Self-reported beta-lactam allergy in government and private hospitals in Cape Town, South Africa.

BACKGROUND: Up to a quarter of inpatients in high-income countries (HICs) self-report beta-lactam allergy (BLA), which if incorrect,increases the use of alternative antibiotics, worsening individual health outcomes and driving bacterial resistance. In HICs, up to 95% ofself-reported BLAs are incorrect. The epidemiology of BLA in low- and middle-income African countries is unknown. OBJECTIVES: To describe the epidemiology and de-labelling outcomes of self-reported BLA in hospitalised South African (SA) patients. METHODS: Point-prevalence surveys were conducted at seven hospitals (adult, paediatric, government and privately funded, district andtertiary level) in Cape Town, SA, between April 2019 and June 2021. Ward prescription records and in-person interviews were conductedto identify and risk-stratify BLA patients using the validated PEN-FAST tool. De-labelling was attempted at the tertiary allergy clinic atGroote Schuur Hospital. RESULTS: A total of 1 486 hospital inpatients were surveyed (1 166 adults and 320 children). Only 48 patients (3.2%) self-reported a BLA,with a higher rate in private than in government-funded hospitals (6.3% v. 2.8%; p=0.014). Using the PEN-FAST tool, only 10.4% (n=5/48)of self-reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (n=34/48)of self-reported BLA patients, with 64.7% (n=22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling atthe allergy clinic, only 3/36 underwent in vivo testing, with no positive results, and 1 patient proceeded to a negative oral challenge. CONCLUSION: Unlike HICs, self-reported BLA is low among inpatients in SA. The majority of those who self-reported BLA were low risk fortype 1 hypersensitivity, but outpatient de-labelling efforts were largely unsuccessful.

Land management explains major trends in forest structure and composition over the last millennium in California's Klamath Mountains.

SignificanceWe provide the first assessment of aboveground live tree biomass in a mixed conifer forest over the late Holocene. The biomass record, coupled with local Native oral history and fire scar records, shows that Native burning practices, along with a natural lightning-based fire regime, promoted long-term stability of the forest structure and composition for at least 1 millennium in a California forest. This record demonstrates that climate alone cannot account for observed forest conditions. Instead, forests were also shaped by a regime of frequent fire, including intentional ignitions by Native people. This work suggests a large-scale intervention could be required to achieve the historical conditions that supported forest resiliency and reflected Indigenous influence.

Brownfield sites promote biodiversity at a landscape scale.

Repurposing of brownfield sites is often promoted, because it is perceived that protecting the "green belt" limits damage to biodiversity; yet brownfield sites provide scarce habitats with limited disturbance, so conversely are also perceived to be ecologically valuable. Combining data from three national-scale UK biological monitoring schemes with location data on historical landfill sites, we show that species richness is positively associated with both the presence and increasing area of ex-landfill sites for birds, plants and several insect taxa. Assemblage rarity of birds is also positively associated with presence of ex-landfill sites. Species richness associated with ex-landfill sites declined over time for birds and insects but increased over time for plants. These findings suggest that development of brownfield sites may have unintended negative consequences for biodiversity, and imply that to minimise loss of biodiversity, brownfield site repurposing could be targeted towards smaller sites, or sites in areas with a high density of other brownfield sites.

A method for reconstructing temporal changes in vegetation functional trait composition using Holocene pollen assemblages.

