Stroma AReactive Invasion Front Areas (SARIFA): a novel histopathologic biomarker in colorectal cancer patients and its association with the luminal tumour proportion.

BACKGROUND: Stroma AReactive Invasion Front Areas (SARIFA) is a novel prognostic histopathologic biomarker measured at the invasive front in haematoxylin & eosin (H&E) stained colon and gastric cancer resection specimens. The aim of the current study was to validate the prognostic relevance of SARIFA-status in colorectal cancer (CRC) patients and investigate its association with the luminal proportion of tumour (PoT). METHODS: We established the SARIFA-status in 164 CRC resection specimens. The relationship between SARIFA-status, clinicopathological characteristics, recurrence-free survival (RFS), cancer-specific survival (CSS), and PoT was investigated. RESULTS: SARIFA-status was positive in 22.6% of all CRCs. SARIFA-positivity was related to higher pT, pN, pTNM stage and high grade of differentiation. SARIFA-positivity was associated with shorter RFS independent of known prognostic factors analysing all CRCs (RFS: hazard ratio (HR) 2.6, p = 0.032, CSS: HR 2.4, p = 0.05) and shorter RFS and CSS analysing only rectal cancers. SARIFA-positivity, which was measured at the invasive front, was associated with PoT-low (p = 0.009), e.g., higher stroma content, and lower vessel density (p = 0.0059) measured at the luminal tumour surface. CONCLUSION: Here, we validated the relationship between SARIFA-status and prognosis in CRC patients and provided first evidence for a potential prognostic relevance in the subgroup of rectal cancer patients. Interestingly, CRCs with different SARIFA-status also showed histological differences measurable at the luminal tumour surface. Further studies to better understand the relationship between high luminal intratumoural stroma content and absence of a stroma reaction at the invasive front (SARIFA-positivity) are warranted and may inform future treatment decisions in CRC patients.

Effects of Natural Habitat Loss and Edge Effects on Wild Bees and Pollination Services in Remnant Prairies.

Habitat loss and edge effects resulting from habitat fragmentation are key processes implicated in the decline of bee populations globally. Their effects on wild bees and their pollination services in natural ecosystems are poorly understood, particularly in North American prairies. Our objectives were to determine whether natural habitat loss and edge effects affect bee abundance and pollination services in the Northern Great Plains. We sampled bee abundance and pollination services along transects beginning at road or tree edges in grasslands located in Manitoba, Canada. We measured bee abundance using pan traps, and pollination services using seed-set of Brassica rapa (L.) (Brassicales: Brassicaceae) phytometers. We collected local-scale habitat data by measuring occurrence of flowering species, vegetation type, and vegetation structure, and we measured habitat amount at 1-km radii using GIS analysis of landscape cover. Increasing amounts of habitat loss resulted in declines in bee abundance, and sometimes in pollination services. Results varied with bee life-history: proximity to road edges negatively affected social bees, and litter depth had negative effects on below- ground-nesting bees. Surprisingly, few effects on bees led to corresponding impacts on pollination services. This suggests that conservation of intact natural habitat across the northern Great Plains is important for maintaining resilient and diverse bee communities, but that efforts to conserve bee populations cannot be assumed to also maintain all associated pollination services.

Tracking progress on the health status and service delivery outcomes for neonates and children in the Metro West geographic service area of the Cape Metropole, 2010 - 2015

