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Sea lamprey Petromyzon marinus is an anadromous and semelparous fish without homing behaviors. Despite being a freshwater, free‐living organism for a large part of their life cycle, its adulthood is spent as a parasite of marine vertebrates. In their native European range, while it is well‐established that sea lampreys comprise a single nearly‐panmictic population, few studies have further explored the evolutionary history of natural populations. Here, we performed the first genome‐wide characterization of sea lamprey's genetic diversity in their European natural range. The objectives were to investigate the connectivity among river basins and explore evolutionary processes mediating dispersal during the marine phase, with the sequencing of 186 individuals from 8 locations spanning the North Eastern Atlantic coast and the North Sea with double‐digest RAD‐sequencing, obtaining a total of 30,910 bi‐allelic SNPs. Population genetic analyses reinforced the existence of a single metapopulation encompassing freshwater spawning sites within the North Eastern Atlantic and the North Sea, though the prevalence of private alleles at northern latitudes suggested some limits to the species' dispersal. Seascape genomics suggested a scenario where oxygen concentration and river runoffs impose spatially varying selection across their distribution range. Exploring associations with the abundance of potential hosts further suggested that hake and cod could also impose selective pressures, although the nature of such putative biotic interactions was unresolved. Overall, the identification of adaptive seascapes in a panmictic anadromous species could contribute to conservation practices by providing information for restoration activities to mitigate local extinctions on freshwater sites. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has disrupted all aspects of life and may raise particular fears for people with rheumatic disease. There is a need for research on fears and perceived risk of SARS‐CoV‐2 so as to understand the impact on wellbeing and inform service provision. Objectives: The aim of this study was to examine the correlates of COVID‐19 fears and perceived risk of SARS‐CoV‐2 among people with rheumatoid arthritis or ankylosing spondylitis. Design: A cross‐sectional survey design was applied in Aotearoa New Zealand in the period after initial nationwide lockdowns. Method: An online survey was completed from July to September 2020 by 126 individuals with rheumatoid arthritis (n = 96) or ankylosing spondylitis (n = 30) who had previously been recruited to the Patient Opinion Real‐Time Anonymous Liaison (PORTAL) study in 2015 or 2018. The survey included demographics and health information as well as measures of COVID‐19 fears and experiences, functional disability and fatigue‐related disability. Results: Fears about COVID‐19 were higher among younger participants, those who had been tested for SARS‐CoV‐2, and those who experienced more flares over the initial lockdown. Perceived risk of SARS‐CoV‐2 infection was also higher among individual who had been tested for SARS‐CoV‐2 and those taking biologic medications. Conclusion: Fears about COVID‐19 and perceived risk of infection are related to age, health and medications among individuals with rheumatoid arthritis or ankylosing spondylitis. These findings inform how health professionals can help address the concerns of particular groups of people with rheumatic disease by providing relevant information about the ongoing effects of the pandemic. [ABSTRACT FROM AUTHOR]

Anthropogenic activities are increasingly threatening aquatic biodiversity, especially anadromous species. Monitoring and conservation measures are thus required to protect, maintain and restore imperilled populations. While many species can be surveyed using traditional capture and visual census techniques, species that use riverine habitats in a less conspicuous manner, such as sea lamprey Petromyzon marinus, can be more challenging to monitor. Sea lamprey larvae (ammocoetes) can spend several years in freshwater burrowed within soft sediments, inhibiting their detection and assessment. Here, we present a qPCR assay based on the detection of environmental DNA (eDNA) to identify the presence of ammocoetes burrowed in the sediment. We present an extensively validated method that ensured both species‐specificity of the assay as well as the capacity to detect ammocoetes when abundances are low. Experiments on burrowing activity suggested that most of the DNA released into the sediment occurs during burrowing. Overall, we demonstrate this new molecular‐based tool is an efficient and effective complement to traditional monitoring activities targeting larval stages of sea lampreys. [ABSTRACT FROM AUTHOR]

