Benchmarks for the interpretation of esophageal high-resolution manometry.

BACKGROUND: Competent interpretation of esophageal high-resolution manometry (HRM) is integral to a quality study. Currently, methods to assess physician competency for the interpretation of esophageal HRM do not exist. The aim of this study was to use formal techniques to (i) develop an HRM interpretation exam, and (ii) establish minimum competence benchmarks for HRM interpretation skills at the trainee, physician interpreter, and master level. METHODS: A total of 29 physicians from 8 academic centers participated in the study: 9 content experts separated into 2 study groups-expert test-takers (n=7) and judges (n=2), and 20 HRM inexperienced trainees ("trainee test-taker"; n=20). We designed the HRM interpretation exam based on expert consensus. Expert and trainee test-takers (n=27) completed the exam. According to the modified Angoff method, the judges reviewed the test-taker performance and established minimum competency cut scores for HRM interpretation skills. KEY RESULTS: The HRM interpretation exam consists of 22 HRM cases with 8 HRM interpretation skills per case: identification of pressure inversion point, hiatal hernia >3 cm, integrated relaxation pressure, distal contractile integral, distal latency, peristaltic integrity, pressurization pattern, and diagnosis. Based on the modified Angoff method, minimum cut scores for HRM interpretation skills at the trainee, physician interpreter, and master level ranged from 65-80%, 85-90% (with the exception of peristaltic integrity), and 90-95%, respectively. CONCLUSIONS & INFERENCES: Using a formal standard setting technique, we established minimum cut scores for eight HRM interpretation skills across interpreter levels. This examination and associated cut scores can be applied in clinical practice to judge competency.

A dinuclear Ru(II) complex capable of photoinduced ligand exchange at both metal centers.

{[Ru(CH3CN)3]2(tppz)}(4+) (tppz = tetra-2-pyridylpyrazine) undergoes photoinduced CH3CN exchange with λirr ≥ 610 nm in H2O. In contrast, cis-{[Ru(tpy)(L)]2(bpm)}(4+) (tpy = 2,2':6',2''-terpyridine, bpm = 2,2'-bipyrimidine, L = CH3CN) is not reactive, but the complex with L = DMSO is photoactive. These complexes are potentially useful for the release of multiply caged drugs.

Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0.17), revealing a tendency for higher values for more complex trait definitions. In terms of genetic selection, all trait definitions identified the best (i.e., most resistant) animals, but only the new trait definitions were able to distinguish between animals with average and high predispositions for DD. Considering repeated measurements resulted in heritability estimates ranging between 0.13 (±0.05) and 0.29 (±0.10).

The effect of digital dermatitis on hoof conformation.

Digital dermatitis (DD) is the most prevalent cause of lameness of infectious origin in cattle. However, little is known about the effects of DD on hoof conformation (HC) during the clinical disease. The objectives of the present study were to (1) evaluate the changes in HC observed in feet affected with clinical DD lesions and (2) investigate the temporal relationship between DD and heel horn erosion (HHE). A longitudinal study was carried out including a cohort of 644 Holstein heifers. Digital dermatitis, HC, and presence of HHE in the rear feet of each heifer were assessed during a period of 6 mo. A total of 1,979 feet evaluations were included in the data set, of which 157 corresponded to feet presenting DD lesions >20mm [mean (SD) size of 27.2 (8.2) mm]. Age, days of pregnancy, hip height, and girth circumference were also recorded at cow level. Significant HC changes were observed in DD-affected feet. Results standardized to a period of 90d of follow-up showed an increase in heel height [mean (95% CI) 3.4 (2.5, 4.4) and 2.8 (2.0, 3.7) mm] and claw angle [0.8 (0.2, 1.4) and 1.4 (0.7, 2.0) degrees] of the medial and lateral claws, respectively. In addition, an increase in depth of the interdigital cleft [3.2 (2.7, 3.7) mm] and on debris accumulation [14% (7, 21) of feet] was also observed. Feet affected with clinical DD lesions also experienced a 46% point increase in the presence of severe HHE. In the short term, HC changes returned to normal levels when clinical cure of DD was achieved after topical treatment. In conclusion, significant HC changes occur in heifers affected by clinical DD before lameness symptoms are detected. The transformation of the heel area in feet affected by DD likely promotes the creation of a local environment that favors the persistence of the disease and the occurrence of severe HHE. To avoid further hoof damage, active surveillance and early intervention to reduce HC changes are recommended to improve DD control programs. Successful restoration of HC can be achieved upon clinical cure of DD. The long-term effects in lifetime performance of the HC changes due to DD remain to be further investigated.

