Microbleed detection using automated segmentation (MIDAS): a new method applicable to standard clinical MR images

Background

Cerebral microbleeds, visible on gradient-recalled echo (GRE) T2* MRI, have generated increasing interest as an imaging marker of small vessel diseases, with relevance for intracerebral bleeding risk or brain dysfunction.

Methodology/Principal Findings

Manual rating methods have limited reliability and are time-consuming. We developed a new method for microbleed detection using automated segmentation (MIDAS) and compared it with a validated visual rating system. In thirty consecutive stroke service patients, standard GRE T2* images were acquired and manually rated for microbleeds by a trained observer. After spatially normalizing each patient''s GRE T2* images into a standard stereotaxic space, the automated microbleed detection algorithm (MIDAS) identified cerebral microbleeds by explicitly incorporating an “extra” tissue class for abnormal voxels within a unified segmentation-normalization model. The agreement between manual and automated methods was assessed using the intraclass correlation coefficient (ICC) and Kappa statistic. We found that MIDAS had generally moderate to good agreement with the manual reference method for the presence of lobar microbleeds (Kappa = 0.43, improved to 0.65 after manual exclusion of obvious artefacts). Agreement for the number of microbleeds was very good for lobar regions: (ICC = 0.71, improved to ICC = 0.87). MIDAS successfully detected all patients with multiple (≥2) lobar microbleeds.

Conclusions/Significance

MIDAS can identify microbleeds on standard MR datasets, and with an additional rapid editing step shows good agreement with a validated visual rating system. MIDAS may be useful in screening for multiple lobar microbleeds.     

Use of SPRAT for peer review of paediatricians in training

Objective To determine whether a multisource feedback questionnaire, SPRAT (Sheffield peer review assessment tool), is a feasible and reliable assessment method to inform the record of in-training assessment for paediatric senior house officers and specialist registrars.Design Trainees'' clinical performance was evaluated using SPRAT sent to clinical colleagues of their choosing. Responses were analysed to determine variables that affected ratings and their measurement characteristics.Setting Three tertiary hospitals and five secondary hospitals across a UK deanery.Participants 112 paediatric senior house officers and middle grades.Main outcome measures 95% confidence intervals for mean ratings; linear and hierarchical regression to explore potential biasing factors; time needed for the process per doctor.Results 20 middle grades and 92 senior house officers were assessed using SPRAT to inform their record of in-training assessment; 921/1120 (82%) of their proposed raters completed a SPRAT form. As a group, specialist registrars (mean 5.22, SD 0.34) scored significantly higher (t = – 4.765) than did senior house officers (mean 4.81, SD 0.35) (P < 0.001). The grade of the doctor accounted for 7.6% of the variation in the mean ratings. The hierarchical regression showed that only 3.4% of the variation in the means could be additionally attributed to three main factors (occupation of rater, length of working relationship, and environment in which the relationship took place) when the doctor''s grade was controlled for (significant F change < 0.001). 93 (83%) of the doctors in this study would have needed only four raters to achieve a reliable score if the intent was to determine if they were satisfactory. The mean time taken to complete the questionnaire by a rater was six minutes. Just over an hour of administrative time is needed for each doctor.Conclusions SPRAT seems to be a valid way of assessing large numbers of doctors to support quality assurance procedures for training programmes. The feedback from SPRAT can also be used to inform personal development planning and focus quality improvements.     

Resting Heart Rate Is Not a Good Predictor of a Clustered Cardiovascular Risk Score in Adolescents: The HELENA Study

