No increase in adverse events with lateral extra-articular tenodesis augmentation of anterior cruciate ligament reconstruction - Results from the stability randomized trial.

OBJECTIVES: Results from the Stability Study suggest that adding a lateral extra-articular tenodesis (LET) to a hamstring tendon autograft reduces the rate of anterior cruciate ligament reconstruction (ACLR) failure in high-risk patients. The purpose of this study is to report adverse events over the 2-year follow-up period and compare groups (ACLR alone vs. ACLR + LET). METHODS: Stability is a randomized clinical trial comparing hamstring tendon ACLR with and without LET. Patients aged 14-25 years with an ACL deficient knee were included. Patients were followed and adverse events documented (type, actions taken, resolution) with visits at 3, 6, 12, and 24 months postoperatively. Adverse events were categorized as none, minor medical, minor surgical, contralateral ACL rupture, or graft rupture. Patient reported outcome measures (PROMs) collected at each visit included the Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee Score (IKDC), and ACL Quality of Life Questionnaire (ACL-QOL). RESULTS: In total, 618 patients were randomized (mean age 18.9 years, 302 (49%) male). Forty-five patients (7%) suffered graft rupture; 34 (11%) in the ACLR group compared to 11 (4%) in the ACLR + LET group (RRR = 0.67, 95% CI 0.36 to 0.83, p < 0.001). There were no differences in effusion or infection rates between groups. The ACLR + LET group experienced an increased number of hardware removals (10 vs. 4). Overall, the rate of minor medical events (11%), minor surgical events (7%), and ipsilateral or contralateral ACL tears (10%) were low considering the high-risk patient profile. Increasing severity of adverse events was associated with lower PROMs at 24 months post-operative. Patients in the ACLR + LET group reported greater degree of pain at 3 months only. There were no clinically significant differences in range of motion between groups. CONCLUSIONS: The addition of LET to hamstring tendon autograft ACLR in young patients at high risk of re-injury resulted in a statistically significant reduction in graft rupture. While the addition of LET may increase rates of hardware irritation, there was no significant increase in overall rates of minor medical adverse events, minor surgical events, or overall re-operation rates. The concerns regarding complications associated with a LET did not materialize in this study. LEVEL OF EVIDENCE: Level I.

Country-specific effects of neonicotinoid pesticides on honey bees and wild bees.

Neonicotinoid seed dressings have caused concern world-wide. We use large field experiments to assess the effects of neonicotinoid-treated crops on three bee species across three countries (Hungary, Germany, and the United Kingdom). Winter-sown oilseed rape was grown commercially with either seed coatings containing neonicotinoids (clothianidin or thiamethoxam) or no seed treatment (control). For honey bees, we found both negative (Hungary and United Kingdom) and positive (Germany) effects during crop flowering. In Hungary, negative effects on honey bees (associated with clothianidin) persisted over winter and resulted in smaller colonies in the following spring (24% declines). In wild bees (Bombus terrestris and Osmia bicornis), reproduction was negatively correlated with neonicotinoid residues. These findings point to neonicotinoids causing a reduced capacity of bee species to establish new populations in the year following exposure.

Extending standard testing period in honeybees to predict lifespan impacts of pesticides and heavy metals using dynamic energy budget modelling.

Concern over reported honeybee (Apis mellifera spp.) losses has highlighted chemical exposure as a risk. Current laboratory oral toxicity tests in A. mellifera spp. use short-term, maximum 96 hour, exposures which may not necessarily account for chronic and cumulative toxicity. Here, we use extended 240 hour (10 day) exposures to examine seven agrochemicals and trace environmental pollutant toxicities for adult honeybees. Data were used to parameterise a dynamic energy budget model (DEBtox) to further examine potential survival effects up to 30 day and 90 day summer and winter worker lifespans. Honeybees were most sensitive to insecticides (clothianidin > dimethoate ≫ tau-fluvalinate), then trace metals/metalloids (cadmium, arsenic), followed by the fungicide propiconazole and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). LC50s calculated from DEBtox parameters indicated a 27 fold change comparing exposure from 48 to 720 hours (summer worker lifespan) for cadmium, as the most time-dependent chemical as driven by slow toxicokinetics. Clothianidin and dimethoate exhibited more rapid toxicokinetics with 48 to 720 hour LC50s changes of <4 fold. As effects from long-term exposure may exceed those measured in short-term tests, future regulatory tests should extend to 96 hours as standard, with extension to 240 hour exposures further improving realism.

