bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Severity Score System in Dogs with Degenerative Mitral Valve Disease
Authors: López‐Alvarez J. , Elliott J. , Pfeiffer D. , Chang Y.‐M. , Mattin M. , Moonarmart W. , Hezzell M.J. , Boswood A.
Published: March 2015

Background

Several risk factors already have been determined for dogs with degenerative mitral valve disease (DMVD). Risk factors often have been considered in isolation and have not always taken into account additional information provided by the history and physical examination (PE).

Hypothesis/Objectives

Data obtained from history and PE of dogs with DMVD provide prognostic information and can be used for risk stratification.

Animals

Client‐owned dogs (n = 244) with DMVD recruited from first opinion practice.

Methods

Prospective longitudinal follow‐up of dogs with DMVD. History and PE data were obtained at 6‐month intervals and analyzed with time‐dependent Cox models to derive relative risk of cardiac death. Independent hazard ratios were used to derive a clinical severity score (CSS), the prognostic value of which was evaluated by analyzing the median survival times for different risk groups and ROC analysis. Analysis of the progression of CSS over time also was undertaken.

Results

History of cough, exercise intolerance, decreased appetite, breathlessness (difficulty breathing) and syncope with PE findings of heart murmur intensity louder than III/VI and absence of respiratory sinus arrhythmia were independently associated with outcome and allowed development of the CSS. Clinical severity score distinguished groups of dogs with significantly different outcomes.

Conclusions and Clinical Importance

Routinely obtained clinical findings allow risk stratification of dogs with DMVD. Results of ancillary diagnostic tests may be complementary to history and PE findings and always should be interpreted in conjunction with these findings.
Experimental Transmission ofCorynebacterium pseudotuberculosisBiovarequiin Horses by House Flies
Authors: Barba M. , Stewart A.J. , Passler T. , Wooldridge A.A. , van Santen E. , Chamorro M.F. , Cattley R.C. , Hathcock T. , Hogsette J.A. , Hu X.P.
Published: March 2015

Background

The route ofCorynebacterium pseudotuberculosisinfection in horses remains undetermined, but transmission by insects is suspected.

Objectives

To investigate house flies (Musca domesticaL.) as vectors ofC. pseudotuberculosistransmission in horses.

Animals

Eight healthy, adult ponies.

Methods

Randomized, controlled, blinded prospective study. Ten wounds were created in the pectoral region where cages for flies were attached. Three ponies were directly inoculated withC. pseudotuberculosis. Four ponies were exposed for 24 hours to 20 hoursC. pseudotuberculosis‐inoculated flies. One negative control pony was exposed to noninoculated flies. Ponies were examined daily for swelling, heat, pain, and drainage at the inoculation site. Blood was collected weekly forCBCand biochemical analysis, and twice weekly for synergistic hemolysis inhibition titers.

Results

Clinical signs of local infection and positive cultures were observed in 7/7 exposed ponies and were absent in the negative control. In exposed ponies, peak serologic titers (1 : 512 to 1 : 2,048) were obtained between days 17 and 21. Seroconversion was not observed in the negative control. Neutrophil counts were higher in the positive and fly‐exposed groups than in the negative control (P = .002 andP = .005) on day 3 postinoculation. Serum amyloid A concentrations were higher in the positive control than in the negative control and fly‐exposed ponies on days 3 (P < .0001) and 7 (P = .0004 andP = .0001). No differences were detected for other biochemical variables.

Conclusions and Clinical Importance

House flies can serve as mechanical vectors ofC. pseudotuberculosisand can transmit the bacterium to ponies.
Plasma Vitamin D Metabolites and C‐Reactive Protein in Stage‐Stop Racing Endurance Sled Dogs
Authors: Spoo J.W. , Downey R.L. , Griffitts C. , Horst R.J. , Levine C.B. , Childs R.M. , Wakshlag J.J.
Published: March 2015

Background

Dogs are a unique model for examining the effects of exercise on vitamin D status because of their lack of vitamin D synthesis byUVexposure. In addition, the inflammatory response may be associated with hypovitaminosis D.

Objectives

To investigate the effects of several days of endurance exercise on plasma vitamin D (25‐(OH)D3, 24,25‐(OH)D3and 1,25(OH)D3) and serum C‐reactive protein (CRP) concentrations in stage‐stop racing sled dogs.

Animals

12 racing sled dogs and 8 control dogs.

Methods

Blood was collected before the race and immediately after racing on days 2 and 8. Plasma vitamin D metabolites and serumCRPconcentrations were measured.

Results

Racing dogs showed a significant increase in 25(OH)D3on day 2 (P = .027) and day 8 of the race (P < .001), whereas no increases were observed in control dogs. The plasma concentration of 24,25(OH)D3showed a significant increase by day 8 (P < .001). There were no significant changes in 1,25(OH) D3concentrations across all time points and groups. Racing dogs had significantly increasedCRPconcentrations by day 2 (39.3 ± 30.1 μg/mL;P < .001).

Conclusions and Clinical Importance

Increases in vitamin D metabolites as well as increases inCRPconcentrations were observed in racing sled dogs. This finding was contrary to the hypothesis that decreases in vitamin D status in athletes may be related to the acute phase inflammatory response during exercise. In addition, the increased 24,25(OH)D3concentrations compared to what is observed in other species suggests metabolic variations in dogs that lead to enhanced disposal of vitamin D.
Mannheimia haemolytica in Feedlot Cattle: Prevalence of Recovery and Associations with Antimicrobial Use, Resistance, and Health Outcomes
Authors: Noyes N.R. , Benedict K.M. , Gow S.P. , Booker C.W. , Hannon S.J. , McAllister T.A. , Morley P.S.
Published: March 2015

Background

Mannheimia haemolytica is an important etiological agent in bovine respiratory disease.

