Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study).

BACKGROUND: The efficacy and toxicity of olaparib as combination therapy in early breast cancer (BC) patients with homologous recombinant deficiency (HRD) [score high and/or germline (g) or tumour (t) BRCA1/2 mutation] is not well described. GeparOLA (ClinicalTrials.gov, NCT02789332) investigated olaparib in combination with paclitaxel in HER2-negative early BC with HRD. PATIENTS AND METHODS: Patients with untreated primary HER2-negative cT2-cT4a-d or cT1c with either cN+ or pNSLN+ or cT1c and triple-negative breast cancer (TNBC) or cT1c and Ki-67>20% BC with HRD were randomised either to paclitaxel (P) 80 mg/m2 weekly plus olaparib (O) 100 mg twice daily for 12 weeks or P plus carboplatinum (Cb) area under the curve 2 weekly for 12 weeks, both followed by epirubicin/cyclophosphamide (EC). Stratification factors were hormone receptor (HR) status (HR+ versus HR-) and age (<40 versus ≥40 years). The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). A two-sided one-group χ2-test was planned to exclude a pCR rate of ≤55% in the PO-EC arm. Secondary end points were other pCR definitions, breast conservation rate, clinical/imaging response, tolerability and safety. RESULTS: A total of 107 patients were randomised between September 2016 and July 2018; 106 (PO N = 69; PCb N = 37) started treatment. Median age was 47.0 years (range 25.0-71.0); 36.2% had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumours; grade 3 tumours: 86.8%; Ki-67>20%: 89.6%; TNBC: 72.6%; confirmed gBRCA1/2 mutation: 56.2%. The pCR rate with PO was 55.1% [90% confidence interval (CI) 44.5% to 65.3%] versus PCb 48.6% (90% CI 34.3% to 63.2%). Analysis for the stratified subgroups showed higher pCR rates with PO in the cohorts of patients <40 years and HR+ patients. CONCLUSION: GeparOLA could not exclude a pCR rate of ≤55% in the PO arm. PO was significantly better tolerated and the combination merits further evaluation.

Evaluating the ventilatory effect of transnasal humidified rapid insufflation ventilatory exchange in apnoeic small children with two different oxygen flow rates: a randomised controlled trial.

Transnasal humidified rapid insufflation ventilatory exchange prolongs safe apnoeic oxygenation time in children. In adults, transnasal humidified rapid insufflation ventilatory exchange is reported to have a ventilatory effect with PaCO2 levels increasing less rapidly than without it. This ventilatory effect has yet to be reproduced in children. In this non-inferiority study, we tested the hypothesis that children weighing 10-15 kg exhibit no difference in carbon dioxide clearance when comparing two different high-flow nasal therapy flow rates during a 10-min apnoea period. Following standardised induction of anaesthesia including neuromuscular blockade, patients were randomly allocated to high-flow nasal therapy of 100% oxygen at 2 or 4 l.kg-1 .min-1 . Airway patency was ensured by continuous jaw thrust. The study intervention was terminated for safety reasons when SpO2 values dropped < 95%, or transcutaneous carbon dioxide levels rose > 9.3 kPa, or near-infrared spectroscopy values dropped > 20% from their baseline values, or after an apnoeic period of 10 min. Fifteen patients were included in each group. In the 2 l.kg-1 .min-1 group, mean (SD) transcutaneous carbon dioxide increase was 0.46 (0.11) kPa.min-1 , while in the 4 l.kg-1 .min-1 group it was 0.46 (0.12) kPa.min-1 . The upper limit of a one-sided 95%CI for the difference between groups was 0.07 kPa.min-1 , lower than the predefined non-inferiority margin of 0.147 kPa.min-1 (p = 0.001). The lower flow rate of 2 l.kg-1 .min-1 was non-inferior to 4 l.kg-1 .min-1 relative to the transcutaneous carbon dioxide increase. In conclusion, an additional ventilatory effect of either 2 or 4 l.kg-1 .min-1 high-flow nasal therapy in apnoeic children weighing 10-15 kg appears to be absent.

Transnasal humidified rapid insufflation ventilatory exchange for oxygenation of children during apnoea: a prospective randomised controlled trial.

