A combined physicochemical approach towards human tenocyte phenotype maintenance.

During in vitro culture, bereft of their optimal tissue context, tenocytes lose their phenotype and function. Considering that tenocytes in their native tissue milieu are exposed simultaneously to manifold signals, combination approaches (e.g. growth factor supplementation and mechanical stimulation) are continuously gaining pace to control cell fate during in vitro expansion, albeit with limited success due to the literally infinite number of possible permutations. In this work, we assessed the potential of scalable and potent physicochemical approaches that control cell fate (substrate stiffness, anisotropic surface topography, collagen type I coating) and enhance extracellular matrix deposition (macromolecular crowding) in maintaining human tenocyte phenotype in culture. Cell morphology was primarily responsive to surface topography. The tissue culture plastic induced the largest nuclei area, the lowest aspect ratio, and the highest focal adhesion kinase. Collagen type I coating increased cell number and metabolic activity. Cell viability was not affected by any of the variables assessed. Macromolecular crowding intensely enhanced and accelerated native extracellular matrix deposition, albeit not in an aligned fashion, even on the grooved substrates. Gene analysis at day 14 revealed that the 130 kPa grooved substrate without collagen type I coating and under macromolecular crowding conditions positively regulated human tenocyte phenotype. Collectively, this work illustrates the beneficial effects of combined physicochemical approaches in controlling cell fate during in vitro expansion.

Copper nanowire array as highly selective electrochemical sensor of nitrate ions in water.

Contamination of water with nitrate ions is a significant problem that affects many areas of the world. For this reason, European legislation has set the maximum permissible concentration of nitrates in drinking water at 44 mg/L. Thus, it is clear that a continuous monitoring of nitrate ions is of high technological interest but it must be rapid, easy to perform and directly performable in situ. In this work we have developed a nanostructured sensor based on array of copper nanowires obtained with the simple method of galvanic deposition. The nanostructured sensors have a very short response time with a detection limit less than 10 µM. Different interfering species were tested finding a negligible effect except for the chloride ions. However, this problem has been solved by removing chloride ions from the water through a simple precipitation of chloride compounds with low solubility. Nanostructured sensors were also used to analyze real water samples (rain, river and drinking water). In the case of drinking water, we have measured a concentration of nitrate ions very close to the that measured by conventional laboratory techniques.

Estimated Weight of Paediatric Patients versus Measured Weight ­ A Prospective Comparison

Introduction Weight measurement is fundamental in the management of paediatric patients. Many methods have been described for estimating a patient's weight. The aim of this study was to assess the accuracy of the APLS 2017 estimated weight guidelines. Methods 100 patient charts were analysed in University Hospital Limerick's Paediatric unit. Measured weights were recorded, and estimated weights were calculated using the APLS 2017 charts. Estimated and measured weight was compared using Bland Altman plots. Results Of 100 subjects, 53 (53%) were female and 47 (47%) male. Fifty subjects (50%) were Pre-School, 32 (32%) Primary School and 18 (18%) Secondary School. Estimated weight was a good predictor for measured weight, however weight was underestimated by between 2.34% and 16.39% of measured weight. Discussion The current APLS guidelines are reasonably accurate; but accuracy decreases with increasing age. Estimation cannot replace an accurate measurement, which is not always feasible in the acute setting.

Promotion of role clarification in the Health Care Team Challenge.

Interprofessional collaboration has consistently been associated with positive client-care outcomes. Role clarification is one facet of interprofessional collaboration that is thought to be crucial for effective interprofessional team functioning. Given the positive outcomes associated with interprofessional collaboration, educators have begun to integrate formal interprofessional education events into healthcare curricula. The Health Care Team Challenge (HCTC) is a collaborative competition designed to promote interprofessional competencies among students in healthcare fields. The current study empirically investigated whether this event promoted role clarification among participants. Sixteen participants in five healthcare professions (occupational therapy, physiotherapy, clinical psychology, nursing, and medicine) completed two questionnaires to assess role clarification before and after participating in this event. Results indicate that participants' understanding of their own and other professions' roles improved after participating in this team activity. These results suggest that the HCTC is effective in promoting role clarification and collaboration among healthcare students.