Objectives

Explore risk factors for recovery of susceptible and resistant M. haemolytica in feedlot cattle and explore associations with health outcomes.

Animals

Cattle (n = 5,498) from 4 feedlots sampled at arrival and later in feeding period.

Methods

Susceptibility of M. haemolytica isolates tested for 21 antimicrobials. Records of antimicrobial use and health events analyzed using multivariable regression.

Results

M. haemolytica recovered from 29% of cattle (1,596/5,498), 13.1% at arrival (95% CI, 12.3–14.1%), and 19.8% at second sampling (95% CI, 18.7–20.9%). Nearly half of study cattle received antimicrobial drugs (AMDs) parenterally, mostly as metaphylactic treatment at arrival. Individual parenteral AMD exposures were associated with decreased recovery of M. haemolytica (OR, 0.2; 95% CI, 0.02–1.2), whereas exposure in penmates was associated with increased recovery (OR, 1.5; 95% CI, 1.05–2.2). Most isolates were pan‐susceptible (87.8%; 95% CI, 87.0–89.4%). AMD exposures were not associated with resistance to any single drug. Multiply‐resistant isolates were rare (5.9%; 95% CI, 5.1–6.9%), but AMD exposures in pen mates were associated with increased odds of recovering multiply‐resistant M. haemolytica (OR, 23.9; 95% CI, 8.4–68.3). Cattle positive for M. haemolytica on arrival were more likely to become ill within 10 days (OR, 1.7; 95% CI, 1.1–2.4).

Conclusions and Clinical Importance

Resistance generally was rare in M. haemolytica. Antimicrobial drug exposures in penmates increased the risk of isolating susceptible and multiply‐resistant M. haemolytica, a finding that could be explained by contagious spread.
Serum Bile Acid Concentrations, Histopathological Features, and Short‐, and Long‐term Survival in Horses with Hepatic Disease
Authors: Dunkel B. , Jones S.A. , Pinilla M.J. , Foote A.K.
Published: March 2015

Background

Serum bile acid concentrations (SBA) and a histopathological biopsy score [Equine Vet J35 (2003) 534] are used prognostically in equine hepatic disease.

Hypothesis

Histopathologic features and scores, but notSBA, differ between survivors and nonsurvivors and correlate with histopathologic evidence of hepatic inflammation and fibrosis.

Animals

Retrospective study. Records (1999–2011) of horses with hepatic disease diagnosed by biopsy and with concurrent measurements ofSBA.

Methods

Retrospective cohort study. Biopsies were examined for inflammatory cell infiltration including type and distribution, fibrosis, irreversible cytopathology affecting hepatocytes, hemosiderin, or other pigment deposition and bile duct proliferation.SBA, histopathological findings and a histological score [Equine Vet J35 (2003) 534] were compared between short‐ (survival to discharge) and long‐term (>6 months) survivors and correlations betweenSBAand histopathological findings investigated.

Results

Of 81 cases 90% survived short‐term and 83% long‐term. Short‐term and long‐term nonsurvival were associated withSBA(P = .009;P = .006), overall (P = .001;P = .002) and parenchymal (short‐term only;P = .01) inflammation, portal and bridging fibrosis (allP < .001), apoptosis or single cell necrosis (P < .001;P = .008), hemosiderin deposition in hepatocytes (P = .011;P = .028), biliary (bothP < .001), vascular (P = .003;P = .045) and endothelial (P < .001;P = .02) hyperplasia, nucleic changes (P = .004;P < .001) and the histopathological score (bothP < .001).SBAwere significantly and positively correlated with overall (P = .001), parenchymal (P < .001) and portal (P = .004) inflammation and portal (P = .036) and bridging (P = .002) fibrosis.

Conclusions and Clinical Importance

SBA, histopathological findings and scores differ between survivors and nonsurvivors.SBAconcentrations are associated with inflammation and fibrosis suggesting interference with hepatic function. A histopathological score >2 and, less so,SBA>20 μmol/L are specific but not sensitive indicators of nonsurvival.
Co‐infections with Respiratory Viruses in Dogs with Bacterial Pneumonia
Authors: Viitanen S.J. , Lappalainen A. , Rajamäki M.M.
Published: March 2015

Background

Bacterial pneumonia (BP) is an inflammation of the lower airways and lung parenchyma secondary to bacterial infection. The pathogenesis ofBPin dogs is complex and the role of canine respiratory viruses has not been fully evaluated.

Objectives

The aim of this study was to investigate the occurrence of viral co‐infections in dogs withBPand to assess demographic or clinical variables as well as disease severity associated with viral co‐infections.

Animals

Twenty household dogs withBPcaused by opportunistic bacteria and 13 dogs with chronic (>30 days) tracheobronchitis caused byBordetella bronchiseptica(BBTB).

Methods

Prospective cross‐sectional observational study. Diagnosis was confirmed by clinical and laboratory findings, diagnostic imaging, and cytologic and microbiologic analysis of bronchoalveolar lavage or transtracheal wash fluid. Canine parainfluenza virus (CPIV), canine adenovirus, canine herpes virus, canine influenzavirus, canine distemper virus, canine respiratory coronavirus (CRCoV) and canine pneumovirus, as well asB. bronchisepticaandMycoplasmaspp. were analyzed in respiratory samples usingPCRassays.

