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BACKGROUND: Programmed cell death protein 1 (PD-1) inhibitors prolong survival versus chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), which often expresses cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-ligand 1 (PD-L1), providing a rationale for combined PD-(L)1 and CTLA-4 blockade. We report a phase I, open-label study of the PD-L1 inhibitor durvalumab plus the CTLA-4 inhibitor tremelimumab (NCT02262741). METHODS: In dose exploration, two cohorts of previously treated patients received durvalumab 10 mg/kg plus tremelimumab 3 mg/kg, or durvalumab 20 mg/kg plus tremelimumab 1 mg/kg, for up to 12 months. Dose expansion comprised two cohorts of previously untreated patients with R/M HNSCC having baseline PD-L1 tumor cell (TC) expression ≥25% and <25% and one cohort of immunotherapy-pretreated patients with any PD-L1 level. All received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg, then durvalumab 10 mg/kg, for up to 12 months. The primary endpoint was safety. The secondary endpoints were objective response rate (ORR) by RECIST version 1.1, pharmacokinetics, pharmacodynamics, and immunogenicity. RESULTS: A total of 71 patients were treated. The median duration of exposure was 13.6 weeks for durvalumab and 13.1 weeks for tremelimumab. In dose exploration, no dose-limiting toxicities occurred. No maximum tolerated dose was identified. Treatment-related adverse events (TRAEs) occurred in 69.0% of patients; grade 3/4 and serious TRAEs occurred in 31.0% and 18.3%, respectively. TRAEs led to discontinuation in 9.9%. There were no treatment-related deaths. The ORR was 5.6% (95% confidence interval 1.6-13.8), including one complete response and three partial responses, all patients were in dose expansion with PD-L1 TC ≥25% and no prior immunotherapy exposure; three had ongoing responses ≥12 months. The median overall survival in the total population was 8.6 months. Soluble PD-L1 suppression was almost

Background Pembrolizumab alone and in combination with platinum-based chemotherapy have become standard first-line treatment options for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC), and there is a growing unmet need for safe and efficacious treatment options for R/M HNSCC that has progressed on or after platinum-based chemotherapy and immunotherapy. Data from Study 111/KEYNOTE-146 showed promising antitumor activity and acceptable safety for the PD-1 inhibitor pembrolizumab given in combination with the multikinase inhibitor lenvatinib in patients with metastatic HNSCC.1 LEAP-009 (NCT04428151), a global, randomized, open-label, phase 2 trial, will assess the efficacy and safety of pembrolizumab in combination with lenvatinib versus SOC chemotherapy, as well as the efficacy and safety of lenvatinib monotherapy, in patients with R/M HNSCC that has progressed after platinum-based chemotherapy and a PD-(L)1 inhibitor. Methods Eligible patients are adults with histologically confirmed, locally incurable R/M HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx, disease progression at any time during or after platinum-containing chemotherapy (with or without cetuximab), disease progression within 12 weeks from the last dose of treatment with ≥2 doses of a PD-(L)1 inhibitor, measurable disease based on RECIST v1.1 as confirmed by BICR, ECOG performance status of 0 or 1, and no major blood vessel invasion/infiltration. Patients will be randomized 3:3:2 to pembrolizumab (200 mg IV Q3W for up to 35 cycles) plus lenvatinib (20 mg orally once daily), investigator’s choice of SOC chemotherapy (docetaxel, paclitaxel, cetuximab, or capecitabine), or lenvatinib monotherapy (24 mg orally once daily). Randomization will be stratified by PD-L1 tumor proportion score (<50% versus ≥50%) and ECOG performance status (0 versus 1). Treatment will continue until centrally verified disease progression, unacceptable toxicity, or decision to withdraw. Patien

Ya-Ting Chang,1 L Kristopher Siu,2 Jann-Tay Wang,3 Tsu-Lan Wu,4 Yu-Hui Chen,5,6 Yin-Ching Chuang,7,8 Jung-Chung Lin,9 Po-Liang Lu1,101Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 2National Institutes of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 4Department of Clinical Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Infection Control Center, Chi Mei Medical Center, Tainan, Taiwan; 6Department of Nursing, College of Medicine and Life Science, Chung Hwa University of Medical Technology, Tainan, Taiwan; 7Department of Internal Medicine and Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 8Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; 9Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 10College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanPurpose: This study aimed to investigate the resistance mechanisms and molecular epidemiology of carbapenem-nonsusceptible Escherichia coli (CnsEC) in Taiwan.Patients and methods: From 2012 to 2015, 237 E. coli isolates with minimum inhibitory concentrations of imipenem or meropenem >1 μg/mL were collected in a nationwide surveillance and subjected to polymerase chain reaction (PCR) for carbapenemase, AmpC-type β-lactamase, and extended spectrum β-lactamase (ESBL) genes. We evaluated outer membrane proteins (OmpF and OmpC) loss and conducted multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Isolates that were resistant to all carbapenems were designated as pan-carbapenem-resistant E. coli (pCREC) in this study.Results: The predominant resistance mechanism of CnsEC in Taiwan was the CMY-2 &beta