Methods of reconstructing changes in plant traits over long time scales are needed to understand the impact of changing environmental conditions on ecosystem processes and services. Although Holocene pollen have been extensively used to provide records of vegetation history, few studies have adopted a functional trait approach that is pertinent to changes in ecosystem processes. Here, for woody and herbaceous fen peatland communities, we use modern pollen and vegetation data combined with pollen records from Holocene deposits to reconstruct vegetation functional dynamics. The six traits chosen (measures of leaf area-to-mass ratio and leaf nutrient content) are known to modulate species' fitness and to vary with changes in ecosystem processes. We fitted linear mixed effects models between community weighted mean (CWM) trait values of the modern pollen and vegetation to determine whether traits assigned to pollen types could be used to reconstruct traits found in the vegetation from pollen assemblages. We used relative pollen productivity (RPP) correction factors in an attempt to improve this relationship. For traits showing the best fit between modern pollen and vegetation, we applied the model to dated Holocene pollen sequences from Fenland and Romney Marsh in eastern and southern England and reconstructed temporal changes in trait composition. RPP adjustment did not improve the linear relationship between modern pollen and vegetation. Leaf nutrient traits (leaf C and N) were generally more predictable from pollen data than mass-area traits. We show that inferences about biomass accumulation and decomposition rates can be made using Holocene trait reconstructions. While it is possible to reconstruct community-level trends for some leaf traits from pollen assemblages preserved in sedimentary archives in wetlands, we show the importance of testing methods in modern systems first and encourage further development of this approach to address issues concerning the pollen-plant abundance relationship and pollen source area.

Surgical management of a retroperitoneal pelvic desmoid tumour involving the sacrifice of external iliac vein and internal iliac vessels.

•Retroperitoneal pelvic desmoid tumours are rare with limited publications.•A rare case of a retroperitoneal pelvic desmoid tumour is discussed.•Excision was challenging requiring the sacrifice of some of the iliac vessels.•No other case reports document a surgical excision requiring this.•To date our patient suffers minimal morbidity and has had no recurrences.

Relation between modern pollen rain, vegetation and climate in northern China: Implications for quantitative vegetation reconstruction in a steppe environment.

Vegetation reconstructions from palaeoecological records depend on adequate understanding of relationships between modern pollen, vegetation and climate. A key parameter for quantitative vegetation reconstructions is the Relative Pollen Productivity (RPP). Differences in both environmental and methodological factors are known to alter the RPP estimated significantly, making it difficult to determine whether the underlying pollen productivity does actually vary, and if so, why. In this paper, we present the results of a replication study for the Bashang steppe region, a typical steppe area in northern China, carried out in 2013 and 2014. In each year, 30 surface samples were collected for pollen analysis, with accompanying vegetation survey using the "Crackles Bequest Project" methodology. Sampling designs differed slightly between the two years: in 2013, sites were located completely randomly, whilst in 2014 sampling locations were constrained to be within a few km of roads. There is a strong inter-annual variability in both the pollen and the vegetation spectra therefore in RPPs, and annual precipitation may be a key influence on these variations. The pollen assemblages in both years are dominated by herbaceous taxa such as Artemisia, Amaranthaceae, Poaceae, Asteraceae, Cyperaceae, Fabaceae and Allium. Artemisia and Amaranthaceae pollen are significantly over-represented for their vegetation abundance. Poaceae, Cyperaceae and Fabaceae seem to have under-represented pollen for vegetation with correspondingly lower RPPs. Asteraceae seems to be well-represented, with moderate RPPs and less annual variation. Estimated Relevant Source Area of Pollen (RSAP) ranges from 2000 to 3000m. Different sampling designs have an effect both on RSAP and RPPs and random sample selection may be the best strategy for obtaining robust estimates. Our results have implications for further pollen-vegetation relationship and quantitative vegetation reconstruction research in typical steppe areas and in other open habitats with strong inter-annual variation.

Controlling working memory with learned instructions.