Results

CPIVwas detected in 7/20 andCRCoVin 1/20 dogs withBP. Respiratory viruses were not detected in dogs withBBTB. There were no significant differences in clinical variables betweenBPdogs with and without a viral co‐infection.

Conclusion and Clinical Importance

Respiratory viruses were found frequently in dogs withBPand may therefore play an important role in the etiology and pathogenesis ofBP. Clinical variables and disease severity did not differ betweenBPdogs with and without viral co‐infection.
Preliminary Investigation of the Area Under the l‐Lactate Concentration–Time Curve (LACAREA) in Critically Ill Equine Neonates
Authors: Wilkins P.A. , Sheahan B.J. , Vander Werf K.A. , Castagnetti C. , Hardy J. , Schoster A. , Boston R.C.
Published: March 2015

Background

A variety of measures of l‐lactate concentration ([LAC]) in the blood of critically ill neonatal foals have shown utility as prognostic indicators. These measures, evaluating either the severity of hyperlactatemia or the duration of exposure to hyperlactatemia, perform fairly well and have correctly classified 75–80% of foals examined in several studies. The area under the l‐lactate concentration versus time curve (LACArea) encompasses both severity and duration of hyperlactatemia and should improve correct classification of patient survival.

Hypothesis/Objectives

LACArea is larger in nonsurviving critically ill neonatal foals.

Animals

Forty‐nine foals admitted for critical illness to 1 of 4 referral hospitals.

Methods

Whole blood was obtained at admission and 6, 12, 18, and 24 hours after admission for measurement of l‐lactate using a handheld lactate meter. LACArea was calculated for: admission–6, 6–12, 12–18, 18–24 hours, and admission–24 hours using the trapezoidal method and summing the 6‐hours interval areas to determine total 24 hours area. Differences between survivors and nonsurvivors were determined using robust regression and Kruskal–Wallis testing, P < .05.

Results

LACArea was significantly larger in nonsurviving foals (n = 9) than in surviving foals (n = 40) at all time periods examined.

Conclusions and Clinical Importance

Differences in LACArea between surviving and nonsurviving critically ill neonatal foals are large and support further investigation of this method as an improved biomarker for survival in critically ill neonatal foals is indicated.
Evaluation of Digital and Optical Refractometers for Assessing Failure of Transfer of Passive Immunity in Dairy Calves
Authors: Elsohaby I. , McClure J.T. , Keefe G.P.
Published: March 2015

Background

Failure of transfer of passive immunity (FTPI) is the underlying predisposing risk factor for most early losses in dairy calves. Refractometers, either optical or digital, can be used to assess FTPI as a part of calf health monitoring program on dairy operations.

Objectives

To evaluate the performance of and differences between digital Brix and optical refractometers for assessing FTPI in dairy calves.

Animals

Two hundred Holstein calves from 1 to 11 days of age.

Methods

A cross‐sectional study was designed to measure serum IgG concentration by radial immunodiffusion (RID) assay, digital Brix and optical refractometers. The correlation coefficients (r) between the 2 refractometers were plotted against each other and against the measured IgG concentration from RID. The Se, Sp, and accuracy of digital Brix and optical refractometers for assessing FTPI using previously recommended cut‐offs were calculated. A receiver operating characteristic curve was created and used to identify the optimal cut‐off for this dataset.

Results

The RID IgG concentration was positively correlated with digital Brix (r = 0.79) and optical (r = 0.74) refractometers. The best combination of Se (85.5%), Sp (82.8%), and accuracy (83.5%) of digital Brix refractometer was at 8.3%Brix. For optical refractometer, the best combination of Se (80%), Sp (80.7%), and accuracy (80.5%) was at 5.5 g/dL.

Conclusions and Clinical Importance

Both refractometers exhibited utility in assessing FTPI in dairy calves.
Prevalence and Prognostic Importance of Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease
Authors: Borgarelli M. , Abbott J. , Braz‐Ruivo L. , Chiavegato D. , Crosara S. , Lamb K. , Ljungvall I. , Poggi M. , Santilli R.A. , Haggstrom J.
Published: March 2015

Background

Pulmonary hypertension (PH) is common in dogs with myxomatous mitral valve disease (MMVD) but its effect on clinical outcome has not been investigated.

Hypothesis/objectives

The presence of PH worsens the outcome in dogs with MMVD. To compare survival times of dogs with MMVD and PH to those without PH.

Animals

Two hundred and twelve client‐owned dogs.

Methods

Case review study. Medical records of dogs diagnosed with ACVIM stage B2 and C MMVD between January 2010 and December 2011 were retrospectively reviewed. Long‐term outcome was determined by telephone interview or from the medical record. End of the observation period was March 2013. PH was identified if tricuspid regurgitation peak velocity was >3 m/s.

Results

Two hundred and twelve were identified. Eighty‐three dogs (39%) had PH. PH was more commonly identified in stage C compared to B2 (P < .0001). One hundred and five (49.5%) dogs died during the observation period. Median survival time for the entire study population was 567 days (95% CI 512–743). Stage C (P = .003), the presence of PH (P = .009), left atrial to aortic root ratio (LA/Ao) >1.7 (P = .0002), normalized left‐ventricular end‐diastolic diameter (LVEDn) >1.73 (P = .048), and tricuspid regurgitation pressure gradient (TRPG) >55 mmHg (P = .009) were associated with worse outcomes in the univariate analyses. The presence of TRPG >55 mmHg (HR 1.8 95% CI 1–2.9; P = .05) and LA/Ao > 1.7 (HR 2 95% CI 1.2–3.4; P = .01) remained significant predictors of worse outcome in the multivariate analysis.

