Acceptance and transfer to a regional severe respiratory failure and veno-venous extracorporeal membrane oxygenation (ECMO) service: predictors and outcomes.

The use of extracorporeal membrane oxygenation for respiratory failure is high risk and resource intensive. In England, five centres provide this service and patients who are referred have four possible outcomes: declined transfer due to perceived futility; accepted in principle but remain at the referring centre with ongoing surveillance; retrieved using conventional ventilation; or retrieved on extracorporeal support. The decision-making process leading to these outcomes has not previously been examined. We evaluated referrals to one centre and identified factors associated with each decision outcome. Five hundred and sixty-four patients were analysed from January 2012 to October 2015. One hundred and fifty-seven patients were declined; multivariate analysis demonstrated associated factors to be: age (odds ratio (95% confidence interval) 1.05 (1.04-1.07)); immunocompromise (4.95 (2.58-9.67)); lactate (1.11 (1.01-1.22)); duration of ventilation (1.08 (1.04-1.14)); and cardiac failure (3.22 (1.04-10.51)). Factors associated with the decision to retrieve an accepted patient were: plateau pressure (1.05 (1.01-1.10)); ratio of arterial oxygen partial pressure to fractional inspired oxygen (0.89 (0.85-0.93)); partial pressure of carbon dioxide in arterial blood (1.13 (1.03-1.25)); and the absence of non-pulmonary infection (0.31 (0.15-0.61)). Only pH was independently associated with the decision to transfer on extracorporeal support (0.020 (0.002-0.017)). Six-month survival in the declined, non-retrieved, conventionally retrieved and extracorporeal-retrieved groups was 16.6%, 71.1%, 76.7% and 72.1%, respectively, substantially supporting the decision-making model. Survival in the accepted group exceeds that reported previously. However, a proportion of those declined do survive and some remotely managed patients die. This suggests the approach does not account for some important survival-determining factors.

International survey on the management of mechanical ventilation during ECMO in adults with severe respiratory failure.

BACKGROUND: No consensus exists on the optimal settings of mechanical ventilation during veno-venous extracorporeal membrane oxygenation (ECMO). Our aim was to describe how mechanical ventilation and related interventions are managed by adult ECMO centres. METHODS: A cross-sectional, multi-centre, international survey of 173 adult respiratory ECMO centres. The survey was generated through an iterative process and assessed for clarity, content and face validity. RESULTS: One hundred thirty-three centres responded (76.8%). Pressure control was the most commonly used mechanical ventilation mode (64.4%). Although the median PEEP was 10 cmH2O, 22.6% set PEEP <10 cmH2O and 15.5% used 15-20 cmH2O. In 63% of centres PEEP was fixed and not titrated. Recruitment maneuvres, were never used in 34.1% of centres, or used daily in 13.2%. Centres reported using either a "lung rest" (45.7%), or an "open lung" strategy (44.2%). Only 24.8% used chest CT to guide mechanical ventilation. Adjunctive treatments were never or occasionally used. Only 10% of centres extubated patients on ECMO, mainly in more experienced centres. 71.3% of centres performed tracheostomy on ECMO, with large variability in timing (most frequent on days 6-10). Only 27.1% of ECMO centres had a protocol for mechanical ventilation on ECMO. CONCLUSION: We found large variability in ventilatory practices during ECMO. The clinicians' training background and the centres' experience had no influence on the approach to ventilation. This survey shows that well conducted studies are necessary to determine the best practice of mechanical ventilation during ECMO and its impact on patient outcome.

Capabilities of a mobile extracorporeal membrane oxygenation service for severe respiratory failure delivered by intensive care specialists.

We conducted a single-centre observational study of retrievals for severe respiratory failure over 12 months. Our intensivist-delivered retrieval service has mobile extracorporeal membrane oxygenation capabilities. Sixty patients were analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The mean (SD) PaO2 /FI O2 ratio at referral was 10.2 (4.1) kPa and median (IQR [range]) Murray score was 3.25 (3.0-3.5 [1.5-4.0]). Forty-eight patients (80%) required veno-venous extracorporeal membrane oxygenation at the referring centre. There were no cannulation or extracorporeal membrane oxygenation-related complications. The median (IQR [range]) retrieval distance was 47.2 (14.9-77.0 [2.3-342.0]) miles. There were no major adverse events during retrieval. Thirty-seven patients (77%) who received extracorporeal membrane oxygenation survived to discharge from the intensive care unit and 36 patients (75%) were alive after six months. Senior intensivist-initiated and delivered mobile extracorporeal membrane oxygenation is safe and associated with a high incidence of survival.

