Pan-serotype diagnostic for foot-and-mouth disease using the consensus antigen of nonstructural protein 3B

An amino acid consensus sequence for the seven serotypes of foot-and-mouth disease virus (FMDV) nonstructural protein 3B, including all three contiguous repeats, and its use in the development of a pan-serotype diagnostic test for all seven FMDV serotypes are described. The amino acid consensus sequence of the 3B protein was determined from a multiple-sequence alignment of 125 sequences of 3B. The consensus 3B (c3B) protein was expressed as a soluble recombinant fusion protein with maltose-binding protein (MBP) using a bacterial expression system and was affinity purified using amylose resin. The MBP-c3B protein was used as the antigen in the development of a competition enzyme-linked immunosorbent assay (cELISA) for detection of anti-3B antibodies in bovine sera. The comparative diagnostic sensitivity and specificity at 47% inhibition were estimated to be 87.22% and 93.15%, respectively. Reactivity of c3B with bovine sera representing the seven FMDV serotypes demonstrated the pan-serotype diagnostic capability of this bioreagent. The consensus antigen and competition ELISA are described here as candidates for a pan-serotype diagnostic test for FMDV infection.

Boron nitride nanosheets improve sensitivity and reusability of surface-enhanced raman spectroscopy

Surface enhanced Raman spectroscopy (SERS) is a useful multidisciplinary analytic technique. However, it is still a challenge to produce SERS substrates that are highly sensitive, reproducible, stable, reusable, and scalable. Herein, we demonstrate that atomically thin boron nitride (BN) nanosheets have many unique and desirable properties to help solve this challenge. The synergic effect of the atomic thickness, high flexibility, stronger surface adsorption capability, electrical insulation, impermeability, high thermal and chemical stability of BN nanosheets can increase the Raman sensitivity by up to two orders, and in the meantime attain long-term stability and extraordinary reusability not achievable by other materials. These advances will greatly facilitate the wider use of SERS in many fields.

Accuracy and usefulness of select methods for assessing complete collection of 24-hour urine: a systematic review.

Twenty-four-hour urine collection is the recommended method for estimating sodium intake. To investigate the strengths and limitations of methods used to assess completion of 24-hour urine collection, the authors systematically reviewed the literature on the accuracy and usefulness of methods vs para-aminobenzoic acid (PABA) recovery (referent). The percentage of incomplete collections, based on PABA, was 6% to 47% (n=8 studies). The sensitivity and specificity for identifying incomplete collection using creatinine criteria (n=4 studies) was 6% to 63% and 57% to 99.7%, respectively. The most sensitive method for removing incomplete collections was a creatinine index <0.7. In pooled analysis (≥2 studies), mean urine creatinine excretion and volume were higher among participants with complete collection (P<.05); whereas, self-reported collection time did not differ by completion status. Compared with participants with incomplete collection, mean 24-hour sodium excretion was 19.6 mmol higher (n=1781 specimens, 5 studies) in patients with complete collection. Sodium excretion may be underestimated by inclusion of incomplete 24-hour urine collections. None of the current approaches reliably assess completion of 24-hour urine collection.

The catheter to vein ratio and rates of symptomatic venous thromboembolism in patients with a peripherally inserted central catheter (PICC): a prospective cohort study.

BACKGROUND: Peripherally inserted central catheters (PICCs) are a common vascular access device used in clinical practice. Their use may be complicated by adverse events such as venous thromboembolism (VTE). The size of the vein used for PICC insertion and thus the catheter to vein ratio is thought to be a controllable factor in the reduction of VTE rates in patients who have a PICC. However, an optimal catheter to vein ratio for PICC insertion has not previously been investigated to inform clinical practice. OBJECTIVES: To determine the effect of the catheter to vein ratio (proportion of the vein measured at the insertion point taken up by the catheter) on rates of symptomatic VTE in patients with a PICC and identify the optimal ratio cut-off point to reduce rates of this adverse event. METHOD: Adult patients waiting for PICC insertion at a large metropolitan teaching hospital were recruited between May and December 2013. Vein diameter at the PICC insertion site was measured using ultrasound with in-built callipers. Participants were followed up at eight weeks to determine if they developed symptomatic VTE. RESULTS: Data were available for 136 patients (50% cancer; 44% infection; 6% other indication for PICC). Mean age was 57 years with 54% males. There were four cases of confirmed symptomatic VTE (two involving the deep veins, one peripheral vein and one pulmonary embolism). Receiver operator characteristic (ROC) analysis determined that a 45% catheter to vein ratio was the ideal cut off point to maximise sensitivity and specificity (AUC 0.761; 95% CI 0.681-0.830). When a ratio of 46% or above was compared to one that was less than or equal to 45% using a log binomial generalised linear model it was found that participants with a catheter to vein ratio >45% were 13 times more likely to suffer VTE (relative risk 13, p=0.022; CI 1.445-122.788). CONCLUSION: It was found that a 45% catheter to vein ratio was the optimal cut off with high sensitivity and specificity to reduce the risk of VTE. However, further research is needed to confirm these results as although adequately powered; the number of cases of VTE was comparatively small, resulting in wide confidence intervals.