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

Cybermanufacturing is a new paradigm that both manufacturing software and hardware tools are seamlessly integrated by enabling information infrastructure and are accessed as services in cyberspace. This paradigm encourages tool sharing and reuse thus can reduce cost and time in product realization. In this research, a new cost estimation framework is developed based on big data analytics tools so that the manufacturing cost associated with a new job can be estimated based on the similar ones in the past. Manufacturers can use this cost analytics service in their job bidding process, which is currently ad hoc and subjective in industry practice. The new framework is implemented and demonstrated for additive manufacturing, where the similarities of 3D geometry of parts and printing processes are established by identifying relevant features. Machine learning algorithms for dynamic clustering, LASSO and elastic net regressions are applied to feature vectors to predict the cost based on historical data. © 2017

BACKGROUND: PhaxanTM (PHAX, Chemic Labs, Canton, MA) is an aqueous solution of 10 mg/mL alphaxalone and 13% 7-sulfobutylether beta-cyclodextrin (betadex). In preclinical studies, PHAX is a fast onset.offset IV anesthetic like propofol, but causes less cardiovascular depression. This firstinman study was designed to find the anesthetic dose of PHAX and to compare it with an equivalent dose of propofol for safety, efficacy, and quality of recovery from anesthesia and sedation. METHOD(S): The study adhered to compliance with Good Clinical Practices regulations (clinical trials registry number, ACTRN12611000343909). This randomized, double-blind study compared PHAX and propofol using a Bayesian algorithm to determine dose equivalence for effects on the bispectral index (BIS). Male volunteers, ASA physical status I, gave written informed consent (n = 12 per group; PHAX or propofol). Parameters assessed for 80 minutes after drug injection (single bolus dose) were pain on injection, involuntary movement, BIS, blood pressure, need for airway support, and, as measures of recovery from sedation, the Richmond Agitation and Sedation Scale and the Digit Symbol Substitution Test. Arterial blood was withdrawn for biochemistry, hematology, and complement levels. RESULT(S): No subject complained of pain on injection with PHAX, whereas 8 of the 12 subjects given propofol did. Nine PHAX and 8 propofol subjects reached BIS values of <=50: median (interquartile range [IQR]) mg/kg dose = 0.5 (0.5-0.6) for PHAX and 2.9 (2.4-3.0) for propofol. The lowest median BIS reached was 27 to 28 for both agents with no significant differences between them for timing of onset and recovery of BIS. The concomitant median changes in systolic and diastolic blood pressures were -11% vs -19% for systolic and.25% vs -37% for diastolic in PHAX- and propofol-treated subjects, respectively. Nine of the 12 propofol-treated subjects and none of 12 PHAX-treated subjects required airway support. For subjects reach

Background. The acid-base, biochemical and hematological effects of crystalloid solutions have not been comprehensively evaluated in patients with liver resection. Methods. Design(s): multicenter, prospective, double-blind randomized controlled trial investigating the biochemical effects of Hartmann's solution (HS) or Plasmalyte-148 (PL) in 60 patients undergoing major liver resection. Primary Outcome: base excess immediately after surgery. Secondary Outcomes: changes in blood biochemistry and hematology. Results. At completion of surgery, patients receiving HS had equivalent mean standard base excess (-1.7+/-2.2 vs. -0.9+/-2.3 meq/L; P=0.17) to those treated with PL. However, patients treated with HS were more hyperchloremic (difference 1.7 mmol/L, 95% CI: 0.2 to 3.2, P=0.03) and hyperlactatemic (difference 0.8 mmol/L, 95% CI: 0.2 to 1.3; P=0.01). In contrast, patients receiving PL had higher mean plasma magnesium levels and lower ionized calcium levels. There were no significant differences in pH, bicarbonate, albumin and phosphate levels. Immediately after surgery, mean PT and aPTT were significantly lower in the PL group. Intraoperatively, the median (IQR) blood loss in the PL group was 300 mL (200:413) vs. 500 mL (300:638) in the HS group (P=0.03). Correspondingly, the postoperative hemoglobin was higher in the PL group. Total complications were more frequent in the HS Group (56% vs. 20%, relative risk 2.8; 95% CI: 1.3 to 6.1; P=0.007). Conclusion. In liver resection patients, HS and PL led to similar base excess values but different post operative plasma biochemistry and hematology values. Understanding of these effects may help clinicians individualize fluid therapy in these patients.Copyright © 2015 EDIZIONI MINERVA MEDICA.

