Prediction of unplanned 30-day readmission for ICU patients with heart failure.

BACKGROUND: Intensive Care Unit (ICU) readmissions in patients with heart failure (HF) result in a significant risk of death and financial burden for patients and healthcare systems. Prediction of at-risk patients for readmission allows for targeted interventions that reduce morbidity and mortality. METHODS AND RESULTS: We presented a process mining/deep learning approach for the prediction of unplanned 30-day readmission of ICU patients with HF. A patient's health records can be understood as a sequence of observations called event logs; used to discover a process model. Time information was extracted using the DREAM (Decay Replay Mining) algorithm. Demographic information and severity scores upon admission were then combined with the time information and fed to a neural network (NN) model to further enhance the prediction efficiency. Additionally, several machine learning (ML) algorithms were developed to be used as the baseline models for the comparison of the results. RESULTS: By using the Medical Information Mart for Intensive Care III (MIMIC-III) dataset of 3411 ICU patients with HF, our proposed model yielded an area under the receiver operating characteristics (AUROC) of 0.930, 95% confidence interval of [0.898-0.960], the precision of 0.886, sensitivity of 0.805, accuracy of 0.841, and F-score of 0.800 which were far better than the results of the best baseline model and the existing literature. CONCLUSIONS: The proposed approach was capable of modeling the time-related variables and incorporating the medical history of patients from prior hospital visits for prediction. Thus, our approach significantly improved the outcome prediction compared to that of other ML-based models and health calculators.

A process mining- deep learning approach to predict survival in a cohort of hospitalized COVID-19 patients.

BACKGROUND: Various machine learning and artificial intelligence methods have been used to predict outcomes of hospitalized COVID-19 patients. However, process mining has not yet been used for COVID-19 prediction. We developed a process mining/deep learning approach to predict mortality among COVID-19 patients and updated the prediction in 6-h intervals during the first 72 h after hospital admission. METHODS: The process mining/deep learning model produced temporal information related to the variables and incorporated demographic and clinical data to predict mortality. The mortality prediction was updated in 6-h intervals during the first 72 h after hospital admission. Moreover, the performance of the model was compared with published and self-developed traditional machine learning models that did not use time as a variable. The performance was compared using the Area Under the Receiver Operator Curve (AUROC), accuracy, sensitivity, and specificity. RESULTS: The proposed process mining/deep learning model outperformed the comparison models in almost all time intervals with a robust AUROC above 80% on a dataset that was imbalanced. CONCLUSIONS: Our proposed process mining/deep learning model performed significantly better than commonly used machine learning approaches that ignore time information. Thus, time information should be incorporated in models to predict outcomes more accurately.

A hermetic on-cryostat helium source for low temperature experiments.

We describe a helium source cell for use in cryogenic experiments that is hermetically sealed in situ on the cold plate of a cryostat. The source cell is filled with helium gas at room temperature and, subsequently, sealed using a cold weld crimping tool before the cryostat is closed and cooled down. At low temperatures, the helium condenses and collects in a connected experimental volume, as monitored via the frequency response of a planar superconducting resonator device sensitive to small amounts of liquid helium. This on-cryostat helium source negates the use of a filling tube between the cryogenic volumes and room temperature, thereby preventing unwanted effects such as temperature instabilities that arise from the thermomechanical motion of helium within the system. This helium source can be used in experiments investigating the properties of quantum fluids or to better thermalize quantum devices.

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee: a randomized controlled trial. 1: clinical effectiveness.

OBJECTIVE: To evaluate the clinical effectiveness of manual physiotherapy and/or exercise physiotherapy in addition to usual care for patients with osteoarthritis (OA) of the hip or knee. DESIGN: In this 2 × 2 factorial randomized controlled trial, 206 adults (mean age 66 years) who met the American College of Rheumatology criteria for hip or knee OA were randomly allocated to receive manual physiotherapy (n = 54), multi-modal exercise physiotherapy (n = 51), combined exercise and manual physiotherapy (n = 50), or no trial physiotherapy (n = 51). The primary outcome was change in the Western Ontario and McMaster osteoarthritis index (WOMAC) after 1 year. Secondary outcomes included physical performance tests. Outcome assessors were blinded to group allocation. RESULTS: Of 206 participants recruited, 193 (93.2%) were retained at follow-up. Mean (SD) baseline WOMAC score was 100.8 (53.8) on a scale of 0-240. Intention to treat analysis showed adjusted reductions in WOMAC scores at 1 year compared with the usual care group of 28.5 (95% confidence interval (CI) 9.2-47.8) for usual care plus manual therapy, 16.4 (-3.2 to 35.9) for usual care plus exercise therapy, and 14.5 (-5.2 to 34.1) for usual care plus combined exercise therapy and manual therapy. There was an antagonistic interaction between exercise therapy and manual therapy (P = 0.027). Physical performance test outcomes favoured the exercise therapy group. CONCLUSIONS: Manual physiotherapy provided benefits over usual care, that were sustained to 1 year. Exercise physiotherapy also provided physical performance benefits over usual care. There was no added benefit from a combination of the two therapies. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12608000130369.

