Rapid Diagnosis of Babesia gibsoni by Point-of-Need Testing by Insulated Isothermal PCR in Dogs at High Risk of Infection.

BACKGROUND: Dogs seized by law enforcement agencies during dogfighting investigations are at increased risk of Babesia gibsoni infection. A rapid and cost-effective diagnostic test would increase the feasibility of mass screening of dogs for infection and monitoring treatment efficacy in B. gibsoni-infected dogs. OBJECTIVE: To determine the performance of a point-of-need insulated isothermal PCR (iiPCR) test for diagnosis of B. gibsoni in dogs rescued in dogfighting investigations. ANIMALS: Two hundred and thirty-three dogs seized in dogfighting investigations. METHODS: Cross-sectional study. Whole blood samples were tested for B. gibsoni and Babesia spp. by iiPCR. Results were compared to a reference standard comprised of concordant results from real-time PCR in a commercial diagnostic laboratory and antibody titers. RESULTS: The iiPCR system was quick to learn, portable, and had a short processing time of <2 hours. Sensitivity and specificity of the iiPCR assay for B. gibsoni were 90% (95% confidence interval [CI] 81-95%) and 99% (CI, 95-100%), respectively. Sensitivity and specificity of the iiPCR assay for Babesia spp. were 87% (CI, 78-93%) and 98% (CI, 0.94-99%), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The iiPCR system produced few false-positive results, indicating that positive results are likely to represent true infections when used in high-risk animals. The iiPCR system can fail to identify 10-15% of truly infected dogs. However, the portability, speed, and economy of the iiPCR system compared to testing through a reference laboratory can allow rescue groups to screen and identify infection in more dogs.

The feasibility and acceptability of a physical activity intervention for older people with chronic musculoskeletal pain: The iPOPP pilot trial protocol.

INTRODUCTION: This pilot trial will inform the design and methods of a future full-scale randomized controlled trial (RCT) and examine the feasibility, acceptability and fidelity of the Increasing Physical activity in Older People with chronic Pain (iPOPP) intervention, a healthcare assistant (HCA)-supported intervention to promote walking in older adults with chronic musculoskeletal pain in a primary care setting. METHODS AND ANALYSIS: The iPOPP study is an individually randomized, multicentre, three-parallel-arm pilot RCT. A total of 150 participants aged ≥65 years with chronic pain in one or more index sites will be recruited and randomized using random permuted blocks, stratified by general practice, to: (i) usual care plus written information; (ii) pedometer plus usual care and written information; or (iii) the iPOPP intervention. A theoretically informed mixed-methods approach will be employed using semi-structured interviews, audio recordings of the HCA consultations, self-reported questionnaires, case report forms and objective physical activity data collection (accelerometry). Follow-up will be conducted 12 weeks post-randomization. Collection of the quantitative data and statistical analysis will be performed blinded to treatment allocation, and analysis will be exploratory to inform the design and methods of a future RCT. Analysis of the HCA consultation recordings will focus on the use of a checklist to determine the fidelity of the iPOPP intervention delivery, and the interview data will be analysed using a constant comparison approach in order to generate conceptual themes focused around the acceptability and feasibility of the trial, and then mapped to the Theoretical Domains Framework to understand barriers and facilitators to behaviour change. A triangulation protocol will be used to integrate quantitative and qualitative data and findings.

Volume responsiveness assessed by passive leg raising and a fluid challenge: a critical review focused on mean systemic filling pressure.

