2 cell monolayers.

Parallel artificial membrane permeability assay (PAMPA) combined with a 10-day multiscreen Caco-2 cell culture as a tool for assessing new drug candidates.

The parallel artificial membrane permeability assay (PAMPA) is extensively used for the evaluation of early drug candidates. It is high throughput, low cost and is amenable to automation. This method has been shown useful in assessing transmembrane, non-energy dependent, diffusion of drugs such that reasonable predictability with in vivo (passive) absorption is possible. Cell cultures mimicking the gastrointestinal tract such as the CACO-2 cultures have the advantage of taking into account other transport mechanism including paracellular and carrier-mediated uptake but are lower throughput and labor-intensive. In this study, the applicability of two high throughput permeability assays namely PAMPA (PSR4p, pION Inc.) and 96-well Caco-2 cell assay (MultiScreen, Millipore) were used to rank drug permeability as well as to predict passive and active drug absorption/secretion for a series of marketed drugs as well as a collection of structurally diverse drug candidates. CACO-2 cells were cultured using MultiScreen hardware over a period of 10 days with the integrity of the cells assessed using transepithelial electrical resistance (TEER) and by the ability of the monolayer to the transport a paracellular marker, sodium fluorescence. Effective permeability (Peff) data were calculated using spectrophotometric data and were binned based on a pre-defined cut-off values as either highly and poorly permeable. A comparison of a well characterized drug training set indicate at least 85% concordance between the data generated from PAMPA and Caco-2 MultiScreen. The values obtained using the MultiScreen approach were also similar to data obtained from the literature using the conventional 21-day Caco-2 cell assay. Differences between PAMPA and CACO-2 ranking were useful indicators of either drug efflux (PAMPA (Peff) > CACO-2 (Peff)) or absorptive transport (CACO-2 (Peff) > PAMPA (Peff)). These results indicate that PAMPA combined with the MultiScreen Caco-2 cell culture may be a useful high throughput screening for predicting passive diffusion and active transport of new drugs.

Probing white dwarf interiors with LISA: periastron precession in eccentric double white dwarfs.

In globular clusters, dynamical interactions give rise to a population of eccentric double white dwarfs detectable by the Laser Interferometer Space Antenna (LISA) up to the Large Magellanic Cloud. In this Letter, we explore the detectability of periastron precession in these systems with LISA. Unlike previous investigations, we consider contributions due to tidal and rotational distortions of the binary components in addition to general relativistic contributions to the periastron precession. At orbital frequencies above a few mHz, we find that tides and stellar rotation dominate, opening up a possibly unique window to the study of the interior and structure of white dwarfs.

Monitoring effects of direct FXa-inhibitors with a new one-step prothrombinase-induced clotting time (PiCT) assay: comparative in vitro investigation with heparin, enoxaparin, fondaparinux and DX 9065a.

UNLABELLED: Selective, direct factor Xa-inhibitors are an emerging new class of antithrombotic drugs but their application in therapy may require adequate laboratory monitoring. A recently introduced assay for monitoring anti-FXa-activity using Russell's viper venom is based on the prothrombinase-induced clotting time (PiCT). In this study comparative data on the performance of PiCT using direct and indirect FXa-inhibitors and measurements of FXa-activity and aPTT are reported. METHODS: Whole citrated blood samples from six healthy volunteers were preincubated with UFH (0-1.0 IU/ml), enoxaparin (0-10 microg/ml), fondaparinux (0-1.0 microg/ ml) and DX 9065a (0-10 microg/ml). PTT, FXa-activity and PiCT in plasma were determined on an ACL coagulation analyzer. PiCT was done with both a 180-sec incubation period before recalcification (2-step), and without (1-step). FXa-activity was based on a chromogenic assay (S2222). RESULTS: FXa-activity was reduced 10-40% by the lowest concentration and by 80-95% by the highest concentration of all agents. At the highest concentration the maximum prolongation in aPTT exceeded 120 sec with UFH, enoxaparin and DX 9065a but was only marginally prolonged (increase 39 +/- 3 sec) by fondaparinux. Prolongation in PiCT was significantly different when the two PiCT-methods were compared e.g. at 1.0 IU/ml UFH, 137 +/- 25 (1-step) vs. 187 +/- 32 sec (2-step) (p < 0.001); at 10 microg/ml enoxaparin 83 +/- 9 sec vs. 130 +/- 15 (p < 0.001); at 1.0 microg/ml fondaparinux 48 +/- 5 sec vs. 73 +/- 9 sec (p < 0.001); at 10 microg/ml DX 9065a 28 +/- 3 vs. 25 +/- 2 (p < 0.01), respectively. The 2-step method was unable to detect a prolongation in the effects of DX 9065a, and at concentrations < 5 microg/ml clotting times were even shorter (e.g. 13 +/- 1 sec at 1.0 microg/ml DX 9065a) than the baseline readings (20 +/- 2 sec). CONCLUSIONS: Only the 1-step method (i.e. without pre-incubation) seems suitable for the monitoring of new, direct selective FXa-inhibitors.

Inhibition of TNF-alpha production by pentoxifylline does not prevent endotoxin-induced decrease in serum IGF-I.

