Implications of bacterial mineralisation in aquatic ecosystem response models.

Widespread wastewater pollution is a major barrier to the sustainable management of freshwater and coastal marine ecosystems worldwide. Integrated multi-disciplinary studies are necessary to improve waterway management and protect ecosystem integrity. This study used the Generalised Likelihood Uncertainty Estimation (GLUE) methodology to link microbial community ecotoxicology laboratory data to a mechanistic aquatic ecosystem response model. The generic model provided good predictive skill for major water quality constituents, including heterotrophic bacteria dynamics (r2 = 0.91). The model was validated against observed data across a gradient of effluent concentrations from community whole effluent toxicity (WET) laboratory tests. GLUE analysis revealed that a combined likelihood measure increased confidence in the predictive capability of the model. This study highlights the importance of calibrating aquatic ecosystem response models with net growth rates (i.e., sum of the growth minus loss rate parameter terms) of biological functional groups. The final calibrated net growth rate value of heterotrophic bacteria determined using the GLUE analysis was selected to be 0.58, which was significantly greater than the average literature value of -0.15. This finding demonstrated that use of literature parameter values without a good understanding of the represented processes could create misleading outputs and result in unsatisfactory conclusions. Further, fixed bulk mineralisation rate literature values are typically higher than realistically required in aquatic ecosystem response models. This indicates that explicitly including bacterial mineralisation is crucial to represent microbial ecosystem functioning more accurately. Our study suggests that improved data collection and modelling efforts in real-world management applications are needed to better address nutrients released into the natural environment. Future studies should aim to better understand the sensitivity of aquatic ecosystem response models to bacterial mineralisation rates.

Wastewater effluents cause microbial community shifts and change trophic status.

Widespread wastewater pollution is one of the greatest challenges threatening the sustainable management of rivers globally. Understanding microbial responses to gradients in environmental stressors, such as wastewater pollution, is crucial to identify thresholds of community change and to develop management strategies that protect ecosystem integrity. This study used multiple lines of empirical evidence, including a novel combination of microbial ecotoxicology methods in the laboratory and field to link pressure-stressor-response relationships. Specifically, community-based whole effluent toxicity (WET) testing and environmental genomics were integrated to determine real-world community interactions, shifts and functional change in response to wastewater pollution. Here we show that wastewater effluents above moderate (>10%) concentrations caused consistent significant shifts in bacterial community structure and function. These thresholds of community shifts were also linked to changes in the trophic state of receiving waters in terms of nutrient concentrations. Differences in the community responses along the effluent concentration gradient were primarily driven by two globally relevant bacterial indicator taxa, namely Malikia spp. (Burkholderiales) and hgcI_clade (Frankiales). Species replacement occurred above moderate effluent concentrations with abundances of Malikia spp. increasing, while abundances of hgcI_clade decreased. The responses of Malikia spp. and hgcI_clade matched gene patterns associated with globally important nitrogen cycling pathways, such as denitrification and nitrogen fixation, which linked the core individual taxa to putative function and ecosystem processes, rarely achieved in previous studies. This study has identified potential indicators of change in trophic status and the functional consequences of wastewater pollution. These findings have immediate implications for both the management of environmental stressors and protection of aquatic ecosystems.

A novel real-world ecotoxicological dataset of pelagic microbial community responses to wastewater.

Real-world observational datasets that record and quantify pressure-stressor-response linkages between effluent discharges and natural aquatic systems are rare. With global wastewater volumes increasing at unprecedented rates, it is urgent that the present dataset is available to provide the necessary information about microbial community structure and functioning. Field studies were performed at two time-points in the Austral summer. Single-species and microbial community whole effluent toxicity (WET) testing was performed at a complete range of effluent concentrations and two salinities, with accompanying environmental data to provide new insights into nutrient and organic matter cycling, and to identify ecotoxicological tipping points. The two salinity regimes were chosen to investigate future scenarios based on a predicted salinity increase at the study site, typical of coastal regions with rising sea levels globally. Flow cytometry, amplicon sequencing of 16S and 18S rRNA genes and micro-fluidic quantitative polymerase-chain reactions (MFQPCR) were used to determine chlorophyll-a and total bacterial cell numbers and size, as well as taxonomic and functional diversity of pelagic microbial communities. This strong pilot dataset could be replicated in other regions globally and would be of high value to scientists and engineers to support the next advances in microbial ecotoxicology, environmental biomonitoring and estuarine water quality modelling.