Tropical freshwater eels (Anguilla bengalensis and Anguilla bicolor) contribute a major share of the world's wild‐caught eel production, having become the next major target owing to the declines in availability of both Anguilla japonica and Anguilla anguilla, species that have traditionally contributed to eel aquaculture and trade.Although both A. bengalensis and A. bicolor are assessed as Near Threatened on the International Union for Conservation of Nature Red List, these assessments are primarily based on anecdotal information and local knowledge on population declines.Demographics and exploitation levels of A. bengalensis and A. bicolor were determined from small coastal river systems, and their adjoining aquascapes in the Western Ghats hotspot of southern peninsular India, and the value of these data for future conservation planning discussed.The computed estimates of annual catch data for freshwater eels from the study region are between 0.17 (A. bicolor) to 0.30 t (A. bengalensis). Virtual population analysis of exploitation showed a drastic decline (in number) in the length groups >45 cm for both species, suggesting that they were less likely to attain their asymptotic length in the region.Current exploitation rates of A. bengalensis are unsustainable, and those for A. bicolor are almost close to reaching this level. Exploitation of all life stages from yellow eels to adults (29–171 cm) is likely to cause recruitment failure and significant mortality of spawning individuals of both species.An integrative conservation approach, including raising awareness (leading to voluntary restrictions), fishing closures in reservoirs, village‐level quotas, and regular monitoring of populations, will ensure a sustainable future for the freshwater eel species in the Western Ghats hotspot, and elsewhere in the tropics where these species are exploited. [ABSTRACT FROM AUTHOR]

Aging and senescence impact CD4 T helper cell (Th) subset differentiation during influenza infection. In the lungs of infected aged mice, there were significantly greater percentages of Th cells expressing the transcription factor FoxP3, indicative of regulatory CD4 T cells (Treg), when compared to young. TGF‐beta levels, which drive FoxP3 expression, were also higher in the bronchoalveolar lavage of aged mice and blocking TGF‐beta reduced the percentage of FoxP3+ Th in aged lungs during influenza infection. Since TGF‐beta can be the product of senescent cells, these were targeted by treatment with senolytic drugs. Treatment of aged mice with senolytics prior to influenza infection restored the differentiation of Th cells in those aged mice to a more youthful phenotype with fewer Th cells expressing FoxP3. In addition, treatment with senolytic drugs induced differentiation of aged Th toward a healing Type 2 phenotype, which promotes a return to homeostasis. These results suggest that senescent cells, via production of cytokines such as TGF‐beta, have a significant impact on Th differentiation. [ABSTRACT FROM AUTHOR]

Objective: Fatigue is common among people with inflammatory arthritis but is hard to manage. The aim of this study was to investigate how daily fluctuations in psychological variables correspond with changes in fatigue-related disability in the daily lives of people with inflammatory arthritis and to identify factors to target in psychological interventions and routine clinical practice.Methods: A cohort of 143 patients with rheumatoid arthritis (n = 97) or ankylosing spondylitis (n = 46) participated in a 10-day online diary study. Each evening participants completed a diary questionnaire assessing their fatigue, pain, fatigue-related disability, and 4 components of psychological flexibility (valued activity, mindfulness, cognitive fusion, and fatigue avoidance).Results: On days when participants were more engaged in valued activities or more mindful, they reported less disability due to fatigue, even when controlling for levels of fatigue and pain that day. The daily psychological flexibility variables explained a total of 15.6% of the variance in daily fatigue-related disability.Conclusion: Psychological flexibility variables are directly associated with fatigue-related disability in the daily lives of inflammatory arthritis patients. Further research is needed to investigate whether interventions that target psychological flexibility are effective at reducing fatigue-related disability. [ABSTRACT FROM AUTHOR]

