Polymerase chain reaction based methods for assessing chimerism following allogeneic bone marrow transplantation

It is important to be able to assess the contribution of donor cells to the graft followmg bone marrow transplantation (BMT), as complete engraftment of marrow progenitors that can give rise to long term donor derived hemopoiesis may be important in long-term disease-free survival. The contribution of the donor marrow, both in terms of filling the marrow "space" created by the intense conditioning regimen and in its ability to mediate a graft versus leukemia effect may be assessed by studying the kinetics of the engraftment process. As BMT involves repopulation of the host hemopoietic system with donor cells, recipients of allogeneic marrow are referred to as hemopoietic chimeras. A donor chimera is an individual who exhibits complete donor hemopoiesis and we would imagine that donor chimertsm carries the best long-term prognosis. A patient who has both donor and recipient cells coexistmg in a stable fashion post-BMT without hematological evidence of relapse or graft rejection is referred to as a mixed chimera. Mixed chimerism may be a prelude to graft rejection or leukemic relapse; therefore, it is important to be able to monitor the presence of these cells in a precise manner.

Empathy in UK pharmacy students: assessing differences by gender, level in the degree programme, part-time employment and medical status

Background: Empathy is an important aspect of patient–healthcare professional interactions.Aims: To investigate whether gender, level in the degree programme, employment and health status affected empathy scores of undergraduate pharmacy students.Method: All undergraduate pharmacy students (n=529) at Queen’s University Belfast were invited via email to completean online validated empathy questionnaire. Empathy scores were calculated and non-parametric tests used to determine associations between factors.Results: Response rate was 60.1% (318/529) and the mean empathy score was 106.19. Scores can range from 20 to 140,with higher scores representing a greater degree of empathy. There was no significant difference between genders (p=0.211). There was a significant difference in scores across the four levels of the programme (p<0.001); scores were lowest at Level 1 and greatest at Level 4 (final year). There were no significant differences in scores for respondents who had a part-time job, a chronic condition, or took regular medication in comparison to those who did not (p=0.028,p=0.880, p=0.456, respectively).Conclusion: A reasonable level of empathy was found relative to other studies; this could be further enhanced at lower levels of the degree pathway.

Assessing the in vivo efficacy of biologic antiangiogenic therapies

PURPOSE: To review key clinical issues underlying the assessment of in vivo efficacy when using antiangiogenic therapies for cancer treatment.

METHODS: Literature relevant to use of antiangiogenic therapies in cancer was reviewed, with particular emphasis on the assessment of in vivo efficacy of these agents, as well as additional angiogenic factors that could play a role in escape from angiogenesis inhibition.

RESULTS: In order to grow and metastasize, tumors need to continually acquire new blood supplies; therefore, therapeutic inhibition of angiogenesis has become a component of anticancer treatment for many tumor types. Bevacizumab, a humanized monoclonal antibody directed at vascular endothelial growth factor A (VEGF-A), has shown activity in combination with chemotherapy in metastatic colorectal cancer. Nevertheless, the use of antiangiogenic therapies remains suboptimal; specifically, optimal dose, duration of therapy, and combination of agents remain unknown. Also, at present, it is not possible to determine which patients are most likely to respond to a given form of antiangiogenic therapy. There has been increased recognition of alternative pathways possibly associated with disease progression in patients undergoing antiangiogenic therapy targeted at VEGF-A. Multiligand-targeted antiangiogenic therapies, such as ziv-aflibercept (formerly known as aflibercept, VEGF Trap), are currently undergoing clinical evaluation. Ziv-aflibercept forms monomeric complexes with VEGF-A, VEGF-B, and PlGF, which have a long half-life, allowing optimization of ziv-aflibercept doses and angiogenic blockage.

CONCLUSIONS: Although antiangiogenic therapies have increased treatment options for cancer patients, their use is limited by a lack of established and standardized methodology to evaluate their efficacy in vivo. Circulating endothelial cells, hypertension, and several molecular and imaging-based markers have potential for use as biomarkers in these patients and may better define appropriate patient populations.

Heller's myotomy and pneumatic dilatation in the treatment of achalasia: a population-based case–control study assessing long-term quality of life

Long-term health-related quality-of-life (HRQL) outcomes have not been widely reported in the
treatment of achalasia. The aims of this study were to examine long-term disease-specific and general HRQL in
achalasia patients using a population-based case–control method, and to assess HRQL between treatment interventions.
Manometrically diagnosed achalasia cases (n = 120) were identified and matched with controls (n = 115)
using a population-based approach. Participants completed general (SF-12) and disease-specific (Achalasia Severity
Questionnaire [ASQ]) HRQL questionnaires, as appropriate, in a structured interview. Mean composite scores
for SF-12 (Mental Component Summary score [MCS-12] and Physical Component Summary score [PCS-12]) and
ASQ were compared between cases and controls, or between intervention groups, using an independent t-test.
Adjusted mean differences in HRQL scores were evaluated using a linear regression model. Achalasia cases were
treated with a Heller’s myotomy (n = 43), pneumatic dilatation (n = 44), or both modalities (n = 33). The median
time from last treatment to HRQL assessment was 5.7 years (interquartile range 2.4–11.5). Comparing achalasia
patients with controls, PCS-12 was significantly worse (40.9 vs. 44.2, P = 0.01), but MCS-12 was similar. However,
both PCS-12 (39.9 vs. 44.2, P = 0.03) and MCS-12 (46.7 vs. 53.5, P = 0.004) were significantly impaired in those
requiring dual treatment compared with controls. Overall however, there was no difference in adjusted HRQL
between patients treated with Heller’s myotomy, pneumatic dilatation or both treatment modalities. In summary,
despite treatment achalasia patients have significantly worse long-term physical HRQL compared with population
controls. No HRQL differences were observed between the treatment modalities to suggest a benefit of one
treatment over another.

