Bronchoalveolar Activation of Coagulation and Inhibition of Fibrinolysis during Ventilator-Associated Lung Injury

Background and Objective. Bronchoalveolar coagulopathy is a characteristic feature of pulmonary inflammation. We compared bronchoalveolar and systemic levels of coagulation in patients who did and patients who did not develop ventilator-associated lung injury (VALI). Methods. Secondary analysis of a randomized controlled trial evaluating the effect of lower tidal volumes versus conventional tidal volumes in patients without acute lung injury or acute respiratory distress syndrome at the onset of mechanical ventilation. Results. Ten patients with VALI and 10 random control patients without lung injury during the course of mechanical ventilation, but all ventilated with conventional tidal volumes, were compared. Patients who developed VALI showed both bronchoalveolar activation of coagulation (increase in thrombin–antithrombin complex levels P < 0.001 versus baseline) and inhibition of fibrinolysis (decline in plasminogen activator activity P < 0.001 versus baseline). The later seemed to be dependent on higher levels of plasminogen activator inhibitor type 1 (P = 0.001 versus baseline). Patients who developed VALI also showed elevated systemic thrombin-antithrombin complex levels and decreased systemic plasminogen activator activity levels. Conclusions. VALI is characterized by bronchoalveolar coagulopathy. Systemic and bronchoalveolar coagulopathy at the onset of mechanical ventilation may be a risk factor for developing VALI in patients ventilated with conventional tidal volumes

Effects of transport age (14 d vs. 28 d of age) on blood total cholesterol, insulin and IGF-1 concentrations of veal calves.

The main aim of the current study was to find biomarkers of health in calves transported at different ages. The selected blood parameters were total cholesterol, insulin and IGF-1 and the longitudinal study investigated whether or not these concentrations were different between calves that were transported from the dairy farm to the veal farm at 14 d or 28 d of age. Relationships between these blood variables and health characteristics of veal calves were investigated. In a 34-wk study period, a total of 683 calves originating from 13 Dutch dairy farms were transported at an age of 14 or 28 d to 8 Dutch veal farms. Calves were blood sampled the first wk after birth (mean and SD: 4.4 ± 2.1 d), a day before transport (mean and SD: 25.8 ± 7.3 d) and in wk 2 post-transport (mean and SD: 36.7 ± 12.2 d). In these samples, insulin, IGF-1 and total cholesterol were determined and analyzed with a linear mixed model (LMM). Individual medical treatments were recorded from birth until the day of transport at the dairy farm, and from the moment of arrival at the veal farm until slaughter, and analyzed as a binary response variable (calf treated or not) with a generalized linear mixed model. Fecal (calf with or without loose or liquid manure) and navel (calves with or without swollen and inflamed navel) scores measured during a single visit in wk 2 post-transport were also analyzed as binary response variables, whereas carcass weights at slaughter age were analyzed with a LMM. Cholesterol, insulin and IGF-1 were included as covariates in the previous models to test their relationships with the likelihood of calves being medically treated, fecal and navel scores, and carcass weights. One day before transport 28 d-old calves had higher blood cholesterol (Δ = 0.40 mmol/l) and IGF-1 (Δ = 53.6 ng/ml) concentrations, and evidence of higher insulin (Δ = 12.2 µU/ml) compared with 14 d-old calves. In wk 2 post-transport, 28-d old calves had higher blood IGF-1 (Δ = 21.1 ng/ml), with evidence of higher insulin (Δ = 12.2 µU/ml) concentrations compared with 14-d old calves. Cholesterol concentration measured one day before transport and in wk 2 post-transport had a positive relationship with carcass weight at slaughter (β = 4.8 and 7.7 kg/mmol/l, respectively). Blood cholesterol concentration in wk 2 post-transport was negatively associated with the fecal score measured at the same sampling moment (β = -0.55/mmol/l), with the likelihood of a calf of being treated with antibiotics (β = -0.36/mmol/l) and other medicines (β = -0.45/mmol/l) at the veal farm. Blood IGF-1 concentration in wk 2 post-transport was negatively associated with the likelihood of a calf of being treated with antibiotics and other medicines (both β = -0.01/ng/ml) at the veal farm, and with fecal score recorded in wk 2 post-transport (β = -0.004/ng/ml). When looking at the blood indicators, it appeared that calves transported at 28 d of age were more developed compared with 14 d old calves, thus transport at an older age might be more beneficial for the animals. It can be concluded that both blood cholesterol and IGF-1 concentrations seemed to be valuable biomarkers of health and energy availability in veal calves

