The discrimination of quick Paediatric Early Warning Scores in the pre-hospital setting.

In our previous study, a Paediatric Early Warning Score could be calculated for only one-fifth of 102,993 children transported by ambulance to hospital, as components other than supplemental oxygen were not reliably measured: respiratory rate 90,358 (88%); Glasgow Coma Score 83,648 (81%); heart rate 83,330 (81%); time to capillary reperfusion 81,685 (79%); oxygen saturation 71,372 (69%); temperature 60,402 (59%); systolic blood pressure 37,088 (36%). We tested 12 abbreviated scores with 3-5 components. The discrimination of these 12 scores for the primary outcome (30-day mortality or admission to paediatric intensive care), as measured by the area under the receiving operator characteristic curve, ranged from 0.69 to 0.80. Scores could be calculated for at most 74,508 (72%) children when heart rate, conscious level and respiratory rate were measured, with or without supplemental oxygen: the discrimination of these two versions was 0.75 and 0.77, respectively. Optimal threshold scores of 3 and 2 for these two abbreviated versions discriminated an outcome rate of 2-3% in about one third of children from the other children who had < 1% rate of outcome.

A phase I/II, open-label, randomised study of nintedanib plus mFOLFOX6 versus bevacizumab plus mFOLFOX6 in first-line metastatic colorectal cancer patients.

BACKGROUND: This randomised, open-label, phase I/II study evaluated the efficacy and safety of nintedanib, an oral, triple angiokinase inhibitor, combined with chemotherapy, relative to bevacizumab plus chemotherapy as first-line therapy in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Patients with histologically confirmed mCRC (adenocarcinoma), an Eastern Cooperative Oncology Group performance status ≤ 2 and adequate organ function were included. Patients were randomised 2:1 to receive nintedanib 150 mg or 200 mg b.i.d. plus mFOLFOX6 (oxaliplatin 85 mg/m(2), l-leucovorin 200 mg/m(2) or d,l-leucovorin 400 mg/m(2), 5-fluoruracil bolus 400 mg/m(2) followed by 2400 mg/m(2), every 2 weeks) or bevacizumab (5 mg/kg every 2 weeks) plus mFOLFOX6. During phase I, patients underwent a 3 + 3 dose-escalation schema to determine the maximum tolerated dose (MTD) of nintedanib in combination with mFOLFOX6. The primary end point was progression-free survival (PFS) rate at 9 months. Objective response (OR) was a secondary end point. RESULTS: The nintedanib recommended phase II dose was 200 mg b.i.d. plus mFOLFOX6 based on safety data from phase I (n = 12). Of 128 patients randomised in the phase II part, 126 received treatment (nintedanib plus mFOLFOX6, n = 85; bevacizumab plus mFOLFOX6, n = 41). PFS at 9 months was 62.1% with nintedanib and 70.2% with bevacizumab [difference: -8.1% (95% confidence interval -27.8 to 11.5)]. Confirmed ORs were recorded in 63.5% and 56.1% of patients in the nintedanib and bevacizumab groups, respectively. The incidence of adverse events (AEs) considered related to treatment was 98.8% with nintedanib and 97.6% with bevacizumab; the incidence of serious AEs was 37.6% with nintedanib and 53.7% with bevacizumab. The pharmacokinetics of nintedanib and the components of mFOLFOX6 were unaffected by their combination. CONCLUSIONS: Nintedanib in combination with mFOLFOX6 showed efficacy as first-line therapy in patients with mCRC with a manageable safety profile and further studies in this population are warranted.

Prospective randomised multi-centre trial comparing the clinical efficacy, safety and patient acceptability of circular stapled anopexy with closed diathermy haemorrhoidectomy.