Immune response against Treponema spp. and ELISA detection of digital dermatitis.

The objective of this longitudinal study was to evaluate the immune response against Treponema spp. infection in dairy heifers affected with digital dermatitis (DD). In addition, the accuracy of an indirect ELISA detecting anti-Treponema IgG antibodies in identifying clinical DD status has been assessed. A cohort of 688 pregnant Holstein heifers was evaluated at least 3 times before calving during a period of 6 mo. Complete clinical assessment of DD presence on the back feet of each heifer and blood extraction were performed in a stand-up chute. Digital dermatitis cases were characterized by the M-stage classification system and size and level of skin proliferation. An ELISA was performed on blood serum samples obtained from a subcohort of 130 heifers. For description purposes, the animals were classified by the number of clinical cases experienced during the study period as type I (no clinical cases were observed), type II (only 1 acute clinical case diagnosed), and type III (at least 2 acute clinical cases diagnosed). Multivariable repeated-measures models were used to evaluate the immune response against Treponema spp. infection. A binormal Bayesian model for the ELISA data without cut-point values was used to assess the accuracy of the ELISA as a diagnostic tool. Animals that never experienced a DD event throughout the study kept a constant low level of antibody titer. A 56% increase in mean ELISA titer was observed in heifers upon a first clinical DD case diagnosis. After topical treatment of an acute DD case with oxytetracycline, the antibody titer decreased progressively in type II heifers, achieving mean levels of those observed in healthy cows after a mean of 223 d. Surprisingly, antibody titer was not increased in the presence of M1 (DD lesion <20mm in diameter surrounded by healthy skin) and M4.1 (DD lesion <20mm in diameter embedded in a circumscribed dyskeratotic or proliferative skin alteration) DD stages. Type III cows showed a slight increase in antibody levels. The presence of skin proliferation at first DD diagnosis was found to be associated with an odds ratio of 2.04 of becoming a type III heifer in relation to heifers presenting first lesions without skin proliferation. The ELISA validity was estimated by an area under the curve of 0.88. Predicted probabilities of infection are provided for a range of ELISA values and prevalence of infection. Early detection and treatment is essential to control DD and the ELISA can be used in understanding the immunopathology of DD and shows great promise for prescreening purposes during DD management programs in combination with traditional clinical inspection.

The spiral enteroscopy training initiative: results of a prospective study evaluating the Discovery SB overtube device during small bowel enteroscopy (with video).

BACKGROUND AND AIM: Indications for small-bowel enteroscopy are increasing, but advancing the endoscope to the ileum remains challenging, especially for less experienced operators. The aim was to evaluate the ease of use, safety, and efficacy of the Discovery SB overtube (Spirus Medical, Stoughton, Massachusetts, USA) during SB enteroscopy by physicians with no experience of the device. PATIENTS AND METHODS: Thirty-three "untrained" endoscopists performed spiral enteroscopy during one of four 2-day training modules. Data were prospectively collected. Patient demographics, depth and time to maximal insertion, total procedure time, and findings were recorded. Trauma was documented during scope withdrawal. Day 1 and day 2 results were compared. RESULTS: Ninety procedures were successfully performed in 95 patients (72.6 % women, age = 48.8 +/- 14.2 years). Endoscopists each performed a mean of five procedures. Mean time to maximal insertion was 20.9 +/- 6.4 minutes. Mean depth achieved was 262.0 +/- 57.4 cm. Total procedure time was 33.6 +/- 8.0 minutes. In 90.3 %, 94.6 %, and 83.9 % of patients, respectively, a trauma score less than 3 was recorded in the esophagus, stomach, and intestine (scale = 0 - 5). There were no perforations, nor significant associations between trauma score and patient age, body mass index, depth of insertion, time to maximal insertion, total procedure time, or day 1 vs. day 2 procedures. Depth of insertion was greater on day 2 than on day 1 (276.9 +/- 53.7 cm vs. 252.0 +/- 58.0 cm, P = 0.043). CONCLUSIONS: Discovery SB provides safe advancement of the enteroscope into the distal small bowel. Maximum depth of insertion appears comparable to that of balloon enteroscopy while taking less time. The device is easy to use and may be effectively operated in as few as five training cases.

Origin of the single chain magnet behavior of the Co(H2L)(H2O) compound with a 1D structure.

