An investigation into the impact of nine catchment characteristics on the accuracy of two phosphorus load apportionment models.

Phosphorus (P) load apportionment models (LAMs), requiring only spatially and temporally paired P and flow (Q) measurements, provide outputs of variable accuracy using long-term monthly datasets. Using a novel approach to investigate the impact of catchment characteristics on accuracy variation, 91 watercourses' Q-P datasets were applied to two LAMs, BM and GM, and bootstrapped to ascertain standard errors (SEs). Random forest and regression analysis on data pertaining to catchments' land use, steepness, size, base flow and sinuosity were used to identify the individual relative importance of a variable on SE. For BM, increasing urban cover was influential on raising SEs, accounting for c.19% of observed variation, whilst analysis for GM found no individually important catchment characteristic. Assessment of model fit evidenced BM consistently outperformed GM, modelling P values to ±10% of actual P values in 85.7% of datasets, as opposed to 17.6% by GM. Further catchment characteristics are needed to account for SE variation within both models, whilst interaction between variables may also be present. Future research should focus on quantifying these possible interactions and should expand catchment characteristics included within the random forest. Both LAMs must also be tested on a wide range of high temporal resolution datasets to ascertain if they can adequately model storm events in catchments with diverse characteristics.

A global assessment of the social and conservation outcomes of protected areas.

Protected areas (PAs) are a key strategy for protecting biological resources, but they vary considerably in their effectiveness and are frequently reported as having negative impacts on local people. This has contributed to a divisive and unresolved debate concerning the compatibility of environmental and socioeconomic development goals. Elucidating the relationship between positive and negative social impacts and conservation outcomes of PAs is key for the development of more effective and socially just conservation. We conducted a global meta-analysis on 165 PAs using data from 171 published studies. We assessed how PAs affect the well-being of local people, the factors associated with these impacts, and crucially the relationship between PAs' conservation and socioeconomic outcomes. Protected areas associated with positive socioeconomic outcomes were more likely to report positive conservation outcomes. Positive conservation and socioeconomic outcomes were more likely to occur when PAs adopted comanagement regimes, empowered local people, reduced economic inequalities, and maintained cultural and livelihood benefits. Whereas the strictest regimes of PA management attempted to exclude anthropogenic influences to achieve biological conservation objectives, PAs that explicitly integrated local people as stakeholders tended to be more effective at achieving joint biological conservation and socioeconomic development outcomes. Strict protection may be needed in some circumstances, yet our results demonstrate that conservation and development objectives can be synergistic and highlight management strategies that increase the probability of maximizing both conservation performance and development outcomes of PAs.

A pocket-sized disposable device for testing the integrity of sensation in the outpatient setting.

AIMS: To compare the Ipswich Touch Test and the VibraTip with the Neuropathy Disability Score and the vibration perception threshold for detecting the 'at-risk' foot. METHODS: We directly compared the Ipswich Touch Test and the VibraTip with both the Neuropathy Disability Score ≥ 6 and the vibration perception threshold ≥ 25 V indicating 'at-risk' feet in 83 individuals. RESULTS: The vibration perception threshold and Neuropathy Disability Score tests exhibited almost perfect agreement with each other (P < 0.001). The VibraTip and Ipswich Touch Test results were identical (P < 0.001). The VibraTip and Ipswich Touch Test results also exhibited almost perfect agreement with the vibration perception threshold (P < 0.001) and the Neuropathy Disability Score (P < 0.001). CONCLUSIONS: These two simple and efficient tests are easy to teach, reliable and can be used in any setting, and neither requires an external power source. We conclude that both the VibraTip and the Ipswich Touch Test are reliable and sensitive tests for identifying the 'high-risk' foot.

An emergent science on the brink of irrelevance: a review of the past 8 years of DNA barcoding.

DNA barcoding has become a well-funded, global enterprise since its proposition as a technique for species identification, delimitation and discovery in 2003. However, the rapid development of next generation sequencing (NGS) has the potential to render DNA barcoding irrelevant because of the speed with which it generates large volumes of genomic data. To avoid obsolescence, the DNA barcoding movement must adapt to use this new technology. This review examines the DNA barcoding enterprise, its continued resistance to improvement and the implications of this on the future of the discipline. We present the consistent failure of DNA barcoding to recognize its limitations and evolve its methodologies, reducing the usefulness of the data produced by the movement and throwing into doubt its ability to embrace NGS.

Sperm competition and male ejaculate investment in Nauphoeta cinerea: effects of social environment during development.

