Ecology, water and enterprise development in selected rural South African towns

South Africa’s imperatives for rural development and job creation raise the question whether water abundance in a region results in improved enterprise development in rural towns. The enterprise assemblages of 2 groups of towns, a river group from water-abundant areas and a Great Karoo group from the arid heartland of South Africa, were examined using a variety of different methods based on approaches used frequently in ecology. The comparisons included factors such as the ages of towns, clusters of towns and enterprise diversity. Although some hints were obtained that water abundance favoured enterprise development positively, the null hypothesis that water abundance would not influence enterprise development positively could not be rejected.Several lessons were learnt: there are regularities in enterprise  development whether in water-abundant or water-scarce areas; these regularities are understandable in terms of recent economic  thinking as well as old concepts such as ‘threshold populations’; money is the basic driver of enterprise success and more enterprises in one town than another reflects differences in the amount of money entering and/or circulating in towns; ‘entrepreneurial space’ in certain business sectors is used very effectively by ‘run-of-the-mill entrepreneurs’; towns will give rise to different types of businesses and in proportion to the needs of the customers present in the towns; the degree of utilisation of certain business sectors differs statistically significantly between clusters of towns; and approaches and tools used effectively in the study of ecology offer many advantages for the study of enterprise development dynamics in towns, which are ‘enterprise ecosystems’. The mere presence of abundant water in a region does not automatically translate into enterprise development in towns. Entrepreneurial development should focus on ways and means to increase the flow of money into towns and not merely on its circulation within communities.Keywords: South African towns; enterprise development; enterprise ecology; entrepreneurial space; water-abundant areas; water-scarce area

Assessing the healthcare resource use associated with inappropriate prescribing of inhaled corticosteroids for people with chronic obstructive pulmonary disease (COPD) in GOLD groups A or B:an observational study using the Clinical Practice Research Datalink (CPRD)

Abstract Background Recent recommendations from the Global Initiative for Chronic Obstructive Lung Disease (GOLD) position inhaled corticosteroids (ICS) for use in chronic obstructive pulmonary disease (COPD) patients experiencing exacerbations (≥ 2 or ≥ 1 requiring hospitalisation); i.e. GOLD groups C and D. However, it is known that ICS is frequently prescribed for patients with less severe COPD. Potential drivers of inappropriate ICS use may be historical clinical guidance or a belief among physicians that intervening early with ICS would improve outcomes and reduce resource use. The objective of this study was to compare healthcare resource use in the UK for COPD patients in GOLD groups A and B (0 or 1 exacerbation not resulting in hospitalisation) who have either been prescribed an ICS-containing regimen or a non-ICS-containing regimen. Methods Linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database were used. For the study period (1 July 2005 to 30 June 2015) a total 4009 patients met the inclusion criteria; 1745 receiving ICS-containing therapy and 2264 receiving non-ICS therapy. Treatment groups were propensity score-matched to account for potential confounders in the decision to prescribe ICS, leaving 1739 patients in both treatment arms. Resource use was assessed in terms of frequency of healthcare practitioner (HCP) interactions and rescue therapy prescribing. Treatment acquisition costs were not assessed. Results Results showed no benefit associated with the addition of ICS, with numerically higher all-cause HCP interactions (72,802 versus 69,136; adjusted relative rate: 1.07 [p = 0.061]) and rescue therapy prescriptions (24,063 versus 21,163; adjusted relative rate: 1.05 [p = 0.212]) for the ICS-containing group compared to the non-ICS group. Rate ratios favoured the non-ICS group for eight of nine outcomes assessed. Outcomes were similar for subgroup analyses surrounding potential influential parameters, including patients with poorer lung function (FEV1 <  50% predicted), one prior exacerbation or elevated blood eosinophils. Conclusions These data suggest that ICS use in GOLD A and B COPD patients is not associated with a benefit in terms of healthcare resource use compared to non-ICS bronchodilator-based therapy; using ICS according to GOLD recommendations may offer an opportunity for improving patient care and reducing resource use

Co-designing a dashboard of predictive analytics and decision support to drive care quality and client outcomes in aged care: a mixed-method study protocol