Successful primary use of VVDL+V ECMO with cephalic drain in neonatal respiratory failure.

OBJECTIVE: To describe the use of double-lumen venovenous (VVDL) extracorporeal membrane oxygenation (ECMO) with cephalic draining cannula (VVDL+V) as a primary approach for all neonatal respiratory diagnoses and to compare our single-center experience with data as collected in the Extracorporeal Life Support Organization (ELSO) database. STUDY DESIGN: We retrospectively reviewed all cases of ECMO for neonatal respiratory failure performed in the neonatal intensive-care unit at a large referral children's hospital, the Children's Healthcare of Atlanta at Egleston (CHOA-E). Comparisons were then made to neonatal respiratory ECMO data retrieved from the ELSO database. RESULTS: At CHOA-E 162 of 189 cases were completed with the VVDL+V approach. Survival in the VVDL+V cohort was 89.1% versus 68.7% from ELSO, P<0.001. For those complications considered, the overall risk of complication favored the CHOA-E VVDL+V group as compared with ELSO (odds ratio (OR) 0.71 (0.52-0.7)) as did the risk of neurologic complications (OR 0.29, (0.15-0.58)), including intracranial hemorrhage (OR 0.39 (0.18-0.97), P=0.011). CONCLUSION: The VVDL+V approach can be used successfully as the primary approach for ECMO for neonatal respiratory failure of various etiologies and in this single-center cohort this approach was associated with improved survival and lower rates of complication as compared with the ELSO database.

Controlling intrathoracic hemorrhage on ECMO: help from Factor VIIa and Virchow.

OBJECTIVE: Thoracentesis with chest tube placement is often needed to decompress a clinically significant pneumothorax or pleural effusion. The risks of such a procedure may be considered too great to perform on a systemically anticoagulated patient supported by extracorporeal membrane oxygenation (ECMO). RESULTS: An 8-year-old child with respiratory failure due to necrotizing pneumonia and autoimmune vasculitis, on veno-venous ECMO, developed a severe tension pneumothorax that required emergent decompression with a chest tube. Post-procedure, the patient developed a hemothorax that was approaching non-sustainability. We developed a strategy based on Virchow's triad to favor homeostasis in the patient while avoiding thrombosis in the ECMO circuit. We employed selective lung ventilation, passive pleural drainage, high flow ECMO, and aggressive coagulation cascade control, including the use of aminocaproic acid and activated factor VIIa. Following this strategy, the hemorrhage was controlled and, later, the patient was able to successfully come off ECMO. CONCLUSIONS: With careful coagulation cascade manipulation, complete lung rest for the affected lung, control of ECMO blood flow, and prudent hemothorax drainage, we were able to facilitate hemostasis that was required for the successful recovery of our patient while avoiding critical ECMO circuit thrombosis. Even with today's highly advanced medical technologies, centuries-old basic medical principles can still assist in the care of our sickest and most complex patients. Chest tube placement while on ECMO is rare and, although necessary, may be a risky procedure. With precise coagulation control, it can be a successful procedure on ECMO.

Children Use Different Cues to Guide Noun and Verb Extensions.

Learning new words involves decoding both how a word fits the current situation and how it could be used in new situations. Three studies explore how two types of cues- sentence structure and the availability of multiple instances-- affect children's extensions of nouns and verbs. In each study, 2½-year-olds heard nouns, verbs or no new word while seeing the experimenter use a novel object to perform an action; at test, they were asked to extend the word. In Study 1, children hearing nouns in simple sentences used object shape as the basis for extension even though, during the learning phase, they saw multiple objects in motion; children in the other conditions responded randomly. Study 2 shows that by changing in the type of sentences used in the noun and verb conditions, not only is the shape bias disrupted but children are successful in extending new verbs. In a final study, access to multiple examples was replaced by a direct teaching context, and produced findings similar to those in Study 2. An implication of this result is that seeing multiple examples can be as effective as receiving direct instruction from an adult. Overall, the set of results suggests the mix of cues available during learning influences noun and verb extensions differently. The findings are important for understanding how the ability to extend words emerges in complex contexts.

