Offset integrity reduces environmental risk: Using lessons from biodiversity and carbon offsetting to inform water quality offsetting in the catchments of the Great Barrier Reef.

Environmental offsetting has been developed as a mechanism to facilitate the benefits from economic development while avoiding or minimizing environmental harm. This is achieved by compensating for environmental impacts at one location by generating equivalent environmental improvements elsewhere. However, experience with biodiversity and carbon offsetting indicates it can be difficult to ensure the integrity of offsets. Under recent legislation in the catchments of the Great Barrier Reef (GBR), Australia, it is mandatory for water quality emissions from new or expanded point source development to be offset by reducing pollution elsewhere, frequently through reducing non-point source pollution (NPSP). Therefore, informed by experience with biodiversity and carbon offsetting, we summarised sources of uncertainty in NPSP reduction that would influence water quality offset integrity; estimated the maximum potential demand for water quality offsets from sewage treatment plants, the largest point source emitter of total nitrogen (TN) in the GBR catchments, between 2018 and 2050; and discussed the implications of both on the ability of offsetting to counterbalance the impact of economic development in catchments where nitrogen loads have a large influence on the health of important GBR ecosystems. The catchments surrounding the population centres of Cairns and Mackay had both a potentially high future demand for nitrogen water quality offsets and nitrogen loads with a strong influence on the health of the GBR. Consequently, any low integrity water quality offsets in these catchments could jeopardise progress toward the water quality improvements needed to ensure the continued health of the GBR. Water quality offsetting has numerous strengths as a policy instrument however substantial uncertainties remain related to environmental outcomes. Until further research can reduce these uncertainties, water quality offsets that are implemented near increased point source emissions and have a high certainty of effectiveness may provide a balance between scientific rigour and policy workability.

Investigation of an outbreak of vomiting in nurseries in South East England, May 2012.

On 30 May 2012, Surrey and Sussex Health Protection Unit was called by five nurseries reporting children and staff with sudden onset vomiting approximately an hour after finishing their lunch that day. Over the following 24 h 50 further nurseries supplied by the same company reported cases of vomiting (182 children, 18 staff affected). Epidemiological investigations were undertaken in order to identify the cause of the outbreak and prevent further cases. Investigations demonstrated a nursery-level attack rate of 55 out of 87 nurseries (63·2%, 95% confidence interval 52·2-73·3). Microbiological tests confirmed the presence of Bacillus cereus in food and environmental samples from the catering company and one nursery. This was considered microbiologically and epidemiologically consistent with toxin from this bacterium causing the outbreak. Laboratory investigations showed that the conditions used by the caterer for soaking of pearl haricot beans (known as navy bean in the USA) used in one of the foods supplied to the nurseries prior to cooking, was likely to have provided sufficient growth and toxin production of B. cereus to cause illness. This large outbreak demonstrates the need for careful temperature control in food preparation.

High-dose ranibizumab monotherapy for neovascular polypoidal choroidal vasculopathy in a predominantly non-Asian population.

PURPOSE: To determine safety and efficacy of intravitreal high-dose ranibizumab in the treatment of active neovascular polypoidal choroidal vasculopathy (PCV). METHODS: In this Phase I/II, single-center, randomized, controlled, double-masked study, predominantly non-Asian, previously treated or treatment-naive, male and female adult patients were randomized to receive high-dose (1.0/0.1 ml or 2.0 mg/0.05 ml; n=15) or standard-dose (0.5 mg/0.05 ml; n=5) ranibizumab in 3 monthly loading doses, followed by 9 months of criteria-based, as-needed retreatment. Safety was evaluated by a descriptive analysis of all non-serious and serious adverse events, angiographic assessments, physical examinations, vital signs, ocular examinations, and visual acuity measurements. Visual acuity and anatomic outcomes are described for the high-dose group. RESULTS: Twenty patients (aged 35-76 years; 8 Black, 11 White, 1 Asian) were enrolled. At baseline, in the high-dose group, mean best-corrected visual acuity (BCVA) was 63.5 letters (Snellen equivalent ~20/50), and mean baseline central foveal thickness (CFT) was 253.7 µm. High-dose ranibizumab was generally well tolerated without evidence of ocular or systemic severe adverse events, including arterial thromboembolic events. At month 12, in the high-dose group, the mean overall change from baseline in BCVA was +6.7 letters and in CFT was -49.7 µm. CONCLUSION: High-dose ranibizumab monotherapy is safe and efficacious for treating patients with PCV.