Outcomes in coeliac disease: a qualitative exploration of patients' views on what they want to achieve when seeing a dietitian.

BACKGROUND: Coeliac disease (CD) is managed by life-long adherence to a gluten-free diet and dietitians have the potential to facilitate this. Patient involvement through shared decision-making is central to behaviour-change skills used by dietitians, although there is little evidence supporting its inclusion in evaluating dietetic interventions. The present study aimed to explore patients' preferences for diet and nutrition-related outcomes in CD. METHODS: Adults with CD or adult carers of children with CD were invited through support networks. Participants took part in a telephone, face-to-face interview or focus group which was audio-recorded and transcribed. Themes were developed using a framework method. Ethical approval was obtained. RESULTS: Twenty-nine adult patients and five parents of CD children participated 0-34 years after diagnosis. Four main outcome-related themes emerged: (i) Participants wanted information specific to their lifestyle and time since diagnosis, focussing on food containing gluten, practical issues, prescribable items and general nutrition. (ii) The degree of satisfaction with the consultation process impacted on participants' experience, including the dietitian's CD expertise, consistency of the dietitian seen, and the frequency and length of appointments. (iii) Health concerns were important to participants and focussed on risk of osteoporosis, unwanted weight gain, and the fat and sugar content of manufactured gluten-free products. (iv) Clinical monitoring, including bone scans and antibody measurements, was mentioned but was not described as being of importance for most participants. CONCLUSIONS: The outcomes preferred by CD patients and carers focussed primarily on information and resources received and satisfaction with their dietetic consultation.

Craniopharyngeal duct: a cause of recurrent meningitis.

Identification of the cause of recurrent meningitis may pose a diagnostic challenge. Evaluation of a patient with recurrent meningitis calls for meticulous review of skull base structures by cross sectional imaging to exclude any underlying anatomical abnormality. Our case highlights the importance of excluding persistent craniopharyngeal duct, a rare but treatable cause of recurrent meningitis. The isolation of Streptococcus pneumoniae in recurrent meningitis may be a clue to the presence of a skull base abnormality. Craniopharyngeal canals have been classified depending on their qualitative and quantitative imaging features. Such imaging based classification is important for identification of patients with associated potential pituitary involvement and also for appropriate surgical planning. Controversy exists as to the approach to surgical treatment of craniopahryngeal duct. The persistent craniopahryngeal duct in our patient was successfully treated by an endoscopic transsphenoidal approach.

Management of paediatric tuberculosis in leading UK centres: unveiling consensus and discrepancies.

SETTING: Large specialist paediatric TB clinics in the UK. OBJECTIVE: To evaluate clinical practice and compare with national and international guidelines. DESIGN: A survey based on an electronic questionnaire on the management of latent tuberculous infection (LTBI) and tuberculosis (TB) disease was conducted in 13 specialist paediatric TB clinics. The consensus and discrepancies were evaluated by descriptive analysis. RESULTS: Practice was reportedly different when choosing age limits for preventive treatment for TB contacts with initially negative tuberculin skin tests (TSTs), interpretation of TST results and use of interferon-gamma release assays (IGRAs) in the context of LTBI. In relation to management of children with TB disease, practices varied for duration of treatment of osteoarticular TB, monitoring for ethambutol ocular toxicity and use of pyridoxine. There was limited experience with multidrug-resistant TB (MDR-TB), and over half of the clinics monitored MDR-TB contacts without giving preventive treatment. CONCLUSIONS: The survey showed heterogeneity in several aspects of clinical care for children with TB. Available paediatric TB guidelines differ substantially, explaining the wide variations in management of childhood TB. Prospective paediatric studies are urgently required to inform and standardise clinical practice, especially in the context of evolving drug resistance.

Pertussis in young infants: clinical presentation, course and prevention.

