α-intercalated cells defend the urinary system from bacterial infection

{alpha}–Intercalated cells (A-ICs) within the collecting duct of the kidney are critical for acid-base homeostasis. Here, we have shown that A-ICs also serve as both sentinels and effectors in the defense against urinary infections. In a murine urinary tract infection model, A-ICs bound uropathogenic E. coli and responded by acidifying the urine and secreting the bacteriostatic protein lipocalin 2 (LCN2; also known as NGAL). A-IC–dependent LCN2 secretion required TLR4, as mice expressing an LPS-insensitive form of TLR4 expressed reduced levels of LCN2. The presence of LCN2 in urine was both necessary and sufficient to control the urinary tract infection through iron sequestration, even in the harsh condition of urine acidification. In mice lacking A-ICs, both urinary LCN2 and urinary acidification were reduced, and consequently bacterial clearance was limited. Together these results indicate that A-ICs, which are known to regulate acid-base metabolism, are also critical for urinary defense against pathogenic bacteria. They respond to both cystitis and pyelonephritis by delivering bacteriostatic chemical agents to the lower urinary system

Organizational and Leadership Implications for Transformational Development

Transformational development is a concept of change that originated in the Christian context but has now become generally used in the work of both secular and faith-based organizations. The growing use of the concept by organizations that are fundamentally different has naturally led to some confusion about what the concept means and what it takes to effectively implement it. In this article, we describe the key features of the concept and how they are important in determining the organizational requirements for its effective implementation. Drawing on a few cases, the paper highlights the centrality of faith in transformational development work

“That Looks Like Me or Something i Can Do”: Affordances and Constraints in the Online Identity Work of US LGBTQ+ Millennials

This article examines how search engines and social networking sites enable and constrain the identity-related information practices of lesbian, gay, bisexual, transgender,and queer (LGBTQ+) millennials in the United States

Fibre reinforcement in earthen construction materials

Earthen construction materials are generally brittle with low tensile strength. To deal with this in practice, it is often proposed that reinforcement be added in the form of fibres of various materials. Construction in earthquake-prone parts of the world is thought to benefit from this form of reinforcement, and indeed fibres (in the form of straw) are a key part of many adobe (unit-based) materials. To remain in harmony with the generally excellent environmental credentials of these materials, the reinforcement should be obtained from a natural material ideally obtained as a waste stream, so natural fibres are often chosen. While some studies have been published on the macroscopic mechanical behaviour of reinforced earthen materials, little is known of what is happening at the interface between the soil matrix and the fibres. In this paper, the authors present laboratory-based studies that attempt to fill this gap, covering pull-out behaviour of natural fibres embedded in earthen construction materials, both stabilised and unstabilised

