Tumor-specific but not nonspecific cell-free circulating DNA can be used to monitor disease response in lymphoma

Recently, nontumor specific circulating DNA was shown to be elevated in a broad range of lymphomas, implicating a role as a potential biomarker. Epstein-Barr virus' (EBV) presence within a proportion of lymphomas implies EBV-DNA has potential as a lymphoma-specific disease response biomarker. However, application would be restricted to EBV-associated lymphomas. Neither detailed comparison has been performed of lymphoma-specific versus nonspecific DNA as disease response biomarkers nor have the kinetics of circulating DNA during treatment been established, and the optimal methodology remains unknown. We prospectively evaluated DNA levels and clinical response of 63 lymphoma patients. DNA was measured in paired serum, plasma, and cell samples at five predetermined time-points taken prior, during and following treatment. Both cell-free (c-f) circulating EBV-DNA (in EBV-associated lymphoma) and nonspecific c-f DNA levels (in all lymphomas) were elevated and discriminatory at presentation compared to healthy controls. Nonspecific c-f DNA was significantly associated with baseline serum lactate dehydrogenase. Within EBV-associated lymphomas at presentation, there was a strong correlation between specific and nonspecific circulating c-f DNA (r = 0.9, P < 0.0001). However, only c-f EBV-DNA correlated with clinical/radiological response. In addition, c-f EBV-DNA, and not nonspecific c-f DNA, provided an early marker of relapsed and refractory disease. Serum versus plasma, and single versus multiple-copy EBV-gene targets were equivalent. Lymphoma-specific DNA is a disease response biomarker; however, nonspecific DNA reflected neither lymphoma-specific DNA nor therapeutic response. Lymphoma disease response can be monitored by blood tests, but new lymphoma-specific biomarkers need to be identified to broaden applicability.     

Evaluation of fluorescent plasma markers for in vivo microscopy of the microcirculation

This study evaluated four fluorescent-protein conjugates to monitor microcirculatory variables using the murine cremaster muscle and determined acute and long-term responses to repeated administration of FITC-BSA [conjugated at the University of Sheffield (UoS)] within a dorsal microcirculatory chamber (DMC) in rats. For analysis of the cremaster muscle, male C3H/HeN mice were anaesthetized, the cremaster muscle was exteriorized, then TRITC-BSA, TRITC-dextran, FITC-BSA, FITC-BSA (UoS) or FITC-dextran (0.25 ml/100 g) were administered systemically. The microcirculation was viewed with epi-illumination every 10 min for 120 min. For analysis of the DMC, male Wistar rats were implanted with the chamber. Three weeks later, FITC-BSA (UoS) was administered systemically, and the microcirculation response was monitored using three different protocols. In addition, in vitro stability of fluorescent conjugates was measured over 8 h. With regard to the cremaster muscle, initially no differences in interstitial fluorescence or vessel diameter were observed between the four fluorescent conjugates. By the end of the study, interstitial fluorescence from TRITC-dextran, FITC-dextran and FITC-BSA (Sigma) was significantly (p < 0.05) increased compared to FITC-BSA (UoS). With regard to the DMC, there was no interstitial fluorescence leakage after 180 min or 5 weeks despite repeated administration, but a significant (p < 0.05) leak was detected between 4 and 24 h. FITC-BSA (UoS) was the most stable fluorescent conjugate both in vitro and in vivo and was comparable with other conjugates for evaluating skeletal muscle microcirculation using fluorescent in vivo microscopy.     

