IDDSI-compliant recipes containing oral contrast agents for radiological dysphagia diagnostics.

Videofluoroscopic swallowing study (VFSS), alongside flexible endoscopic evaluation of swallowing, represents the gold standard for diagnosing swallowing disorders and to determine severity, pathophysiology, and effective interventions, including texture modification. The clinical swallowing examination and assessment supplements these instrumental methods and serves as the basis for the modules of swallowing diagnostics. The adaptation of food and drink consistencies in dysphagia management has become widespread. For valid results of a VFSS with respect to confirming swallowing safety and efficiency of different liquid and food consistencies and textures, the use of uniform recipes containing radio-opaque contrast media is important. Our goal was to identify recipes that would produce consistencies that conform to the liquid and food levels of 0-7, as defined by the International Dysphagia Diet Standardization Initiative (IDDSI), with barium- and iodine-based contrast media, xanthan gum-based thickeners, and other edible components, which also show sufficient contrast on VFSS. In this study, we determined the different recipes using IDDSI testing methods and explored their radiological characteristics using a Philips MultiDiagnost Eleva fluoroscopy system and two different fluid contrast agents: barium- (Micropaque®) and iodine-based (Telebrix®). All recipes showed sufficient contrast on fluoroscopy and could be visualized in the amounts used for swallowing examinations. They were practical and easy to implement in terms of production and availability of the components. The homogeneity of the recipes diminished with higher IDDSI levels, which represent transitional food, but appeared still sufficient for fluoroscopic examination. The opacity did not significantly differ between the barium- and iodine-based contrast media.

Seroprevalence of Coxiella burnetii antibodies in wild deer populations in eastern Australia.

Coxiella burnetii causes significant reproduction losses in livestock and the disease Q fever in humans. Transmission of C. burnetii is facilitated by the stability of the bacterium in the environment and the susceptibility of a variety of host species to infection. Consequently, inter-species transmission occurs frequently through either direct or indirect contact. Wildlife may represent reservoirs of C. burnetii and could therefore be a source of infection for domestic animals. Understanding the prevalence of C. burnetii infections at the wildlife-livestock interface is important for disease control. This study aimed to investigate the extent of C. burnetii exposure in wild deer in eastern Australia. Serum samples were obtained from 413 wild deer from seven regions in four eastern Australian states from 2017 to 2020. Antibodies were detected using a commercial Q fever antibody kit validated for ruminants. Seroprevalence of C. burnetii antibodies in deer was determined and true prevalence estimated, for each region. The overall seroprevalence of C. burnetii antibodies in wild deer was 3.4% (14 seropositive of 413 deer sampled) with true prevalence estimated to be 4.3% (95% credible interval: 0.6%, 10.9%). Seropositive deer were identified only in Queensland (7/108 seropositive) and northern New South Wales (7/120 seropositive). This geospatial distribution is consistent with seropositivity in other animal species and indicative of the level of C. burnetii in the environment. The low seroprevalence suggests that wild deer are unlikely to be a major reservoir species for C. burnetii in eastern Australia but may still be implicated in inter-species transmission cycles.

Characterization of carrier behavior in photonically excited 6H silicon carbide exhibiting fast, high voltage, bulk transconductance properties.

Unabated, worldwide trends in CO2 production project growth to > 43-BMT per year over the next two decades. Efficient power electronics are crucial to fully realizing the CO2 mitigating benefits of a worldwide smart grid (~ 18% reduction for the United States alone). Even state-of-the-art SiC high voltage junction devices are inefficient because of slow transition times (~ 0.5-µs) and limited switching rates at high voltage (~ 20-kHz at ≥ 15-kV) resulting from the intrinsically limited charge carrier drift speed (< 2 × 107-cm-s-1). Slow transition times and limited switch rates waste energy through transition loss and hysteresis loss in external magnetic components. Bulk conduction devices, where carriers are generated and controlled nearly simultaneously throughout the device volume, minimize this loss. Such devices are possible using below bandgap excitation of semi-insulating (SI) SiC single crystals. We explored carrier dynamics with a 75-fs single wavelength pump/supercontinuum probe and a modified transient spectroscopy technique and also demonstrated a new class of efficient, high-speed, high-gain, bi-directional, optically-controlled transistor-like power device. At a performance level six times that of existing devices, for the first time we demonstrated prototype operation at multi-10s of kW and 20-kV, 125-kHz in a bulk conduction transistor-like device using direct photon-carrier excitation with below bandgap light.

