What makes a biostatistician?

Biostatisticians play an important role in medical research. They are co-responsible for an appropriate and efficient study design, they are involved in monitoring the study conduct, they plan and perform the data analysis, and they are involved in interpreting and publishing the results. However, how are the biostatisticians prepared for their tasks and responsibilities? Graduate programs in biostatistics are being offered, but some practicing biostatisticians completed their studies in a mathematical or epidemiological program, or obtained their degree in subject-specific fields (such as medicine or biology). Therefore, the expertise and the competencies can vary widely between the individual biostatisticians, also depending on the application field. In this article, focusing on European and US practices, we discuss the required professional expertise for the main areas of applications in the medical field as well as the necessary soft skill competencies of a biostatistician.     

Zur Radikaloperation der Darmbrüche mit inkompletem Bruchsack (Darmgleitbrüche)

Ohne Zusammenfassung (Mit 5 Abbildungen.)     

Effect of Down syndrome on the dimensions of dental crowns and tissues

Abnormal growth in Down syndrome (DS) is reflected by variable reduction in size and simplification in form of many physical traits. This study aimed to compare the thickness of enamel and dentine in deciduous and permanent mandibular incisor teeth between DS and non‐DS individuals and to clarify how these tissues contribute to altered tooth size in DS. Sample groups comprised 61 mandibular incisors (29 permanent and 32 deciduous) from DS individuals and 55 mandibular incisors (29 permanent and 26 deciduous) from non‐DS individuals. Maximum mesiodistal and labiolingual crown dimensions were measured initially, then the crowns were sectioned midsagittally and photographed using a stereomicroscope. Linear measurements of enamel and dentine thickness were obtained on the labial and lingual surfaces of the crowns, together with enamel and dentine–pulp areas and lengths of the dentino‐enamel junction. Reduced permanent crown size in DS was associated with a reduction in both enamel and dentine thickness. After adjustments were made for tooth size, DS permanent incisors had significantly thinner enamel than non‐DS permanent teeth. The DS permanent teeth also exhibited significant differences in shape and greater variability in dimensions than the non‐DS permanent teeth. Crown dimensions of deciduous incisors were similar in size or larger in DS compared with non‐DS deciduous teeth. Enamel and dentine thicknesses of the deciduous teeth were similar in DS and non‐DS individuals. The findings indicate that growth retardation in DS reduces both enamel and dentine deposition in the permanent incisors but not in the earlier‐forming deciduous predecessors. The results are also consistent with the concept of amplified developmental instability for dental traits in DS. Am. J. Hum. Biol. 13:690–698, 2001. © 2001 Wiley‐Liss, Inc.     

Photorefractive keratectomy with the erbium: YAG laser

BACKGROUND: Ablation experiments and preclinical studies have shown increased thermal damage and surface roughness after photorefractive keratectomy (PRK) with the erbium: YAG laser. MATERIALS AND METHODS: In this study, the thermal damage was investigated on enucleated pig corneas for various laser pulse durations (80 ns to 1 ms) and radiant exposures (0.2-5 J/cm2). The "scanning-spot" method and the fundamental mode photo-ablation were used for spherical corrections. SEM pictures and surface roughness measurements enabled comparison with the morphology after ArF-excimer laser treatment. The surface roughness is one order of magnitude higher compared to the ArF-excimer laser ablation. The surface of the tissue after ablation looks melted. RESULTS: The thermal damage reduces with increased intensity, and at high intensities the thermal damage results in a constant thickness of > 5 microns. CONCLUSIONS: Laser-induced melting processes might be the main reason for the high thermal damage and the increased surface roughness after erbium: YAG laser treatment. This leads to the conclusion that the erbium: YAG laser is not a real alternative to the ArF-excimer laser in PRK.     

Tetrahydrobiopterin improves endothelial function in human saphenous veins

OBJECTIVES: Diminished production of nitric oxide has been linked to saphenous vein endothelial dysfunction. Tetrahydrobiopterin is an obligate cofactor for the oxidation of L -arginine by nitric oxide synthase in the production of nitric oxide by endothelial cells. The objective of the present study was to examine whether the exogenous addition of tetrahydrobiopterin improves endothelial function in saphenous veins from patients undergoing coronary artery bypass graft operations. METHODS: Vascular segments of saphenous veins were obtained from 17 patients undergoing elective coronary artery bypass grafting, and in vitro endothelium-dependent and endothelium-independent responses to acetylcholine and sodium nitroprusside were assessed. Isometric dose-response curves were constructed in precontracted rings in the presence and absence of tetrahydrobiopterin (0.1 mmol/L) with the use of the organ bath apparatus. The percentages of maximum relaxation and sensitivity were compared between interventions. RESULTS: Acetylcholine caused dose-dependent endothelium-mediated relaxation in saphenous veins. In the presence of tetrahydrobiopterin, acetylcholine-induced relaxation was significantly augmented (percentage maximum relaxation, 16.8% +/- 2.9% vs control 7.5% +/- 1.8%; P =.003) without an effect on agonist sensitivity. These effects were endothelium-specific because endothelium-independent responses to sodium nitroprusside were preserved. CONCLUSIONS: These data uncover beneficial effects of acute tetrahydrobiopterin addition on endothelial function in human vessels. Because endothelial dysfunction has been implicated in the development of graft failure, studies aimed at chronic delivery of tetrahydrobiopterin would be useful in determining the contribution of this cofactor toward saphenous vein atherosclerosis.     

