A Bilayer Method for Measuring Toughness and Strength of Dental Ceramics.

The ever-increasing usage of ceramic materials in restorative dentistry necessitates a simple and effective method to evaluate flexural strength σF and fracture toughness KC. We propose a novel method to determine these quantities using a bilayer specimen composed of a brittle plate adhesively bonded onto a transparent polycarbonate substrate. When this bilayer structure is placed under spherical indentation, tunneling radial cracks initiate and propagate in the lower surface of the brittle layer. The failure analysis is based on previous theoretical relationships, which correlate σF with the indentation force P and layer thickness d, and KC with P and mean length of radial cracks. This work examines the accuracy and limitations of this approach using a wide range of contemporary dental ceramic materials. The effect of layer thickness, indenter radius, load level, and length and number of radial cracks are carefully examined. The accuracy of the predicted σF and KC is similar to those obtained with other concurrent test methods, such as biaxial flexure and 3-point bending (σF), and bending specimens with crack-initiation flaws (KC). The benefits of the present approach include treatment for small and thin plates, elimination of the need to introduce a precrack, and avoidance of dealing with local material nonlinearity effects for the KC measurements. Finally, the bilayer configuration resembles occlusal loading of a ceramic restoration (brittle layer) bonded to a posterior tooth (compliant substrate).

Evaluating the accuracy of variant calling methods using the frequency of parent-offspring genotype mismatch.

The use of next-generation sequencing (NGS) data sets has increased dramatically over the last decade, but there have been few systematic analyses quantifying the accuracy of the commonly used variant caller programs. Here we used a familial design consisting of diploid tissue from a single lodgepole pine (Pinus contorta) parent and the maternally derived haploid tissue from 106 full-sibling offspring, where mismatches could only arise due to mutation or bioinformatic error. Given the rarity of mutation, we used the rate of mismatches between parent and offspring genotype calls to infer the single nucleotide polymorphism (SNP) genotyping error rates of FreeBayes, HaplotypeCaller, SAMtools, UnifiedGenotyper, and VarScan. With baseline filtering HaplotypeCaller and UnifiedGenotyper yielded more SNPs and higher error rates by one to two orders of magnitude, whereas FreeBayes, SAMtools and VarScan yielded lower numbers of SNPs and more modest error rates. To facilitate comparison between variant callers we standardized each SNP set to the same number of SNPs using additional filtering, where UnifiedGenotyper consistently produced the smallest proportion of genotype errors, followed by HaplotypeCaller, VarScan, SAMtools, and FreeBayes. Additionally, we found that error rates were minimized for SNPs called by more than one variant caller. Finally, we evaluated the performance of various commonly used filtering metrics on SNP calling. Our analysis provides a quantitative assessment of the accuracy of five widely used variant calling programs and offers valuable insights into both the choice of variant caller program and the choice of filtering metrics, especially for researchers using non-model study systems.

Obesity significantly alters the human sperm proteome, with potential implications for fertility.

PURPOSE: In men, obesity may lead to poor semen parameters and reduced fertility. However, the causative links between obesity and male infertility are not totally clear, particularly on a molecular level. As such, we investigated how obesity modifies the human sperm proteome, to elucidate any important implications for fertility. METHODS: Sperm protein lysates from 5 men per treatment, classified as a healthy weight (body mass index (BMI) ≤ 25 kg/m2) or obese (BMI ≥ 30 kg/m2), were FASP digested, submitted to liquid chromatography tandem mass spectrometry, and compared by label-free quantification. Findings were confirmed for several proteins by qualitative immunofluorescence and a quantitative protein immunoassay. RESULTS: A total of 2034 proteins were confidently identified, with 24 proteins being significantly (p < 0.05) less abundant (fold change < 0.05) in the spermatozoa of obese men and 3 being more abundant (fold change > 1.5) compared with healthy weight controls. Proteins with altered abundance were involved in a variety of biological processes, including oxidative stress (GSS, NDUFS2, JAGN1, USP14, ADH5), inflammation (SUGT1, LTA4H), translation (EIF3F, EIF4A2, CSNK1G1), DNA damage repair (UBEA4), and sperm function (NAPA, RNPEP, BANF2). CONCLUSION: These results suggest that oxidative stress and inflammation are closely tied to reproductive dysfunction in obese men. These processes likely impact protein translation and folding during spermatogenesis, leading to poor sperm function and subfertility. The observation of these changes in obese men with no overt andrological diagnosis further suggests that traditional clinical semen assessments fail to detect important biochemical changes in spermatozoa which may compromise fertility.