Identifying the source of bullet wipe: a randomised blind trial.

OBJECTIVE: To assess the usefulness of scanning electron microscopy and energy dispersive x-ray spectroscopy in matching bullet wipe to the bullet. HYPOTHESIS: Bullet wipe can be used to match a bullet type to a crime scene.

Gunshot induced indirect femoral fracture: mechanism of injury and fracture morphology.

INTRODUCTION: Indirect ballistic fractures occur when a projectile passes close to, but not contacting, the bone. The mechanism of how these fractures occur is not yet proven, but recently the acoustic shockwave has been excluded as a cause. The objective of this study is to determine whether the expanding temporary cavity, the collapse of this cavity or its oscillation causes these fractures. In addition, we describe the fracture morphology and biomechanical causes of this injury. METHOD: 40 fresh deer femora were strain gauged and embedded in ballistic gelatin before being shot with four different projectiles with varying distances off the bone. Pressure recordings, chronographs and radar allowed assessment of local pressures and energy transfer. High-speed video allowed the temporal relationship between the temporary cavity and fracture formation to be analysed, while sample dissection allowed the fracture morphology to be described. RESULTS: The fractures produced were consistently wedge-shaped and caused by the expansion of the temporary cavity, flexing the bone beyond its yield point, causing tension failure on the cortex opposite the expanding temporary cavity and a compression wedge on the side of the cavity. Local pressure was not predictive of fracture formation but the energy transfer to the gelatin block was predictive. CONCLUSIONS: Indirect fractures are caused by the expansion of the temporary cavity and relate to the proximity of this cavity to the bone. Fractures occur from flexion of the bone and classically display wedge-shaped fracture patterns with the apex of the wedge pointing away from the expanding cavity.

Variability of blood lactate during and between given constant prolonged cycling power.

AIM: Blood lactate concentration (BLC) has been the basis of rational performance diagnostics for almost five decades. Aim of this study was to identify the variability of the BLC during repeated constant power tests (VC-BLC) and to quantify the corresponding variability of changes in the BLC over time (VC-BLC-Difference). METHODS: Twelve healthy male subjects (24.8±3-8 years, 182.9±7.5 cm, 75.7±7.1 kg, ·VO2peak: 4.1±0.6 l min-1) performed four series of three constant power tests at exercise intensities of 45% (A), 60% (B), 75% (C) and 90% (D) of VO2peak. Blood sampling was conducted before, at the end of every 5th min and at the end of each test terminated ahead of schedule. RESULTS: BLC was different at all exercise intensities from minute five onwards. Power output was equivalent to 142.1±18.9 W (A), 196.3±25.2 W (B), 247.9±30.3 W (C) and 302.5±38.4 W (D). VC-BLC varied between 9±2.2% and 21±10.1%. VC-BLC and VC-BLC-Difference between 10th and 30th min correlated inversely with mean BLC level and BLC-Difference respectively. CONCLUSION: By providing first data on constant power test VC-BLC and VC-BLC-Difference this study might help to improve performance diagnostics and training control in sports medicine and medical exercise therapy by assisting in selecting and monitoring exercise intensity. Performance monitoring with BLC-Differences is feasible at moderate and high exercise intensities; single BLC measurements at termination of tests might not be sufficient.

United States (US) multi-center study to assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III).

