Evaluation of the nation-wide implementation of ALS home monitoring & coaching: an e-health innovation for personalized care for patients with motor neuron disease.

BACKGROUND: To improve the care for patients with motor neuron disease an e-health innovation for continuous monitoring of disease progression and patients' well-being (ALS H&C) was implemented in 10 multidisciplinary rehabilitation settings. The first aim was to evaluate the implementation of ALS H&C by assessing several implementation outcomes, technology acceptance and usability of the innovation according to the end users. The secondary aim was to explore differences in these outcomes between the teams with sustainable and unsustainable implementation. METHODS: The chosen implementation strategy was a combination of the implementation process model by Grol & Wensing and a participatory action research approach. In three meetings with multidisciplinary project groups the innovation was introduced, the expected barriers/facilitators identified, and action plans to resolve each barrier developed. After a 3-month pilot phase, patients and their healthcare providers were asked to complete an online evaluation survey to assess implementation outcomes, based on Proctor's evaluation framework (i.e., acceptability, feasibility, fidelity, sustainability). Telemedicine technology acceptance was assessed according the technology acceptance model of Chau, and user experiences with the System Usability Scale (SUS). Implementation outcomes of teams with sustainable implementation (continuation after completion of the pilot phase) and unsustainable implementation (discontinuation after the pilot phase) were compared. RESULTS: The implementation outcomes from the patients' perspective (N = 71) were positive; they found ALS H&C to be an acceptable and feasible care concept. Patients' technology acceptance was high, with positive attitudes towards ALS H&C, and positive views on perceived technology control, usefulness, and ease of use. Patients rated their satisfaction with the (web) app on a scale from 1 (not satisfied at all) to 10 (very satisfied) with a 7.0 (median; IQR 1.0). Healthcare providers (N = 76) also found ALS H&C acceptable and appropriate as well, but were less positive about the feasibility and usability of ALS H&C (mean SUS 58.8 [SD 11.3]). ALS H&C has largely been implemented as intended and the implementation was sustainable in 7 teams. Teams who discontinued ALS H&C after the pilot phase (N = 2) had more fidelity issues. CONCLUSIONS: A participatory action research approach supported by theoretical approaches used in implementation science led to a sustainable implementation of ALS H&C in 7 of the participating teams. To improve implementation success, additional implementation strategies to increase feasibility, usability and fidelity are necessary. TRIAL REGISTRATION: Trial NL8542 registered at Netherlands Trial Register (trialregister.nl) on 15th April 2020.

Affinity purification of in vivo assembled whirlin-associated protein complexes from the zebrafish retina.

Mutations in WHRN lead to Usher syndrome type 2d or to non-syndromic hearing impairment. The WHRN-encoded gene product whirlin directly interacts with the intracellular regions of the other two Usher syndrome type 2-associated proteins, usherin and ADGRV1. In photoreceptor cells, this protein complex constitutes fibrous links between the periciliary membrane and the connecting cilium. However, the molecular mechanism(s) of retinal degeneration due to compromised formation and function of the USH2-associated protein complex remains elusive. To unravel this pathogenic mechanism, we isolated and characterized whirlin-associated protein complexes from zebrafish photoreceptor cells. We generated transgenic zebrafish that express Strep/FLAG-tagged Whrna, a zebrafish ortholog of human whirlin, under the control of a photoreceptor-specific promoter. Affinity purification of Strep/FLAG-tagged Whrna and associated proteins from adult transgenic zebrafish retinas followed by mass spectrometry identified 19 novel candidate associated proteins. Pull down experiments and dedicated yeast two-hybrid assays confirmed the association of Whrna with 7 of the co-purified proteins. Several of the co-purified proteins are part of the synaptic proteome, which indicates a role for whirlin in the photoreceptor synapse. Future studies will elucidate which of the newly identified protein-protein interactions contribute to the development of the retinal phenotype observed in USH2d patients. SIGNIFICANCE: Since protein-protein interactions identified using targeted in vitro studies do not always recapitulate interactions that are functionally relevant in vivo, we established a transgenic zebrafish line that stably expresses a Strep/FLAG-tagged ortholog of human whirlin (SF-Whrna) in photoreceptor cells. Affinity purification of in vivo-assembled SF-Whrna-associated protein complexes from retinal lysates followed by mass spectrometry, identified 19 novel candidate interaction partners, many of which are enriched in the synaptic proteome. Two human orthologs of the identified candidate interaction partners, FRMPD4 and Kir2.3, were validated as direct interaction partners of human whirlin using a yeast two-hybrid assay. The strong connection of whirlin with postsynaptic density proteins was not identified in previous in vitro protein-protein interaction assays, presumably due to the absence of a biologically relevant context. Isolation and identification of in vivo-assembled whirlin-associated protein complexes from the tissue of interest is therefore a powerful methodology to obtain novel insight into tissue specific protein-protein interactions and has the potential to improve significantly our understanding of the function of whirlin and the molecular pathogenesis underlying Usher syndrome type 2.

Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2.

Usher syndrome (USH) is a rare, autosomal recessively inherited disorder resulting in a combination of sensorineural hearing loss and a progressive loss of vision resulting from retinitis pigmentosa (RP), occasionally accompanied by an altered vestibular function. More and more evidence is building up indicating that also sleep deprivation, olfactory dysfunction, deficits in tactile perception and reduced sperm motility are part of the disease etiology. USH can be clinically classified into three different types, of which Usher syndrome type 2 (USH2) is the most prevalent. In this review, we, therefore, assess the genetic and clinical aspects, available models and therapeutic developments for USH2. Mutations in USH2A, ADGRV1 and WHRN have been described to be responsible for USH2, with USH2A being the most frequently mutated USH-associated gene, explaining 50% of all cases. The proteins encoded by the USH2 genes together function in a dynamic protein complex that, among others, is found at the photoreceptor periciliary membrane and at the base of the hair bundles of inner ear hair cells. To unravel the pathogenic mechanisms underlying USH2, patient-derived cellular models and animal models including mouse, zebrafish and drosophila, have been generated that all in part mimic the USH phenotype. Multiple cellular and genetic therapeutic approaches are currently under development for USH2, mainly focused on preserving or partially restoring the visual function of which one is already in the clinical phase. These developments are opening a new gate towards a possible treatment for USH2 patients.

Harmonizing light transmission aggregometry in the Netherlands by implementation of the SSC-ISTH guideline.

Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations.

The distribution of total vitamin B12, holotranscobalamin, and the active vitamin B12 fraction in the first 5 weeks postpartum.

INTRODUCTION: Total vitamin B12 levels decrease significantly during pregnancy and recover to normal values within 8-week postpartum. Holotranscobalamin (holoTC) reflects the active part of vitamin B12 and has been shown to remain constant during pregnancy and postpartum. A mechanism of redistribution of vitamin B12 is suggested, with a shift toward holoTC if there is insufficient total vitamin B12 available. Our objective was to examine vitamin B12 deficiency and the active vitamin B12 fraction in postpartum women. METHODS: Total vitamin B12 and holoTC were measured in 171 women within 48 hours (T0) and at 5 weeks (T5) postpartum. Vitamin B12 deficiency was defined as total vitamin B12 < 180 pmol/L or holoTC <32 pmol/L. The active vitamin B12 fraction was defined as holoTC/total vitamin B12. RESULTS: Without intervention, vitamin B12 deficiency based on both serum total vitamin B12 and holoTC changed from 75% and 60%, to respectively 10% and 6% at T5. The fraction of active vitamin B12 was significant higher in vitamin B12 deficient women at both time points and across time (P < .0001 and P = .002). A high fraction of active vitamin B12 was only present in women with total vitamin B12 deficiency at T0. At T5, no high vitamin B12 fraction was found. CONCLUSION: The changes in total vitamin B12 levels seem to be based on a physiological changes rather than vitamin B12 deficiency. The results of this study confirm the hypothesis that a shift toward the metabolic active vitamin B12 (holoTC) occurs in women with insufficient available total vitamin B12.

An added value for the hemoglobin content in reticulocytes (CHr) and the mean corpuscular volume (MCV) in the diagnosis of iron deficiency in postpartum anemic women.