BackgroundResting heart rate (RHR) reflects sympathetic nerve activity a significant association between RHR and all-cause and cardiovascular mortality has been reported in some epidemiologic studies.MethodsTo analyze the predictive power and accuracy of RHR as a screening measure for individual and clustered cardiovascular risk in adolescents. The study comprised 769 European adolescents (376 boys) participating in the HELENA cross-sectional study (2006–2008) were included in this study. Measurements on systolic blood pressure, HOMA index, triglycerides, TC/HDL-c, VO₂máx and the sum of four skinfolds were obtained, and a clustered cardiovascular disease (CVD) risk index was computed. The receiver operating characteristics curve was applied to calculate the power and accuracy of RHR to predict individual and clustered CVD risk factors.ResultsRHR showed low accuracy for screening CVD risk factors in both sexes (range 38.5%–54.4% in boys and 45.5%–54.3% in girls). Low specificity’s (15.6%–19.7% in boys; 18.1%–20.0% in girls) were also found. Nevertheless, the sensitivities were moderate-to-high (61.4%–89.1% in boys; 72.9%–90.3% in girls).ConclusionRHR is a poor predictor of individual CVD risk factors and of clustered CVD and the estimates based on RHR are not accurate. The use of RHR as an indicator of CVD risk in adolescents may produce a biased screening of cardiovascular health in both sexes.     

The Use of Global Rating Scales for OSCEs in Veterinary Medicine

OSCEs (Objective Structured Clinical Examinations) are widely used in health professions to assess clinical skills competence. Raters use standardized binary checklists (CL) or multi-dimensional global rating scales (GRS) to score candidates performing specific tasks. This study assessed the reliability of CL and GRS scores in the assessment of veterinary students, and is the first study to demonstrate the reliability of GRS within veterinary medical education. Twelve raters from two different schools (6 from University of Calgary [UCVM] and 6 from Royal (Dick) School of Veterinary Studies [R(D)SVS] were asked to score 12 students (6 from each school). All raters assessed all students (video recordings) during 4 OSCE stations (bovine haltering, gowning and gloving, equine bandaging and skin suturing). Raters scored students using a CL, followed by the GRS. Novice raters (6 R(D)SVS) were assessed independently of expert raters (6 UCVM). Generalizability theory (G theory), analysis of variance (ANOVA) and t-tests were used to determine the reliability of rater scores, assess any between school differences (by student, by rater), and determine if there were differences between CL and GRS scores. There was no significant difference in rater performance with use of the CL or the GRS. Scores from the CL were significantly higher than scores from the GRS. The reliability of checklist scores were .42 and .76 for novice and expert raters respectively. The reliability of the global rating scale scores were .7 and .86 for novice and expert raters respectively. A decision study (D-study) showed that once trained using CL, GRS could be utilized to reliably score clinical skills in veterinary medicine with both novice and experienced raters.     

Gestational Age at Birth and ‘Body-Mind’ Health at 5 Years of Age: A Population Based Cohort Study

Numerous studies have identified the effects of prematurity on the neonate’s physical health, however few studies have explored the effects of prematurity on both the physical and mental health of the child as they develop. Secondary analysis of data from the Millennium Cohort Study, a longitudinal study of infants (n = 18 818, born 2000–2002 in the United Kingdom) was performed. Effects of gestational age at birth on health outcomes at 5 years were measured using parental rating of their children’s general health and severity of behavior problems. The association between parent’s general health ratings and behavior problem ratings was low: 86% of those reporting serious behavior problems (5% of the sample, n = 764) rated their child as being in excellent, very good, or good health. Still, a gradient of increasing risk of poorer outcome with decreasing gestational age was observed for a composite health measure (poor/fair health and/or serious behavior problems), suggesting an association with prematurity for this composite assessment of health status. The greatest contribution to the childhood composite health measure at 5 years was for children born at 32–36 weeks gestation: population attributable fractions for having poor outcomes was 3.4% (Bonferroni-adjusted 95% confidence interval 1.1%–6.2%), compared to 1% (0.2–2.3) for birth at less than 32 weeks. Results suggest that preterm children, by school entry, are not only at high risk of physical health problems, but also of behavioral health problems. The recognition of, and response to comprehensive health and well-being outcomes related to prematurity are important in order to correctly plan and deliver adequate paediatric health services and policies.     