Outcomes associated with a thrice-weekly antimicrobial stewardship programme in a 253-bed community hospital.

WHAT IS KNOWN AND OBJECTIVES: Antimicrobial stewardship programmes (ASPs) have been shown to decrease antimicrobial resistance, reduce hospital-acquired infections and decrease overall antimicrobial expenditures. At St. Joseph Medical Center in Bellingham, WA, a thrice-weekly ASP was initiated in 2010 with the goals of decreasing carbapenem, fluoroquinolone and vancomycin use and tailoring duration of therapy. METHODS: Antibiotic use per 1000 patient-days and carbapenem, fluoroquinolone and vancomycin use were evaluated pre- and post-implementation of the ASP. Total antimicrobial expenditures were evaluated for the 3 years prior to ASP implementation and three years following implementation. RESULTS AND DISCUSSION: Antimicrobial days of therapy per 1000 patient-days declined by 6·4% after implementation of our ASP. There was a 37% reduction in total antimicrobial expenditures after implementation. Carbapenems, vancomycin and levofloxacin use decreased considerably. Ciprofloxacin use increased during the same time period. WHAT IS NEW AND CONCLUSION: A thrice-weekly, pharmacist-driven ASP can decrease antimicrobial expenditure, shorten duration of therapy and decrease the utilization of carbapenems, vancomycin and levofloxacin.

Winter food provisioning reduces future breeding performance in a wild bird.

Supplementation of food to wild birds occurs on an enormous scale worldwide, and is often cited as an exemplar of beneficial human-wildlife interaction. Recently it has been speculated that winter feeding could have negative consequences for future reproduction, for example by enabling low quality individuals to recruit into breeding populations. However, evidence that winter feeding has deleterious impacts on reproductive success is lacking. Here, in a landscape-scale study of blue tits (Cyanistes caeruleus) across multiple years, we show that winter food supplementation reduced breeding performance the following spring. Compared to unfed populations, winter-fed birds produced offspring that weighed less, were smaller, and had lower survival. This impairment was observed in parents that had received fat only, or in combination with vitamin E, suggesting some generality in the mechanism by which supplementary feeding affected reproduction. Our results highlight the potential for deleterious population-level consequences of winter food supplementation on wild birds.

Does organic farming benefit farmland birds in winter?

The generally higher biodiversity on organic farms may be influenced by management features such as no synthetic pesticide and fertilizer inputs and/or by differences in uncropped habitat at the site and landscape scale. We analysed bird and habitat data collected on 48 paired organic and conventional farms over two winters to determine the extent to which broad-scale habitat differences between systems could explain overall differences in farmland bird abundance. Density was significantly higher on organic farms for six out of 16 species, and none on conventional. Total abundance of all species combined was higher on organic farms in both years. Analyses using an information-theoretic approach suggested that both habitat extent and farm type were important predictors only for starling and greenfinch. Organic farming as currently practised may not provide significant benefits to those bird species that are limited by winter food resources, in particular, several declining granivores.

A national scheme for public access defibrillation in England and Wales: early results.

BACKGROUND: Automated external defibrillators (AEDs) operated by lay persons are used in the UK in a National Defibrillator Programme promoting public access defibrillation (PAD). METHODS: Two strategies are used: (1) Static AEDs installed permanently in busy public places operated by those working nearby. (2) Mobile AEDs operated by community first responders (CFRs) who travel to the casualty. RESULTS: One thousand five hundred and thirty resuscitation attempts. With static AEDs, return of spontaneous circulation (ROSC) was achieved in 170/437 (39%) patients, hospital discharge in 113/437 (26%). With mobile AEDs, ROSC was achieved in 110/1093 (10%), hospital discharge in 32 (2.9%) (P<0.001 for both variables). More shocks were administered with static AEDS 347/437 (79%) than mobile AEDs 388/1093 (35.5%) P<0.001. Highly significant advantages existed for witnessed arrests, administration of shocks, bystander CPR before arrival of AED and short delays to start CPR and attach AED. These factors were more common with static AEDs. For CFRs, patients at home did less well than those at other locations for ROSC (P<0.001) and survival (P=.006). Patients at home were older, more arrests were unwitnessed, fewer shocks were given, delays to start CPR and attach electrodes were longer. CONCLUSIONS: PAD is a highly effective strategy for patients with sudden cardiac arrest due to ventricular fibrillation who arrest in public places where AEDs are installed. Community responders who travel with an AED are less effective, but offer some prospect of resuscitation for many patients who would otherwise receive no treatment. Both strategies merit continuing development.

