Surfactancy in a tadpole model of proteins.

We model the environment of eukaryotic nuclei by representing macromolecules by only their entropic properties, with globular molecules represented by spherical colloids and flexible molecules by polymers. We put particular focus on proteins with both globular and intrinsically disordered regions, which we represent with 'tadpole' constructed by grafting single polymers and colloids together. In Monte Carlo simulations, we find these tadpoles support phase separation via depletion flocculation, and demonstrate several surfactant behaviours, including being found preferentially at interfaces and forming micelles in single phase solution. Furthermore, the model parameters can be tuned to give a tadpole a preference for either bulk phase. However, we find entropy too weak to drive these behaviours by itself at likely biological concentrations.

Peroxone activated persulfate oxidation of 1,4-Dioxane under column scale conditions.

The research presented herein investigates a peroxone activated persulfate (PAP) oxidant, commercialized under the trade name OxyZone®, and its effects on 1,4-Dioxane (dioxane) contaminated water under column scale conditions in the presence of porous material. There is a limited understanding of the underlying processes that govern PAP oxidation, including the oxidation rates in the presence of aquifer material, and how these reactions proceed once the oxidant is injected into a contaminant plume. Initial batch experiments with porous material (e.g. sand) provided data on the reaction rates of dioxane oxidation as a function of the oxidant: contaminant ratio. The observed degradation rates were approximately 4 times lower than those reported for aqueous solutions containing no porous media. Subsequent column experiments simulated two PAP injections schemes along the flowpath of a dioxane plume to study if the injection of one oxidant slug may yield different results than injecting the same oxidant volume at two separate locations. The injection of one oxidant slug was found more effective, resulting in near complete destruction of dioxane over a prolonged time at a rate more than an order of magnitude greater than in the two-slug injection scenario. Tracer test results suggest that the prolonged oxidant reactivity was in part caused by the high density of the injected oxidant solution. Overall, the results underline the importance of accounting for the properties of both the oxidant solution and the porous material when considering the injection of PAP oxidant into an impacted aquifer.

The role of illicit drugs in developing medication-related osteonecrosis (MRONJ): a systematic review.

Medication-related osteonecrosis of the jaw (MRONJ) is a challenging condition to treat. It has primarily been associated with anti-resorptive and anti-angiogenic drugs, which are increasingly being used to prevent adverse skeletally-related complications in patients with cancer and bone pathologies. Although these medications have been proven to cause osteonecrosis of the jaws (ONJ) there are also a number of other drugs that could potentially cause this condition. The aim of this systematic review is to ascertain whether there is an associated risk of osteonecrosis of the jaw (ONJ) in recreational drug users (RDU). Three authors independently searched PubMed, MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials for published reports of osteonecrosis of the jaw (ONJ) in recreational drug users (RDU) or illicit drug users (IDU) who had no history of treatment with anti-angiogenic or anti-resorptive agents. Only 30 studies were eligible for analysis, and all were independently assessed for risk of bias. There was a total of 101 patients with ONJ attributed solely to illicit drug consumption. The most common site of ONJ was the maxilla (n=54). The most common illicit drug related to ONJ was desmorphine, known as 'Krokodil', this was followed by cocaine, methamphetamine, anabolic steroids, and hydrocodone/acetaminophen. In 52 of the cases, the ONJ resolved following treatment, however, eight showed a recurrence. Although all the studies were judged to be at a high risk of bias, the limited data suggest that some patients are at risk of developing ONJ as a result of illicit drug usage. Studies of higher quality are needed to establish the relative risk of ONJ in this patient group.

Costochondral grafting for paediatric temporomandibular joint reconstruction: 10-year outcomes in 55 cases.