Background: The objective of this meta‐analysis of randomised controlled clinical trials (RCT) was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. Aims: Febuxostat is a xanthine oxidase inhibitor that decreases uric acid production. Recent studies suggested the renoprotective effect of febuxostat among hyperuricaemia patients. The aim of this study was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia. Methods: We conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify RCT that examined the effects of febuxostat in adult patients with hyperuricaemia on serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria, blood pressure parameters, major cardiovascular events, diarrhoea, joint pain, stroke and arrhythmia. Results: Nine RCT with 2141 participants were included in this meta‐analysis. Compared to placebo, the febuxostat group showed a higher eGFR at 6 months with a weighted mean difference (WMD) of 2.86 mL/min/1.73 m2 (P < 0.001), as well as the end of studies (eGFR WMD 2.69 mL/min/1.73 m2, P < 0.001). There was also lower serum creatinine (SrCr WMD = −0.04 mg/dL, P < 0.001), reduction in systolic blood pressure (SBP WMD = −1.18 mmHg, P < 0.001) and diastolic blood pressure (DBP WMD = −1.14 mmHg, P = 0.04). There was no statistical difference between febuxostat and placebo in major cardiovascular events, diarrhoea, joint symptoms, stroke events and arrhythmia. Subgroup analysis among chronic kidney disease showed the febuxostat group had higher eGFR than the placebo group (eGFR WMD = 2.69 mL/min/1.73 m2, P < 0.001). Conclusion: Treating hyperuricaemia with febuxostat may slow the progression of chronic kidney disease irrespective of baseline renal function without significantly associated increased risks of major cardiovascular events, diarrhoea, joint symptoms, arrhythmia and stroke, compared to placebo. [ABSTRACT FROM AUTHOR]

Aim: Implementation of treat‐to‐target (T2T) for rheumatoid arthritis (RA) presents many challenges and an evidence‐practice gap has emerged. This study assessed clinician and patient barriers to the implementation of an RA‐T2T strategy and developed a knowledge translation (KT) tool for use in "real‐life" clinical settings. Methods: Surveys of patients and rheumatologists measured agreement with RA‐T2T recommendations and use in daily practice. Patient knowledge and perceptions were assessed as was clinician willingness to alter practice and barriers to RA‐T2T using visual analog scales. An electronic KT‐tool was developed and a two‐phase usability trial undertaken to assess use in clinical interactions. Results: Ninety‐one percent of patients had no prior knowledge of RA‐T2T but agreed with the recommendations showing mean level agreement scores (8.39‐9.54, SD 2.37‐1.54). Ninety percent were willing to try RA‐T2T, 49% felt their treatment could be improved and 28% wanted more involvement in treatment decisions. Rheumatologists agreed with RA‐T2T recommendations (7.30‐9.27, SD 2.59‐0.91). Barriers to implementation identified by rheumatologists included time, appointment availability and perceived patient reluctance to escalate medications. Usability experiences with the KT‐tool were tracked and clinicians reported it was easy to use (100%), resulted in a discussion of RA‐T2T (73%) and a target being set for 63% of consults. Patients reported they read (92%) and understood (87%) the information in the KT‐tool, and that a target was set in 62% of interactions. Conclusions: RA‐T2T uptake in clinical practice may be improved through understanding local clinician and patient barriers and an implementation strategy utilizing a patient‐driven KT‐tool. [ABSTRACT FROM AUTHOR]

Currently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD are limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline estimated glomerular filtration rate (eGFRs) between 15 and 59 mL/min/1.73 m2. This study was composed of a nationwide retrospective cohort of adult T2DM patients from 831 public hospitals in Thailand during the year 2015. T2DM patients with CKD stages 3 and 4 were followed up, until development of CKD stage 5, requirement of chronic dialysis, loss to follow‐up, death, or 31 May 2018, whichever came first. Cox proportional hazard regression was utilized for analysis. A total of 8464 participants were included; 30.4% were male. The mean age was 69 ± 10 years. The mean eGFR was 45 ± 11 mL/min/1.73 m2. The incidence of CKD stage 5 or the need for chronic dialysis was 16.4 per 1000 person‐years. The annual rate of eGFR decline during a mean follow‐up of 29 months was −2.3 mL/min/1.73 m2; 14.4% had a rapid decline in eGFR. The risk factors associated with progression to CKD stage 5 or the need for chronic dialysis were diabetes duration, systolic blood pressure, serum uric acid, albuminuria, and baseline eGFR. Conversely, older age and the use of renin‐angiotensin aldosterone system blockade were associated with decreased risks for rapid CKD progression and incidence CKD stage 5 or dialysis. This study identifies multiple predictive risk factors that support a multifaceted approach to prevent progression of advanced CKD. [ABSTRACT FROM AUTHOR]