The paper is aimed at the elucidation of the main factors responsible for the single-chain magnet behavior of the cobalt(II) disphosphonate compound Co(H2L)(H2O) with a 1D structure. The model takes into account the spin-orbit interaction, the axial component of the octahedral crystal field acting on the ground-state cubic 4T1 terms of the Co(II) ions, the antiferromagnetic exchange interaction between Co(II) ions as well as the difference in the crystallographic positions of these ions. The conditions that favor the single-chain magnet behavior based on spin canting in a 1D chain containing inequivalent Co(II) centers are discussed. The peculiarities of this behavior in chains containing orbitally degenerate ions are revealed. The qualitative explanation of the experimental data is given.

2.45 GHz radiofrequency fields alter gene expression in cultured human cells.

The biological effect of radiofrequency (RF) fields remains controversial. We address this issue by examining whether RF fields can cause changes in gene expression. We used the pulsed RF fields at a frequency of 2.45 GHz that is commonly used in telecommunication to expose cultured human HL-60 cells. We used the serial analysis of gene expression (SAGE) method to measure the RF effect on gene expression at the genome level. We observed that 221 genes altered their expression after a 2-h exposure. The number of affected genes increased to 759 after a 6-h exposure. Functional classification of the affected genes reveals that apoptosis-related genes were among the upregulated ones and the cell cycle genes among the downregulated ones. We observed no significant increase in the expression of heat shock genes. These results indicate that the RF fields at 2.45 GHz can alter gene expression in cultured human cells through non-thermal mechanism.

Detection of mycobacterial DNA from sputum of patients with cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at high risk from atypical mycobacterial infections. There have been few attempts to delineate the intensity of mycobacterial infection in CF patients in Ireland. AIMS: To examine the incidence of mycobacterial DNA in an archived collection of genomic DNA extracted from the sputa of CF patients within the Northern Ireland population. METHODS: One hundred and eighty-two CF patients (66 adults and 116 children) were examined for the presence of mycobacterial DNA in their sputum by a genus specific PCR assay based on 16S rRNA, followed by direct automated sequencing of the PCR amplicons. RESULTS: One of 116 (0.9%) children and 2 of 66 adults were positive. Sequence identity revealed Mycobacterium xenopi in the paediatric patient and M. xenopi and M. chelonei in the two adult patients. False-positive results occurred in 11 patients (four adults), mainly due to Corynebacterium spp. CONCLUSIONS: There was a low prevalence of Mycobacterium spp in the CF patient population. All PCR positive results should be confirmed by direct automated sequencing and an alternative specific assay employed. Enhanced molecular screening will contribute in understanding their role as opportunistic pathogens in patients with worsening lung function.

Clinical outcome of Burkholderia cepacia complex infection in cystic fibrosis adults.

BACKGROUND: The Burkholderia cepacia complex (BCC) is one of the most important groups of organisms infecting cystic fibrosis (CF) patients. The aim of the study was to examine how infection with BCC affects clinical outcome. METHODS: Nineteen CF adults infected with BCC and 19 controls infected with Pseudomonas aeruginosa were studied over a 4-year period. The best forced expiratory volume in 1 s (FEV(1)) and body mass index (BMI) for each year were recorded and annual rate of decline calculated. RESULTS: The BCC infected group displayed a significantly greater reduction of FEV(1) and BMI compared to the P. aeruginosa infected group (p=0.001 and p=0.009, respectively). Sixteen patients infected with a single Burkholderia cenocepacia strain had a significantly greater rate of FEV(1) decline compared to those infected with Burkholderia multivorans (n=3) or P. aeruginosa (p=0.01 and p<0.0001, respectively). The rate of BMI decline was significantly greater in patients infected with B. cenocepacia compared to those with P. aeruginosa (p=0.007), but not significantly different in those with B. multivorans (p=0.29). CONCLUSION: BCC infection is associated with an accelerated decline in pulmonary function and BMI. Infection with a single B. cenocepacia strain was associated with a more rapid decline in lung function than those infected with either B. multivorans or P. aeruginosa.

A comparison of pulmonary exacerbations with single and multiple organisms in patients with cystic fibrosis and chronic Burkholderia cepacia infection.

STUDY OBJECTIVES: To compare pulmonary exacerbations with single and multiple organisms in patients with chronic Burkholderia cepacia infection. DESIGN: Data was collected over a 23-month period and for each of the patients two episodes of pulmonary exacerbation were identified, one with B. cepacia isolated as the sole respiratory pathogen and the other with one or more coinfecting organisms grown from the sputum culture. SETTING: Regional tertiary referral center for Respiratory Medicine and Adult Cystic Fibrosis Center for Northern Ireland, Belfast City Hospital. PATIENTS: Adult (over 16 years) CF patients with chronic (more than 4 years) B. cepacia complex infection who attended the Belfast City Hospital between January 1997 and November 1998. MEASUREMENTS: Forced expiratory volume in 1s, forced vital capacity, forced expiratory flow rate 25-75, C-reactive protein, leucocyte count and body mass index were measured before and after two weeks of treatment and analysed for any differences in change between the two episodes. RESULTS: All variables in both groups improved following treatment except for body mass index, which remained unchanged. No significant differences between the measurements were identified on comparison of single (monomicrobial) and multiple (polymicrobial) isolate episodes. CONCLUSION: Patients with chronic B. cepacia infection who develop a pulmonary exacerbation improve, as reflected by clinical and biochemical markers, following IV antibiotic treatment. Pulmonary exacerbations with multiple organisms are no more severe than those where only B. cepacia is isolated.