Background. Monitoring the health status of populations of children is one of the building blocks of the health system. The provision of an indicator dashboard with disaggregated data that are collected over time can be used to gauge the performance of the health system, guide the allocation of resources and prioritise health interventions within districts.Objectives. To determine neonatal and child mortality, morbidity and health service outcomes over a 6-year period in the Metro West geographic service area (GSA) of the Cape Town metropole.Methods. A dashboard with key indicators was developed using existing data.Results. From 2010 to 2015, there was a decrease in the perinatal mortality rate from 31.7 to 24.8 per 1 000 deliveries, and the early neonatal and neonatal mortality rates from 7.8 and 8.6 to 7.0 and 8.2 per 1 000 live births, respectively. The main obstetric causes of early neonatal deaths were antepartum haemorrhage (22 - 24%) and unexplained intrauterine death (13 - 16%); the main neonatal causes were immaturity (17 - 34%), congenital abnormalities (23 - 29%) and hypoxia (23 - 26%). Under-five mortality decreased in 2013 from 25 to 22 per 1 000 live births, with the main causes being neonatal conditions (32%), pneumonia (25%), congenital abnormalities (9%), injuries (8%) and diarrhoea (8%). Fifty percent of child deaths were out of hospital, with pneumonia and diarrhoea accounting for more than half of these. There was an improvement in health service coverage rates in 2015: immunisation <1 year old (99%); measles second dose (85%), pneumococcal third dose (100%) and rotavirus second dose (100%); maternal antiretroviral coverage (90%); HIV testing in mothers (93%); HIV DNA polymerase chain reaction testing in babies (97%); and a decrease in HIV transmission (2%). Exclusive breastfeeding coverage rates at 14 weeks, and vitamin A supplementation at 12 - 59 months, were only 30% and 44%,respectively, across the GSA.Conclusion. There was a decrease in perinatal, early neonatal, infant and under-five mortality in Metro West over the 6 years. Further reductions in under-five mortality will require focusing on interventions to reduce neonatal and out-of-hospital deaths across the service delivery platform. Home visits to at-risk mothers and infants by community health workers could prevent out-of-hospital deaths and improve exclusive breastfeeding and vitamin A coverage. This will require increasing the number of community health workers and broadening their scope of practice

Climate change is catchy--but when will it really hurt?

Concern and general awareness about the impacts of climate change in all sectors of the social-ecological-economic system is growing as a result of improved climate science products and information, as well as increased media coverage of the apparent manifestations of the phenomenon in our society. However, scales of climate variability and change, in space and time, are often confused and so attribution of impacts on various sectors, including the health sector, can be misunderstood and misrepresented. In this review, we assess the mechanistic links between climate and infectious diseases in particular, and consider how this relationship varies, and may vary according to different time scales, especially for aetiologically climate-linked diseases. While climate varies in the medium (inter-annual) time frame, this variability itself may be oscillating and/or trending on cyclical and long-term (climate change) scales because of regional and global scale climate phenomena such as the El-Nino southern oscillation coupled with global-warming drivers of climate change. As several studies have shown, quantifying and modelling these linkages and associations at appropriate time and space scales is both necessary and increasingly feasible with improved climate science products and better epidemiological data. The application of this approach is considered for South Africa, and the need for a more concerted effort in this regard is supported.

Transition from child- to adult-orientated care for children with long-term health conditions: a process, not an event.

Long-term health conditions in childhood include both congenital conditions and acquired diseases. Children with long-term health conditions face issues and potential secondary problems that are different from those of adults with chronic diseases. Transition to adult-orientated care for such children and adolescents is a major challenge. Transition needs to be prepared for and planned. A variety of possible transition models exists, depending on circumstances.

Vital signs for children at triage: a multicentre validation of the revised South African Triage Scale (SATS) for children.

OBJECTIVE: To validate a revised version of the paediatric South African Triage Scale (SATS) against admission as a reference standard and compare the sensitivity of triage using: (i) clinical discriminators; (ii) an age-appropriate physiological composite score; and (iii) a combination of both. METHODS: A prospective cohort study was undertaken validating the revised paediatric SATS against outcome markers of children at six emergency centres during a 2-month period in 2011. The primary outcome marker was the proportion of children admitted. Validity indicators including sensitivity (Se), specificity, positive predictive value and negative predictive value (NPV) were used to estimate the validity. Associated percentages for over-/under-triage were used to further assess practical application of the paediatric SATS. RESULTS: A total of 2 014 children were included. The percentage of hospital admissions increased with an increase in the level of urgency from 5% in the non-urgent patients to 73% in the emergency patients. The data demonstrated that sensitivity increased substantially when using the SATS, which is a combination of clinical discriminators and the Triage Early Warning Score (TEWS) (Se 91.0%, NPV 95.3%), compared with use of clinical discriminators in isolation (Se 57.1%, NPV 86.3%) or the TEWS in isolation (Se 75.6%, NPV 89.1%). CONCLUSION: The results of this study illustrate that the revised paediatric SATS is a safe and robust triage tool.