Selective pressure arising from sperm competition has been predicted to influence evolutionary and behavioural adjustment of ejaculate investment, but also may influence developmental adjustment of ejaculate investment. Immature males able to target resources strategically based on the competitive environment they will experience when they become sexually mature should be at a selective advantage. In our study we investigated how the presence of potential competitors or mates affects ejaculate and testes investment during development in the cockroach Nauphoeta cinerea, a species where males control female remating via their ejaculate size (large spermatophores prevent females from remating and therefore function to avoid sperm competition for males) and females store sperm. Our aim was to determine whether the social environment influences developmental adjustment of ejaculate investment and the relative importance of ejaculate components with different functions; avoidance of or engagement in sperm competition. We conclude that the social environment can influence developmental and behavioural flexibility in specific ejaculate components that may function to avoid or engage in sperm competition.

Sexual conflict and cooperation under naturally occurring male enforced monogamy.

An evolutionary conflict often exists between the sexes in regard to female mating patterns. Females can benefit from polyandry, whereas males mating with polyandrous females lose reproductive opportunities because of sperm competition. Where this conflict occurs, the evolution of mechanisms whereby males can control female remating, often at a fitness cost to the female, are expected to evolve. The fitness cost to the female will be increased in systems where a few high status males monopolise mating opportunities and thus have limited sperm supplies. Here we show that in the cockroach Nauphoeta cinerea, a species where males enforce female monogamy in the first reproductive cycle, males that have become sperm depleted continue to be able to manipulate female remating behaviour. Although the manipulation severely decreases fecundity in females mated to sperm-depleted males, males benefit, increasing their relative fitness by preventing other males from reproducing. Our results suggest that there is selection on maintaining the mechanism of manipulation rather than maintaining sperm numbers. Taken with previous research on sexual conflict in N. cinerea, this study suggests that the causes and consequences of sexual conflict are complex and can change across the life history of an individual.

The potential role of community pharmacists in care management.

The traditional dispensing role of the community pharmacist is increasingly being questioned and greater emphasis is being placed on the provision of advice. Introduction of the NHS Community Care Act provides an opportunity to consider the potential role of community pharmacists in care management and in carrying out assessment of individual need. This paper describes the introduction of Community Care training for community pharmacists in Derbyshire and the results of a study to evaluate assessment and referrals that the community pharmacists routinely carried out. Fourteen pharmacists who participated in the study recorded assessments that they carried out over a 10-week period between January and April 1994. A total of 858 assessments were self-reported by the community pharmacists, of which 57% resulted from enquiries relating to physical symptoms, 27% relating to prescription medication and 8% from social problems. A further 7% arose from a combination of these categories. Nearly one third of all assessments were made at the request of a carer. Health care professionals had initiated 7% of the enquiries, with a greater proportion of these associated with prescription medication (46%) and social care (29%) compared with those initiated by patients (20% prescription medication, 6% social care) or carers (26% prescription medication, 6% social care). If a pharmacist intervened to initiate an enquiry, a greater proportion of assessments led to referral (33%) compared with 14-21% for other types of enquirer. This paper discusses the possibility of providing greater access to care-management, care planning and monitoring through making this process more widely available from community pharmacies on the high-street.

An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome.

