Evaluation of ensemble Monte Carlo variable selection for identification of metabolite markers on NMR data.

The aim of this study was to investigate the potential of the recently developed ensemble Monte Carlo Variable Selection (EMCVS) method to identify the relevant portions of high resolution 1H NMR spectra as a metabolite fingerprinting tool and compare to a widely used method (Variable importance on projection (VIP)) and recently proposed variable selected methods i.e. selectivity ratio (SR) and significance multivariate correlation (sMC). As case studies two quantitative publicly available datasets: wine samples, urine samples of rats, and an experiment on mushroom (Agaricus bisporus) were examined. EMCVS outperformed the three other variable selection methods in most cases, selecting fewer chemical shifts and leading to improved classification of mushrooms and prediction of onion by-products intake and wine components. These fewer chemical shift regions facilitate the interpretation of the NMR spectra, fingerprinting and identification of metabolite markers.

Welfare of anaesthesia trainees survey.

This study was designed to investigate levels of stress, anxiety or depression and to identify factors compounding or relieving stress in anaesthesia trainees within the Australian and New Zealand College of Anaesthetists (ANZCA) training scheme. An electronic survey was sent to 999 randomly selected trainees and 428 responses were received. In addition to demographics, psychological wellbeing was assessed using the Kessler Psychological Distress Scale (K10) and questions were asked about depression and anxiety, exacerbating factors, personal healthcare and strategies used to manage stress. The majority of respondents (73%) reported being satisfied or very satisfied with their job and training. However, 28% of respondents had K10 scores indicating high or very high distress levels. Eleven percent reported being currently on treatment for anxiety and/or depression. Twenty-two percent reported having experienced bullying and 14% sexism. Twenty-eight percent reported that they did not have a regular general practitioner (GP), and 41% reported having not visited their GP in the previous year. Forty-seven percent of trainees reported that they self-prescribe medications. Major stressors reported were exams, critical clinical events and fear of making errors. Two stressors previously not identified in similar studies were concern about job prospects in 71% of respondents and workplace-based assessments in 51%. This survey demonstrates significant psychological impairment and poor personal healthcare amongst many trainees. Education, careful continuing assessment of trainees' welfare and a review of current support and remedial measures may be required.

On the feasibility of near infrared spectroscopy to detect contaminants in water using single salt solutions as model systems.

This research work evaluates the feasibility of NIRS to detect contaminants in water using single salt solutions as model systems. Previous research has indicated the potential of near infrared spectroscopy (NIRS) for detecting solutes in water; however, a comprehensive investigation of the limit of detection of this technique has not been carried out. Near infrared transmittance spectra of aqueous salt solutions in the concentration range 0.002-0.1 mol L(-1) (equivalent to 117-13,334 ppm or 0.0001-0.01% mass/mass) were investigated. The first overtone region of the near infrared spectrum (1300-1600 nm) was found to be the most effective wavelength range for prediction of salt concentration in aqueous solutions. Calibration models built using this wavelength range and employing the extended multiplicative scatter spectral pre-treatment resulted in root mean squared error of prediction values ranging from 0.004 to 0.01 mol L(-1). The limit of detection (LOD) was estimated to be of the order of 0.1% (mass/mass) or 1000 ppm. Within the framework of Aquaphotomics, it was possible to examine the effect of different salts on the NIR spectra of water in the first overtone range. Our results were confirmed through test experiments at various geographical locations employing dispersive and Fourier transform type NIRS instruments.

Ascertainment of acute liver injury in two European primary care databases.

PURPOSE: The purpose of this study was to ascertain acute liver injury (ALI) in primary care databases using different computer algorithms. The aim of this investigation was to study and compare the incidence of ALI in different primary care databases and using different definitions of ALI. METHODS: The Clinical Practice Research Datalink (CPRD) in UK and the Spanish "Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria" (BIFAP) were used. Both are primary care databases from which we selected individuals of all ages registered between January 2004 and December 2009. We developed two case definitions of idiopathic ALI using computer algorithms: (i) restrictive definition (definite cases) and (ii) broad definition (definite and probable cases). Patients presenting prior liver conditions were excluded. Manual review of potential cases was performed to confirm diagnosis, in a sample in CPRD (21%) and all potential cases in BIFAP. Incidence rates of ALI by age, sex and calendar year were calculated. RESULTS: In BIFAP, all cases considered definite after manual review had been detected with the computer algorithm as potential cases, and none came from the non-cases group. The restrictive definition of ALI had a low sensitivity but a very high specificity (95% in BIFAP) and showed higher rates of agreement between computer search and manual review compared to the broad definition. Higher incidence rates of definite ALI in 2008 were observed in BIFAP (3.01 (95% confidence interval (CI) 2.13-4.25) per 100,000 person-years than CPRD (1.35 (95% CI 1.03-1.78)). CONCLUSIONS: This study shows that it is feasible to identify ALI cases if restrictive selection criteria are used and the possibility to review additional information to rule out differential diagnoses. Our results confirm that idiopathic ALI is a very rare disease in the general population. Finally, the construction of a standard definition with predefined criteria facilitates the timely comparison across databases.