BACKGROUND: Transnasal humidified rapid insufflation ventilatory exchange (THRIVE) comprises the administration of heated, humidified, and blended air/oxygen mixtures via nasal cannula at rates of ≥2 litres kg-1 min-1. The aim of this randomized controlled study was to evaluate the length of the safe apnoea time using THRIVE with two different oxygen concentrations (100% vs 30% oxygen) compared with standard low-flow 100% oxygen administration. METHODS: Sixty patients, aged 1-6 yr, weighing 10-20 kg, undergoing general anaesthesia for elective surgery, were randomly allocated to receive one of the following oxygen administration methods during apnoea: 1) low-flow 100% oxygen at 0.2 litres kg-1 min-1; 2) THRIVE 100% oxygen at 2 litres kg-1 min-1; and 3) THRIVE 30% oxygen at 2 litres kg-1 min-1. Primary outcome was time to desaturation to 95%. Termination criteria included SpO2 decreased to 95%, transcutaneous CO2 increased to 65 mmHg, or apnoea time of 10 min. RESULTS: The median (interquartile range) [range] apnoea time was 6.9 (5.7-7.8) [2.8-10.0] min for low-flow 100% oxygen, 7.6 (6.2-9.1) [5.2-10.0] min for THRIVE 100% oxygen, and 3.0 (2.4-3.7) [0.2-5.3] min for THRIVE 30% oxygen. No significant difference was detected between apnoea times with low-flow and THRIVE 100% oxygen administration (P=0.15). THRIVE with 30% oxygen demonstrated significantly shorter apnoea times (P<0.001) than both 100% oxygen modalities. The overall rate of transcutaneous CO2 increase was 0.57 (0.49-0.63) [0.29-8.92] kPa min-1 without differences between the 3 groups (P=0.25). CONCLUSIONS: High-flow 100% oxygen (2 litres kg-1 min-1) administered via nasal cannulas did not extend the safe apnoea time for children weighing 10-20 kg compared with low-flow nasal cannula oxygen (0.2 litres kg-1 min-1). No ventilatory effect was observed with THRIVE at 2.0 litres kg-1 min-1. CLINICAL TRIAL REGISTRATION: NCT02979067.

Lower Magnetization Transfer Ratio in the Forceps Minor Is Associated with Poorer Gait Velocity in Older Adults.

BACKGROUND AND PURPOSE: Gait disturbances in the elderly are disabling and a major public health issue but are poorly understood. In this multimodal MR imaging study, we used 2 voxel-based analysis methods to assess the voxelwise relationship of magnetization transfer ratio and white matter hyperintensity location with gait velocity in older adults. MATERIALS AND METHODS: We assessed 230 community-dwelling participants of the Austrian Stroke Prevention Family Study. Every participant underwent 3T MR imaging, including magnetization transfer imaging. Voxel-based magnetization transfer ratio-symptom mapping correlated the white matter magnetization transfer ratio of each voxel with gait velocity. To assess a possible relationship between white matter hyperintensity location and gait velocity, we applied voxel-based lesion-symptom mapping. RESULTS: We found a significant association between the magnetization transfer ratio within the forceps minor and gait velocity (ß = 0.134; 95% CI, 0.011-0.258; P = .033), independent of demographics, general physical performance, vascular risk factors, and brain volume. White matter hyperintensities did not significantly change this association. CONCLUSIONS: Our study provides new evidence for the importance of magnetization transfer ratio changes in gait disturbances at an older age, particularly in the forceps minor. The histopathologic basis of these findings is yet to be determined.

X-ray transport and radiation response assessment (XTRRA) experiments at the National Ignition Facility.

Our team has developed an experimental platform to evaluate the x-ray-generated stress and impulse in materials. Experimental activities include x-ray source development, design of the sample mounting hardware and sensors interfaced to the National Ignition Facility's diagnostics insertion system, and system integration into the facility. This paper focuses on the X-ray Transport and Radiation Response Assessment (XTRRA) test cassettes built for these experiments. The test cassette is designed to position six samples at three predetermined distances from the source, each known to within ±1% accuracy. Built-in calorimeters give in situ measurements of the x-ray environment along the sample lines of sight. The measured accuracy of sample responses as well as planned modifications to the XTRRA cassette is discussed.