Costochondral grafting (CCG) can be used for the reconstruction of ankylotic, hypoplastic, and resected temporomandibular joint (TMJ) defects. CCGs have previously been considered the gold standard in children due to their growth potential and autogenous origin, but the disadvantages are unpredictable growth and joint ankylosis. This was a retrospective study of all children who received CCGs for TMJ reconstruction from 1985 to 2004, to allow a 10-year follow-up. Fifty-five patients were included in this study, with 74 grafts being placed; their mean age was 7.9±4.2years. Infection-related ankylosis (18.2%) and craniofacial microsomia (16.4%) were the most common diagnoses. Overall, 58.2% of patients suffered one or more complications over the follow-up period, with ankylosis (32.7%) and overgrowth (16.4%) being most common. There was a significant correlation between those with infection-related ankylosis and subsequent complications (χ2=8.8, df=1, P<0.005), while ankylotic patients in general exhibited greater overall complication rates (χ2=9.0, df=1, P<0.005). Patients with congenital TMJ defects were more likely to be complication-free than those with acquired defects (χ2=4.0, df=1, P<0.05). Caution is advised when placing CCGs in paediatric patients with ankylosed TMJs, especially those with infection-related ankylosis.

Patient Outcomes and Cerebral Infarction after Ruptured Anterior Communicating Artery Aneurysm Treatment.

BACKGROUND AND PURPOSE: Anterior communicating artery aneurysm rupture and treatment is associated with high rates of dependency, which are more severe after clipping compared with coiling. To determine whether ischemic injury might account for these differences, we characterized cerebral infarction burden, infarction patterns, and patient outcomes after surgical or endovascular treatment of ruptured anterior communicating artery aneurysms. MATERIALS AND METHODS: We performed a retrospective cohort study of consecutive patients with ruptured anterior communicating artery aneurysms. Patient data and neuroimaging studies were reviewed. A propensity score for outcome measures was calculated to account for the nonrandom assignment to treatment. Primary outcome was the frequency of frontal lobe and striatum ischemic injury. Secondary outcomes were patient mortality and clinical outcome at discharge and at 3 months. RESULTS: Coiled patients were older (median, 55 versus 50 years; P = .03), presented with a worse clinical status (60% with Hunt and Hess Score >2 versus 34% in clipped patients; P = .02), had a higher modified Fisher grade (P = .01), and were more likely to present with intraventricular hemorrhage (78% versus 56%; P = .03). Ischemic frontal lobe infarction (OR, 2.9; 95% CI, 1.1-8.4; P = .03) and recurrent artery of Heubner infarction (OR, 20.9; 95% CI, 3.5-403.7; P < .001) were more common in clipped patients. Clipped patients were more likely to be functionally dependent at discharge (OR, 3.2; P = .05) compared with coiled patients. Mortality and clinical outcome at 3 months were similar between coiled and clipped patients. CONCLUSIONS: Frontal lobe and recurrent artery of Heubner infarctions are more common after surgical clipping of ruptured anterior communicating artery aneurysms, and are associated with poorer clinical outcomes at discharge.

Signatures of the collapse and incipient recovery of an overexploited marine ecosystem.

The Northwest Atlantic cod stocks collapsed in the early 1990s and have yet to recover, despite the subsequent establishment of a continuing fishing moratorium. Efforts to understand the collapse and lack of recovery have so far focused mainly on the dynamics of commercially harvested species. Here, we use data from a 33-year scientific trawl survey to determine to which degree the signatures of the collapse and recovery of the cod are apparent in the spatial and temporal dynamics of the broader groundfish community. Over this 33-year period, the groundfish community experienced four phases of change: (i) a period of rapid, synchronous biomass collapse in most species, (ii) followed by a regime shift in community composition with a concomitant loss of functional diversity, (iii) followed in turn by periods of slow compositional recovery, and (iv) slow biomass growth. Our results demonstrate how a community-wide perspective can reveal new aspects of the dynamics of collapse and recovery unavailable from the analysis of individual species or a combination of a small number of species. Overall, we found evidence that such community-level signals should be useful for designing more effective management strategies to ensure the persistence of exploited marine ecosystems.

Calibration and validation of a carbon oxidation system and determination of the bicarbonate retention factor and the dietary phenylalanine requirement, in the presence of excess tyrosine, of adult, female, mixed-breed dogs,.