A prospective study of human papillomavirus (HPV) testing to resolve uncertainty in colposcopy.

OBJECTIVE: UK colposcopy services are seeing increased workloads, a large proportion of which are follow-up appointments. The English Cervical Screening Programme HPV Special Interest Group identified five subcategories of colposcopy clinic patients who often require prolonged follow-up regimes for low-grade abnormalities. Human papillomavirus (HPV) testing has a high negative predictive value, meaning that HPV-negative women are at very low risk of underlying disease. Our objectives were to quantify the number of HPV-negative women in each study subcategory and to evaluate the number who could potentially be discharged from colposcopy on the basis of their results. METHODS: Four colposcopy clinics prospectively identified women according to five categories over 12 months. All women underwent cytological testing and high-risk HPV (hrHPV) testing using the Hybrid Capture 2 test. Management outcomes and decisions based on a knowledge of the HPV status were recorded. RESULTS: Data available on 755 women showed that 422/755 (55.9%) and 260/755 (34.4%) had persistent cervical intraepithelial neoplasia grade 1 (CIN1) (Category 1) or a minor abnormality following treatment (Category 2), respectively. In Categories 1 and 2, 51.7% and 60.2%, respectively, were hrHPV negative. The rates with biopsies of CIN2 or worse (CIN2+) across the two categories were 3/355 (0.8%) and 21/291 (7.0%) for hrHPV-negative and hrHPV-positive women, respectively. CONCLUSION: The incorporation of hrHPV testing within organized cervical screening programmes has been widely accepted. hrHPV testing for the clinical scenarios outlined in this study detects women who are hrHPV negative and therefore at low risk of underlying disease, potentially reducing anxiety and inconvenience for women and costs to colposcopy services.

Detrimental role of the airway mucin Muc5ac during ventilator-induced lung injury.

Acute lung injury (ALI) is associated with high morbidity and mortality in critically ill patients. At present, the functional contribution of airway mucins to ALI is unknown. We hypothesized that excessive mucus production could be detrimental during lung injury. Initial transcriptional profiling of airway mucins revealed a selective and robust induction of MUC5AC upon cyclic mechanical stretch exposure of pulmonary epithelia (Calu-3). Additional studies confirmed time- and stretch-dose-dependent induction of MUC5AC transcript or protein during cyclic mechanical stretch exposure in vitro or during ventilator-induced lung injury in vivo. Patients suffering from ALI showed a 58-fold increase in MUC5AC protein in their bronchoalveolar lavage. Studies of the MUC5AC promoter implicated nuclear factor κB in Muc5ac induction during ALI. Moreover, mice with gene-targeted deletion of Muc5ac⁻/⁻ experience attenuated lung inflammation and pulmonary edema during injurious ventilation. We observed that neutrophil trafficking into the lungs of Muc5ac⁻/⁻ mice was selectively attenuated. This implicates that endogenous Muc5ac production enhances pulmonary neutrophil trafficking during lung injury. Together, these studies reveal a detrimental role for endogenous Muc5ac production during ALI and suggest pharmacological strategies to dampen mucin production in the treatment of lung injury.

Time series hyperspectral chemical imaging data: challenges, solutions and applications.

Hyperspectral chemical imaging (HCI) integrates imaging and spectroscopy resulting in three-dimensional data structures, hypercubes, with two spatial and one wavelength dimension. Each spatial image pixel in a hypercube contains a spectrum with >100 datapoints. While HCI facilitates enhanced monitoring of multi-component systems; time series HCI offers the possibility of a more comprehensive understanding of the dynamics of such systems and processes. This implies a need for modeling strategies that can cope with the large multivariate data structures generated in time series HCI experiments. The challenges posed by such data include dimensionality reduction, temporal morphological variation of samples and instrumental drift. This article presents potential solutions to these challenges, including multiway analysis, object tracking, multivariate curve resolution and non-linear regression. Several real world examples of time series HCI data are presented to illustrate the proposed solutions.

Influence of polymer packaging films on hyperspectral imaging data in the visible-near-infrared (450-950 nm) wavelength range.

Hyperspectral imaging (HSI) has recently emerged as a useful tool for quality analysis of consumer goods (e.g., food and pharmaceutical products). These products are typically packaged in polymeric film prior to distribution; however, HSI experiments are typically carried out on such samples ex-packaging (either prior to or after removal from packaging). This research examines the effects of polymer packaging films (polyvinyl chloride (PVC) and polyethylene terephthalate (PET)) on spectral and spatial features of HSI data in order to investigate the potential of HSI for quality evaluation of packaged goods. The effects of packaging film were studied for hyperspectral images of samples obtained in the visible-near-infrared (Vis-NIR, i.e., 450-950 nm) wavelength range, which is relevant to many food, agricultural, and pharmaceutical products. The dominant influence of the films tested in this wavelength range could be attributed to light scattering. Relative position of the light source, film, and detector were shown to be highly influential on the scattering effects observed. Detection of features on samples imaged through film was shown to be possible after some data preprocessing. This suggests that quality analysis of products packaged in polymer film is feasible using HSI. These findings would be useful in the development of quality monitoring tools for consumer products post-packaging using HSI.

