Common community acquired infections and subsequent risk of chronic lymphocytic leukaemia

Emerging evidence supports a role for immune-related factors in the causation of chronic lymphocytic leukemia (CLL). Using the population-based U.S. SEER-Medicare database, we identified 10,171 elderly CLL patients and 122,531 frequency-matched controls to evaluate several community acquired infections associated with subsequent CLL risk. Odds ratios (ORs) were adjusted for gender, age, race, calendar year, and number of physician claims. We found increased CLL risk following Medicare claims for sinusitis (OR=1.11; 95%CI=1.05–1.17), pharyngitis (OR=1.15; 1.08–1.22), bronchitis (OR=1.14; 1.08–1.19), pneumonia (OR=1.17; 1.11–1.24), influenza (OR=1.10; 1.01–1.19), cellulitis (OR=1.08; 1.02–1.14), and herpes zoster (OR=1.26; 1.15–1.37). Associations with pneumonia and cellulitis remained significant when the 5-year period before diagnosis/control was excluded. CLL risk increased with increasing severity/frequency of pneumonia (p=0.005), cellulitis (p<0.001), and herpes zoster (p<0.001). Our findings suggest that common infections may play a role in CLL etiology. Alternatively, the associations might reflect an underlying immune disturbance present several years prior to CLL diagnosis

Using High Throughput Genomic Sequencing to Predict Ecological Impacts on Sea Turtle Populations

Marine turtles are long-lived, migratory vertebrates that encounter a variety of human and natural stressors throughout their lives. Understanding the biology and threats of these animals is challenging because they are hard to observe, and can migrate across whole ocean basins. Minimally invasive sampling techniques (e.g., blood samples) allow us to learn about their physiology, genetics, and the environmental conditions they have experienced. In this project, we developed a novel method to extract the RNA from whole green and loggerhead turtle blood from animals inhabiting a variety of sites across the Pacific Ocean. Some habitats are more pristine, while others have been heavily altered by humans. These samples will be used for high throughput genomic sequencing to provide data on the gene expression, genetic relatedness, and functional genomics of these animals. First, we will look at the genes that are up-regulated in animals inhabiting polluted environments to understand contaminant impacts on marine turtle health. Secondly, we will identify single nucleotide polymorphisms that will be used as tools in future studies to examine fine-scale structure and adaptive variation in future studies. We then pair these data with other data from our research group on sex, size, migration, and foraging ecology. These approaches allow us to generate large amounts of data that can be used for a variety of scientific and conservation studies from small samples. This allows us to sample the animals while having little to no impact, and to monitor health and physiology in live populations over time. This will provide a better understanding of threats to sea turtle populations that can be used by both conservation biologists and ecologists in protecting habitats of sea turtles worldwide

The SPARC Data Initiative: comparisons of CFC-11, CFC-12, HF and SF6 climatologies from international satellite limb sounders