Conclusions and Clinical Importance

In dogs with MMVD, moderate to severe PH worsens outcome.
Longitudinal Evaluation of Serum Pancreatic Enzymes and Ultrasonographic Findings in Diabetic Cats Without Clinically Relevant Pancreatitis at Diagnosis
Authors: Zini E. , Hafner M. , Kook P. , Lutz T.A. , Ohlerth S. , Reusch C.E.
Published: March 2015

Background

Cats with diabetes mellitus can have subclinical pancreatitis but prospective studies to confirm this are lacking. Metabolic control of diabetic cats with pancreatitis is difficult.

Hypothesis

Subclinical pancreatitis occurs in diabetic cats at the time diabetes is diagnosed or might develop during the follow‐up period, hampering diabetic remission.

Animals

Thirty cats with newly diagnosed diabetes without clinical signs of pancreatitis on admission.

Methods

Prospective study. On admission and 2 and 6 months later, serum Spec fPL and DGGR‐lipase were measured and the pancreas underwent ultrasonographic examination. Pancreatitis was suspected if serum markers were increased or ≥2 ultrasonographic abnormalities were detected. Cats were treated with insulin glargine and diabetic remission was defined as euglycemia ≥4 weeks after discontinuation of insulin. Nonparametric statistical tests were used for analysis.

Results

Subclinical pancreatitis at the time of diagnosis was suspected in 33, 50, and 31% of cats based on Spec fPL, DGGR‐lipase and ultrasonography, respectively; and in 60% when diagnostic criteria were combined. During the follow‐up period, suspected pancreatitis developed in additional 17–30% cats. Only 1 cat had transient clinical signs compatible with pancreatitis. Seventeen of the 30 cats (57%) achieved remission. Frequency of abnormal Spec fPL and DGGR‐lipase and abnormal ultrasonographic findings did not differ in cats achieving remission and those who did not. Cats achieving remission had significantly lower Spec fPL at 2 months (P < .001).

Conclusions and Clinical Importance

Based on laboratory and ultrasonographic measurements, many cats with diabetes might have pancreatitis, although without clinical signs. Cats with high Spec fPL might have a reduced chance of diabetic remission; however, this topic needs further studies in large cohorts of diabetic cats.
Urinary and Plasma Catecholamines and Metanephrines in Dogs with Pheochromocytoma, Hypercortisolism, Nonadrenal Disease and in Healthy Dogs
Authors: Salesov E. , Boretti F.S. , Sieber‐Ruckstuhl N.S. , Rentsch K.M. , Riond B. , Hofmann‐Lehmann R. , Kircher P.R. , Grouzmann E. , Reusch C.E.
Published: March 2015

Background

Diagnosis of pheochromocytoma (PC) is based on a combination of clinical suspicion, finding an adrenal mass, increased plasma, and urine concentrations of catecholamine metabolites and is finally confirmed with histopathology. In human medicine, it is controversial whether biochemically testing plasma is superior to testing urine.

Objectives

To measure urinary and plasma catecholamines and metanephrines in healthy dogs, dogs with PC, hypercortisolism (HC), and nonadrenal diseases (NAD) and to determine the test with the best diagnostic performance for dogs with PC.

Animals

Seven PC dogs, 10 dogs with HC, 14 dogs with NAD, 10 healthy dogs.

Methods

Prospective diagnostic clinical study. Urine and heparin plasma samples were collected and stored at −80°C before analysis using high‐pressure liquid chromatography (HPLC) coupled to electrochemical detection or tandem mass spectrometry were performed. Urinary variables were expressed as ratios to urinary creatinine concentration.

Results

Dogs with PC had significantly higher urinary normetanephrine and metanephrine : creatinine ratios and significantly higher plasma‐total and free normetanephrine and plasma‐free metanephrine concentrations compared to the 3 other groups. There were no overlapping results of urinary normetanephrine concentrations between PC and all other groups, and only one PC dog with a plasma normetanephrine concentration in the range of the dogs with HC and NAD disease. Performances of total and free plasma variables were similar. Overlap of epinephrine and norepinephrine results between the groups was large with both urine and plasma.

Conclusion and clinical importance

Measurement of normetanephrine is the preferred biochemical test for PC and urine was superior to plasma.
Association of Tricuspid Annular Plane Systolic Excursion with Survival Time in Boxer Dogs with Ventricular Arrhythmias
Authors: Kaye B.M. , Borgeat K. , Mõtsküla P.F. , Luis Fuentes V. , Connolly D.J.
Published: March 2015

Background

Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown.

Hypothesis

TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time.

Animals

Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004–2011).

Methods

Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine‐loops using anatomic M‐mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan‐Meier curves and Cox proportional hazards models.

Results

TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15–16.9, P < .029).

Conclusions and Clinical Importance

TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis.
Impact of Incremental Perfusion Loss on Oxygen Transport in a Capillary Network Mathematical Model
Authors: Fraser Graham M. , Sharpe Michael D. , Goldman Daniel , Ellis Christopher G.
Published: March 2015

Objectives

To quantify how incremental capillary PL, such as that seen in experimental models of sepsis, affects tissue oxygenation using a computation model of oxygen transport.

Methods

A computational model was applied to capillary networks with dimensions 84 × 168 × 342 (NI) and 70 × 157 × 268 (NII) μm, reconstructed in vivo from rat skeletal muscle. FCD loss was applied incrementally up to ~40% and combined with high tissue oxygen consumption to simulate severe sepsis.