Phenotypic expression of the 3120+1G>A mutation in non-Caucasian children with cystic fibrosis in South Africa.

INTRODUCTION: Cystic fibrosis (CF) is the most common genetic disorder in Caucasians. Presentation of CF in non-Caucasians is less well studied. OBJECTIVE: This audit was undertaken to determine the phenotypic expression of the 3120+1G>A mutation in black and mixed race children in South Africa. METHODS: A multi-centre retrospective chart review of clinical, laboratory and spirometry data of non-Caucasian CF patients in four CF centres in South Africa was collected. Data was collected at diagnosis and after a five-year follow-up period. Ethical approval was granted for the study. RESULTS: A total of 30 participants were enrolled of whom 14 (47%) were homozygous and 16 (53%) heterozygous for the 3120+1G>A mutation. The mean age of diagnosis was 13 months. Twenty-four (80%) patients had malnutrition (mean weight z-score -3.6) or failure to thrive (77%) at presentation. Twenty (67%) presented with non-specific abdominal symptoms, whilst fifteen (50%) had recurrent respiratory tract infections. Pseudomonas aeruginosa was detected at a mean age of 21 months. The mean FEV1 was 73% predicted (95% CI 54.0-91.1) at study entry and 68% predicted (95% CI 49.74-87.06) at follow-up. CONCLUSION: Failure to thrive and a diagnosis of protein energy malnutrition (kwashiorkor) are the common presenting features of CF in children with the 3120+1G>A mutation. Meconium ileus is a rare presenting feature of CF in black and mixed race children with this deletion in South Africa.

An adapted triage tool (ETAT) at Red Cross War Memorial Children's Hospital Medical Emergency Unit, Cape Town: an evaluation.

OBJECTIVE: To evaluate the efficacy of an adapted Emergency Triage Assessment and Treatment (ETAT) tool at a children's hospital. DESIGN: A two-armed descriptive study. SETTING: Red Cross War Memorial Children's Hospital, Cape Town, South Africa. METHODS: Triage data on 1 309 children from October 2007 and July 2009 were analysed. The number of children in each triage category (red (emergency), orange (urgent or priority) and green (non-urgent)) and their disposal were evaluated. RESULTS: 1. The October 2007 series: 902 children aged 5 days - 15 years were evaluated. Their median age was 20 (interquartile range (IQR) 7 - 50) months, and 58.8% (n=530) were triaged green, 37.5% (n=338) orange and 3.8% (n=34) red. Over 90% of children in the green category were discharged (478/530), while 32.5% of children triaged orange (110/338) and 52.9% of children triaged red (18/34) were admitted. There was a significant increase in admission rate for each triage colour change from green through orange to red after adjustment for age category (risk ratio (RR) 2.6; 95% confidence interval (CI) 2.2 - 3.1). 2. The July 2009 cohort: 407 children with a median age of 22 months (IQR 7 - 53 months) were enrolled. Twelve children (2.9%) were triaged red, 187 (45.9%) orange and 208 (51.1%) green. A quarter (101/407) of the children triaged were admitted: 91.7% (11/12) from the red category and 36.9% (69/187) from the orange category were admitted, while 89.9% of children in the green category (187/208) were discharged. After adjusting for age category, admissions increased by more than 300% for every change in triage acuity (RR 3.2; 95% CI 2.5 - 4.1). CONCLUSIONS: The adapted ETAT process may serve as a reliable triage tool for busy paediatric medical emergency units in resource-constrained countries and could be evaluated further in community emergency settings.