Bumble bee species' responses to a targeted conservation measure depend on landscape context and habitat quality.

The global decline of insect pollinators, especially bees, is cause for concern, and there is an urgent need for cost-effective conservation measures in agricultural landscapes. While landscape context and habitat quality are known to influence species richness and abundance of bees, there is a lack of evidence from manipulative field experiments on bees' responses to adaptive management across differently structured landscapes. We present the results of a large-scale study that investigated the effects of a targeted agri-environment scheme (AES) on bumble bees (Bombus spp.) over three years in the United Kingdom. Forage patches of different sizes were sown with a conservation flower mixture across eight sites covering a broad range of agricultural land use types. Species richness and worker densities (especially of the longer-tongued Bombus species for which the mixture was targeted) were significantly higher on sown forage patches than on existing non-crop control habitats throughout the three-year study, but the strength of this response depended on both the proportions of arable land and abundance of herbaceous forb species in the surrounding landscape. The size of sown patches also affected worker density, with smaller patches (0.25 ha) attracting higher densities of some species than larger patches (1.0 ha). Our models show that a targeted AES can deliver greater net benefits in more intensively farmed areas, in terms of the number and species richness of bumble bees supported, than in heterogeneous landscapes where other foraging habitats exist. These findings serve to strengthen the evidence base for extending agri-environment schemes to boost declining pollinator populations to a larger number of agricultural landscapes across the globe.

[The alliance of the parent, child and the nurse to challenge medical error]. / L'alliance parents-enfant-soignants à l'épreuve de l'erreur médicale.

A group composed of parents, nurses, and physicians involved in pediatric cancerology has reflected on medical errors within the Espace Éthique de l'Assistance publique-Hôpitaux de Paris. Based on narratives and qualitative analysis of histories and testimonies, this discussion aimed at exploring the causes, circumstances, and impacts of medical errors on the relations between these individuals. The study demonstrated that some circumstances actually promote medical errors, such as hard working conditions, mistrust, unreliable control procedures, not listening to parents, and caring for children in extreme situations of pain and suffering. Errors almost always result from the accumulation of several shortcomings. The tensions raised by a medical error can be overcome, provided that parents and caregivers trust each other from the onset of disease and that the medical errors are disclosed in a sincere way, whatever the medical consequences. The feelings raised by the painful experience of a medical error do not solely depend on the severity of the consequences, since seemingly benign errors may lead to long-term trauma, whereas severe errors, even those leading to death, do not necessarily breach trust. The keyword here is permanent vigilance. The capacity of caregivers to question their practice, from both a technical and ethical point of view, will determine their ability to learn from an error for the future. The depth and quality of this questioning, in the best of times encouraged by the institution, may also help children affected by a medical error and their family to move forward in their personal history, beyond such painful experiences.

[Risk announcement in paediatric cancerology: strengthen the therapeutic alliance]. / L'annonce des risques en cancérologie pédiatrique: consolider l'alliance thérapeutique.

Although announcement of the risks related to treatment has become a general rule in the healthcare relationship, doctors, nurses and parents of severely ill children tend to feel uncomfortable in relation to this mandatory information. The work conducted by the AP-HP Espace éthique working party in collaboration with parents, healthcare personnel and a philosopher demonstrates the need to announce these risks, even beyond the legal framework, while bearing in mind the difficulties and hazards inherent to changes in legislation and by observing the philosophical values that subtend this legislation. Faced with the broad range of diverse and complex risks, the working party proposes a classification of risks and hierarchisation of the difficulties encountered by the doctor during this announcement, which is difficult to make, and difficult to hear, as intimately related to the child's quality of life. The very concept of the probability of a risk raises concepts that are difficult to accept: chance, randomness, and uncertainty. Informing the patient involves hearing as much as talking, listening as much as explaining and requires availability, time, space and an ability to listen to the patient. This article proposes several good practice guidelines designed to consolidate the therapeutic alliance by sharing the uncertainty of the risk and allowing the various partners to remain actors. Nonconfiscation of knowledge by doctors does not lead to a loss or transfer of their responsibility, but allows decisions to be taken in the context of the alliance, while taking the risks into account.