IntroductionThere is a clear need for improved care quality and quality monitoring in aged care. Aged care providers collect an abundance of data, yet rarely are these data integrated and transformed in real-time into actionable information to support evidence-based care, nor are they shared with older people and informal caregivers. This protocol describes the co-design and testing of a dashboard in residential aged care facilities (nursing or care homes) and community-based aged care settings (formal care provided at home or in the community). The dashboard will comprise integrated data to provide an 'at-a-glance' overview of aged care clients, indicators to identify clients at risk of fall-related hospitalisations and poor quality of life, and evidence-based decision support to minimise these risks. Longer term plans for dashboard implementation and evaluation are also outlined.MethodsThis mixed-method study will involve (1) co-designing dashboard features with aged care staff, clients, informal caregivers and general practitioners (GPs), (2) integrating aged care data silos and developing risk models, and (3) testing dashboard prototypes with users. The dashboard features will be informed by direct observations of routine work, interviews, focus groups and co-design groups with users, and a community forum. Multivariable discrete time survival models will be used to develop risk indicators, using predictors from linked historical aged care and hospital data. Dashboard prototype testing will comprise interviews, focus groups and walk-through scenarios using a think-aloud approach with staff members, clients and informal caregivers, and a GP workshop.Ethics and disseminationThis study has received ethical approval from the New South Wales (NSW) Population & Health Services Research Ethics Committee and Macquarie University's Human Research Ethics Committee. The research findings will be presented to the aged care provider who will share results with staff members, clients, residents and informal caregivers. Findings will be disseminated as peer-reviewed journal articles, policy briefs and conference presentations

Quantum Criticality in Heavy Fermion Metals

Quantum criticality describes the collective fluctuations of matter undergoing a second-order phase transition at zero temperature. Heavy fermion metals have in recent years emerged as prototypical systems to study quantum critical points. There have been considerable efforts, both experimental and theoretical, which use these magnetic systems to address problems that are central to the broad understanding of strongly correlated quantum matter. Here, we summarize some of the basic issues, including i) the extent to which the quantum criticality in heavy fermion metals goes beyond the standard theory of order-parameter fluctuations, ii) the nature of the Kondo effect in the quantum critical regime, iii) the non-Fermi liquid phenomena that accompany quantum criticality, and iv) the interplay between quantum criticality and unconventional superconductivity.Comment: (v2) 39 pages, 8 figures; shortened per the editorial mandate; to appear in Nature Physics. (v1) 43 pages, 8 figures; Non-technical review article, intended for general readers; the discussion part contains more specialized topic

Concomitant malaria among visceral leishmaniasis in-patients from Gedarif and Sennar States, Sudan: a retrospective case-control study

In areas where visceral leishmaniasis (VL) and malaria are co-endemic, co-infections are common. Clinical implications range from potential diagnostic delay to increased disease-related morbidity, as compared to VL patients. Nevertheless, public awareness of the disease remains limited. In VL-endemic areas with unstable and seasonal malaria, vulnerability to the disease persists through all age-groups, suggesting that in these populations, malaria may easily co-occur with VL, with potentially severe clinical effects

Circulating endothelial cells in oncology: pitfalls and promises

Adequate blood supply is a prerequisite in the pathogenesis of solid malignancies. As a result, depriving a tumour from its oxygen and nutrients, either by preventing the formation of new vessels, or by disrupting vessels already present in the tumour, appears to be an effective treatment modality in oncology. Given the mechanism by which these agents exert their anti-tumour activity together with the crucial role of tumour vasculature in the pathogenesis of tumours, there is a great need for markers properly reflecting its impact. Circulating endothelial cells (CEC), which are thought to derive from damaged vasculature, may be such a marker. Appropriate enumeration of these cells appears to be a technical challenge. Nevertheless, first studies using validated CEC assays have shown that CEC numbers in patients with advanced malignancies are elevated compared to healthy controls making CEC a potential tool for among other establishing prognosis and therapy-induced effects. In this review, we will address the possible clinical applications of CEC detection in oncology, as well as the pitfalls encountered in this process

Using dissolved H₂O in rhyolitic glasses to estimate palaeo-ice thickness during a subglacial eruption at Bláhnúkur(Torfajökull, Iceland)