Carbon oxidation methods have been used as rapid and sensitive methods to determine whole-body AA requirements in multiple species. The objectives of the current studies were to validate complete CO recovery, determine the bicarbonate retention factor, and estimate the Phe requirement, in the presence of excess Tyr, in adult dogs using the direct oxidation technique. In this series of studies, 2 oxidation chambers were constructed and calibrated to ensure accurate collection of breath CO. First, 104.6 ± 7.1% CO was recovered from chambers and suggests that the chambers were appropriately designed for complete and efficient CO recovery. Second, we determined bicarbonate retention in 5 dogs using repeated oral dosing of a bicarbonate tracer (NaHCO) with small meals. At isotopic and physiological steady state, 102.5 ± 2.6% of the delivered NaHCO was recovered in breath. Third, the Phe requirement, when Tyr was supplied in excess, was determined by the rate of appearance of CO in the breath (CO). Dogs ( = 5) were fed test diets with different concentrations of Phe ranging from deficient to excessive for 2 d prior to conducting the tracer studies. The mean Phe requirement (when Tyr was supplied in excess) was 0.535% of diet (upper 95% confidence interval = 0.645% diet) on an as-fed basis or 0.575% of diet (upper 95% confidence interval = 0.694% of diet) on a DM basis and was based on a calculated (modified Atwater calculation) dietary ME density of 3.73 Mcal/kg DM. These data support the use of carbon oxidation methods and oral dosing of isotope to measure whole-body requirements of indispensable AA in adult dogs and suggest the current recommendations may be low.

Boric Acid Is Reproductively Toxic to Adult Xenopus laevis, but Not Endocrine Active.

The potential reproductive and endocrine toxicity of boric acid (BA) in the African clawed frog, Xenopus laevis, was evaluated using a 30-day exposure of adult frogs. Adult female and male frogs established as breeders were exposed to a culture water control and 4 target (nominal) test concentrations [5.0, 7.5, 10.0, and 15 mg boron (B)/L, equivalent to 28.5, 42.8, 57.0, and 85.5 mg BA/L] using flow-through diluter exposure system. The primary endpoints measured were adult survival, growth (weight and snout-vent length [SVL]), necropsy data, reproductive fecundity, and development of progeny (F1) from the exposed frogs. Necropsy endpoints included gonad weight, gonado-somatic index (GSI), ovary profile (oocyte normalcy and stage distribution), sperm count, and dysmorphology. Endocrine endpoints included plasma estradiol (E2), testosterone (T), dihydrotestosteone (DHT), gonadal CYP 19 (aromatase), and gonadal 5α-reductase (5-AR). BA exposure to adult female X. laevis increased the proportion of immature oocytes (< stage II) in the ovaries of females, reduced sperm counts and increased sperm cell dysmorphology frequency in male frogs exposed to 15 mg B/L. No effects on the other general, developmental (F1), or endocrine endpoints were observed. Based on the results of the present study, the no observed adverse effects concentration (NOAEC) for the reproductive endpoints was 10 mg B/L; and 15 mg B/L for reproductive fecundity, F1 embryo larval development, and endocrine function. These results confirmed that although BA is capable of inducing reproductive toxicity at high concentrations, it is not an endocrine disrupting agent.

Can Natural Language Processing Improve the Efficiency of Vaccine Adverse Event Report Review?

BACKGROUND: Individual case review of spontaneous adverse event (AE) reports remains a cornerstone of medical product safety surveillance for industry and regulators. Previously we developed the Vaccine Adverse Event Text Miner (VaeTM) to offer automated information extraction and potentially accelerate the evaluation of large volumes of unstructured data and facilitate signal detection. OBJECTIVE: To assess how the information extraction performed by VaeTM impacts the accuracy of a medical expert's review of the vaccine adverse event report. METHODS: The "outcome of interest" (diagnosis, cause of death, second level diagnosis), "onset time," and "alternative explanations" (drug, medical and family history) for the adverse event were extracted from 1000 reports from the Vaccine Adverse Event Reporting System (VAERS) using the VaeTM system. We compared the human interpretation, by medical experts, of the VaeTM extracted data with their interpretation of the traditional full text reports for these three variables. Two experienced clinicians alternately reviewed text miner output and full text. A third clinician scored the match rate using a predefined algorithm; the proportion of matches and 95% confidence intervals (CI) were calculated. Review time per report was analyzed. RESULTS: Proportion of matches between the interpretation of the VaeTM extracted data, compared to the interpretation of the full text: 93% for outcome of interest (95% CI: 91-94%) and 78% for alternative explanation (95% CI: 75-81%). Extracted data on the time to onset was used in 14% of cases and was a match in 54% (95% CI: 46-63%) of those cases. When supported by structured time data from reports, the match for time to onset was 79% (95% CI: 76-81%). The extracted text averaged 136 (74%) fewer words, resulting in a mean reduction in review time of 50 (58%) seconds per report. CONCLUSION: Despite a 74% reduction in words, the clinical conclusion from VaeTM extracted data agreed with the full text in 93% and 78% of reports for the outcome of interest and alternative explanation, respectively. The limited amount of extracted time interval data indicates the need for further development of this feature. VaeTM may improve review efficiency, but further study is needed to determine if this level of agreement is sufficient for routine use.

