Corneal confocal microscopy : a novel means to detect nerve fibre damage in idiopathic small fibre neuropathy

Patients with idiopathic small fibre neuropathy (ISFN) have been shown to have significant intraepidermal nerve fibre loss and an increased prevalence of impaired glucose tolerance (IGT). It has been suggested that the dysglycemia of IGT and additional metabolic risk factors may contribute to small nerve fibre damage in these patients. Twenty-five patients with ISFN and 12 aged-matched control subjects underwent a detailed evaluation of neuropathic symptoms, neurological deficits (Neuropathy deficit score (NDS); Nerve Conduction Studies (NCS); Quantitative Sensory Testing (QST) and Corneal Confocal Microscopy (CCM)) to quantify small nerve fibre pathology. Eight (32%) patients had IGT. Whilst all patients with ISFN had significant neuropathic symptoms, NDS, NCS and QST except for warm thresholds were normal. Corneal sensitivity was reduced and CCM demonstrated a significant reduction in corneal nerve fibre density (NFD) (Pb0.0001), nerve branch density (NBD) (Pb0.0001), nerve fibre length (NFL) (Pb0.0001) and an increase in nerve fibre tortuosity (NFT) (Pb0.0001). However these parameters did not differ between ISFN patients with and without IGT, nor did they correlate with BMI, lipids and blood pressure. Corneal confocal microscopy provides a sensitive non-invasive means to detect small nerve fibre damage in patients with ISFN and metabolic abnormalities do not relate to nerve damage.

Increased Langerhan cell density and corneal nerve damage in diabetic patients : role of immune mechanisms in human diabetic neuropathy

Aim/hypothesis Immune mechanisms have been proposed to play a role in the development of diabetic neuropathy. We employed in vivo corneal confocal microscopy (CCM) to quantify the presence and density of Langerhans cells (LCs) in relation to the extent of corneal nerve damage in Bowman's layer of the cornea in diabetic patients. Methods 128 diabetic patients aged 58±1 yrs with a differing severity of neuropathy based on Neuropathy Deficit Score (NDS—4.7±0.28) and 26 control subjects aged 53±3 yrs were examined. Subjects underwent a full neurological evaluation, evaluation of corneal sensation with non-contact corneal aesthesiometry (NCCA) and corneal nerve morphology using corneal confocal microscopy (CCM). Results The proportion of individuals with LCs was significantly increased in diabetic patients (73.8%) compared to control subjects (46.1%), P=0.001. Furthermore, LC density (no/mm2) was significantly increased in diabetic patients (17.73±1.45) compared to control subjects (6.94±1.58), P=0.001 and there was a significant correlation with age (r=0.162, P=0.047) and severity of neuropathy (r=−0.202, P=0.02). There was a progressive decrease in corneal sensation with increasing severity of neuropathy assessed using NDS in the diabetic patients (r=0.414, P=0.000). Corneal nerve fibre density (P<0.001), branch density (P<0.001) and length (P<0.001) were significantly decreased whilst tortuosity (P<0.01) was increased in diabetic patients with increasing severity of diabetic neuropathy. Conclusion Utilising in vivo corneal confocal microscopy we have demonstrated increased LCs in diabetic patients particularly in the earlier phases of corneal nerve damage suggestive of an immune mediated contribution to corneal nerve damage in diabetes.

INTS3 controls the hSSB1-mediated DNA damage response

Human SSB1 (single-stranded binding protein 1 [hSSB1]) was recently identified as a part of the ataxia telangiectasia mutated (ATM) signaling pathway. To investigate hSSB1 function, we performed tandem affinity purifications of hSSB1 mutants mimicking the unphosphorylated and ATM-phosphorylated states. Both hSSB1 mutants copurified a subset of Integrator complex subunits and the uncharacterized protein LOC58493/c9orf80 (henceforth minute INTS3/hSSB-associated element [MISE]). The INTS3–MISE–hSSB1 complex plays a key role in ATM activation and RAD51 recruitment to DNA damage foci during the response to genotoxic stresses. These effects on the DNA damage response are caused by the control of hSSB1 transcription via INTS3, demonstrating a new network controlling hSSB1 function.