Bibliotherapy and information prescriptions: a summary of the published evidence-base and recommendations from past and ongoing Books on Prescription projects.

This paper summarizes the published evidence and reports from ongoing and completed projects that used Bibliotherapy and Information Prescription to deliver patient care. A literature search was conducted and relevant papers were summarized into: type of study, type of Bibliotherapy, client group and recommendations. In total, 65 papers were considered with 57 reviewed. A survey was also sent to Library Authorities subscribing to national survey standards asking for details about delivery of Information Prescription projects. There were 21 returned surveys. The experiences and recommendations were then summarized. The aim of the paper is to collate the evidence-base of written research and the experience and recommendations of projects into an easy format so that practitioners interested in using Bibliotherapy/Information Prescription/Books on Prescription have an understanding what they are, the extent of the evidence-base to inform practice, and highlight gaps in the research.

Intrinsic stability and functional properties of disulfide bond-stabilized coagulation factor VIIIa variants.

BACKGROUND: The utility of purified coagulation factor (F)VIII for treatment of hemophilia A is limited in part by its instability following activation by thrombin, which is caused by spontaneous dissociation of the A2 domain from the activated FVIII (FVIIIa) heterotrimer. To prevent this A2 domain dissociation in FVIIIa, we previously engineered a cysteine pair (C664-C1826) in recombinant FVIII that formed a disulfide bond cross-linking the A2 domain in the heavy chain to the A3 domain in the light chain. This engineered disulfide bond resulted in a more stable FVIIIa. AIMS: Here, we characterize the functional parameters of C664-C1828 FVIII and of a new disulfide bond-stabilized FVIII (C662-C1828 FVIII). METHODS: In order to assess whether these FVIII variants might be good candidates for a new therapeutic agent to treat hemophilia A, we investigated a variety of functional parameters that might affect the in vivo properties of the variants, including half-life of disulfide bond-stabilized FVIII and FVIIIa and the potency of these FVIIIa molecules in the FXase complex. RESULTS: Both disulfide bond-stabilized variants had improved affinity for von Willebrand factor (VWF). In studies of FX activation by purified FIXa and FVIIIa, C662-C1828 FVIIIa had normal activity while C664-C1826 FVIIIa had reduced activity. Both C664-C1826 FVIIIa and C662-C1828 FVIIIa were inactivated by activated protein C (APC) but the rates of inactivation were different. CONCLUSION: Overall, the specific location of the disulfide bridge between the A2 and A3 domains appears to affect functional properties of FVIIIa. In summary, introduction of engineered interdomain disulfides results in FVIIIa variants that resist spontaneous loss of activity while retaining susceptibility to APC proteolytic inactivation and maintaining VWF binding.

Interventional versus conservative treatment in acute non-ST elevation coronary syndrome: time course of patient management and disease events over one year in the RITA 3 trial.

OBJECTIVE: To determine whether, in acute non-ST elevation coronary syndrome, the benefit from early invasive coronary intervention compared with a conservative strategy of later symptom-guided intervention varies over time. METHODS: In RITA 3 (Randomised Intervention Trial of unstable Angina 3) patients were randomly assigned to coronary angiography (median 2 days after randomisation) and appropriate intervention (n = 895) or to a symptom-guided conservative strategy (n = 915). RESULTS: In the first week patients in both groups were at highest risk of death, myocardial infarction (MI) or refractory angina (incidence rate 40 times higher than in months 5-12 of follow up). There were 22 MIs and 6 deaths in the intervention group (largely due to procedure-related events, 14 MIs and 3 deaths) versus 17 MIs and 3 deaths in the conservative group. In the rest of the year there were an additional 12 versus 27 MIs, respectively (treatment-time interaction p = 0.021). Over one year in the intervention group there was a 43% reduction in refractory angina; 22% of patients underwent coronary artery bypass surgery and 35% underwent percutaneous coronary intervention only, which reduced refractory angina but provoked some early MIs; and 43% were still treated medically, mostly because of a favourable initial angiogram. CONCLUSION: Any intervention policy needs to recognise the high risk of events in the first week and the substantial minority of patients not needing intervention. Intervention may be best targeted at higher risk patients, as the early hazards of the procedure are then offset by reduced subsequent events.

A national programme for on-site defibrillation by lay people in selected high risk areas: initial results.