Pill testing at music festivals: is it evidence-based harm reduction?

Recent pill-related deaths of young people at music festivals in Australia have led to a concerted push for on-site pill testing as a means for preventing such events. However, whether pill testing (also termed 'safety checking') is an effective harm reduction strategy remains uncertain. This narrative review concludes that pill testing currently lacks evidence of efficacy sufficient to justify publicly funded national roll-out of on-site pill-testing programmes. Australian governments, addiction specialists and public health experts should collaborate in conducting properly designed field studies aimed at confirming clear benefits from such programmes in reducing pill-related harm.

Forensic reconstruction of two military combat related shooting incidents using an anatomically correct synthetic skull with a surrogate skin/soft tissue layer.

Six synthetic head models wearing ballistic protective helmets were used to recreate two military combat-related shooting incidents (three per incident, designated 'Incident 1' and 'Incident 2'). Data on the events including engagement distances, weapon and ammunition types was collated by the Defence Science and Technology Laboratory. The models were shot with 7.62 × 39 mm ammunition downloaded to mean impact velocities of 581 m/s (SD 3.5 m/s) and 418 m/s (SD 8 m/s), respectively, to simulate the engagement distances. The damage to the models was assessed using CT imaging and dissection by a forensic pathologist experienced in reviewing military gunshot wounds. The helmets were examined by an MoD engineer experienced in ballistic incident analysis. Damage to the helmets was consistent with that seen in real incidents. Fracture patterns and CT imaging on two of the models for Incident 1 (a frontal impact) were congruent with the actual incident being modelled. The results for Incident 2 (a temporoparietal impact) produced realistic simulations of tangential gunshot injury but were less representative of the scenario being modelled. Other aspects of the wounds produced also exhibited differences. Further work is ongoing to develop the models for greater ballistic injury fidelity.

Assessment of polyurethane spheres as surrogates for military ballistic head injury.

SYNBONE® spheres were impacted with 7.62 × 39 mm mild steel core ammunition at a mean impact velocity of 654 m/s, SD 7 m/s, to simulate engagement distances of around 50-100 m. The wounds and fracture patterns were assessed by two forensic pathologists familiar with military cranial injury. The overall fracture pattern was assessed as being too comminuted when compared with actual injury. This suggests the SYNBONE® spheres have less utility for simulating military injury than other purposes described in the literature.

HMGA2 is regulated by LIN28 and BRCA1 in human placental cells.

The chromatin associated transcription factor HMGA2 is a downstream target of let-7 miRNAs and binds to chromatin to regulate gene expression. Inhibition of let-7 miRNAs by RNA-binding proteins LIN28A and LIN28B is necessary during early embryogenesis to ensure stable expression of HMGA2. In addition to LIN28, HMGA2 is regulated by a BRCA1/ZNF350/CtIP repressor complex. In normal tissues, the BRCA1/ZNF350/CtIP complex binds to the HMGA2 promoter to prevent transcription. However, in many cancers the oncomiR miR-182 targets BRCA1, preventing BRCA1 translation and allowing for increased HMGA2. Little is known about the regulation of HMGA2 during early placental development; therefore, we hypothesized that both LIN28 and BRCA1 can regulate HMGA2 in placental cells. Using siRNA and CRISPR gene editing techniques, we found that knockdowns of both LIN28A and LIN28B increase HMGA2 levels in ACH-3P cells. These cells also demonstrated deficiencies in cell differentiation, seemingly differentiating solely towards the syncytiotrophoblast sublineage, secreting higher amounts of hCG, and displaying upregulated ERVW-1. Additionally, we found that a knockout of both LIN28A and LIN28B caused a significant increase of miR-182 and a decrease in BRCA1 allowing HMGA2 mRNA levels to increase and protein levels to remain the same. Using chromatin immunoprecipitation, we saw binding of the BRCA1 repressor complex to HMGA2. We also saw a decrease in binding to HMGA2's promoter in the LIN28A/B knockout cells. These findings suggest a novel role for BRCA1 during early human placental development.

Ballistic impacts on an anatomically correct synthetic skull with a surrogate skin/soft tissue layer.