Tubal damage, infertility and tubal ectopic pregnancy : chlamydia trachomatis and other microbial aetiologies

Infertility is a worldwide health problem with one in six couples suffering from this condition and with a major economic burden on the global healthcare industry. Estimates of the current global infertility rate suggest that 15% of couples are infertile (Zegers-Hochschild et al 2009) defined as: (1) failure to conceive after 12 months of unprotected sexual intercourse (i.e. infertility); (2) repeated implantation failure following ART cycles; or (3) recurrent miscarriage without difficulty conceiving (natural conceptions). Tubal factor infertility is among the leading causes of female factor infertility accounting for 7-9.8% of all female factor infertilities. Tubal disease directly causes from 36% to 85% of all cases of female factor infertility in developed and developing nations respectively and is associated with polymicrobial aetiologies. One of the leading global causes of tubal factor infertility is thought to be symptomatic (and asymptomatic in up to 70% cases) infection of the female reproductive tract with the sexually transmitted pathogen, Chlamydia trachomatis. Infection-related damage to the Fallopian tubes caused by Chlamydia accounts for more than 70% of cases of infertility in women from developing nations such as sub-Saharan Africa (Sharma et al 2009). Bacterial vaginosis, a condition associated with increased transmission of sexually transmitted infections including those caused by Neisseria gonorrhoeae and Mycoplasma genitalium is present in two thirds of women with pelvic inflammatory disease (PID). This review will focus on (1) the polymicrobial aetiologies of tubal factor infertility and (2) studies involved in screening for, and treatment and control of, Chlamydial infection to prevent PID and the associated sequelae of Fallopian tube inflammation that may lead to infertility and ectopic pregnancy.

Attenuation of muscle damage by preconditioning with muscle hyperthermia

This study investigated the hypothesis that muscle damage would be attenuated in muscles subjected to passive hyperthermia 1 day prior to exercise. Fifteen male students performed 24 maximal eccentric actions of the elbow flexors with one arm; the opposite arm performed the same exercise 2-4 weeks later. The elbow flexors of one arm received a microwave diathermy treatment that increased muscle temperature to over 40°C, 16-20 h prior to the exercise. The contralateral arm acted as an untreated control. Maximal voluntary isometric contraction strength (MVC), range of motion (ROM), upper arm circumference, muscle soreness, plasma creatine kinase activity and myoglobin concentration were measured 1 day prior to exercise, immediately before and after exercise, and daily for 4 days following exercise. Changes in the criterion measures were compared between conditions (treatment vs. control) using a two-way repeated measures ANOVA with a significance level of P < 0.05. All measures changed significantly following exercise, but the treatment arm showed a significantly faster recovery of MVC, a smaller change in ROM, and less muscle soreness compared with the control arm. However, the protective effect conferred by the diathermy treatment was significantly less effective compared with that seen in the second bout performed 4-6 weeks after the initial bout by a subgroup of the subjects (n = 11) using the control arm. These results suggest that passive hyperthermia treatment 1 day prior to eccentric exercise-induced muscle damage has a prophylactic effect, but the effect is not as strong as the repeated bout effect. © Springer-Verlag 2006.

Structural damage identification with noise polluted Frequency Response Functions (FRFs)

Damage detection in structures has become increasingly important in recent years. While a number of damage detection and localization methods have been proposed, very few attempts have been made to explore the structure damage with noise polluted data which is unavoidable effect in real world. The measurement data are contaminated by noise because of test environment as well as electronic devices and this noise tend to give error results with structural damage identification methods. Therefore it is important to investigate a method which can perform better with noise polluted data. This paper introduces a new damage index using principal component analysis (PCA) for damage detection of building structures being able to accept noise polluted frequency response functions (FRFs) as input. The FRF data are obtained from the function datagen of MATLAB program which is available on the web site of the IASC-ASCE (International Association for Structural Control– American Society of Civil Engineers) Structural Health Monitoring (SHM) Task Group. The proposed method involves a five-stage process: calculation of FRFs, calculation of damage index values using proposed algorithm, development of the artificial neural networks and introducing damage indices as input parameters and damage detection of the structure. This paper briefly describes the methodology and the results obtained in detecting damage in all six cases of the benchmark study with different noise levels. The proposed method is applied to a benchmark problem sponsored by the IASC-ASCE Task Group on Structural Health Monitoring, which was developed in order to facilitate the comparison of various damage identification methods. The illustrated results show that the PCA-based algorithm is effective for structural health monitoring with noise polluted FRFs which is of common occurrence when dealing with industrial structures.

Effects of whole-body cryotherapy (-110 degrees C) on proprioception and indices of muscle damage

The purpose of this study was to investigate the effects of whole-body cryotherapy (WBC) on proprioceptive function, muscle force recovery following eccentric muscle contractions and tympanic temperature (TTY). Thirty-six subjects were randomly assigned to a group receiving two 3-min treatments of −110 ± 3 °C or 15 ± 3 °C. Knee joint position sense (JPS), maximal voluntary isometric contraction (MVIC) of the knee extensors, force proprioception and TTY were recorded before, immediately after the exposure and again 15 min later. A convenience sample of 18 subjects also underwent an eccentric exercise protocol on their contralateral left leg 24 h before exposure. MVIC (left knee), peak power output (PPO) during a repeated sprint on a cycle ergometer and muscles soreness were measured pre-, 24, 48 and 72 h post-treatment. WBC reduced TTY, by 0.3 °C, when compared with the control group (P<0.001). However, JPS, MVIC or force proprioception was not affected. Similarly, WBC did not effect MVIC, PPO or muscle soreness following eccentric exercise. WBC, administered 24 h after eccentric exercise, is ineffective in alleviating muscle soreness or enhancing muscle force recovery. The results of this study also indicate no increased risk of proprioceptive-related injury following WBC.