Many neural network models of cognition rely heavily on the modeler for control over aspects of model behavior, such as when to learn and whether an item is judged to be present in memory. Developing neurocomputational methods that allow these cognitive control mechanisms to be performed autonomously has proven to be surprisingly difficult. Here we present a general purpose framework called GALIS that we believe is amenable to developing a broad range of cognitive control models. Models built using GALIS consist of a network of interacting "regions" inspired by the organization of primate cerebral cortex. Each region is an attractor network capable of learning temporal sequences, and the individual regions not only exchange task-specific information with each other, but also gate the others' functions and interactions. As a result, GALIS models can learn both task-specific content and also the necessary cognitive control procedures (instructions) needed to perform a task in the first place. As an initial test of this approach, we use GALIS to implement a model that is trained simultaneously to perform five versions of the n-Back task. Not only does the resulting n-Back model function correctly, determining when to learn or remove items in working memory, but its accuracy and response times correlate strongly with those of human subjects performing the same task. The n-Back model also makes testable predictions about how human accuracy would be affected by intra-trial changes in n's value. We conclude that GALIS opens a potentially effective pathway toward developing a range of cognitive control models with improved autonomy.

The quality of operative notes at a general surgery unit.

AIM: With the increasingly litigious nature of medical practice, accurate documentation is critical. This is particularly true for operative procedures, and medical councils have identified this and published guidelines to aid surgeons. However, these remain a frequently cited weakness in their defence in medico-legal cases. This study assessed the accuracy of operative notes in a general surgery unit in order to improve our practice. METHOD: An audit of 100 consecutive operative notes was performed, and notes were assessed using the Royal College of Surgeons guidelines. The quality of note-taking of trainees was compared with that of consultant surgeons. A series of operation note pro formas was designed in response to the findings. RESULTS: Of the notes, 66% were completed by trainees. The vast majority of notes had no diagram to demonstrate the surgical findings or illustrate the actions. Specialist surgeons were more likely to describe the actions accurately, but less likely to describe wound closure methods or dressings used. They were also less likely to complete adequate postoperative orders. CONCLUSIONS: This study identifies key areas of weakness in our operative note-keeping. Pro formas should be introduced and made available for commonly performed procedures, and diagrams should be used wherever possible.

Audit of appendicectomies at Frere Hospital, Eastern Cape.

OBJECTIVE: We sought to evaluate the surgical service in the central part of the Eastern Cape Province by reviewing the practice of appendicectomy at Frere Hospital. Specifically, it was our aim to compare the service to those patients who reside in and outside the East London metropolitan area and the outcomes of patients according to their operative finding. PATIENTS AND METHODS: A retrospective study was performed on the medical records of all patients who underwent appendicectomy in a 26-month period. This entailed a thorough review of demographic factors, mode of presentation, operation factors and findings, and the postoperative course. RESULTS: . In the study period, 436 appendicectomies were performed, of which 81% were performed after hours, with a consultant surgeon present in only 6% of cases. Of the group, 51% had a perforated appendix at surgery, and 12% a normal appendix. There was a significantly increased risk of perforation at the extremes of age and in patients from outside East London (63% v. 35% in East London). Those with perforated appendices stayed an average of 7.3 days in hospital, compared with 5 days for those with earlier appendicitis. Of the perforated group, 21% developed a complication, with 86% of all complications occurring in this group. The hospital stays were longer in those perforated appendices that were drained (10.7 days v. 6.1 days), and the rate of complications higher in this subgroup. Four patients died (1%)--all in the perforated group. DISCUSSION: The perforation rate in our setting is significantly higher than other published results. Patients with perforated appendices have longer hospital stays and are more likely to develop significant complications, including re-operation. Patients from outside East London, males and those at the extremes of age are more likely to have perforated appendices. This study lends little support to the advocates of drains, and recommends the use of non-absorbable sutures for skin closure. The majority of procedures are performed after hours by medical officers and registrars, but there is no evidence to suggest that this practice be altered, particularly in light of the high perforation rate. The main factor identified as contributing to the huge discrepancy between perforation rates (and hence morbidity) is delay in presentation to the operating surgeon for the region. Patient factors may contribute, but service factors are regarded as significant, including poor access to clinics and hospitals, transport and ambulance services, and the expertise of the referring medical staff. The need to improve the quality of patient care in the under-serviced rural areas of the Eastern Cape is highlighted.

Temporary closure of open abdominal wounds by the modified sandwich-vacuum pack technique.