STUDY DESIGN: Multi-center, prospective, cohort study. OBJECTIVES: To assess the validity and reliability of the Spinal Cord Independence Measure (SCIM III) in measuring functional ability in persons with spinal cord injury (SCI). SETTING: Inpatient rehabilitation hospitals in the United States (US). METHODS: Functional ability was measured with the SCIM III during the first week of admittance into inpatient acute rehabilitation and within one week of discharge from the same rehabilitation program. Motor and sensory neurologic impairment was measured with the American Spinal Injury Association Impairment Scale. The Functional Independence Measure (FIM), the default functional measure currently used in most US hospitals, was used as a comparison standard for the SCIM III. Statistical analyses were used to test the validity and reliability of the SCIM III. RESULTS: Total agreement between raters was above 70% on most SCIM III tasks and all κ-coefficients were statistically significant (P<0.001). The coefficients of Pearson correlation between the paired raters were above 0.81 and intraclass correlation coefficients were above 0.81. Cronbach's-α was above 0.7, with the exception of the respiration task. The coefficient of Pearson correlation between the FIM and SCIM III was 0.8 (P<0.001). For the respiration and sphincter management subscale, the SCIM III was more responsive to change, than the FIM (P<0.0001). CONCLUSION: Overall, the SCIM III is a reliable and valid measure of functional change in SCI. However, improved scoring instructions and a few modifications to the scoring categories may reduce variability between raters and enhance clinical utility.

Predicting the transition from acute to persistent low back pain.

BACKGROUND: Most people experience low back pain (LBP) at least once in their lifetime. Only a minority of them go on to develop persistent LBP. However, the socioeconomic costs of persistent LBP significantly exceed the costs of the initial acute LBP episode. AIMS: To identify factors that influence the progression of acute LBP to the persistent state at an early stage. METHODS: Prospective inception cohort study of patients attending a health practitioner for their first episode of acute LBP or recurrent LBP after a pain free period of at least 6 months. Patients were assessed at baseline addressing occupational and psychological factors as well as pain, disability, quality of life and physical activity and followed up at 3, 6, 12 weeks and 6 months. Variables were combined to the three indices 'working condition', 'depression and maladaptive cognitions' and 'pain and quality of life'. RESULTS: The index 'depression and maladaptive cognitions' was found to be a significant baseline predictor for persistent LBP up to 6 months (OR 5.1; 95% CI: 1.04-25.1). Overall predictive accuracy of the model was 81%. CONCLUSIONS: In this study of patients with acute LBP in a primary care setting psychological factors at baseline correlated with a progression to persistent LBP up to 6 months. The benefit of including factors such as 'depression and maladaptive cognition' in screening tools is that these factors can be addressed in primary and secondary prevention.

Identification of prognostic factors for chronicity in patients with low back pain: a review of screening instruments.

Low back pain (LBP) is currently the most prevalent and costly musculoskeletal problem in modern societies. Screening instruments for the identification of prognostic factors in LBP may help to identify patients with an unfavourable outcome. In this systematic review screening instruments published between 1970 and 2007 were identified by a literature search. Nine different instruments were analysed and their different items grouped into ten structures. Finally, the predictive effectiveness of these structures was examined for the dependent variables including "work status", "functional limitation", and "pain". The strongest predictors for "work status" were psychosocial and occupational structures, whereas for "functional limitation" and "pain" psychological structures were dominating. Psychological and occupational factors show a high reliability for the prognosis of patients with LBP. Screening instruments for the identification of prognostic factors in patients with LBP should include these factors as a minimum core set.

The structure and function of yeast ARS elements.

The past year has seen significant advances in our understanding of the structure and function of yeast ARS elements. These elements, some of which function as chromosomal origins of DNA replication, are modular in structure. An essential domain, the ARS consensus sequence, binds a multiprotein complex that might be the long-sought initiator protein. The flanking domain contains a DNA unwinding element and a binding site for a multifunctional protein that acts as a replication enhancer.

Implant retention in infected joint replacements: a surgeon's perspective.

There is no standard treatment for infected joint replacements. The surgical options are varied and treatment choices may pose problems in relation to both efficacy and cost effectiveness. Surgical debridement combined with antibiotic therapy is an appealing option for surgeons and patients as it can lead to eradication of the infection with implant retention and good functional outcome. It avoids major revision surgery which can result in significant morbidity and mortality in an elderly group of patients.The author reviewed 73 patients with hip and knee periprosthetic infections and the data was analyzed in terms of outcome of primary treatment and final outcome, including bacteriology and prosthesis retention. Out of the 73 patients (53 hips and 20 knees), the majority (69%) were managed by primary surgical debridement followed by antibiotics and about one third (34%) lost their implants as a result of the infection. Retention of implants was higher in acute infections (85-100%) as opposed to late infections (20-50%). The microbiological analysis showed that Staphylococcus and Streptococcus caused the majority (76%) of infections. In this series, patients with an infected joint replacement had roughly the same probability (30%) of retaining the original prosthesis, undergoing a successful revision, or having no implants in situ at the end of treatment.