Landscape context not patch size determines bumble-bee density on flower mixtures sown for agri-environment schemes.

Bumble-bee declines across Europe have been linked to loss of habitat and forage availability due to agricultural intensification. These declines may have severe ecological and commercial consequences since bumble-bees pollinate a range of wildflowers and crops. In England, attempts are being made to reintroduce forage resources through agri-environment schemes, yet there are few data on how the area of forage, or the landscape context in which it is provided, affects their success. We investigated the effects of sown forage patches on bumble-bees across sites varying in landscape characteristics. Bumble-bee densities were higher on sown patches compared with control habitats but did not vary with patch size, i.e. total forager numbers were proportional to patch area. Importantly, the relative response to sown forage patches varied widely across a landscape gradient such that their impact in terms of attracting foraging bumble-bees was greatest where the proportion of arable land was highest.

[End of life and clinical research in pediatric oncology]. / Fin de vie de l'enfant et recherche clinique en cancérologie pédiatrique.

The objective of a phase I trials in paediatrics is to determine the recommended dose of a new treatment in children while evaluating its toxicity. These trials are proposed when no effective curative treatment is available. The probability of a benefit in terms of disease control is certainly very low, but greater than zero. On the basis of the work conducted by an Assistance publique-Hôpitaux de Paris Espace éthique group in collaboration with parents, healthcare personnels and a philosopher, phase I therapeutic trials can be considered to be an ethically acceptable proposal provided the criteria and risks of inclusion in such a trial are clearly defined. This article discusses the main elements of this process and is designed to provide guidelines for healthcare personnel and parents. The need for an information provided gently but honestly, the importance of a sufficient time to think about the proposed trial, a two-sided dialogue and partnership between the various actors, and the priority given to the child's best interest, as should always be the case, constitute the decisive elements to guide the proposed inclusion in a phase I trial. These conditions help to ensure that a decision is reached which appears to be morally founded for all parties, while allowing the child to remain alive up until the end, i.e. a human being capable of relating. This decision allows parents and healthcare personnel to retain a good self-image; if the child dies, it is by keeping their self-esteem that parents can live with their bereavement and healthcare personnel can reinvest in other patients.

Effects of genetically modified herbicide-tolerant cropping systems on weed seedbanks in two years of following crops.

The Farm Scale Evaluations (FSEs) showed that genetically modified herbicide-tolerant (GMHT) cropping systems could influence farmland biodiversity because of their effects on weed biomass and seed production. Recently published results for winter oilseed rape showed that a switch to GMHT crops significantly affected weed seedbanks for at least 2 years after the crops were sown, potentially causing longer-term effects on other taxa. Here, we seek evidence for similar medium-term effects on weed seedbanks following spring-sown GMHT crops, using newly available data from the FSEs. Weed seedbanks following GMHT maize were significantly higher than following conventional varieties for both the first and second years, while by contrast, seedbanks following GMHT spring oilseed rape were significantly lower over this period. Seedbanks following GMHT beet were smaller than following conventional crops in the first year after the crops had been sown, but this difference was much reduced by the second year for reasons that are not clear. These new data provide important empirical evidence for longer-term effects of GMHT cropping on farmland biodiversity.

Determinants of species richness in the Park Grass Experiment.