OBJECTIVE: Unlike excisional haemorrhoidectomy, stapled anopexy (SA), which does not involve radical excision, has theoretical advantages, thus offering potential patient benefits. We compared the clinical efficacy, safety and patient acceptability of SA, with closed haemorrhoidectomy (CH). PATIENTS AND METHODS: 182 patients with symptomatic haemorrhoids (grades II, III, IV) were randomly assigned to receive SA or CH and were followed for up to 1 year (6, 12, 24, 48 weeks) after operation. Postoperative pain, symptom control, complications, re-treatment rates, patient satisfaction, and quality of life were compared on an intention-to-treat basis. RESULTS: Postoperative pain in the SA group (n = 91) was significantly lower (p = 0.004, Mann-Whitney U test). At 1 year there were no significant differences in the symptom load, symptom severity or the disease severity between the two groups. Overall complication rates were similar but faecal urgency was reported more frequently following SA (p = 0.093, Fisher's exact test). Despite a similar rate of residual symptoms, prolapse control was better with CH (p = 0.087, Fisher's exact test), and more patients in the SA group required re-treatment for residual prolapse at 1 year (p = 0.037, Fisher's exact test). However, more patients rated SA as an excellent operation at 6 and 12 weeks (p = 0.008 and 0.033, binary logistic regression) and were willing to undergo a repeat procedure if required (p = 0.018, Fisher's exact test). CONCLUSION: Stapled anopexy offers a significantly less painful alternative to excisional haemorrhoidectomy and achieves a higher patient acceptability. Although the overall symptom control and safety are similar in the majority of the patients, the re-treatment rate for recurrent prolapse at 1 year is higher following SA when compared to CH.

Advanced Fenton processing of aqueous phenol solutions: a continuous system study including sonication effects.

Our previous report based on a batch reactor system for the Advanced Fenton Process (AFP) showed that pH, hydrogen peroxide and the organic substances treated are among the most important factors affecting the oxidation efficiency. As an extended study towards its potential commercialisation, this paper reports the effects of the main process parameters including those relating to a new laboratory scale AFP flow-through system. In order to systemise and correlate the results, the Taguchi experimental design method was used. Total organic carbon (TOC) removal was utilised as the measure of the oxidation efficiency and it was found that the removal of phenol from aqueous solution at pH 2.0 and 2.5 was very similar but hydrogen peroxide supply significantly affected the TOC removal with the change of flow rate from 14.4 ml/h to 60 ml/h. Also, the initial concentration of phenol was a highly significant factor, with higher concentrations resulting in a lower TOC removal rate. The temperature effects in the range of 14-42 degrees C were investigated and it was found that there was accelerated oxidation of phenol in the early stages but after 90 min there was no significant difference between the results. Sonication with a bath type sonicator resulted in relatively small enhancements of TOC removal but further studies with cup-horn sonication showed that TOC removal increased with higher intensity of sonication.

Paediatric early warning scores are predictors of adverse outcome in the pre-hospital setting: A national cohort study.

INTRODUCTION: Physiological deterioration often precedes clinical deterioration as patients develop critical illness. Use of a specific Paediatric Early Warning Score (PEWS), based on basic physiological measurements, may help identify children prior to their clinical deterioration. NHS Scotland has adopted a single national PEWS - PEWS (Scotland). We aim to look at the utility of PEWS (Scotland) in unselected paediatric ambulance patients. METHODS: We performed a retrospective cohort of all ambulance patients aged under 16 years conveyed to hospital in Scotland between 2011 and 2015. Patients were matched to their 30 day mortality and ICU admission using data linkage. RESULTS: Full results were available for 21,202 children and young people (CYP). On multivariate logistic regression, PEWS (Scotland) was an independent predictor of the primary outcome (ICU admission within 48 h or death within 30 days) with an odds ratio of 1.403 (95%CI 1.349-1.460, p < 0.001). Area Under Receiving Operator Curve (AUROC) for aggregated PEWS was 0.797 (95% CI 0.759 to 0.836, p < 0.001). The optimal PEWS using Youlden's Index was 5. DISCUSSION: These data show PEWS (Scotland) to be a useful tool in a pre-hospital setting. A single set of physiological observations undertaken prior to arrival at hospital can identify a group of children at higher risk of an adverse in-hospital outcome. Paediatric care is becoming more specialised and focussed on a smaller number of centres. In this context, use of PEWS (Scotland) in the pre-hospital phase may allow changes to paediatric pre-hospital pathways to improve both admission to ICU and child mortality rates.

Increased permeability of the malaria-infected erythrocyte to organic cations.