Environmental quality standards for trace metals in the aquatic environment

The scientific basis for the regulation of metals that are potentially toxic to aquatic life is widely debated, especially with respect to bioavailability. Environmetal Quality Standards (EQSs) based on total metal concentrations and laboratory toxicity data for conditions unrepresentative of field situations, may both underprotect and overprotect. The setting of EQSs could be informed by knowledge about dose-response relationships in the field. The work described in this report was performed to attempt to establish dose-response relationships for macroinvertebrates and diatoms in streamwaters contaminated to different extents with trace metals (nickel, copper, zinc, cadmium, lead). Different possible variables were used to express metal concentrations and bioavailability. The results obtained were then used to evaluate different approaches to EQS setting. We carried out field studies of the ecology and chemistry of upland streams, influenced by past mining activity. We conducted field sampling and performed analyses at carefully-chosen field sites, and analysed the data to attempt to establish quantitative relationships between the chemical and ecological variables. The chosen sites were perceived to have several advantages, notably similarity in their physical characteristics, appreciable ranges of water and metal chemistries, and the absence of other pollutants. Therefore they made it possible to explore the effects of differences in streamwater chemistry on ecological response, with few confounding factors. The ecological part of the field work was conducted in Spring 2006, and comprised sampling and enumeration of benthic invertebrates and diatoms. Chemical characterisation of the streamwaters was achieved by repeated sampling during the 6 weeks before the ecological fieldwork. As well as carrying out conventional chemical analyses, we also used analytical speciation techniques (Diffusive Gradients in Thin films, DGT, and the Donnan Membrane Technique, DMT), and applied the WHAM chemical speciation model to calculate free metal ion activities and other variables. We collected separate samples of key invertebrate taxa and analysed them for metal body burdens, and we collected samples of stream bryophytes and analysed them for metals. In another supporting study, we collected water samples from the study sites and used them in laboratory toxicity experiments with an algal and a daphnid species. We carried out a literature review of metal mixture effects, to aid interpretation of field data from those sites (the majority) where more than one metal may exert a toxic effect. We also reviewed methods for setting EQSs. The chemical compositions of the study streams covered appreciable ranges of acidity, alkalinity, total ionic concentration and DOC concentration. The nutrient concentrations were sufficiently low for there to be negligible effects on either macroinvertebrates or diatoms. Suspended particulate matter concentrations were in the range 0 - 50 mg l-1. As expected because of the historical mining activities, most of the streamwaters were contaminated with trace metals, at levels exceeding EQS values. The study sites included several acid streamwaters, some of which were contaminated with trace metals, but all of which had high levels of aluminium. The results of DGT and DMT measurements, and of chemical speciation calculations, indicated that zinc and cadmium are present largely in inorganic forms in the streamwaters, whereas there was appreciable organic complexation of aluminium, copper and lead, and to a lesser extent nickel. The metal contents of both bryophytes and macroinvertebrates varied considerably with streamwater chemistry. The metal contents of both types of organism were approximately predictable using chemical speciation concepts, which is direct evidence that biota respond to the chemistry of the medium. Analysis of the relationships between ecological and chemical variables, and of the results of the laboratory toxicity measurements, led to the following conclusions. 1. Toxic metals were demonstrated to reduce species numbers of both macroinvertebrates and diatoms in the field. 2. Laboratory tests confirmed that 8 of the streamwaters in which field effects were observed contained metals at toxic concentrations. 3. The macroinvertebrate community provides an effective and sensitive tool for detecting metal toxicity. In the study sites, toxicity could be attributed definitely to Al and Zn, and there was some evidence of toxic effects due to H+ and Cu. 4. For diatoms, which were less sensitive than macroinvertebrates, the most likely toxicant was zinc, but cadmium may also have been active. 5. A function combining free metal ion concentrations and pH provided the best solution-based measure of metal toxicity towards macroinvertebrates, because it accounted best for aluminium effects. 6. Toxicity towards diatoms was expressed best, in terms of solution concentrations, by either total dissolved metal concentration or the metal concentration measured by DGT. 7. The field data permitted the formulation and partial parameterisation of the Toxicity Binding Model (TBM), which is based on Biotic Ligand Model principles, but applicable to mixtures of metals. The model permits clear toxicity thresholds to be identified, and quantifies the contributions of different metals to the overall toxicity. 8. Because of the dominant effect of zinc, among the trace metals, the available data did not permit conclusions to be drawn about the effect of chemical speciation on copper or lead toxicity. However, the finding that aluminium effects are best expressed in terms of the free ion, and the promising results from the TBM, imply that speciation-based measures provide the best way to describe the toxic effects of metals in the field. We considered the implications of the results of this work in the assessment and setting of Environmental Quality Standards for metals in freshwaters. The following points can be made. A. The results of the present study add significant weight to the use of bioavailability and chemical speciation in deriving EQSs. B. A full assessment of the effects of toxic metals in contemporary waters requires knowledge about past “pristine” conditions. In the contaminated streamwaters of the present study, dissolved concentrations of trace metals were considerably higher (by 10 to 1000 times) than those estimated for similar uncontaminated sites under pristine conditions. As well as solution concentrations, calculated loadings of biotic ligands with toxic metals can be compared, and when this is done with the TBM it appears that at present-day uncontaminated sites the loadings can be substantial, not much lower than threshold values. C. If bioavailability and chemical speciation are to be used in EQS setting, the biotic ligand approach is currently the best way forward. Although its application relies on calculations, the chemical speciation results can be tested with in situ analytical devices (DGT and DMT), lending robustness to the method. D. There may be regulatory advantages to confining EQS setting to individual metals. However, the results of the present study suggest a significant role of “natural” Al in field toxicity, and this implies that the issue of mixtures should be addressed. This can be done using biotic ligand concepts. E. By showing that metal toxicity operates in the field, with dose-response relationships, and in line with bioavailability and chemical speciation concepts, the study provides support for metals regulation through EQSs. It further shows that targeted fieldwork can provide the information necessary for EQS evaluation and modification

A comparison of acute and long-term management of stroke patients in Barbados and South London