Body Shape Preferences: Associations with Rater Body Shape and Sociosexuality

There is accumulating evidence of condition-dependent mate choice in many species, that is, individual preferences varying in strength according to the condition of the chooser. In humans, for example, people with more attractive faces/bodies, and who are higher in sociosexuality, exhibit stronger preferences for attractive traits in opposite-sex faces/bodies. However, previous studies have tended to use only relatively simple, isolated measures of rater attractiveness. Here we use 3D body scanning technology to examine associations between strength of rater preferences for attractive traits in opposite-sex bodies, and raters’ body shape, self-perceived attractiveness, and sociosexuality. For 118 raters and 80 stimuli models, we used a 3D scanner to extract body measurements associated with attractiveness (male waist-chest ratio [WCR], female waist-hip ratio [WHR], and volume-height index [VHI] in both sexes) and also measured rater self-perceived attractiveness and sociosexuality. As expected, WHR and VHI were important predictors of female body attractiveness, while WCR and VHI were important predictors of male body attractiveness. Results indicated that male rater sociosexuality scores were positively associated with strength of preference for attractive (low) VHI and attractive (low) WHR in female bodies. Moreover, male rater self-perceived attractiveness was positively associated with strength of preference for low VHI in female bodies. The only evidence of condition-dependent preferences in females was a positive association between attractive VHI in female raters and preferences for attractive (low) WCR in male bodies. No other significant associations were observed in either sex between aspects of rater body shape and strength of preferences for attractive opposite-sex body traits. These results suggest that among male raters, rater self-perceived attractiveness and sociosexuality are important predictors of preference strength for attractive opposite-sex body shapes, and that rater body traits –with the exception of VHI in female raters– may not be good predictors of these preferences in either sex.     

Symmetry: Modeling the Effects of Masking Noise,Axial Cueing and Salience

Symmetry detection is an interesting probe of pattern processing because it requires the matching of novel patterns without the benefit of prior recognition. However, there is evidence that prior knowledge of the axis location plays an important role in symmetry detection. We investigated how the prior information about the symmetry axis affects symmetry detection under noise-masking conditions. The target stimuli were random-dot displays structured to be symmetric about vertical, horizontal, or diagonal axes and viewed through eight apertures (1.2° diameter) evenly distributed around a 6° diameter circle. The information about axis orientation was manipulated by (1) cueing of axis orientation before the trial and (2) varying axis salience by including or excluding the axis region within the noise apertures. The percentage of correct detection of the symmetry was measured at for a range of both target and masking noise densities. The threshold vs. noise density function was flat at low noise density and increased with a slope of 0.75–0.8 beyond a critical density. Axis cueing reduced the target threshold 2–4fold at all noise densities while axis salience had an effect only at high noise density. Our results are inconsistent with an ideal observer or signal-to-noise account of symmetry detection but can be explained by a multiple-channel model is which the response in each channel is the ratio between the nonlinear transform of the responses of sets of early symmetry detectors and the sum of external and intrinsic sources of noise.     

Place and Cause of Death in Centenarians: A Population-Based Observational Study in England, 2001 to 2010

Background

Centenarians are a rapidly growing demographic group worldwide, yet their health and social care needs are seldom considered. This study aims to examine trends in place of death and associations for centenarians in England over 10 years to consider policy implications of extreme longevity.

Methods and Findings

This is a population-based observational study using death registration data linked with area-level indices of multiple deprivations for people aged ≥100 years who died 2001 to 2010 in England, compared with those dying at ages 80-99. We used linear regression to examine the time trends in number of deaths and place of death, and Poisson regression to evaluate factors associated with centenarians’ place of death. The cohort totalled 35,867 people with a median age at death of 101 years (range: 100–115 years). Centenarian deaths increased 56% (95% CI 53.8%–57.4%) in 10 years. Most died in a care home with (26.7%, 95% CI 26.3%–27.2%) or without nursing (34.5%, 95% CI 34.0%–35.0%) or in hospital (27.2%, 95% CI 26.7%–27.6%). The proportion of deaths in nursing homes decreased over 10 years (−0.36% annually, 95% CI −0.63% to −0.09%, p = 0.014), while hospital deaths changed little (0.25% annually, 95% CI −0.06% to 0.57%, p = 0.09). Dying with frailty was common with “old age” stated in 75.6% of death certifications. Centenarians were more likely to die of pneumonia (e.g., 17.7% [95% CI 17.3%–18.1%] versus 6.0% [5.9%–6.0%] for those aged 80–84 years) and old age/frailty (28.1% [27.6%–28.5%] versus 0.9% [0.9%–0.9%] for those aged 80–84 years) and less likely to die of cancer (4.4% [4.2%–4.6%] versus 24.5% [24.6%–25.4%] for those aged 80–84 years) and ischemic heart disease (8.6% [8.3%–8.9%] versus 19.0% [18.9%–19.0%] for those aged 80–84 years) than were younger elderly patients. More care home beds available per 1,000 population were associated with fewer deaths in hospital (PR 0.98, 95% CI 0.98–0.99, p<0.001).

