Measurements of knee rotation-reliability of an external device in vivo

<p>Abstract</p> <p>Background</p> <p>Knee rotation plays an important part in knee kinematics during weight-bearing activities. An external device for measuring knee rotation (the Rottometer) has previously been evaluated for validity by simultaneous measurements of skeletal movements with Roentgen Stereometric Analysis (RSA). The aim of this study was to investigate the reliability of the device.</p> <p>Method</p> <p>The within-day and test-retest reliability as well as intertester reliability of the device in vivo was calculated. Torques of 3, 6 and 9 Nm and the examiner's apprehension of end-feel were used at 90°, 60° and 30° of knee flexion. Intraclass Correlation Coefficient _2,1(ICC _2,1), 95% confidence interval (CI) of ICC and 95% CI between test trials and examiners were used as statistical tests.</p> <p>Result</p> <p>ICC_2,1ranged from 0.50 to 0.94 at all three flexion angles at 6 and 9 Nm as well as end-feel, and from 0.22 to 0.75 at 3 Nm applied torque.</p> <p>Conclusion</p> <p>The Rottometer was a reliable measurement instrument concerning knee rotation at the three different flexion angles (90°, 60° and 30°) with 6 and 9 Nm applied torques as well as the examiner's apprehension of end-feel. Three Nm was not a reliable torque. The most reliable measurements were made at 9 Nm applied torque.</p

Population pharmacokinetics in phase I drug development: a phase I study of PK1 in patients with solid tumours

Doxorubicin pharmacokinetics were determined in 33 patients with solid tumours who received intravenous doses of 20–320 mg m−2 HPMA copolymer bound doxorubicin (PK1) in a phase I study. Since assay constraints limited the data at lower doses, conventional analysis was not feasible and a ‘population approach’ was used. Bound concentrations were best described by a biexponential model and further analyses revealed a small influence of dose or weight on V1 but no identifiable effects of age, body surface area, renal or hepatic function. The final model was: clearance (Q) 0.194 l h−1; central compartment volume (V1) 4.48 × (1+0.00074 × dose (mg)) l; peripheral compartment volume (V2) 7.94 l; intercompartmental clearance 0.685 l h−1. Distribution and elimination half-lives had median estimates of 2.7 h and 49 h respectively. Free doxorubicin was present at most sampling times with concentrations around 1000 times lower than bound doxorubicin values. Data were best described using a biexponential model and the following parameters were estimated: apparent clearance 180 l h−1; apparent V1 (l) 1450 × (1+0.0013 × dose (mg)), apparent V2 (l) 21 300 × (1–0.0013 × dose (mg)) × (1+2.95 × height (m)) and apparent Q 6950 l h−1. Distribution and elimination half-lives were 0.13 h and 85 h respectively. © 1999 Cancer Research Campaig

Laboratory evolution of Pyrococcus furiosus alcohol dehydrogenase to improve the production of (2S,5S)-hexanediol at moderate temperatures

There is considerable interest in the use of enantioselective alcohol dehydrogenases for the production of enantio- and diastereomerically pure diols, which are important building blocks for pharmaceuticals, agrochemicals and fine chemicals. Due to the need for a stable alcohol dehydrogenase with activity at low-temperature process conditions (30°C) for the production of (2S,5S)-hexanediol, we have improved an alcohol dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus (AdhA). A stable S-selective alcohol dehydrogenase with increased activity at 30°C on the substrate 2,5-hexanedione was generated by laboratory evolution on the thermostable alcohol dehydrogenase AdhA. One round of error-prone PCR and screening of ∼1,500 mutants was performed. The maximum specific activity of the best performing mutant with 2,5-hexanedione at 30°C was tenfold higher compared to the activity of the wild-type enzyme. A 3D-model of AdhA revealed that this mutant has one mutation in the well-conserved NADP(H)-binding site (R11L), and a second mutation (A180V) near the catalytic and highly conserved threonine at position 183