Background: To compare health care utilisation between stroke patients living in a middle-income country with similar patients in a high-income country in terms of the type and amount of health care received following a stroke. Methods: Data were collected from the population-based South London Stroke Register (SLSR) and the Barbados Register of Strokes (BROS) from January 2001 to December 2004. Differences in management and diagnostic procedures used in the acute phase were adjusted for age, sex, ethnic group, living conditions pre-stroke and socio-economic status by multivariable logistic regression. Comparison of subsequent management was made for 3 months and 1 year post-stroke. Results: Patients in BROS were less likely to be admitted to a hospital ward (OR 0.22; 95% CI 0.13-0.37), but the difference for the lower use of brain scans in BROS was smaller (OR 0.62; 95% CI 0.25-1.52). Additional adjustment for stroke severity (Glasgow Coma Score) showed that BROS patients were more likely to have a swallow test on admission (OR 2.95; 95% CI 1.17-7.45). BROS patients were less likely to be in nursing care at 3 months (OR 0.37; 95% CI 0.17-0.81), and less likely to be receiving speech and language therapy at 3 months (OR 0.10; 95% CI 0.03-0.33) and 1 year (OR 0.05; 95% CI 0.00-0.55). Conclusions: The lower use of hospital admission and nursing care at 3 months suggests that in Barbados, family and friends take greater responsibility for patient care around the time of the stroke and in the medium term thereafter.Peer reviewe

Post-stroke survival for Black-Caribbean populations in Barbados and South London

Background and Purpose—There are variations in mortality rates for stroke in black communities, but the factors associated with survival remain unclear. Methods—The authors studied population-based stroke registers with follow up in South London (270 participants, 1995 to 2002) and Barbados (578 participants, 2001 to 2003). Differences in sociodemographic factors, stroke risk factors and their management, case severity, and acute management between London and Barbados were studied. Survival analysis used Kaplan-Meier curves, log-rank test, and Cox proportional hazards model with stratification. Results—There were 1411 person-years of follow-up. Patients in Barbados had poorer survival (log-rank test P=0.037), particularly those with a prestroke Barthel index scores between 15 and 20 (1-year survival, 56.4% versus 74.3%; P<0.001). This disadvantage remained significant (hazard ratio [HR], 1.99; 95% CI, 1.23 to 3.21, P=0.005) after adjustment for age and year of stroke and stratification for stroke subtype and socioeconomic status (SES). After stratification by SES, clinical stroke subtype, and Glasgow Coma Score, and adjustment for other potential confounders, additional factors reducing survival were untreated atrial fibrillation (AF; HR, 8.54; 95% CI, 2.14 to 34.08, P=0.002), incontinence after stroke (HR, 2.64; 95% CI, 1.79 to 3.89), and dysphagia (HR, 2.25; 95% CI, 1.57 to 3.24). Patients not admitted to the hospital had improved survival (HR, 0.35; 95% CI, 0.21 to 0.58). Interaction terms between location and Barthel score, location and AF, and location and transient ischemic attack were included in the final model to reflect the greater difference in survival with a high Barthel score of 15 or more, absence of untreated AF, and having untreated transient ischemic attack. Conclusions—Black-Caribbean people with stroke living in Barbados have worse survival than similar patients in South London, particularly if they have good mobility before the stroke. Further exploration and refinement of measurement of confounding factors such as SES and poststroke management along with exploring the cultural/environmental differences between the communities is required to understand these stark differences.Peer reviewe

Estimation of the risk of stroke in Black populations in Barbados and South London

Background and Purpose— The incidence of stroke in black populations is a public health issue, but how risk varies between black communities is unclear. Methods— Population-based registers in South London (SLSR) and Barbados (Barbados Register of Strokes [BROS]). Stroke incidence estimated by age group, gender and stroke subtype from January 1995 to December 2002 (SLSR), and October 2001 to September 2003 (BROS). Incidence rate ratios [IRR] estimated adjusting for age and sex. Results— Two hundred and seventy-one cases registered in SLSR and 628 cases in BROS. Average age of stroke was 66.1 years (SD 13.7) in SLSR and 71.5 years (SD 14.9) in BROS (P<0.001). The incidence rate/1000 population in SLSR was 1.61 (European adjusted; 95% CI, 1.41 to 1.81) and 1.08 (world adjusted; 95% CI, 0.95 to 1.21). For Barbados incidence rates were 1.29 (European adjusted; 95% CI, 1.19 to1.39) and 0.85 (world adjusted; 95% CI, 0.78 to 0.92). Overall IRR for SLSR: BROS adjusted for age and sex was 1.26 (95% CI, 1.09 to 1.46). Statistically significant subtype differences included total anterior cerebral infarction (IRR, 1.82; 95% CI, 1.23 to 2.69), posterior cerebral infarction (IRR, 2.12; 95% CI, 1.28 to 3.53), primary intracerebral hemorrhage (IRR, 1.56; 95% CI, 1.03 to 2.35) and subarachnoid hemorrhage (IRR, 5.04; 95% CI, 2.54 to 9.97). Conclusions— The risk of stroke in black Caribbeans is higher in South London than Barbados, and particularly so for specific stroke subtypes. The risk in Barbados approaches that in the white population in South London and strokes occur at an older age. Whether environmental factors mediate these differences in migrant populations requires further study.Peer reviewe