The Bioperl toolkit: Perl modules for the life sciences

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.     

Cross-regulatory role of interferon-gamma (IFN-gamma), IL-4 and IL-10 in schistosome egg granuloma formation: in vivo regulation of Th activity and inflammation.

This study examined the relationship of IL-4, IL-10 and IFN-gamma with regard to the local granuloma (GR) and draining lymph node (LN) response to Schistosoma mansoni eggs. Synchronized GR were induced in naive and schistosome-infected mice at the vigorous (8 weeks) and late chronic (20 weeks) stages. In LN cultures, IL-10 and IFN production peaked on day 4 and was greatest for 8 week-infected mice. All GR cultures contained IFN, but compared with naive mice IL-10 production was accelerated at 8 weeks and abrogated at 20 weeks, consistent with expansion and abatement of Th2 activity. Cytokine neutralization was performed in egg-challenged, naive mice that were adoptively sensitized with lymphoid cells from 8 week-infected donors. GR size, GR macrophage tumour necrosis factor (TNF) production and egg antigen-elicited IL-2, IL-4, IL-5, IL-10 and IFN were examined on day 4 of GR formation. Anti-IFN augmented GR area by 40%, increased local IL-4 and IL-10, but decreased IFN and TNF production. In corresponding LN cultures, IFN decreased by about 50%, while IL-2, IL-4, IL-10 and IL-5 increased by nearly two-, four-, five- and six-fold, respectively. Anti-IL-10 did not affect GR size or GR cytokines, but abrogated GR area by 40%, along with a reduction in local IL-4 and TNF production. In LN, IL-4 depletion reduced IL-4 and IL-5 by 60-70% and increased IFN levels. These results support the notion of a cross-regulatory network in which IFN inhibits Th2 and IL-10 inhibits Th1 cells. IL-4 fosters Th2 cells differentiation in LN, but also performs a critical recruitment function in the eosinophil-rich schistosome egg-induced GR, whereas IFN contributes to enhanced GR macrophage function.     

Factors affecting place of death in Washington State, 1968–1981

A study was carried out to determine factors affecting place of death (home, hospital, nursing home or other places) among all 426,115 resident deaths in Washington State during 1968–1981, using death certificate information. Sixteen percent of deaths occurred at home, 74% in institutions (51% in hospitals, 23% in nursing homes) and 9% at other places. Age, marital status and cause of death all strongly affect place of death. Further, the effect of each factor was strongly dependent on the others. Sex had no effect on place of death after controlling for other factors. Elderly people died relatively more frequently in nursing homes, infants and middle aged people in hospitals and young adults in other places. The frequency of deaths at home was quite constant by age. Hospitals were the most common place of death following both vascular disease (including heart attack) and neoplasms, and nursing homes were the most common place of death following cerebrovascular disease (including stroke). Race, socioeconomic status and urban or rural residents affected the place of death only slightly or not at all. The place of death pattern changed little during the time period 1968–1981, except for a slight increase in frequency of home deaths and a corresponding decrease in the frequency of deaths in other places.Among cancer patients, the likelihood of death at home was positively associated with longer periods of survival after diagnosis. Cancer patients of hospitals serving targeted populations, such as veterans, were relatively more likely to die in a hospital and less likely to die in a nursing home compared to other cancer patients, suggesting that the targeted hospitals are sometimes serving a nursing home function. There was a marked difference in the terminal cancer caseload by hospital. The number of cancer deaths per cancer diagnosis varied widely across hospitals (0.1 to 1.6) and was unrelated to size of the hospital or level of services offered.Intervention aimed at affecting place of death, such as increasing the number of deaths at home, will need to take account of the joint effect of age, marital status and disease.Lincoln Polissar, Ph.D., is Associate Member, Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA and Associate Professor, Department of Biostatistics, University of Washington in Seattle. Richard K. Severson, M.S., is the Project Coordinator, Fred Hutchinson Cancer Research Center. Norman K. Brown, M.D., is Clinical Professor of Medicine, School of Medicine, University of Washington.This research was supported by NCI Grant Nos. NCI-SR18, CA 29770–03 Requests for reprints should be sent to Lincoln Polissar, Ph.D., Fred Hutchinson Cancer Research Center, 1124 Columbia Street, Seattle, WA 98104     

The spectrum of atrioventricular discordance. A clinical study.