Results

A loss of ~40% FCD loss decreased median tissue PO2 to 22.9 and 20.1 mmHg in NI and NII compared to 28.1 and 27.5 mmHg under resting conditions. Increasing RBC SR to baseline levels returned tissue PO2 to within 5% of baseline. HC combined with a 40% FCD loss, resulted in tissue anoxia in both network volumes and median tissue PO2 of 11.5 and 8.9 mmHg in NI and NII respectively; median tissue PO2 was recovered to baseline levels by increasing total SR 3–4 fold.

Conclusions

These results suggest a substantial increase in total SR is required in order to compensate for impaired oxygen delivery as a result of loss of capillary perfusion and increased oxygen consumption during sepsis.
Control of macaw palm seed germination by the gibberellin/abscisic acid balance
Authors: Bicalho E. M. , Pintó‐Marijuan M. , Morales M. , Müller M. , Munné‐Bosch S. , Garcia Q. S.
Published: March 2015

The hormonal mechanisms involved in palm seed germination are not fully understood. To better understand how germination is regulated in Arecaceae, we used macaw palm (Acrocomia aculeata (Jacq.) Lodd. Ex Mart.) seed as a model. Endogenous hormone concentrations, tocopherol and tocotrienol and lipid peroxidation during germination were studied separately in the embryo and endosperm. Evaluations were performed in dry (D), imbibed (I), germinated (G) and non‐germinated (NG) seeds treated (+GA3) or not treated (control) with gibberellins (GA). With GA3 treatment, seeds germinated faster and to a higher percentage than control seeds. The +GA3 treatment increased total bioactive GA in the embryo during germination relative to the control. Abscisic acid (ABA) concentrations decreased gradually from D to G in both tissues. Embryos of G seeds had a lower ABA content than NG seeds in both treatments. The GA/ABA ratio in the embryo was significantly higher in G than NG seeds. The +GA3 treatment did not significantly affect the GA/ABA ratio in either treatment. Cytokinin content increased from dry to germinated seeds. Jasmonic acid (JA) increased and 1‐aminocyclopropane‐1‐carboylic acid (ACC) decreased after imbibition. In addition, α‐tocopherol and α‐tocotrienol decreased, while lipid peroxidation increased in the embryo during germination. We conclude that germination in macaw palm seed involves reductions in ABA content and, consequently, increased GA/ABA in the embryo. Furthermore, the imbibition process generates oxidative stress (as observed by changes in vitamin E and MDA).
A Proof of Bell's Inequality in Quantum Mechanics Using Causal interactions
Authors: Robins James M. , VanderWeele Tyler J. , Gill Richard D.
Published: March 2015

We give a simple proof of Bell's inequality in quantum mechanics using theory from causal interaction, which, in conjunction with experiments, demonstrates that the local hidden variable assumption is false. The proof sheds light on relationships between the notion of causal interaction and interference between treatments.
Estimation of the Jump Size Density in a Mixed Compound Poisson Process
Authors: Comte Fabienne , Duval Celine , Genon‐Catalot Valentine , Kappus Johanna
Published: March 2015

In this paper, we consider a mixed compound Poisson process, that is, a random sum of independent and identically distributed (i.i.d.) random variables where the number of terms is a Poisson process with random intensity. We study nonparametric estimators of the jump density by specific deconvolution methods. Firstly, assuming that the random intensity has exponential distribution with unknown expectation, we propose two types of estimators based on the observation of an i.i.d. sample. Risks bounds and adaptive procedures are provided. Then, with no assumption on the distribution of the random intensity, we propose two non‐parametric estimators of the jump density based on the joint observation of the number of jumps and the random sum of jumps. Risks bounds are provided, leading to unusual rates for one of the two estimators. The methods are implemented and compared via simulations.
Immunogenicity of virosomal adjuvanted trivalent influenza vaccination in allogeneic stem cell transplant recipients
Authors: Ambati A. , Einarsdottir S. , Magalhaes I. , Poiret T. , Bodenstein R. , LeBlanc K. , Brune M. , Maeurer M. , Ljungman P.
Published: March 2015

Background

Influenza vaccination is generally recommended to hematopoietic stem cell transplant (HSCT) recipients. However, the seasonal subunit vaccination response is frequently suboptimal, and alternate more efficient vaccination systems must be examined. We compared the immunogenicity of an adjuvanted virosomal influenza and subunit vaccine in HSCT recipients.

Methods

The immunogenicity after a single dose (0.5 mL) of adjuvanted trivalent virosomal vaccination was evaluated in a study cohort of 21 HSCT recipients and compared to a control cohort of 30 HSCT recipients who received a single dose (0.5 mL) of non‐adjuvanted seasonal trivalent subunit vaccination over 4 seasons from 2010 to 2014. Whole blood interferon‐gamma (IFN‐γ) release assays were tested, both before and 30 days after vaccination, in response to influenza pandemic (pdm) H1N1, H3N2, and B antigens. HLA‐A*02 dextramers, to gauge for the absolute number of antigen‐specific CD8+ T‐cells, and pdm 2009 hemagglutinin inhibition (HI) assays, to test for neutralizing antibodies, were used as immunological readouts.

Results

The pdm HI titers were poor in both cohorts with only 23% (5/21) after virosomal vaccination and 13.3% (4/30) in the seasonal vaccine cohort having protective titers (≥40). The delta change of IFN‐γ production in response to influenza pdm H1N1 (P = 0.005) and influenza B antigens (P = 0.01) were significantly elevated in blood from individuals who received the virosomal as compared to the seasonal vaccine. The IFN‐γ response to pdm H1N1 was stronger (P < 0.001), as compared to seasonal vaccination, in patients vaccinated >6 month post HSCT. We detected a significant increase in the frequency of matrix 1 (GILGFVTL) dextramer‐specific CD8+ T‐cells after the virosomal vaccine (P = 0.01). No differences were seen in the hemagglutinin‐specific CD8+ T‐cells between the 2 cohorts.