The uptake and partitioning of cadmium in two cultivars of potato (Solanum tuberosum L.).

The uptake and distribution of Cd in potatoes over the course of a growing season was investigated in two cultivars of potatoes that differed in tuber Cd concentration. Plants were grown in soil with supplemental Cd. The concentrations of Cd in different tissues varied greatly in the order roots>shoots>> tubers. After the initiation of tuber bulking, shoot growth ceased and the increase in total plant Cd was mostly due to accumulation in the tubers. The constancy of the Cd concentration in shoots suggested that import of Cd via the xylem must be matched by export in the phloem, which implied that Cd must have significant phloem mobility. It was found that the differences in tuber Cd between cultivars Wilwash and Kennebec were not due to differences in total uptake or growth, but to differences in Cd partitioning within the plant. This partitioning was specific to Cd and was not observed for a range of nutrient elements. Most of the differences in tuber Cd concentration between the cultivars could be accounted for by a 3-fold higher retention of Cd in the roots of cv. Wilwash. The involvement of root sequestration, and xylem and phloem pathways in the loading of Cd into tubers is considered.

A case-control study examining the role of physical trauma in the onset of fibromyalgia syndrome.

OBJECTIVE: To investigate whether physical trauma may precipitate the onset of fibromyalgia syndrome (FMS). DESIGN: A case-control study was carried out to compare fibromyalgia out-patients with controls attending non-rheumatology out-patient clinics. METHOD: One hundred and thirty-six FMS patients and 152 age- and sex-matched controls completed a postal questionnaire about any physical trauma in the 6 months before the onset of their symptoms. RESULTS: Fifty-three (39%) FMS patients reported significant physical trauma in the 6 months before the onset of their disease, compared with only 36 (24%) of controls (P<0.007). There was no significant difference between FMS patients who had a history of physical trauma and those who did not have physical trauma with regard to age, sex, disease duration, employment status and whether their job at onset was manual. CONCLUSION: Physical trauma in the preceding 6 months is significantly associated with the onset of FMS.

Cytokine concentrations and neutrophil elastase activity in bronchoalveolar lavage and induced sputum from patients with cystic fibrosis, mild asthma and healthy volunteers.

BACKGROUND: Induced sputum (IS) has been proposed as a non-invasive alternative to bronchoalveolar lavage (BAL) for the assessment and monitoring of airways inflammation. The aim of this study was to compare both methods in patients with cystic fibrosis (CF). The possible differences between subjects with CF, mild asthma and healthy volunteers (HV) was also assessed. METHOD: In a single centre, randomised, two way crossover study, 11 patients with CF, 9 mild asthmatics (MA) and 11 HV underwent BAL and hypertonic saline induction on consecutive days. Free neutrophil elastase (NE), neutrophil elastase/alpha(1)-anti-trypsin complex (NE-AAT), tumour necrosis factor receptor (p55) and interleukin-8 (IL-8) were measured in cell free supernatants. RESULTS: Three CF patients reported serious adverse events following BAL. NE was usually undetectable in both IS or BAL samples and NE-AAT concentrations did not differ consistently between the two sampling methods. IL-8 and p55 levels in the CF patients tended to be higher in IS samples compared with BAL samples (median 19,860 vs. 3,855 pg/ml and 2.55 vs. 0.29 ng/ml, respectively). There was a significant difference in mean p55 concentrations between CF, MA and HV in IS samples (P=0.003) but not in BAL samples (P=0.36). The difference in mean IL-8 concentrations in IS samples between subject groups was statistically different (P=0.023). CONCLUSIONS: IS samples can be safely obtained from CF patients. Analysis of IS samples can help to characterize the inflammatory process in the airways of CF patients. The serious adverse events following BAL in 3 CF patients highlight an inherent risk associated with this procedure.

PCR-based detection and identification of Burkholderia cepacia complex pathogens in sputum from cystic fibrosis patients.