Variations in the management of significant polyps and early colorectal cancer: results from a multicentre observational study of 383 patients.

AIM: The concept of significant polyps and early colorectal cancer (SPECC) encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. Surgical resection (SR) offers definitive treatment, but is overtreatment for the majority which are benign and amenable to less invasive endoscopic resection (ER). The aim of this study was to investigate variations in the management and outcomes of significant colorectal polyps. METHOD: This was a retrospective observational study of significant colorectal polyps, defined as nonpedunculated lesions of ≥ 20 mm size, diagnosed across nine UK hospitals in 2014. Inclusion criteria were endoscopically or histologically benign polyps at biopsy. RESULTS: A total of 383 patients were treated by primary ER (87.2%) or SR (12.8%). Overall, 108/383 (28%) polyps were detected in the Bowel Cancer Screening Programme (BCSP). Primary SR was associated with a significantly longer length of stay and major complications (P < 0.01). Of the ER polyps, 290/334 (86.8%) patients were treated without undergoing surgery. The commonest indication for secondary surgery was unexpected polyp cancer, and of these cases 60% had no residual cancer in the specimen. Incidence of unexpected cancer was 10.7% (n = 41) and was similar between ER and SR groups (P = 0.11). On multivariate analysis, a polyp size of > 30 mm and non-BCSP status were independent risk factors for primary SR [OR 2.51 (95% CI 1.08-5.82), P = 0.03]. CONCLUSION: ER is safe and feasible for treating significant colorectal polyps. Robust accreditation within the BCSP has led to improvements in management, with lower rates of SR compared with non-BCSP patients. Standardization, training in polyp assessment and treatment within a multidisciplinary team may help to select appropriate treatment strategies and improve outcomes.

A new technique for probing chirality via photoelectron circular dichroism.

We present a proof-of-principle approach for discriminating chiral enantiomers based on the phenomenon of multiphoton photoelectron circular dichroism. A novel stereo detection setup was used to measure the number of photoelectrons emitted from chiral molecules in directions parallel or anti-parallel to the propagation of the ionising femtosecond laser pulses. In this study, we show how these asymmetries in the ketones camphor and fenchone depend upon the ellipticity of the laser pulses and the enantiomeric excess of the sample. By using a high repetition rate femtosecond laser, enantiomer excesses with uncertainties at the few-percent level could be measured in close to real-time. As the instrument is compact, and commercial turnkey femtosecond lasers are readily available, the development of a stand-alone chiral analysis instrument for a range of applications is now possible.

The LOREC APE registry: operative technique, oncological outcome and perineal wound healing after abdominoperineal excision.

AIM: The Low Rectal Cancer Development programme (LOREC) perineal wound healing registry was developed to record data on abdominoperineal excision (APE) for rectal cancer in colorectal units in England between 2012 and 2014, to understand current practice in operative technique and results. METHOD: Surgeons wishing to participate received secure Web-based access to the registry. Data were collected on preoperative staging, neoadjuvant treatment, operative details, histopathology, early outcome and follow up at 12 months. RESULTS: Forty-two units entered 266 patients. Of these, 172 (65%) patients underwent extralevator APE (ELAPE) and 94 had non-ELAPE procedures. On preoperative staging, 64% were mrT3/4, and 67% received neoadjuvant treatment. For the ELAPE group the perineal wound was closed primarily with mesh in 55% of patients, without mesh in 15% and with a flap in 21%. For non-ELAPE procedures, 54% of wounds were closed primarily without mesh, 29% primarily with mesh and 5% by a flap. Wound breakdown occurred in 30% and 31% of patients in the ELAPE and non-ELAPE groups, respectively, and was more common after neoadjuvant radiotherapy. Donor-site complications occurred in 17% of patients treated with a flap. Perineal morbidity was recorded in 11% of patients at 12 months. On histopathology, the resection margin was positive in 13% of patients in the ELAPE group and in 4% of patients in the non-ELAPE group. CONCLUSION: The LOREC registry provides a picture of current APE practice in England. ELAPE was used in two-thirds of patients but does not appear to confer any additional morbidity. Primary closure with mesh appeared as effective as flap reconstruction. The prevalence of an involved resection margin was lower than reported in many historical series but still remains high in the ELAPE group.