Conclusion

Vaccination using a virosomal delivery system is beneficial in eliciting robust cellular immune responses to pdm H1N1 influenza in SCT recipients.
Declining prevalence of hepatitis E antibodies among Danish blood donors
Authors: Holm Dorte K. , Moessner Belinda K. , Engle Ronald E. , Zaaijer Hans L. , Georgsen Jørgen , Purcell Robert H. , Christensen Peer B.
Published: March 2015

BACKGROUND

The increasing incidence of reported hepatitis E cases in Europe has focused attention on hepatitis E virus (HEV) and the risk of transfusion‐transmitted hepatitis E. The aim of this study was to investigate the prevalence of antibodies to HEV (anti‐HEV) among Danish blood donors in 2013 and to compare it to previous studies in Denmark. In addition we wanted to compare the relative reactivity of two different assays.

STUDY DESIGN AND METHODS

Samples from 504 blood donors were collected and analyzed for anti‐HEV with an in‐house assay developed at the National Institutes of Health (NIH). In addition the samples were analyzed with the Wantai anti‐HEV assay. Demographic information and possible HEV exposure was collected by self‐administered questionnaire.

RESULTS

Using the NIH assay the prevalence of anti‐HEV among Danish blood donors was 10.7% and with the Wantai assay the prevalence of anti‐HEV was 19.8% (p < 0.001). In both cases the presence of anti‐HEV was significantly correlated with increasing age. In addition, anti‐HEV as measured by the Wantai test was significantly associated with contact with children (p = 0.01), but in multivariate analysis only age was associated with anti‐HEV in both assays. By the NIH assay, the prevalence had declined from 20.6% in 2003 to 10.7% in 2013.

CONCLUSIONS

Anti‐HEV prevalence had decreased by half among Danish blood donors over 10 years, but was still highly prevalent. The difference in reactivity of the two assays demonstrates the importance of using the same assay when comparing the anti‐HEV prevalence in populations over time.
A prospective study of the prevalence of corneal surface disease in dogs receiving prophylactic topical lubrication under general anesthesia
Authors: Dawson Charlotte , Sanchez Rick F.
Published: March 2015

Objective

To identify the prevalence of corneal ulceration in dogs receiving prophylactic gel lubrication under general anesthesia (GA).

Materials and methods

An ophthalmic examination was performed before premedication and 24 h after GA in 100 dogs (199 eyes) undergoing nonophthalmic procedures. Individuals with known pre‐existing ocular surface conditions were excluded. An ocular lubricating gel containing carmellose sodium was applied by the anesthetist at induction and every 2–4 h until extubation. Logistic regression analysis was used to calculate risk factors for ulcerative disease, including signalment, length of GA, patient position, procedure performed, pre‐, and post‐GA ophthalmic examination findings and admitting service. A Wilcoxon rank sum test compared pre‐ and post‐GA Schirmer tear test‐1 (STT‐1) values.

Results

One dog (0.5% of total eyes) developed fluorescein stain uptake consistent with superficial corneal ulceration that resolved within 48 h with supportive treatment. Twenty‐five (18.6% of total eyes) developed a faint, patchy corneal uptake of stain in the axial cornea that was consistent with epithelial erosion. All erosions resolved with lubrication 24 h later. The decrease in STT‐1 readings at 24 h post‐GA was statistically significant from those pre‐GA (P < 0.001). No significant risk factors for corneal erosion/ulceration were identified.

Conclusions

The results of this study show that a basic protocol of prophylactic lubrication during GA was associated with a low prevalence of corneal ulceration but a higher prevalence of epithelial erosion. In addition, the study supports the need for post‐GA corneal examination.
Teaching Systematic Searching in a Baccalaureate Nursing Research Course
Authors: Whalen Kimberly J. , Zentz Suzanne E.
Published: March 2015

This column shares the best evidence‐based strategies and innovative ideas on how to facilitate the learning of EBP principles and processes by clinicians as well as nursing and interprofessional students. Guidelines for submission are available at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1741‐6787
In-situ etch rate study of HfxLayOz in Cl2/BCl3 plasmas using the quartz crystal microbalance
Authors: Marchack Nathan , Kim Taeseung , Blom Hans-Olof , Chang Jane P.
Published: March 2015

The etch rate of HfxLayOz films in Cl2/BCl3 plasmas was measured in-situ in an inductively coupled plasma reactor using a quartz crystal microbalance and corroborated by cross-sectional SEM measurements. The etch rate depended on the ion energy as well as the plasma chemistry. In contrast to other Hf-based ternary oxides, the etch rate of HfxLayOz films was higher in Cl2 than in BCl3. In the etching of Hf0.25La0.12O0.63, Hf appeared to be preferentially removed in Cl2 plasmas, per surface compositional analysis by x-ray photoelectron spectroscopy and the detection of HfCl3 generation in mass spectroscopy. These findings were consistent with the higher etch rate of Hf0.25La0.12O0.63 than that of La2O3.
Protection of extreme ultraviolet lithography masks. I. Thermophoretic protection factors at low pressure for diffusing nanoscale particles
Authors: Klebanoff Leonard E. , Geller Anthony S. , Torczynski John R. , Gallis Michael A. , Rader Daniel J. , Chilese Frank C. , Garcia Rudy F. , Delgado Gil
Published: March 2015