Spinodal decomposition in a mean-field model of the cortex: Emergence of hexagonally symmetric activation patterns.

Spinodal decomposition is a well-known pattern-forming mechanism in metallurgic alloys, semiconductor crystals, and colloidal gels. In metallurgy, if a heated sample of a homogeneous Zn-Al alloy is suddenly quenched below a critical temperature, then the sample can spontaneously precipitate into inhomogenous textures of Zn- and Al-rich regions with significantly altered material properties such as ductility and hardness. Here we report on our recent discovery that a two-dimensional model of the human cortex with inhibitory diffusion can, under particular homogeneous initial conditions, exhibit a form of nonconserved spinodal decomposition in which regions of the cortex self-organize into hexagonally distributed binary patches of activity and inactivity. Fine-scale patterns precipitate rapidly, and then the dynamics slows to render coarser-scale shapes which can ripen into a range of slowly evolving patterns including mazelike labyrinths, hexagonal islands and continents, nucleating "mitotic cells" which grow to a critical size then subdivide, and inverse nucleations in which quiescent islands are surrounded by a sea of activity. One interesting class of activity coalesces into a soliton-like narrow ribbon of depolarization that traverses the cortex at ∼4cm/s. We speculate that this may correspond to the thus far unexplained interictal waves of cortical activation that precede grand-mal seizure in an epileptic event. We note that spinodal decomposition is quite distinct from the Turing mechanism for symmetry breaking in cortex investigated in earlier work by the authors [Steyn-Ross et al., Phys. Rev. E 76, 011916 (2007)PLEEE81539-375510.1103/PhysRevE.76.011916].

[The subjective perception of the vertical-a valuable parameter for determination of peripheral vestibular disorder in Menière's disease in the chronic phase?] / Die subjektive Vertikalenwahrnehmung ­ ein wertvoller Parameter für die Bestimmung der peripher vestibulären Störung bei M. Menière in der chronischen Phase?

The perception of verticality is mainly based on utricular afferent signals and central processing of the transmitted signals. However, there are also extracranial receptors that make a considerable contribution to the perception of verticality. With the subjective visual vertical (SVV) for the utricle and the subjective trunk vertical (STV), two different parameters are available that are not fully understood in terms of their response to physiologic and pathologic changes. The aim of this work was to determine SVV and STV under certain positions of the head and trunk as well as under the influence of Menière's disease (MD) as a chronic vestibular disease. In a prospective clinical study, 26 patients with MD and 39 healthy volunteers were recruited. Subjects were examined with C­SVV glasses and with the three-dimensional trunk excursion chair, while head and torso positions were varied. In both groups, SVV determination is clearly more accurate with an earth-vertical head alignment than with a lateral head tilt (right: MM and control group: p = 0.001; left: MM p = 0.001, control group p = 0.000). If the torso is deflected laterally and the head is held straight, the SVV is significantly more accurate (left p = 0.003, right p = 0.015). The SRV was not affected by the presence of unilateral MD, while pathologic SVV values, if present, indicated the affected side. The results of our study support the assumption that in addition to SVV, SRV is an independent parameter for verticality perception and differs from the SVV in terms of lateralizing a peripheral vestibular deficit. These results suggest that the STV may depend not only on utricular function but also on extracranial afferent signals, and not be significantly altered by the presence of a hydropic peripheral vestibular lesion.

[Pilot study: Determination of the subjective trunk vertical in upright head position]. / Pilotstudie: Bestimmung der subjektiven Rumpfvertikalen in lotrechter Kopfposition.