Conclusions

Centenarians are more likely to have causes of death certified as pneumonia and frailty and less likely to have causes of death of cancer or ischemic heart disease, compared with younger elderly patients. To reduce reliance on hospital care at the end of life requires recognition of centenarians’ increased likelihood to “acute” decline, notably from pneumonia, and wider provision of anticipatory care to enable people to remain in their usual residence, and increasing care home bed capacity. Please see later in the article for the Editors'' Summary     

Assessing agreement between multiple raters with missing rating information, applied to breast cancer tumour grading

Background

We consider the problem of assessing inter-rater agreement when there are missing data and a large number of raters. Previous studies have shown only ‘moderate’ agreement between pathologists in grading breast cancer tumour specimens. We analyse a large but incomplete data-set consisting of 24177 grades, on a discrete 1–3 scale, provided by 732 pathologists for 52 samples.

Methodology/Principal Findings

We review existing methods for analysing inter-rater agreement for multiple raters and demonstrate two further methods. Firstly, we examine a simple non-chance-corrected agreement score based on the observed proportion of agreements with the consensus for each sample, which makes no allowance for missing data. Secondly, treating grades as lying on a continuous scale representing tumour severity, we use a Bayesian latent trait method to model cumulative probabilities of assigning grade values as functions of the severity and clarity of the tumour and of rater-specific parameters representing boundaries between grades 1–2 and 2–3. We simulate from the fitted model to estimate, for each rater, the probability of agreement with the majority. Both methods suggest that there are differences between raters in terms of rating behaviour, most often caused by consistent over- or under-estimation of the grade boundaries, and also considerable variability in the distribution of grades assigned to many individual samples. The Bayesian model addresses the tendency of the agreement score to be biased upwards for raters who, by chance, see a relatively ‘easy’ set of samples.

Conclusions/Significance

Latent trait models can be adapted to provide novel information about the nature of inter-rater agreement when the number of raters is large and there are missing data. In this large study there is substantial variability between pathologists and uncertainty in the identity of the ‘true’ grade of many of the breast cancer tumours, a fact often ignored in clinical studies.     

Hepatitis C Virus Epidemiology in Djibouti,Somalia, Sudan,and Yemen: Systematic Review and Meta-Analysis

Objectives

To characterize hepatitis C virus (HCV) epidemiology and assess country-specific population-level HCV prevalence in four countries in the Middle East and North Africa (MENA) region: Djibouti, Somalia, Sudan, and Yemen.

Methods

Reports of HCV prevalence were systematically reviewed as per PRISMA guidelines. Pooled HCV prevalence estimates in different risk populations were conducted when the number of measures per risk category was at least five.

Results

We identified 101 prevalence estimates. Pooled HCV antibody prevalence in the general population in Somalia, Sudan and Yemen was 0.9% (95% confidence interval [95%CI]: 0.3%–1.9%), 1.0% (95%CI: 0.3%–1.9%) and 1.9% (95%CI: 1.4%–2.6%), respectively. The only general population study from Djibouti reported a prevalence of 0.3% (CI: 0.2%–0.4%) in blood donors. In high-risk populations (e.g., haemodialysis and haemophilia patients), pooled HCV prevalence was 17.3% (95%CI: 8.6%–28.2%) in Sudan. In Yemen, three studies of haemodialysis patients reported HCV prevalence between 40.0%-62.7%. In intermediate-risk populations (e.g.. healthcare workers, in patients and men who have sex with men), pooled HCV prevalence was 1.7% (95%CI: 0.0%–4.9%) in Somalia and 0.6% (95%CI: 0.4%–0.8%) in Sudan.