Model calculations are presented for thermophoretic protection of an extreme ultraviolet (EUV) mask placed face down in an EUV mask inspection tool. The protection factors, defined as the ratio of challenge particles to deposited particles, are calculated for a variety of test conditions (temperature gradient, gas type, particle density, and particle position) for a reticle bathed in clean gas from a facing showerhead. Thermophoretic protection (in combination with gravity) provides robust protection for particle sizes greater than ∼20 nm. However, for particle sizes less than ∼20 nm, protection falters quickly and is severely degraded for highly diffusing 10 nm particles that are of concern for mask contamination. Estimates are made for the required level of particle protection in both EUV mask inspection and EUV projection lithography. When compared with these estimates for the required protection, it is clear that thermophoresis alone cannot successfully defend against particles smaller than ∼20 nm, and must be augmented or replaced by another approach. Initial calculations are presented that suggest a cross-cutting gas flow, in combination with thermophoresis and a face-down mask orientation, can successfully protect mask surfaces from particle deposition for particles with 10 nm diameter or greater, motivating more detailed calculations of flow-based mask protection in a companion paper Part II.
Parameterization of an interfacial force field for accurate representation of peptide adsorption free energy on high-density polyethylene
Authors: Abramyan Tigran M. , Snyder James A. , Yancey Jeremy A. , Thyparambil Aby A. , Wei Yang , Stuart Steven J. , Latour Robert A.
Published: March 2015

Interfacial force field (IFF) parameters for use with the CHARMM force field have been developed for interactions between peptides and high-density polyethylene (HDPE). Parameterization of the IFF was performed to achieve agreement between experimental and calculated adsorption free energies of small TGTG–X–GTGT host–guest peptides (T = threonine, G = glycine, and X = variable amino-acid residue) on HDPE, with ±0.5 kcal/mol agreement. This IFF parameter set consists of tuned nonbonded parameters (i.e., partial charges and Lennard–Jones parameters) for use with an in-house-modified CHARMM molecular dynamic program that enables the use of an independent set of force field parameters to control molecular behavior at a solid–liquid interface. The R correlation coefficient between the simulated and experimental peptide adsorption free energies increased from 0.00 for the standard CHARMM force field parameters to 0.88 for the tuned IFF parameters. Subsequent studies are planned to apply the tuned IFF parameter set for the simulation of protein adsorption behavior on an HDPE surface for comparison with experimental values of adsorbed protein orientation and conformation.
Slit‐scanning differential x‐ray phase‐contrast mammography: Proof‐of‐concept experimental studies
Authors: Koehler Thomas , Daerr Heiner , Martens Gerhard , Kuhn Norbert , Löscher Stefan , van Stevendaal Udo , Roessl Ewald
Published: March 2015

Purpose:

The purpose of this work is to investigate the feasibility of grating‐based, differential phase‐contrast, full‐field digital mammography (FFDM) in terms of the requirements for field‐of‐view (FOV), mechanical stability, and scan time.

Methods:

A rigid, actuator‐free Talbot interferometric unit was designed and integrated into a state‐of‐the‐art x‐ray slit‐scanning mammography system, namely, the Philips MicroDose L30 FFDM system. A dedicated phase‐acquisition and phase retrieval method was developed and implemented that exploits the redundancy of the data acquisition inherent to the slit‐scanning approach to image generation of the system. No modifications to the scan arm motion control were implemented.

Results:

The authors achieve a FOV of 160 × 196 mm consisting of two disjoint areas measuring 77 × 196 mm with a gap of 6 mm between them. Typical scanning times vary between 10 and 15 s and dose levels are lower than typical FFDM doses for conventional scans with identical acquisition parameters due to the presence of the source‐grating G0. Only minor to moderate artifacts are observed in the three reconstructed images, indicating that mechanical vibrations induced by other system components do not prevent the use of the platform for phase contrast imaging.

Conclusions:

To the best of our knowledge, this is the first attempt to integrate x‐ray gratings hardware into a clinical mammography unit. The results demonstrate that a scanning differential phase contrast FFDM system that meets the requirements of FOV, stability, scan time, and dose can be build.
Health technology assessment in Switzerland: a descriptive analysis of “Coverage with Evidence Development” decisions from 1996 to 2013
Authors: Brügger Urs , Horisberger Bruno , Ruckstuhl Alexander , Plessow Rafael , Eichler Klaus , Gratwohl Alois
Published: March 2015

Objectives

To identify factors associated with the decisions of the Federal Department of Home Affairs concerning coverage with evidence development (CED) for contested novel medical technologies in Switzerland.

Design

Quantitative, retrospective, descriptive analysis of publicly available material and prospective, structured, qualitative interviews with key stakeholders.

Setting

All 152 controversial medical services decided on by the Federal Commission on Health Insurance Benefits within the framework of the new federal law on health insurance in Switzerland from 1997 to 2013, with focus on 33 technologies assigned initially to CED and 33 to evidence development without coverage.

Main outcome measures

Factors associated with numbers and type of contested services assigned to CED per year, the duration and final outcome of the evaluations and perceptions of key stakeholders.

Results

The rate of CED decisions (82 total; median 1.5/year; range 0–9/year), the time to final decision (4.5 years median; 0.75 to +11 years) and the probability of a final ‘yes’ varied over time. In logistic regression models, the change of office of the commission provided the best explanation for the observed outcomes. Good intentions but absence of scientific criteria for decisions were reported as major comments by the stakeholders.