Classification of the reduced vertical component of the ground reaction force in late stance in cerebral palsy gait.

Children with cerebral palsy (CP) often experience significant problems supporting their bodyweight (BW) and decelerating the downward velocity of the centre of mass (CoM) in late stance. This is seen as a decreased second peak of vertical ground reaction force (GRF) nominated FZ(2). This study categorises gait data by the degree of reduced FZ(2). Kinetic data were analysed from a CP database. Data from 129 patients, able to walk barefoot unaided, were investigated. Of these, 84 had kinetic data, 59 diplegics (both legs) and 15 hemiplegics (affected leg only), thus providing data from 133 legs. A reduced FZ(2) was observed in 116 legs (87%). Of the 133 legs, 44% failed to generate FZ(2)>BW. By including the Type 2 data this figure rises to, a staggering 66% who are having difficulty supporting BW at this stage of the stance phase. Only 12% of the legs showed a normal pattern (FZ(2) approximately equal to FZ(1)). In conclusion, the majority of CP children referred to the gait laboratory exhibited some degree of reduced FZ(2) and can be categorised as having a 'Ben Lomonding' gait pattern. 'Ben Lomonding,' is the term used to describe this phenomenon of reduced FZ(2), as the shape of the GRF graph resembles the shape of the Scottish mountain, Ben Lomond, which has two peaks, the second peak being much smaller than the first. Crucially, clinicians should be aware that nearly half of the CP children in this study were in difficulty supporting their BW in late stance and must use compensatory mechanisms to prevent collapse of the affected limb.

Not just vicariance: phylogeography of a Sonoran Desert euphorb indicates a major role of range expansion along the Baja peninsula.

To examine the generality of population-level impacts of ancient vicariance identified for numerous arid-adapted animal taxa along the Baja peninsula, we tested phylogeographical hypotheses in a similarly distributed desert plant, Euphorbia lomelii (Euphorbiaceae). In light of fossil data indicating marked changes in the distributions of Baja floristic assemblages throughout the Holocene and earlier, we also examined evidence for range expansion over more recent temporal scales. Two classes of complementary analytical approaches - hypothesis-testing and hypothesis-generating - were used to exploit phylogeographical signal from chloroplast DNA sequence data and genotypic data from six codominant nuclear intron markers. Sequence data are consistent with a scenario of mid-peninsular vicariance originating c. 1 million years ago (Ma). Alternative vicariance scenarios representing earlier splitting events inferred for some animals (e.g. Isthmus of La Paz inundation, c. 3 Ma; Sea of Cortez formation, c. 5 Ma) were rejected. Nested clade phylogeographical analysis corroborated coalescent simulation-based inferences. Nuclear markers broadened the temporal spectrum over which phylogeographical scenarios could be addressed, and provided strong evidence for recent range expansions along the north-south axis of the Baja peninsula. In contrast to previous plant studies in this region, however, the expansions do not appear to have been in a strictly northward direction. These findings contribute to a growing appreciation of the complexity of organismal responses to past climatic and geological changes - even when taxa have evolved in the same landscape context.

Pressure distributions on the medial tibial plateau after medial meniscal surgery and tibial plateau levelling osteotomy in dogs.

OBJECTIVE: To evaluate the effect of medial meniscal release (MMR) and medial, caudal pole hemimeniscectomy (MCH) on pressure distribution in the cranial cruciate ligament (CCL) deficient canine stifle, and with tibial plateau levelling osteotomy (TPLO). ANIMALS: Twelve adult dogs. METHODS: In experiment one, six pairs of cadaveric canine stifles with an intact CCL were axially loaded with a servo-hydraulic material testing machine and pressure distributions were mapped and quantified using pressure sensitive films. Axial loading of each joint was then repeated following MMR, and again after MCH. In experiment two, six pairs of cadaveric canine stifles with or without TPLO were tested before and after CCL transection, and each MMR and MCH procedure using the same methods of experiment 1. RESULTS: In experiment one, MMR and MCH had significant effects on the pressure distribution resulting in a 2.5-fold increase in the percentage of surface area with pressure higher than 10 MPa. In experiment two, CCL transection resulted in a significant change in pressure distribution only in the stifle without TPLO (P<0.05). Both MMR and MCH resulted in a 1.7-fold increase in the percentage of area with peak pressure in the stifle with TPLO (P<0.05). CONCLUSIONS: Meniscal surgery results in a change in pressure distribution and magnitude within the medial compartment of the stifle. CLINICAL RELEVANCE: Compromised function of the meniscus by either MMR or MCH result in stress concentration which may predispose to osteoarthritis.