This review applied cardiovascular principles relevant to the physiology of venous return in interpreting studies on the utility of a passive leg-raising manoeuvre to identify patients who do (responders) or do not respond to a subsequent intravenous volume challenge with an increase in cardiac output. Values for cardiac output, mean arterial and central venous pressure, and the calculated cardiovascular variables mean systemic filling pressure analogue, heart efficiency, cardiac power indexed by volume state and volume efficiency, before and after passive leg raising as well as before and after fluid volume challenge, were extracted from published studies. Eleven studies including 572 patients and 52% responders were analysed. Cardiac output increased by 12% in responders during passive leg raising and by 22% following a volume challenge. No statistically significant differences were found between responders and non-responders in cardiac output, mean arterial or central venous pressure before the passive leg-raising manoeuvre or the volume challenge. In contrast, the calculated mean (SD) systemic filling pressure analogue, reflecting the intravascular volume, was significantly lower in responders (14.2 (1.8) mmHg) than non-responders (17.5 (3.4) mmHg; p = 0.007) before the passive leg-raising manoeuvre, as well as before fluid volume challenge (14.6 (2.2) mmHg vs. 17.6 (3.5) mmHg, respectively; p = 0.02). The scalar measure volume efficiency was higher in responders at 0.35 compared with non-responders at 0.10. Non-responders also demonstrated deteriorating heart efficiency of -15% and cardiac power of -7% when given an intravenous fluid volume challenge. The results demonstrate that the calculation of mean systemic filling pressure analogue and derived variables can identify patients likely to respond to a fluid volume challenge and provides scalar results rather than merely a dichotomous outcome of responder or non-responder.

Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies.

Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared with bone marrow grafts (2.5 vs 7.3%; P<0.001). A fourfold increase of PGF was observed in myeloproliferative disorders compared with acute leukemia (P<0.001). Other risk factors for PGF included recipient age <30, HLA mismatch, male recipients of female donor grafts, ABO incompatibility, busulfan/cyclophosphamide conditioning and cryopreservation. In bone marrow transplants, total nucleated cell doses ⩽2.4 × 10(8) per kg were associated with PGF (odds ratio 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post transplant may provide the rationale for an early request for additional hematopoietic stem cells.

Molybdenum doped titanium dioxide photocatalytic coatings for use as hygienic surfaces: the effect of soiling on antimicrobial activity.

Titanium dioxide (TiO2) surfaces doped with molybdenum (Mo) were investigated to determine if their photocatalytic ability could enhance process hygiene in the brewery industry. Doping TiO2 with Mo showed a 5-log reduction in bacterial counts within 4 to 24 h and a 1-log reduction in yeast numbers within 72 h. The presence of a dilute brewery soil on the surface did not interfere with antimicrobial activity. The TiO2-Mo surface was also active in the dark, showing a 5-log reduction in bacteria within 4 to 24 h and a 1-log reduction in yeast numbers within 72 h, suggesting it could have a novel dual function, being antimicrobial and photocatalytic. The study suggests the TiO2-Mo coating could act as a secondary barrier in helping prevent the build-up of microbial contamination on surfaces within the brewery industry, in particular in between cleaning/disinfection regimes during long production runs.

Disseminated Bacillus Calmette-Guérin (BCG) infection following allogeneic hematopoietic stem cell transplant in a patient with Bare Lymphocyte Syndrome type II.

We describe the first case, to our knowledge, of disseminated Mycobacterium bovis Bacillus Calmette-Guérin infection in a child with Bare Lymphocyte Syndrome type II after undergoing hematopoietic stem cell transplantation (HSCT). The patient presented 30 days post HSCT with fever and lymphadenitis. Lymph node, blood, and gastric aspirates were positive for M. bovis. The patient received a prolonged treatment course with a combination of isoniazid, levofloxacin, and ethambutol. Her course was further complicated by granulomatous lymphadenitis and otitis media associated with M. bovis that developed during immune suppression taper and immune reconstitution. Ultimately, the patient recovered fully, in association with restoration of immune function, and has completed 12 months of therapy.

Effects of spleen status on early outcomes after hematopoietic cell transplantation.