Effect of regional climate warming on the phenology of butterflies in boreal forests in Manitoba, Canada.

We examined the effect of regional climate warming on the phenology of butterfly species in boreal forest ecosystems in Manitoba, Canada. For the period 1971-2004, the mean monthly temperatures in January, September, and December increased significantly, as did the mean temperatures for several concurrent monthly periods. The mean annual temperature increased ≈ 0.05°C/yr over the study period. The annual number of frost-free days and degree-day accumulations increased as well. We measured the response of 19 common butterfly species to these temperature changes with the date of first appearance, week of peak abundance, and the length of flight period over the 33-yr period of 1972-2004. Although adult butterfly response was variable for spring and summer months, 13 of 19 species showed a significant (P < 0.05) increase in flight period extending longer into the autumn. Flight period extensions increased by 31.5 ± 13.9 (SD) d over the study period for 13 butterfly species significantly affected by the warming trend. The early autumn and winter months warmed significantly, and butterflies seem to be responding to this warming trend with a change in the length of certain life stages. Two species, Junonia coenia and Euphydryas phaeton, increased their northerly ranges by ≈ 150 and 70 km, respectively. Warmer autumns and winters may be providing opportunities for range extensions of more southerly butterfly species held at bay by past climatic conditions.

Rate of Pulmonary Function Decline in South African Children with Cystic Fibrosis

Background. Pulmonary function tests (PFTs) objectively measure the extent and progression of cystic fibrosis (CF) lung disease. The rate of lung function decline in developing countries has not previously been studied. Aim. To investigate the average annual rates of pulmonary function decline in South African children with CF from 1999 to 2006. Methodology: The medical records and best PFT over 3-monthly intervals of children attending the CF clinic at Red Cross War Memorial Children's Hospital; Cape Town; were retrospectively reviewed and analysed using the mixed model regression method. Results. A total of 1 139 PFT were recorded on 79 patients; with a median (interquartile range) of 14 (6 - 21) PFTs per patient. The mean (standard error) forced expiratory volume in 1 second (FEV1) at age 6 years was estimated at 73.83 (3.34) per cent predicted with an FEV1 decline of 0.23 (0.43)per annum. FEV1 at age 6 was affected by age at CF diagnosis; genotype; and year of birth. Rate of FEV1 decline was significantly affected by Pseudomonas aeruginosa colonisation and genotype. Conclusions. Although FEV1 at age 6 years was low compared with developed countries; the annual rate of FEV1 decline in South African children with CF was minimal; setting the scene for improved survival in this population

Identification of the correct lumbar level using passive intersegmental motion testing.

This study aimed to assess the accuracy and agreement between examiners when attempting to identify a single lumbar spinal level using passive intersegmental motion testing, a technique commonly used by physical therapists. Thirty-five adults were examined independently by an experienced and a novice clinician. Each examiner was asked to identify and note the interspace between the fifth lumbar vertebra and the first sacral vertebra, and to mark it. The mark was invisible to the second clinician asked to identify the same lumbar interspace. The true level was then identified by fluoroscopic imaging and was correct in 54-57% of cases. Interobserver agreement was poor. A significant learning effect was found for the experienced examiner, with proportionately more correct levels identified during the second part of the study (79%) when compared to the first (31%). The results show that intersegmental motion testing is a relatively unreliable method of identifying the correct spinal level.

Immunisation against plague by transcutaneous and intradermal application of subunit antigens.