Objective: To determine whether training increases accuracy of self‐reported joint counts in people with rheumatoid arthritis (RA) and describe the knowledge and techniques for self‐examination of joints for reporting of RA disease activity. Methods: This mixed‐methods study included 10 patients with RA and four rheumatologists. A rheumatologist presented about joint inflammation and disease monitoring in RA. Patients then self‐examined and reported 28‐tender joint count (28‐TJC) and 28‐swollen joint count (28‐SJC). Next, two paired rheumatologists examined patients and reported 28‐TJC and 28‐SJC. After watching a joint examination video for training physicians, patients discussed their training needs for self‐examination, with discussion analyzed using thematic analysis. Self‐examination techniques were determined by consensus. Finally, patients self‐examined and reported 28‐TJC and 28‐SJC. Reliability between the first and second patient‐reported 28‐TJCs and 28‐SJCs and rheumatologist pair‐reported 28‐TJC and 28‐SJC was determined with the intraclass coefficient. Results: The reliability for patient self‐reported joint counts was higher for the 28‐TJC than for the 28‐SJC. Reliability improved following rheumatologist examination and training. Patients identified a preference for practical information rather than detailed information on joint anatomy and pathophysiology. Clear definitions of "swollen" and "tender" were important; patients found the concept of "tenderness" difficult. Techniques for self‐examination and reporting of joint counts were agreed on and demonstrated in an instructional video. Conclusion: Training increased reliability of patient‐reported joint counts. Patients with RA identified important aspects of training for self‐examination and reporting of joint counts. An 8‐minute instructional video was codeveloped; the next step is the evaluation of the video's impact on patient‐reported joint counts. [ABSTRACT FROM AUTHOR]

Aims: The prevalence of urinary dysfunction increases with age, yet therapies are often suboptimal. Incomplete understanding of the linkages between system, organ, and tissue domains across lifespan remains a knowledge gap. If tissue‐level changes drive the aging bladder phenotype, parallel changes should be observed across these domains. In contrast, a lack of inter‐domain correlation across age groups would support the hypothesis that urinary performance is a measure of the physiologic reserve, dependent on centrally‐mediated adaptive mechanisms in the aging system. Methods: Male and female mice across four age groups underwent sequential voiding spot assays, pressure/flow cystometry, bladder strip tension studies, histology, and quantitative PCR analyses. The primary objective of this study was to test the impact of age on the cortical, autonomic, tissue functional and structural, and molecular domains, and identify inter‐domain correlations among variables showing significant changes with age within these domains. Results: Behavior revealed diminished peripheral voiding and spot size in aged females. Cystometry demonstrated increased postvoid residual and loss of volume sensitivity, but the preservation of voiding contraction power, with almost half of oldest‐old mice failing under cystometric stress. Strip studies revealed no significant differences in adrenergic, cholinergic, or EFS sensitivity. Histology showed increased detrusor and lamina propria thickness, without a change in collagen/muscle ratio. Adrb2 gene expression decreased with age. No consistent inter‐domain correlations were found across age groups. Conclusions: Our findings are consistent with a model in which centrally‐mediated adaptive failures to aging stressors are more influential over the aging bladder phenotype than local tissue changes. [ABSTRACT FROM AUTHOR]