Using transprofessional care in the emergency department to reduce patient admissions: A retrospective audit of medical histories

The demand for emergency department (ED) services has increased significantly, due to our increasingly ageing population and limited access to primary care. This article reports outcomes from a transprofessional model of care in an ED in Victoria, Australia. Nurses, physiotherapists, social workers, and occupational therapists undertook additional education to increase the range of services they could provide and thereby expedite patient flow through the ED. One hundred patients who received this service were matched against 50 patients who did not. The most common reasons for patient admission were limb injury/limb pain (n = 47, 23.5%) and falls (n = 46, 23.0%). Transprofessional interventions included applying supportive bandages, slings, zimmer splints and controlled ankle motion (CAM) boots, and referral to new services such as case management and mental health teams. The rate of hospital admissions was significantly lower in the transprofessional group (n = 27, 18.0%) than in the reference group (n = 19, 38%, p = 0.005). This group also had a slightly lower re-presentation rate (n = 4, 2.7%) than patients in the reference group (n = 2, 4.0%). There are many benefits that support this model of care that in turn reduces ED overcrowding and work stress. A transprofessional model may offer a creative solution to meeting the varied needs of patients presenting for emergency care.     

Alcohol-related affordances and group subjectivities: A Q-Methodology study

Aims: An Ecological approach to alcohol behaviour focuses on understanding individual–environment transactions, rather than on cognitive antecedents of behaviour. Meaning exists in the interdependence of individuals and their environments, in terms of affordances. Through subjective experience, this study focussed on group viewpoints related to alcohol-related affordances, or opportunities to consume alcohol in shared drinking environments. Methods: Forty students with a range of self-reported drinking behaviours participated in a Q-Methodology study, ranking 60 statements along a symmetrical grid. This varied concourse of alcohol-related affordances was obtained from a previous observation study within licenced premises and a photo-elicitation interview study with drinkers. Findings: Factor analysis and post-sort interviews revealed four subjective perspectives held by groups about their drinking behaviour: 13 participants were aware of contextual influences, but autonomous in their drinking choices; 12 participants were conscious of influences and compliant to their effects; six participants were unaware of influences, but unanimous with their peers; two participants were concerned about acting appropriately in a context by taking up canonical affordances. Conclusions: Grouping subjectivities from a varied concourse of affordances can reveal subjective experience in relation to drinking environments and alcohol behaviour. This conceptual approach for understanding drinking behaviour should be studied further.     

The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

Heart Failure Reviews - The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important...     

Weight status and breast cancer incidence in the UK Women's Cohort Study: a survival analysis

BackgroundBreast cancer is the most common type of cancer in the UK, even though it predominantly affects women. Some research suggests that obesity before menopause can be protective against breast cancer, whereas postmenopausal obesity poses increased risk. Because of a period of latency in the development of cancer, longitudinal cohort studies are essential. The aim of this research was to investigate the association between body-mass index (BMI) and breast cancer incidence.MethodsThe UK Women's Cohort Study was established in the 1990s to investigate patterns between diet and health. 35 000 women were recruited and followed up via cancer incidence and mortality data reports from the National Health Service information centre. Self-reported height and weight were used to calculate BMI. WHO cut-off points were used to define BMI categories. Age-adjusted Cox proportional hazards regression was applied with Stata (version IC12).Findings1445 (4%) of 35 372 women developed breast cancer during a median time to follow-up of 14·9 years (IQR 1·4). Cases prevalent at baseline were excluded. There were significant differences between the observed and expected outcomes by BMI category (p=0·0003, log-rank test), with underweight and normal weight having lower observed than expected incidence. Overweight and obese women had higher observed than expected incidence. Test for trend of survivor functions showed a significant trend of increasing breast cancer incidence with increasing BMI for the whole cohort (p=0·0001) and the postmenopausal subgroup (p=0·0001), but not for premenopausal women. Hazard ratios in an age-adjusted model were significant in postmenopausal women: underweight 1·0 (reference); normal weight 1·6, 95% CI 0·8–3·2; overweight 2·0, 1·0–4·1; obese 2·1, 1·0–4·3.InterpretationWe found a clear association between BMI and breast cancer incidence, especially in postmenopausal women. We did not see an association in premenopausal women. These results are supportive of existing scientific literature and highlight the importance of maintaining a healthy weight in adulthood, especially after the menopause. Health-care professionals should consider referral of overweight and obese women to weight loss services as a protective measure before menopause.FundingThis research was funded as part of an Economic and Social Research Council/Medical Research Council interdisciplinary PhD studentship.