Development and evaluation of a Sarcocystis neurona-specific IgM capture enzyme-linked immunosorbent assay.

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease of horses caused primarily by the protozoal parasite Sarcocystis neurona. Currently available antemortem diagnostic testing has low specificity. The hypothesis of this study was that serum and cerebrospinal fluid (CSF) of horses experimentally challenged with S neurona would have an increased S neurona-specific IgM (Sn-IgM) concentration after infection, as determined by an IgM capture enzyme linked immunoassay (ELISA). The ELISA was based on the S neurona low molecular weight protein SNUCD-1 antigen and the monoclonal antibody 2G5 labeled with horseradish peroxidase. The test was evaluated using serum and CSF from 12 horses experimentally infected with 1.5 million S neurona sporocysts and 16 horses experimentally infected with varying doses (100 to 100,000) of S neurona sporocysts, for which results of histopathologic examination of the central nervous system were available. For horses challenged with 1.5 million sporocysts, there was a significant increase in serum Sn-IgM concentrations compared with values before infection at weeks 2-6 after inoculation (P < .0001). For horses inoculated with lower doses of S neurona, there were significant increases in serum Sn-IgM concentration at various points in time after inoculation, depending on the challenge dose (P < .01). In addition, there was a significant increase between the CSF Sn-IgM concentrations before and after inoculation (P < .0001). These results support further evaluation of the assay as a diagnostic test during the acute phase of EPM.

A spreadsheet-based model demonstrating the nonuniform economic effects of varying reproductive performance in Ohio dairy herds.

A spreadsheet-based model was developed to estimate the economic effect of varying reproductive performance in dairy herds. Scenarios were created to model an average cow with respect to production, herd lifetime, and reproductive events. Average milk yield per day of life as well as lifetime calf and replacement heifer production were examined. Additional inputs representing milk, feed, semen, calf, and salvage prices were used to calculate net cash flow for each day of herd life for the average cow in a scenario. Economic comparison of different scenarios was accomplished using an equivalent annual cash flow (annuity) methodology.Herd performance measures and prices representative of Ohio dairy herds were used to establish a baseline average cow that had a 160-d calving-to-conception interval [days open (DO)]. Alternative scenarios that differed from baseline in DO, annual culling rate, and feed and milk prices were created to characterize the effects of changes. Under scenario inputs representative of typical Ohio dairy herds, the model indicated that a lower annual culling rate (25%) was preferable to higher annual culling rates (34 or 45%). The model estimated maximum average milk yield per day of life to occur at 110 DO. At 34% annual culling rate, calves and replacement heifers produced per lifetime declined as DO increased; beyond 150 DO, the modeled cow produced less than 1 replacement heifer per lifetime. The model also estimated a loss of $1.37 per cow per year for a 1-d increase in DO beyond 160 d. At 20% higher feed and milk prices, the model estimated a loss of $1.52 per cow per year; at 20% lower feed and milk prices, the model estimated a loss of $1.23 per cow per year. Furthermore, the model suggested that the loss associated with a 1-d increase in DO changed as DO changed. Using baseline inputs, the model calculated losses for a 1-d increase of $0.44 per cow per year at 130 DO and $1.71 per cow per year at 190 DO. The nonuniform nature of the cost of additional DO is important to veterinarians and producers. The implication is that inefficient reproduction becomes marginally more costly to producers as performance declines and warrants increased attention. Conversely, marginal benefits of improved reproduction decrease as performance improves. Herds with strong reproductive performance have less opportunity to capture economic benefits of improvement.

A survey of dairy farming in Pennsylvania: nutrient management practices and implications.