Objectives: To determine the level of agreement among patients with rheumatoid arthritis (RA) with the principles and recommendations of the treat‐to‐target (T2T) initiative in New Zealand (NZ) and to further explore specific patient opinions via online iterative surveys. Methods: Participants with RA were recruited from rheumatology clinics in NZ and invited to receive and reply to surveys administered via the Patient Opinion Real‐Time Anonymous Liaison (PORTAL) system. An enrolment survey recorded demographics, disease duration and treatment and then RA T2T surveys were administered weekly. A Likert scale 1‐5 measured agreement with the principles and recommendations and further surveys explored responses of interest identified by investigators from each prior survey. Results: One hundred and ninety patients consented to participate in PORTAL and 132 in the RA T2T surveys. Level of agreement with RA T2T principles was: 93.3% to 99.3% and to the recommendations: 77.3%‐100%. The lowest level of agreement 77.3% was with recommendation 8, 3 monthly treatment adjustment, and the highest was 100% agreement with recommendation 10, shared decision‐making. Patients agreed less with low disease activity as the target compared with remission (91.4% and 98%). Despite high‐level agreement for the use of a disease activity score (95.7%), 23% did not feel the individual components reflected their disease control. Patients rated difficulty coping, erosions on imaging, health‐related quality of life and pain all significantly higher than C‐reactive protein as indicators of worsening arthritis. Conclusions: Despite a high level of patient agreement with RA T2T this study highlights the importance of patient engagement in the RA T2T process to individualize therapy adjustments, make shared decisions and decide on targets that accurately reflect disease control according to patients. [ABSTRACT FROM AUTHOR]

Aim: To update recommendations based on current best evidence concerning the treatment of rheumatoid arthritis (RA), focusing particularly on the role of targeted therapies, to inform clinicians on new developments that will impact their current practice. Materials and methods: A search of relevant literature from 2014 to 2016 concerning targeted therapies in RA was conducted. The RA Update Working Group evaluated the evidence and proposed updated recommendations using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, to describe the quality of evidence and strength of recommendations. Recommendations were finalized through consensus using the Delphi technique. Results: This update provides 16 RA treatment recommendations based on current best evidence and expert clinical opinion. Recommendations 1‐3 deal with the use of conventional synthetic disease‐modifying antirheumatic drugs. The next three recommendations (4‐6) cover the need for screening and management of infections and comorbid conditions prior to starting targeted therapy, while the following seven recommendations focus on use of these agents. We address choice of targeted therapy, switch, tapering and discontinuation. The last three recommendations elaborate on targeted therapy for RA in special situations such as pregnancy, cancer, and major surgery. Conclusion: Rheumatoid arthritis remains a significant health problem in the Asia‐Pacific region. Patients with RA can benefit from the availability of effective targeted therapies, and these updated recommendations provide clinicians with guidance on their use. [ABSTRACT FROM AUTHOR]

Lyme disease is an infectious disease caused by the bacterium Borrelia burgdorferi. When untreated, infection may spread to the heart, nervous system, and joints. Cardiac involvement usually manifests as abnormalities of the conduction system and bradycardia. Treatment of Lyme disease is generally effective, with a subset of patients experiencing persistent, sometimes long-term symptoms called posttreatment Lyme disease syndrome. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) and its severity after transcatheter aortic valve replacement (TAVR) have been associated with worse outcomes. Studies have shown that AKI duration (transient or persistent) affects outcomes independently of AKI severity. This study was undertaken to determine the association, risk factors, and outcomes associated with persistent AKI (pAKI) after TAVR.Methods: Adult patients undergoing TAVR at Mayo Clinic between January 1, 2008 and June 30, 2014 were enrolled. pAKI was defined as an increased serum creatinine at hospital discharge (≥0.3 mg/dL or ≥50% from baseline). Risk factors associated with pAKI were identified with multivariate logistic regression.Results: A total of 386 patients met the inclusion criteria. Fifty patients (13%) had pAKI. Independent risk factors for pAKI on multivariate analysis included diabetes mellitus (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.29-4.66), prior percutaneous coronary intervention (PCI) (OR, 2.39; 95%CI, 1.24-4.80), intra-aortic balloon pump (IABP) use (OR, 8.14; 95%CI, 1.60-45.78), and blood transfusion (OR, 2.22; 95%CI, 1.15-4.27). Protective factors for pAKI included a higher baseline estimated glomerular filtration rate (eGFR) (OR, 0.83 per 10-mL/min/1.73 m2 increase in eGFR; 95%CI, 0.71-0.99). After adjusting for the Society of Thoracic Surgeons cardiac surgery risk score, pAKI occurrence remained significantly associated with increased 2-year mortality among hospital survivors (hazard ratio, 2.65; 95%CI, 1.51-4.41).Conclusion: pAKI was significantly associated with higher mortality risk following TAVR. Baseline eGFR, diabetes mellitus, previous PCI, IABP, and blood transfusion were risk factors for post-procedural pAKI. [ABSTRACT FROM AUTHOR]