BACKGROUND: Consensus has been established that the subjective vertical (SV) is a result of multimodal sensory integration. In order to be able to calculate the vestibulocervical sensory competence for the SV, the isolated subjective trunk vertical axis (STV) was measured under conditions of vertical head fixation. MATERIALS AND METHODS: Young, healthy volunteers (n = 49) were compared to older, healthy volunteers (n = 50) on a three-dimensionally deflectable (tilt, torsion, pitch) trunk excursion chair in which the volunteer's head remains in an upright position. Another young, healthy group was divided into a placebo (n = 27) and a monophasic cervical transcutaneous electrical nerve stimulation (C-TENS; n = 22) group to examine verticality perception. RESULTS: In the STV after trunk pitch, age was a significant variable (p = 0.021). The older, healthy group of subjects missed the physical vertical by an average of 1.8° more than the younger group. Only the placebo group showed an average improvement in STV of 4.3° after torsion. CONCLUSION: Apart from the macular organs the vestibulocervical sensory afference is involved in finding the trunk vertical. A difference in age to the disadvantage of the older healthy subjects was observed, as well as a lack of learning success after applied C­TENS. The presented pilot study was able to confirm that a correct vertical trunk sensation is caused by vestibulocervical sensory afference in upright head position.

Evidence for energy conservation during pubertal growth. A 10-year longitudinal study (EarlyBird 71).

BACKGROUND: Diabetes is closely linked to obesity, and obesity rates climb during adolescence for reasons that are not clear. Energy efficiency is important to obesity, and we describe a temporary but substantial fall in absolute energy expenditure, compatible with improved energy efficiency, during the rapid growth phase of puberty. METHODS: In a longitudinal cohort study lasting 10 years, we measured voluntary energy expenditure as physical activity (PA) by accelerometry, involuntary energy expenditure as resting energy expenditure (REE) by oxygen consumption, body mass index (BMI) and body composition by dual energy X-ray absorptiometry annually on 10 occasions from 7 to 16 years in the 347 children of the EarlyBird study. We used mixed effects modelling to analyse the trends in REE and their relationship to BMI, lean mass (LM), fat mass (FM), age, PA and pubertal stage. RESULTS: Relative REE and total PA fell during puberty, as previously described, but the longitudinal data and narrow age-range of the cohort (s.d.±4m) revealed for the first time a substantial fall in absolute REE during the period of maximum growth. The fall became clearer still when adjusted for FM and LM. The fall could not be explained by fasting insulin, adiponectin, leptin, luteinising hormone or follicle stimulating hormone. CONCLUSIONS: There appears to be a temporary but substantial reduction in energy expenditure during puberty, which is unrelated to changes in body composition. If it means higher energy efficiency, the fall in REE could be advantageous in an evolutionary context to delivering the extra energy needed for pubertal growth, but unfavourable to weight gain in a contemporary environment.

Childhood obesity: evidence for distinct early and late environmental determinants a 12-year longitudinal cohort study (EarlyBird 62).

BACKGROUND/OBJECTIVE: The prevalence of childhood obesity continues to rise in most countries, but the exposures responsible remain unclear. The shape of the body mass index (BMI) distribution curve defines how a population responds, and can be described by its three parameters-skew (L), median (M) and variance (S). We used LMS analysis to explore differences in the BMI trajectories of contemporary UK children with those of 25 years ago, and to draw inferences on the exposures responsible. SUBJECTS/METHODS: We applied Cole's LMS method to compare the BMI trajectories of 307 UK children (EarlyBird cohort) measured annually from 5-16 years (2000-2012) with those of the BMI data set used to construct the UK 1990 growth centiles, and used group-based trajectory modelling (GBTM) to establish whether categorical trajectories emerged. RESULTS: Gender-specific birth weights were normally distributed and similar between both data sets. The skew and variance established by 5 years in the 1990 children remained stable during the remainder of their childhood, but the pattern was different for children 25 years on. The skew at 5 years among the EarlyBird children was greatly exaggerated, and involved selectively the offspring of obese parents, but returned to 1990 levels by puberty. As the skew diminished, so the variance in BMI rose sharply. The median BMI of the EarlyBird children differed little from that of 1990 before puberty, but diverged from it as the variance rose. GBTM uncovered four groups with distinct trajectories, which were related to parental obesity. CONCLUSIONS: There appear to be two distinct environmental interactions with body mass among contemporary children, the one operating selectively according to parental BMI during early childhood, the second more generally in puberty.

Awareness of body weight by mothers and their children: repeated measures in a single cohort (EarlyBird 64).