A quality assessment of the CFC-11 (CCl3F), CFC-12 (CCl2F2), HF, and SF6 products from limb-viewing satellite instruments is provided by means of a detailed intercomparison. The climatologies in the form of monthly zonal mean time series are obtained from HALOE, MIPAS, ACE-FTS, and HIRDLS within the time period 1991–2010. The intercomparisons focus on the mean biases of the monthly and annual zonal mean fields and aim to identify their vertical, latitudinal and temporal structure. The CFC evaluations (based on MIPAS, ACE-FTS and HIRDLS) reveal that the uncertainty in our knowledge of the atmospheric CFC-11 and CFC-12 mean state, as given by satellite data sets, is smallest in the tropics and mid-latitudes at altitudes below 50 and 20 hPa, respectively, with a 1σ multi-instrument spread of up to ±5 %. For HF, the situation is reversed. The two available data sets (HALOE and ACE-FTS) agree well above 100 hPa, with a spread in this region of ±5 to ±10 %, while at altitudes below 100 hPa the HF annual mean state is less well known, with a spread ±30 % and larger. The atmospheric SF6 annual mean states derived from two satellite data sets (MIPAS and ACE-FTS) show only very small differences with a spread of less than ±5 % and often below ±2.5 %. While the overall agreement among the climatological data sets is very good for large parts of the upper troposphere and lower stratosphere (CFCs, SF6) or middle stratosphere (HF), individual discrepancies have been identified. Pronounced deviations between the instrument climatologies exist for particular atmospheric regions which differ from gas to gas. Notable features are differently shaped isopleths in the subtropics, deviations in the vertical gradients in the lower stratosphere and in the meridional gradients in the upper troposphere, and inconsistencies in the seasonal cycle. Additionally, long-term drifts between the instruments have been identified for the CFC-11 and CFC-12 time series. The evaluations as a whole provide guidance on what data sets are the most reliable for applications such as studies of atmospheric transport and variability, model–measurement comparisons and detection of long-term trends. The data sets will be publicly available from the SPARC Data Centre and through PANGAEA (doi:10.1594/PANGAEA.849223)

Validity of the Actigraph GT3X accelerometer in identification of body position and step count in adult hospitalised patients recovering from critical illness

Purpose: Physical recovery from critical illness is complicated by neuromuscular weakness. Evidence suggests mobility commencing within the intensive care unit results in improved function upon discharge. Despite this, persistent inactivity is reported throughout hospital admission. Greater attention should be given to monitoring activity in this setting. Observation and self-report methods may encounter difficulties. Activity monitors (accelerometers) may offer a solution. This PhD thesis aimed to systematically review evidence investigating the validity of accelerometry to quantify purposeful activity within hospitalised adults experiencing acute or critical illness. It also aimed to investigate the validity of the Actigraph GT3X accelerometer in identification of body position (lying, sitting and standing) and step count in patients recovering from critical illness. Methods: A systematic review explored how accelerometer validity had previously been investigated within acute and critically ill hospitalised populations. Another study investigated the feasibility of the GT3X to identify body position and quantify typical activities undertaken by patients’ recovering from critical illness. Thirty healthy participants (mean age 58.8, SD 6.8) simulated this patient group, performing a movement protocol. Twenty ward based patients’ (mean age 62.3, SD 11.5), who had required prolonged ventilation in the ICU (≥ 48 hours) also completed a movement protocol containing typical daily activities. The validity of the GT3X to identify body position and step count was investigated using observation as the criterion measure. Results: A median (interquartile range) of Kappa = 0.94 (0.90, 0.98) for identification of body position was determined interpreting data from two GT3X accelerometers positioned in combination at the ankle and thigh. A mean difference (95% limits of agreement) of -0.84 steps (2.2 to -3.88) compared to observation was found for the ankle placement in step count quantification. Conclusions: The GT3X accelerometer is valid in identification of body position when positioned in combination on the thigh and ankle of the non-dominant leg in patients recovering from critical illness. An ankle placement is valid in quantification of step count