Aim To review inpatient management of acute gout in a New Zealand hospital. Methods A retrospective file review of all acute episodes of gout at Hutt Hospital, Wellington, New Zealand over a 1 year period. Results In the course of a year, there were 90 admissions for, or complicated by, acute gout. In 31 cases, gout was the primary diagnosis. Median length of stay was 5 days and readmissions were common. The majority of patients (87%) were known to have gout before admission, yet only 50% of these patients were on uric acid lowering treatment. Serum urate was measured in only 60% of patients with a mean level of 0.471 mmol/L. Treatment for the acute attack was evenly split between monotherapy (49%) and polytherapy (49%). Treatment modalities used were: prednisone (61%), non-steroidal anti-inflammatories (40%), colchicine (40%), adrenocorticotrophic hormone ( ACTH) (15%) and intrarticular steroids (7%). Patients were generally treated in a timely manner with few patients experiencing delays. Patients seen by the Rheumatology Department were more likely to receive polytherapy, be treated with intra-articular steroids or ACTH and to start allopurinol. The 'treat-to-target' approach to the management of elevated serum urate was mentioned in only 9% of cases. Conclusion There was considerable variability in the investigation and management of acute gout, with significant deviation from published protocols. The 'treat-to-target' approach to the management of elevated urate has not yet been widely adopted by the physicians in this New Zealand hospital. [ABSTRACT FROM AUTHOR]

Pain in cancer therapy is a common condition and there is a need for new options in therapeutic management. While phytochemicals have been proposed as one pain management solution, knowledge of their utility is limited. The objective of this study was to performa systematic reviewof the biomedical literature for the use of phytochemicals for management of cancer therapy pain in human subjects. Of an initial database search of 1,603 abstracts, 32 full-text articles were eligible for further assessment. Only 7 of these articles met all inclusion criteria for this systematic review. The average relative risk of phytochemical versus control was 1.03 [95% CI 0.59 to 2.06]. In other words (although not statistically significant), patients treated with phytochemicals were slightlymore likely than patients treated with control to obtain successful management of pain in cancer therapy. We identified a lack of quality research literature on this subject and thus were unable to demonstrate a clear therapeutic benefit for either general or specific use of phytochemicals in the management of cancer pain. This lack of data is especially apparent for psychotropic phytochemicals, such as the Cannabis plant (marijuana). Additional implications of our findings are also explored. [ABSTRACT FROM AUTHOR]

Aims Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue. Materials and methods The AGREE II instrument and the ADAPTE Collaboration framework were applied to systematically identify, appraise, synthesize, and adapt international rheumatoid arthritis guidelines for use in the Asia-Pacific region. Results Forty rheumatoid arthritis treatment recommendations, based on evidence and expert opinion, were drafted and are presented in this report. Conclusion The Asia Pacific of Associations for Rheumatology rheumatoid arthritis treatment recommendations are intended to serve as a reference for best practice management of rheumatoid arthritis in Asia-Pacific, focusing on local issues to ensure the delivery of basic care for these patients, and to improve their outcomes. In addition, the document will serve as a reference for national rheumatology associations in Asia-Pacific for developing guidelines in their respective countries. [ABSTRACT FROM AUTHOR]