BACKGROUND: Mothers often do not realize when their child is overweight. We aimed to compare mothers' perceptions of children's weight before and during puberty, and to explore factors at 7 years predicting recognition of overweight at 16 years. METHODS: Mothers of 237 children (136 boys) from the EarlyBird study estimated their own weight category and that of their child aged 7 years and 16 years. The children estimated their own weight category at 16 years. Annual measures: body mass index standard deviation score (BMIsds), per cent fat, physical activity. Pubertal development assessed by age at peak height velocity (APHV). MATERNAL MEASURES: BMI, education, socio-economic status. RESULTS: At 7 years 21% of girls and 16% of boys were overweight or obese, rising to 27% and 22% respectively at 16 years. The accuracy of the mother's perception of her child's weight category improved from 44% at 7 years to 74% at 16 years, but they were less able to judge overweight in sons than daughters. The mothers' level of concern about overweight was greater for girls than boys, and increased for girls (52% mothers of overweight/obese girls were worried at 7 years, 62% at 16 years), but remained static in the boys (42% vs. 39%). Over 80% of the youngsters realized when they were overweight, but 25% normal-weight girls also classed themselves as overweight. Only BMI predicted a mother's ability to correctly perceive her child's weight. Neither her awareness, nor concern, about the child's weight at 7 years had any impact on the trajectory of the child's BMI from 7 years to 16 years. CONCLUSIONS: Parents are central to any successful weight reduction programme in their children, but will not engage while they remain ignorant of the problem. Crucially, any concern mothers may have about their child's excess weight at 7 years appears to have no impact on subsequent weight change.

Electrical impedance of mouse brain cortex in vitro from 4.7 kHz to 2.0 MHz.

The electrical impedance of samples of mouse brain cortex has been measured between 4.7 kHz and 2.0 MHz. Brain slices of thickness 400 µm were prepared from two mice. Each slice was placed in either normal artificial cerebrospinal fluid or magnesium-free artificial cerebrospinal fluid; the latter induces seizure-like electrical behaviour. A total of 74 samples of cortex of approximate size 2 mm × 2 mm were then cut from these slices. Each sample in turn was placed between two flat Ag/AgCl electrodes and electrical impedance measured with an Agilent E4980A four-point impedance monitor. The measurements showed two regions of significant dispersion. Circuits based on the Cole-Cole and Fricke models, consisting of inductive, nonlinear capacitive and resistive elements were used to model the behaviour. Distributions of values for each circuit element have been determined for the samples prepared in seizing and non-seizing conditions. Few differences were found between the values of circuit elements between the seizing and non-seizing groups.

Gender-assortative waist circumference in mother-daughter and father-son pairs, and its implications. An 11-year longitudinal study in children (EarlyBird 59).

BACKGROUND/OBJECTIVES: Body mass index (BMI) is reportedly gender assortative (mother-daughter, father-son) in contemporary children. We investigated the corresponding transmission of waist circumference (WC) and its implications. METHODS: We measured parental WC at baseline and WC, height, weight and para-umbilical skin-fold (USF) annually in their offspring from 5 to 15 years (n = 223 trios). Parents were deemed normal metabolic risk (NR) or high risk (HR) according to World Health Organization (WHO) cut-points for WC (mothers 80 cm, fathers 94 cm). The residual from WC adjusted for BMI (WC|BMI ) was used as a surrogate for excess intra-abdominal fat, and its association with insulin resistance (HOMA2-IR) was sought. RESULTS: WC and USF were both gender assortative, while WC|BMI was not. WC was greater by 1.62 cm (P < 0.05, confidence interval [CI]: 0.09-3.16) and USF by 0.37 cm (P < 0.01, CI: 0.19-0.56) among the daughters (but not the sons) of HR compared with those of NR mothers, and by 1.32 cm (P < 0.05, CI: 0.09-2.55) and 0.18 cm (P < 0.05, CI: 0.04-0.32), respectively in the corresponding father-son (but not father-daughter) pairings. No such differences could be demonstrated for WC|BMI . A standard deviation score 1(SDS) change in WC|BMI , independent of BMI, was associated with a 7.14% change in IR in girls (P < 0.01, CI: 1.76-12.80) and 8.02% in boys (P < 0.001, CI: 2.93-13.36), but there was no relationship between IR and USF. CONCLUSION: The relationship of offspring WC to metabolic health and to parental size is complex. Subcutaneous abdominal fat is gender assortative but harmless, while intra-abdominal fat (its surrogate in this analysis) is unrelated to parental waist circumference, but metabolically harmful.