The human malaria parasite, Plasmodium falciparum, induces in the plasma membrane of its host red blood cell new permeation pathways (NPP) that allow the influx of a variety of low molecular weight solutes. In this study we have demonstrated that the NPP confer upon the parasitised erythrocyte a substantial permeability to a range of monovalent organic (quaternary ammonium) cations, the largest having an estimated minimum cross-sectional diameter of 11-12 A. The rate of permeation of these cations showed a marked dependence on the nature of the anion present, increasing with the lyotropicity of the anion. There was no clear relationship between the permeation rate and either the size or the hydrophobicity of these solutes. However, the data were consistent with the rate of permeation being influenced by a combination of these two factors, with the pathways showing a marked preference for the relatively small and hydrophobic phenyltrimethylammonium ion over larger or less hydrophobic solutes. Large quaternary ammonium cations inhibited flux via the NPP, as did long-chain n-alkanols. For both classes of compound the inhibitory potency increased with the size and hydrophobicity of the solute. This study extends the range of solutes known to permeate the NPP of malaria-infected erythrocytes as well as providing some insight into the factors governing the rate of permeation.

Malaria parasite Plasmodium gallinaceum up-regulates host red blood cell channels.

The properties of the malaria parasite-induced permeability pathways in the host red blood cell have been a major area of interest particularly in the context of whether the pathways are host- or parasite-derived. In the present study, the whole-cell configuration of the patch-clamp technique has been used to show that, compared with normal cells, chicken red blood cells infected by Plasmodium gallinaceum exhibited a 5-40-fold larger membrane conductance, which could be further increased up to 100-fold by raising intracellular Ca(2+) levels. The increased conductance was not due to pathways with novel electrophysiological properties. Rather, the parasite increased the activity of endogenous 24 pS stretch-activated non-selective cationic (NSC) and 62 pS calcium-activated NSC channels, and, in some cases, of endogenous 255 pS anionic channels.

Transport properties of the host cell membrane.

The malaria-infected erythrocyte shows an increased permeability to a wide range of solutes. The increase is mediated in part by parasite-induced new permeation pathways (NPP) and in part (for some solutes, under some conditions) by increased activity of endogenous transporters. The NPP provide the major route for the influx into the infected cell of a number of essential nutrients, but although the functional characteristics of these pathways are understood in some detail, they are yet to be identified at a molecular level. Lucifer yellow, a fluorescent anion, is taken up by malaria-infected erythrocytes to a much greater extent than uninfected erythrocytes via a pathway that differs in its pharmacological characteristics from the NPP. The nature, origin and location of this pathway remain to be established.

Semen quality in captive Houbara bustard, Chlamydotis undulata undulata.

Semen quality in captive-bred Houbara bustards, Chlamydotis undulata undulata, was assessed during three consecutive breeding seasons. In any one season, sperm quality, in terms of the proportion of eosin-permeable spermatozoa and of spermatozoa with abnormally large nuclei, varied among individual males, but not among their ejaculates. Neither the proportion of spermatozoa with large nuclei, nor those permeable to eosin were related to the total sperm output of males. The fertilizing ability of males was related to their mean seasonal proportion of eosin-permeable spermatozoa, but not the proportion of spermatozoa with large nuclei. The ranking of males on the basis of the proportion of spermatozoa with large nuclei in their ejaculates was significantly positively correlated between seasons, although ranking on the basis of sperm eosin-permeability was not. The cause or consequence of producing spermatozoa with large nuclei (and excess DNA) remains to be elucidated, but appears to be a trait that is characteristic of houbara bustard males that is maintained between breeding seasons.

Repeat dispensing by community pharmacists: advantages for patients and practitioners.

Repeat prescribing is an appreciable chore for general practitioners (GPs), and often lacks rigorous clinical control. This paper reports on a pilot repeat dispensing system, which employed community pharmacists to streamline the process and provide clinical supervision. The system described operated within the current regulations, was popular, and worked well for patients on stable treatment regimes.

Day surgery in Scotland: patient satisfaction and outcomes.

