Using mobility and exception handling to achieve mobile agents that survive server crash failures

Mobile agent technology, when designed and used effectively, can minimize bandwidth consumption and autonomously provide a snapshot of the current context of a distributed system. Protecting mobile agents from server crashes is a challenging issue, since developers normally have no control over remote servers. Server crash failures can leave replicas, instable storage, unavailable for an unknown time period. Furthermore, few systems have considered the need for using a fault tolerant protocol among a group of collaborating mobile agents. This thesis uses exception handling to protect mobile agents from server crash failures. An exception model is proposed for mobile agents and two exception handler designs are investigated. The first exists at the server that created the mobile agent and uses a timeout mechanism. The second, the mobile shadow scheme, migrates with the mobile agent and operates at the previous server visited by the mobile agent. A case study application has been developed to compare the performance of the two exception handler designs. Performance results demonstrate that although the second design is slower it offers the smaller trip time when handling a server crash. Furthermore, no modification of the server environment is necessary. This thesis shows that the mobile shadow exception handling scheme reduces complexity for a group of mobile agents to survive server crashes. The scheme deploys a replica that monitors the server occupied by the master, at each stage of the itinerary. The replica exists at the previous server visited in the itinerary. Consequently, each group member is a single fault tolerant entity with respect to server crash failures. Other schemes introduce greater complexity and performance overheads since, for each stage of the itinerary, a group of replicas is sent to servers that offer an equivalent service. In addition, future research is established for fault tolerance in groups of collaborating mobile agents

A randomised controlled trial of three very brief interventions for physical activity in primary care.

BACKGROUND: Very brief interventions (VBIs) for physical activity are promising, but there is uncertainty about their potential effectiveness and cost. We assessed potential efficacy, feasibility, acceptability, and cost of three VBIs in primary care, in order to select the most promising intervention for evaluation in a subsequent large-scale RCT. METHODS: Three hundred and ninety four adults aged 40-74 years were randomised to a Motivational (n = 83), Pedometer (n = 74), or Combined (n = 80) intervention, delivered immediately after a preventative health check in primary care, or control (Health Check only; n = 157). Potential efficacy was measured as the probability of a positive difference between an intervention arm and the control arm in mean physical activity, measured by accelerometry at 4 weeks. RESULTS: For the primary outcome the estimated effect sizes (95 % CI) relative to the Control arm for the Motivational, Pedometer and Combined arms were respectively: +20.3 (-45.0, +85.7), +23.5 (-51.3, +98.3), and -3.1 (-69.3, +63.1) counts per minute. There was a73% probability of a positive effect on physical activity for each of the Motivational and Pedometer VBIs relative to control, but only 46 % for the Combined VBI. Only the Pedometer VBI was deliverable within 5 min. All VBIs were acceptable and low cost. CONCLUSIONS: Based on the four criteria, the Pedometer VBI was selected for evaluation in a large-scale trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02863077 . Retrospectively registered 05/10/2012.This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0608-10079). ATP and JV were supported by the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The funder had no role in study design, data collection, data analysis, data interpretation, the writing of the manuscript, and decision to submit the manuscript for publication.This is the final version of the article. It first appeared from BioMed Central via https://doi.org/10.1186/s12889-016-3684-

Evaluation of a very brief pedometer-based physical activity intervention delivered in NHS Health Checks in England: The VBI randomised controlled trial.