The aim of this work was to further develop a synthetic model of ballistic head injury by the addition of skin and soft tissue layers to an anatomically correct polyurethane skull filled with gelatine 10% by mass. Six head models were impacted with 7.62 x 39 mm full metal jacket mild steel core (FMJ MSC) bullets with a mean velocity of 652 m/s. The impact events were filmed with high-speed cameras. The models were imaged pre- and post-impact using computed tomography. The models were assessed post impact by two experienced Home Office pathologists and the images assessed by an experienced military radiologist. The findings were scored against real injuries. The entry wounds, exit wounds and fracture patterns were scored positively, but the synthetic skin and soft tissue layer was felt to be too extendable. Further work is ongoing to address this.

Metriculator: quality assessment for mass spectrometry-based proteomics.

SUMMARY: Quality control in mass spectrometry-based proteomics remains subjective, labor-intensive and inconsistent between laboratories. We introduce Metriculator, a software designed to facilitate long-term storage of extensive performance metrics as introduced by NIST in 2010. Metriculator features a web interface that generates interactive comparison plots for contextual understanding of metric values and an automated metric generation toolkit. The comparison plots are designed for at-a-glance determination of outliers and trends in the datasets, together with relevant statistical comparisons. Easy-to-use quantitative comparisons and a framework for integration plugins will encourage a culture of quality assurance within the proteomics community. AVAILABILITY AND IMPLEMENTATION: Available under the MIT license at http://github.com/princelab/metriculator.

Long-term sleep disturbances in children: a cause of neuronal loss.

Short-term sleep loss is known to cause temporary difficulties in cognition, behaviour and health but the effects of persistent sleep deprivation on brain development have received little or no attention. Yet, severe sleep disorders that last for years are common in children especially when they have neurodevelopmental disabilities. There is increasing evidence that chronic sleep loss can lead to neuronal and cognitive loss in children although this is generally unrecognized by the medical profession and the public. Without the restorative functions of sleep due to total sleep deprivation, death is inevitable within a few weeks. Chronic sleep disturbances at any age deprive children of healthy environmental exposure which is a prerequisite for cognitive growth more so during critical developmental periods. Sleep loss adversely effects pineal melatonin production which causes disturbance of circadian physiology of cells, organs, neurochemicals, neuroprotective and other metabolic functions. Through various mechanisms sleep loss causes widespread deterioration of neuronal functions, memory and learning, gene expression, neurogenesis and numerous other changes which cause decline in cognition, behaviour and health. When these changes are long-standing, excessive cellular stress develops which may result in widespread neuronal loss. In this review, for the first time, recent research advances obtained from various fields of sleep medicine are integrated in order to show that untreated chronic sleep disorders may lead to impaired brain development, neuronal damage and permanent loss of developmental potentials. Further research is urgently needed because these findings have major implications for the treatment of sleep disorders.

Ontology mapping and data discovery for the translational investigator.

An integrated data repository (IDR) containing aggregations of clinical, biomedical, economic, administrative, and public health data is a key component of an overall translational research infrastructure. But most available data repositories are designed using standard data warehouse architecture that employs arbitrary data encoding standards, making queries across disparate repositories difficult. In response to these shortcomings we have designed a Health Ontology Mapper (HOM) that translates terminologies into formal data encoding standards without altering the underlying source data. We believe the HOM system promotes inter-institutional data sharing and research collaboration, and will ultimately lower the barrier to developing and using an IDR.

Cost-effectiveness of venlafaxine XL compared with diazepam in the treatment of generalised anxiety disorder in the United Kingdom.

This study used decision modelling to compare the cost-effectiveness of venlafaxine XL (Efexor XL) to that of diazepam to treat non-depressed patients suffering from generalised anxiety disorder (GAD), from the perspective of the United Kingdom's National Health Service (NHS). Starting treatment with venlafaxine XL instead of diazepam significantly increased the expected probability of being in remission by 83% at 6 months (from 16.8% to 30.7%), and the expected probability of relapsing at 6 months was decreased by 79% (from 16.9% to 3.5%). The expected 6-month NHS cost of using venlafaxine XL to treat GAD was estimated to be pounds sterling 353 compared to pounds sterling 311 with diazepam. Hence starting GAD treatment with venlafaxine XL (75 mg per day) instead of diazepam (5 mg three times per day) is clinically more effective and the cost-effective strategy for managing non-depressed patients suffering from GAD in the UK.