To assess the impact of spleen status on engraftment, and early morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT), we analyzed 9,683 myeloablative allograft recipients from 1990 to 2006; 472 had prior splenectomy (SP), 300 splenic irradiation (SI), 1,471 with splenomegaly (SM), and 7,440 with normal spleen (NS). Median times to neutrophil engraftment (NE) and platelet engraftment (PE) were 15 vs 18 days and 22 vs 24 days for the SP and NS groups, respectively (P<0.001). Hematopoietic recovery at day +100 was not different across all groups, however the odds ratio of days +14 and +21 NE and day +28 PE were 3.26, 2.25 and 1.28 for SP, and 0.56, 0.55, and 0.82 for SM groups compared to NS (P<0.001), respectively. Among patients with SM, use of peripheral blood grafts improved NE at day +21, and CD34+ cell dose >5.7 × 10(6)/kg improved PE at day+28. After adjusting variables by Cox regression, the incidence of GVHD and OS were not different among groups. SM is associated with delayed engraftment, whereas SP prior to HCT facilitates early engraftment without having an impact on survival.

The effect of vascular risk factors on the efficacy of rivastigmine patch and capsule treatment in Alzheimer's disease.

BACKGROUND: Vascular risk factors (VRF) may influence response to rivastigmine in Alzheimer's disease (AD). METHODS: AD patients who participated in a randomized, double-blind, placebo-controlled trial of rivastigmine patch and capsule treatment were stratified by baseline VRF status. Treatment response was evaluated using the AD Assessment Scale-cognitive subscale (ADAS-cog), AD Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) and the AD Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. RESULTS: ADAS-cog scores significantly improved in all rivastigmine-treated patients (p < 0.05 vs. placebo), except 9.5 mg/24 h patch-treated patients with VRF, and were significantly affected by VRF status in the study population as a whole. Significant benefits were seen on the ADCS-ADL in 9.5 mg/24 h patch- and capsule-treated patients with, but not without, VRF. The ADCS-CGIC significantly improved in capsule-treated patients with, and patch-treated patients without VRF. Although non-significant, patients without VRF showed an apparent faster rate of placebo decline. CONCLUSION: VRF may influence AD progression and response to rivastigmine.

Early experience of tomotherapy-based intensity-modulated radiotherapy for breast cancer treatment.

AIMS: New technology - specifically intensity-modulated radiotherapy (IMRT) - is now being applied to breast radiotherapy and a recent dosimetric analysis confirmed the advantages of IMRT over 'wedge-only' plans. Such application to everyday practice raises new issues and here we present the early experience of IMRT-based breast irradiation in a single centre. MATERIALS AND METHODS: We present cases of breast cancer treated by Tomotherapy-based IMRT, where the perceived advantages of IMRT are considerable. Cases presented are bilateral disease, left breast irradiation, pectus excavatum, prominent contralateral prosthesis and internal mammary chain disease. We discuss the practicalities of such treatment and the advantages over standard breast irradiation techniques. RESULTS: Advantages include better conformity of treatment with lowering of dosages to underlying organs at risk, for example ipsilateral lung and heart. There is improved coverage of the planning target volume, including regional nodes, without field junction problems. Planning, quality assurance and treatment delivery are more time consuming than for standard breast irradiation and the low dose 'bath' is increased. CONCLUSIONS: The standard radiotherapy tangential technique for breast/chest wall treatments has not significantly changed over many decades, whereas across many other tumour sites there have been great advances in radiotherapy technology. The dosimetric advantages of IMRT are readily apparent from our early experience. The wider spread of the lower dose zone (the low dose 'bath' of radiation) is a potential concern regarding late oncogenesis and methods to minimise such risks should be considered.

Performance of lactating dairy cows fed ryegrass silage and corn silage with ground corn, steam-flaked corn, or hominy feed.