Background. The acid-base, biochemical and hematological effects of crystalloid solutions have not been comprehensively evaluated in patients with liver resection. Methods. Design(s): multicenter, prospective, double-blind randomized controlled trial investigating the biochemical effects of Hartmann's solution (HS) or Plasmalyte-148 (PL) in 60 patients undergoing major liver resection. Primary Outcome: base excess immediately after surgery. Secondary Outcomes: changes in blood biochemistry and hematology. Results. At completion of surgery, patients receiving HS had equivalent mean standard base excess (-1.7+/-2.2 vs. -0.9+/-2.3 meq/L; P=0.17) to those treated with PL. However, patients treated with HS were more hyperchloremic (difference 1.7 mmol/L, 95% CI: 0.2 to 3.2, P=0.03) and hyperlactatemic (difference 0.8 mmol/L, 95% CI: 0.2 to 1.3; P=0.01). In contrast, patients receiving PL had higher mean plasma magnesium levels and lower ionized calcium levels. There were no significant differences in pH, bicarbonate, albumin and phosphate levels. Immediately after surgery, mean PT and aPTT were significantly lower in the PL group. Intraoperatively, the median (IQR) blood loss in the PL group was 300 mL (200:413) vs. 500 mL (300:638) in the HS group (P=0.03). Correspondingly, the postoperative hemoglobin was higher in the PL group. Total complications were more frequent in the HS Group (56% vs. 20%, relative risk 2.8; 95% CI: 1.3 to 6.1; P=0.007). Conclusion. In liver resection patients, HS and PL led to similar base excess values but different post operative plasma biochemistry and hematology values. Understanding of these effects may help clinicians individualize fluid therapy in these patients.Copyright © 2015 EDIZIONI MINERVA MEDICA.

BACKGROUND: PhaxanTM (PHAX, Chemic Labs, Canton, MA) is an aqueous solution of 10 mg/mL alphaxalone and 13% 7-sulfobutylether beta-cyclodextrin (betadex). In preclinical studies, PHAX is a fast onset.offset IV anesthetic like propofol, but causes less cardiovascular depression. This firstinman study was designed to find the anesthetic dose of PHAX and to compare it with an equivalent dose of propofol for safety, efficacy, and quality of recovery from anesthesia and sedation. METHOD(S): The study adhered to compliance with Good Clinical Practices regulations (clinical trials registry number, ACTRN12611000343909). This randomized, double-blind study compared PHAX and propofol using a Bayesian algorithm to determine dose equivalence for effects on the bispectral index (BIS). Male volunteers, ASA physical status I, gave written informed consent (n = 12 per group; PHAX or propofol). Parameters assessed for 80 minutes after drug injection (single bolus dose) were pain on injection, involuntary movement, BIS, blood pressure, need for airway support, and, as measures of recovery from sedation, the Richmond Agitation and Sedation Scale and the Digit Symbol Substitution Test. Arterial blood was withdrawn for biochemistry, hematology, and complement levels. RESULT(S): No subject complained of pain on injection with PHAX, whereas 8 of the 12 subjects given propofol did. Nine PHAX and 8 propofol subjects reached BIS values of <=50: median (interquartile range [IQR]) mg/kg dose = 0.5 (0.5-0.6) for PHAX and 2.9 (2.4-3.0) for propofol. The lowest median BIS reached was 27 to 28 for both agents with no significant differences between them for timing of onset and recovery of BIS. The concomitant median changes in systolic and diastolic blood pressures were -11% vs -19% for systolic and.25% vs -37% for diastolic in PHAX- and propofol-treated subjects, respectively. Nine of the 12 propofol-treated subjects and none of 12 PHAX-treated subjects required airway support. For subjects reach