Subcutaneous Trastuzumab for HER2-positive Breast Cancer - Evidence and Practical Experience in 7 German Centers.

A subcutaneous formulation of trastuzumab to treat patients with HER2-positive breast cancer is available since August 2013. The subcutaneous formulation is administered as a fixed dose of 600 mg over a period of up to 5 minutes. The HannaH trial compared subcutaneous with intravenous administration and found comparable pharmacokinetics, efficacy and tolerability for both administration forms of trastuzumab in the neoadjuvant setting. The randomized crossover study PrefHer reported a clear preference from the patient's point of view for subcutaneous over intravenous administration of trastuzumab. The accompanying time-and-motion study reported a reduction concerning the total time spent for the institution as well as for the patient receiving trastuzumab s. c.. The experience of 7 German centers largely corresponded with the results of these studies. Patients expressed a clear preference for subcutaneous trastuzumab administration, with the time saved by the subcutaneous administration route cited as the greatest benefit. Although the existing reimbursement terms mean that centers will receive a lower remuneration, the centers' overall evaluation of the subcutaneous administration route for trastuzumab was overwhelmingly positive. The greatest benefit cited by the centers was the flexibility in scheduling patient appointments. This increased flexibility improved conditions in some centers which were experiencing pressures due to a shortage of staff, particularly at peak times. The general consensus, however, was that the remuneration systems for oncological treatments urgently need to be amended to ensure that the real costs of treatment are covered, even if the administration route has changed.

Loss of Nogo-A-expressing neurons in a rat model of Parkinson's disease.

The myelin-associated protein Nogo-A is among the most potent neurite growth inhibitors in the adult CNS. Recently, Nogo-A expression was demonstrated in a number of neuronal subpopulations of the adult and developing CNS but at present, little is known about the expression of Nogo-A in the nigrostriatal system, a brain structure severely affected in Parkinson's disease (PD). The present study sought to characterize the expression pattern of Nogo-A immunoreactive (ir) cells in the adult ventral mesencephalon of control rats and in the 6-hydroxydopamine (6-OHDA) rat model of PD. Immunohistochemical analyses of normal adult rat brain showed a distinct expression of Nogo-A in the ventral mesencephalon, with the highest level in the substantia nigra pars compacta (SNc) where it co-localized with dopaminergic neurons. Analyses conducted 1week and 1 month after unilateral striatal injections of 6-OHDA disclosed a severe loss of the number of Nogo-A-ir cells in the SNc. Notably, at 1week after treatment, more dopaminergic neurons expressing Nogo-A were affected by the 6-OHDA toxicity than Nogo-A-negative dopaminergic neurons. However, at later time points more of the surviving dopaminergic neurons expressed Nogo-A. In the striatum, both small and large Nogo-A-positive cells were detected. The large cells were identified as cholinergic interneurons. Our results suggest yet unidentified functions of Nogo-A in the CNS beyond the inhibition of axonal regeneration and plasticity, and may indicate a role for Nogo-A in PD.

Prognostic impact of renal function in precapillary pulmonary hypertension.