Pertussis is a highly contagious disease caused by the Gram negative aerobic coccobacillus, Bordetella pertussis. It may present with severe symptoms and complications in infants and can pose a diagnostic challenge. This is a vaccine preventable illness covered by the Irish Childhood Immunisation Schedule. In 2011, a retrospective review was conducted of the records of infants, under six months, with a confirmed diagnosis of pertussis, presenting to Temple Street Children's University Hospital (TSCUH). A summery of notifications of pertussis nationally, from 2001 to 2012, was also examined as part of the study. This found that the rate of reported cases of pertussis has been increasing in Ireland. This national increase corresponds with a rising number of cases identified at TSCUH. Patients commonly presented severely ill with cyanosis and apnoea, on a background of prolonged cough. We found that pertussis was diagnosed rapidly in most cases however in all cases there was a delay to commencement of appropriate macrolide therapy.

The effect of head movement on CT perfusion summary maps: simulations with CT hybrid phantom data.

Head movement is common during CT brain perfusion (CTP) acquisition of patients with acute ischemic stroke. The effects of this movement on the accuracy of CTP analysis has not been studied previously. The purpose of this study was to quantify the effects of head movement on CTP analysis summary maps using simulated phantom data. A dynamic digital CTP phantom dataset of 25 time frames with a simulated infarct volume was generated. Head movement was simulated by specific translations and rotations of the phantom data. Summary maps from this transformed phantom data were compared to the original data using the volumetric dice similarity coefficient (DSC). DSC for both penumbra and core strongly decreased for rotation angles larger than approximately 1°, 2°, and 7° for, respectively, pitch, roll, and yaw. The accuracy is also sensitive for small translations in the z-direction only. Sudden movements introduced larger errors than gradual movement. These results indicate that CTP summary maps are sensitive to head movement, even for small rotations and translations. CTP scans with head movement larger than the presented values should be interpreted with extra care.

Head movement during CT brain perfusion acquisition of patients with suspected acute ischemic stroke.

OBJECTIVE: Computed Tomography Perfusion (CTP) is a promising tool to support treatment decision for acute ischemic stroke patients. However, head movement during acquisition may limit its applicability. Information of the extent of head motion is currently lacking. Our purpose is to qualitatively and quantitatively assess the extent of head movement during acquisition. METHODS: From 103 consecutive patients admitted with suspicion of acute ischemic stroke, head movement in 220 CTP datasets was qualitatively categorized by experts as none, minimal, moderate, or severe. The movement was quantified using 3D registration of CTP volume data with non-contrast CT of the same patient; yielding 6 movement parameters for each time frame. The movement categorization was correlated with National Institutes of Health Stroke Scale (NIHSS) score and baseline characteristic using multinomial logistic regression and student's t-test respectively. RESULTS: Moderate and severe head movement occurred in almost 25% (25/103) of all patients with acute ischemic stroke. The registration technique quantified head movement with mean rotation angle up to 3.6° and 14°, and mean translation up to 9.1mm and 22.6mm for datasets classified as moderate and severe respectively. The rotation was predominantly in the axial plane (yaw) and the main translation was in the scan direction. There was no statistically significant association between movement classification and NIHSS score and baseline characteristics. CONCLUSIONS: Moderate or severe head movement during CTP acquisition of acute stroke patients is quite common. The presented registration technique can be used to automatically quantify the movement during acquisition, which can assist identification of CTP datasets with excessive head movement.

CT brain perfusion protocol to eliminate the need for selecting a venous output function.

BACKGROUND AND PURPOSE: In CTP, an arterial input function is used for cerebral blood volume measurement. AIFs are often influenced by partial volume effects resulting in overestimated CBV. A venous output function is manually selected to correct for partial volume. This can introduce variability. Our goal was to develop a CTP protocol that enables AIF selection unaffected by partial volume. MATERIALS AND METHODS: First, the effects of partial volume on artery sizes/types including the MCA were estimated by using a CTP phantom with 9 protocols (section thicknesses of 1, 1.8, and 5 mm and image resolutions of 0.5, 1, and 1.5 mm). Next, these protocols were applied to clinical CTP studies from 6 patients. The influence of the partial volume effect was measured by comparison of the time-attenuation curves from different artery locations with reference veins. RESULTS: AIFs from MCAs were unaffected by partial volume effects when using high image resolution (1 mm) and medium section thickness (1.8 mm). For the clinical data, a total of 104 arteries and 60 veins was selected. The data confirmed that high image resolution and thin section thickness enable selection of MCAs for AIFs free of partial volume influences. In addition, we found that large veins were not insusceptible to partial volume effects relative to large arteries, questioning the use of veins for partial volume correction. CONCLUSIONS: A CTP protocol with 1.8-mm section thickness and 1-mm image resolution allows AIF selection unaffected by partial volume effects in MCAs.