Damage quantification techniques in acoustic emission monitoring

Acoustic emission (AE) analysis is one of the several diagnostic techniques available nowadays for structural health monitoring (SHM) of engineering structures. Some of its advantages over other techniques include high sensitivity to crack growth and capability of monitoring a structure in real time. The phenomenon of rapid release of energy within a material by crack initiation or growth in form of stress waves is known as acoustic emission (AE). In AE technique, these stress waves are recorded by means of suitable sensors placed on the surface of a structure. Recorded signals are subsequently analysed to gather information about the nature of the source. By enabling early detection of crack growth, AE technique helps in planning timely retrofitting or other maintenance jobs or even replacement of the structure if required. In spite of being a promising tool, some challenges do still exist behind the successful application of AE technique. Large amount of data is generated during AE testing, hence effective data analysis is necessary, especially for long term monitoring uses. Appropriate analysis of AE data for quantification of damage level is an area that has received considerable attention. Various approaches available for damage quantification for severity assessment are discussed in this paper, with special focus on civil infrastructure such as bridges. One method called improved b-value analysis is used to analyse data collected from laboratory testing.

Severity of driver injury and vehicle damage in traffic crashes at intersections: A Bayesian hierarchical analysis

Most crash severity studies ignored severity correlations between driver-vehicle units involved in the same crashes. Models without accounting for these within-crash correlations will result in biased estimates in the factor effects. This study developed a Bayesian hierarchical binomial logistic model to identify the significant factors affecting the severity level of driver injury and vehicle damage in traffic crashes at signalized intersections. Crash data in Singapore were employed to calibrate the model. Model fitness assessment and comparison using Intra-class Correlation Coefficient (ICC) and Deviance Information Criterion (DIC) ensured the suitability of introducing the crash-level random effects. Crashes occurring in peak time, in good street lighting condition, involving pedestrian injuries are associated with a lower severity, while those in night time, at T/Y type intersections, on right-most lane, and installed with red light camera have larger odds of being severe. Moreover, heavy vehicles have a better resistance on severe crash, while crashes involving two-wheel vehicles, young or aged drivers, and the involvement of offending party are more likely to result in severe injuries.

The spatial distribution of rodent damage in Australian macadamia (Macadamia integrifolia) orchards

The Black Rat (Rattus rattus), a global pest within the macadamia production industry, causes up to 30% crop damage in Australian orchards. During early stages of production in Australia, research demonstrated the importance of non crop adjacent habitats as significant in affecting the patterns of crop damage seen throughout orchards. Where once rodent damage was limited to the outside edges of orchard blocks, growers are now reporting finding crop damage throughout entire orchards. This study therefore aims to explore the spatial patterns of rodent distribution and damage now occurring in Australian macadamia orchards. We show that rodent damage and rodent distribution in these newer production regions differ from that shown in previous Australian research. Previous Australian research has shown damage patterns which were associated with the edges of orchard blocks however this study demonstrates a more widespread damage distribution. In the current study there is no relationship between rodent damage and the orchard edge. Arboreal rodent nests were identified within these newer orchard systems, suggesting rodents are residing within the tree component of the orchard system and not dependent on adjacent non-crop habitat for shelter. Results from this study confirm that rodents have modified their nesting and foraging behaviour in newer orchards systems in Australia. We suggest that this is a response of increased and prolonged availability of macadamia nuts in newer production regions enabling populations to be maintained throughout the year. Management strategies will require modification if control is to be achieved.

INT6/EIF3E interacts with ATM and is required for proper execution of the DNA damage response in human cells

Altered expression of the INT6 gene, encoding the e subunit of the translational initiation factor eIF3, occurs in human breast cancers, but how INT6 relates to carcinogenesis remains unestablished. Here, we show that INT6 is involved in the DNA damage response. INT6 was required for cell survival following γ-irradiation and G(2)-M checkpoint control. RNA interference-mediated silencing of INT6 reduced phosphorylation of the checkpoint kinases CHK1 and CHK2 after DNA damage. In addition, INT6 silencing prevented sustained accumulation of ataxia telangiectasia mutated (ATM) at DNA damage sites in cells treated with γ-radiation or the radiomimetic drug neocarzinostatin. Mechanistically, this result could be explained by interaction of INT6 with ATM, which together with INT6 was recruited to the sites of DNA damage. Finally, INT6 silencing also reduced ubiquitylation events that promote retention of repair proteins at DNA lesions. Accordingly, accumulation of the repair factor BRCA1 was defective in the absence of INT6. Our findings reveal unexpected and striking connections of INT6 with ATM and BRCA1 and suggest that the protective action of INT6 in the onset of breast cancers relies on its involvement in the DNA damage response.