In vitro electrical conductivity of seizing and non-seizing mouse brain slices at 10 kHz.

The electrical conductivity of small samples of mouse cortex (in vitro) has been measured at 10 kHz through the four-electrode method of van der Pauw. Brain slices from three mice were prepared under seizing and non-seizing conditions by changing the concentration of magnesium in the artificial cerebrospinal fluid used to maintain the tissue. These slices provided 121 square samples of cortical tissue; the conductivity of these samples was measured with an Agilent E4980A four-point impedance monitor. Of these, 73 samples were considered acceptable on the grounds of having good electrical contact between electrodes and tissue excluding outlier measurements. Results show that there is a significant difference (p = 0.03) in the conductivities of the samples under the two conditions. The seizing and non-seizing samples have mean conductivities of 0.33 and 0.36 S m(-1), respectively; however, these quantitative values should be used with caution as they are both subject to similar systematic uncertainties due to non-ideal temperature conditions and non-ideal placement of electrodes. We hypothesize that the difference between them, which is more robust to uncertainty, is due to the changing gap junction connectivity during seizures.

Body fat in children does not adversely influence bone development: a 7-year longitudinal study (EarlyBird 18).

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Both negative and positive associations have been reported between body fat and bone density. Extra mechanical loading from excess fat may lead to greater bone mass. Excess ectopic fat may lead to bone demineralisation through inflammatory pathways. WHAT THIS STUDY ADDS: Longitudinally collected data from narrow-angle beam densitometry gives a novel insight into bone growth through adolescence. There is no evidence of a deleterious effect of body fat on children's growing bones after adjustment for height and age. Body fat, mediated by puberty, is associated with larger bones in boys and bones that are both denser and larger in girls. OBJECTIVE: Bone growth is an important determinant of peak bone mass and fracture risk, but there is limited data on the impact of fat-on-bone development at a time when childhood obesity is reaching epidemic proportions. Accordingly, we explored the effect of body fat (BF) on bone growth over time in the context of age, pubertal tempo and gender. METHOD: A cohort of 307 children was measured biannually from 9-16 years for height and weight, and every 12 months for percent BF, bone area (BA), bone mineral content and areal bone mineral density (aBMD) by dual-energy X-ray absorptiometry. Pubertal tempo was determined quantitatively by age at peak height velocity. RESULTS: Percent BF increased and then fell in the boys, but increased throughout in the girls. aBMD and BA increased in both genders (P < 0.001). Greater BF was associated with higher aBMD and BA in girls (P < 0.001), but only BA in boys (P < 0.001). The extra aBMD associated with increased BF was greater in older girls. The rise in aBMD and BA was associated with earlier puberty in both genders (P < 0.001). The impact of BF on aBMD was greater in later puberty in girls (0.0025 g cm(-2) per 10% BF at 10 years versus 0.016 g cm(-2) per 10% BF at 14 years, P < 0.001). CONCLUSION: Greater BF is associated with larger bones, but also denser bones in girls. The effects of fat and puberty are complex and gender specific, but BF of contemporary UK children does not appear to be deleterious to bone quality.

Redifferentiation of dedifferentiated human articular chondrocytes: comparison of 2D and 3D cultures.