BACKGROUND: Impairment of renal function is associated with adverse outcome in various diseases. Patients with pulmonary hypertension (PH) show diminished cardiac function and organ perfusion. The aim of this study was to investigate the associations between renal function and both haemodynamic parameters and long-term survival in patients with PH. METHODS: Blood was collected from 64 patients with PH (Dana Point class 1, 3 and 4) during right heart catheterization, and plasma was prepared. Creatinine, blood urea nitrogen (BUN), cystatin C, neutrophil-gelatinase-associated lipocalin (NGAL), fibroblast growth factor 23 (FGF-23) and α-Klotho levels were determined, and glomerular filtration rate (GFR) was estimated (eGFR). Parameters were evaluated using c-statistics and dichotomized for survival analysis based on receiver operating characteristic curves. RESULTS: The median follow-up time was 9.92 years with all-cause mortality as the primary end-point. Elevated BUN, cystatin C and creatinine levels were associated with decreased survival, with hazard ratios (HRs) of 3.237, 4.514 and 2.006, respectively, and equivalent performance according to c-statistics. Estimating GFR by CKD-EPI, MDRD and Cockcroft-Gault formulas resulted in HRs of 2.942, 2.694 and 3.306, respectively. Amongst these formulas, eGFR (Cockcroft-Gault) had the highest c-statistics of 0.674. There was a correlation between BUN and both cardiac index (τ = -0.39) and pulmonary vascular resistance index (τ = 0.249), whereas eGFR (CKD-EPI) was correlated with cardiac index (τ = 0.225). No correlations between either BUN or eGFR and right atrial pressure (RAP) were observed. NGAL, FGF-23 and α-Klotho had no prognostic impact or association with haemodynamic parameters. CONCLUSION: Comparison of markers of renal function for prognosis in PH demonstrated superiority of creatinine, cystatin C and BUN over NGAL, FGF-23 and α-Klotho. Minor decreases in eGFR influence long-term prognosis, and measurement of cystatin C levels might be useful to detect renal impairment in patients with a normal serum concentration of creatinine. Renal function in patients with PH is linked to cardiac index rather than RAP.

Using static and dynamic canonical correlation coefficients as quantitative EEG markers for Alzheimer's disease severity.

We analyzed the relation between Alzheimer's disease (AD) severity as measured by Mini-Mental State Examination (MMSE) scores and quantitative electroencephalographic (qEEG) markers that were derived from canonical correlation analysis. This allowed an investigation of EEG synchrony between groups of EEG channels. In this study, we applied the data from 79 participants in the multi-centric cohort study PRODEM-Austria with probable AD. Following a homogeneous protocol, the EEG was recorded both in resting state and during a cognitive task. A quadratic regression model was used to describe the relation between MMSE and the qEEG synchrony markers. This relation was most significant in the δ and θ frequency bands in resting state, and between left-hemispheric central, temporal and parietal channel groups during the cognitive task. Here, the MMSE explained up to 40% of the qEEG marker's variation. QEEG markers showed an ambiguous trend, i.e. an increase of EEG synchrony in the initial stage of AD (MMSE>20) and a decrease in later stages. This effect could be caused by compensatory brain mechanisms. We conclude that the proposed qEEG markers are closely related to AD severity. Despite the ambiguous trend and the resulting diagnostic ambiguity, the qEEG markers could provide aid in the diagnostics of early-stage AD.

Efficacy and side effects of intravenous remifentanil patient-controlled analgesia used in a stepwise approach for labour: an observational study.

BACKGROUND: Remifentanil has a suitable pharmacological profile for labour analgesia. In this prospective, observational study, intravenous patient-controlled analgesia with remifentanil, using stepwise bolus doses without background infusion, was examined during the first and second stages of labour. Outcomes were pain reduction, maternal satisfaction, maternal and neonatal side effects and remifentanil metabolism in the neonate. METHODS: Parturients with normal term singleton pregnancies were recruited. The initial remifentanil bolus dose was 0.15 µg/kg, increasing in steps of 0.15 µg/kg, with a 2-min lock-out. Pain scores using a 100 mm visual analogue scale, systolic and diastolic blood pressures, respiratory rate and maternal sedation were recorded every 15 min. Maternal oxygen saturation and heart rate were monitored continuously. Neonatal data included Apgar scores, clinical examination, naloxone use, resuscitation, umbilical cord blood gases and remifentanil concentrations. RESULTS: Forty-one parturients were enrolled. Pain scores were significantly reduced in the first 3 h of patient-controlled analgesia use compared to baseline, and at the end of the first and second stages of labour (P<0.05). Maximal pain reduction was 60% (P<0.01). One patient had inadequate pain relief and converted to epidural analgesia. The mean highest dose of remifentanil was 0.7 µg/kg [range 0.3-1.05]. Ninety-three percent of patients were satisfied with their analgesia. The lowest oxygen saturation was 91% and the lowest respiratory rate was 9 breaths/min. Eleven parturients (27%) received supplemental oxygen due to oxygen saturations <92%. Maternal sedation was moderate, and neonatal data reassuring. CONCLUSIONS: Remifentanil intravenous patient-controlled analgesia provides adequate pain relief and high maternal satisfaction during the first and second stages of labour. Maternal sedation and respiratory depression may occur, but no serious neonatal side effects were recorded. Careful monitoring is mandatory.