Forty-eight mid-lactation Holstein cows were used in a 6-wk completely randomized block design trial with a 4 x 3 factorial arrangement of treatments to determine the effects of feeding different proportions of corn silage and ryegrass silage with supplemental ground corn (GC), steam-flaked corn (SFC), and hominy feed (HF) on the performance of lactating dairy cows. Forage provided 49% of the dietary dry matter in the experimental diets, which were formulated to meet National Research Council requirements. Ryegrass silage provided 100, 75, 50, or 25% of the total forage dry matter, with corn silage supplying the remainder. There were no interactions between the proportion of forage provided by ryegrass silage and energy supplement. Dry matter intake and milk protein percentage decreased linearly with increasing proportions of ryegrass silage, but milk protein yield was similar among forage treatments. There were no differences among forage treatments in milk yield, milk fat percentage and yield, and energy-corrected milk yield. Dry matter intake was higher and there was a tendency for increased milk fat percentage for GC compared with SFC or HF. No other differences were observed in milk yield or composition among energy supplements. Plasma urea nitrogen and glucose concentrations were similar among treatments. Under the conditions of this trial, our results indicate that feeding a combination of corn silage and ryegrass silage is more desirable than feeding ryegrass silage alone, whereas supplementation with GC, SFC, or HF supports similar levels of milk production.

Indications for tomotherapy/intensity-modulated radiation therapy in paediatric radiotherapy: extracranial disease.

The potential conformality advantages of intensity-modulated radiation therapy (IMRT; TomoTherapy Hi Art system) over conventional linear accelerator based therapy was assessed in six consecutive children referred for extracranial radiotherapy. IMRT/tomotherapy was considered advantageous for (i) small abdominal tumours, compared with parallel opposed or single portal technology using a conventional linear accelerator, and (ii) re-treatment of an ethmoidal sarcoma, but not for palliation of a small spinal metastasis, or therapy for a whole deep cervical node chain or a pelvic side wall tumour in a young child. Considerations integral to the treatment decision included target volume dose conformality, "low-dose bath" effects (oncogenic and late growth sequelae) and treatment delivery time. IMRT/tomotherapy was the selected modality for therapy when the conformality advantages were perceived to outweigh any disadvantages in three out of the six cases. The dose conformality advantages of IMRT/tomotherapy are sufficient to selectively recommend its availability to the paediatric practice in accordance to the following criteria: (i) where conformality of radiation therapy to the target/tumour is critical and where the margin of safety (from gross/clinical target volume to planning target volume (PTV)) around the tumour is narrow; (ii) where adjacent organs at risk of radiation damage have a low threshold for damage; and (iii) where the "low-dose bath" phenomenon, which occurs between the upper and lower axial limits of the PTV, is not sufficiently disadvantageous (with regard to late oncogenesis or growth retardation) to outweigh the more confined (non-tumour) integral doses received in higher dose corridors through the body when utilizing conventional radiation techniques.

Performance of dairy cows fed annual ryegrass silage and corn silage with steam-flaked or ground corn.

Twenty-four lactating Holstein cows were used in a 6-wk randomized block design trial with a 2 x 2 factorial arrangement of treatments to determine the effects of feeding ground corn (GC) or steam-flaked corn (SFC) in diets based on either annual ryegrass silage (RS) or a 50:50 blend of annual ryegrass and corn silages (BLEND). Experimental diets contained 49.6% forage and were fed as a total mixed ration once daily for 4 wk after a 2-wk preliminary period. No interactions were observed among treatments. Cows fed BLEND consumed more dry matter (DM), organic matter (OM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) than those fed RS, but total-tract digestibility of OM, NDF, and ADF was greater for RS than for BLEND. No differences in nutrient intake were observed among treatments during wk 4 when nutrient digestibility was measured, but digestibility of DM and OM was greater for SFC than for GC. Cows fed BLEND tended to produce more energy-corrected milk than those fed RS, resulting in improved efficiency (kg of milk per kg of DM intake). When diets were supplemented with SFC, cows consumed less DM and produced more milk that tended to have lower milk fat percentage. Yield of milk protein and efficiency was greatest with SFC compared with GC. Blood glucose and milk urea nitrogen concentrations were similar among treatments, but blood urea nitrogen was greater for cows fed GC compared with those fed SFC. Results of this trial indicate that feeding a blend of annual ryegrass and corn silage is more desirable than feeding diets based on RS as the sole forage. Supplementing diets with SFC improved performance and efficiency compared with GC across forage sources.

A dosimetric comparison between two intensity-modulated radiotherapy techniques: tomotherapy vs dynamic linear accelerator.