Sepsis and endotoxin (LPS or lipopolysaccharide) injection induce a state of growth hormone (GH) resistance leading to decreased circulating insulin-like growth factor (IGF)-I. Because the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta inhibit the GH-stimulated IGF-I expression in vitro, it was tempting to speculate that these two cytokines might play an important role in the reduction of circulating IGF-I levels caused by LPS. Pentoxifylline, a methylxanthine usually used in the treatment of peripheral arterial circulatory disorders, has been reported to inhibit TNF-alpha synthesis. The goal of our study was to investigate whether inhibition of TNF-alpha production by pentoxifylline could prevent the decrease in IGF-I and the GH resistance caused by LPS injection. Because previous studies demonstrated that pentoxifylline can reduce muscle catabolism induced by sepsis, we also assessed whether pentoxifylline could exert its anticatabolic effect by preventing the decrease in circulating IGF-I. LPS injection in rats decreased serum IGF-I (-45% at 12 h; P<0.01 vs time 0) and its liver mRNA (-67% at 12 h; P<0.01 vs time 0) while it induced circulating TNF-alpha and IL-1beta and their hepatic expression (P<0.01). Pretreatment of LPS-treated animals by pentoxifylline abolished the LPS-induced rise in serum TNF-alpha (-98% at 90 min; P<0.001 vs LPS alone) and to a lesser extent in serum IL-1beta (-44% at 3 h; not significant vs LPS alone). Despite its dramatic inhibitory effect on TNF-alpha induction, however, pentoxifylline failed to suppress both the decrease in IGF-I and the GH resistance induced by LPS in rats. These results suggest that mediators other than TNF-alpha, in particular IL-1beta or IL-6, could contribute to the GH resistance induced by LPS. They also suggest that the anticatabolic effect of pentoxifylline is not due to prevention of the decline of circulating IGF-I.

The urge to smoke depends on the expectation of smoking.

AIMS: An earlier study (Dols et al. 2000) suggested that cue-induced urge to smoke depends on the expectation of smoking. The present study tried to replicate the findings under stringently controlled conditions. DESIGN: A 2 (context) x 2 (cues) x 6 (trial) within-subject design. Each smoker entered two different contexts; one context predicted the future occurrence of smoking (i.e. one puff of a cigarette) and one context predicted the non-occurrence of smoking. In each context smokers were exposed to smoking cues (i.e. cigarettes and lighter) or not. SETTING: Laboratory at Maastricht University. PARTICIPANTS: Thirty-two daily smokers, smoking at least five cigarettes a day for at least 2 years. MEASUREMENTS: Participants reported their urge to smoke in each context in the presence and absence of smoking cues using a computerized visual analogue scale (VAS). FINDINGS: The results revealed that the urge to smoke was higher in a context in which smoking was expected relative to a context in which it was not expected. As in the previous study the urge-inducing effect of smoking cues was larger in the smoking context than in the non-smoking context. Moreover, smoking cues did not have a significant effect in the non-smoking context. CONCLUSIONS: It was shown that smoking cues elicit craving due mainly to a generated expectation of the occurrence of smoking and less due to salience or long history of associative learning. Theoretical and practical implications of the results are discussed.

Genetic variability of the V1 and V2 env domains of SIVcpz-ant and neutralization pattern of plasma viruses in a chimpanzee infected naturally.

Specific neutralizing epitope changes have been observed in a chimpanzee infected naturally with SIVcpz, which differ from HIV-1 infecting humans. To characterize further these changes, a longitudinal study of env genomic sequence variation of SIVcpz-ant isolates was undertaken in this animal. The V1 and V2 regions of the env were determined to arise from specific recombination events. To determine whether recombination of the V1 and V2 domains was possibly associated with the emergence of neutralization escape viruses, envelope sequences and gene length polymorphisms from PBMC and plasma viral variants were studied over a 7-year period. PBMCs and plasma-associated infectious virus titers as well as plasma RNA viral loads were monitored longitudinally. The first 5 viruses isolated from the plasma were found to be neutralization escape variants. Sequence analysis of their V1 and the V2 regions indicated that a 20 amino acid stretch of the V1 region had undergone recombination and was also associated with the emergence of isolates eliciting strong neutralization responses. These findings support the hypothesis that recombination of the V1 and V2 regions of the envelope play a role in neutralization escape of SIVcpz in chimpanzees infected naturally. Furthermore, the data confirm that the neutralizing antibody response plays an important role in the decline of plasma infectious virus titers in HIV-1 related SIVcpz nonpathogenic infection.

Multiple routes to object matching from different viewpoints: mental rotation versus invariant features.

Previous research has shown that object recognition from different viewpoints often yields strong effects of viewpoint. However, for some objects and experimental paradigms almost complete viewpoint invariance is obtained. This suggests the existence of multiple routes to object recognition. In this study we further strengthen this notion by designing two different conditions using the same experimental paradigm (simultaneous matching) and highly similar objects (multiblock figures). In the first condition (involving a handedness violation), strong effects of viewpoint were obtained. In the second condition (involving an invariance violation), the effects of viewpoint were negligible. This result illustrates that asking under what circumstances object recognition is viewpoint dependent or independent is more fruitful than attempting to show that object recognition is either viewpoint dependent or independent.

Matching multicomponent objects from different viewpoints: mental rotation as normalization?

Novel multicomponent objects were created, and 3 distractors were created for each object by changing the relations between the parts of the object. In a set of 5 experiments, target objects were presented as a motion sequence of multiple views or as a single view. Participants were asked to determine whether an image of an object, viewed from another viewpoint, was the same as the target object. The axis of rotation was aligned with one of the environmental axes or with the main axis of the object. The effects of viewpoint on performance imply that the matching of objects is viewpoint dependent and requires a process of normalization to undo the differences between the perceptual description and the stored object descriptions. The lack of a systematic effect of the axis of rotation, however, suggests that this normalization is best understood as not involving a 3-D transformation of stored 3-D object models.