Adaptations to aerobic interval training: interactive effects of exercise intensity and total work duration.

To compare the effects of three 7-week interval training programs varying in work period duration but matched for effort in trained recreational cyclists. Thirty-five cyclists (29 male, 6 female, VO(2peak) 52 ± 6 mL kg/min) were randomized to four training groups with equivalent training the previous 2 months (∼6 h/wk, ∼1.5 int. session/wk). Low only (n=8) trained 4-6 sessions/wk at a low-intensity. Three groups (n=9 each) trained 2 sessions/wk × 7 wk: 4 × 4 min, 4 × 8 min, or 4 × 16 min, plus 2-3 weekly low-intensity bouts. Interval sessions were prescribed at the maximal tolerable intensity. Interval training was performed at 88 ± 2, 90 ± 2, and 94 ± 2% of HR(peak) and 4.9, 9.6, and 13.2 mmol/L blood lactate in 4 × 16, 4 × 8, and 4 × 4 min groups, respectively (both P<0.001). 4 × 8 min training induced greater overall gains in VO(2) peak, power@VO(2) peak, and power@4 mM bLa- (Mean ± 95%CI): 11.4 (8.0-14.9), vs 4.2 (0.4-8.0), 5.6 (2.1-9.1), and 5.5% (2.0-9.0) in Low, 4 × 16, and 4 × 4 min groups, respectively (P<0.02 for 4 × 8 min vs all other groups). Interval training intensity and accumulated duration interact to influence the adaptive response. Accumulating 32 min of work at 90% HR max induces greater adaptive gains than accumulating 16 min of work at ∼95% HR max despite lower RPE.

A Langmuir probe diagnostic for time-of-flight measurements of transient plasmas produced by high-energy laser ablation.

We discuss here the development of a Langmuir probe (LP) diagnostic to examine high-density, high-temperature inhomogeneous plasmas such as those that can be created at the University of Rochester's Laboratory for Laser Energetics OMEGA facility. We have configured our diagnostic to examine the velocity of the plasma expanding from the target. We observe velocities of approximately 16-17 cm/µs, with individual LP currents displaying complex structures, perhaps due to the multiple atomic species and ionization states that exist.

Radiochromic film measurement of spatial uniformity for a laser generated x-ray environment.

An existing x-ray source application (XRSA) test cassette was modified to hold multiple x-ray filter materials followed by two radiochromic film types (FWT-60 and HD-810 Gafchromic® film) to qualitatively characterize the spectral-spatial uniformity over the XRSA sample field of view. Multiple sets of film were examined and nominal set was determined. These initial, qualitative measurements suggest a low-energy regime (E < 3 keV) spatial anisotropy and spatial isotropy at higher energies (E > 3 keV).

Cerebral microbleeds: a review.

Cerebral microbleeds (CMBs) are frequent findings in MRI scans of elderly subjects. Depending on the MRI protocols applied 4.7% to 24.4% of community-based subjects show incidental CMBs. The rates reported for various types of ischemic strokes and intracerebral hemorrhages vary between 19.4% and 68.5%. Most studies also demonstrated CMBs in approximately one third of Alzheimer cases. A lobar distribution of CMBs is considered to relate to cerebral amyloid angiopathy, while CMBs located in the basal ganglia or in infratentorial brain regions are thought to relate to hypertensive vasculopathy. Besides age, hypertension, diabetes mellitus, and low serum cholesterol have so far been identified as risk factors for CMBs. Presence of an APOE ε4 allele is the only genetic factor that was consistently shown to increase the risk for CMB development. There are only few longitudinal studies on the predictive value of CMBs. For incident ischemic strokes and intracerebral hemorrhages hazard ratios of 4.48 and 50.2 have been reported. CMBs also doubled the risk for conversion to dementia in MCI patients, and there are indications for CMBs being possible predictors of increased mortality. Given the small number of longitudinal investigations with often small sample sizes the role of CMBs as predictors of disease needs to be further elucidated. CMBs were significantly more common in warfarin-treated stroke patients who developed intracerebral hemorrhages (ICH). These data are cross-sectional. They do not provide enough evidence to consider CMBs as a contraindication for antithrombotic agents in primary and secondary stroke prevention. CMBs are likely to unfavourably affect cognitive functioning. It remains to be determined if direct lesion-related effects are responsible for this finding or if CMBs are sole markers of more extensive tissue damage in the wake of cerebral small vessel disease leading to widespread visible but also non-visible tissue destruction with a high likelihood for cognitive consequences.