PCR amplification of the recA gene followed by restriction fragment length polymorphism (RFLP) analysis was investigated for the rapid detection and identification of Burkholderia cepacia complex genomovars directly from sputum. Successful amplification of the B. cepacia complex recA gene from cystic fibrosis (CF) patient sputum samples containing B. cepacia genomovar I, Burkholderia multivorans, B. cepacia genomovar III, Burkholderia stabilis, and Burkholderia vietnamiensis was demonstrated. In addition, the genomovar identifications determined directly from sputum were the same as those obtained after selective culturing. Sensitivity experiments revealed that recA-based PCR could reliably detect B. cepacia complex organisms to concentrations of 10(6) CFU g of sputum(-1). To fully assess the diagnostic value of the method, sputum samples from 100 CF patients were screened for B. cepacia complex infection by selective culturing and recA-based PCR. Selective culturing identified 19 samples with presumptive B. cepacia complex infection, which was corroborated by phenotypic analyses. Of the culture-positive sputum samples, 17 were also detected directly by recA-based PCR, while 2 samples were negative. The isolates cultured from both recA-negative sputum samples were subsequently identified as Burkholderia gladioli. RFLP analysis of the recA amplicons revealed 2 patients (12%) infected with B. multivorans, 11 patients (65%) infected with B. cepacia genomovar III-A, and 4 patients (23%) infected with B. cepacia genomovar III-B. These results demonstrate the potential of recA-based PCR-RFLP analysis for the rapid detection and identification of B. cepacia complex genomovars directly from sputum. Where the sensitivity of the assay proves a limitation, sputum samples can be analyzed by selective culturing followed by recA-based analysis of the isolate.

Analogy use in naturalistic settings: the influence of audience, emotion, and goals.

The ways in which analogy was used in a nonexperimental environment-politics-was investigated. We used the framework developed in analogy research to analyze the selection of analogical sources in political discourse. We took all the analogies reported in newspapers during the final week of a referendum campaign in Canada and analyzed the features of the different analogies used. We identified 234 analogies and analyzed the range over which analogies were used, semantic categories of analogies, goals of the analogizer, and emotional connotation of the analogies. Our results reveal that analogy was frequently used, that over two-thirds of the analogical sources were nonpolitical, and that many of the sources had strong emotional connotations. Furthermore, the goal of the analogizer influenced the selection of sources. We conclude that characteristics of the audience and emotionality of the source analog are important features in the selection of source analogs.

Improved cultural detection of Burkholderia cepacia from sputum in patients with cystic fibrosis.

AIMS: To evaluate the sensitivity and specificity of two selective media for the isolation of Burkholderia cepacia from sputum specimens in patients with cystic fibrosis (CF). METHODS: In total, 149 expectorated sputum specimens from 113 patients with CF (32 cepacia colonised patients and 81 non-cepacia colonised patients) attending three CF centres were examined for the presence of B cepacia on two selective media: (1) MAST selective agar, a commercially available selective medium widely used in the UK and (2) BCSA (B cepacia selective agar), a new medium recently described, which is used predominantly in North America. RESULTS: Burkholderia cepacia was isolated from 53 of 149 (35.6%) specimens examined, representing 32 of 113 (28.3%) patients, using both the MAST and BCSA media. Growth was most rapid on BCSA with all (53 of 53) isolates detectable after 48 hours, compared with 50 of the 53 isolates on MAST agar, with the remaining three isolates detectable at five days. Twenty eight contaminants were identified on MAST agar and 13 on BCSA agar; mainly Alcaligenes xylosoxidans and yeast on MAST agar and Flavobacterium indologenes on BCSA medium. BCSA was equivalent to MAST agar in its ability to isolate B cepacia from patients with CF with a history of B cepacia infection. CONCLUSIONS: The increased selectivity and reduced time to detection of BCSA makes it an attractive alternative to MAST. However, its present limited commercial availability in the UK may delay its use in routine diagnostic laboratories because of complications with media preparation and quality control.

The in vivo/in vitro approach to cognition: the case of analogy.

A new way of investigating cognition is proposed that combines naturalistic (in vivo) and experimental (in vitro) methods into a single approach. Investigating analogical reasoning by scientists 'live' at laboratory meetings (in vivo) we found that the types of analogies they use change with their goals. Unlike subjects in many cognitive 'reminding' experiments, scientists frequently used structural similarities in their analogies, as opposed to superficial similarities. By subsequently using the in vitro approach, we found that the use of structural information was associated with being asked to generate analogies and with the use of complex scenarios. Similar results are obtained in other areas of reasoning such as hypothesis testing and causal reasoning.