Continuous measurement of intra‐oral pH and temperature: development,validation of an appliance and a pilot study

To describe a novel approach for continuous measurement of intra‐oral pH and temperature in individuals carrying out normal daily activities over 24 h. We designed, validated and constructed a custom‐made appliance fitted with a pH probe and a thermocouple. Six subjects wore the appliance over a 24‐h period for two non‐consecutive days, while the intra‐oral pH and temperature were measured continuously and recorded. Intra‐oral pH and temperature were very similar across different recording days, the difference being not statistically significant (P ≥ 0·14). There was a noticeable difference in the pattern of variation of pH between day and night. During the day, the mean pH was 7·3 (±0·4) and dropped markedly only after consumption of acidic food and drinks. The intra‐oral pH decreased slowly during sleep with an average pH of 6·6 (±0·4) being recorded. The difference between day and night was statistically significant (P = 0·002). The mean intra‐oral temperature was 33·9 °C (±0·9) during daytime and 35·9 °C (±0·5) during sleep (P = 0·013) with minor fluctuations occurring over 24 h. The continuous and simultaneous intra‐oral pH and temperature measurement system described in this report is reliable, easy to construct, able to measure variables over a sustained period and may serve as a future diagnostic tool in a number of applications.     

Factors associated with pain induced by orthodontic separators

Pain resulting from the application of orthodontic forces varies markedly across individuals. The reasons of this variability are still largely unknown. To investigate factors that may be associated with orthodontic pain following the application of orthodontic separators. One hundred and seven participants were screened for pain response over 48 h following placement of orthodontic elastomeric separators. The highest (n = 10) and lowest (n = 10) pain responders were identified, and data collected on tooth pain sensitivity to electrical stimulation in conjunction with using the Pain Catastrophising Scale (PCS), Dental Anxiety Scale (DAS) and cold pressor test (CPT). There were statistically significant differences between high‐ and low‐pain responders in catastrophising score (P ≤ 0·023). For every PCS magnification score of 1 unit higher, the relative risk of being a high‐pain responder was 1·6 (P = 0·002); those scoring higher on helplessness had a lower risk of being so. DAS scores of high‐pain responders were twice as high as those of low‐pain responder (P = 0·043). During the first 2 min of CPT, the high‐pain responders experienced more pain than the low‐pain responders (P ≤ 0·029). Tooth pain thresholds did not differ between the two different pain responder groups. Pain catastrophising, dental anxiety and cold sensitivity appear to modify the pain experienced following placement of orthodontic separators. Further research is needed to determine the validity of screening questions to identify at‐risk patients prior to commencing orthodontic treatment.     

Measuring Intraoral Pressure: Adaptation of a Dental Appliance Allows Measurement During Function

This article introduces a new way of recording intraoral pressures from a range of locations within the oral cavity. To measure pressure flow dynamics during swallowing, we fitted eight miniature pressure transducers capable of measuring absolute pressures to a chrome-cobalt palatal appliance with a labial bow. Unlike previous devices, our design provides a rigid, custom-fitted platform for the simultaneous recording of pressures at eight locations within the oral cavity during function. We placed an anterior pair of gauges to measure lingual and labial contact against the left central incisor tooth, and two pairs of gauges to measure pressure contributions of the lateral tongue margin and cheeks on the canine and first molar teeth. Finally, lingual pressure on the midline of the palate was measured by two gauges, one at the position of the premolars and one on the posterior boundary of the hard palate. We then recorded intraoral pressures in five adult volunteers seated in an upright position and asked to swallow 10 ml of water. Labial pressures on the canine rose rapidly from a resting level of 10 kPa to 33 kPa, while pressure profiles from the labial aspects of the incisor and first molar teeth followed a negative pattern, peaking at -12 kPa for the incisor and -15 kPa for the molar sensor. Pressure profiles recorded from the palatal aspects of the first molar and the canine appeared to be similar, but the former fell to -13 kPa before rising to 9 kPa, and the canine pressure rapidly increased to 22 kPa before returning to its resting level of 4 kPa. The pressure profile of the palatal aspect of the central incisor was strikingly different; at the start of the swallow, pressure dropped precipitously to -20 kPa, before slowly rising to 10 kPa. It then followed the general pattern of the other two sensors, before peaking again at 10 kPa and then returning to a resting level of 4 kPa. We also showed that there were significant negative pressures in the mouth during function, and that pressure profiles varied markedly between individuals.     

Mutation of the surface-exposed amino acid Trp to Ala in the FVIII C2 domain results in defective secretion of the otherwise functional protein

The C2 domain of factor VIII (FVIII) is important for FVIII-phospholipid (PL) and FVIII-von Willebrand factor (VWF) interactions. A FVIII structural model, derived by electron crystallography, suggests four hydrophobic loops at the FVIII C2 domain-PL interface. Within loop four, the solvent-exposed amino acid, Trp(2313), is believed to contribute to FVIII-PL binding. To analyse this interaction, the amino-acid exchange Trp(2313) to Ala (W2313A) was introduced into the C2 domain of B-domain-deleted FVIII (dBFVIII). Both proteins, dBFVIII and W2313A, were expressed in a mammalian expression system. Labelling experiments showed that the mutation W2313A resulted in reduced secretion but did not affect intracellular synthesis of the protein. Specific activity, kinetic parameters, binding to VWF and haemostatic potential in a murine model of haemophilia A were found to be similar for both proteins. Binding studies to synthetic 4% phosphatidyl-l-serine vesicles showed, however, a 28-fold higher K(D) for W2313A, indicating the important role of Trp(2313) in the FVIII-PL interaction. In conclusion, the C2-domain-surface-exposed residue Trp(2313), is critical for secretion of the protein. The W2313A mutation weakens binding to phosphatidyl-l-serine vesicles but the mutant protein has the same effector function as dBFVIII in vitro and in vivo.