OBJECTIVE: To evaluate patients' views on the process and outcome of day surgery in Scotland, and to study patients' satisfaction with care in a range of specific procedures. DESIGN: Questionnaires completed by a census of day case surgery patients within a band of 25 procedures under the umbrella of five broad groups: (1) general surgery; (2) urology; (3) gynaecology; (4) orthopaedics; (5) ear, nose, and throat; ophthalmology. SETTING: 13 hospitals in six health board areas in Scotland. SUBJECTS: During the period 1995-6, 5069 day case patients were asked to complete a questionnaire within two weeks of their operation and discharge from hospital. MAIN OUTCOME MEASURES: Arrangements before admission; immediate postoperative symptoms and complications; problems experienced after discharge; readmission after discharge. RESULTS: A response rate of 68% was obtained from 13 sites ranging from 43% to 82%. The overall satisfaction score was 85. A total of 894 patients (26%) experienced pain after surgery and 783 (23%) had relatively minor medical problems after discharge. In total, 265 (7.8%) patients were readmitted to hospital after discharge. Few notable differences existed between specialties or hospitals in terms of satisfaction scores, although notable pain was experienced more frequently in gynaecology and general surgery patients. Readmission was more common for urological procedures. CONCLUSION: Overall, patient satisfaction with day case surgery was high. Dissatisfaction was largely related to waiting times between admission, operation, and discharge. The amount of pain experienced also had a notable impact on the level of patient satisfaction. Day surgery is not without complications, with 26% of patients experiencing notable degrees of pain; 23% having minor medical problems after discharge; and 8% of respondents having to reattend hospital with problems relating to their original operations.

Regulating plant/insect interactions using CO2 enrichment in model ecosystems.

The greenhouse environment is a challenging artificial ecosystem in which it is possible to study selected plant/insect interaction in a controlled environment. Due to a combination of "direct" and "indirect" effects of CO2 enrichment on plant photosynthesis and plant development, canopy productivity is generally increased. In this paper, we discuss the effects of daytime and nighttime CO2 enrichment protocols on gas exchange of pepper plants (Capsicum annuum L, cv Cubico) grown in controlled environments. In addition, we present the effects of thrips, a common Insect pest, on the photosynthetic and respiratory activity of these plant canopies. Carbon dioxide has diverse effects on the physiology and mortality of insects. However, our data indicate that thrips and whiteflies, at least, are not killed "directly" by CO2 levels used to enhance photosynthesis and plant growth. Together the data suggest that the insect population is affected "indirectly" by CO2 and that the primary effect of CO2 is via its effects on plant metabolism.

Measuring sperm:egg interaction to assess breeding efficiency in chickens and turkeys.

Systems used to measure fertility in poultry have themselves presented a major impediment to progress in maintaining or improving fertility. Generally, these systems have been time-consuming, quantitatively inadequate, or both. A simplistic illustration of the basis of the problem is that if six fertile eggs were laid by a turkey hen during 1 wk after insemination, then all we know is what happened to six sperm: they fertilized the eggs. If 100 million sperm were inseminated, then information on the other 999,999,994 is missing. A better approach for quantitating breeding efficiency is to estimate the numbers of sperm that interact with the egg in the infundibulum. These can be identified in laid eggs, as sperm in the outer perivitelline layer (OPVL sperm), or holes produced by sperm in the inner perivitelline layer (IPVL holes). Eggs can contain up to 250,000 OPVL sperm, so the scale improves on binary estimation of fertilization status. The number of spermatozoa interacting with the perivitelline layer is related to the artificial insemination (AI) dose, the number of oviducal sperm, and the probability of fertilization, not just for one egg, but for subsequent eggs laid by the same hen. Practical applications of sperm:egg interaction measurements include: replacement of fertility trials for evaluation of semen; general fertility evaluation; and monitoring breeding efficiency of commercial turkey and broiler breeders. Furthermore, studies of sperm transfer into eggs raise interesting questions about the efficiency of turkey hens' response to AI or mating frequency of broiler hens in commercial flocks.

Biometric analysis of phenotypic characters of potato shoot-tips recovered from tissue culture, dimethyl sulphoxide treatment and cryopreservation.

A biometric approach partly involving principal component analysis has been used to examine the changes in phenotypic characters of shoot-tip derived potato plants recovered from tissue culture, dimethyl sulphoxide (DMSO) and cryopreservation in comparison with field-grown tuber-derived plants. There were significant differences in the quantitative characters height and tuber weight in the cryopreserved plants compared to those derived from DMSO treatment and tissue culture. These three experimental groups were shown to significantly differ from field-grown plants in the characters, tuber weight followed by height and length of petiole. The use of biometrics as an analytical approach in genetic stability assessments of plants recovered from cryopreservation to relatively small sample sizes is discussed.