We have investigated immunological responses in BALB/c mice following transcutaneous (TC) delivery of fraction 1 (F1) and V subunits from Yersinia pestis in conjunction with an enterotoxin-derived adjuvant (cholera toxin, CT). It was found that two or more TC applications of F1 and V subunits (admixed with cholera toxin) served to elicit significant levels of anti-F1 and V antibodies in the serum of immunised mice. IL-6 secretion from cultured splenocytes derived from immunised mice indicated that a single TC application of F1 and V subunits (admixed with cholera toxin) conferred a cell-mediated response. As compared with intranasal or direct intradermal injection of F1 and V, the numbers of F1/V-specific antibody-forming cells in the spleens of animals immunised by TC application of F1 and V (admixed with CT) was relatively low. It was noted that TC application of F1 and V admixed with CT was very effective for priming responses that were boosted by intranasal or intradermal routes. Similarly, it was found that TC application of F1 and V admixed with CT could be used to efficiently boost pre-existing responses engendered by intradermal injection or intranasal instillation of F1 and V. In order to assess if TC application of F1 and V admixed with CT could protect experimental animals from plague, immunised mice were injected with a virulent strain of Y. pestis. It was found that two TC applications of F1 and V admixed with CT conferred only limited protection against 10(2) MLDs. However, three TC applications of F1 and V admixed with CT conferred solid protection against 10(2) MLDs. Hence we have shown, for the first time, that TC application of F1 and V admixed with CT can protect animals against challenge with a virulent strain of plague causing bacteria. These data suggest that transcutaneous immunisation may be a simple and non-invasive method for immunising individuals against plague.

Polycythemia vera: analysis of DNA from blood granulocytes using comparative genomic hybridization.

BACKGROUND AND OBJECTIVES: The diagnosis of polycythemia vera (PV) is supported by the finding of an abnormal karyotype in patients with erythrocytosis. However, most PV patients have normal marrow cytogenetics at presentation and there is reluctance to use this test routinely. Comparative genomic hybridization (CGH) is a cytogenetic screening technique that analyzes interphase cells. This approach offers practical advantages over conventional cytogenetics and interphase fluorescence in-situ hybridization (IFISH). We have therefore evaluated the diagnostic utility of CGH applied to blood granulocytes in PV. DESIGN AND METHODS: Blood granulocytes from 17 PV patients were analyzed using CGH and the results compared with those from previous conventional cytogenetics and IFISH studies. RESULTS: Three patients had abnormal CGH profiles. One case had gain of 9p. This patient had normal IFISH results using a centromere-9 probe. The second case had complete gain of chromosomes 8 and 9 and the third had complete gain of chromosome 9, all confirmed by IFISH: Cytogenetics had not been performed in two of these cases and had failed in the third. Three cases with 20q deletion according to cytogenetics and/or IFISH, were normal by CGH. The remaining subjects were normal by all methods. INTERPRETATION AND CONCLUSIONS: CGH analysis of blood granulocytes can detect the chromosome gains commonly observed in PV. However, CGH cannot be relied on to detect 20q deletions, which are the most frequent cytogenetic abnormality in PV. Thus, CGH has a role in the diagnosis and follow-up of PV patients, but must be used in conjunction with other methods.

p53 abnormalities in splenic lymphoma with villous lymphocytes.

The incidence and role of p53 abnormalities have not been reported in splenic lymphoma with villous lymphocytes (SLVL), the leukemic counterpart of splenic marginal zone lymphoma. Because p53 abnormalities correlate with progressive and refractory disease in cancer and isochromosome 17q has been described in SLVL, a low-grade lymphoma that behaves aggressively in a minority of patients, this study investigated p53 changes by molecular and immunophenotypic methods in samples from 59 patients. The p53 deletion was analyzed by fluorescence in situ hybridization, and p53 protein expression was assessed by immunocytochemistry in 35 of 59 cases and by flow cytometry in 20 of 35 patients. Ten patients (17%) had a monoallelic p53 loss, 3 (9%) of 35 nuclear protein expression by immunocytochemistry, and 2 (10%) of 20 by flow cytometry. Two patients had both deletion and protein expression. Direct sequencing of all p53 exons was used to delineate mutations in 9 of 11 patients with an identified abnormality. Mutations, both compromising p53 DNA binding, were identified in the 2 patients with deletion and protein accumulation. Kaplan-Meier analysis revealed a significantly worse survival for patients with p53 abnormalities. Although p53 abnormalities are infrequent in SLVL, they underlie a more aggressive disease course and poor prognosis. (Blood. 2001;97:3552-3558)