A comparison of four functional test in discriminating fallers from non-fallers in older people

Purpose : Which functional tests on mobility and balance can better screen older people at risk of falls is unclear. This study aims to compare the Berg Balance Scale (BBS), Tinetti Mobility Score (TMS), Elderly Mobility Scale (EMS) and Timed Up and Go test (TUG) in discriminating fallers from non-fallers in older people.
Method : This was a case-control study involving one rater who conducted a mobility and balance assessment on subjects using the four functional tests in random sequence. Subjects recruited included 17 and 22 older people with a history of single and multiple falls respectively from a public Falls Clinic, and 39 community-dwellers without fall history and whose age, sex and BMI matched those of the fallers. All subjects underwent the mobility and balance assessment within one day.
Results : Single fallers performed better than multiple fallers in all four functional tests but were worse than non-fallers in the BBS, TMS and TUG. The BBS demonstrated the best discriminating ability, with high sensitivity and specificity. The BBS item 'pick up an object from the floor' was the best at screening fallers.
Conclusion : BBS was the most powerful functional test of the four in discriminating fallers from non-faller.

The performance of solarscan : an automated dermoscopy image analysis instrument for the diagnosis of primary melanoma

Objective To describe the diagnostic performance of SolarScan (Polartechnics Ltd, Sydney, Australia), an automated instrument for the diagnosis of primary melanoma.

Design Images from a data set of 2430 lesions (382 were melanomas; median Breslow thickness, 0.36 mm) were divided into a training set and an independent test set at a ratio of approximately 2:1. A diagnostic algorithm (absolute diagnosis of melanoma vs benign lesion and estimated probability of melanoma) was developed and its performance described on the test set. High-quality clinical and dermoscopy images with a detailed patient history for 78 lesions (13 of which were melanomas) from the test set were given to various clinicians to compare their diagnostic accuracy with that of SolarScan.

Setting Seven specialist referral centers and 2 general practice skin cancer clinics from 3 continents. Comparison between clinician diagnosis and SolarScan diagnosis was by 3 dermoscopy experts, 4 dermatologists, 3 trainee dermatologists, and 3 general practitioners.

Patients Images of the melanocytic lesions were obtained from patients who required either excision or digital monitoring to exclude malignancy.

Main Outcome Measures Sensitivity, specificity, the area under the receiver operator characteristic curve, median probability for the diagnosis of melanoma, a direct comparison of SolarScan with diagnoses performed by humans, and interinstrument and intrainstrument reproducibility.

Results The melanocytic-only diagnostic model was highly reproducible in the test set and gave a sensitivity of 91% (95% confidence interval [CI], 86%-96%) and specificity of 68% (95% CI, 64%-72%) for melanoma. SolarScan had comparable or superior sensitivity and specificity (85% vs 65%) compared with those of experts (90% vs 59%), dermatologists (81% vs 60%), trainees (85% vs 36%; P =.06), and general practitioners (62% vs 63%). The intraclass correlation coefficient of intrainstrument repeatability was 0.86 (95% CI, 0.83-0.88), indicating an excellent repeatability. There was no significant interinstrument variation (P = .80).

Conclusions SolarScan is a robust diagnostic instrument for pigmented or partially pigmented melanocytic lesions of the skin. Preliminary data suggest that its performance is comparable or superior to that of a range of clinician groups. However, these findings should be confirmed in a formal clinical trial.