Physical activity related energy expenditure in children by doubly labeled water as compared with the Caltrac accelerometer.

OBJECTIVE: The objective of this study was to determine whether the Caltrac accelerometer was a meaningful predictor of physical activity related energy expenditure (AEE) in free-living, pre-adolescent children. SUBJECTS: The sample consisted of 31 children (14 girls, 17 boys; 22 Caucasian, 9 Mohawk) with a mean age of 8.3 (+/- 2.0) y. MEASUREMENTS: AEE was measured by subtracting postprandial resting metabolic rate (RMR), measured via indirect calorimetry, from total daily energy expenditure (TDEE), derived from the doubly labeled water (DLW) method. Average daily activity counts (AC) were measured using a Caltrac accelerometer, which was worn for three days, two weekdays and one weekend day, within the DLW dosing period. RESULTS: AEE was related to gender (r = 0.42, P = 0.02), fat mass (FM, r = 0.32; P = 0.07), and fat free mass (FFM, r = 0.32; P = 0.07), but not to AC (r = -0.09; P = 0.63). After adjusting for gender, race, FM and FFM using multiple correlation regression analysis (R = 0.53), AC did not significantly increase the amount of variation explained in AEE. An estimate of the calories expended in physical activity was derived from AC using a formula developed by Sallis et al. This estimate was significantly higher than AEE (956 kcal/d vs 469 kcal/d, respectively, t = 5.9, P < 0.001). CONCLUSION: The Caltrac was not a meaningful predictor of AEE in our sample. The caloric estimates of energy expended in physical activity derived from the Caltrac AC, were significantly higher in comparison with measured AEE in these free-living children.

Eating and ruminating behavior of steers fed Coastal Bermudagrass hay at four levels.

Effects of feeding level on chewing behavior and physical reduction of particles during ingestive mastication and rumination were examined in four ruminally cannulated steers fed Coastal bermudagrass (Cynodon dactylon [L.] Pers.) hay in the long form. The experimental design was a 4 x 4 latin square with 18-d periods. Treatments based on previous intakes were set at 50, 70, 90 and 110% of feed consumed per animal. Steers were fed at 12-h intervals. Chewing behavior was monitored over 4 d with a computerized system. Boli of ingested, masticated hay (MH), collected at the cardia, and serial samples of digesta taken from the ruminal upper strata (RUS) were wet-sieved. Dimensions of MH particles retained on 4.0- and 2.0-mm sieves were determined by image analysis. Increasing feeding level resulted in a linear increase in the number of boli ruminated (P less than .01) and in linear increases in eating (P less than .01), ruminating (P less than .05) and total chewing time (P less than .01). Linear increases in number of eating (P less than .01), ruminating (P less than .01) and total chews (P less than .01) also were observed. Feeding level had no effect on bolus duration, number of chews/bolus, number of boli/min rumination time and number of chews/min rumination time. The extent of particle breakdown during ingestive mastication was a determinant of the number of boli ruminated daily and their associated number of chews. Number of boli ruminated daily also was related to the RUS mean particle size. Eating time did not provide a reliable indication of how well feed was chewed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ingestive mastication on particle dimensions and weight distribution of coastal bermudagrass hay fed to steers at four levels.

Coastal bermudagrass (Cynodon dactylon [L.] Pers.) hay was fed in the long form to four ruminally cannulated steers to evaluate the effects of intake level on the physical reduction of feed particles during ingestive mastication. The experimental design was a 4 x 4 latin square with 18-d periods. Treatments based on previous intakes were set at 50, 70, 90 and 110% of feed consumed per animal and fed at 12-h intervals. Boli of ingested, masticated hay were collected at the cardia and separated by wet-sieving into fragments retained on sieves of .0027 to 4.0 mm (mesh aperture). In addition, particles retained on the 4.0-mm and 2.0-mm sieves were scanned by image analysis. Ingestive mastication resulted in a linear decrease (P less than .05) in the proportion of boli particles retained on the top (4.0-mm) sieve and linear increases on the 2.0- (P less than .02), 1.0- (P less than .06) and .25-mm (P less than .06) sieves with increasing level of intake. Sixteen to 21% of the ingested hay particles passed through a 1.0-mm sieve. Mean particle size, as determined by sieving data, decreased linearly (P less than .05) as feeding level increased. Image analysis showed no differences in length (L) or width (W) of particles retained on the 4.0- and 2.0-mm sieves as feeding level increased, but L/W decreased linearly (P less than .05) on both sieves. The frequency of jaw movements following feeding was very similar across feeding levels and averaged 71.3 chews/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume determination of TEM specimens containing particles or precipitates.