Towards a Mobile Assistive Technology for Monitoring and Assessing Cognitive Fatigue in Individuals with Acquired Brain Injury

Those living with an acquired brain injury often have issues with fatigue due to factors resulting from the injury. Cognitive impairments such as lack of memory, concentration and planning have a great impact on an individual’s ability to carry out general everyday tasks, which subsequently has the effect of inducing cognitive fatigue. Moreover, there is difficulty in assessing cognitive fatigue, as there are no real biological markers that can be measured. Rather, it is a very subjective effect that can only be diagnosed by the individual. Consequently, the traditional way of assessing cognitive fatigue is to use a self-assessment questionnaire that is able to determine contributing factors. State of the art methods to evaluate cognitive! fa tigue employ cognitive tests in order to analyse performance on predefined tasks. However, one primary issue with such tests is that they are typically carried out in a clinical environment, therefore do not have the ability to be utilized in situ within everyday life. This paper presents a smartphone application for the evaluation of fatigue, which can be used daily to track cognitive performance in order to assess the influence of fatigue.

The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis

BACKGROUND: Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan.

RESULTS: Thirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration.

CONCLUSIONS: Concomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009).

Repeatability and reliability of new air and water permeability tests for assessing the durability of high-performance concretes

This paper reports on the accuracy of new test methods developed to measure the air and water permeability of high-performance concretes (HPCs). Five representative HPC and one normal concrete (NC) mixtures were tested to estimate both repeatability and reliability of the proposed methods. Repeatability acceptance was adjudged using values of signal-noise ratio (SNR) and discrimination ratio (DR), and reliability was investigated by comparing against standard laboratory-based test methods (i.e., the RILEM gas permeability test and BS EN water penetration test). With SNR and DR values satisfying recommended criteria, it was concluded that test repeatability error has no significant influence on results. In addition, the research confirmed strong positive relationships between the proposed test methods and existing standard permeability assessment techniques. Based on these findings, the proposed test methods show strong potential to become recognized as international methods for determining the permeability of HPCs.

Farm animal welfare:Assessing risks attributable to the prenatal environment

An ever-expanding scientific literature highlights the impact of the prenatal environment on many areas of biology. Across all major farmed species, experimental studies have clearly shown that prenatal experiences can have a substantial impact on outcomes relevant to later health, welfare and productivity. In particular, stress or sub-optimal nutrition experienced by the mother during pregnancy has been shown to have wide-ranging and important effects on how her offspring cope with their social, physical and infectious environment. Variation in the conditions for development provided by the reproductive tract or egg, for instance by altered nutritional supply or hormonal exposure, may therefore explain a large degree of variation in many welfare- and productivity-relevant traits. The scientific literature suggests a number of management practices for pre-birth/hatch individuals that could compromise their later welfare. Such studies may have relevance for the welfare of animals under human care, depending on the extent to which real life conditions involve exposure to these practices. Overall, the findings highlight the importance of extending the focus on animal welfare to include the prenatal period, an aspect which until recently has been largely neglected. © 2012 Universities Federation for Animal Welfare The Old School.

Assessing the impact of shore-based shellfish collection on under-boulder communities in Strangford Lough.

Under-boulder communities are listed as a priority habitat as they provide shelter, shade and moisture and play an important role in the life-cycle of many marine algae and animals.

Assessing elements of a family approach to reduce adolescent drinking frequency: parent-adolescent relationship, knowledge management, and keeping secrets

AIMS: To estimate 1) the associations between parent-adolescent relationship, parental knowledge and subsequent adolescent drinking frequency and 2) the influence of alcohol use on parental knowledge.

DESIGN: Path analysis of school based cohort study with annual surveys SETTING: Post primary schools from urban and intermediate/rural areas in Northern Ireland PARTICIPANTS: 4,937 post primary school students aged around 11 years in 2000 followed until around age 16 in 2005.

MEASUREMENTS: Pupil reported measures of: frequency of alcohol use; parental-child relationship quality; sub-dimensions of parental monitoring: parental control, parental solicitation, child disclosure and child secrecy.

FINDINGS: Higher levels of parental control (Ordinal logistic OR 0.86 95% CI 0.78, 0.95) and lower levels of child secrecy (OR 0.83 95% CI 0.75 0.92) were associated with less frequent alcohol use subsequently. Parental solicitation and parent-child relationship quality were not associated with drinking frequency. Weekly alcohol drinking was associated with higher subsequent secrecy (Beta -0.42 95% CI -0.53, -0.32) and lower parental control (Beta -0.15 95% CI -0.26, -0.04). Secrecy was more strongly predictive of alcohol use at younger compared with older ages (P=0.02), and alcohol use was less strongly associated with parental control among families with poorer relationships (P=0.04).

CONCLUSIONS: Adolescent alcohol use appears to increase as parental control decreases and child secrecy increases. Greater parental control is associated with less frequent adolescent drinking subsequently, while parent-child attachment and parental solicitation have little influence on alcohol use.