Cytomegalovirus replication kinetics in solid organ transplant recipients managed by preemptive therapy.

After allotransplantation, cytomegalovirus (CMV) may be transmitted from the donor organ, giving rise to primary infection in a CMV negative recipient or reinfection in one who is CMV positive. In addition, latent CMV may reactivate in a CMV positive recipient. In this study, serial blood samples from 689 kidney or liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was managed using preemptive antiviral therapy and no patient received antiviral prophylaxis. Dynamic and quantitative measures of viremia and treatment were assessed. Median peak viral load, duration of viremia and duration of treatment were highest during primary infection, followed by reinfection then reactivation. In patients who experienced a second episode of viremia, the viral replication rate was significantly slower than in the first episode. Our data provide a clear demonstration of the immune control of CMV in immunosuppressed patients and emphasize the effectiveness of the preemptive approach for prevention of CMV syndrome and end organ disease. Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission.

Mortality and morbidity of nosocomial respiratory syncytial virus (RSV) infection in ventilated children--a ten year perspective.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the most common pathogens involved in nosocomial infection in children. The aim of the study was to determine the impact of nosocomial RSV infection on mortality and pediatric intensive care unit (PICU) morbidity of ventilated children. METHODS: This is a prospective observational cohort study of all children ventilated with RSV infection in a tertiary-referral PICU over a 10-year period. Determinants of the relationship of nosocomial (PICU-acquired and hospital ward-acquired) RSV infection to mortality and PICU morbidity were adjusted for by performing multiple regression analysis. RESULTS: Of 525 RSV-positive children ventilated on PICU during the ten-year study period, 38 (7.2%) acquired their RSV infection following PICU admission and 38 (7.2%) had acquired RSV in hospital. Ten (26%) children that acquired RSV on PICU died (RR 6.4, 95%CI 3.2-12.9) and 11 (29%) with hospital ward-acquired infection died (RR 9.8, 95%CI 5.1-18.9), compared to 18 (4%) with community-acquired RSV infection. Nosocomial RSV infection was significantly and independently associated with death which was more strongly predicted by immunodeficiency and congenital heart disease (P<0.01). Nosocomial RSV infection was the strongest predictor for morbidity as reflected in duration of ventilation and length of stay on PICU (P<0.01). CONCLUSION: Nosocomial RSV infection was independently associated with increased mortality and was the strongest predictor of duration of ventilation and length of stay in children on PICU. Decreasing nosocomial RSV infection would reduce deaths in ventilated children.

Dielectrophoretic self-assembly of polarized light emitting poly(9,9-dioctylfluorene) nanofibre arrays.

Conjugated polymer based 1D nanostructures are attractive building blocks for future opto-electronic nanoscale devices and systems. However, a critical challenge remains the lack of manipulation methods that enable controlled and reliable positioning and orientation of organic nanostructures in a fast, reliable and scalable manner. To address this challenge, we explore dielectrophoretic assembly of discrete poly(9,9-dioctylfluorene) nanofibres and demonstrate site selective assembly and orientation of these fibres. Nanofibre arrays were assembled preferentially at receptor electrode edges, being aligned parallel to the applied electric field with a high order parameter fit (∼ 0.9) and exhibiting an emission dichroic ratio of ∼ 4.0. As such, the dielectrophoretic method represents a fast, reliable and scalable self-assembly approach for manipulation of 1D organic nanostructures. The ability to fabricate nanofibre arrays in this manner could be potentially important for exploration and development of future nanoscale opto-electronic devices and systems.

Relationships between race earnings and horse age, sex, gait, track surface and number of race starts for Thoroughbred and Standardbred racehorses in North America.