Nutrition screening in long-term care facilities : an evaluation of the methodological quality of available instruments

A variety of nutrition screening instruments have been developed and implemented for identifying the risk of undernutrition among community and hospitalized older adults. Despite the high prevalence of undernutrition amongst older adults in long-term care, few screening instruments have been developed or evaluated in this setting. This review aims to evaluate the validity, reproducibility and feasibility of nutrition screening instruments developed for use, or described as being used, with older adults in long-term care. Ten publications encompassing nine independent nutrition screening tools were identified using electronic databases and manual searches of reference lists. The Mini Nutritional Assessment-Short Form (MNA-SF) was the most widely evaluated nutrition screening instrument and met the requirements for a valid instrument (sensitivity and specificity >0.9) for use in the long-term care setting. Modified versions of the MNA for use in China and South Africa also demonstrated acceptable levels of sensitivity and specificity. Other nutrition screening instruments were found to have variable levels of sensitivity and specificity and while some demonstrated levels consistent with the MNA-SF, only two were evaluated across more than one study population, Body Mass Index (BMI)+weight loss and BMI+albumin. These same instruments reported the highest levels of inter-rater and test-retest reproducibility, although this was only tested in one other instrument (Chinese Nutrition Screen -modified MNA). In conclusion, it is evident from this review that further work in this area is needed. Based on validity, reproducibility and feasibility it appears that BMI+weight loss is the most suitable nutrition screening instrument for use in the long-term care setting at this time. MNA-SF is promising; however, there is currently no data for inter-rater or test-retest reproducibility in the long-term care setting.

Screening pregnant women for chlamydia : what are the predictors of infection?

Objectives: To determine the risk factors associated with chlamydial infection in pregnancy and the sensitivity and specificity of these when used for selective screening.

Methods: A prospective, cross-sectional study of pregnant women aged 16–25 years attending four major public antenatal services across Melbourne, Australia. Between October 2006 and July 2007, women were approached consecutively and asked to complete a questionnaire and to provide a first-pass urine specimen for Chlamydia trachomatis testing using PCR.

Results: Of 1180 eligible women, 1087 were approached and 1044 (88%) consented to participate. Among the 987 women for whom a questionnaire and a definitive diagnostic assay were available, the prevalence of chlamydia was 3.2% (95% CI 1.8 to 5.9). In a multiple logistic regression model, more than one sexual partner in the past year (AOR 11.5; 95% CI 7.1 to 18.5) was associated with chlamydia infection. The use of any antibiotic within 3 months (AOR 0.2; 95% CI 0.1 to 0.6) was associated with a decreased risk of infection. Screening restricted to women who reported more than one sexual partner in the past year would have detected 44% of infections in women aged 16–25 years and would have required only 7% of women to be screened. The addition of those women aged 20 years and under would have required 27% of women to be screened and detection of 72% of infections.

Conclusions: Selective chlamydia screening of pregnant women based on risk factors can improve the yield from screening. However, the potential harm of missed infections among excluded women would need to be considered.

Recurrent events counted in evaluations of predictive accuracy

Objectives: To describe an alternate approach for the calculation of sensitivity and specificity when analyzing the accuracy of screening tools, which can be used when standard calculations may be inappropriate. Sensitivity^ER (ER denoting event rate) is the number of events correctly predicted, divided by the total number of events. Specificity^ER is the amount of time that study participants are predicted to be event negative, divided by the total amount of participant observed time. Variance estimates for these statistics are constructed by bootstrap resampling, taking into account event dependence.

Methods: Standard and alternate approaches for calculating sensitivity and specificity were applied to hospital falls risk screening tool data. In this application, the outcome of interest was a recurrent event, there were multiple applications of the screening tool, delays in screening tool  completion, and patients' follow-up durations were unequal.

Results: Application of sensitivity^ER and specificity^ER to this data not only provided a clearer description of the screening tool's overall accuracy, but also allowed examination of accuracy over time, accuracy in predicting specific event numbers, and evaluation of the added value that screening tool reapplications may have.

Conclusion: Sensitivity^ER and specificity^ER provide a valuable approach to screening tool evaluation in the clinical setting.