The Park Grass Experiment at Rothamsted in southeast England was started in 1856, making it the longest-running experiment in plant ecology anywhere in the world. Experimental inputs include a range of fertilizers (nitrogen, phosphorus, potassium, and organic manures) applied annually, with lime applied occasionally, and these have led to an increase in biomass and, where nitrogen was applied in the form of ammonium sulfate, to substantial decreases in soil pH. The number of species per plot varies from three to 44 per 200 m(2), affording a unique opportunity to study the determinants of plant species richness and to estimate the effect sizes attributable to different factors. The response of species richness to biomass depends on the amount and type of nitrogen applied; richness declined monotonically with increasing biomass on plots receiving no nitrogen or receiving nitrogen in the form of sodium nitrate, but there was no relationship between species richness and biomass on plots acidified by ammonium sulfate application. The response to lime also depended on the type of nitrogen applied; there was no relationship between lime treatment and species richness, except in plots receiving nitrogen in the form of ammonium sulfate, where species richness increased sharply with increasing soil pH. The addition of phosphorus reduced species richness, and application of potassium along with phosphorus reduced species richness further, but the biggest negative effects were when nitrogen and phosphorus were applied together. The analysis demonstrates how multiple factors contribute to the observed diversity patterns and how environmental regulation of species pools can operate at the same spatial and temporal scale as biomass effects.

Didelphic uterus and obstructed hemivagina with renal agenesis: case report and review of the literature.

Congenital disorders of development are more common than previously reported and the correct diagnosis is frequently missed leading to suboptimal treatment. Eight cases of uterus didelphys with obstructed hemivagina referred to the Gynecology service at Baylor College of Medicine over a 2-year period were reviewed. Initial presenting symptoms and signs were followed by an incorrect diagnosis by the referring physician 100% of the time. MRI, the most sensitive imaging modality for congenital anomalies (Kublik, RA: Female pelvis. Eur Radiol 1999; 9:1715), was utilized in only 50% of the cases. In this group of patients, hematocolpos and pyocolpos were discovered in equal numbers upon exploration. Ipsilateral renal anomalies were present 100% of the time, while coexisting contralateral anomalies were present 50% of the time. Resection of the vaginal septum was required for abatement of symptoms in all cases presented here. Laparoscopy provided additional information beyond radiologic tests regarding pelvic and urological anatomy. In two cases, resection of the ipsilateral uterine horn was required. These cases demonstrate the difficulty in diagnosis, heterogeneity in presentation, and need for expertise not only in this rare congenital anomaly but also all the other disorders of development of the female genital tract.

Ban on triazine herbicides likely to reduce but not negate relative benefits of GMHT maize cropping.

The UK Farm-Scale Evaluations (FSE) compared the effects on biodiversity of management of genetically modified herbicide-tolerant (GMHT) spring-sown crops with conventional crop management. The FSE reported larger weed abundance under GMHT management for fodder maize, one of three crops studied. Increased seed production may be important for the long-term persistence of these arable weeds and may benefit invertebrates, small mammals and seed-eating birds. In three-quarters of FSE maize fields, growers used atrazine on the conventionally managed half, reflecting contemporary commercial practice. Withdrawal of the triazine herbicides atrazine, simazine and cyanazine from approved lists of EU chemicals could therefore reduce or even reverse the reported benefits of GMHT maize. Here we analyse effects of applications of triazine herbicides in conventional maize regimes on key indicators, using FSE data. Weed abundances were decreased greatly relative to all other regimes whenever atrazine was applied before weeds emerged. Here, we forecast weed abundances in post-triazine herbicide regimes. We predict weed abundances under future conventional herbicide management to be considerably larger than that for atrazine used before weeds emerged, but still smaller than for the four FSE sites analysed that used only non-triazine herbicides. Our overall conclusion is that the comparative benefits for arable biodiversity of GMHT maize cropping would be reduced, but not eliminated, by the withdrawal of triazines from conventional maize cropping.

On the rationale and interpretation of the Farm Scale Evaluations of genetically modified herbicide-tolerant crops.

Farmland biodiversity and food webs were compared in conventional and genetically modified herbicide-tolerant (GMHT) crops of beet (Beta vulgaris L.), maize (Zea mays L.) and both spring and winter oilseed rape (Brassica napus L.). GMHT and conventional varieties were sown in a split-field experimental design, at 60-70 sites for each crop, spread over three starting years beginning in 2000. This paper provides a background to the study and the rationale for its design and interpretation. It shows how data on environment, field management and the biota are used to assess the current state of the ecosystem, to define the typical arable field and to devise criteria for selecting, sampling and auditing experimental sites in the Farm Scale Evaluations. The main functional and taxonomic groups in the habitat are ranked according to their likely sensitivity to GMHT cropping, and the most responsive target organisms are defined. The value of the seedbank as a baseline and as an indicator of historical trends is proposed. Evidence from experiments during the twentieth century is analysed to show that large changes in field management have affected sensitive groups in the biota by ca. 50% during a year or short run of years--a figure against which to assess any positive or negative effects of GMHT cropping. The analysis leads to a summary of factors that were, and were not, examined in the first 3 years of the study and points to where modelling can be used to extrapolate the effects to the landscape and the agricultural region.

