Dairy farmers' perceptions toward the implementation of on-farm Johne's disease prevention and control strategies.

Implementation of specific management strategies on dairy farms is currently the most effective way to reduce the prevalence of Johne's disease (JD), an infectious chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). However, dairy farmers often fail to implement recommended strategies. The objective of this study was to assess perceptions of farmers participating in a JD prevention and control program toward recommended practices, and explore factors that influence whether or not a farmer adopts risk-reducing measures for MAP transmission. Semi-structured interviews were conducted with 25 dairy farmers enrolled in a voluntary JD control program in Alberta, Canada. Principles of classical grounded theory were used for participant selection, interviewing, and data analysis. Additionally, demographic data and MAP infection status were collected and analyzed using quantitative questionnaires and the JD control program database. Farmers' perceptions were distinguished according to 2 main categories: first, their belief in the importance of JD, and second, their belief in recommended JD prevention and control strategies. Based on these categories, farmers were classified into 4 groups: proactivists, disillusionists, deniers, and unconcerned. The first 2 groups believed in the importance of JD, and proactivists and unconcerned believed in proposed JD prevention and control measures. Groups that regarded JD as important had better knowledge about best strategies to reduce MAP transmission and had more JD risk assessments conducted on their farm. Although not quantified, it also appeared that these groups had more JD prevention and control practices in place. However, often JD was not perceived as a problem in the herd and generally farmers did not regard JD control as a "hot topic" in communications with their herd veterinarian and other farmers. Recommendations regarding how to communicate with farmers and motivate various groups of farmers according to their specific perceptions were provided to optimize adoption of JD prevention and control measures and thereby increase success of voluntary JD control programs.

[Systematic Readability Analysis of Medical Texts on Websites of German University Clinics for General and Abdominal Surgery]. / Systematische Analyse der Lesbarkeit von Patienteninformationstexten auf Internetseiten von Kliniken für Allgemein- und Viszeralchirurgie deutscher Universitätskliniken.

Background: Besides the function as one of the main contact points, websites of hospitals serve as medical information portals. As medical information texts should be understood by any patients independent of the literacy skills and educational level, online texts should have an appropriate structure to ease understandability. Materials and Methods: Patient information texts on websites of clinics for general surgery at German university hospitals (n = 36) were systematically analysed. For 9 different surgical topics representative medical information texts were extracted from each website. Using common readability tools and 5 different readability indices the texts were analysed concerning their readability and structure. The analysis was furthermore stratified in relation to geographical regions in Germany. Results: For the definite analysis the texts of 196 internet websites could be used. On average the texts consisted of 25 sentences and 368 words. The reading analysis tools congruously showed that all texts showed a rather low readability demanding a high literacy level from the readers. Conclusion: Patient information texts on German university hospital websites are difficult to understand for most patients. To fulfill the ambition of informing the general population in an adequate way about medical issues, a revision of most medical texts on websites of German surgical hospitals is recommended.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

Liquid dextran does not increase the elution rate of different antibiotics from bone cement.

PURPOSE: To investigate the possibility of increasing elution of fosfomycin, gentamicin, clindamycin, and vancomycin by the addition of dextran fluid during the cement-mixing phase. METHODS: In 12 test series, we produced standardized, antibiotic-loaded test specimens of cement, with and without addition of dextran, and determined their effectiveness against three reference pathogens in agar diffusion and elution tests. RESULTS: In the test series using combined agents, Refobacin(®)-Palacos(®)R plus fosfomycin continuously produced the largest zone of inhibition, both against methicillin-sensitive Staphylococcus aureus (p = 0.009) and against methicillin-resistant Staphylococcus aureus (p = 0.009). The addition of dextran to the various test series had no useful effect on the size of the zone of inhibition for any of the antibiotics tested. CONCLUSIONS: Dextran supplementation in Refobacin(®)-Palacos(®)R bone cement did not have the hope for positive effect on the elution rate of bound antibiotics.

