Wave Speed Measurements in Non-Ideal Compressible Flows Using the Flexible Asymmetric Shock Tube (FAST)

Non-ideal compressible fluid dynamics (NICFD) are defined as compressible fluid flows occurring in the dense vapour, dense vapour-liquid equilibrium or supercritical thermodynamic region. This type of flow can occur in expanders of organic Rankine cycle power plants. In order to study NICFD, a Ludwieg tube-type facility has been designed and constructed at Delft University of Technology. A large variety of fluids can be employed in the facility, but for this study D6 siloxane is chosen as working fluid due to its high thermal stability and the possibility of encountering non-classical gasdynamic phenomena. This compound belongs to the siloxane class, which are also used as working fluids in ORC power systems. Gasdynamic experiments within the NICFD region are presented from which the wave speed and speed of sound can be inferred using the time-of-flight technique. These data can be used to improve and validate thermodynamic models

Diagnostic accuracy of history taking, physical examination and imaging for phalangeal, metacarpal and carpal fractures: a systematic review update.

BACKGROUND: The standard diagnostic work-up for hand and wrist fractures consists of history taking, physical examination and imaging if needed, but the supporting evidence for this work-up is limited. The purpose of this study was to systematically examine the diagnostic accuracy of tests for hand and wrist fractures. METHODS: A systematic search for relevant studies was performed. Methodological quality was assessed and sensitivity (Se), specificity (Sp), accuracy, positive predictive value (PPV) and negative predictive value (NPV) were extracted from the eligible studies. RESULTS: Of the 35 eligible studies, two described the diagnostic accuracy of history taking for hand and wrist fractures. Physical examination with or without radiological examination for diagnosing scaphoid fractures (five studies) showed Se, Sp, accuracy, PPV and NPV ranging from 15 to 100%, 13-98%, 55-73%, 14-73% and 75-100%, respectively. Physical examination with radiological examination for diagnosing other carpal bone fractures (one study) showed a Se of 100%, with the exception of the triquetrum (75%). Physical examination for diagnosing phalangeal and metacarpal fractures (one study) showed Se, Sp, accuracy, PPV and NPV ranging from 26 to 55%, 13-89%, 45-76%, 41-77% and 63-75%, respectively. Imaging modalities of scaphoid fractures showed predominantly low values for PPV and the highest values for Sp and NPV (24 studies). Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Ultrasonography (US) and Bone Scintigraphy (BS) were comparable in diagnostic accuracy for diagnosing a scaphoid fracture, with an accuracy ranging from 85 to 100%, 79-100%, 49-100% and 86-97%, respectively. Imaging for metacarpal and finger fractures showed Se, Sp, accuracy, PPV and NPV ranging from 73 to 100%, 78-100%, 70-100%, 79-100% and 70-100%, respectively. CONCLUSIONS: Only two studies were found on the diagnostic accuracy of history taking for hand and wrist fractures in the current review. Physical examination was of moderate use for diagnosing a scaphoid fracture and of limited use for diagnosing phalangeal, metacarpal and remaining carpal fractures. MRI, CT and BS were found to be moderately accurate for the definitive diagnosis of clinically suspected carpal fractures

Irinotecan pharmacokinetics-pharmacodynamics: the clinical relevance of prolonged exposure to SN-38

We have shown previously that the terminal disposition half-life of SN-38, the active metabolite of irinotecan, is much longer than earlier thought. Currently, it is not known whether this prolonged exposure has any relevance toward SN-38-induced toxicity. Here, we found that SN-38 concentrations present in human plasma for up to 3 weeks after a single irinotecan infusion induce significant cytotoxicity in vitro. Using pharmacokinetic data from 26 patients, with sampling up to 500 h, relationships were evaluated between systemic exposure (AUC) to SN-38 and the per cent decrease in absolute neutrophil count (ANC) at nadir, or by taking the entire time course of ANC into account (AOC). The time course of SN-38 concentrations (AUC500 h) was significantly related to this AOC (P<0.001). Based on these findings, a new limited-sampling model was developed for SN-38 AUC500 h using only two timed samples: AUC500 h=(6.588×C2.5 h)+(146.4×C49.5 h)+15.53, where C2.5 h and C49.5 h are plasma concentrations at 2.5 and 49.5 h after start of infusion, respectively. The use of this limited-sampling model may open up historic databases to retrospectively obtain information about SN-38-induced toxicity in patients treated with irinotecan