BACKGROUND: A 5-year experience with the modified sandwich-vacuum pack technique, using an opened 3-litre urological irrigation bag and continuous high-pressure suction, for temporary abdominal wall closure is presented. METHODS: The records of all patients who underwent temporary abdominal wall closure using this method from January 1996 to December 2000 were examined. RESULTS: The modified sandwich-vacuum pack was used 139 times in 55 patients. Forty patients sustained penetrating trauma while 15 patients sustained blunt trauma. The mean Injury Severity Score was 19 (range 9-34). Intra-abdominal sepsis (51 per cent) was the commonest indication, followed by visceral oedema (18 per cent), abdominal compartment syndrome (16 per cent), intra-abdominal packing (11 per cent) and abdominal wall defects (4 per cent). The overall mortality rate was 45 per cent. Three patients (5 per cent) developed enterocutaneous fistula. Of the 30 survivors, 16 patients underwent primary fascial closure. CONCLUSION: The modified sandwich-vacuum pack technique of temporary abdominal wall closure is easy and rapid, cost effective and provides an effective means of containing abdominal wall contents.

The cocktail party phenomenon revisited: the importance of working memory capacity.

Wood and Cowan (1995) replicated and extended Moray's (1959) investigation of the cocktail party phenomenon, which refers to a situation in which one can attend to only part of a noisy environment, yet highly pertinent stimuli such as one's own name can suddenly capture attention. Both of these previous investigations have shown that approximately 33% of subjects report hearing their own name in an unattended, irrelevant message. Here we show that subjects who detect their name in the irrelevant message have relatively low working-memory capacities, suggesting that they have difficulty blocking out, or inhibiting, distracting information.

A mouse model of familial porphyria cutanea tarda.

Approximately one-third of patients with porphyria cutanea tarda (PCT), the most common porphyria in humans, inherit a single mutant allele of the uroporphyrinogen decarboxylase (URO-D) gene. PCT associated with URO-D mutations is designated familial PCT. The phenotype is characterized by a photosensitive dermatosis with hepatic accumulation and urinary excretion of uroporphyrin and hepta-carboxylic porphyrins. Most heterozygotes for URO-D mutations do not express a porphyric phenotype unless hepatic siderosis is present. Hemochromatosis gene (HFE) mutations are frequently found when the phenotype is expressed. We used homologous recombination to disrupt one allele of murine URO-D. URO-D(+/-) mice had half-wild type (wt) URO-D protein and enzymatic activity in all tissues but did not accumulate hepatic porphyrins, indicating that half-normal URO-D activity is not rate limiting. When URO-D(+/-) mice were injected with iron-dextran and given drinking water containing delta-aminolevulinic acid for 21 days, hepatic porphyrins accumulated, and hepatic URO-D activity was reduced to 20% of wt. We bred mice homozygous for an HFE gene disruption (HFE(-/-)) to URO-D(+/-) mice, generating mice with the URO-D(+/-)/HFE(-/-) genotype. These animals developed a porphyric phenotype by 14 weeks of age without ALA supplementation, and URO-D activity was reduced to 14% of wt. These data indicate that iron overload alone is sufficient to reduce URO-D activity to rate-limiting levels in URO-D(+/-) mice. The URO-D(+/-) mouse serves as an excellent model of familial PCT and affords the opportunity to define the mechanism by which iron influences URO-D activity.

Differential haemodynamic effects of endothelin receptor antagonist, SB 209670, in conscious hypertensive and normotensive rats.