OBJECTIVE: To report on the effectiveness of an initiative to reduce deaths from sudden cardiac arrest occurring in busy public places. SETTING: 110 such places identified from ambulance service data as high risk sites. PATIENTS: 172 members of the public who developed cardiac arrest at these sites between April 2000 and March 2004. 20,592 defibrillator months' use is reported, representing one automated external defibrillator (AED) use every 120 months. INTERVENTION: 681 AEDs were installed; staff present at the sites were trained in basic life support and to use AEDs. MAIN OUTCOME MEASURES: Initial rhythm detected by AED, restoration of spontaneous circulation, survival to hospital discharge. RESULTS: 172 cases of cardiac arrest were treated by trained lay staff working at the site before the arrival of the emergency services during the period. A shockable rhythm was detected in 135 (78%), shocks being administered in 134 an estimated 3-5 minutes after collapse; 38 (28.3%) patients subsequently survived to hospital discharge. Spontaneous circulation was restored in five additional patients who received shocks but died later in hospital. In 37 cases no shock was initially indicated; one patient survived after subsequent treatment by paramedics, cardiopulmonary resuscitation having been given soon after collapse. Overall, irrespective of the initial rhythm, 39 patients (22.7%), were discharged alive from hospital. For witnessed arrests of presumed cardiac cause in ventricular fibrillation (an international Utstein comparator) survival was 37 of 124 (29.8%). CONCLUSIONS: The use of AEDs by lay people at sites where cardiac arrest commonly occurs is an effective strategy to reduce deaths at these sites.

International multicentre trial protocol to assess the efficacy and safety of tenecteplase during cardiopulmonary resuscitation in patients with out-of-hospital cardiac arrest: the Thrombolysis in Cardiac Arrest (TROICA) Study.

Prehospital cardiac arrest has been associated with a very poor prognosis. Acute myocardial infarction and massive pulmonary embolism are the underlying causes of out-of-hospital cardiac arrest in 50-70% of patients. Although fibrinolysis is an effective treatment strategy for both myocardial infarction and pulmonary embolism, clinical experience for this therapy performed during resuscitation has been limited owing to the anticipated risk of severe bleeding complications. The TROICA study is planned as one of the largest randomized, double-blind, placebo-controlled trials to assess the efficacy and safety of prehospital thrombolytic therapy in cardiac arrest of presumed cardiac origin. Approximately 1000 patients with cardiac arrest will be randomized at approximately 60 international study centres to receive either a weight-adjusted dose of tenecteplase or placebo after the first dose of a vasopressor. Patients can be included if they are at least 18 years, presenting with a witnessed cardiac arrest of presumed cardiac origin, and if either basic life support had started within 10 min of onset and had been performed up to 10 min or advanced life support is started within 10 min of onset of cardiac arrest. Primary endpoint of the study is the 30-day survival rate, and the coprimary endpoint is hospital admission. Secondary endpoints are the return of spontaneous circulation (ROSC), survival after 24 h, survival to hospital discharge, and neurological performance. Safety endpoints include major bleeding complications and symptomatic intracranial haemorrhage.

Primary pleural epithelioid haemangioendothelioma with metastases to the skin. A case report and literature review.

Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour of intermediate behaviour. It can arise from various sites including the liver, spleen, pleura, or lung. Cutaneous EHE can be primary or secondary. This report describes the case of a 51 year old man who presented with a history of dry cough, shortness of breath, and pleural effusion, and who developed two cutaneous nodules in the anterior abdominal wall a few weeks later. He had a previous history of asbestos exposure. Computed tomography scan showed a left sided pleural effusion and nodular pleural mass. Histology of both the pleural and cutaneous lesions was compatible with EHE. Electron microscopic examination demonstrated the presence of Weibel-Palade bodies. The patient underwent elliptical excision of the metastatic cutaneous nodules after decortication of the primary pleural tumour and adjuvant treatment. A few reports have described metastasis of intrathoracic EHE to the skin. Despite treatment with interferon, the patient developed more cutaneous lesions two years after the initial diagnosis. Even though the tumour has the classic light histological and ultrastructural features of EHE, it behaved in an aggressive manner.

Benefits of organic farming to biodiversity vary among taxa.

Habitat and biodiversity differences between matched pairs of organic and non-organic farms containing cereal crops in lowland England were assessed by a large-scale study of plants, invertebrates, birds and bats. Habitat extent, composition and management on organic farms was likely to favour higher levels of biodiversity and indeed organic farms tended to support higher numbers of species and overall abundance across most taxa. However, the magnitude of the response varied; plants showed larger and more consistent responses than other taxa. Variation in response across taxa may be partly a consequence of the small size and isolated context of many organic farms. Extension of organic farming could contribute to the restoration of biodiversity in agricultural landscapes.