Diagnostic accuracy of history taking, physical examination and imaging for phalangeal, metacarpal and carpal fractures: a systematic review update

BACKGROUND: The standard diagnostic work-up for hand and wrist fractures consists of history taking, physical examination and imaging if needed, but the supporting evidence for this work-up is limited. The purpose of this study was to systematically examine the diagnostic accuracy of tests for hand and wrist fractures. METHODS: A systematic search for relevant studies was performed. Methodological quality was assessed and sensitivity (Se), specificity (Sp), accuracy, positive predictive value (PPV) and negative predictive value (NPV) were extracted from the eligible studies. RESULTS: Of the 35 eligible studies, two described the diagnostic accuracy of history taking for hand and wrist fractures. Physical examination with or without radiological examination for diagnosing scaphoid fractures (five studies) showed Se, Sp, accuracy, PPV and NPV ranging from 15 to 100%, 13-98%, 55-73%, 14-73% and 75-100%, respectively. Physical examination with radiological examination for diagnosing other carpal bone fractures (one study) showed a Se of 100%, with the exception of the triquetrum (75%). Physical examination for diagnosing phalangeal and metacarpal fractures (one study) showed Se, Sp, accuracy, PPV and NPV ranging from 26 to 55%, 13-89%, 45-76%, 41-77% and 63-75%, respectively. Imaging modalities of scaphoid fractures showed predominantly low values for PPV and the highest values for Sp and NPV (24 studies). Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Ultrasonography (US) and Bone Scintigraphy (BS) were comparable in diagnostic accuracy for diagnosing a scaphoid fracture, with an accuracy ranging from 85 to 100%, 79-100%, 49-100% and 86-97%, respectively. Imaging for metacarpal and finger fractures showed Se, Sp, accuracy, PPV and NPV ranging from 73 to 100%, 78-100%, 70-100%, 79-100% and 70-100%, respectively. CONCLUSIONS: Only two studies were found on the diagnostic accuracy of history taking for hand and wrist fractures in the current review. Physical examination was of moderate use for diagnosing a scaphoid fracture and of limited use for diagnosing phalangeal, metacarpal and remaining carpal fractures. MRI, CT and BS were found to be moderately accurate for the definitive diagnosis of clinically suspected carpal fractures

Line managers' hiring intentions regarding people with mental health problems:A cross-sectional study on workplace stigma

Objectives Stigma may negatively affect line managers’ intention to hire people with mental health problems (MHP). This study aims to evaluate line managers’ knowledge and attitudes concerning job applicants with MHP, and to assess which factors are associated with the intention (not) to hire an applicant with MHP. Methods A sample of Dutch line managers (N=670) filled out a questionnaire on their knowledge, attitudes and experiences concerning applicants/employees with MHP. Descriptive analyses and multiple regression analyses were used. Results The majority (64%) was reluctant to hire a job applicant with MHP, despite the fact that only 7% had negative and 52% had positive personal experiences with such employees. Thirty per cent were reluctant to hire an applicant if they knew the applicant had past MHP. Associated with higher reluctance to hire an applicant with MHP were the concerns that it will lead to long-term sickness absence (β (95% CI)=0.39 (0.23 to 0.55)), that the employee cannot handle the work (β (95% CI)=0.16 (0.00 to 0.33)) that one cannot count on the employee (β (95% CI)=0.41 (0.23 to 0.58)) and higher manager education level (β (95% CI)=0.25 (0.05 to 0.44)). Conversely, associated with positive hiring intentions was being in favour of diversity and/or inclusive enterprise (β(95% CI)=−0.64 (−0.87 to −0.41)). Conclusions As the majority of managers were reluctant to hire applicants with MHP, and even 30% were reluctant to hire applicants who had past MHP, these findings have major implications for social inclusion in the Netherlands, where about 75% of employees would disclose MHP at work

Stability of and change in substance use risk personality:Gender differences and smoking cigarettes among early adolescents