OBJECTIVE: No means exist for predicting the acute respiratory distress syndrome (ARDS), which complicates sepsis, trauma, and a variety of clinical disorders. Because activation of phospholipid-signaling pathways involving the acyl chains oleate and linoleate may initiate and amplify the inflammatory response, and thereby lead to the development of ARDS, we examined whether serum concentrations of these bioactive lipids increase and are predictive of ARDS in at-risk patients. DESIGN: Part I: A prospective, single-blind trial. Part II: A prospective, randomized, double-blind trial. SETTING: General intensive therapy units in five university teaching hospitals. SUBJECTS: Part I: Thirty-nine healthy control patients were studied to determine normal distribution of serum acyl values, followed by 30 patients admitted with onset of sepsis, trauma, or development of ARDS (within 24 hrs of admission) over a 1-yr period. Part II: Eight patients admitted with sepsis syndrome over a 2-month period. INTERVENTIONS: Part II: Patients were randomized to receive the substituted methylxanthine, lisofylline (CT1501R), or an identically presented placebo. MEASUREMENTS AND MAIN RESULTS: We measured the serum free fatty acid concentrations in the 39 healthy control subjects, and then we prospectively examined the serum free fatty acid concentrations in 30 age-matched patients in samples obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS. We then prospectively studied eight septic, at-risk patients who were matched for age, Acute Physiology and Chronic Health Evaluation II scores, Multiple Organ Failure index, and Glasgow Coma Score, in a double-blind, placebo-controlled, pilot study. These patients included four patients who received no treatment and four patients who received lisofylline, a compound that decreases serum unsaturated free fatty acids and diminishes acute lung injury in animals caused by sepsis and/or trauma. The calculated ratios of serum free fatty acids (Le., the ratio of C18 unsaturated fatty acids linoleate and oleate to fully saturated palmitate, C16:0) increased and predicted the development of ARDS in at-risk patients. Serum samples from the 30 patients, obtained within 24 hrs from the onset of sepsis, trauma, or development of ARDS, had significantly increased mean acyl chain ratios (1.42 +/- 0.35 [SD]) compared with healthy control subjects (0.86 +/- 0.25; p < .01). Sera from 13 patients with sepsis or trauma who did not develop ARDS (group A [at-risk, non-pre-ARDS]) also had increased acyl ratios (1.23 +/- 0.27) compared with sera from healthy control subjects (0.86 +/- 0.25; p < .01). Sera from seven patients who subsequently developed ARDS (group B [at-risk, pre-ARDS]) had higher acyl ratios (1.70 +/- 0.21) than group A at-risk patients who did not develop ARDS (1.23 +/- 0.27; p < .01) or healthy control subjects (0.86 +/- 0.25; p < .001). Sera from ten group C patients with ARDS at the time of admission to the study had the highest acyl ratios (1.80 +/- 0.75), which exceeded values for healthy control subjects (p < .001) and group A at-risk patients without ARDS (p = .01), but were not significantly different then group B at-risk, pre-ARDS patients (p = .17). Prospective study of eight septic, at-risk patients demonstrated significantly (p < .05) increased serum acyl ratios in the four untreated patients (findings consistent with the first study) but a significantly (p = .02) reduced ratio in the four at-risk patients treated with lisofyline. CONCLUSIONS: Increases in unsaturated serum acyl chain ratios differentiate between healthy and seriously iII patients, and identify those patients likely to develop ARDS. Thus, the serum acyl ratio may not only prospectively identify and facilitate the assessment of new treatments in patients at highest risk for developing ARDS, but may also lead to new insights about the pathogenesis of ARDS.

Interleukin-1 stimulates phosphatidic acid-mediated phospholipase D activity in human mesangial cells.

Previous studies suggest that signal transduction mediated by interleukin-1 (IL-1), acting through an IL-1 receptor type found on T-cells and mesangial cells, may use phosphatidylethanolamine (PE) as a signaling molecule. Evidence presented here indicates that stimulation of human mesangial cells by IL-1 results in activation of a phospholipase D (PLD) that hydrolyzes PE to phosphatidic acid (PA). PLD acts on a subfraction of PE enriched in 1-o-alkyl and 1-o-alkenyl, sn-2-unsaturated species, generating a unique PA subspecies 30-120 s after stimulation. This PA species is subsequently converted to diradylglycerols by phosphatidate phosphohydrolase. The PE-directed PLD activity is abolished by antibodies against the IL-1 type I receptor and against IL-1. This specific PLD activity is also stimulated by low concentrations of 1,2-sn-dilinoleoyl PA, but not by high concentrations of 1-palmitoyl or 1-oleoyl lyso-PA. Blockade of PLD activation by IL-1 antibodies or antibody against the IL-1 receptor is bypassed by stimulation of human mesangial cells with 1,2-sn-dilinoleoyl PA. A novel system of signal cytokine mediation through PA self-amplification is indicated.

Generation of phosphatidic acid and diacylglycerols following ligation of surface immunoglobulin in human B lymphocytes: potential role in PKC activation.

We have examined signal transduction via membrane IgM (mIgM) in resting and cycling human B cells. Crosslinking mIgM on all of the cell types studied transduced a signal through the phosphatidylinositol pathway, producing inositol 1,4,5-trisphosphate and release of intracellular free calcium. These second messengers were formed regardless of quantitative or qualitative differences in the surface expression of mIgM: cells that had low levels of surface IgM (T-51) or had no light chain associated with surface heavy chain (DB) signaled phosphatidylinositol pathway activation after mIgM crosslinking. Production of specific lipid products in nonquiescent B cells differed from that in normal resting cells. Ligation of surface immunoglobulin on resting B cells resulted in sustained increases of both diacylglycerol and phosphatidic acid, two lipids that can influence PKC activation. Whereas PKC was strongly activated in normal tonsillar B cells, several cell lines had reduced PKC activation following crosslinking of mIgM. The reduction in protein kinase C activation correlated with the absence or reduced levels of phosphatidic acid or diacylglycerol following stimulation: protein kinase C translocated and was activated only in cells that had elevated levels of both diacylglycerides and phosphatidic acid. Anti-IgM-induced phosphorylation of a protein kinase C substrate protein CD20, also increased in those cells having PKC activation and not in cells in which kinase activity was reduced. CD20 phosphorylation also increased following the direct addition of exogenous phosphatidic acid to resting B cells. Together, these observations show that the generation of lipid products following mIgM crosslinking in resting cells can vary from that in cycling cells and may relate to the different levels of PKC activation. In a companion study we report that ligation of surface IgM activates both an acyltransferase and phospholipase D to form phosphatidic acid.