How well do adolescents recall use of mobile telephones? Results of a validation study

<p>Abstract</p> <p>Background</p> <p>In the last decade mobile telephone use has become more widespread among children. Concerns expressed about possible health risks have led to epidemiological studies investigating adverse health outcomes associated with mobile telephone use. Most epidemiological studies have relied on self reported questionnaire responses to determine individual exposure. We sought to validate the accuracy of self reported adolescent mobile telephone use.</p> <p>Methods</p> <p>Participants were recruited from year 7 secondary school students in Melbourne, Australia. Adolescent recall of mobile telephone use was assessed using a self administered questionnaire which asked about number and average duration of calls per week. Validation of self reports was undertaken using Software Modified Phones (SMPs) which logged exposure details such as number and duration of calls.</p> <p>Results</p> <p>A total of 59 adolescents participated (39% boys, 61% girls). Overall a modest but significant rank correlation was found between self and validated number of voice calls (ρ = 0.3, P = 0.04) with a sensitivity of 57% and specificity of 66%. Agreement between SMP measured and self reported duration of calls was poorer (ρ = 0.1, P = 0.37). Participants whose parents belonged to the 4^thsocioeconomic stratum recalled mobile phone use better than others (ρ = 0.6, P = 0.01).</p> <p>Conclusion</p> <p>Adolescent recall of mobile telephone use was only modestly accurate. Caution is warranted in interpreting results of epidemiological studies investigating health effects of mobile phone use in this age group.</p

Mobile phone use and risk of acoustic neuroma: results of the Interphone case–control study in five North European countries

There is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of the acoustic nerve to the handset. We conducted, to a shared protocol, six population-based case–control studies in four Nordic countries and the UK to assess the risk of acoustic neuroma in relation to mobile phone use. Data were collected by personal interview from 678 cases of acoustic neuroma and 3553 controls. The risk of acoustic neuroma in relation to regular mobile phone use in the pooled data set was not raised (odds ratio (OR)=0.9, 95% confidence interval (CI): 0.7–1.1). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR=1.8, 95% CI: 1.1–3.1). The study suggests that there is no substantial risk of acoustic neuroma in the first decade after starting mobile phone use. However, an increase in risk after longer term use or after a longer lag period could not be ruled out

Milk and dairy products: good or bad for human health? An assessment of the totality of scientific evidence

Background: There is scepticism about health effects of dairy products in the public, which is reflected in an increasing intake of plant-based drinks, for example, from soy, rice, almond, or oat. Objective: This review aimed to assess the scientific evidence mainly from meta-analyses of observational studies and randomised controlled trials, on dairy intake and risk of obesity, type 2 diabetes, cardiovascular disease, osteoporosis, cancer, and all-cause mortality. Results: The most recent evidence suggested that intake of milk and dairy products was associated with reduced risk of childhood obesity. In adults, intake of dairy products was shown to improve body composition and facilitate weight loss during energy restriction. In addition, intake of milk and dairy products was associated with a neutral or reduced risk of type 2 diabetes and a reduced risk of cardiovascular disease, particularly stroke. Furthermore, the evidence suggested a beneficial effect of milk and dairy intake on bone mineral density but no association with risk of bone fracture. Among cancers, milk and dairy intake was inversely associated with colorectal cancer, bladder cancer, gastric cancer, and breast cancer, and not associated with risk of pancreatic cancer, ovarian cancer, or lung cancer,while the evidence for prostate cancer risk was inconsistent.Finally,consumption of milk and dairy products was not associated with all-cause mortality. Calcium-fortified plant-based drinks have been included as an alternative to dairy products in the nutrition recommendations in several countries. However, nutritionally, cow’s milk and plant-based drinks are completely different foods,and an evidence-based conclusion on the health value of the plant-based drinks requires more studies in humans. Conclusion: The totality of available scientific evidence supports that intake of milk and dairy products contribute to meet nutrient recommendations, and may protect against the most prevalent chronic diseases, whereas very few adverse effects have been reported