OBJECTIVE: Adolescents show a steadily increasing inclination toward health risk behaviors, including smoking cigarettes. There is ample evidence that personality traits are related to smoking behavior. However, less is known about the stability of and change in these personality traits during early adolescence and whether smoking behavior affects the developmental trajectories. Moreover, less is known about the influence of gender on the course of personality. METHOD: Longitudinal data of three waves were used from 1121 early adolescents. To measure personality, the Substance Use Risk Profile Scale was used. Individual growth curve models were conducted to measure the stability, mean-level change and individual differences in change for personality. RESULTS: Stability of personality was moderate for boys and ranged from moderate to high for girls. On average early adolescents became more impulsive and more sensation seeking over a period of 18 months. Furthermore, hopelessness for girls increased and the increase in sensation seeking was higher for girls than for boys. Third, smoking behavior was related to all personality traits, indicating that smoking adolescents are more anxious, hopeless, impulsive and sensation seeking than non-smoking adolescents. CONCLUSIONS: Our results are in line with the disruption hypothesis, i.e., during early adolescence there is a dip in personality maturity. There are clear differences between girls and boys in stability of and change in personality traits. Besides, although smoking behavior is related to personality, the change in personality is probably related to other variables

Stakeholder perspectives on primary school pupils and sickness absence:Exploring opportunities and challenges

School absenteeism and its underlying causes can have negative effects on the cognitive, psychosocial and health development of a child. Research in primary education shows high rates of sickness absence. Many stakeholders are involved in addressing school absenteeism, including primary school professionals, child and youth healthcare physicians, school attendance officers and parents. This study explores these stakeholders’ perspectives, their approaches and what they envisage to be necessary in order to improve. It also aims to unveil opportunities and challenges in addressing sickness absence among primary school pupils. Qualitative research was performed with six semi-structured focus group interviews and involving 27 participants from the West-Brabant and Amsterdam regions of the Netherlands. Thematic analysis was used. The overarching theme was aiming for the child’s wellbeing. Each focus group interview started with low awareness of sickness absence as a threat to this wellbeing, but awareness grew during the interviews. The participating stakeholders regarded problematic sickness absence as complex due to a wide variety of causes, and felt that each other’s expertise was necessary to reduce sickness absence. Schools registered absence, but only occasionally used planned steps; they based the identification of problematic sickness on gut feeling rather than any agreed-upon criteria. To be able to systematically address sickness absence and thus improve the wellbeing of children, stakeholders felt the need for a clearly structured approach, including monitoring of sickness absence of all pupils, identifying problematic absence and promoting collaboration with other stakeholders. An approach should allow for tailoring solutions to the individual child

A phase I dose-escalation and pharmacokinetic study of a micellar nanoparticle with entrapped docetaxel (CPC634) in patients with advanced solid tumours

Background: CPC634 is docetaxel entrapped in core-cross linked polymeric micelles. In preclinical studies, CPC634 demonstrated enhanced pharmacokinetics and improved therapeutic index. This phase I dose escalation study is the first-in-human study with CPC634. Methods: adult patients with advanced solid tumours received CPC634 intravenously either 3-weekly (Q3W) (part 1, dose range 15–100 mg/m2 ), 2-weekly (Q2W) (part 2, 45 mg/m2 ) or Q3W with dexamethasone premedication (part 3, 60 mg/m2 ). Results: thirty-three patients were enrolled. Skin toxicity was dose limiting (DLT) at ≥60 mg/m2 in part 1 and at 45 mg/m2 in part 2 and was the most common CPC634 related grade ≥ 3 adverse event (24%). With dexamethasone premedication no DLTs were observed at 60 mg/m2 Q3W. CPC634 exhibited a dose-proportional\ud pharmacokinetic profile. At 60 mg/m2 , the plasma area under the curve was 4067.5 ± 2974.0 ng/h/mL and the peak plasma level 217.3 ± 91.9 ng/mL with a half-life of 39.7 ± 9.4 h for released docetaxel. Conclusion: CPC634 could be administered safely upon pretreatment with dexamethasone. Cumulative skin toxicity was the main DLT. The recommended phase 2 dose was determined at 60 mg/m2 Q3W with dexamethasone premedication