Factors influencing theoretical knowledge and practical skill acquisition in student nurses: an empirical experiment.

A previous qualitative study [Nurse Education Today 20 (2000) 499] investigated perceptions of nurse teachers, student nurses and preceptors of the theory-practice gap said to exist within nursing. One theme was views of how the theory-practice gap could be closed. A subsequent quantitative study is reported here, in which this theme was translated into three factors. A full factorial experimental design was used to study the effect of these factors on theoretical knowledge and practical skill acquisition in a sample of first year undergraduate student nurses from one institution of higher education (n=19). The effect of whether a nurse teacher or preceptor taught students theoretical elements relating to a clinical specialty, whether the nurse teacher and preceptor collaborated on the content of what was taught to students and whether students went straight to, or delayed the clinical specialty following theoretical input, was examined. The results demonstrated preceptors were more effective than nurse teachers in promoting theoretical knowledge relating to their clinical specialty. Collaboration between the preceptors and nurse teachers on teaching content was ineffective at increasing theoretical knowledge. Delay between theoretical input and clinical experience was not detrimental for medical placements and for rehabilitation placements, resulted in an improved theoretical knowledge.

Activated factor XII type A predicts long-term mortality in patients admitted with chest pain.

BACKGROUND: We assessed the relation between admission levels of activated factor XII type A (XIIaA), and long-term all-cause and cardiac mortality and recurrent troponin T (TnT) positive cardiovascular events in a consecutive cohort of 870 patients admitted with a clinically strongly suspected acute coronary syndrome (ACS). METHODS AND RESULTS: After a 24-month follow-up period, 138 patients (15.8%) had died and 155 (17.8%) had suffered from a recurrent TnT positive (TnT > 0.05 ng mL(-1)) event. XIIaA levels were significantly lower in long-term survivors than in patients who died (22.9 (17.7-32.1) vs. 27.2 (20.0-39.7) pmol L(-1) [median, 25 and 75% percentiles], P < 0.001). The unadjusted hazard ratio for death within 2 years in patients with XIIaA in the highest quartile was 2.49 (95% confidence interval (CI), 1.52-4.06) as compared with patients with XIIaA in the lowest quartile. In a stepwise Cox regression model for death within 2 years, XIIaA added prognostic information for all-cause mortality (HR 2.05; 95% CI, 1.21-3.47) above and beyond age, a history of heart failure, ST-segment elevation, TnT and B-type natriuretic peptide (BNP). In the subgroup of patients with an admission TnT < or = 0.05 ng mL(-1), XIIaA provided independent prognostic information for all-cause mortality (HR 3.88; 95% CI, 1.66-9.08) and for the combined endpoint of death or recurrent TnT positive event (HR 2.46; 95% CI, 1.34-4.50). CONCLUSION: XIIaA, a recently identified in vivo form of activated factor XII is an independent indicator of long-term all-cause mortality in patients admitted with chest pain, providing prognostic information above and beyond conventional risk factors.

Assessing the breeding efficiency of broiler breeder flocks by measuring sperm transfer into laid eggs.

1. The breeding efficiency of broiler flocks was assessed by estimating the numbers of spermatozoa trapped in a 5.5 mm2 area of the perivitelline layer of laid eggs. 2. In samples of approximately 60 eggs taken from flocks on the same day, the numbers of spermatozoa ranged from 0 to several hundred. 3. Within each sample of eggs, there appeared to be two distinct populations: eggs in which perivitelline spermatozoa could not be found; and eggs containing spermatozoa for which the logarithm of the number of perivitelline spermatozoa can be approximated by a normal distribution. 4. When data from 15 flocks were considered, the overall flock fertility was linearly correlated with: the median of the number of spermatozoa per 5.5 mm2 of perivitelline layer (r = 0.678); the mean of positive values of the logarithm of the number of spermatozoa (r = 0.620); and the proportion of sampled eggs in which the number of perivitelline spermatozoa was greater than 0 (r = 0.714). 5. Flock age was the major factor influencing fertility and all the variables of perivitelline sperm distribution.

Increased choline transport in erythrocytes from mice infected with the malaria parasite Plasmodium vinckei vinckei.