The acid-base, biochemical and hematological effects of crystalloid solutions have not been comprehensively evaluated in patients with liver resection. multicenter, prospective, double-blind randomized controlled trial investigating the biochemical effects of Hartmann's solution (HS) or Plasmalyte-148 (PL) in 60 patients undergoing major liver resection. base excess immediately after surgery. changes in blood biochemistry and hematology. At completion of surgery, patients receiving HS had equivalent mean standard base excess (-1.7±2.2 vs. -0.9±2.3 meq/L; P=0.17) to those treated with PL. However, patients treated with HS were more hyperchloremic (difference 1.7 mmol/L, 95% CI: 0.2 to 3.2, P=0.03) and hyperlactatemic (difference 0.8 mmol/L, 95% CI: 0.2 to 1.3; P=0.01). In contrast, patients receiving PL had higher mean plasma magnesium levels and lower ionized calcium levels. There were no significant differences in pH, bicarbonate, albumin and phosphate levels. Immediately after surgery, mean PT and aPTT were significantly lower in the PL group. Intraoperatively, the median (IQR) blood loss in the PL group was 300 mL (200:413) vs. 500 mL (300:638) in the HS group (P=0.03). Correspondingly, the postoperative hemoglobin was higher in the PL group. Total complications were more frequent in the HS Group (56% vs. 20%, relative risk 2.8; 95% CI: 1.3 to 6.1; P=0.007). In liver resection patients, HS and PL led to similar base excess values but different post operative plasma biochemistry and hematology values. Understanding of these effects may help clinicians individualize fluid therapy in these patients.

The acid-base, biochemical and hematological effects of crystalloid solutions have not been comprehensively evaluated in patients with liver resection. multicenter, prospective, double-blind randomized controlled trial investigating the biochemical effects of Hartmann's solution (HS) or Plasmalyte-148 (PL) in 60 patients undergoing major liver resection. base excess immediately after surgery. changes in blood biochemistry and hematology. At completion of surgery, patients receiving HS had equivalent mean standard base excess (-1.7±2.2 vs. -0.9±2.3 meq/L; P=0.17) to those treated with PL. However, patients treated with HS were more hyperchloremic (difference 1.7 mmol/L, 95% CI: 0.2 to 3.2, P=0.03) and hyperlactatemic (difference 0.8 mmol/L, 95% CI: 0.2 to 1.3; P=0.01). In contrast, patients receiving PL had higher mean plasma magnesium levels and lower ionized calcium levels. There were no significant differences in pH, bicarbonate, albumin and phosphate levels. Immediately after surgery, mean PT and aPTT were significantly lower in the PL group. Intraoperatively, the median (IQR) blood loss in the PL group was 300 mL (200:413) vs. 500 mL (300:638) in the HS group (P=0.03). Correspondingly, the postoperative hemoglobin was higher in the PL group. Total complications were more frequent in the HS Group (56% vs. 20%, relative risk 2.8; 95% CI: 1.3 to 6.1; P=0.007). In liver resection patients, HS and PL led to similar base excess values but different post operative plasma biochemistry and hematology values. Understanding of these effects may help clinicians individualize fluid therapy in these patients.

Background Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. Methods/Design This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. Trial Registration ClinicalTrials.gov: NCT00842608

Background Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. Methods/Design This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. Trial Registration ClinicalTrials.gov: NCT00842608

Background Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. Methods/Design This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. Trial Registration ClinicalTrials.gov: NCT00842608

Background Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. Methods/Design This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. Trial Registration ClinicalTrials.gov: NCT00842608

BACKGROUND: The USCOM1A continuous wave cardiac output monitor (USCOM Pty Ltd., Sydney, NSW, Australia) is a novel Doppler-based device used to measure cardiac output noninvasively. The proper alignment of the transducer, and hence the ultrasound beam to the aortic or pulmonary outflow tracts, is essential to acquire accurate measurements and often much time is spent on transducer and/or patient positioning. In this prospective, observational, crossover study, we investigated the effect of patient positioning on the acquisition of cardiac output measurement with USCOM1A. METHOD(S): We measured cardiac output using USCOM1A in 30 healthy adult volunteers, each in five different positions: sitting, supine, Trendelenburg (20 degrees), left lateral tilt (20 degrees), and right lateral tilt (20 degrees) and compared the time required to obtain acceptable measurements. We also compared the quality of the Doppler signal obtained in these positions using a scoring system designed for this study. RESULT(S): There was a higher rate of failed measurement, the mean time to obtain the first acceptable measurement was prolonged and the optimal measurement obtained within a 5-min period was of a lower quality in the sitting position compared with the other four positions. CONCLUSION(S): Our results suggested the sitting position is the least suitable and least reliable position in which to perform cardiac output measurements using USCOM1A compared with the supine, Trendelenburg (20 degrees), left lateral tilt (20 degrees), and right lateral tilt (20 degrees) positions. © 2008 International Anesthesia Research Society.