Damage detection in slab-on-girder bridges using vibration characteristics

This paper develops and applies a multi-criteria procedure, incorporating changes in natural frequencies, modal flexibility and the modal strain energy, for damage detection in slab-on-girder bridges. The proposed procedure is first validated through experimental testing of a model bridge. Numerically simulated modal data obtained through finite element analyses are then used to evaluate the vibration parameters before and after damage and used as the indices for assessment of the state of structural health. The procedure is illustrated by its application to full scale slab-on-girder bridges under different damage scenarios involving single and multiple damages on the deck and girders.

Comparison of two suspension control strategies for multi-axle heavy truck

Two simple and effective control strategies for a multi-axle heavy truck, modified skyhook damping (MSD) control and proportional-integration-derivative (PID) control, were implemented into functional virtual prototype (FVP) model and compared in terms of road friendliness and ride comfort. A four-axle heavy truck-road coupling system model was established using FVP technology and validated through a ride comfort test. Then appropriate passive air suspensions were chosen to replace the rear tandem suspensions of the original truck model for preliminary optimization. The mechanical properties and time lag of dampers were taken into account in simulations of MSD and PID semi-active dampers implemented using MATLAB/Simulink. Through co-simulations with Adams and MATLAB, the effects of semi-active MSD and PID control were analyzed and compared, and control parameters which afforded the best comprehensive performance for each control strategy were chosen. Simulation results indicate that compared with the passive air suspension truck, semi-active MSD control improves both ride comfort and road-friendliness markedly, with optimization ratios of RMS vertical acceleration and RMS tyre force ranging from 10.1% to 44.8%. However, semi-active PID control only reduces vertical vibration of the driver’s seat by 11.1%, 11.1% and 10.9% on A, B and C level roads respectively. Both strategies are robust to the variation of road level.

Chromatin modifications involved in the DNA damage response to double strand breaks

In eukaryotes, genomic DNA is tightly compacted into a protein-DNA complex known as chromatin. This dense structure presents a barrier to DNA-dependent processes including transcription, replication and DNA repair. The repressive structure of chromatin is overcome by ATP-dependent chromatin remodelling complexes and chromatin-modifying enzymes. There is now ample evidence that DNA double-strand breaks (DSBs) elicit various histone modifications (such as acetylation, deacetylation, and phosphorylation) that function combinatorially to control the dynamic structure of the chromatin microenvironment. The role of these mechanisms during transcription and replication has been well studied, while the research into their impact on regulation of DNA damage response is rapidly gaining momentum. How chromatin structure is remodeled in response to DNA damage and how such alterations influence DSB repair are currently significant questions. This review will summarise the major chromatin modifications and chromatin remodelling complexes implicated in the DNA damage response to DSBs.

Applying quantile regression for modeling equivalent property damage only crashes to identify accident blackspots

Hot spot identification (HSID) aims to identify potential sites—roadway segments, intersections, crosswalks, interchanges, ramps, etc.—with disproportionately high crash risk relative to similar sites. An inefficient HSID methodology might result in either identifying a safe site as high risk (false positive) or a high risk site as safe (false negative), and consequently lead to the misuse the available public funds, to poor investment decisions, and to inefficient risk management practice. Current HSID methods suffer from issues like underreporting of minor injury and property damage only (PDO) crashes, challenges of accounting for crash severity into the methodology, and selection of a proper safety performance function to model crash data that is often heavily skewed by a preponderance of zeros. Addressing these challenges, this paper proposes a combination of a PDO equivalency calculation and quantile regression technique to identify hot spots in a transportation network. In particular, issues related to underreporting and crash severity are tackled by incorporating equivalent PDO crashes, whilst the concerns related to the non-count nature of equivalent PDO crashes and the skewness of crash data are addressed by the non-parametric quantile regression technique. The proposed method identifies covariate effects on various quantiles of a population, rather than the population mean like most methods in practice, which more closely corresponds with how black spots are identified in practice. The proposed methodology is illustrated using rural road segment data from Korea and compared against the traditional EB method with negative binomial regression. Application of a quantile regression model on equivalent PDO crashes enables identification of a set of high-risk sites that reflect the true safety costs to the society, simultaneously reduces the influence of under-reported PDO and minor injury crashes, and overcomes the limitation of traditional NB model in dealing with preponderance of zeros problem or right skewed dataset.