INTRODUCTION: To evaluate the use of reticulocyte hemoglobin content (CHr) and mean corpuscular volume (MCV) to identify truly iron-deficient women with postpartum anemia (PPA), in order to reduce unnecessary iron supplementation. METHODS: Three hundred women with more than 500 mL of blood loss or clinical signs of anemia were divided in a control (Hb ≥ 10.5 g/dL, N = 150) and postpartum anemia group (PPA, Hb < 10.5 g/dL; N = 150). PPA women were given ferrous fumarate for a period of 4 weeks. Efficacy of the treatment was evaluated by comparing Hb, CHr, and MCV at baseline (T(0)) and after 4 weeks (T(4)). Using standard iron deficiency cut off values for MCV (80 fL) and CHr (28 pg) at T(0), we divided the PPA group of both parameters into two subgroups, one suggestive for iron deficiency and one suggestive for noniron deficiency. RESULTS: Irrespective of the parameter or the subdivision, delta Hb concentrations (T(4) -T(0)) showed a similar increase in all PPA subgroups investigated. Both parameters in the PPA subgroups below their respective cut off value showed a significant improvement toward normalization, while the MCV and CHr in the PPA subgroups above their respective cut off value did not show any significant increase. CONCLUSION: Our data suggest that the etiology of the anemia in postpartum anemic women is not always iron deficiency. Using a combination of Hb, MCV and CHr, we increased the stringency to identify truly iron-deficient postpartum anemic women, thereby reducing unnecessary iron supplementation in those women with sufficient iron stores.

New erythrocyte and reticulocyte parameters on CELL-DYN Sapphire: analytical and preanalytical aspects.

INTRODUCTION: Extended RBC and reticulocyte parameters are useful in diagnosing functional iron deficiency and various other clinical conditions. The newest software of the CELL-DYN Sapphire measures extended RBC and reticulocyte parameters. The aims of the present communication were to assess the analytical aspects of these parameters compared with the Siemens Advia 120 analyzer, to study the effect of sample aging and to briefly explore their clinical usefulness in patients with anemia. METHODS: Blood samples were obtained from the routine workload of two hospital laboratories and were run on Siemens Advia and Abbott CELL-DYN Sapphire analyzers in parallel. Data analysis was performed using standard statistics. RESULTS: In total, 1416 patient samples were analyzed. There was close correlation in microcytic and macrocytic RBC (r(2) > 0.97) with small bias. The hypo- and hyperchromic RBC showed reasonable correlations, Advia 120 giving higher values. Reticulocyte MCV showed acceptable agreement, with significant proportional bias (Advia 8-9% higher). CELL-DYN Sapphire MCHr correlated rather well with Advia CHr (r(2) > 0.91) with significant absolute bias. Remarkably, the correlation data differed significantly between the two laboratories. It was found that aging of EDTA samples had significant effect on most of the RBC parameters. CONCLUSIONS: The new RBC parameters of CELL-DYN Sapphire generally correlated well with those of Advia 120, although significant systematic differences were present, particularly in reticulocyte MCH and MCV. These differences necessitate instrument-specific reference ranges and clinical decision values. To minimize preanalytical effects, these parameters should be measured in fresh blood samples.

The influence of adaptogens on ultraweak biophoton emission: a pilot-experiment.

In the present study, the effect of plant adaptogens (Rhodiola rosea and ADAPT-232) on human photon emission has been determined. In a randomized double blind placebo-controlled study, 30 subjects were randomly assigned to three groups: one group (n = 10) taking placebo pills, one group (n = 10) taking Rhodiola rosea (SHR-5) pills and one group (n = 10) taking ADAPT-232 supplements (the latter being a fixed combination of the following three adaptogens: Eleutherococcus senticosus, Rhodiola rosea and Schisandra chinensis). All subjects underwent measurements to determine ultra-weak photon emission (UPE) of the dorsal side of their hands using a photon-counting device, both before and after a week of taking the supplements. In addition, the experienced levels of stress and fatigue (tiredness) were evaluated. After 1 week of supplementation, the Rhodiola group showed a significant decrease (p = 0.027) in photon emission in comparison with the placebo group. Furthermore, after supplementation, a significant decrease (p = 0.049) concerning the experienced level of fatigue in the Rhodiola group was observed compared with the placebo group. No significant changes were observed between the ADAPT-232 and the placebo group.

Relative economic benefits of tactical anthelmintic treatment and urea-molasses block supplementation of Boer goats raised under extensive grazing conditions at Onderstepoort, Pretoria, South Africa.

The potential economic benefits of combining tactical anthelmintic treatment for gastrointestinal nematodes and nutritional supplementation with urea-molasses blocks were examined in Boer goats raised under extensive grazing conditions in the summer rainfall area of South Africa. Eight groups of nine goats were monitored over a 12-month period from 1 October 2002 to 9 October 2003. Ad libitum nutritional supplementation with urea-molasses blocks was provided when the goats were housed at night, during the summer (wet season--December 2002 to February 2003), and/or the winter (dry season--June 2003 to August 2003). All the goats were treated symptomatically for Haemonchus contortus infection when deemed necessary by clinical examination of the conjunctiva for anaemia using the FAMACHA system. Half the groups were tactically treated for gastrointestinal nematodes in mid-summer (28 January 2003). Under the symptomatic treatment, climatic and extensive grazing conditions encountered during the trial, feed supplementation in the winter dry season had the greatest economic benefit and is therefore recommended. Tactical anthelmintic treatment afforded no additional advantage, but the nematode challenge was low.

VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement.

In a prospective follow-up study of the effects of VKORC1 and CYP2C9 genotypes on the anticoagulation status of patients, we assessed the CYP2C9 and the VKORC1 C1173T genotypes of patients during the initial 6 months of phenprocoumon treatment. We used linear regression models and Cox proportional hazard models to determine the effects of the VKORC1 and CYP2C9 genotypes on phenprocoumon dose requirements, overanticoagulation, and time to achieve stability. Allele frequencies of interest within the cohort (N=281) were 40.8% VKORC1 T-1173, 12.8% CYP2C9*2, and 6.9% CYP2C9*3. In patients with the VKORC1 CC genotype, carriers of a CYP2C9 polymorphism needed dosages that were nearly 30% lower than those for CYP2C9*1/*1 patients (P<0.001). In patients with a VKORC1 polymorphism, differences between carriers of a CYP2C9 polymorphism and CYP2C9*1/*1 were far smaller and largely not statistically significant. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (28.7% and 7.2%, respectively). Carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had a strongly increased risk of severe overanticoagulation (hazard ratio (HR) 7.20, P=0.002). Only carriers of a CYP2C9*2 allele had a decreased chance to achieve stability compared to CYP2C9*1/*1 patients (HR 0.61, P=0.004). In conclusion, the VKORC1 genotype modifies the effect of the CYP2C9 genotype on phenprocoumon dose requirements. A combination of polymorphisms of both genotypes is associated with a strongly increased risk of overanticoagulation, whereas delayed stabilization is mainly associated with the CYP2C9 genotype.

A mutation in the gamma actin 1 (ACTG1) gene causes autosomal dominant hearing loss (DFNA20/26).

Linkage analysis in a multigenerational family with autosomal dominant hearing loss yielded a chromosomal localisation of the underlying genetic defect in the DFNA20/26 locus at 17q25-qter. The 6-cM critical region harboured the gamma-1-actin (ACTG1) gene, which was considered an attractive candidate gene because actins are important structural elements of the inner ear hair cells. In this study, a Thr278Ile mutation was identified in helix 9 of the modelled protein structure. The alteration of residue Thr278 is predicted to have a small but significant effect on the gamma 1 actin structure owing to its close proximity to a methionine residue at position 313 in helix 11. Met313 has no space in the structure to move away. Moreover, the Thr278 residue is highly conserved throughout eukaryotic evolution. Using a known actin structure the mutation could be predicted to impair actin polymerisation. These findings strongly suggest that the Thr278Ile mutation in ACTG1 represents the first disease causing germline mutation in a cytoplasmic actin isoform.

Effect of sevoflurane on the ex vivo secretion of TNF-alpha during and after coronary artery bypass surgery.

BACKGROUND AND OBJECTIVE: Sevoflurane has been used for the induction and maintenance of anaesthesia during cardiac surgery owing to its favourable haemodynamic effects. It has been suggested that it offers protection against myocardial ischaemia-reperfusion injury. METHODS: We investigated the effect of sevoflurane on plasma concentrations of tumour necrosis factor-alpha (TNF-alpha) after ex vivo stimulation of whole-blood leukocytes by lipopolysaccharide from 20 patients undergoing coronary artery bypass surgery. The patients were randomized to two groups. Group 1 patients were induced and maintained with sevoflurane; those in Group 2 were anaesthetized with moderate doses of midazolam-sufentanil. Blood samples were drawn from the patients on seven occasions from before induction of anaesthesia until 24 h after skin closure. RESULTS: Plasma concentrations of TNF-alpha were lower in Group 1 than in Group 2 after cessation of cardiopulmonary bypass (median (interquartiles): 25 (21-30) versus 37 (28-79) pg mL(-1); P < 0.05) and 24h after skin closure (196 (100-355) versus 382 (233-718) pg mL(-1); P < 0.05). Postoperatively, two cases of myocardial infarction were recorded, one in each group. Six patients in Group 2 needed continued inotropic support after the first morning to maintain haemodynamic stability versus one patient in Group 1 (P < 0.05). The length of stay in the intensive care unit was significantly lower in Group 1 than in Group 2 (mean +/- SD: 25 +/- 16 versus 54 +/- 30 h; P < 0.05). CONCLUSIONS: Sevoflurane reduces production of TNF-alpha more than total intravenous anaesthesia with midazolam-sufentanil during cardiac surgery. This may reduce cardiac morbidity and the length of stay in the intensive care unit.