A survey was conducted to collect information on nutrient management practices on dairy farms in south-central Pennsylvania. Of the 994 responding farms, the average farm consisted of 64 lactating cows, 10 dry cows, 41 heifers, and 17 calves with 69.7 ha of tillable land. Manure from lactating cows was mainly collected on a daily basis (84% of the farms) and stored as slurry or liquid (73%), while dry cow and heifer manure was collected weekly or less frequently (69 and 85% of the farms) and stored as solid stack or bedded pack (67 and 82%). Manure utilization featured consistent use of on-farm spreading, with limited incorporation, to corn or small grain fields before planting. Spreading on perennial forages or pasture was also common. Irrigation or injection of manure occurred on less than 5% of the farms. Only 20% of the farms reported manure nutrient testing, contrasting to over 90% for soil testing. Farm advisors and their services can be of vital importance in helping producers make conscientious management decisions for enhanced nutrient utilization. For example, ration balancing involved the services of feed and mineral sales representatives (85% of the farms), independent consultants (12%), and veterinarians (5%). Manure nutrient crediting to determine manure application rates was made by fertilizer dealers (40%), crop advisors and independent consultants (31%), and others. Nutrient management strategies and efforts must address the specific needs of farms with different animal densities and nutrient balances in order to be effective and applicable on the majority of farms.

Simultaneous detection of C282Y and H63D hemochromatosis mutations by dual-color probes.

BACKGROUND: Hemochromatosis is a common genetic disease, affecting one in every 200 individuals in the United States. A PCR assay was designed using fluorescent melting curve analysis to simultaneously detect the G845-->A (C282Y) and C187-->G (H63D) mutations. The G845-->A and C187-->G loci are distinguished by color, and mutant alleles are distinguished from wild type by probe melting temperature (Tm). METHODS AND RESULTS: The probe sets used two fluorophore pairs, fluorescein with LCRed 640 for G845-->A and fluorescein with LCRed 705 for C187-->G. The probes, complementary to the mutant allele, dissociate from the product at specific Tms. Wild-type alleles form mismatches with the probes, reducing the Tms by 6 degrees C (G845-->A) and 10 degrees C (C187-->G). One of 133 samples had a Tm shift 4 degrees C less than the wild-type Tm for the G845-->A locus. Sequencing confirmed the sample to be homozygous for G845-->A and heterozygous for a C-->A substitution at position 842 (C842-->A), substituting lysine for threonine. CONCLUSIONS: Multiplexing by color and Tm allows for simultaneous genotyping of each mutation. A novel base-pair alteration was detected in cis with a G845-->A mutation.

N-(cyclohexanecarboxyl)-O-phospho-l-serine, a minimal substrate for the dual-specificity protein phosphatase IphP.

Three dual-specific phosphatases [DSPs], IphP, VHR, and Cdc14, and three protein-tyrosine phosphatases [PTPs], PTP-1B, PTP-H1, and Tc-PTPa, were challenged with a set of low molecular weight phosphoesters to probe the factors underlying the distinct substrate specificities displayed by these two mechanistically homologous families of protein phosphatases. It was observed that beta-naphthyl phosphate represented an excellent general substrate for both PTPs and DSPs. While DSPs tended to hydrolyze alpha-naphthyl phosphate at rates comparable to that of the beta-isomer, the PTPs PTP-1B and Tc-PTPa did not. PTP-H1, however, displayed high alpha-naphthyl phosphatase activity. Intriguingly, PTP-H1 also displayed much higher protein-serine phosphatase activity in vitro, 0.2-0.3% that toward equivalent tyrosine phosphorylated proteins, than did PTP-1B or Tc-PTPa. The latter two PTPs discriminated between the serine- and tyrosine-phosphorylated forms of two test proteins by factors of >/=10(4)-10(6). While free phosphoserine represented an extremely poor substrate for all of the DSPs examined, the addition of a hydrophobic "handle" to form N-(cyclohexanecarboxyl)-O-phospho-l-serine produced a compound that was hydrolyzed by IphP with high efficiency, i.e., at a rate comparable to that of free phosphotyrosine or p-nitrophenyl phosphate. VHR also hydrolyzed N-(cyclohexanecarboxyl)-O-phospho-l-serine (1 mM) at a rate approximately one-tenth that of beta-naphthyl phosphate. None of the PTPs tested exhibited significant activity against this compound. However, N-(cyclohexanecarboxyl)-O-phospho-l-serine did not prove to be a universal substrate for DSPs as Cdc14 displayed little propensity to hydrolyze it.