BACKGROUND: Discrepancies in ABO grouping arise due to different reasons, posing a threat to patient safety. Underlying causes include mixed-field agglutination after transfusion, chimerism, fetomaternal exchange, or inheritance of unusual alleles resulting in weak A/B antigen expression. Cord blood from the infant of a group A2B mother typed as group O, H+. Samples were investigated to elucidate this conundrum. STUDY DESIGN AND METHODS: Genomic DNA was analyzed by ABO genotyping and sequencing. Red blood cells (RBCs) were characterized by routine serology and flow cytometry. Glycosyltransferase structure was predicted with 3D-modeling software. RESULTS: The mother genotyped as ABO*A1.01/B.01, and the baby, ABO*A1.01/O.01.01. Sequencing revealed a substitution, 311T>A, in the ABO*A1-like allele, which predicts Ile104Asn. Flow cytometry demonstrated A antigen on the mother's RBCs equivalent to the A2 phenotype while no A was detectable on cord RBCs. However, blood from the 11-month-old child demonstrated markedly increased A expression, likely reflecting initiation of carbohydrate chain branching. CONCLUSION: We unraveled a novel Aweak allele (ABO*AW.29) in a case of apparent nonmaternity. Residue 104 is far from the catalytic site and may be involved in stabilizing the glycosyltransferase by dimerization. Our data support that the group AB mother's B-transferase stabilizes the altered A-transferase by heterodimerization, exemplifying the allelic enhancement phenomenon. [ABSTRACT FROM AUTHOR]

Translational stories range from straightforward to complex. In this commentary, the story of the rapid and successful translation of rituximab therapy for the treatment of non-Hodgkin's lymphoma (NHL) is examined. Development of this monoclonal antibody therapy began in the late 1980s. In 1994, rituximab received its first approval for the treatment of NHL by the United States Food and Drug Administration (FDA). Rituximab has since been approved for additional indications and has transformed medical practice. However, the social and political implications of these rapid successes are only beginning to become clear. In this commentary, key events in the rapid translation of rituximab from the bench to bedside are highlighted and placed into this historical framework. To accomplish this, the story of rituximab is divided into the following six topics, which we believe to be widely applicable to case studies of translation: (1) underlying disease, (2) key basic science, (3) key clinical studies in translation, (4) FDA approval process, (5) changes to medical practice, and (6) the social and political influences on translation. [ABSTRACT FROM AUTHOR]

Objective To identify demographic and geographic factors associated with non-attendance for first specialist assessment ( FSA) at a publicly funded rheumatology clinic and identify changes in service provision that might improve attendance rates. Method Administrative data for 1953 new referrals over a 2-year period was collected from a New Zealand public rheumatology unit. Patient characteristics and location variables were tested for significance and odds ratios were generated to determine the relationship between non-attendance and referrals data. Results Patients in the 20-29 years age-group were least likely to attend appointments ( P ≤ 0.001, OR 2.81, 95% CI 1.59-4.98). Māori and Pacific Peoples were each almost twice as likely to miss a FSA ( P = 0.02, OR 1.87, 95% CI 1.11-3.15 and OR 1.89, 95% CI 1.11-3.22) as New Zealand Europeans. Non-attendance was independently associated with longer waiting times to FSA; with residential location and the uneven provision of services being strong predictors of longer waiting times ( P ≤ 0.001). Conclusion Non-attendance is associated with ethnicity, age and waiting times. It is likely that high deprivation influences ethnic variations in attendance but reasons for young people's non-attendance were difficult to identify. Patients domiciled further from the main rheumatology clinic were also less likely to attend. The influence of ethnicity and deprivation may be underestimated in this study as high Maori and Pacific ethnic populations live closer to well-resourced clinics. Focusing administrative resources on at-risk groups and restructuring the clinical service to improve uneven waiting times would be expected to improve attendance rates across the region. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate and compare the biocompatibility profiles of hyaluronic acid (HA) viscosupplements from avian and non-mammalian sources. Inflammatory and immune reactions were assessed in models of both clinically relevant and stringent immunological exposure conditions. Experiments were conducted to evaluate tissue reactions and immunological responses and assess antibody formation with the capacity to bind directly to and cross-react with the different viscosupplements. Mice were exposed to viscosupplements using the air pouch inflammation model and specific immunization using Freund's complete adjuvant (FCA). Murine pouch membrane tissue reactions revealed generally mild to moderate responses, with cellular infiltration and cytokine profiles of pouch tissue characteristic of predominantly fibroblastic responses rather than marked inflammatory reactions. In vitro testing indicated that pouch injections did not elicit detectable T-cell proliferative responses, while antibody assays revealed that mice immunized with viscosupplements in FCA and subsequently boosted were capable of mounting an antibody response with a range of specificities. High reactivity to avian serum albumin was seen in sera from mice injected with HA from an avian source, while low positive reactivity to the bacterial antigen Staphylococcal Lipotechoic Acid was observed in sera from mice injected with HA from bacterial sources. These specificities did not indicate any propensity to cross-react, suggesting that patients with adverse immune responses to HA from an avian source should be unresponsive to subsequent injection with HA from a non-avian source. Overall, the findings demonstrate that viscosupplements exhibit good biocompatibility profiles in the murine air pouch, but when provoked to elicit immunological reactions exhibit unique antigenic spectra. These findings suggest that an immunologically mediated immune reaction directed against avian proteins should not necessarily be a contraindication for the administration of non-avian viscosupplements. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012. [ABSTRACT FROM AUTHOR]