Effect of VIMA with sevoflurane versus TIVA with propofol or midazolam-sufentanil on the cytokine response during CABG surgery.

BACKGROUND AND OBJECTIVE: Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). We investigated whether different anaesthetic techniques alter the pro-inflammatory cytokine response to cardiac surgery. METHODS: Thirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomized into three groups of 10 patients. They received either volatile inhalation induction and maintenance (Group 1) or total intravenous anaesthesia with propofol and a minimal dose sufentanil (Group 2) or a moderate dose midazolam-sufentanil (Group 3). The effect of the different anaesthetic techniques on plasma levels of TNF-alpha, IL-6 and IL-8 were examined during and after anaesthesia. RESULTS: Concentrations of TNF-alpha, and IL-8 were comparable in the three groups throughout all measurements. Before the start of cardiopulmonary bypass, IL-6 was significantly higher in Group 1 than in Group 2 (P = 0.009) or Group 3 (P = 0.030), but there were no differences between groups after cardiopulmonary bypass or postoperatively. In the three groups there was a positive correlation between aortic clamping time and serum concentrations of IL-6 (r = 0.54) and IL-8 (r = 0.62). Length of stay in intensive care was correlated with high levels of TNF-alpha (r = 0.78). CONCLUSIONS: Albeit there is difference between the volatile induction and maintenance of the anaesthesia method and the total intravenous anaesthesia technique on the pro-inflammatory cytokine response to surgical stimulation before starting of cardiopulmonary bypass, neither technique can modify the pro-inflammatory cytokine response to ischaemia-reperfusion or extracorporeal circulation.

Dexamethasone decreases the pro- to anti-inflammatory cytokine ratio during cardiac surgery.

BACKGROUND: Cytokines regulate inflammation associated with cardiopulmonary bypass (CPB). Pro-inflammatory cytokines may cause myocardial dysfunction and haemodynamic instability after CPB, but the release of anti-inflammatory cytokines is potentially protective. We studied the effects of dexamethasone on pro- and anti-inflammatory cytokine responses during coronary artery bypass grafting surgery. METHODS: Seventeen patients were studied: nine patients received dexamethasone 100 mg before induction of anaesthesia (group 1) and eight patients acted as controls (group 2). Plasma levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, IL-10 and IL-4 were measured perioperatively. RESULTS: TNF-alpha and IL-8 did not increase significantly in group 1 whereas they increased in group 2 to greater than preoperative values (P<0.05). IL-6 increased in both groups, with lower values in group 1 than in group 2 (P<0.05). IL-10 increased in both groups, with higher values in group 1 (P<0.05). IL-4 did not change in group 1 but decreased in group 2 compared with pre-induction values (P<0.05). After surgery, patients in group 2 had tachycardia, hyperthermia, a greater respiratory rate and higher pulmonary artery pressure, and a longer stay in the intensive care unit. CONCLUSION: Dexamethasone given before cardiac surgery changes circulating cytokines in an anti-inflammatory direction. Postoperative outcome may be improved by inhibition of the systemic inflammatory response.

Haemonchus spp. in sheep farmed under resource-poor conditions in South Africa--effect on haematocrit, conjunctival mucous membrane colour and body condition.

A longitudinal study was conducted on the differential faecal egg counts, haematocrits and body condition scores of sheep belonging to resource-poor farmers at Rust de Winter, Gauteng province, and Kraaipan, North West Province, South Africa. The animals were scored for level of anaemia using the FAMACHA method, an assay for the clinical evaluation of anaemia caused by Haemonchus spp. Periods of higher Haemonchus egg counts occurred from October to March for sheep at Rust de Winter and from September/October to February or April for sheep at Kraaipan. Lower haematocrit values were registered during these periods as was a higher incidence of anaemic conjunctival mucous membrane colour scores compared to the period April to September. No clear relationship between the faecal egg counts and the body condition scores was evident. Although wider application of the FAMACHA system in sheep raised by resource-poor farmers should be investigated, the present study indicates that this method may certainly prove to be a valuable worm control strategy for such livestock owners.