The impact of study design on prevalence estimates of female sexual dysfunction

Introduction, objectives Despite increasing research, the true prevalence of Female Sexual Dysfunction (FSD) remains a contentious issue. Previous research suggests that aspects of study design affect the reported prevalence of FSD. We compare commonly used instruments for assessing FSD. Methods A random sample of 240 Australian women aged 20-70 participated in this population based, cross-sectional study. A questionnaire mailed to women across Australia included four instruments for assessing FSD. The Sexual Function Questionnaire combined with the Female Sexual Distress Scale (SFQ-FSDS) was employed as a standard, validated instrument. Alternative instruments were the SFQ alone and two modified versions of a set of questions originally developed by Laumann et al. Results When assessed by the SFQ-FSDS, prevalence estimates (and 95% confidence intervals) of Hypoactive Sexual Desire Disorder, Female Sexual Arousal Disorder (genital subtype), Female Orgasmic Disorder, and Dysparunia were 16%(11-20%), 8%(4-11%), 9%(6-13%), 2%(0.1-3%) respectively. The prevalence estimates of these same disorders obtained using alternative instruments were 32-55%, 17-35%, 17-33% and 3-25% respectively. The sensitivity of alternative instruments varied widely (0 to 1.0). Specificities ranged from 0.51 to 0.99. Positive predictive values ranged from 0 to 0.57. Negative predictive values were all above 0.90. Changing the time span for recalling sexual experiences in an instrument altered the prevalence estimates, sensitivity and specificity. 32% of women with low desire, 31% with low genital arousal, 36% with orgasm difficulty and 57% with sexual pain were sexually distressed. Conclusion Over a third of women who were classified as suffering FSD by alternative instruments did not have FSD when assessed by SFQ-FSDS. Alternative instruments produced substantially higher prevalence estimates of FSD and identified different groups of women. Consequently, the instruments researchers choose to assess FSD may affect both the prevalence estimates and risk factors they report.

Paramedic identification of stroke : community validation of the Melbourne ambulance stroke screen

Background: Paramedics require an effective prehospital tool to eliminate stroke mimics and to assist in the identification of suitable candidates for thrombolytic therapy. The Faster Access to Stroke Therapies study combined two validated stroke assessment tools (the Los Angeles Prehospital Stroke Screen, LAPSS, and the Cincinnati Prehospital Stroke Scale, CPSS) to form the Melbourne Ambulance Stroke Screen (MASS), and performed an in-field validation by Australian paramedics.

Methods: Over a 12-month period, 18 paramedics participated in the Faster Access to Stroke Therapies study and prospectively collected data contained in the MASS on all stroke dispatches, and for other patients with a focal neurological deficit. Sensitivity and specificity analysis of the LAPSS, CPSS and MASS was calculated and equivalence analysis performed.

Results: Paramedics completed 100 MASS assessments for 73 (73%) stroke/transient ischemic attack patients and 27 (27%) stroke mimics. The sensitivity of the MASS (90%, 95% CI: 81-96%) showed statistical equivalence to the sensitivity of the CPSS (95%, p = 0.45) and superiority to the LAPSS (78%, p = 0.008). The specificity of the MASS (74%, 95% CI: 53-88%) was equivalent to that of the LAPSS (85%, p = 0.25) and superior to the CPSS (54%, p = 0.007). All patients misidentified by the MASS (7 strokes, 7 mimics) were ineligible for thrombolytic therapy.

Conclusion: The MASS is simple to use, with accurate prehospital identification of stroke. It distinguishes stroke mimics, with good recognition of suitable patients for thrombolytic therapy.

Evolution of distinct EGF domains with specific functions

EGF domains are extracellular protein modules cross-linked by three intradomain disulfides. Past studies suggest the existence of two types of EGF domain with three-disulfides, human EGF-like (hEGF) domains and complement C1r-like (cEGF) domains, but to date no functional information has been related to the two different types, and they are not differentiated in sequence or structure databases. We have developed new sequence patterns based on the different C-termini to search specifically for the two types of EGF domains in sequence databases. The exhibited sensitivity and specificity of the new pattern-based method represents a significant advancement over the currently available sequence detection techniques. We re-annotated EGF sequences in the latest release of Swiss-Prot looking for functional relationships that might correlate with EGF type. We show that important post-translational modifications of three-disulfide EGFs, including unusual forms of glycosylation and post-translational proteolytic processing, are dependent on EGF subtype. For example, EGF domains that are shed from the cell surface and mediate intercellular signaling are all hEGFs, as are all human EGF receptor family ligands. Additional experimental data suggest that functional specialization has accompanied subtype divergence. Based on our structural analysis of EGF domains with three-disulfide bonds and comparison to laminin and integrin-like EGF domains with an additional interdomain disulfide, we propose that these hEGF and cEGF domains may have arisen from a four-disulfide ancestor by selective loss of different cysteine residues.