The English national low rectal cancer development programme: key messages and future perspectives.

AIM: Adenocarcinoma of the lower rectum is clinically challenging because of the need to choose between a wide excision to achieve oncological clearance, on the one hand, and sphincter conservation to maintain anal function, on the other. The English National Low Rectal Cancer Development Programme (LOREC) was developed under the auspices of the Association of Coloproctology of Great Britain and Ireland and the English National Cancer Action Team to improve the outcome of low rectal cancer in England. METHOD: LOREC was initiated focusing on preoperative imaging, selective neoadjuvant therapy, optimal surgical treatment and detailed pathological assessment of the excised specimen. Its key elements were 1-day multidisciplinary team (MDT) workshops, cadaveric surgical training, surgical mentoring, pathological audit and radiological workshops. RESULTS: Overall, 147 (89.6%) of 164 MDTs from 151 National Health Service (NHS) Trusts (some with two MDTs) in England participated in 15 workshops in Basingstoke or Leeds. In addition, 112 surgeons attended a 1-day cadaveric training programme in Bristol, Newcastle or Nottingham, with the main focus on extralevator abdominoperineal excision and pelvic reconstruction, with input from anatomists and from colorectal and plastic surgeons. CONCLUSION: Optimal staging, selective preoperative chemoradiotherapy and precise surgery were considered as crucial to improve the outcome for patients with low rectal cancer.

A multicentre randomised controlled trial of the use of continuous positive airway pressure and non-invasive positive pressure ventilation in the early treatment of patients presenting to the emergency department with severe acute cardiogenic pulmonary oedema: the 3CPO trial.