BACKGROUND:The majority of people do not achieve recommended levels of physical activity. There is a need for effective, scalable interventions to promote activity. Self-monitoring by pedometer is a potentially suitable strategy. We assessed the effectiveness and cost-effectiveness of a very brief (5-minute) pedometer-based intervention ('Step It Up') delivered as part of National Health Service (NHS) Health Checks in primary care. METHODS AND FINDINGS:The Very Brief Intervention (VBI) Trial was a two parallel-group, randomised controlled trial (RCT) with 3-month follow-up, conducted in 23 primary care practices in the East of England. Participants were 1,007 healthy adults aged 40 to 74 years eligible for an NHS Health Check. They were randomly allocated (1:1) using a web-based tool between October 1, 2014, and December 31, 2015, to either intervention (505) or control group (502), stratified by primary care practice. Participants were aware of study group allocation. Control participants received the NHS Health Check only. Intervention participants additionally received Step It Up: a 5-minute face-to-face discussion, written materials, pedometer, and step chart. The primary outcome was accelerometer-based physical activity volume at 3-month follow-up adjusted for sex, 5-year age group, and general practice. Secondary outcomes included time spent in different intensities of physical activity, self-reported physical activity, and economic measures. We conducted an in-depth fidelity assessment on a subsample of Health Check consultations. Participants' mean age was 56 years, two-thirds were female, they were predominantly white, and two-thirds were in paid employment. The primary outcome was available in 859 (85.3%) participants. There was no significant between-group difference in activity volume at 3 months (adjusted intervention effect 8.8 counts per minute [cpm]; 95% CI -18.7 to 36.3; p = 0.53). We found no significant between-group differences in the secondary outcomes of step counts per day, time spent in moderate or vigorous activity, time spent in vigorous activity, and time spent in moderate-intensity activity (accelerometer-derived variables); as well as in total physical activity, home-based activity, work-based activity, leisure-based activity, commuting physical activity, and screen or TV time (self-reported physical activity variables). Of the 505 intervention participants, 491 (97%) received the Step it Up intervention. Analysis of 37 intervention consultations showed that 60% of Step it Up components were delivered faithfully. The intervention cost £18.04 per participant. Incremental cost to the NHS per 1,000-step increase per day was £96 and to society was £239. Adverse events were reported by 5 intervention participants (of which 2 were serious) and 5 control participants (of which 2 were serious). The study's limitations include a participation rate of 16% and low return of audiotapes by practices for fidelity assessment. CONCLUSIONS:In this large well-conducted trial, we found no evidence of effect of a plausible very brief pedometer intervention embedded in NHS Health Checks on objectively measured activity at 3-month follow-up. TRIAL REGISTRATION:Current Controlled Trials (ISRCTN72691150)

Inverse association between blood pressure and pulse oximetry accuracy: an observational study in patients with suspected or confirmed COVID-19 infection

BackgroundPulse oximeters are a standard non-invasive tool to measure blood oxygen levels, and are used in multiple healthcare settings. It is important to understand the factors affecting their accuracy to be able to use them optimally and safely. This analysis aimed to explore the association of the measurement error of pulse oximeters with systolic BP, diastolic BP and heart rate (HR) within ranges of values commonly observed in clinical practice.MethodsThe study design was a retrospective observational study of all patients admitted to a large teaching hospital with suspected or confirmed COVID-19 infection from February 2020 to December 2021. Data on systolic and diastolic BPs and HR levels were available from the same time period as the pulse oximetry measurements.ResultsData were available for 3420 patients with 5927 observations of blood oxygen saturations as measured by pulse oximetry and ABG sampling within 30 min. The difference in oxygen saturation using the paired pulse oximetry and arterial oxygen saturation difference measurements was inversely associated with systolic BP, increasing by 0.02% with each mm Hg decrease in systolic BP (95% CI 0.00% to 0.03%) over a range of 80–180 mm Hg. Inverse associations were also observed between the error for oxygen saturation as measured by pulse oximetry and with both diastolic BP (+0.03%; 95% CI 0.00% to 0.05%) and HR (+0.04%; 95% CI 0.02% to 0.06% for each unit decrease in the HR).ConclusionsCare needs to be taken in interpreting pulse oximetry measurements in patients with lower systolic and diastolic BPs, and HRs, as oxygen saturation is overestimated as BP and HR decrease. Confirmation of the oxygen saturation with an ABG may be appropriate in some clinical scenarios

Pulse oximeter measurements vary across ethnic groups: an observational study in patients with COVID-19

The pulse oximeter provides regular non-invasive measurements of blood oxygenation and is used in a wide range of clinical settings [1]. The light wave transmission that this technology uses is modified by skin pigmentation and thus may vary by skin colour. A recent study of paired measures of oxygen saturation from pulse oximetry and arterial blood gas reported differing outputs in patients with black skin compared to patients with white skin that has the potential to adversely impact on patient care [2]

Respiratory rate responses to both hypercapnia and acidaemia are modified by age in patients with acidosis