Conclusion

National HCV prevalence in Yemen appears to be higher than in Djibouti, Somalia, and Sudan as well as most other MENA countries; but otherwise prevalence levels in this subregion are comparable to global levels. The high HCV prevalence in patients who have undergone clinical care appears to reflect ongoing transmission in clinical settings. HCV prevalence in people who inject drugs remains unknown.     

Educational Differences in Postmenopausal Breast Cancer – Quantifying Indirect Effects through Health Behaviors,Body Mass Index and Reproductive Patterns

Studying mechanisms underlying social inequality in postmenopausal breast cancer is important in order to develop prevention strategies. Standard methods for investigating indirect effects, by comparing crude models to adjusted, are often biased. We applied a new method enabling the decomposition of the effect of educational level on breast cancer incidence into indirect effects through reproductive patterns (parity and age at first birth), body mass index and health behavior (alcohol consumption, physical inactivity, and hormone therapy use). The study was based on a pooled cohort of 6 studies from the Copenhagen area including 33,562 women (1,733 breast cancer cases) aged 50–70 years at baseline. The crude absolute rate of breast cancer was 399 cases per 100,000 person-years. A high educational level compared to low was associated with 74 (95% CI 22–125) extra breast cancer cases per 100,000 person-years at risk. Of these, 26% (95% CI 14%–69%) could be attributed to alcohol consumption. Similar effects were observed for age at first birth (32%; 95% CI 10%–257%), parity (19%; 95%CI 10%–45%), and hormone therapy use (10%; 95% CI 6%–18%). Educational level modified the effect of physical activity on breast cancer. In conclusion, this analysis suggests that a substantial number of the excess postmenopausal breast cancer events among women with a high educational level compared to a low can be attributed to differences in alcohol consumption, use of hormone therapy, and reproductive patterns. Women of high educational level may be more vulnerable to physical inactivity compared to women of low educational level.     

Evaluating the effects of rater and subject factors on measures of association

Large‐scale agreement studies are becoming increasingly common in medical settings to gain better insight into discrepancies often observed between experts' classifications. Ordered categorical scales are routinely used to classify subjects' disease and health conditions. Summary measures such as Cohen's weighted kappa are popular approaches for reporting levels of association for pairs of raters' ordinal classifications. However, in large‐scale studies with many raters, assessing levels of association can be challenging due to dependencies between many raters each grading the same sample of subjects' results and the ordinal nature of the ratings. Further complexities arise when the focus of a study is to examine the impact of rater and subject characteristics on levels of association. In this paper, we describe a flexible approach based upon the class of generalized linear mixed models to assess the influence of rater and subject factors on association between many raters' ordinal classifications. We propose novel model‐based measures for large‐scale studies to provide simple summaries of association similar to Cohen's weighted kappa while avoiding prevalence and marginal distribution issues that Cohen's weighted kappa is susceptible to. The proposed summary measures can be used to compare association between subgroups of subjects or raters. We demonstrate the use of hypothesis tests to formally determine if rater and subject factors have a significant influence on association, and describe approaches for evaluating the goodness‐of‐fit of the proposed model. The performance of the proposed approach is explored through extensive simulation studies and is applied to a recent large‐scale cancer breast cancer screening study.     

Diagnostic accuracy of cervical cancer screening and screening–triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study

BackgroundCervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen–triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa.Methods and findingsWLHIV aged 25–50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol’s iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%–52.7%) and CIN3+ (56.1%, 95% CI 43.3%–68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%–81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%–93.2%) for CIN2+ and 86.4% (95% CI 75.7%–93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%–58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%–76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%–86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28–2.32; CIN3+: 1.18, 95% CI 0.94–1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%–77.9%; CIN3+: 80.8%, 95% CI 67.5%–90.4%) and specificity (81.6%, 95% CI 77.6%–85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%–91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%–47.1%; relative specificity = 0.57, 95% CI 0.52–0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%–3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%–3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%–1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today.ConclusionsIn this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.