Mechanical Ventilation and the Titer of Antibodies as Risk Factors for the Development of Transfusion-Related Lung Injury

Purpose. Onset of transfusion-related acute lung injury (TRALI) is suggested to be a threshold-event. Data is lacking on the relation between titer of antibodies infused and onset of TRALI. We determined whether onset of TRALI is dependent on the titer of MHC-I antibodies infused in a combined model of ventilator-induced lung injury and antibody-induced TRALl. Methods. BALB/c mice were ventilated for five hours with low (7.5 ml/kg) or high (15 ml/kg) tidal volume. After three hours of MV, TRALI was induced by infusion of 0.5 mg/kg, 2.0 mg/kg or 4.5 mg/kg MHC-I antibodies. Control animals received vehicle. After five hours of MV, animals were sacrificed. Results. MV with high tidal volumes resulted in increased levels of all markers of lung injury compared to animals ventilated with low tidal MV. In ventilator-induced lung injury, infusion of 4.5 mg/kg of antibodies further increased pulmonary wet-to-dry ratio, pulmonary neutrophil influx and pulmonary KC levels, whereas infusion of lower dose of antibodies did not augment lung injury. In contrast, mice ventilated with low tidal volumes did not develop lung injury, irrespective of the dose of antibody used. Conclusions. In the presence of injurious MV, onset of TRALI depends on the titer of antibodies infused

Mechanical ventilation with lower tidal volumes does not influence the prescription of opioids or sedatives

INTRODUCTION: We compared the effects of mechanical ventilation with a lower tidal volume (V(T)) strategy versus those of greater V(T) in patients with or without acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) on the use of opioids and sedatives. METHODS: This is a secondary analysis of a previously conducted before/after intervention study, which consisting of feedback and education on lung protective mechanical ventilation using lower V(T). We evaluated the effects of this intervention on medication prescriptions from days 0 to 28 after admission to our multidisciplinary intensive care unit. RESULTS: Medication prescriptions in 23 patients before and 38 patients after intervention were studied. Of these patients, 10 (44%) and 15 (40%) suffered from ALI/ARDS. The V(T) of ALI/ARDS patients declined from 9.7 ml/kg predicted body weight (PBW) before to 7.8 ml/kg PBW after the intervention (P = 0.007). For patients who did not have ALI/ARDS there was a trend toward a decline from 10.2 ml/kg PBW to 8.6 ml/kg PBW (P = 0.073). Arterial carbon dioxide tension was significantly greater after the intervention in ALI/ARDS patients. Neither the proportion of patients receiving opioids or sedatives, or prescriptions at individual time points differed between pre-intervention and post-intervention. Also, there were no statistically significant differences in doses of sedatives and opioids. Findings were no different between non-ALI/ARDS patients and ALI/ARDS patients. CONCLUSION: Concerns regarding sedation requirements with use of lower V(T) are unfounded and should not preclude its use in patients with ALI/ARD

Prevalence and Predictors of Abnormal Cardiovascular Responses to Exercise Testing Among Individuals With Type 2 Diabetes: The Look AHEAD (Action for Health in Diabetes) study