This manuscript describes a direct comparison between radiation treatment plans in terms of dosimetric outcomes created by two different IMRT systems: TomoTherapy HiArt and dynamic linac intensity-modulated radiotherapy (dIMRT). Three patient cases were selected (with disease in different anatomical areas): vertebral metastasis re-treatment, radical prostate therapy and an ethmoid sarcoma re-treatment. Each case presents significant and varying dosimetric difficulties with respect to avoidance of adjacent organs. The patients were each planned and treated at the Cromwell Hospital (London, UK) using the TomoTherapy HiArt system, with planning replicated at St Bartholomew's Hospital (London, UK) using Eclipse Treatment Planning System and a 6EX linac with a 120-leaf multileaf collimator (Varian Medical Systems). For both modalities, all treatment plans conformed to the stringent clinical dose constraints set. For the vertebral body re-treatment, both techniques demonstrated adequate and similar planning target volume (PTV) coverage and sparing of the spinal cord. The critical structure sparing and PTV coverage for the prostate treatment was again similar for both modalities. For re-treatment of the paediatric ethmoid sarcoma, tomotherapy was able to produce slightly better organ sparing whilst producing PTV coverage similar to linac dIMRT. The data presented in this manuscript demonstrate subtle dosimetric differences between the two techniques but no marked advantage with either system. Therefore, other factors may need to be considered when making a decision between tomotherapy and linac dIMRT.

Predictors of oxygen uptake and performance during tennis.

Tennis ball machine tests permit the concurrent measurement of physiological function and groundstroke performance in a sport specific manner. The purpose of this study was to understand further the demands of groundstroke performance during a test with progressively increasing ball frequency, by determining the running speed between strokes, upper and lower limb acceleration and pulmonary gas exchange throughout. Sixteen tennis players (n = 8, male; n = 8, female; all right handed) completed three 4 min stages of hitting against a ball feed frequency of 15, 20, 25 ball.min(-1) interspersed by 8 min of rest. Stepwise multiple regression analysis identified a predictive model of VO2 containing the variables of left arm acceleration and right ankle acceleration but not running speed (p < 0.0001; adjusted r2 = 0.93; left wrist acceleration Beta = 1.04; right ankle acceleration Beta = - 0.12; S. E. E. = 2.61 ml.kg(-1).min(-1)). Regression analysis found that the strongest predictors of stroke performance (ball speed [m.s(-1)] x stroke accuracy [%]) were right wrist acceleration and stroke economy (p < 0.0001; adjusted r2 = 0.28; right wrist acceleration Beta = - 0.59; movement economy Beta = - 0.28). The findings of this study highlight the contribution of limb acceleration and not running speed to the oxygen cost of tennis groundstroke performance.

Performance and ruminal fermentation of dairy cows fed whole cottonseed with elevated concentrations of free fatty acids in the oil.

Twenty-four lactating Holstein cows were used in an 8-wk completely randomized design trial to examine the effects of feeding whole cottonseed (WCS) with elevated concentrations of free fatty acids (FFA) in the oil on intake and performance. Treatments included WCS with normal concentrations of FFA (6.8%, control) and 2 sources of WCS with elevated FFA [HFFA1 (24.1%) or HFFA2 (22.3%)]. The 2 sources of WCS with elevated FFA differed in that HFFA2 were discolored from being initially stored with excess moisture, which led to heating and deterioration during storage, whereas HFFA1 were normal in appearance and the increase in FFA occurred without heating and visible damage to the WCS. Nutrient concentrations were similar among WCS treatments, which provided 14% of the total dietary dry matter. Dry matter intake tended to be higher for cows fed HFFA2 compared with control and HFFA1. Yield of milk and components was similar among treatments, but milk fat percentage was lower for HFFA1 and HFFA2 compared with control. In a concurrent 3 x 3 Latin square trial with 6 ruminally cannulated Holstein cows, molar proportions of isobutyrate were higher for HFFA2 than control and HFFA1, but no differences were observed in acetate or propionate. Results of these trials indicate that feeding WCS with high concentrations of FFA decreases milk fat percentage but does not alter dry matter intake, milk yield, or concentrations of other components. The minor changes in ruminal fermentation that were observed do not account for the decrease in milk fat percentage.