OBJECTIVES: To determine whether non-invasive ventilation reduces mortality and whether there are important differences in outcome by treatment modality. DESIGN: Multicentre open prospective randomised controlled trial. SETTING: Patients presenting with severe acute cardiogenic pulmonary oedema in 26 emergency departments in the UK. PARTICIPANTS: Inclusion criteria were age > 16 years, clinical diagnosis of acute cardiogenic pulmonary oedema, pulmonary oedema on chest radiograph, respiratory rate > 20 breaths per minute, and arterial hydrogen ion concentration > 45 nmol/l (pH < 7.35). INTERVENTIONS: Patients were randomised to standard oxygen therapy, continuous positive airway pressure (CPAP) (5-15 cmH2O) or non-invasive positive pressure ventilation (NIPPV) (inspiratory pressure 8-20 cmH2O, expiratory pressure 4-10 cmH2O) on a 1:1:1 basis for a minimum of 2 hours. MAIN OUTCOME MEASURES: The primary end point for the comparison between NIPPV or CPAP and standard therapy was 7-day mortality. The composite primary end point for the comparison of NIPPV and CPAP was 7-day mortality and tracheal intubation rate. Secondary end points were breathlessness, physiological variables, intubation rate, length of hospital stay and critical care admission rate. Economic evaluation took the form of a cost-utility analysis, taken from an NHS (and personal social services) perspective. RESULTS: In total, 1069 patients [mean age 78 (SD 10) years; 43% male] were recruited to standard therapy (n = 367), CPAP [n = 346; mean 10 (SD 4) cmH2O] or NIPPV [n = 356; mean 14 (SD 5)/7 (SD 2) cmH2O]. There was no difference in 7-day mortality for standard oxygen therapy (9.8%) and non-invasive ventilation (9.5%; p = 0.87). The combined end point of 7-day death and intubation rate was similar, irrespective of non-invasive ventilation modality (CPAP 11.7% versus NIPPV 11.1%; p = 0.81). Compared with standard therapy, non-invasive ventilation was associated with greater reductions (treatment difference, 95% confidence intervals) in breathlessness (visual analogue scale score 0.7, 0.2-1.3; p = 0.008) and heart rate (4/min, 1-6; p = 0.004) and improvement in acidosis (pH 0.03, 0.02-0.04; p < 0.001) and hypercapnia (0.7 kPa, 0.4-0.9; p < 0.001) at 1 hour. There were no treatment-related adverse events or differences in other secondary outcomes such as myocardial infarction rate, length of hospital stay, critical care admission rate and requirement for endotracheal intubation. Economic evaluation showed that mean costs and QALYs up to 6 months were 3023 pounds and 0.202 for standard therapy, 3224 pounds and 0.213 for CPAP, and 3208 pounds and 0.210 for NIPPV. Modelling of lifetime costs and QALYs produced values of 15,764 pounds and 1.597 for standard therapy, 17,525 pounds and 1.841 for CPAP, and 17,021 pounds and 1.707 for NIPPV. These results suggest that both CPAP and NIPPV accrue more QALYs but at higher cost than standard therapy. However, these estimates are subject to substantial uncertainty. CONCLUSIONS: Non-invasive ventilatory support delivered by either CPAP or NIPPV safely provides earlier improvement and resolution of breathlessness, respiratory distress and metabolic abnormality. However, this does not translate into improved short- or longer-term survival. We recommend that CPAP or NIPPV should be considered as adjunctive therapy in patients with severe acute cardiogenic pulmonary oedema in the presence of severe respiratory distress or when there is a failure to improve with pharmacological therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN07448447.

The changing incidence of oesophageal and gastric adenocarcinoma by anatomic sub-site.

BACKGROUND: The incidence rates of gastric and oesophageal adenocarcinoma are changing significantly, but little is known about specific sub-sites. AIM: To use a population-based approach to describe the trends in the site-specific incidence of oesophageal and gastric adenocarcinoma. METHODS: Using the Rochester Epidemiology Project, all cases of gastric and oesophageal adenocarcinoma among Olmsted County, Minnesota, residents first diagnosed between 1971 and 2000 were identified (n = 186). Complete in-patient and out-patient records were reviewed and site determined from pathological, surgical, endoscopic and radiological reports. RESULTS: Between the decades of 1971-1980 and 1991-2000, the incidence of oesophageal adenocarcinoma increased significantly from 0.4 to 2.5 per 100 000 person-years. The incidence of adenocarcinoma of the oesophagogastric junction also increased from a rate of 0.6 to 2.2 per 100 000 person-years. The incidence rate of cancer involving the gastric cardia was stable but the incidence of adenocarcinoma involving distal gastric sites declined. Combined oesophageal and oesophagogastric junction adenocarcinoma (4.7 per 1 000 000 person-years) was as common as gastric adenocarcinoma (3.4 per 100 000 person-years) in 1991-2000. CONCLUSIONS: The incidence rates of adenocarcinoma involving proximal gastric sub-sites do not appear to be increasing in a manner similar to those involving oesophageal sub-sites.

Accuracy of radiographers red dot or triage of accident and emergency radiographs in clinical practice: a systematic review.