The volume of thin foil specimens, which contain precipitate or other particles, viewed in the TEM is needed to determine particle density and spacing. It can be determined from the locations of the particles, measured using stereo pairs. A calculation that determines the volume between planes (not necessarily parallel or horizontal) that enclose the points is described. These planes will systematically underestimate the actual surface spacing and hence the volume, but a simple correction factor based on the number of points used in the fit can be used to estimate the actual volume. The method is tested, and its accuracy is evaluated using simulated data and applied to precipitate particles in creep-tested silicon carbide.

Determining risk for chronic otitis media with effusion.

Chronic otitis media with effusion (OME) has been observed in 10 to 20% of children following acute, symptomatic otitis media. To determine factors that place children at increased risk of chronic OME, we conducted a 6-week prospective study of 386 children who had 3 or more recent episodes of otitis media and who had middle ear effusion present for at least 2 weeks. Of these children 23% developed chronic OME (i.e. effusion lasting 8 continuous weeks or more), and 26% developed chronic OME complicated by acute, symptomatic otitis media. Predictors for chronic OME were (1) bilateral OME, (2) duration of effusion for greater than 2 weeks at enrollment and (3) day care attendance. Children with these 3 factors had twice the risk of developing chronic OME as children lacking all 3 factors. These risk factors can be used to target children for early, aggressive OME therapy.

Kinetics of peritoneal dialysis in children: role of lymphatics.

Intraperitoneal fluid is absorbed continuously by convective flow into the peritoneal cavity lymphatics. We evaluated the role of lymphatic absorption in the kinetics of peritoneal dialysis during standardized four hour exchanges in six children using 40 ml/kg of 2.5% dextrose dialysis solution. Cumulative lymphatic absorption averaged 10.4 +/- 1.6 ml/kg and reduced the total net transcapillary ultrafiltration during the dwell time by 73 +/- 10%. Due to the considerable lymphatic absorption rate, maximum intraperitoneal volume was observed before osmolar equilibrium. Extrapolated to four study exchanges per day, lymphatic absorption decreased the potential daily drain volumes in the children by 27 +/- 5% and daily peritoneal urea and creatinine clearances by 24 +/- 4% and 22 +/- 5%, respectively. Compared with four hour exchanges using two liters of 2.5% dextrose dialysis solution in 10 adult CAPD patients with average peritoneal transport, the children had more rapid equilibration of urea, greater absorption of dialysate glucose, higher lymphatic absorption and lower net ultrafiltration (P less than 0.01 to P less than 0.05). Lymphatic absorption therefore causes a relatively greater reduction in net ultrafiltration and solute clearances in children than in adults.

[Effectiveness of bronchial lavage with a new double-lumen catheter]. / Untersuchungen zur Effektivität der Bronchialtoilette mit einer neuen doppellumigen Sonde.

The effectiveness of tracheobronchial lavage in the traditional manner with application of a rinsing solution into the endotracheal tube of artificially ventilated patients is unsatisfactory. In order to improve this a new double lumen catheter was developed. Beside the suction channel with a normal diameter is another very small channel, through which a rinsing solution or drugs can easily be applied endobronchially. The rinsing solution can be poured with high speed through this small channel into the peripheral bronchi. In comparison with the traditional method, endobronchial saline instillation and suctioning can be done more quickly during continuous artificial respiration. The tube was compared with a common suction catheter in 16 patients. These patients were intubated and given artificial respiration. Endobronchial rinsing and suctioning were done periodically. The suctioned bronchial secretion was measured and arterial blood gases were evaluated. Using the dual lumen probe, the suctioned volume was 3.8 times higher. In a short time the arterial oxygen pressure rose from 100% to 123%. An obvious improvement in ventilation could be seen even after 1 h. There was a positive correlation between the suctioned volume and the rise in oxygen pressure. Only suctioning of more than 3.7 ml was accompanied by a rise in the arterial oxygen pressure. Because of continuous artificial respiration, the arterial carbon dioxide pressure was kept constant. Therefore, there is a catheter available that makes it possible to perform a much more effective endobronchial lavage in a shorter period of time.