Risk factors for heterotopic ossification and spur formation after total knee arthroplasty.

INTRODUCTION: The present study investigated the incidence and risk factors of heterotopic ossification (HO) after implantation of knee prosthesis. MATERIALS AND METHODS: We undertook a retrospective cohort study in 434 cases (363 patients) treated with a total knee replant using a Press-Fit-Condylar (P.F.C.(®)Sigma(®)) prosthesis. The occurrence of HO in radiograph after a follow-up period of 11.2 ± 2.4 months was correlated in a regression model with a variety of influencing factors. RESULTS: 21 patients (4.8 %) developed heterotopic ossifications, all located in the area of the distal femur. The only risk factor found concerning the development of HO was osteoarthritis when compared to rheumatoid arthritis (OR = 4.07, 95 % CI 1.18-14.05; p = 0.0201) and postoperative wound healing problems (OR = 11.32, 95 % CI 3.26-39.33; p = 0.0001). Notching (OR = 2.22, 95 % CI 0.92-5.36; p = 0.0765) and osteophyte forming (hypertrophic) arthrosis (OR = 2.40, 95 % CI 0.97-5.95; p = 0.0596), however, were associated with the development of a bony spur in the contact area of the femoral component of the prosthesis. CONCLUSIONS: Our study has revealed that patients with rheumatoid arthritis are at lower risk of HO than patients with osteoarthritis. An impairment of wound healing would appear to promote the development of a HO. Notching and hypertrophic arthrosis are highly likely to be associated with the development of a bony spur in the ventral contact area of the prosthesis.

[Systematic analysis of the readability of patient information on websites of German nonuniversity ENT hospitals]. / Systematische Analyse der Lesbarkeit von Patienteninformationstexten auf Internetseiten deutscher nichtuniversitärer HNO-Kliniken.

BACKGROUND: Besides their function as one of the main contact points, websites of hospitals serve as medical information portals. All patients should be able to understand medical information texts; regardless of their literacy skills and educational level. Online texts should thus have an appropriate structure to ease their comprehension. MATERIALS AND METHODS: Patient information texts on every German nonuniversity ENT hospital website (n = 125) were systematically analysed. For ten different ENT topics a representative medical information text was extracted from each website. Using objective text parameters and five established readability indices, the texts were analysed in terms of their readability and structure. Furthermore, we stratified the analysis in relation to the hospital organisation system and geographical region in Germany. RESULTS: Texts from 142 internet sites could be used for the definite analysis. On average, texts consisted of 15 sentences and 237 words. Readability indices congruously showed that the analysed texts could generally only be understood by a well-educated or even academic reader. CONCLUSION: The majority of patient information texts on German hospital websites are difficult to understand for most patients. In order to fulfil their goal of adequately informing the general population about disease, therapeutic options and the particular focal points of the clinic, a revision of most medical texts on the websites of German ENT hospitals is recommended.

Rnx deficiency results in congenital central hypoventilation.

The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa.

Inadequate levels of all-trans-retinol in the blood cause retinal dysfunction; hence, genes implicated in retinal vitamin-A metabolism represent candidates for inherited retinal degenerations. In the current study, molecular genetic analysis of a consanguineous pedigree segregating for non-syndromic autosomal recessive retinitis pigmentosa (arRP) indicated that the affected siblings were homozygous by descent for a G4763A nucleotide substitution in RLBP1, the gene encoding cellular retinaldehyde-binding protein (CRALBP). This substitution is predicted to replace an arginine with glutamine at residue 150. CRALBP is not expressed in photoreceptors but is abundant in the retinal pigment epithelium (RPE) and Müller cells of the neuroretina, where it carries 11-cis-retinol and 11-cis-retinaldehyde. When expressed in bacteria, recombinant CRALBP (rCRALBP) containing the R150Q substitution was less soluble than wild-type rCRALBP. Mutant rCRALBP was purified from the soluble cell lysate and the protein structure was verified by mass spectrometry. The mutant protein lacked the ability to bind 11-cis-retinaldehyde. These findings suggest that arRP in the current pedigree results from a lack of functional CRALBP, presumably leading to disruption of retinal vitamin-A metabolism.