Application of mid-infrared spectroscopy to the prediction of maturity and sensory texture attributes of cheddar cheese.

The objective of this study was to determine the potential of mid-infrared spectroscopy in conjunction with partial least squares (PLS) regression to predict various quality parameters in cheddar cheese. Cheddar cheeses (n= 24) were manufactured and stored at 8 degrees C for 12 mo. Mid-infrared spectra (640 to 4000/cm) were recorded after 4, 6, 9, and 12 mo storage. At 4, 6, and 9 mo, the water-soluble nitrogen (WSN) content of the samples was determined and the samples were also evaluated for 11 sensory texture attributes using descriptive sensory analysis. The mid-infrared spectra were subjected to a number of pretreatments, and predictive models were developed for all parameters. Age was predicted using scatter-corrected, 1st derivative spectra with a root mean square error of cross-validation (RMSECV) of 1 mo, while WSN was predicted using 1st derivative spectra (RMSECV = 2.6%). The sensory texture attributes most successfully predicted were rubbery, crumbly, chewy, and massforming. These attributes were modeled using 2nd derivative spectra and had corresponding RMSECV values in the range of 2.5 to 4.2 on a scale of 0 to 100. It was concluded that mid-infrared spectroscopy has the potential to predict age, WSN, and several sensory texture attributes of cheddar cheese.

Evaluating mid-infrared spectroscopy as a new technique for predicting sensory texture attributes of processed cheese.

The objective of this study was to investigate the potential application of mid-infrared spectroscopy for determination of selected sensory attributes in a range of experimentally manufactured processed cheese samples. This study also evaluates mid-infrared spectroscopy against other recently proposed techniques for predicting sensory texture attributes. Processed cheeses (n = 32) of varying compositions were manufactured on a pilot scale. After 2 and 4 wk of storage at 4 degrees C, mid-infrared spectra (640 to 4,000 cm(-1)) were recorded and samples were scored on a scale of 0 to 100 for 9 attributes using descriptive sensory analysis. Models were developed by partial least squares regression using raw and pretreated spectra. The mouth-coating and mass-forming models were improved by using a reduced spectral range (930 to 1,767 cm(-1)). The remaining attributes were most successfully modeled using a combined range (930 to 1,767 cm(-1) and 2,839 to 4,000 cm(-1)). The root mean square errors of cross-validation for the models were 7.4 (firmness; range 65.3), 4.6 (rubbery; range 41.7), 7.1 (creamy; range 60.9), 5.1 (chewy; range 43.3), 5.2 (mouth-coating; range 37.4), 5.3 (fragmentable; range 51.0), 7.4 (melting; range 69.3), and 3.1 (mass-forming; range 23.6). These models had a good practical utility. Model accuracy ranged from approximate quantitative predictions to excellent predictions (range error ratio = 9.6). In general, the models compared favorably with previously reported instrumental texture models and near-infrared models, although the creamy, chewy, and melting models were slightly weaker than the previously reported near-infrared models. We concluded that mid-infrared spectroscopy could be successfully used for the nondestructive and objective assessment of processed cheese sensory quality.

Topical tacrolimus in the management of lichen sclerosus.

The effective management of vulval lichen sclerosus (LS) currently depends upon the use of topical steroids and emollients. There are concerns with regard to the long-term toxicity of potent steroids and therefore is a need to consider effective alternatives. Immunomodulatory macrolactams offer an alternative to steroids in the management of some other inflammatory skin disorders and it would seem reasonable therefore to assess their activity in LS. This pilot study of 16 histologically confirmed cases of LS suggests that macrolactams have a positive pharmacological effect.

Underlying chronic granulomatous disease in a patient with bronchocentric granulomatosis.

We present a case of bronchocentric granulomatosis in a woman with no history of asthma who was colonised with Aspergillusfumigatus. A family history of chronic granulomatous disease prompted further testing that demonstrated severely depressed neutrophil oxidant production and gp91(phox) deficiency compatible with the X linked carrier state of chronic granulomatous disease. Only one report of the association of these two rare diseases has previously appeared in the literature. We postulate that an ineffective immune response led to the prolonged colonisation of Afumigatus resulting in a hypersensitivity reaction that was manifest clinically as bronchocentric granulomatosis.

A unique renal lesion in common variable immunodeficiency.

This article reports the case of a 33-year-old woman with common variable immunodeficiency (CVI) who developed renal failure 17 years after diagnosis and initiation of treatment with monthly IVIG. A renal biopsy revealed mesangial and paramesangial immune complex deposition and interstitial granulomatous infiltration. Renal function improved with oral corticosteroids, but did not return to normal. Decreasing the dose of IVIG had no effect on renal function. Immune dysfunction can be associated with both granulomatous disease and immune complex glomerulonephritis, or the latter may be related to chronic infection or immunoglobulin use. This is the first report of concomitant glomerular-tubulointerstitial lesions in this immunodeficiency syndrome. Renal function should be closely followed in patients with CVI.