Parasitized erythrocytes from mice infected with the murine malaria parasite Plasmodium vinckei vinckei showed a marked increase in the rate of influx of choline compared with erythrocytes from uninfected mice. In contrast, uninfected erythrocytes from P. vinckei-infected animals transported choline at the same rate as those from uninfected mice. The increased influx of choline into parasitized cells was via two discrete routes. One was a saturable pathway with a Km similar to that of the choline carrier of normal erythrocytes but a Vmax approx. 20-fold higher than that observed in uninfected cells. The other was a non-saturable pathway inhibited by furosemide. At choline concentrations within the normal physiological plasma concentration range, the former pathway contributed approx. two-thirds and the latter approx. one-third of the influx of choline into parasitized cells. The characteristics of the furosemide-sensitive pathway were similar to those of a broad-specificity pathway that is induced in human erythrocytes infected in vitro with Plasmodium falciparum. The results of this study rule out the possibility that the induced transport pathway of P. falciparum-infected erythrocytes is an artifact arising in vitro from the long-term culture of parasitized cells and provide evidence that this pathway makes a significant contribution to the uptake of choline into the parasitized cells of malaria-infected animals.

'You feel helpless, that's exactly it': parents' and young people's control beliefs about bed-wetting and the implications for practice.

'You feel helpless, that's exactly it': parents' and young people's control beliefs about bed-wetting and the implications for practice Young people wet the bed when they fail to wake up to a full bladder. The causes of bed-wetting are far from certain and this uncertainty is reflected in the diversity of treatments on offer and the lack of any guarantee that treatment will work in a particular case. Most young people are sad and ashamed about the bed-wetting and want it to stop, but they vary widely in their belief in their own capacity to influence the situation, and in their optimism about what the future holds. The problem can persist into adolescence or even adulthood, with far reaching social and emotional consequences, both for the young people and their families. In an ethnographic study involving 19 families 'perceived helplessness' emerged as a key issue permeating the whole system and often activating a downward spiral, leading to abdication of effort and responsibility by the young people themselves, by their parents and sometimes by health care professionals. Informed by the insights gained from this study and an extensive review of the literature on perceived control the Family Perspectives on Bed Wetting Questionnaire has been developed to explore family members' feelings, degree of concern and dimensions of perceived control relating to: effort, ability, luck, important others and the unknown. This questionnaire was used as a basis for structured interviews with family members in a longitudinal survey, involving 40 families attending one of nine community-based, nurse-led enuresis clinics in Greater Glasgow. It was found that only 38% of the young people were entering into treatment with the belief that they had the ability to be dry at night. This became self-fulfilling, with only 33% achieving initial success of 14 consecutive dry nights in a 16-week period (chi-squared test, P=0.029). Seventy per cent of young people felt that luck was important, while most parents felt that luck had little part to play. Implications for practice include the need to assess the families' readiness to engage in treatment, to create opportunities for effective control and to encourage realistic expectations.

Weekly monitoring of broiler breeder flock mating efficiency by sperm transfer into eggs.

1. Sample fertility and the median number of points of hydrolysis produced by spermatozoa in the perivitelline layer from the germinal disc area were determined in samples of 60 eggs taken weekly from each of two commercial broiler breeder flocks. 2. Flock fertility remained above 90% from weeks 30 to 45, after which it fell in both flocks, reaching 85% in Flock A by week 51 and 76% in Flock B by week 55. 3. Sample fertility, as assessed by the Kosin test, followed a similar trend, but showed more variation; the same was true for the proportion of eggs with at least one perivitelline hole. 4. In Flock A, the median number of perivitelline holes in samples increased from 145 in week 30 to reach a maximum of 323 on week 39, thereafter falling to 109 in week 51; for Flock B, the equivalent figures for weeks 30, 36 and 55 were 160, 266 and 29, respectively. A quadratic model confirmed that the weekly sample median perivitelline holes peaked at weeks 40 and 37 in Flocks A and B, respectively. 5. The results show that transfer of spermatozoa by males into females and subsequently into eggs begins to decline 8 (Flock A) to 9 (Flock B) weeks before it is noticeable as a significant reduction in flock fertility and that mating efficiency, unlike fertility, is never in apparent equilibrium, but rises to a peak before 40 weeks and then falls. 6. The pattern of sperm transfer suggests that the reduction in fertility of broiler flocks could well be for social or for physiological reasons other than those associated with 'ageing'.