AIM: To determine the accuracy of radiographers red dot or triage of accident and emergency (A&E) radiographs in clinical practice. MATERIALS AND METHODS: Eligible studies assessed radiographers red dot or triage of A&E radiographs in clinical practice compared with a reference standard and provided accuracy data to construct 2 x 2 tables. Data were extracted on study eligibility and characteristics, quality, and accuracy. Pooled sensitivities and specificities and chi-square tests of heterogeneity were calculated. RESULT: Three red dot and five triage studies were eligible for inclusion. Radiographers' red dot of A&E radiographs in clinical practice compared with a reference standard is 0.87 [95% confidence interval (CI) 0.85-0.89] and 0.92 (0.91-0.93) sensitivity and specificity, respectively. Radiographers' triage of A&E radiographs of the skeleton is 0.90 (0.89-0.92) and 0.94 (0.93-0.94) sensitivity and specificity, respectively; and for chest and abdomen is 0.78 (0.74-0.82) and 0.91 (0.88-0.93). Radiographers' red dot of skeletal A&E radiographs without training is 0.71 (0.62-0.79) and 0.96 (0.93-0.97) sensitivity and specificity, respectively; and with training is 0.81 (0.72-0.87) and 0.95 (0.93-0.97). Pooled sensitivity and specificity for radiographers without training for the triage of skeletal A&E radiographs is 0.89 (0.88-0.91) and 0.93 (0.92-0.94); and with training is 0.91 (0.88-0.94) and 0.95 (0.93-0.96). CONCLUSION: Radiographers red dot or triage of A&E radiographs in clinical practice is affected by body area, but not by training.

Radiographers and radiologists reporting plain radiograph requests from accident and emergency and general practice.

AIM: To assess selectively trained radiographers and consultant radiologists reporting plain radiographs for the Accident and Emergency Department (A&E) and general practitioners (GPs) within a typical hospital setting. METHODS: Two radiographers, a group of eight consultant radiologists, and a reference standard radiologist independently reported under controlled conditions a retrospectively selected, random, stratified sample of 400 A&E and 400 GP plain radiographs. An independent consultant radiologist judged whether the radiographer and radiologist reports agreed with the reference standard report. Clinicians then assessed whether radiographer and radiologist incorrect reports affected confidence in their diagnosis and treatment plans, and patient outcome. RESULTS: For A&E and GP plain radiographs, respectively, there was a 1% (95% confidence interval (CI) -2 to 5) and 4% (95% CI -1 to 8) difference in reporting accuracy between the two professional groups. For both A&E and GP cases there was an 8% difference in the clinicians' confidence in their diagnosis based on radiographer or radiologist incorrect reports. For A&E and GP cases, respectively, there was a 2% and 8% difference in the clinicians' confidence in their management plans based on radiographer or radiologist incorrect reports. For A&E and GP cases, respectively, there was a 1% and 11% difference in effect on patient outcome of radiographer or radiologist incorrect reports. CONCLUSION: There is the potential to extend the reporting role of selectively trained radiographers to include plain radiographs for all A&E and GP patients. Further research conducted during clinical practice at a number of sites is recommended.

The costs and effects of introducing selectively trained radiographers to an A&E reporting service: a retrospective controlled before and after study.

The costs and effects of introducing selectively trained radiographers reporting accident and emergency (A&E) radiographs of the appendicular skeleton in a district general hospital were assessed using a retrospective controlled before and after design. Reference standard reports were compared with a random stratified sample of 200 A&E and 200 general practitioner (GP) reports before and after the intervention. GP reports were used as a non-intervention, non-equivalent control group. An A&E specialist registrar judged whether incorrect A&E reports might have a clinically important effect on patient management. The effect of incorrect A&E reports on outcome was assessed by patient re-attendance to the hospital because of missed abnormalities. The annual, average and incremental costs of radiographers and radiologists reporting A&E radiographs were calculated and a sensitivity analysis was undertaken. The introduction of the radiographers resulted in a 1% (95% CI -7.9 to 5.9) fall in A&E radiograph reporting accuracy and 11% (95% CI -33.7 to 11.3) reduction of cases in which incorrect A&E reports might have a clinically important effect on patient management. Only two A&E reports (one before and one after the intervention) affected patient outcome in that a fracture missed at the first visit resulted in patient re-attendance to the X-ray Department. There was a saving of 361 pounds per annum to the X-ray Department. In conclusion this study provides further evidence that selectively trained radiographers can accurately report A&E plain radiographs and at no additional cost.

Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema.