Testing for clinical anaemia caused by Haemonchus spp. in goats farmed under resource-poor conditions in South Africa using an eye colour chart developed for sheep.

A novel clinical assay for the assessment and subsequent treatment of Haemonchus infection in sheep to slow down the development of anthelmintic resistance--the FAMACHA system--has been developed, tested and validated in South Africa. The system is based on a colour chart with five colour categories depicting varying degrees of anaemia that are compared with the colour of the mucous membranes of the eyes of sheep. The animal is then scored from severely anaemic (pale) through anaemic to non-anaemic (red) and those animals considered in danger of succumbing to the effects of haemonchosis are treated. This method was tested in goats farmed under resource-poor conditions in South Africa. Analyses in goats performed during the summers of 1998/1999 and 1999/2000 show a test sensitivity of 76 and 85%, respectively, meaning that the system may be used to identify correctly 76-85% of those animals in need of treatment with an anthelmintic. However, the test specificity remains low at 52-55%. This means that a large proportion of those animals that would not require treatment would in fact be treated. However, when the use of the FAMACHA system is compared with conventional dosing practices where all the animals are treated, using the FAMACHA system would result in a large proportion of the animals being left untreated. The untreated animals are then able to deposit the eggs of anthelmintic-susceptible worms on the pasture, while the treated ones should pass very few ova, given an effective anthelmintic. This maintains a reservoir of susceptible larvae in refugia, and should slow down the development of anthelmintic resistance. The validation of the FAMACHA system for goats for use by resource-poor farmers, which this paper describes, may have wide application in the tropics and subtropics of sub-Saharan Africa and elsewhere.

Behavioural control by simultaneous and serial features in feature-positive and feature-negative discriminations.

Two experiments with rats examined behavioural control by feature stimuli in appetitive conditioning using latency of food-magazine visits as the dependent measure. In experiment 1, a feature-positive (FP) discrimination was presented in which a target stimulus was consistently followed by food when preceded by a serial feature and accompanied by a simultaneous feature, and not followed by food when presented alone. The reverse condition, a feature-negative (FN) discrimination procedure, was in effect in experiment 2. Groups of rats differed in the physical identity of the stimuli used as target and features. In the FP discrimination, all groups came to respond faster on reinforced than on nonreinforced trials. Subsequent tests revealed that the serial feature was responsible for this performance in all groups, whereas the simultaneous feature had not acquired significant control in all groups. Only one half of the groups solved the FN discrimination and they did this on the basis of only the simultaneous feature, which was a relatively intense stimulus in these groups. These results suggest a propensity to use the serial feature in FP discriminations and the simultaneous feature in FN discriminations.

Effects of air temperature, air movement and artificial rain on the heat production of brushtail possums (Trichosurus vulpecula): an exploratory study.

Two groups of six mature brushtail possums (Trichosurus vulpeculu) were housed in two respiration chambers, and their heat production, whole body conductance and lower critical temperatures were measured under a variety of simulated weather patterns. The possums were subjected to ambient temperatures of 30, 20 and 3 degrees C. At 20 and 3 degrees C, the animals were exposed to near still air and light winds (wind speed 0.8 and 6.7 km/h), both with, and without, simulated rain every 8 hours. The lower critical temperature in near still air lies between 7 and 10 degrees C. This temperature increases by about 2, 6 and 8 degrees C respectively for a wind velocity of 6.7 km/h, simulated rain and a combination of the two factors. Weather in New Zealand, especially in the cooler part of the year, will often produce conditions below the lower critical temperature of the thermoneutral zone of possums. This will necessitate significant increases in metabolic rate and hence food consumption or mobilisation of body fat reserves, which if not sustainable will result in the death of possums. Field studies have shown that this is often the case in the wild. It is proposed that this stress may be sufficient to decrease the resistance (especially cell-mediated immunity) of some possums and allow acceleration of the disease process in those infected with Mycobacterium bovis.

[Resistance of small strongyles in an equine stud in South Africa to the benzimidazole anthelmintics]. / Weerstand van klein strongiele van 'n perdestoetery in Suid-Afrika teen die bensimidasool wurmmiddels.

This paper is apparently the first report of resistance of helminths of equids to anthelmintics in South Africa. While a strain of Cyathostominae from an Arab horse stud near Pretoria showed greatly reduced susceptibility to benzimidazoles in faecal egg reduction tests, ivermectin was apparently still unaffected. It is suggested that integrated methods of control such as alternation of horses and ruminants on pasture and mechanical removal of faeces should be used in addition to anthelmintics.