The last decade has seen the refinement of a technique for reconstructing palaeo-ice thicknesses based on using the retained H2O and CO2 content in glassy eruptive deposits to infer quenching pressures and therefore ice thicknesses. The method is here applied to Bláhnúkur, a subglacially erupted rhyolitic edifice in Iceland. A decrease in water content from ~0.7 wt.% at the base to ~0.3 wt.% at the top of the edifice suggests that the ice was 400 m thick at the time of the eruption. As Bláhnúkur rises 350 m above the surrounding terrain, this implies that the eruption occurred entirely within ice, which corroborates evidence obtained from earlier lithofacies studies. This paper presents the largest data set (40 samples) so far obtained for the retained volatile contents of deposits from a subglacial eruption. An important consequence is that it enables subtle but significant variations in water content to become evident. In particular, there are anomalous samples which are either water-rich (up to 1 wt.%) or water-poor (~0.2 wt.%), with the former being interpreted as forming intrusively within hyaloclastite and the latter representing batches of magma that were volatile-poor prior to eruption. The large data set also provides further insights into the strengths and weaknesses of using volatiles to infer palaeo-ice thicknesses and highlights many of the uncertainties involved. By using examples from Bláhnúkur, the quantitative use of this technique is evaluated. However, the relative pressure conditions which have shed light on Bláhnúkur’s eruption mechanisms and syn-eruptive glacier response show that, despite uncertainties in absolute values, the volatile approach can provide useful insight into the mechanisms of subglacial rhyolitic eruptions, which have never been observed

Mapping the Interactions between a RUN Domain from DENND5/Rab6IP1 and Sorting Nexin 1

Eukaryotic cells have developed a diverse repertoire of Rab GTPases to regulate vesicle trafficking pathways. Together with their effector proteins, Rabs mediate various aspects of vesicle formation, tethering, docking and fusion, but details of the biological roles elicited by effectors are largely unknown. Human Rab6 is involved in the trafficking of vesicles at the level of Golgi via interactions with numerous effector proteins. We have previously determined the crystal structure of Rab6 in complex with DENND5, alternatively called Rab6IP1, which comprises two RUN domains (RUN1 and RUN2) separated by a PLAT domain. The structure of Rab6/RUN1-PLAT (Rab6/R1P) revealed the molecular basis for Golgi recruitment of DENND5 via the RUN1 domain, but the functional role of the RUN2 domain has not been well characterized. Here we show that a soluble DENND5 construct encompassing the RUN2 domain binds to the N-terminal region of sorting nexin 1 by surface plasmon resonance analyses

The role of LINEs and CpG islands in dosage compensation on the chicken Z chromosome

Most avian Z genes are expressed more highly in ZZ males than ZW females, suggesting that chromosome-wide mechanisms of dosage compensation have not evolved. Nevertheless, a small percentage of Z genes are expressed at similar levels in males and females, an indication that a yet unidentified mechanism compensates for the sex difference in copy number. Primary DNA sequences are thought to have a role in determining chromosome gene inactivation status on the mammalian X chromosome. However, it is currently unknown whether primary DNA sequences also mediate chicken Z gene compensation status. Using a combination of chicken DNA sequences and Z gene compensation profiles of 310 genes, we explored the relationship between Z gene compensation status and primary DNA sequence features. Statistical analysis of different Z chromosomal features revealed that long interspersed nuclear elements (LINEs) and CpG islands are enriched on the Z chromosome compared with 329 other DNA features. Linear support vector machine (SVM) classifiers, using primary DNA sequences, correctly predict the Z compensation status for >60% of all Z-linked genes. CpG islands appear to be the most accurate classifier and alone can correctly predict compensation of 63% of Z genes. We also show that LINE CR1 elements are enriched 2.7-fold on the chicken Z chromosome compared with autosomes and that chicken chromosomal length is highly correlated with percentage LINE content. However, the position of LINE elements is not significantly associated with dosage compensation status of Z genes. We also find a trend for a higher proportion of CpG islands in the region of the Z chromosome with the fewest dosage-compensated genes compared with the region containing the greatest concentration of compensated genes. Comparison between chicken and platypus genomes shows that LINE elements are not enriched on sex chromosomes in platypus, indicating that LINE accumulation is not a feature of all sex chromosomes. Our results suggest that CpG islands are not randomly distributed on the Z chromosome and may influence Z gene dosage compensation status

Late Replicating Domains Are Highly Recombining in Females but Have Low Male Recombination Rates: Implications for Isochore Evolution

In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in analysis of GC content and rates of evolution