OBJECTIVE: Three-dimensional (3D) cultures are widely used to redifferentiate chondrocytes. However, the rationale behind the choice for 3D above two-dimensional (2D) cultures is poorly systematically investigated and mainly based on mRNA expression and glycosaminoglycan (GAG) content. The objective was to determine the differential redifferentiation characteristics of human articular chondrocytes (HACs) in monolayer, alginate beads and pellet culture by investigating mRNA expression, protein expression, GAG content and cell proliferation. DESIGN: Dedifferentiated HACs from six individuals were redifferentiated in identical medium conditions for 7 days in monolayer, alginate beads or pellet culture. Read-out parameters were expression of chondrogenic and hypertrophic mRNAs and proteins, GAG content and cell proliferation. RESULTS: 3D cultures specifically expressed chondrogenic mRNAs [collagen type II (COL2A1), SRY (sex determining region Y)-box 9 (SOX9), aggrecan (ACAN)), whereas 2D cultures did not. Hypertrophic mRNAs (collagen type X (COL10A1), runt-related transcription factor 2 (RUNX2), matrix metalloproteinase 13 (MMP13), vascular endothelial growth factor A (VEGFA), osteopontin (OPN), alkaline phosphatase (ALP)) were highly increased in 2D cultures and lower in 3D cultures. Collagen type I (COL1A1) mRNA expression was highest in 3D cultures. Protein expression supports most of the mRNA data, although an important discrepancy was found between mRNA and protein expression of COL2A1 and SOX9 in monolayer culture, stressing on the importance of protein expression analysis. GAG content was highest in 3D cultures, whereas chondrocyte proliferation was almost specific for 2D cultures. CONCLUSIONS: For redifferentiation of dedifferentiated HACs, 3D cultures exhibit the most potent chondrogenic potential, whereas a hypertrophic phenotype is best achieved in 2D cultures. This is the first human study that systematically evaluates the differences between proliferation, GAG content, protein expression and mRNA expression of commonly used 2D and 3D chondrocyte culture techniques.

Measuring the effects of sevoflurane on electroencephalogram using sample entropy.

BACKGROUND: Monitoring the effect of anesthetic drugs on the neural system is a major ongoing challenge for anesthetists. During the past few years, several electroencephalogram (EEG)-based methods such as the response entropy (RE) as implemented in the Datex-Ohmeda M-Entropy Module have been proposed. In this paper, sample entropy is used to quantify the predictability of EEG series, which could provide an index to show the effect of sevoflurane anesthesia. The dose-response relation of sample entropy is compared with that of RE. METHODS: EEG data from 21 subjects is collected during the induction of general anesthesia with sevoflurane. The sample entropy is applied to the EEG recording. Pharmacokinetic-pharmacodynamic modeling and prediction probability statistic are used to evaluate the efficiency of sample entropy in comparison with RE. RESULTS: Both methods track the gross changes in EEG, especially the occurrence of burst-suppression pattern at high doses of anesthetics. However, our method produces faster reaction to transients in EEG during the induction of anesthesia as indicated from the pharmacokinetic and pharmacodynamic modeled parameters and analysis around the point of loss of consciousness. Also, sample entropy correlated more closely with effect-site sevoflurane concentration than the RE. In addition, our proposed method exhibits greater resistance to noise in the EEG signals. CONCLUSION: The results demonstrate that sample entropy can estimate the sevoflurane drug effect on the EEG more effectively than the commercial RE index with a stronger noise resistance.

The contribution of parental BMI to the metabolic health of their offspring: a longitudinal cohort study (EarlyBird 55).

OBJECTIVE: The objective of this study was to establish the extent to which parental factors influence the metabolic health of their offspring. DESIGN: The study was designed as a prospective longitudinal cohort study SUBJECTS: The study's subjects were 226 healthy trios from a 1995 to 1996 birth cohort randomly recruited in the city of Plymouth, UK MEASUREMENTS: Body mass index (BMI) and metabolic z-score (derived from natural log HOMA-IR, triglycerides, total/high-density lipoprotein cholesterol ratio), measured at nine annual time points, from 5 to 13 years. RESULTS: As expected, the metabolic z score was closely related to BMI in both genders and at all ages (r = 0.40-0.57, P < 0.001). Accordingly, there were large and significant differences in the metabolic z-score between children categorized as normal weight or overweight/obese. At 13 years, for example, the metabolic z score of the overweight/obese girls was 14-fold greater than that of the normal-weight girls (P < 0.001). However, parental BMI and metabolic status had little effect on these differences. Indeed, mixed effects modelling showed that, as the child's BMI increased, so the influence of parental factors became less relevant. Time-lag analyses confirmed that weight gain preceded metabolic disturbances in the children. CONCLUSION: The impact of obesity on the metabolic health of contemporary children is a function of their own weight gain, rather than that of their parents, and is therefore potentially preventable.