The FDA's sentinel initiative--A comprehensive approach to medical product surveillance.

In May 2008, the Department of Health and Human Services announced the launch of the Sentinel Initiative by the US Food and Drug Administration (FDA) to create the Sentinel System, a national electronic system for medical product safety surveillance. This system complements existing FDA surveillance capabilities that track adverse events reported after the use of FDA regulated products by allowing the FDA to proactively assess the safety of these products.

BMP signaling and microtubule organization regulate synaptic strength.

The strength of synaptic transmission between a neuron and multiple postsynaptic partners can vary considerably. We have studied synaptic heterogeneity using the glutamatergic Drosophila neuromuscular junction (NMJ), which contains multiple synaptic connections of varying strengths between a motor axon and muscle fiber. In larval NMJs, there is a gradient of synaptic transmission from weak proximal to strong distal boutons. We imaged synaptic transmission with the postsynaptically targeted fluorescent calcium sensor SynapCam, to investigate the molecular pathways that determine synaptic strength and set up this gradient. We discovered that mutations in the Bone Morphogenetic Protein (BMP) signaling pathway disrupt production of strong distal boutons. We find that strong connections contain unbundled microtubules in the boutons, suggesting a role for microtubule organization in transmission strength. The spastin mutation, which disorganizes microtubules, disrupted the transmission gradient, supporting this interpretation. We propose that the BMP pathway, shown previously to function in the homeostatic regulation of synaptic growth, also boosts synaptic transmission in a spatially selective manner that depends on the microtubule system.

How is income generated by outpatient parenteral antibiotic treatment (OPAT) in the UK? Analysis of payment tariffs for cellulitis.

OBJECTIVES: We determined the available mechanisms to generate income from outpatient parenteral antimicrobial therapy (OPAT) in the UK and calculated the revenue generated from treatment of an episode of cellulitis. METHODS: Revenue was calculated for patients receiving treatment for cellulitis as an inpatient and for patients receiving OPAT by a series of different payment pathways. Selected established OPAT services in Northern Ireland, Scotland and Wales, where Payment-by-Results (PbR) does not operate, were contacted to determine individual national funding arrangements. RESULTS: In England, a traditional inpatient episode for uncomplicated cellulitis requiring 7 days of treatment generated £1361 of revenue, while OPAT generated revenue ranging from £773 to £2084 for the same length of treatment depending on the payment pathway used. Treatment using OPAT to avoid admission entirely generated £2084, inpatient admission followed by transfer to a virtual OPAT ward at day 2 generated £1361 and inpatient admission followed by discharge from hospital to OPAT at day 2 generated £773. In Northern Ireland, Scotland and Wales block contracts were used and no income was calculable for an individual episode of cellulitis. CONCLUSIONS: No single funding mechanism supports OPAT across the UK. In England, revenue generated by OPAT providers from treatment of cellulitis varied with the OPAT payment pathway used, but equalled or exceeded the income generated from equivalent inpatient care. Cost savings for OPAT and reuse of released inpatient beds will increase revenue further. A single OPAT tariff is proposed.

Sperm sex-sorting and preservation for managing the sex ratio and genetic diversity of the southern white rhinoceros (Ceratotherium simum simum).