The association between cycling to school and being overweight in Rotterdam (The Netherlands) and Kristiansand (Norway).

Active transportation is a behavior that might contribute to energy balance. However, no clear association between active commuting to school and weight status has been reported in the international literature. Also, new studies indicate that cycling to school might have a greater health potential than walking to school. The purpose of the present study is to assess the potential association between cycling to school and weight status in two European cities, Rotterdam and Kristiansand, where cycling to school remains common. Data from two studies, ENDORSE (Rotterdam) and Youth in Balance (Kristiansand), were used including, respectively, 1361 and 1197 adolescents with mean ages of 14.1 and 14.4 years. The adolescents were categorized as cyclist or non-cyclist based on questionnaires on the usual mode of transportation to school. A total of 25% and 18% were categorized as overweight, and 35% and 31% were categorized as cyclists, in Rotterdam and Kristiansand, respectively. In multilevel logistic analyses, after adjusting for potential moderators, the odds ratios for cyclists being overweight compared with non-cyclists were, respectively, 0.63 (95% CI=0.45-0.89) and 0.52 (95% CI=0.34-0.78) in Rotterdam and Kristiansand. The results presented clearly show a negative association between cycling to school and overweight among adolescents both in Rotterdam and in Kristiansand.

Impaired weight gain predicts risk of late death after surgery for congenital heart defects.

OBJECTIVES: To describe long-term somatic growth in terms of weight for age in children operated on for congenital heart defects who die late (after the first 30 postoperative days) and to study the relationship between postoperative weight gain and survival after surgery for congenital heart defects. METHODS: This was a nested case-control study of 80 children born in 1990-2002 who died late after surgery for congenital heart defects at Rikshospitalet, Norway. Weight data were obtained for 74 children, of whom 31 with no extra-cardiac anomalies were defined as cases and 31 surviving children with similar surgical complexity were defined as controls. RESULTS: In the 74 children who died late, mean weight for age converted to z scores at birth, at last operation and at last recorded weight were 0.12, -1.31 and -2.09. In the 31 children defined as cases, the same weight z scores were 0.07, -1.21 and -2.01 compared with 0.05, -1.10 and -0.99 in the 31 matched controls. The odds ratio (OR) for death was 13.5 (95% CI 3.6 to 51.0) if there was a decrease in weight z score of >0.67 after the last operation. Median follow-up time after operation was 5.7 months. CONCLUSIONS: A decrease in weight for age during the first months after surgery for congenital heart defects of more than 0.67 z scores, corresponding to a downward percentile crossing through at least one of the displayed percentile lines on standard growth charts, is strongly related to late mortality in children operated on for congenital heart defects.

CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients.

Migration of monocytes into the vessel wall contributes to the onset and progression of atherosclerosis. Because monocytes are a heterogeneous population, we determined potential associations between monocyte subsets and cardiovascular events in a prospective cohort of 94 dialysis patients followed for 35 months. The incidence of cardiovascular events and death measured by Kaplan-Meier plots and flow cytometric analysis of monocyte subsets showed that total leukocyte and monocyte numbers failed to predict event-free survival. Among monocyte subsets, a high CD14(++)CD16(+) monocyte number was associated with higher rates of cardiovascular events and death. In a multivariate proportional hazards model adjusted for classical cardiovascular risk factors, patients with CD14(++)CD16(+) monocyte numbers in the top quartile were at higher risk of cardiovascular events and death compared to patients in the lowest quartile. Our study suggests that the number of CD14(++)CD16(+) monocytes was independently associated with cardiovascular events and death in a high-risk population of dialysis patients.