The parasympathetic system in exercise-induced rhinorrhoea.

The present study demonstrates that ipratropium bromide significantly reduces normal resting nasal secretion (p less than 0.05) and also significantly reduces exercise induced rhinorrhoea compared with a placebo (p less than 0.01). It also demonstrates that there may be another non-parasympathetic cause for the increase in nasal secretion with exercise.

Lipid A activation of glomerular mesangial cells: mimicry of the bioactive lipid, phosphatidic acid.

Lipid A, the active component of bacterial endotoxin, stimulates multiple cell types, including glomerular mesangial cells (MC), and yet the molecular mechanisms of cell activation remain unclear. Lipid A, in its monosaccharyl form, structurally resembles the biologically active lipid phosphatidic acid (PA). Given this, it was postulated that lipid A activates cells by acting as a structural and functional mimetic of PA. Lipid A was found to specifically stimulate an MC lyso-PA acyl transferase activity, leading to enhanced synthesis of sn-2-unsaturated forms of PA. Sn-2-unsaturated PA itself, in contrast to sn-2-saturated PA, also stimulated the lyso-PA acyl transferase activity, a positive feedback feature previously noted with lyso-lecithin acyl transferase. Structure-function correlations demonstrated that the phosphate moieties in both PA and lipid A were necessary to feedback stimulation of lyso-PA acyl transferase (AT), as dephosphorylated lipid A and 2-unsaturated 1,2-sn-diacylglycerol had no stimulatory effect on lyso-PA AT. The biologic relevance of the lipid A and PA-mediated increases in lyso-PA acyl transferase activity was shown, whereby limited exposure to these lipids rapidly induced identical MC morphologic and functional alterations characteristic of cellular activation. By mimicking the stimulatory action of PA, per se, on lyso-PA acyl transferase activity, lipid A may initiate a positive feedback cycle of acylation, yielding increased amounts of PA enriched in unsaturated fatty acids. This newly synthesized PA may subsequently act as the proximal mediator of cellular activation.

Interleukin-1 rapidly stimulates lysophosphatidate acyltransferase and phosphatidate phosphohydrolase activities in human mesangial cells.

Phosphatidic acid (PA) is a cytokine in a variety of cell types, and an intermediary in cell activation. It is produced from membrane phospholipids by either lysophosphatidate acyl-CoA:acyltransferase (lyso-PA AT) or phospholipase D. Interleukin-1 (IL-1) stimulation of human mesangial cells (HMC) induced activation of lyso-PA AT, and synthesis of new PA species with significant increase in PA mass. These PA species were enriched in long-chain unsaturated acyl side chains (C18:1, C18:2, C20:5, and C22:6) in both the sn-2 and sn-1 positions, and stimulated the action of the lyso-PA AT as a positive feedback mechanism. Gas-liquid chromatography and mass spectrometry demonstrate that the acyl composition of phosphatidic acid does not resemble that of the major phospholipid fractions of this preparation and therefore is not the product of phospholipase D. The PA species were rapidly converted to 1,2-sn-diacylglycerols by phosphatidate phosphohydrolase, which also was activated by IL-1 via a separate mechanism involving a pertussis-sensitive G-protein. The activities of lyso-PA AT and phosphatidate phosphohydrolase were associated with plasma membrane enriched and refined microsomal fractions. IL-1 stimulation of a murine T cell (thymoma) line, EL-4, also caused stimulation of lyso-PA AT, resulting in PA formation. EL-4 mutants with defective IL-1 receptors did not demonstrate stimulation of lyso-PA AT, showing the necessity of intact IL-1 receptors for activation of this enzyme. We conclude that PA is a significant signaling intermediary for IL-1 via activation of lyso-PA AT and a G-protein, which activates phosphatidate phosphohydrolase. This system suggests a novel mechanism whereby a low intensity signal may be translated into cellular activation.

Rapid activation of phosphatidate phosphohydrolase in mesangial cells by lipid A.