White rhinoceros ejaculates (n=9) collected by electroejaculation from four males were shipped (10°C, 12h) to develop procedures for the production of chilled and frozen-thawed sex-sorted spermatozoa of adequate quality for artificial insemination (AI). Of all electroejaculate fractions, 39.7% (31/78) exhibited high quality post-collection (≥70% total motility and membrane integrity) and of those, 54.8% (17/31) presented reduced in vitro quality after transport and were retrospectively determined to exhibit urine-contamination (≥21.0µg creatinine/ml). Of fractions analyzed for creatinine concentration, 69% (44/64) were classified as urine-contaminated. For high quality non-contaminated fractions, in vitro parameters (motility, velocity, membrane, acrosome and DNA integrity) of chilled non-sorted and sorted spermatozoa were well-maintained at 5°C up to 54h post-collection, whereby >70% of post-transport (non-sorted) or post-sort (sorted) values were retained. By 54h post-collection, some motility parameters were higher (P<0.05) for non-sorted spermatozoa (total motility, rapid velocity, average path velocity) whereas all remaining motion parameters as well as membrane, acrosome and DNA integrity were similar between sperm types. In comparison with a straw method, directional freezing resulted in enhanced (P<0.05) motility and velocity of non-sorted and sorted spermatozoa, with comparable overall post-thaw quality between sperm types. High purity enrichment of X-bearing (89±6%) or Y-bearing (86±3%) spermatozoa was achieved using moderate sorting rates (2540±498X-spermatozoa/s; 1800±557Y-spermatozoa/s). Collective in vitro characteristics of sorted-chilled or sorted-frozen-thawed spermatozoa derived from high quality electroejaculates indicate acceptable fertility potential for use in AI.

Tryptophan requirement of pregnant sows.

Amino acid requirements of sows may change from early to late gestation due to the accelerated growth of products of conception after d 70 of pregnancy. The objective of this study was to determine the Trp requirement, Phe kinetics, and energy expenditure in early (d 35 to 53) and late (d 92 to 111) pregnancy using the indicator amino acid oxidation method and indirect calorimetry. The same 6 second parity sows were fed 6 diets in a Latin square design in both early and late pregnancy. The diets based on corn, corn starch, and sugar provided 20 to 120% of the current recommended Trp intake (2.5 g/d) in early pregnancy and 60 to 180% in late pregnancy. Feed allowance was constant for each sow at 2.41 kg/d (SE 0.029). Expired air and blood were collected every 30 min for 5 1/2 h. After three 30-min periods to determine background (13)C enrichment in expired CO2 and plasma Phe, L[1-(13)C]Phe was given orally at a rate of 2 mg/(kg BW · h) with 8 1/2 hourly meals. Expired air and plasma were analyzed for (13)CO2 and (13)C-Phe enrichment, respectively. Requirements were determined as the breakpoint of 2-phase linear models. Sows grew from 167.7 kg (SE 3.93) at breeding to 211.9 kg (SE 5.18) post-farrowing and had litters of 14.5 piglets (SE 0.43) weighing 19.0 kg (SE 1.41) at birth. The Trp requirement was 1.7 g/d (SE 0.29, P = 0.001) in early pregnancy and 2.6 g/d (SE 0.37, P = 0.013) in late pregnancy, or 0.7 g/kg and 1.1 g/kg diet of total Trp, respectively, for a feed allowance of 2.4 kg/d. The Trp requirement in late pregnancy tended (P = 0.056) to be greater than in early pregnancy. Quantitative Phe kinetics were not affected by Trp intake except for a quadratic response of Phe oxidation and retention (P < 0.1) to Trp intake in early pregnancy. In late pregnancy, sows oxidized less Phe and retained more Phe (P = 0.001) than in early pregnancy, indicating that young, growing pregnant sows increase the efficiency of utilizing AA in late pregnancy to maintain protein synthesis in both maternal and fetal tissues. Oxidation and body protein breakdown contributed less to Phe flux in late than early pregnancy while protein synthesis contributed more (P < 0.01). Heat production and energy retention were not affected by Trp level or stage of gestation. To meet both energy and AA requirements in late gestation, a phase feeding program with 2 diets is recommended. The feed allowance in late pregnancy should be greater than in early pregnancy to account for the increased energy expenditure.

Simulating adverse event spontaneous reporting systems as preferential attachment networks: application to the Vaccine Adverse Event Reporting System.