Crop management and agronomic context of the Farm Scale Evaluations of genetically modified herbicide-tolerant crops.

The Farm Scale Evaluations of genetically modified herbicide-tolerant crops (GMHT) were conducted in the UK from 2000 to 2002 on beet (sugar and fodder), spring oilseed rape and forage maize. The management of the crops studied is described and compared with current conventional commercial practice. The distribution of field sites adequately represented the areas currently growing these crops, and the sample contained sites operated at a range of management intensities, including low intensity. Herbicide inputs were audited, and the active ingredients used and the rates and the timings of applications compared well with current practice for both GMHT and conventional crops. Inputs on sugar beet were lower than, and inputs on spring oilseed rape and forage maize were consistent with, national averages. Regression analysis of herbicide-application strategies and weed emergence showed that inputs applied by farmers increased with weed densities in beet and forage maize. GMHT crops generally received only one herbicide active ingredient per crop, later and fewer herbicide sprays and less active ingredient (for beet and maize) than the conventional treatments. The audit of inputs found no evidence of bias.

Weeds in fields with contrasting conventional and genetically modified herbicide-tolerant crops. I. Effects on abundance and diversity.

We compared the seedbanks, seed rains, plant densities and biomasses of weeds under two contrasting systems of management in beet, maize and spring oilseed rape. Weed seedbank and plant density were measured at the same locations in two subsequent seasons. About 60 fields were sown with each crop. Each field was split, one half being sown with a conventional variety managed according to the farmer's normal practice, the other half being sown with a genetically modified herbicide-tolerant (GMHT) variety, with weeds controlled by a broad-spectrum herbicide. In beet and rape, plant densities shortly after sowing were higher in the GMHT treatment. Following weed control in conventional beet, plant densities were approximately one-fifth of those in GMHT beet. In both beet and rape, this effect was reversed after the first application of broad-spectrum herbicide, so that late-season plant densities were lower in the GMHT treatments. Biomass and seed rain in GMHT crops were between one-third and one-sixth of those in conventional treatments. The effects of differing weed-seed returns in these two crops persisted in the seedbank: densities following the GMHT treatment were about 20% lower than those following the conventional treatment. The effect of growing maize was quite different. Weed density was higher throughout the season in the GMHT treatment. Late-season biomass was 82% higher and seed rain was 87% higher than in the conventional treatment. The difference was not subsequently detectable in the seedbank because the total seed return was low after both treatments. In all three crops, weed diversity was little affected by the treatment, except for transient effects immediately following herbicide application.

Weeds in fields with contrasting conventional and genetically modified herbicide-tolerant crops. II. Effects on individual species.

We compared the effects of the management of genetically modified herbicide-tolerant (GMHT) and conventional beet, maize and spring oilseed rape on 12 weed species. We sampled the seedbank before and after cropping. During the season we counted plants and measured seed rain and biomass. Ratios of densities were used to calculate emergence, survival, reproduction and seedbank change. Treatments significantly affected the biomass of six species in beet, eight in maize and five in spring oilseed rape. The effects were generally consistent, with biomass lower in GMHT beet and spring oilseed rape and higher in GMHT maize. With few exceptions, emergence was higher in GMHT crops. Subsequent survival was significantly lowered for eight species in beet and six in spring oilseed rape in the GMHT treatments. It was increased for five species in maize and one in spring oilseed rape. Significant effects on seedbank change were found for four species. However, for many species in beet and spring oilseed rape (19 out of 24 cases), seed densities were lower in the seedbank after GMHT cropping. These differences compounded over time would result in large decreases in population densities of arable weeds. In maize, populations may increase.