BACKGROUND: Continuous positive airways pressure (CPAP) and bilevel non-invasive ventilation may have beneficial effects in the treatment of patients with acute cardiogenic pulmonary oedema. The efficacy of both treatments was assessed in the UK emergency department setting, in a randomised comparison with standard oxygen therapy. METHODS: Sixty patients presenting with acidotic (pH<7.35) acute, cardiogenic pulmonary oedema, were randomly assigned conventional oxygen therapy, CPAP (10 cm H(2)O), or bilevel ventilation (IPAP 15 cm H(2)O, EPAP 5 cm H(2)O) provided by a standard ventilator through a face mask. The main end points were treatment success at two hours and in-hospital mortality. Analyses were by intention to treat. RESULTS: Treatment success (defined as all of respiratory rate<23 bpm, oxygen saturation of>90%, and arterial blood pH>7.35 (that is, reversal of acidosis), at the end of the two hour study period) occurred in three (15%) patients in the control group, seven (35%) in the CPAP group, and nine (45%) in the bilevel group (p = 0.116). Fourteen (70%) of the control group patients survived to hospital discharge, compared with 20 (100%) in the CPAP group and 15 (75%) in the bilevel group (p = 0.029; Fisher's test). CONCLUSIONS: In this study, patients presenting with acute cardiogenic pulmonary oedema and acidosis, were more likely to survive to hospital discharge if treated with CPAP, rather than with bilevel ventilation or with conventional oxygen therapy. There was no relation between in hospital survival and early physiological changes. Survival rates were similar to other studies despite a low rate of endotracheal intubation.

Risk stratification of patients with syncope in an accident and emergency department.

OBJECTIVES: This study categorised syncopal patients, in a British accident and emergency (A&E) department, into three prognostic groups, using American College of Physicians (ACP) guidelines. The one year mortality of the three groups was studied to see if risk stratification using these guidelines is applicable to these patients and also whether admission improved outcome. METHODS: The records of all syncopal patients presenting to the Leeds General Infirmary A&E department during an eight week period from 2 November 1998 were identified. The cohort was grouped according to ACP guidelines into those who had an absolute indication for admission (group 1), a probable indication for admission (group 2) and no indication for admission (group 3). The actual disposal was recorded and for each patient mortality data were retrieved from general practices or health authorities one year later. The three groups were compared. RESULTS: Two hundred and ten records (1.7% of all new patients aged 16 years or above) were analysed. Forty per cent of the cohort were not assigned a diagnosis after their assessment in A&E. Forty seven (22%) were placed in ACP group 1, 63 (30%) in ACP group 2 and 100 (48%) in ACP group 3. Thirty six per cent of those in group 1 had died within a year, 14% of those in group 2 and none of those in group 3. In neither group 1 patients ("high risk") nor group 2 patients ("moderate risk") did admission to the hospital seem to influence outcome. However, three patients died within a week of their presentation, and two of them had been discharged from A&E. CONCLUSION: It is possible to stratify syncopal patients presenting acutely to A&E, according to prognosis, using ACP guidelines. Disposal decisions for these patients should be based on their apparent prognosis (as defined in the ACP guidelines) and not on the diagnosis, which is often difficult to make.

Visual categorical perception by rats with temporal, striate, or sham ablations.

Rats were trained to discriminate a 0 degrees stripe from a 90 degrees stripe in a two choice water maze. They were prepared with either Te2/3, partial striate (PS), or sham lesions and retrained on the preoperative discrimination. In two separate experiments, excellent savings was observed for all groups. Next, trials were administered with novel stripe orientations defined as either between- or within-category problems. Performance accuracy eroded rapidly for all groups in the first experiment, and no between-group differences were observed. In the second experiment, each session with categorical stimuli was preceded by four reminder trials with the original stimuli. This improved accuracy for all groups, but it was found that animals with PS lesions, not animals with T2/3 lesions, were impaired on between-category judgements. The impairment was not secondary to a disruption of basic visual sensory processing or significantly larger lesions relative to the Te2/3 group. As is the case for monkeys, accuracy with within-category stimuli was inferior to between-category stimuli for all groups. Possible reasons for this inter-species difference are discussed.