Using the Hilbert-Huang transform to measure the electroencephalographic effect of propofol.

Monitoring the effect of anesthetic drugs on the central nervous system is a major ongoing challenge in anesthesia research. A number of electroencephalogram (EEG)-based monitors of the anesthetic drug effect such as the bispectral (BIS) index have been proposed to analyze the EEG signal during anesthesia. However, the BIS index has received some criticism. This paper offers a method based on the Hilbert-Huang transformation to calculate an index, called the Hilbert-Huang weighted regional frequency (HHWRF), to quantify the effect of propofol on brain activity. The HHWRF and BIS indices are applied to EEG signals collected from nine patients during a controlled propofol induction and emergence scheme. The results show that both the HHWRF and BIS track the gross changes in the EEG with increasing and decreasing anesthetic drug effect (the prediction probability P(k) of 0.85 and 0.83 for HHWRF and BIS, respectively). Our new index can reflect the transition from unconsciousness to consciousness faster than the BIS, as indicated from the pharmacokinetic and pharmacodynamic modeled parameters and also from the analysis around the point of reawakening. This method could be used to design a new EEG monitoring system to estimate the propofol anesthetic drug effect.

Late presentation for HIV diagnosis and care in Germany.

OBJECTIVES: Antiretroviral therapy reduces mortality and morbidity in HIV-infected individuals most markedly when initiated early, before advanced immunodeficiency has developed. Late presentation for diagnosis and care remains a significant challenge. To guide public health interventions effectively it is crucial to describe the factors associated with late presentation. METHODS: Case surveillance data for all individuals newly diagnosed with HIV infection in Germany in the years 2001-2010 and data for the years 1999-2010 from the German Clinical Surveillance of HIV Disease (ClinSurv) cohort study, a large multicentre observational study, were analysed. Factors associated with late presentation (CD4 count < 350 cells/µL or clinical AIDS) were assessed using descriptive statistics and multivariable logistic regression methods. RESULTS: Among 22 925 eligible patients in the national surveillance database, 49.5% were late presenters for HIV diagnosis. Among 6897 treatment-naïve patients in the ClinSurv cohort, 58.1% were late presenters for care. Late presenters for care were older (median 42 vs. 39 years for early presenters), more often heterosexuals from low-prevalence countries (18.1% vs. 15.5%, respectively) and more often migrants (18.2% vs. 9.7%, respectively; all P < 0.005). The probability of late presentation was >65% throughout the observation period in migrants. The probability of late presentation for care clearly decreased in men who have sex with men (MSM) from 60% in 1999 to 45% in 2010. CONCLUSIONS: In Germany, the numbers of late presenters for HIV diagnosis and care remain high. The probability of late presentation for HIV diagnosis seems to be particularly high for migrants. These results argue in favour of targeted test promotion rather than opt-out screening. Late presentation for care seems to be an additional problem after HIV diagnosis.

Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification.

Skeletogenesis and bone fracture healing involve endochondral ossification, a process during which cartilaginous primordia are gradually replaced by bone tissue. In line with a role for cyclooxygenase-2 (COX-2) in the endochondral ossification process, non-steroidal anti-inflammatory drugs (NSAIDs) were reported to negatively affect bone fracture healing due to impaired osteogenesis. However, a role for COX-2 activity in the chondrogenic phase of endochondral ossification has not been addressed before. We show that COX-2 activity fulfils an important regulatory function in chondrocyte hypertrophic differentiation. Our data reveal essential cross-talk between COX-2 and bone morphogenic protein-2 (BMP-2) during chondrocyte hypertrophic differentiation. BMP-2 mediated chondrocyte hypertrophy is associated with increased COX-2 expression and pharmacological inhibition of COX-2 activity by NSAIDs (e.g., Celecoxib) decreases hypertrophic differentiation in various chondrogenic models in vitro and in vivo, while leaving early chondrogenic development unaltered. Our findings demonstrate that COX-2 activity is a novel factor partaking in chondrocyte hypertrophy in the context of endochondral ossification and these observations provide a novel etiological perspective on the adverse effects of NSAIDs on bone fracture healing and have important implications for the use of NSAIDs during endochondral skeletal development.