Advances in in vitro and in vivo models for studying the staphylococcal factors involved in implant infections.

Implant infections due to staphylococci are one of the greatest threats facing patients receiving implant devices. For many years researchers have sought to understand the mechanisms involved in the adherence of the bacterium to the implanted device and the formation of the unique structure, the biofilm, which protects the indwelling bacteria from the host defence and renders them resistant to antibiotic treatment. A major goal has been to develop in vitro and in vivo models that adequately reflect the real-life situation. From the simple microtiter plate assay and scanning electron microscopy, tools for studying adherence and biofilm formation have since evolved to include specialised equipment for studying adherence, flow cell systems, real-time analysis of biofilm formation using reporter gene assays both in vitro and in vivo, and a wide variety of animal models. In this article, we discuss advances in the last few years in selected in vitro and in vivo models as well as future developments in the study of adherence and biofilm formation by the staphylococci.

On the weight-bearing function of the medial coronoid process in dogs.

The shape of and proportions between the surface areas of the medial coronoid process (MCP) and the fovea of the radial head were determined in 88 juvenile dogs and 146 adult dogs grouped as giant, large, mid-sized, chondrodystrophic, or small dogs. Thereby, the longitudinal (length) and transverse (width) extension of the MCP and fovea of the radial head have been measured. Original values were used to describe changes of the parameters attributed to growth. Normalized values (i.e. values expected in case of a width of the fovea of the radial head of 20 mm) were used to determine potential differences between constitutional types. All original values increased during growth (P < 0.05) except for the width and length of the MCP in chondrodystrophic and small breeds. Normalized values revealed a proportional decrease in width and length of the MCP during growth (P < 0.05) compared with the radial head. In adults, the normalized MCP was widest in giant dogs followed by large, mid-sized, small, and chondrodystrophic breeds. The MCP was also longest in giant dogs but shortest in large and chondrodystrophic dogs with those of large dogs being significantly (P < 0.05) shorter than those in giant, mid-sized and small dogs. Present results suggest that a deficiency in length-growth of the MCP--which has been present especially in large dogs--results in smaller humeral contact areas and decreased weight-bearing capacity of the MCP. Because loading forces acting on the MCP increase with body weight, the condition noted in large dogs might increase the risk of fragmentation of the MCP in these.

Postnatal modelling of the humeroantebrachial contact areas of radius and ulna in dogs.

Necropsy dogs (n = 234) ranging in age between 2 days and 17 years were examined to characterize the cross-sectional shape of the humeroantebrachial contact area of the radius and ulna on radioulnar scans of giant, large, mid-sized, small, and chondrodystrophic breeds. During growth, the contact areas became more circular in shape in all breeds, those in small dogs remained most elliptic. Smallest normalized heights (distance between the tip of the anconeal process and the most proximal aspect of the cranial margin of the radial head = RUH, distance between the tip of the anconeal process and the cranial tip of the medial coronoid process = UH) and depths (distance determined in a right angle to RUH = RUD, distance determined in a right angle to UH = UD) were noted in large and giant breeds with no significant difference between these. In juveniles, a decrease in UD was correlated with a decrease in UH in all breeds as was a decrease in RUD correlated with a decrease in RUH, whereas in non-arthrotic adults this condition could only be proven for mid-sized dogs and small breeds but not for giant, large and chondrodystrophic dogs. The average radioulnar and ulnar heights and depths (as seen in non-arthrotic adults) were calculated to be obtained in mid-sized dogs at least 3-4 weeks earlier than in large dogs. Lipping of the cranial margin of the radial head was significantly (P < 0.001) associated with lesion(s) of the articular surface (i.e. erosion of the articular cartilage and subchondral bone and/or fragmentation of the medial coronoid process) and caused additional change in shape of this contact area, which was then even more circular. However, the variables evaluated (RUH, RUD, UH, UD) allowed only poor discrimination between constitution types and between non-arthrotic and arthrotic joints.