In this cohort study, Helen Kelly and colleagues explore cervical cancer screening strategies for women living with HIV.     

Derivation and Validation of Two Decision Instruments for Selective Chest CT in Blunt Trauma: A Multicenter Prospective Observational Study (NEXUS Chest CT)

Background

Unnecessary diagnostic imaging leads to higher costs, longer emergency department stays, and increased patient exposure to ionizing radiation. We sought to prospectively derive and validate two decision instruments (DIs) for selective chest computed tomography (CT) in adult blunt trauma patients.

Methods and Findings

From September 2011 to May 2014, we prospectively enrolled blunt trauma patients over 14 y of age presenting to eight US, urban level 1 trauma centers in this observational study. During the derivation phase, physicians recorded the presence or absence of 14 clinical criteria before viewing chest imaging results. We determined injury outcomes by CT radiology readings and categorized injuries as major or minor according to an expert-panel-derived clinical classification scheme. We then employed recursive partitioning to derive two DIs: Chest CT-All maximized sensitivity for all injuries, and Chest CT-Major maximized sensitivity for only major thoracic injuries (while increasing specificity). In the validation phase, we employed similar methodology to prospectively test the performance of both DIs.We enrolled 11,477 patients—6,002 patients in the derivation phase and 5,475 patients in the validation phase. The derived Chest CT-All DI consisted of (1) abnormal chest X-ray, (2) rapid deceleration mechanism, (3) distracting injury, (4) chest wall tenderness, (5) sternal tenderness, (6) thoracic spine tenderness, and (7) scapular tenderness. The Chest CT-Major DI had the same criteria without rapid deceleration mechanism. In the validation phase, Chest CT-All had a sensitivity of 99.2% (95% CI 95.4%–100%), a specificity of 20.8% (95% CI 19.2%–22.4%), and a negative predictive value (NPV) of 99.8% (95% CI 98.9%–100%) for major injury, and a sensitivity of 95.4% (95% CI 93.6%–96.9%), a specificity of 25.5% (95% CI 23.5%–27.5%), and a NPV of 93.9% (95% CI 91.5%–95.8%) for either major or minor injury. Chest CT-Major had a sensitivity of 99.2% (95% CI 95.4%–100%), a specificity of 31.7% (95% CI 29.9%–33.5%), and a NPV of 99.9% (95% CI 99.3%–100%) for major injury and a sensitivity of 90.7% (95% CI 88.3%–92.8%), a specificity of 37.9% (95% CI 35.8%–40.1%), and a NPV of 91.8% (95% CI 89.7%–93.6%) for either major or minor injury. Regarding the limitations of our work, some clinicians may disagree with our injury classification and sensitivity thresholds for injury detection.

Conclusions

We prospectively derived and validated two DIs (Chest CT-All and Chest CT-Major) that identify blunt trauma patients with clinically significant thoracic injuries with high sensitivity, allowing for a safe reduction of approximately 25%–37% of unnecessary chest CTs. Trauma evaluation protocols that incorporate these DIs may decrease unnecessary costs and radiation exposure in the disproportionately young trauma population.     

A Computer-Based Automated Algorithm for Assessing Acinar Cell Loss after Experimental Pancreatitis