Knowledge of rapid events in cell signaling initiated by lipid A, the core moiety of bacterial lipopolysaccharide, is limited. In the present study we have demonstrated that cis-parinaric acid (cis-PnA) rapidly labels 1,2-sn-diacylglycerol (DAG) subsequent to labeling of phosphatidic acid (PA). Stimulation of microsomal membranes with lipid A decreased the level of PA labeled with cis-PnA within 5 s and increased the proportion of fluorescent label in DAG. Lipid A stimulation of DAG synthesis at 5-15 s was inhibited by incubation of mesangial cells with pertussis toxin prior to isolation of microsomal membranes. Inhibition of DAG formation was accompanied by an accumulation of the mass and fluorescent label in the cis-PnA-labeled phosphatidic acid pool. GTP gamma S caused a decrease in labeled PA and an increase in labeled 1,2-DAG. We conclude that the PA pool was enlarged via the lipid A sensitive lyso-PA acyl transferase (lyso-PA-AT) and was decreased by a phosphatidate phosphohydrolase to form DAG. The phosphatidate phosphohydrolase was at least partly regulated by a pertussis-sensitive G-protein. Lipid A or 1,2-dilinoleyl-PA, a product of lyso-PA-AT, induced cell activation as monitored by actin reorganization and cellular shape changes. Pretreatment of cells with pertussis toxin prevented the morphological changes normally induced by lipid A or 1,2-dilinoleyl-PA. In contrast, 1-oleoyl-2-acetylglycerol induced rapid actin reorganization and shape change, presumably bypassing the pertussis blockade. We propose that specific pools of PA and PA-derived DAG are key elements in rapid signaling in mesangial cells and are independent of the PI cycle and phospholipase C.

Is a single quinsy an indication for tonsillectomy?

There has recently been some discussion on whether a single quinsy is an indication for tonsillectomy. This paper presents a retrospective study of 36 patients who presented with a quinsy over the past 37 years but did not have interval tonsillectomy. Prolonged follow-up shows that the rate of recurrence of a quinsy can double compared to the recurrence rate under 5 years. Despite this it remains relatively low and an uncomplicated quinsy does not warrant tonsillectomy.

A lingual thyroid cyst complicating a foreign body in the oesophagus.

A case report is presented of a man who had a foreign body in his oesophagus complicated by the fact that he also had a large cyst of a lingual thyroid. The problems encountered and his subsequent management are discussed. The possibility that a cyst of the tongue base may contain the only functioning thyroid tissue and the dangers of haemorrhage at its removal are emphasized.

A comparison between coupler gain and insertion gain of hearing aids as used in partially hearing units in five schools in Belfast.

A group of 30 school-children attending partially hearing units at ordinary schools had their hearing aids assessed with reference to coupler gain and insertion gain. The results showed no statistically significant difference between the coupler and insertion gain at 250, 500 and 1000 Hz, but a small statistically significant difference with insertion gain greater at 2000, 4000 and 5000 Hz. A large individual variation in results is noted, which would suggest that a standard 2 cm3 coupler is of little use in predicting the output of an aid in a specific child's ear. The presence of wax in the ear canals seems to affect the insertion gain in a positive fashion but this is not statistically significant and further investigation is warranted.

Origin of the gamma polypeptide of the Na+/K+-ATPase.

The Na+/K+-ATPase purified from lamb kidney contains a gamma polypeptide fraction which is a collection of fragments derived from the alpha and beta polypeptides of the enzyme. This fraction has the solubility characteristics of a proteolipid and was isolated either by high performance liquid chromatography (size exclusion chromatography) in 1% sodium dodecyl sulfate or by sequential organic extraction of purified lamb kidney Na+/K+-ATPase. Formation of gamma polypeptide(s) from detergent solubilized holoenzyme was accelerated by sulfhydryl containing reagents and was unaffected by addition of inhibitors of proteolytic enzymes. Treatment of the holoenzyme with the photoaffinity reagent N-(2-nitro-4-azidophenyl)[3H]ouabain ([3H]NAP-ouabain) labeled the alpha polypeptide and the gamma polypeptide fraction but not the beta polypeptide. Amino acid sequence analysis of one gamma polypeptide preparation revealed homology of one component of this fraction with the N-terminus of the beta subunit of the Na+/K+-ATPase. Amino acid analysis of two preparations of proteolipid showed similar amino acid compositions with a peptide derived from the alpha subunit. The insolubility and complexity of the gamma polypeptide(s)/proteolipid fraction appears to preclude a conclusive sequence analysis of all components of this fraction.