BACKGROUND: Spontaneous Reporting Systems [SRS] are critical tools in the post-licensure evaluation of medical product safety. Regulatory authorities use a variety of data mining techniques to detect potential safety signals in SRS databases. Assessing the performance of such signal detection procedures requires simulated SRS databases, but simulation strategies proposed to date each have limitations. OBJECTIVE: We sought to develop a novel SRS simulation strategy based on plausible mechanisms for the growth of databases over time. METHODS: We developed a simulation strategy based on the network principle of preferential attachment. We demonstrated how this strategy can be used to create simulations based on specific databases of interest, and provided an example of using such simulations to compare signal detection thresholds for a popular data mining algorithm. RESULTS: The preferential attachment simulations were generally structurally similar to our targeted SRS database, although they had fewer nodes of very high degree. The approach was able to generate signal-free SRS simulations, as well as mimicking specific known true signals. Explorations of different reporting thresholds for the FDA Vaccine Adverse Event Reporting System suggested that using proportional reporting ratio [PRR] > 3.0 may yield better signal detection operating characteristics than the more commonly used PRR > 2.0 threshold. DISCUSSION: The network analytic approach to SRS simulation based on the principle of preferential attachment provides an attractive framework for exploring the performance of safety signal detection algorithms. This approach is potentially more principled and versatile than existing simulation approaches. CONCLUSION: The utility of network-based SRS simulations needs to be further explored by evaluating other types of simulated signals with a broader range of data mining approaches, and comparing network-based simulations with other simulation strategies where applicable.

Implementing a low-starch biscuit-free diet in zoo gorillas: the impact on behavior.

In the wild, western lowland gorillas travel long distances while foraging and consume a diet high in fiber and low in caloric density. In contrast, gorillas in zoos typically consume a diet that is low in fiber and calorically dense. Some items commonly used in captive gorilla diets contain high levels of starch and sugars, which are present at low levels in the natural diet of gorillas. Diet items high in simple carbohydrates are associated with obesity and heart disease in humans. Typical captive gorilla diets may also encourage undesirable behaviors. In response to these issues, we tested the behavioral impact of a diet that was biscuit-free, had low caloric density, and which was higher in volume at five institutions. We hypothesized that this diet change would reduce abnormal behaviors such as regurgitation and reingestion (R/R), decrease time spent inactive, and increase time spent feeding. The biscuit-free diet significantly reduced (and in the case of one zoo eliminated) R/R and may have reduced hair-plucking behavior. However, an increase in coprophagy was observed in many individuals following the diet change. The experimental diet caused a general increase in time the gorillas spent feeding, but this increase did not occur across all institutions and varied by individual. Interestingly, the overall time gorillas spent inactive actually increased with this diet change. Future research will examine these behavioral changes in a greater number of individuals to determine if the results remain consistent with these preliminary findings. Additionally, future research will examine the physiological impact of this diet change.

Implementing a low-starch biscuit-free diet in zoo gorillas: the impact on health.

In the wild, western lowland gorillas consume a diet high in fiber and low in caloric density. In contrast, many gorillas in zoos consume a diet that is high-calorie and low in fiber. Some items commonly used in captive gorilla diets contain high levels of starch and sugars, which are minimal in the natural diet of gorillas. There is a growing concern that captive gorillas may qualify as obese. Furthermore, the leading cause of death for adult male gorillas in zoos is heart disease. In humans, a diet that is high in simple carbohydrates is associated with both obesity and the incidence of heart disease. In response to these issues, we implemented a biscuit-free diet (free of biscuits and low in fruit) and measured serum biomarkers of obesity and insulin resistance pre- and post-diet change at three institutions: North Carolina Zoological Garden, Cleveland Metroparks Zoo, and Columbus Zoo and Aquarium. We also added a resistant starch supplement to gorilla diets at two of the above institutions. We anticipated that these diet changes would positively affect biomarkers of obesity and insulin resistance. Both diet manipulations led to a reduction in insulin. Resistant starch also decreased overall serum cholesterol levels. Future research will examine these health changes in a greater number of individuals to determine if the results remain consistent with these preliminary findings.