[Readability of medical texts on websites of German ENT university hospitals]. / Lesbarkeit von medizinischen Texten im Internetangebot deutscher HNO-Universitätskliniken.

BACKGROUND: A certain proportion of the population has limited literacy skills; therefore, it is important that any patient information published on the internet is readable to the majority of patients for whom the information is intended. MATERIALS AND METHODS: Texts for 10 representative ear nose and throat (ENT) topics were extracted from each website of the 36 German ENT university hospitals. The texts were systematically analyzed by use of the German version of the Flesch ease of reading index. The texts of two topics were additionally analyzed with four more readability tools for the German language. Texts were analyzed in relation to the topic and to the geographical region. RESULTS: On average the texts of 185 websites consisted of 34 sentences and 401 words. Comparably, texts on cochlear implants showed the best readability scores and texts on middle ear pathology the worst. The results of the reading ease index and of the other reading analysis tools showed that all texts require a relatively high literacy level. CONCLUSIONS: To fulfil the ambition of informing the general population about medical issues in an adequate way, a revision of most medical texts on websites of German ENT departments at university hospitals is recommended.

Phase II study of first-line sagopilone plus prednisone in patients with castration-resistant prostate cancer: a phase II study of the Department of Defense Prostate Cancer Clinical Trials Consortium.

BACKGROUND: Preclinical studies in prostate cancer (PC) models demonstrated the anti-tumour activity of the first fully synthetic epothilone, sagopilone. This is the first study to investigate the activity and safety of sagopilone in patients with metastatic castration-resistant PC (CRPC). METHODS: Chemotherapy-naïve patients with metastatic CRPC received sagopilone (one cycle: 16 mg m(-2) intravenously over 3 h q3w) plus prednisone (5 mg twice daily). The primary efficacy evaluation was prostate-specific antigen (PSA) response rate (≥50% PSA reduction confirmed ≥28 days apart). According to the Simon two-stage design, ≥3 PSA responders were necessary within the first 13 evaluable patients for recruitment to continue until 46 evaluable patients were available. RESULTS: In all, 53 patients received ≥2 study medication cycles, with high compliance. Mean individual dose was 15.1±1.4 mg m(-2) during initial six cycles, mean dose intensity 94±9%. The confirmed PSA response rate was 37%. Median overall progression-free survival was 6.4 months. The most commonly reported adverse events (>10% of patients) were peripheral neuropathy (94.3%), fatigue (54.7%) and pain in the extremities (47.2%). Sagopilone was associated with very little haematological toxicity. CONCLUSION: This study shows that first-line sagopilone has noteworthy anti-tumour activity and a clinically significant level of neuropathy for patients with metastatic chemotherapy-naïve CRPC.

Against all odds: a qualitative study of rehabilitation of persons with spinal cord injury in Afghanistan.

STUDY DESIGN: Cross-sectional, survey. OBJECTIVES: To describe the challenges in rehabilitating patients with spinal cord injury in the orthopaedic centres of the International Committee of the Red Cross in Afghanistan. SETTING: Afghanistan (Kabul, Herat, Mazar-i-Sharif, Jalalabad, Gulbahar), April 2012. METHODS: Semi-structured interviews were conducted with managers and professional staff of ICRC and other concerned organizations/institutions (Ministries, hospitals, non-governmental organizations), and with people with SCI and their families. Quantitative data were extracted from routine statistics. RESULTS: A reported annual incidence of roughly 21 SCI cases per million in Afghanistan could be established for the year 2011. Acts of violence were the most frequent cause, followed by spinal tuberculosis. Despite very elementary prehospital and hospital care, SCI individuals are rehabilitated within the limits set by available technology and socio-economic factors. Support to community reintegration is effective for the ones living within a radius determined by distance and security. CONCLUSION: Rehabilitation of SCI patients would be ineffective without covering at least part of the services usually provided during the phases of acute hospital care and community reintegration. The question of whether services currently provided by foreign-based or funded organizations can be extended into a potential postconflict period, and by whom, remains open.