REASONS FOR PERFORMING STUDY: There is no consensus on objective outcome measures that can be used to determine if a medical or surgical treatment affects race performance. OBJECTIVE: To determine the association between 2 commonly used outcome measures (total starts and total earnings) and age, sex, gait and race surface. METHODS: A cross-sectional study was performed using the race performance data for all Thoroughbred horses age 2, 3, 4 and 5 years racing in the United States, and Standardbred horses of the same ages racing in the United States and Canada during the year 2006. Median earnings and starts were determined for each combination of age, sex and track surface (for Thoroughbred) or gait (for Standardbred). The effect these variables had on starts on race earnings ($) was determined using linear regression. RESULTS: Race records for 68,649 Thoroughbreds and 25,830 Standardbreds were obtained. All independent variables (age, breed, sex, gait, track surface and total number of starts) had a significant impact on total earnings (P<0.0001). CONCLUSIONS: The data show considerable variation across age groups and track surfaces for Thoroughbreds and across age groups for Standardbreds. They also show that the decision to use earnings or starts as outcome measures could have a marked effect on reported success for a particular treatment. POTENTIAL RELEVANCE: Both earning and start data should be reported in studies evaluating outcome following surgery or other intervention. Considerations of age, breed, sex, track surface and gait should be included in the design of these studies.

How to use: C-reactive protein.

C-reactive protein (CRP) is an acute-phase protein that increases 4-6 h after an inflammatory trigger and peaks at 36-50 h. Levels decrease rapidly with the resolution of inflammation. CRP is generally highly elevated in invasive bacterial infections and is often used as a marker of inflammation. A single CRP level is neither sensitive nor specific enough to identify all children with serious bacterial infection. However, a raised CRP does suggest serious bacterial infection and should suggest further assessment is needed. CRP levels that fail to decrease, or continue to rise, after 48 h of antibiotic therapy suggest treatment failure. In infants with suspected neonatal sepsis, two CRP measurements 24 h apart that are <10 mg/l are useful in excluding sepsis.

An evaluation of the completeness of reporting of childhood tuberculosis.

The sensitivity of the Enhanced Tuberculosis Surveillance (ETS) scheme for monitoring tuberculosis in children is unknown. We used the British Paediatric Surveillance Unit (BPSU) reporting scheme to conduct a prospective observational study of tuberculosis in children aged <16 yrs in the UK. Reported cases were then matched with records from the ETS database. A total of 320 cases were reported to the BPSU between January and December 2004. We estimated that there were 557 paediatric cases in England, Wales and Northern Ireland in 2004: 222 (40%) cases reported to both BPSU and ETS, 98 (18%) reported to BPSU but not ETS and 237 (42%) reported to ETS but not BPSU. Children aged <5 yrs were significantly less likely to be reported to ETS compared with older children (p<0.01). There is substantial under-reporting of childhood tuberculosis, especially of children aged <5 yrs. ETS provides a representative picture of the demographics but may miss approximately 20% of cases. This should be taken into account when planning training and resource requirements for tuberculosis. Increased efforts are needed to ensure that all paediatric cases are reported to ETS.

Tuberculosis in the United Kingdom and Republic of Ireland.

AIMS: To describe the clinical features, diagnosis and management of children with tuberculosis in the United Kingdom and Republic of Ireland. METHODS: Cases of culture-confirmed and clinically diagnosed tuberculosis were reported to the British Paediatric Surveillance Unit from December 2003 to January 2005. RESULTS: 385 eligible cases were reported. Pulmonary disease was present in 154 (40%) children. Just over half (197, 51%) of children presented clinically and most of the remainder (166, 43%) at contact tracing. A probable source case was identified for 73/197 (36%) of the children presenting clinically. The majority (253, 66%) of children had a microbiological and/or histological investigation, and culture results were available for 240 (62%), of whom 102 (26%) were culture positive. Drug resistance was reported in 15 (0.4%) cases. 44% (128/292) of non-white children did not receive the recommended quadruple drug therapy. Seven children died. Only 57% (217) of children were managed by a paediatric subspecialist in respiratory or infectious diseases or a general paediatrician with a special interest in one of these areas. Fewer than five cases were reported from 119/143 (83%) respondents and 72 of 96 (75%) centres. CONCLUSIONS: Many paediatricians and centres see few children with tuberculosis. This may affect adherence to national guidelines. Managed clinical networks for children with tuberculosis may improve management and should be the standard of care.