The clinical, investigative, and surgical findings were reviewed in 47 patients with atrioventricular discordance who presented to the Brompton Hospital between January 1962 and June 1981. Although the unifying feature was the atria connecting to morphologically inappropriate ventricles, the hearts differed widely in other respects. In most cases there was the usual visceral and atrial arrangement, but six had a mirror image arrangement of the atria and viscera. Among those patients with usual atrial arrangement (solitus) the aorta was not always anterior and left sided, and ventricular "inversion" was not invariable. Only 35 of the 47 patients also had a discordant ventriculoarterial connexion, the majority of the remainder having a double outlet right ventricle. The specific diagnosis of atrioventricular discordance depended on echocardiographic and angiographic examination. The other investigations did not distinguish between different ventriculoarterial connexions and were not specific even for the presence of atrioventricular discordance. For those patients with the usual atrial arrangement the anticipated right heart border was present in only just over one third, and the reversal of Q wave progression in the precordial leads of the standard electrocardiogram was found in under a half. Many patients with atrioventricular discordance progressed normally to adult life. In 20 cases no surgery was performed. The results of total correction showed a mortality of 25% (three cases), including two deaths after a modified Fontan procedure for exceedingly complex associated lesions. The results of surgery in the survivors were excellent, and awareness of the disposition of the atrioventricular conduction tissue made it possible to avoid atrioventricular dissociation.     

Long-Term Functional Outcomes and Quality of Life at Minimum 10-Year Follow-Up After Fixed-Bearing Unicompartmental Knee Arthroplasty and Total Knee Arthroplasty for Isolated Medial Compartment Osteoarthritis

BackgroundThe aim of this study is to compare the long-term functional outcome and quality of life between total knee arthroplasty (TKA) and fixed-bearing unicompartmental knee arthroplasty (UKA) for the treatment of isolated medial compartment osteoarthritis.MethodsBetween 2000 and 2008, a total of 218 patients underwent primary UKA at our tertiary hospital. A TKA group was matched through 1:1 propensity score matching and adjusted for age, gender, body mass index, preoperative knee flexion, and function scores. All patients had medial compartment osteoarthritis. The patients were assessed with the range of motion, Knee Society Knee Score and Knee Society Function Score, Oxford Knee Score, Short Form-36 physical component score (PCS) and mental component score preoperatively, at 6 months, 2 years, and 10 years. Patients’ satisfaction, expectation fulfillment, and minimal clinically important difference were analyzed.ResultsThere were no differences in baseline characteristics between groups after propensity score matching (P > .05). UKA had greater knee flexion at all time points. Although the Knee Society Function Score was superior in UKA by 5.5, 3, and 4.3 points at 6 months, 2 years, and 10 years, respectively (P < .001), these differences did not exceed the minimal clinically important difference (Knee Society Knee Score 6.1). There were no significant differences in the Oxford Knee Score and Short Form-36 physical component score/mental component score. At 10 years, similar proportions of UKA and TKA were satisfied (90.8% vs 89.9%, P = .44) and had expectation fulfillment (89.4% vs 88.5%, P = .46). Between 2 and 10 years, all function scores deteriorated significantly for both groups (P < .01).ConclusionUKA and TKA are excellent treatment modalities for isolated medial compartment osteoarthritis, with similar functional outcomes, quality of life, and satisfaction at 10 years.     

Change in Body Mass Index after Simultaneous Bilateral Total Knee Arthroplasty: Risk Factors and Its Influence on Functional Outcomes

BackgroundPrevious studies evaluating weight changes following total knee arthroplasty (TKA) were performed on heterogenous cohorts. However, no study has evaluated weight changes in a cohort of simultaneous-bilateral TKA (SB-TKA) patients. This study aimed to evaluate the prevalence of patients who lost or gained weight, determine if postoperative weight change influences functional outcome, and identify predictors of weight change after SB-TKA.MethodsProspectively collected registry data of 560 patients who underwent SB-TKA were reviewed. Patients were assessed preoperatively, at 6 months, and 2 years using the Knee Society Score, Oxford Knee Score, Short-Form 36, and range of motion. Change in body mass index (BMI) >5% was used to categorize patients into 3 groups: lost, maintained, or gained weight. Analysis of variance, Kruskal-Wallis test, and chi-squared test were used to compare functional outcomes between groups. Multivariable logistic regression evaluated predictors for postoperative weight changes.ResultsAt 2 years, 59% of patients maintained weight, 28% of patients gained weight, and 13% of patients lost weight. All groups experienced similar improvements in functional outcomes, rates of minimal clinically important difference attainment, and patient satisfaction (P > .05). Older patients were more likely to gain weight (P < .05). Patients with higher preoperative BMI were more likely to gain weight (P < .05) and less likely to lose weight (P < .05). Patients with greater preoperative comorbidities were less likely to lose weight (P < .05).ConclusionUp to 41% of patients experience significant weight changes after SB-TKA. Older patients with higher preoperative BMI were more likely to gain weight, while higher preoperative BMI with more comorbidities were less likely to lose weight following SB-TKA; however, postoperative weight changes do not appear to affect functional outcomes.Level of EvidenceIII, therapeutic study.     