Accuracy of national mortality codes in identifying adjudicated cardiovascular deaths

Objective: This study investigated the sensitivity and specificity of the national mortality codes in identifying cardiovascular disease (CVD) deaths and documents methods of verification.

Methods: A 12-year retrospective case ascertainment of all ICD-coded CVD deaths was performed for deaths between 1990 and 2002 in the Melbourne Collaborative Cohort Study, comprising 41,528 subjects. Categories of non-CVD codes were also examined. Stratified samples of 750 deaths were adjudicated from a total of 2,230 deaths. Expert panels of cardiologists and neurologists adjudicated deaths.

Results: Of the 750 deaths adjudicated, 582 were verified as CVD [392 coronary heart disease (CHD) and 92 stroke] and 168 non-CVD. Estimated sensitivity and specificity of national mortality codes for identifying specific causes of death were: CHD 74.2% (95% CI: 69.8–78.5%) and 97.6% (96.0–99.2%), respectively; myocardial infarction 59.9% (50.9–69.0%) and 94.2% (92.4–96.0%), respectively; haemorrhagic stroke 58.9% (46.0–71.7%) and 99.8% (99.4–100.0%), respectively and; ischaemic stroke 38.7% (20.5–56.9%) and 99.9% (99.6–100.0%), respectively. Misclassification was most common for deaths with primary ICD codes for endocrine-metabolic and genito-urinary diseases.

Conclusions: National mortality coding under-estimated the true proportion of CHD and stroke deaths in the cohort by 13.6% and 50.8%, respectively.

Validity of the Beck Depression Inventory as a screening tool for a clinical mood disorder in Bariatric surgery candidates

Background : The Beck Depression Inventory (BDI) is one of the most commonly used instruments to assess depression in persons with obesity. While it has been validated in normal and psychiatric populations, in obese populations, its validity remains uncertain. This study aimed to investigate the validity and reliability of the BDI-IA and BDI-II in severely obese bariatric surgery candidates.

Methods : Consecutive new candidates at a bariatric surgery clinic were invited to participate in the study by their consulting surgeon. All candidates were assessed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I); 118 completed the BDI-IA and 83 completed the BDI-II. Two hundred one patients (response rate, 88 %) participated in the study. The current sample (82 % female) had an average body mass index of 42.83 ± 6.34 and an average age of 45 ± 12 years.

Results : Based on the SCID-I, 54 candidates (26.9 %) met the criteria for a mood disorder, with 37 meeting the criteria for current major depressive disorder. Individuals diagnosed with a clinical mood disorder had significantly higher scores on the BDI (BDI-IA, 23.59 ± 9.69 vs. 12.76 ± 8.29; BDI-II, 22.93 ± 5.22 vs. 11.25 ± 8.44). Our results indicated that, as a screening tool for a clinical mood disorder, the BDI-II had an optimal cutoff of 13, with a sensitivity of 100 and specificity of 67.75.

Conclusions : Results indicated that the BDI-IA should not be used as a tool to measure depressive symptomatology in obese bariatric surgery candidates. No cutoff was identified with adequate sensitivity and specificity, and over 20 % of patients were misclassified. As a screening tool for a clinical mood disorder, the BDI-II was adequate; however, prevalence rates were significantly overestimated.

Regional homogeneity of resting-state brain abnormalities in violent juvenile offenders: A biomarker of brain immaturity?

The authors investigated whether male violent juvenile offenders demonstrate any differences in local functional connectivity indicative of delayed maturation of the brain that may serve as a biomarker of violence. Twenty-nine violent juvenile offenders and 28 age-matched controls were recruited. Regional homogeneity (ReHo) method was used to analyze resting-state magnetic resonance images. Violent offenders showed significantly lower ReHo values in the right caudate, right medial prefrontal cortex, and left precuneus, and higher values in the right supramarginal gyrus than the controls. These regions had both high sensitivity and specificity in distinguishing between the two groups suggesting that dysfunction in these regions can be used to correctly classify those individuals who are violent. Dysfunction in the right medial prefrontal-caudate circuit may, therefore, represent an important biomarker of violence juvenile males.