Computational ballistic analysis of the cranial shot to John F. Kennedy.

Almost 60 years after the assassination of President John F. Kennedy in 1963, the majority of Americans are still reluctant to believe official reports presented by the commissions gathered in 1964 and again in 1976 that determined the direction of the shot resulting in the fatal head injury. Long-withheld, confidential government files released in 2017 reignited the controversy. The present investigation computationally simulated projectile-skull-impacts from the direction specified in official reports and from three other directions. Detailed geometric models of the human head and ammunition, as well as known parameters from the assassination site served as the supportive base for analysis. Constitutive mathematical models for the impact of projectile material with skull tissues at supersonic speed were employed to analyze bone and bullet fragmentation mechanics. Simulated fracture characteristics of bone and bullet were compared with photographic and X-ray evidence. The most likely origin of the fatal shot was determined based on the degree of corresponding deformation and fragmentation between simulation and documented evidence. Computational corroboration could be established as physically consistent with high-speed impact from the rear, as established by the official commissions. Simulations of three other speculative shot origins did not correspond with the documented evidence.

DNA microarrays and beyond: completing the journey from tissue to cell.

For the cell biologist, identifying changes in gene expression using DNA microarrays is just the start of a long journey from tissue to cell. We discuss how chip users can first filter noise (false-positives) from daunting microarray datasets. Combining laser capture microdissection with real-time polymerase chain reaction and reverse transcription is a helpful follow-up step that allows expression of selected genes to be quantified using sensitive new in situ hybridization and immunohistochemical methods based on tyramide signal amplification.

Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon.

The isolated homeobox gene Enx (Hox11L1) is expressed in enteric neurons innervating distal ileum, and proximal and distal colon. Enx-deficient mice develop megacolon with massive distension of the proximal colon. The number of myenteric ganglia, total neurons per ganglion, and NADPH diaphorase presumptive inhibitory neurons per ganglion are increased in the proximal and distal colon, but decreased in the distal ileum of all Enx-/- mice. Enx-/- mice provide a model for human neuronal intestinal dysplasia (NID), in which myenteric neuronal hyperplasia and megacolon are seen. These results suggest that Enx is required for the proper positional specification and differentiative cell fate of enteric neurons.

Murine gamma-herpesvirus 68 causes severe large-vessel arteritis in mice lacking interferon-gamma responsiveness: a new model for virus-induced vascular disease.

Fundamental issues remain unresolved regarding the possible contribution of viruses to vascular pathology, as well as the role of the immune system in regulating these processes. Here we demonstrate that infection of mice with gamma-herpesvirus 68 (gammaHV68) provides a novel model for addressing these issues. Interferon-gamma receptor-deficient (IFNgammaR-/-) mice died weeks to months after gammaHV68 infection from a severe large-vessel panarteritis. GammaHV68-infected B cell-deficient and normal weanling mice exhibited milder large-vessel arteritis. Immunohistochemical analyses demonstrated gammaHV68 antigen in arteritic lesions and revealed a striking tropism of gammaHV68 for smooth muscle cells. These studies demonstrate that IFN-gamma is essential for control of chronic vascular pathology induced by gammaHV68 and suggest gamma-herpesviruses as candidate etiologic agents for human vasculitis.

The afterglow and elliptical host galaxy of the short gamma-ray burst GRB 050724.