Two compound replication origins in Saccharomyces cerevisiae contain redundant origin recognition complex binding sites.

While many of the proteins involved in the initiation of DNA replication are conserved between yeasts and metazoans, the structure of the replication origins themselves has appeared to be different. As typified by ARS1, replication origins in Saccharomyces cerevisiae are <150 bp long and have a simple modular structure, consisting of a single binding site for the origin recognition complex, the replication initiator protein, and one or more accessory sequences. DNA replication initiates from a discrete site. While the important sequences are currently less well defined, metazoan origins appear to be different. These origins are large and appear to be composed of multiple, redundant elements, and replication initiates throughout zones as large as 55 kb. In this report, we characterize two S. cerevisiae replication origins, ARS101 and ARS310, which differ from the paradigm. These origins contain multiple, redundant binding sites for the origin recognition complex. Each binding site must be altered to abolish origin function, while the alteration of a single binding site is sufficient to inactivate ARS1. This redundant structure may be similar to that seen in metazoan origins.

Domain B of ARS307 contains two functional elements and contributes to chromosomal replication origin function.

ARS307 is highly active as a replication origin in its native location on chromosome III of Saccharomyces cerevisiae. Its ability to confer autonomous replication activity on plasmids requires the presence of an 11-bp autonomously replicating sequence (ARS) consensus sequence (ACS), which is also required for chromosomal origin function, as well as approximately 100 bp of sequence flanking the ACS called domain B. To further define the sequences required for ARS function, a linker substitution mutagenesis of domain B was carried out. The mutations defined two sequences, B1 and B2, that contribute to ARS activity. Therefore, like ARS1, domain B of ARS307 is composed of functional subdomains. Constructs carrying mutations in the B1 element were used to replace the chromosomal copy of ARS307. These mutations caused a reduction in chromosomal origin activity, demonstrating that the B1 element is required for efficient chromosomal origin function.

Biological, seasonal and environmental factors associated with Pulex irritans infestation of dairy goats in Greece.

The objectives of the present study were to study the fauna of fleas infesting dairy goats in Greece, the spectrum of hosts each flea species infests, identify risk factors in the environment, and goat management practices that favour flea infestation of goats, and describe the seasonal variation of infestation in goats. For this purpose, a total of 64 herds, with a history of flea infestation in goats, were visited during June and July of 2002 for data collection on flea burdens, species of fleas on goats, and other farm or pet animal species in the farm. Also data were collected on herd characteristics and management along with the flea infestation status of the village where it was located through a questionnaire survey. Data on elevation and climatic characteristics of the villages where the herds were located were also used in the study. All fleas collected from goats, sheep, pigs, and cattle were identified as being Pulex irritans. All fleas collected from cats were identified as being Ctenocephalides felis. Dogs were infested either with P. irritans, C. canis, or C. felis, or with both C. canis and C. felis. Kids had a significantly higher flea burden than goats and the Skopelos breed had the highest flea burden of all breeds followed in diminishing order by the breeds Capra prisca, Saanen cross mix, and Alpine cross mix (p < 0.05). The gender of the animal had no significant effect on flea burden. Factors significantly affecting the flea burden of goats were duration of flea infestation in the herd, type of flea control, and manure imported prior to the appearance of fleas in the herd (p < 0.05). The flea burden of goats was highest during summer and lowest during winter (p < 0.01), with complete an absence of infestation in January and February. Finally, a significant difference (p < 0.05) was found between the average annual temperature of villages with flea infestation (15.59 degrees C) and villages without flea infestation (17.14 degrees C). It was concluded that P. irritans was a true infestation of goats in Greece.

Perioperative mortality in New Zealand related to hip and knee replacement surgery: comparing administrative and registry data.

INTRODUCTION: Perioperative mortality is of considerable importance, but few national assessments are available. New Zealand has a clinical registry and an administrative dataset that both capture national information about hip and knee arthroplasties. National perioperative mortality rates were compared between the two data sources. METHOD: Data related to all patients undergoing an elective hip or knee replacement procedure (primary or revision) between 1 January 2007 and 31 December 2011 were separately extracted from the New Zealand Joint Registry and the National Minimum Dataset. The procedure date was used to define the occurrence of an event and dates were compared between datasets plus or minus 3 days. Date of death information was obtained from the National Mortality Collection and used to estimate 30 day mortality rates. RESULTS: No statistically significant differences in perioperative mortality were evident between comparisons from the two data sources although more deaths were recorded among Registry-only procedures. CONCLUSIONS: Estimates of 30 day perioperative mortality related to hip and knee arthroplasty procedures in New Zealand 2007-2011 are very similar regardless of data source. These data, coupled with perioperative mortality review using structured reports obtained from clinicians, could be used to develop a surveillance system to promote surgical safety.

Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance: the causative role of improper dissolution of Cremophor EL.

PURPOSE: An unusually high incidence of anaphylactoid reactions was observed during a phase I/II trial of high-dose intravenous cyclosporine (CsA) therapy to attenuate tumor multidrug resistance (MDR). Five of 21 children experienced severe anaphylactoid reactions shortly after initiation of the first or second CsA infusion. We hypothesized that improper dissolution of the vehicle Cremophor EL may have been a cause for these anaphylactoid reactions. METHODS: All nurses who had administered intravenous CsA were interviewed regarding their technique of preparing the infusion and the occurrence of an anaphylactoid reaction. The responses were statistically analyzed. The effect of various mixing techniques on the distribution of Cremophor EL in the infusion was experimentally evaluated. Different mixing techniques were used to assess their effect on the distribution of Cremophor EL in the solution. RESULTS: Analysis of the preparation techniques of the CsA infusion showed significant correlation between suboptimal mixing of CsA by nurses and the occurrence of anaphylactoid reactions (P = .02). Experimental simulation showed that suboptimal mixing results in an uneven distribution of Cremophor EL, which subsequently sinks to the bottom of the vial. CONCLUSION: Improper mixing of high-dose CsA infusions causes nonsolubilized Cremophor EL to sink to the outflow area of the bottle. An initial bolus infusion of highly concentrated Cremophor EL may produce an anaphylactoid-like response. This mechanism of toxicity is important to recognize, because it is easily preventable by proper preparation of the infusion, thus reducing the incidence of potentially life-threatening anaphylactoid reactions.

Conservation of ARS elements and chromosomal DNA replication origins on chromosomes III of Saccharomyces cerevisiae and S. carlsbergensis.

DNA replication origins, specified by ARS elements in Saccharomyces cerevisiae, play an essential role in the stable transmission of chromosomes. Little is known about the evolution of ARS elements. We have isolated and characterized ARS elements from a chromosome III recovered from an alloploid Carlsberg brewing yeast that has diverged from its S. cerevisiae homeologue. The positions of seven ARS elements identified in this S. carlsbergensis chromosome are conserved: they are located in intergenic regions flanked by open reading frames homologous to those that flank seven ARS elements of the S. cerevisiae chromosome. The S. carlsbergensis ARS elements were active both in S. cerevisiae and S. monacensis, which has been proposed to be the source of the diverged genome present in brewing yeast. Moreover, their function as chromosomal replication origins correlated strongly with the activity of S. cerevisiae ARS elements, demonstrating the conservation of ARS activity and replication origin function in these two species.

DNA sequence and functional analysis of homologous ARS elements of Saccharomyces cerevisiae and S. carlsbergensis.

ARS elements of Saccharomyces cerevisiae are the cis-acting sequences required for the initiation of chromosomal DNA replication. Comparisons of the DNA sequences of unrelated ARS elements from different regions of the genome have revealed no significant DNA sequence conservation. We have compared the sequences of seven pairs of homologous ARS elements from two Saccharomyces species, S. cerevisiae and S. carlsbergensis. In all but one case, the ARS308-ARS308(carl) pair, significant blocks of homology were detected. In the cases of ARS305, ARS307, and ARS309, previously identified functional elements were found to be conserved in their S. carlsbergensis homologs. Mutation of the conserved sequences in the S. carlsbergensis ARS elements revealed that the homologous sequences are required for function. These observations suggested that the sequences important for ARS function would be conserved in other ARS elements. Sequence comparisons aided in the identification of the essential matches to the ARS consensus sequence (ACS) of ARS304, ARS306, and ARS310(carl), though not of ARS310.

Parasitic central nervous system infections: echinococcus and schistosoma.

Central nervous system (CNS) manifestations of Echinococcus and Schistosoma infections occur throughout the world, with incidence increasing in developed regions. A detailed literature review generated a current summary on epidemiology, parasitology, pathology, clinical manifestations, imaging studies, diagnosis, and treatment of neuroechinococcosis and neuroschistosomiasis. Recent advancements have been made in diagnosis, treatment, and prevention of these parasitic CNS infections. Ongoing advancements in neuroimaging and diagnostic studies, as well as efforts to better understand the parasite genome and host-parasite relationships, will likely continue to improve patient management.