Performance of lactating dairy cows fed whole cottonseed coated with gelatinized starch plus urea or yeast culture.

Thirty lactating Holstein cows were used in an 8-wk randomized design trial to test the viability of select additives included in the gelatinized corn starch coating applied to whole cottonseed (WCS) on nutrient intake and digestibility and milk yield and composition. Treatments included WCS coated with 2.5% gelatinized corn starch (control); control plus 0.5% urea; or control plus 2.0% yeast culture. The treated WCS represented 12.6% of the dietary dry matter. Cellulose intake was lower for the control coating compared with either the urea or yeast coating because of slightly lower cellulose concentrations in the control treatment. Intake of all other nutrients was similar for all treatments. Whole-tract nutrient apparent digestibility was not altered by treatment. Dry matter intake and milk yield were similar among treatments. Percentage solids-not-fat was lower for the yeast treatment compared with control, but no other differences were observed in milk composition among treatments. Efficiency of milk production (energy-corrected milk yield per unit of dry matter intake) was higher for the urea and yeast treatments compared with control because of slightly higher yield of milk fat and energy-corrected milk. No differences were observed in body weight change during the trial between treatments. Results of this trial indicate that including urea or yeast culture in the gelatinized starch coating does not change whole tract digestibility, but does improve milk production efficiency.

The reliability and validity of a field hockey skill test.

High test retest reliability is essential in tests used for both scientific research and to monitor athletic performance. Thirty-nine (20 male and 19 female) well-trained university field hockey players volunteered to participate in the study. The reliability of the in house designed test was determined by repeating the test (3 - 14 days later) following full familiarisation. The validity was assessed by comparing coaches ranks of players with ranked performance on the skill test. The mean difference and confidence limits in overall skill test performance was 0.0 +/- 1.0 % and the standard error (confidence limits) was 2.1 % (1.7 to 2.8 %). The mean difference and confidence limits for the "decision making" time was 0.0 +/- 1.0 % and the standard error (confidence limits) was 4.5 % (3.6 to 6.2 %). The validity correlation (Pearson) was r = 0.83 and r = 0.73 for female players and r = 0.61 and r = 0.70 for male players for overall time and "decision making" time respectively. We conclude that the field hockey skill test is a reliable measure of skill performance and that it is valid as a predictor of coach-assessed hockey performance, but the validity is greater for female players.

The use of laparoscopic liver biopsies in pediatric patients with hepatic dysfunction following allogeneic hematopoietic stem cell transplantation.

Hepatic dysfunction following hematopoietic stem cell transplantation (HSCT) is common, but making the correct diagnosis can be challenging. Liver biopsies can serve as an important diagnostic tool when the etiology cannot be clearly determined by laboratory data, physical examination, and imaging studies. We reviewed 12 consecutive pediatric patients (seven males, five females, age 9-23 years) who received allogeneic HSCT and underwent a laparoscopic-guided liver biopsy for hepatic dysfunction of unknown etiology from 1998 to 2005. Biopsies were performed using a single-port technique with a 16 or 18 gauge, spring-loaded biopsy gun. The time from HSCT to biopsy ranged from 31 days to 821 days (median 92 days). No intra- or postoperative complications were observed. The initial clinical diagnosis was confirmed in seven patients, whereas the initial working diagnosis was inaccurate in the remaining five patients. Our results suggest that laparoscopic-guided liver biopsy is an informative and safe procedure in pediatric HSCT recipients; this approach helped delineate the true cause of hepatic dysfunction and changed our therapeutic approach in approximately 40% of the patients reviewed. While the safety record at our institution appears promising, a larger multi-institutional study would be necessary to more accurately describe the overall efficacy of this procedure in pediatric HSCT patients.