OBJECTIVE We examined maximal graded exercise test (GXT) results in 5,783 overweight/obese men and women, aged 45–76 years, with type 2 diabetes, who were entering the Look AHEAD (Action for Health in Diabetes) study, to determine the prevalence and correlates of exercise-induced cardiac abnormalities. RESEARCH DESIGN AND METHODS Participants underwent symptom-limited maximal GXTs. Questionnaires and physical examinations were used to determine demographic, anthropometric, metabolic, and health status predictors of abnormal GXT results, which were defined as an ST segment depression ≥1.0 mm, ventricular arrhythmia, angina pectoris, poor postexercise heart rate recovery (<22 bpm reduction 2 min after exercise), or maximal exercise capacity less than 5.0 METs. Systolic blood pressure response to exercise was examined as a continuous variable, without a threshold to define abnormality. RESULTS Exercise-induced abnormalities were present in 1,303 (22.5%) participants, of which 693 (12.0%) consisted of impaired exercise capacity. ST segment depression occurred in 440 (7.6%), abnormal heart rate recovery in 206 (5.0%), angina in 63 (1.1%), and arrhythmia in 41 (0.7%). Of potential predictors, only greater age was associated with increased prevalence of all abnormalities. Other predictors were associated with some, but not all, abnormalities. Systolic blood pressure response decreased with greater age, duration of diabetes, and history of cardiovascular disease. CONCLUSIONS We found a high rate of abnormal GXT results despite careful screening for cardiovascular disease symptoms. In this cohort of overweight and obese individuals with type 2 diabetes, greater age most consistently predicted abnormal GXT. Long-term follow-up of these participants will show whether these abnormalities are clinically significant. Cardiovascular disease (CVD) risk factors improve with exercise in individuals with diabetes (1). Similarly, individuals with diabetes who are physically active or have higher fitness levels have reduced CVD incidence and mortality (2,3). Nevertheless, participation in exercise may involve risks for individuals with diabetes because of their high prevalence of CVD, including silent ischemia, and other comorbid conditions (4). Knowledge about the typical cardiovascular responses to exercise in individuals with type 2 diabetes has come mainly from small clinic-based studies (5) and a few larger studies in the general population (4,6,7). The Look AHEAD (Action for Health in Diabetes) study is a multicenter randomized clinical trial designed to evaluate the long-term effects of an intensive lifestyle intervention program of weight loss and physical activity on morbidity and mortality from CVD in overweight and obese individuals with type 2 diabetes (8). Graded exercise tests (GXTs) with electrocardiographic monitoring were conducted at baseline in 5,783 individuals, providing the largest sample of systematic stress testing ever conducted in individuals with type 2 diabetes. The aims of this analysis are to examine the range of abnormal exercise responses and to examine the degree to which demographic factors, health characteristics, and medication use associate with abnormal exercise responses. Identifying predictors from readily available demographic and clinical data may assist risk stratification before exercise testing or exercise prescription for individuals with diabetes

Effect of disorder on quantum phase transitions in anisotropic XY spin chains in a transverse field

We present some exact results for the effect of disorder on the critical properties of an anisotropic XY spin chain in a transverse field. The continuum limit of the corresponding fermion model is taken and in various cases results in a Dirac equation with a random mass. Exact analytic techniques can then be used to evaluate the density of states and the localization length. In the presence of disorder the ferromagnetic-paramagnetic or Ising transition of the model is in the same universality class as the random transverse field Ising model solved by Fisher using a real space renormalization group decimation technique (RSRGDT). If there is only randomness in the anisotropy of the magnetic exchange then the anisotropy transition (from a ferromagnet in the $x$ direction to a ferromagnet in the $y$ direction) is also in this universality class. However, if there is randomness in the isotropic part of the exchange or in the transverse field then in a non-zero transverse field the anisotropy transition is destroyed by the disorder. We show that in the Griffiths' phase near the Ising transition that the ground state energy has an essential singularity. The results obtained for the dynamical critical exponent, the typical correlation length, and the temperature dependence of the specific heat near the Ising transition agree with the results of the RSRGDT and numerical work.Comment: 22 pages, RevTeX + epsf, 4 figure

Design, calibration, and performance of the MINERvA detector

The MINERvA(6) experiment is designed to perform precision studies of neutrino-nucleus scattering using nu(mu) and (nu) over bar (mu) neutrinos incident at 1-20 GeV in the NuMI beam at Fermilab. This article presents a detailed description of the MINERvA detector and describes the ex situ and in situ techniques employed to characterize the detector and monitor its performance. The detector is composed of a finely segmented scintillator-based inner tracking region surrounded by electromagnetic and hadronic sampling calorimetry. The upstream portion of the detector includes planes of graphite, iron and lead interleaved between tracking planes to facilitate the study of nuclear effects in neutrino interactions. Observations concerning the detector response over sustained periods of running are reported. The detector design and methods of operation have relevance to future neutrino experiments in which segmented scintillator tracking is utilized. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/)