BACKGROUND: The USCOM1A continuous wave cardiac output monitor (USCOM Pty Ltd., Sydney, NSW, Australia) is a novel Doppler-based device used to measure cardiac output noninvasively. The proper alignment of the transducer, and hence the ultrasound beam to the aortic or pulmonary outflow tracts, is essential to acquire accurate measurements and often much time is spent on transducer and/or patient positioning. In this prospective, observational, crossover study, we investigated the effect of patient positioning on the acquisition of cardiac output measurement with USCOM1A. METHOD(S): We measured cardiac output using USCOM1A in 30 healthy adult volunteers, each in five different positions: sitting, supine, Trendelenburg (20 degrees), left lateral tilt (20 degrees), and right lateral tilt (20 degrees) and compared the time required to obtain acceptable measurements. We also compared the quality of the Doppler signal obtained in these positions using a scoring system designed for this study. RESULT(S): There was a higher rate of failed measurement, the mean time to obtain the first acceptable measurement was prolonged and the optimal measurement obtained within a 5-min period was of a lower quality in the sitting position compared with the other four positions. CONCLUSION(S): Our results suggested the sitting position is the least suitable and least reliable position in which to perform cardiac output measurements using USCOM1A compared with the supine, Trendelenburg (20 degrees), left lateral tilt (20 degrees), and right lateral tilt (20 degrees) positions. © 2008 International Anesthesia Research Society.

In electrified railways, the traction power systems carry power to trains and their reliability is vital to the quality of train services. There are many components in the traction power system, from interface with utility distribution network to contacts with trains, and they are physically located along the rail line. Subject to usage, environment, and ageing, conditions of components deteriorate with time. Regular maintenance has to be carried out to restore their conditions and prevent them from failure. However, the decisions on the suitable length of maintenance intervals often lead railway operators to the dilemma of minimizing both risk of failure and operation cost. On the basis of a stochastic lifetime model, this article presents a generic software evaluation tool that enables the operators to manage risk of failure and cost quantitatively in order to match their preferred levels of service quality. The lifetime model includes the effects of condition restoration because of maintenance of regular intervals and ageing acceleration because of electrical stress from traffic demands. Examples of simulation results are given to illustrate the applicability of this lifetime model.

Aim - To determine the importance and contribution of compliance in a pelvic muscle exercise program as a factor in reducing the severity of urinary stress incontinence amongst Chinese women. Methods - Two hundred fourteen women presenting with urinary stress incontinence who agreed to undertake a program of pelvic muscle exercises were recruited into the study. Incontinence (wetting episodes), pelvic muscle strength, exercises compliance, correctness of pelvic muscle exercise technique, duration of stress incontinence, and previous history of pelvic surgery were recorded on four occasions: baseline (first clinic session) and second to fourth clinic sessions. Demographic data were also collected at baseline. Stepwise multiple regression analyses were used to determine the relative importance of compliance to exercise regime in predicting the severity of incontinence. Path analysis was used to provide a summary description of the influence of compliance on the outcomes over the four visits. Results - The pelvic muscle training program appears to be able to reduce the overall urinary incontinence episodes by 85.2% and achieved a 73.1% increase in pelvic muscle strength. Although the number of wetting episodes in any visit are causally linked to that recorded in previous visit, those who were more compliant had a greater reduction. Age, mode of delivery, menopausal status, history of pelvic surgery, and duration of incontinence did not appear to contribute significantly to predicting incontinence. Conclusion - Compliance with pelvic muscle exercises significantly contributed to a reduction in urinary stress incontinence.

Given a continuous function $f(x)$, suppose that the sign of $f$ only has finitely many discontinuous points in the interval $[0,1]$. We show how to use a sequence of one dimensional deterministic binary cellular automata to determine the sign of $f(\rho)$ where $\rho$ is the (number) density of 1s in an arbitrarily given bit string of finite length provided that $f$ satisfies certain technical conditions., Comment: Revtex, uses amsfonts, 10 pages