We have previously discovered that probes containing runs of four or more contiguous guanines are not reliable for measuring gene expression in the Human HG U133A Affymetrix GeneChip data. These probes are not correlated with other members of their probe set, but they are correlated with each other. We now extend our analysis to different 3' GeneChip designs of mouse, rat, and human. We find that, in all these chip designs, the G-stack probes (probes with a run of exactly four consecutive guanines) are correlated highly with each other, indicating that such probes are not reliable measures of gene expression in mammalian studies. Furthermore, there is no specific position of G-stack where the correlation is highest in all the chips. We also find that the latest designs of rat and mouse chips have significantly fewer G-stack probes compared to their predecessors, whereas there has not been a similar reduction in G-stack density across the changes in human chips. Moreover, we find significant changes in RMA values (after removing G-stack probes) as the number of G-stack probes increases. [ABSTRACT FROM AUTHOR]

In this paper, we discuss a real-world application scenario that uses three distinct types of workflow within the Triana problem-solving environment: serial scientific workflow for the data processing of gravitational wave signals; job submission workflows that execute Triana services on a testbed; and monitoring workflows that examine and modify the behaviour of the executing application. We briefly describe the Triana distribution mechanisms and the underlying architectures that we can support. Our middleware independent abstraction layer, called the Grid Application Prototype (GAP), enables us to advertise, discover and communicate with Web and peer-to-peer (P2P) services. We show how gravitational wave search algorithms have been implemented to distribute both the search computation and data across the European GridLab testbed, using a combination of Web services, Globus interaction and P2P infrastructures. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of endoscopic medial and lateral orbital wall surgery to 3-wall decompression in patients with thyroid eye disease. Study design and setting: A retrospective study of patients with thyroid eye disease with severe proptosis, exposure keratitis, or compressive optic neuropathy was conducted. Results: Mean reduction in proptosis was 4.37 mm in the 2-wall approach and 4.59 mm in the 3-wall group. Seventy-five percent of patients in the 2-wall group demonstrated improved visual acuity; 50% improved after 3-wall decompression. Vertical palpebral fissure height decreased by an average of 2.50 mm in the 2-wall group and by 2.03 mm in the 3-wall group. New onset diplopia was 11.8% and 12.5%, respectively. Conclusions: Improvement in the degree of proptosis, visual acuity, and palpebral fissure height was seen in the majority of our patients and compared favorably to our results with 3-wall orbital decompression. EBM rating: C-4 [Copyright &y& Elsevier]