Endothelin has been implicated in the pathogenesis and/or maintenance of hypertension. Endothelin receptor antagonists lower blood pressure in the spontaneously hypertensive rat (SHR), but the regional haemodynamic effects of such drugs in the SHR remain unknown. The aim of this study was to examine the regional haemodynamic effects of the endothelin receptor antagonist, (+/-)-(1S,2R,3S)-3-(2-carboxymethoxy-4-methoxyphenyl)-1-(3, 4-methylenedioxyphenyl)-5-(prop-1-yloxy)-indane-2-carboxylic acid (SB 209670), in SHR and Wistar-Kyoto (WKY) rats. Rats underwent a two-stage operation for implantation of Doppler flow probes and intravascular catheters. Recordings were made of mean arterial pressure (MAP), heart rate (HR) and renal (Ren), mesenteric (Mes) and hindquarters (HQ) blood flows and conductances (Cond). SHR and WKY received 4.5 h infusions of saline or SB 209670 (5 mg/kg priming dose+1 or 5 mg/kg/h, i.v.). SB 209670 lowered blood pressure in both SHR (-23+/-2 mm Hg) and WKY rats (-13+/-1 mm Hg). In addition, a lower dose infusion of SB 209670 also had an antihypertensive effect in SHR (-15+/-5 mm Hg). In SHRs which received the higher dose of antagonist, Ren, Mes and HQ Cond were significantly increased as was the HQ Cond in a low-dose group. In WKY rats, SB 209670 decreased Ren blood flow whilst increasing Mes and HQ blood flows and Cond. SB 209670 also attenuated the regional vasoconstrictor effects of endothelin-1, except in the Mes circulation in SHR. This study illustrates that SB 209670 causes differential haemodynamic effects in SHR and WKY rats. In SHR, the antihypertensive effect of SB 209670 was accompanied by a generalised vasodilatation in the Ren, Mes and HQ vascular beds. In WKY rats, the hypotensive effect of SB 209670 was accompanied by Mes and HQ vasodilatation, but with Ren vasoconstriction. Thus, endothelin is involved in the maintenance of blood pressure and vascular tone in both SHR and WKY rats, but the haemodynamic profiles of these effects differ between the two strains.

Targeting genes for self-excision in the germ line.

A procedure is described that directs the self-induced deletion of DNA sequences as they pass through the male germ line of mice. The testes-specific promoter from the angiotensin-converting enzyme gene was used to drive expression of the Cre-recombinase gene. Cre was linked to the selectable marker Neor, and the two genes flanked with loxP elements. This cassette was targeted to the Hoxa3 gene in mouse ES cells that were in turn used to generate chimeric mice. In these chimeras, somatic cells derived from the ES cells retained the cassette, but self-excision occurred in all ES-cell-derived sperm.

Protein kinase C regulates the nuclear localization of diacylglycerol kinase-zeta.

Diacylglycerol kinases (DGKs) terminate signalling from diacylglycerol by converting it to phosphatidic acid. Diacylglycerol regulates cell growth and differentiation, and its transient accumulation in the nucleus may be particularly important in this regulation. Here we show that a fraction of DGK-zeta is found in the nucleus, where it regulates the amount of nuclear diacylglycerol. Reducing nuclear diacylglycerol levels by conditional expression of DGK-zeta attenuates cell growth. The nuclear-localization signal of DGK-zeta is located in a region that is homologous to the phosphorylation-site domain of the MARCKS protein. This is, to our knowledge, the first evidence that this domain, which is a major target for protein kinase C, can localize a protein to the nucleus. Two isoforms of protein kinase C, but not others, regulate the localization of DGK-zeta. Our results define a cycle in which diacylglycerol activates protein kinase C, which then regulates the metabolism of diacylglycerol by alternating the intracellular location of DGK-zeta. This may be a general mechanism to control mitogenic signals that depend on nuclear diacylglycerol.

Effects of the CCK(A) receptor antagonists SR 27897B and PD140548 on baroreflex function in conscious rats.