A comparison of polylactic acid granules and decalcified freeze-dried bone allograft in human periodontal osseous defects.

The purpose of this study was to compare the effectiveness of polylactic acid (PLA) granules as an alloplastic grafting material to that of decalcified freeze-dried bone allograft (DFDBA) and a flap procedure for debridement without graft (FPD) when treating periodontal intrabony defects. Ten patients presenting with advanced adult periodontitis, including at least 3 similar periodontal osseous defects (2- and 3-walled), comprised the study group. After completion of a hygienic phase of treatment, measurements were made with calibrated periodontal probes and stents to determine soft tissue recession, probing pocket depths, and probing attachment levels. Each defect was surgically exposed and hard tissue measurements were obtained. Defects were treated with one of the 3 methods above chosen randomly prior to the surgical appointment. Six months postsurgery, soft tissue measurements were repeated and all sites were surgically reentered to obtain hard tissue measurements. All surgical sites healed without clinical complication. The initial pocket depths and initial depth of osseous defects were compared between the groups using ANOVA and no significant differences were found. A mean osseous defect fill of 0.4 mm (11.2%) occurred with the flap procedure for debridement, 3.0 mm (65%) with DFDBA, and 0.1 mm (2.2%) with PLA. Mean crestal bone loss was 1.30 mm for FPD, 0.60 mm for DFDBA, and 1.55 mm for PLA. No statistically significant differences were found in soft tissue recession between groups or in the osseous defect measurement between PLA and FPD. A statistically significant improvement (P < 0.001) was found in the fill of the osseous defects when using DFDBA compared to the initial defect depth and to the other 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Selection of bulls for progeny testing using pedigree indices and characteristics of potential bull-dams' herds.

A total of 209 bulls selected from herds in the northeastern US by Eastern AI Coop., Inc. from 1978 to 1981 were identified. The DHI data were obtained for the 145 herds from which these bulls were sampled. Also acquired were evaluations from both Modified Contemporary Comparison and animal model on these bulls and their ancestors and on cows and their sires in the bull-dam herds. From evaluation by animal model, animals appeared to have contributed information to each other effectively through relationship matrix, and thus the accuracy of cow evaluation has been improved. Bulls selected from herds of high genetic level were genetically superior to those from herds of low genetic level. However, there was no evidence that bulls from low intraherd milk variation herds were superior to those from high variation herds in the northeastern population, as was the case in Michigan herds. Parent indices were greater than bull PTA in herds of lower genetic level but less than bull PTA in herds of higher genetic level. The correlation between herd yield average and herd genetic level and that between herd yield average and intraherd yield SD were moderate but significantly different from zero. Other correlations between phenotypic and genetic measures of bull-dam herds were negligible. None of the herd characteristics showed promise in characterizing herds that were more successful in having their sampled bulls returned by AI organization after progency test.

Folate deficiency and an abnormal lymphocyte deoxyuridine suppression test in monkeys.

Cebus albifrons were fed folate-deficient diets in order to assess folate status at the cellular level with the deoxyuridine suppression test. Plasma and red blood cell folates were significantly lower at 2 months, compared to control values. Hematologic signs of megaloblastic anemia occurred after 6 months, with significantly lower hematocrit, hemoglobin and red blood cell number values and increased polymorphonuclear leukocyte lobe counts. Urinary formiminoglutamic acid excretion also was elevated significantly. Whole blood lymphocyte cultures exhibited abnormal deoxyuridine suppression of [3H]-thymidine incorporation into DNA with folate deficiency. Thus this deoxyuridine suppression test can be used in isolated whole blood lymphocytes of these nonhuman primates to document folate deficiency.

The Edinburgh-ORLAU prosthetic system to provide reciprocal locomotion in children and adults with complete transverse lower limb deficiency.

A novel prosthetic system to provide reciprocal locomotion in children and adults with complete transverse lower limb deficiency is described. This is based on the hip joints from the ORLAU ParaWalker, a system with a proven record of success in the orthotic management of paraplegic patients. The fitting of the prototype system to an eight year old girl is described. This experience shows that the orthotic principles of the ParaWalker, which provides reciprocal locomotion for the paraplegic, is equally applicable to the prosthetic situation. Developments are therefore continuing to improve the design and to enable further fittings.