Underlying chronic granulomatous disease in a patient with bronchocentric granulomatosis.

We present a case of bronchocentric granulomatosis in a woman with no history of asthma who was colonised with Aspergillusfumigatus. A family history of chronic granulomatous disease prompted further testing that demonstrated severely depressed neutrophil oxidant production and gp91(phox) deficiency compatible with the X linked carrier state of chronic granulomatous disease. Only one report of the association of these two rare diseases has previously appeared in the literature. We postulate that an ineffective immune response led to the prolonged colonisation of Afumigatus resulting in a hypersensitivity reaction that was manifest clinically as bronchocentric granulomatosis.

Effects of dietary amino acid balance on the response of dairy cows to an increase of milking frequency from twice to three times daily.

An experiment was conducted to examine how the response of dairy cows to a change from twice to three times-daily milking is affected by deficiencies in the dietary supplies of three amino acids, His, Met, and Lys. Six cows were used in a 6 x 6 Latin square with 14-d periods. The three dietary treatments were: grass silage and a cereal-based supplement containing feather meal as the sole protein supplement; the same silage-cereal diet supplying similar amounts of metabolizable and rumen-undegradable protein but with additional amounts of His, Met, and Lys in the form of fish meal; and the fish meal diet with additional metabolizable energy in the form of an additional 2 kg/d of sugar beet pulp. Within each of these dietary treatments, the cows were milked twice and three times daily, making a total of six treatments. When cows were given the feather meal diet, even though dietary metabolizable energy was in considerable excess, a deficiency of specific amino acids prevented any increase in milk yield in response to increasing the frequency of milking from twice to three times daily. In contrast, when cows consumed a similar level of excess metabolizable energy and a similar level of rumen-undegradable protein for which the protein was of better amino acid balance (fish meal), the increased frequency of milking led to increased yield of milk and milk protein.

Effects of amino acid nutrition on the responses of dairy cows to milking more frequently with or without injection of growth hormone.

The influence of amino acid nutrition on the response to milking more frequently, with or without injection of growth hormone, was examined in eight dairy cows in two 4 x 4 Latin squares with 28-d periods. The four treatments were a diet adequate in amino acids with or without injection of growth hormone and a diet inadequate in amino acids with or without injection of growth hormone. For all four treatments, during the last 14 d of each period, one half of the mammary gland was milked three times a day (3x), while the other half remained on twice-daily milking (2x). Both diets were based on grass silage given ad libitum and 4 kg/d of sugar beet pulp together with a supplement containing either fish meal (adequate diet) or feather meal (inadequate diet) as the only protein feeds. The diet containing feather meal is known to be deficient in His, Met, and Lys. On the fish meal diet, the cows responded positively to growth hormone and to milking more frequently and the responses to both treatments were additive. On the feather meal diet, however, even though injection of growth hormone increased the yield of milk protein by around 10%, milking more frequently did not affect milk production. It is concluded that milking more frequently has a weaker effect on the partitioning of amino acid use between body and udder than does growth hormone treatment.

Effects of changes in dietary amino acid balance on milk yield and mammary function in dairy cows.

Two experiments were conducted to determine whether longer-term deficiencies in the supply of limiting amino acids would be accompanied by a decline in mammary function (total DNA, cell proliferation rate and activities of key enzymes), and whether this would adversely affect the cow's ability to respond to a return to a nutritionally adequate diet. The first experiment was performed in early/mid lactation, and the second, using the same cows, was carried out in mid/late lactation. A control group of six cows were given a grass silage-cereal diet containing fish meal as the sole protein supplement (amino acid adequate) throughout the experiments, whereas another group of six cows in treatment received the control diet for 2 wk (lactation wk 5 and 6) and then were changed to a diet in which the fish meal was replaced by an equivalent amount of protein as feather meal (amino acid deficient) for 6 wk before returning to the fish meal diet for 4 wk (Experiment 1). After a rest period of 5 wk, the experimental procedure was repeated (Experiment 2). Although there was a fall in milk yield as lactation advanced, leading to lower milk yields in Experiment 2, the marked difference in milk yield between treatments was similar for the two stages of lactation (21% vs 16% in Experiment 1 and 2, respectively). In both experiments, the marked fall of milk yield in cows given the feather meal diet was completely recovered by a return to the fish meal diet. Despite the markedly lower milk yield with the amino acid-deficient diet, however, there was no clear evidence of corresponding changes in measurements of mammary function.