Despite a rich phenomenology, gamma-ray bursts (GRBs) are divided into two classes based on their duration and spectral hardness--the long-soft and the short-hard bursts. The discovery of afterglow emission from long GRBs was a watershed event, pinpointing their origin to star-forming galaxies, and hence the death of massive stars, and indicating an energy release of about 10(51) erg. While theoretical arguments suggest that short GRBs are produced in the coalescence of binary compact objects (neutron stars or black holes), the progenitors, energetics and environments of these events remain elusive despite recent localizations. Here we report the discovery of the first radio afterglow from the short burst GRB 050724, which unambiguously associates it with an elliptical galaxy at a redshift z = 0.257. We show that the burst is powered by the same relativistic fireball mechanism as long GRBs, with the ejecta possibly collimated in jets, but that the total energy release is 10-1,000 times smaller. More importantly, the nature of the host galaxy demonstrates that short GRBs arise from an old (> 1 Gyr) stellar population, strengthening earlier suggestions and providing support for coalescing compact object binaries as the progenitors.

The afterglow of GRB 050709 and the nature of the short-hard gamma-ray bursts.

The final chapter in the long-standing mystery of the gamma-ray bursts (GRBs) centres on the origin of the short-hard class of bursts, which are suspected on theoretical grounds to result from the coalescence of neutron-star or black-hole binary systems. Numerous searches for the afterglows of short-hard bursts have been made, galvanized by the revolution in our understanding of long-duration GRBs that followed the discovery in 1997 of their broadband (X-ray, optical and radio) afterglow emission. Here we present the discovery of the X-ray afterglow of a short-hard burst, GRB 050709, whose accurate position allows us to associate it unambiguously with a star-forming galaxy at redshift z = 0.160, and whose optical lightcurve definitively excludes a supernova association. Together with results from three other recent short-hard bursts, this suggests that short-hard bursts release much less energy than the long-duration GRBs. Models requiring young stellar populations, such as magnetars and collapsars, are ruled out, while coalescing degenerate binaries remain the most promising progenitor candidates.

Is there a secular decline in motor skills in preschool children?

Current research seems to confirm a secular decline in movement skills in school children. Only few data are available for preschool children and no clear trend can be identified. In the year 2007, height, weight, and motor performance were determined in 726 preschool children [Prevention through Activity in Kindergarten Trial (PAKT)] and compared with historical samples from 1973, 1985, and 1989. There was no difference in height and weight between the samples of 1973 and 2007. Older boys of today were smaller and lighter than those of 1989. Regardless of age, PAKT children fared significantly better in standing long jump than those assessed in 1989. Compared with the sample of 1973, PAKT children did equally well in this task. There were no differences in performance in an obstacle course between children of 1989 and 2007. In balancing backwards, PAKT children performed significantly worse than those in 1985. Regarding target throwing only the PAKT 4-year-olds achieved significantly worse results than those in 1985.Therefore, in preschool children, a secular decline is only evident in some, but not all, motor skills, which may indicate a change in behavior activity over the last decades.

Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death.

There has been a growing controversy regarding the continued use of glucocorticoid therapy to treat respiratory dysfunction associated with prematurity, as mounting clinical evidence has shown neonatal exposure produces permanent neuromotor and cognitive deficits. Here we report that, during a selective neonatal window of vulnerability, a single glucocorticoid injection in the mouse produces rapid and selective apoptotic cell death of the proliferating neural progenitor cells in the cerebellar external granule layer and permanent reductions in neuronal cell counts of their progeny, the cerebellar internal granule layer neurons. Our estimates suggest that this mouse window of vulnerability would correspond in the human to a period extending from approximately 20 weeks gestation to 6.5 weeks after birth. This death pathway is critically regulated by the proapoptotic Bcl-2 family member Puma and is independent of p53 expression. These rodent data indicate that there exists a previously unknown window of vulnerability during which a single glucocorticoid exposure at clinically relevant doses can produce neural progenitor cell apoptosis and permanent cerebellar pathology that may be responsible for some of the iatrogenically induced neurodevelopmental abnormalities seen in children exposed to this drug. This vulnerability may be related to the physiological role of glucocorticoids in regulating programmed cell death in the mammalian cerebellum.