Efficacy of m-Health for the detection of adverse events following immunization – The stimulated telephone assisted rapid safety surveillance (STARSS) randomised control trial

IntroductionPassive surveillance is recommended globally for the detection of adverse events following immunisation (AEFI) but this has significant challenges. Use of Mobile health for vaccine safety surveillance enables a consumer-centred approach to reporting. The Stimulated Telephone Assisted Rapid Safety Surveillance (STARSS) a randomised control trial (RCT) sought to evaluate the efficacy and acceptability of SMS for AEFI surveillance.MethodsMulti-centre RCT, participants were adult vaccinees or parents of children receiving any vaccine at a trial site. At enrolment randomisation occurred to one of two SMS groups or a control group. Prompts on days 2, 7 and 14 post-immunisation, were sent to the SMS group, to ascertain if a medical event following immunisation (MEFI) had occurred. No SMS’s were sent to the control participants. Those in the SMS who notified an MEFI were pre-randomised to complete a computer assisted telephone interview or a web based report to determine if an AEFI had occurred whilst an AEFI in the controls was determined by a search for passive reports. The primary outcome was the AEFI detection rate in the SMS group compared to controls.ResultsWe enrolled 6,338 participants, who were equally distributed across groups and who received 11,675 vaccines. The SMS group (4,225) received 12,675 surveillance prompts with 9.8% being non-compliant and not responding. In those that responded 90% indicated that no MEFI had been experienced and 184 had a verified AEFI. 6 control subjects had a reported AEFI. The AEFI detection rate was 13 fold greater in the SMS group when compared with controls (4.3 vs 0.3%).ConclusionWe have demonstrated that the STARSS methodology improves AEFI detection. Our findings should inform the wider use of SMS-based surveillance which is particularly relevant since establishing robust and novel pharmacovigilance systems is critical to monitoring novel vaccines which includes potential COVID vaccines.     

Right aortic arch with aberrant subclavian arteries: a cause of esophageal compression

We report a case of symptomatic partial vascular ring that to our knowledge has not been previously described. This anomaly includes a right aortic arch with an aberrant left subclavian artery and an atypical origin of the right subclavian artery.     

Randomized, controlled trial to evaluate increased intensity of physiotherapy treatment of arm function after stroke

BACKGROUND AND PURPOSE: Many patients have impaired arm function after stroke, for which they receive physiotherapy. The aim of the study was to determine whether increasing the amount of physiotherapy early after stroke improved the recovery of arm function and to compare the effects of this therapy when administered by a qualified therapist or a trained, supervised assistant. The physiotherapy followed a typical British approach, which is Bobath derived. Ten hours of additional therapy were given over a 5-week period. METHODS: The study design was a single-blind, randomized, controlled trial. Stroke patients were recruited from those admitted to the hospital in the 5 weeks after stroke. They were randomly allocated to routine physiotherapy, additional treatment by a qualified physiotherapist, or additional treatment by a physiotherapy assistant. Outcome was assessed after 5 weeks of treatment and at 3 and 6 months after stroke on measures of arm function and of independence in activities of daily living. RESULTS: There were 282 patients recruited to the study. The median initial Barthel score was 6.5, and the median age of the patients was 73 years. The median initial Rivermead Motor Assessment Arm score was 1. There were no significant differences between the groups at randomization or on any of the outcome measures. Only half of the patients allocated to the 2 additional-therapy groups completed the program. CONCLUSIONS: This increase in the amount of physiotherapy for arm impairment with a typical British approach given early after stroke did not significantly improve the recovery of arm function in the patients studied. A number of other studies of interventions aimed at rehabilitation of arm function have reported positive results. Such findings may have been due to the content of these interventions, to the greater intensity of the interventions, or to the selection of patients to whom the treatments were applied.