ObjectiveTo explore the associations between arterial pO2, pCO2 and pH and how these are modified by age.MethodsAn analysis of 2598 patients admitted with a diagnosis of Covid-19 infection to a large UK teaching hospital.ResultsThere were inverse associations for arterial pO2, pCO2 and pH with respiratory rate. The effects of pCO2 and pH on respiratory rate were modified by age; older patients had higher respiratory rates at higher pCO2 (p = 0.004) and lower pH (p = 0.007) values.ConclusionsThis suggests that ageing is associated with complex changes in the physiological feedback loops that control respiratory rate. As well as having clinical relevance, this may also impact on the use of respiratory rate in early warning scores across the age range

Chest Radiograph Scoring Alone or Combined with Other Risk Scores for Predicting Outcomes in COVID-19

Background Radiographic severity may help predict patient deterioration and outcomes from COVID-19 pneumonia. Purpose To assess the reliability and reproducibility of three chest radiograph reporting systems (radiographic assessment of lung edema [RALE], Brixia, and percentage opacification) in patients with proven SARS-CoV-2 infection and examine the ability of these scores to predict adverse outcomes both alone and in conjunction with two clinical scoring systems, National Early Warning Score 2 (NEWS2) and International Severe Acute Respiratory and Emerging Infection Consortium: Coronavirus Clinical Characterization Consortium (ISARIC-4C) mortality. Materials and Methods This retrospective cohort study used routinely collected clinical data of patients with polymerase chain reaction-positive SARS-CoV-2 infection admitted to a single center from February 2020 through July 2020. Initial chest radiographs were scored for RALE, Brixia, and percentage opacification by one of three radiologists. Intra- and interreader agreement were assessed with intraclass correlation coefficients. The rate of admission to the intensive care unit (ICU) or death up to 60 days after scored chest radiograph was estimated. NEWS2 and ISARIC-4C mortality at hospital admission were calculated. Daily risk for admission to ICU or death was modeled with Cox proportional hazards models that incorporated the chest radiograph scores adjusted for NEWS2 or ISARIC-4C mortality. Results Admission chest radiographs of 50 patients (mean age, 74 years ± 16 [standard deviation]; 28 men) were scored by all three radiologists, with good interreader reliability for all scores, as follows: intraclass correlation coefficients were 0.87 for RALE (95% CI: 0.80, 0.92), 0.86 for Brixia (95% CI: 0.76, 0.92), and 0.72 for percentage opacification (95% CI: 0.48, 0.85). Of 751 patients with a chest radiograph, those with greater than 75% opacification had a median time to ICU admission or death of just 1-2 days. Among 628 patients for whom data were available (median age, 76 years [interquartile range, 61-84 years]; 344 men), opacification of 51%-75% increased risk for ICU admission or death by twofold (hazard ratio, 2.2; 95% CI: 1.6, 2.8), and opacification greater than 75% increased ICU risk by fourfold (hazard ratio, 4.0; 95% CI: 3.4, 4.7) compared with opacification of 0%-25%, when adjusted for NEWS2 score. Conclusion Brixia, radiographic assessment of lung edema, and percentage opacification scores all reliably helped predict adverse outcomes in SARS-CoV-2 infection. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Little in this issue

Infants and newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB registry: a unique and challenging population

SIMPLE SUMMARY: Malignant rhabdoid tumors (MRT) are deadly tumors that predominantly affect infants and young children. Even when considering the generally young age of these patients, the treatment of infants below the age of six months represents a particular challenge due to the vulnerability of this patient population. The aim of our retrospective study was to assess the available information on prognostic factors, genetics, toxicity of treatment and long-term outcomes of MRT. We confirmed that, in a cohort of homogenously treated infants with MRT, significant predictors of outcome were female sex, localized stage, absence of a GLM and maintenance therapy, and these significantly favorably influence prognosis. Stratification-based biomarker-driven tailored trials may be a key option to improve survival rates. ABSTRACT: Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option

Infants and Newborns with Atypical Teratoid Rhabdoid Tumors (ATRT) and Extracranial Malignant Rhabdoid Tumors (eMRT) in the EU-RHAB Registry: A Unique and Challenging Population

Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option