The role of the immune system in regression of the bovine corpus luteum

In recent years there has been increasing interest in the role of the immune system in reproductive physiology. The aim of this study was to quantify immune cell populations within the cow corpus luteum (CL) throughout the oestrous cycle in order to investigate whether these cells could be involved in controlling luteal function, particularly around the time of luteolysis. Although prostaglandin F2a (PGF₂α) released from the uterus is known to be the luteolytic substance in the cow, events occurring at the level of the CL at this time are less clearly defined. Immune cells and their cytokine products have significant potential to influence the cells of the CL at luteolysisSix CL were collected from each of four stages of the oestrous cycle, identified on the basis of their gross appearance, for preliminary immunohistochemical studies. Immune cell populations and MHC II expression varied throughout the oestrous cycle. In particular, the number of macrophages, T-lymphocytes (CD5+, CD4+) and MHC II expression was significantly higher in late stage CL (after luteolysis) compared to all other stages. To study in more detail the cellular events associated with luteolysis, the oestrous cycles of 19 cows were synchronised. CL were collected between days 16 and 20 of the following oestrous cycle. A significant increase in the number of Tlymphocytes (CD5+, CD8+) was detected in CL collected from day 16 onwards, compared to days 13-14. This increase occurred prior to functional luteolysis. Artificially-induced luteolysis was then assessed as a potential model for further studies around luteolysis. CL collected 6, 12 and 24 hours after luteolysis, induced using a single injection of 25mg PGF₂α, had undergone dramatic structural regression which bore little resemblance to events during normal luteolysis and so this model was rejected. The role of endogenous PGF₂α in inducing the influx of T-lymphocytes was then investigated. Production of PGF₂α was inhibited in 12 cows between days 15 and 18 of the oestrous cycle and artificially replaced in six cows for 24 hours before collection of the C.L on day 18. The number of macrophages was significantly lower in all animals in which PGF2a was inhibited compared to control animals but Tlymphocyte numbers were not significantly alteredCytokine production within the CL was also studied using the reverse trancriptase polymerase chain reaction (RT-PCR). Tumour necrosis factor-a, (TNF-α), interleukin1ß (II-Iß (3) and interferon-γ (IFN-γ) were detectable in similar amounts in CL at all stages of the oestrous cycle and after induced luteolysis and PGF₂α inhibition. Monocyte chemoattractant protein-1 (MCP-1) was higher in CL from animals after functional luteolysis compared to CL collected prior to luteolysis but the increase occurred before macrophage numbers in the CL increased. MCP-1 may be involved in chemotaxis of monocytes into the CL during luteal regression.In conclusion, these results provide further evidence of a role for immune cells, particularly T-lymphocytes, in controlling CL function, outwith their involvement in structural luteolysis. Increasing concentrations of PGF₂α may be one of the major factors influencing the presence of macrophages, and possibly other immune cells, in luteal tissue. The presence of mRNA for TNF-α, IL-1ß, IFN-γ and MCP-1 at all stages studied indicates a potential role for these substances in the CL although more detailed investigations are required. MCP-1 appears to have a specific involvement in the chemotaxis of monocytes to the CL in preparation for structural regression

Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies

Some autoimmune conditions are associated with increased risk of lymphoid malignancies, but information on specific malignancy subtypes is limited. From the U.S. Surveillance Epidemiology and End Results-Medicare database, we selected 44,350 lymphoid malignancy cases (≥67 years) and 122,531 population-based controls. Logistic regression was used to derive odds ratios (ORs) comparing the prevalence of autoimmune conditions in cases and controls, by lymphoid malignancy subtype, adjusted for gender, age at malignancy/selection, year of malignancy/selection, race and number of physician claims. The strongest associations observed by Non-Hodgkin lymphoma (NHL) subtypes were diffuse large B-cell lymphoma with rheumatoid arthritis (OR 1.4, 95%CI 1.2-1.5) and Sjögren syndrome (2.0, 1.5-2.8); T-cell lymphoma with hemolytic anemia (9.7, 4.3-22), psoriasis (3.1, 2.5-4.0), discoid lupus erythematosus (4.4, 2.3-8.4), and celiac disease (5.0, 2.4-14.); and marginal zone lymphoma with Sjögren syndrome (6.6, 4.6-9.5), systemic lupus erythematosus (2.8, 1.7-4.7), and hemolytic anemia (7.4, 3.1-18). Hodgkin lymphoma was associated with several autoimmune conditions. Multiple myeloma was associated only with pernicious anemia (1.5, 1.3-1.7). Several autoimmune conditions were associated with increased risk of lymphoid neoplasms, especially NHLs of diffuse large B-cell, marginal zone and T-cell subtypes. These results support a mechanism whereby chronic antigenic stimulation leads to lymphoid malignancy