Since the cardiovascular effects of cholecystokinin (CCK) seem to particularly involve the A ('peripheral') subtype of CCK (CCK[A]) receptor, we examined the actions of two novel, highly selective CCK(A) receptor antagonists, PD140548 (N-alpha-methyl-N[(tricyclo[3.3.1.1(3,7)]dec-2-yloxy)carbony l]-L-tryptophyl]-D-3-(phenylmethyl)-beta-alanine) and SR 27897B (1-[[2-(4-(2-chlorophenyl)thiazol-2-yl)aminocarbonyl]acetic acid) on CCK-induced alterations in blood pressure and heart rate, and on the baroreceptor reflex in the conscious, instrumented rat. CCK (2 microg, i.v.) produced a pressor response and biphasic effects on heart rate involving an initial bradycardia followed by a pronounced tachycardia. Administration of PD140548 (10 mg/kg, i.v.) and SR 27897B (0.6 mg/kg, i.v.) significantly inhibited the pressor effects of CCK (35 and 47%, respectively), whilst reversing the bradycardic responses to a tachycardia. The CCK(A) receptor antagonists had different effects on the baroreceptor heart rate reflex since only PD140548 caused a significant increase in the gain or sensitivity of the reflex. This effect of PD140548 on gain is likely to occur via a central mechanism and may reflect the increased lipophilicity of PD140548 relative to SR 27897B. Overall, these investigations provide new evidence for the involvement of the CCK(A) receptor in cardiovascular regulation.

Role of the brain renin-angiotensin system in the maintenance of blood pressure in conscious spontaneously hypertensive and sinoaortic baroreceptor-denervated rats.

1. Evidence suggesting an involvement of the brain renin-angiotensin system (RAS) in the development/maintenance of hypertension in spontaneously hypertensive rats (SHR) relies, in part, on early experimental data reporting centrally mediated antihypertensive effects of saralasin. However, recent data using non-peptide AT1 receptor antagonists does not always support this theory because these compounds usually do not lower blood pressure when given centrally. 2. In the present study we have re-assessed the central effects of saralasin in conscious SHR as well as in sinoaortic baroreceptor-denervated (SAD) rats. Both of these models exhibit heightened sensitivity to the central pressor effects of angiotensin II (AngII) and, thus, any potential antihypertensive activity would provide functional evidence of activated brain RAS mechanisms in these models. 3. In SHR, saralasin failed to lower mean arterial pressure (MAP) when given intracerebroventricularly (i.c.v.) as bolus or infusion doses that blocked the centrally mediated pressor effect of AngII. 4. In SAD rats, there was a marked impairment of the baroreceptor-heart rate reflex function and enhanced centrally mediated pressor responses to AngII. However, i.c.v. saralasin infusions again did not alter MAP. 5. Collectively, these results suggest that the central RAS is not involved in the maintenance of MAP in SHR and SAD rats, both of which are models exhibiting a functional hyperresponsiveness to AngII.

Alpha toxin from Clostridium perfringens induces proinflammatory changes in endothelial cells.

Alpha toxin from Clostridium perfringens type A, a phospholipase C, has been implicated in many of the localized and systemic features of gas gangrene. We demonstrated that human endothelial cells synthesize two vasoactive lipids, platelet-activating factor (PAF) and prostacyclin, in response to alpha toxin treatment. The stimulated synthesis of PAF required the enzymatic activity of the toxin and subsequent protein kinase C activation. Alpha toxin-treated endothelial cells accumulated the products of the phospholipase C reaction, diacylglycerol and ceramide, and exhibited a decrease in the enzymatic precursors phosphatidylcholine and sphingomyelin. Furthermore, the temporal accumulation of PAF depended on the concentration of the toxin in the overlying medium and was blocked in the presence of a neutralizing antibody. The cultured endothelial cells also exhibited enhanced neutrophil adhesion in response to alpha toxin which was mediated through the PAF receptor and P-selectin. P-selectin expression by endothelial cells and extravascular neutrophil accumulation were also observed in tissue sections from alpha toxin-injected Sprague-Dawley rats. These endothelial cell-mediated processes are important in maintaining vascular homeostasis and, when activated in a dysregulated manner by C. perfringens alpha toxin, may contribute to localized and systemic manifestations of gas gangrene including enhanced vascular permeability, localized neutrophil accumulation, and myocardial dysfunction.