Conclusions

The introduction of CED enabled access to some promising technologies early in their life cycle, and might have triggered establishment of registries and research. Impact on patients’ outcome and costs remain unknown. The primary association of institutional changes with measured end points illustrates the need for evaluation of the current health technology assessment (HTA) system.
An investigation into the therapeutic effects of statins with metformin on polycystic ovary syndrome: a meta-analysis of randomised controlled trials
Authors: Sun Jie , Yuan Yang , Cai Rongrong , Sun Haixia , Zhou Yi , Wang Pin , Huang Rong , Xia Wenqing , Wang Shaohua
Published: March 2015

Objectives

To investigate the therapeutic effects of statins with metformin on polycystic ovary syndrome (PCOS).

Settings

Endocrinology department.

Participants

MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials were searched until October 2014. Studies comparing statins and placebo, as well as the combination of statins and metformin and metformin alone, were included in the analysis.

Interventions

Data were independently extracted by two researchers; any convergence was resolved by a third reviewer.

Primary and secondary outcome measures

The following properties were extracted from the qualified trials to identify the effects of statins: clinical variables, metabolic characteristics, hormone outcomes, sign of inflammation, glucose parameters and insulin outcomes.

Results

Data from four trials comparing statin and metformin with metformin alone were analysed. The combination of statins and metformin decreases the levels of C reactive protein (standardised mean difference (SMD) −0.91; 95% CI −1.81 to −0.02; p=0.046), triglyceride (SMD −1.37; 95% CI −2.46 to −0.28; p=0.014), total cholesterol (SMD −1.28; 95% CI −1.59 to −0.97; p=0.000) and low-density lipoprotein (LDL) cholesterol (SMD −0.74; 95% CI −1.03 to −0.44; p=0.000). However, the combined therapy fails to reduce fasting insulin (SMD −0.92; 95% CI −2.07 to 0.24; p=0.120), homeostasis model assessment of insulin resistance (SMD −1.15; 95% CI −3.36 to 1.06; p=0.309) and total testosterone (SMD −1.12; 95% CI −2.29 to 0.05; p=0.061). Analysis of the five trials comparing statin with placebo shows that statin monotherapy reduces LDL-cholesterol, triglyceride and total cholesterol.

Conclusions

Combined statin and metformin therapy can improve lipid and inflammation parameters, but cannot effectively improve insulin sensitivity and reduce hyperandrogenism in women with PCOS. A large-scale randomised controlled study must be conducted to ascertain the long-term effects of the therapy.
Exploring the effect of space and place on response to exercise therapy for knee and hip pain—a protocol for a double-blind randomised controlled clinical trial: the CONEX trial
Authors: Sandal Louise Fleng , Thorlund Jonas Bloch , Ulrich Roger S , Dieppe Paul A , Roos Ewa M
Published: March 2015

Introduction

Context effectsare described as effects of a given treatment, not directly caused by the treatment itself, but rather caused by the context in which treatment is delivered. Exercise is a recommended core treatment in clinical guidelines for musculoskeletal disorders. Although moderately effective overall, variation is seen in size of response to exercise across randomised controlled trial (RCT) studies. Part of this variation may be related to the fact that exercise interventions are performed in different physical environments, which may affect participants differently. The study aims to investigate the effect of exercising in a contextually enhanced physical environment for 8 weeks in people with knee or hip pain.

Methods and analysis

The study is a double-blind RCT. Eligible participants are 35 years or older with persisting knee and/or hip pain for 3 months. Participants are randomised to one of three groups: (1) exercise in a contextually enhanced environment, (2) exercise in a standard environment and (3) waiting list. The contextually enhanced environment is located in a newly built facility, has large windows providing abundant daylight and overlooks a recreational park. The standard environment is in a basement, has artificial lighting and is marked by years of use; that is, resembling many clinical environments. The primary outcome is the participant's global perceived effect rated on a seven-point Likert scale after 8 weeks exercise. Patient-reported and objective secondary outcomes are included.

Ethics and dissemination

The Regional Scientific Ethical Committee for Southern Denmark has approved the study. Study findings will be disseminated in peer-reviewed publications and presented at national and international conferences.

Trial registration number

NCT02043613.
Should whole blood replace the shock pack?
Authors: Davies Rhys L
Published: March 2015

When haemorrhage occurs on the battlefield, the soldier rapidly loses whole blood; it therefore stands to reason that the optimum fluid for resuscitation is whole blood. Indeed, this was the case for the first 250 years of transfusion practice, but since the 1970s component therapy has been used, with little evidence for that change. It is hardly surprising that ‘balanced’ component therapy, which seeks to replicate whole blood, has been found to offer the best results in resuscitation. This article explores the role of whole blood in resuscitation and how it may be useful in the contemporary military environment.
Bacterial meningitis and subdural empyema caused by Actinomyces canis in a dog
Authors: Mickelson Megan , Olby Natasha , Schwartz Malte
Published: March 2015

Actinomyces canis, a Gram‐positive facultative anaerobe, was identified as the cause of subdural empyema in a two‐year‐old labrador retriever. The dog was initially treated for conjunctivitis and a week later presented for progressive neurologic abnormalities. Thoracic radiographs showed pulmonary nodules and MRI of the head was suggestive of right retrobulbar cellulitis and presumably consequential, subdural empyema and meningoencephalitis associated with caudal transtentorial herniation. A craniectomy was performed and the aetiologic diagnosis was confirmed by anaerobic bacterial culture. The dog made a complete recovery, including resolution of pulmonary nodules, with surgical decompression and antibiotic treatment.