Transfusion-associated circulatory overload (TACO) and potential risk factors among the inpatient US elderly as recorded in Medicare administrative databases during 2011.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is a serious transfusion complication resulting in respiratory distress. The study's objective was to assess TACO occurrence and potential risk factors among elderly Medicare beneficiaries (ages 65 and older) in the inpatient setting during 2011. MATERIALS AND METHODS: This retrospective claims-based study utilized Medicare administrative databases in coordination with Centers for Medicare & Medicaid Services. Transfusions were identified by recorded procedure and revenue centre codes, while TACO was ascertained via ICD-9-CM diagnosis code. We evaluated TACO diagnosis code rates overall and by age, gender, race, number of units and blood components transfused. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 2,147,038 inpatient transfusion stays for elderly in 2011, 1340 had TACO diagnosis code, overall rate of 62·4 per 100,000 stays. TACO rates increased significantly with age and units transfused (P < 0·0001). After adjustment for confounding, significantly higher odds of TACO were found for women vs. men (OR = 1·40, 95% CI 1·26-1·60), White people vs. non-White people (OR = 1·38, 95% CI 1·20-1·62) and persons with congestive heart failure (OR = 1·61, 95% CI 1·44-1·88), chronic pulmonary disease (OR = 1·19, 95% CI 1·08-1·32) and different anaemias. CONCLUSION: Our study identified largest number of potential TACO cases to date and showed a substantial increase in TACO occurrence with age and number of units transfused. The study suggested increased TACO risk in elderly with congestive heart failure, chronic pulmonary disease and anaemias. Overall, study shows importance of large administrative databases as an additional epidemiological tool.

Isoleucine requirement of pregnant sows.

The objective of this study was to determine the Ile requirement in early (d 39 to 61) and late (d 89 to 109) pregnancy using the indicator AA oxidation method. The same 7 Large White × Landrace sows in their fourth parity were used in early and late pregnancy. Each sow received 6 diets based on corn, corn starch, and sugar in both early and late pregnancy at constant feed allowances (2.5 kg/d). Diets provided Ile at 20, 40, 60, 80, 100, and 120% of the Ile requirement (6.2 g/d based on the 1998 NRC) in early and 60, 80, 100, 140, 160, and 180% in late pregnancy. After determination of (13)C background in expired CO2 and plasma free Phe for 1.5 h when confined in respiration chambers, sows were fed the tracer, L[1-(13)C]Phe, a rate of 2.0 mg/(kg BW·h) over 4 h divided into eight 30-min meals. Expired CO2 and plasma free Phe were analyzed for (13)C enrichment above background. Requirements were determined as the breakpoint in 2-phase nonlinear models. Sow BW was 246.5 kg in early and 271.6 kg in late pregnancy. Daily gain of the 6 sows was similar in early (344 g/d) and late pregnancy (543 g/d). During pregnancy, sow maternal gain was 19.1 ± 4.4 kg and litters of 17.7 ± 0.8 piglets weighed 22.6 ± 0.9 kg at birth. The Ile requirement was 3.6 ± 1.2 g/d (P = 0.001) in early pregnancy with a Phe retention (-0.59 g/d) and energy retention (-0.31 MJ/d) that were not different from 0. This indicates that the fourth parity sows had requirements close to maintenance in early pregnancy. The Ile requirement in late pregnancy was 9.7 ± 1.9 g/d (P = 0.001) when sows retained 3.30 g/d of Phe and -1.45 MJ/d of energy. The greater Ile requirement in late pregnancy was probably caused by the increased conceptus growth after d 70 of pregnancy. Phenylalanine flux, oxidation, and nonoxidative disposal increased (P < 0.1) from early to late pregnancy, but body protein breakdown did not. Phenylalanine oxidation, nonoxidative disposal, and retention increased (P < 0.01) with increasing Ile intake in early pregnancy but were not affected by Ile intake in late pregnancy. Body protein breakdown did not respond to Ile intake in early or late pregnancy. Although energy retention was similar in early and late pregnancy, the respiratory quotient decreased (P = 0.047) from early (1.05) to late pregnancy (0.98), indicating lipid mobilization in late pregnancy when Ile was at or above the requirement. The results of this study show that the Ile requirement of sows increases from early to late pregnancy.