The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections. In this study, we utilized a novel computer-generated learning algorithm to construct an accurate and rapid method of quantifying acinar content. The algorithm works by learning differences in pixel characteristics from input examples provided by human experts. HE-stained pancreatic sections were obtained in mice recovering from a 2-day, hourly caerulein hyperstimulation model of experimental pancreatitis. For training data, a pathologist carefully outlined discrete regions of acinar and non-acinar tissue in 21 sections at various stages of pancreatic injury and recovery (termed the “ground truth”). After the expert defined the ground truth, the computer was able to develop a prediction rule that was then applied to a unique set of high-resolution images in order to validate the process. For baseline, non-injured pancreatic sections, the software demonstrated close agreement with the ground truth in identifying baseline acinar tissue area with only a difference of 1%±0.05% (p = 0.21). Within regions of injured tissue, the software reported a difference of 2.5%±0.04% in acinar area compared with the pathologist (p = 0.47). Surprisingly, on detailed morphological examination, the discrepancy was primarily because the software outlined acini and excluded inter-acinar and luminal white space with greater precision. The findings suggest that the software will be of great potential benefit to both clinicians and researchers in quantifying pancreatic acinar cell flux in the injured and recovering pancreas.     

The Mpumalanga Men's Study (MPMS): Results of a Baseline Biological and Behavioral HIV Surveillance Survey in Two MSM Communities in South Africa

The Mpumalanga Men''s Study (MPMS) is the assessment of the Project Boithato HIV prevention intervention for South African MSM. Boithato aims to increase consistent condom use, regular testing for HIV-negative MSM, and linkage to care for HIV-positive MSM. The MPMS baseline examined HIV prevalence and associated risk behaviors, and testing, care, and treatment behaviors among MSM in Gert Sibande and Ehlanzeni districts in Mpumalanga province, South Africa in order to effectively target intervention activities. We recruited 307 MSM in Gert Sibande and 298 in Ehlanzeni through respondent-driven sampling (RDS) between September 2012-March 2013. RDS-adjusted HIV prevalence estimates are 28.3% (95% CI 21.1%–35.3%) in Gert Sibande, and 13.7% (95% CI 9.1%–19.6%) in Ehlanzeni. Prevalence is significantly higher among MSM over age 25 [57.8% (95% CI 43.1%–72.9%) vs. 17.9% (95% CI 10.6%–23.9%), P<0.001 in Gert Sibande; 34.5% (95%CI 20.5%–56.0%) vs. 9.1% (95% CI 4.6%–13.9%), P<0.001 in Ehlanzeni]. In Gert Sibande, prevalence is higher among self-identified gay and transgender MSM vs. other MSM [39.3% (95%CI, 28.3%–47.9%), P<0.01], inconsistent condom users [38.1% (18.1%–64.2%), P<0.05], those with a current regular male partner [35.0% (27.1%–46.4%), P<0.05], and those with lifetime experience of intimate partner violence with men [40.4%, (95%CI 28.9%–50.9%), P<0.05]. Prevalence of previous HIV testing was 65.8% (95%CI 58.8%–74.0%) in Gert Sibande, and 69.3% (95%CI 61.9%–76.8%) in Ehlanzeni. Regular HIV testing was uncommon [(34.6%, (95%CI 27.9%–41.4%) in Gert Sibande; 31.0% (95%CI 24.9%–37.8%) in Ehlanzeni]. Among HIV-positive participants, few knew their status (28.1% in Gert Sibande and 14.5% in Ehlanzeni), or were appropriately linked to care (18.2% and 11.3%, respectively), or taking antiretroviral therapy (13.6% and 9.6% respectively). MPMS results demonstrate the importance of implementing interventions for MSM to increase consistent condom use, regular HIV testing, and linkage and engagement in care for HIV-infected MSM.     

Vector Selection of a Quadripolar Left Ventricular Pacing Lead Affects Acute Hemodynamic Response to Cardiac Resynchronization Therapy: A Randomized Cross-Over Trial

Background

A suboptimal left ventricular (LV) pacing site may account for non-responsiveness of patients to cardiac resynchronization therapy (CRT). The vector selection of a novel quadripolar LV pacing lead, which was mainly developed to overcome technical issues with stimulation thresholds and phrenic nerve capture, may affect hemodynamic response, and was therefore assessed in this study. (German Clinical Trials Register DRKS00000573).

Methods and Results

Hemodynamic effects of a total of 145 LVPCs (9.1 per patient) of CRT devices with a quadripolar LV lead (Quartet™, St. Jude Medical) were assessed in 16/20 consecutive patients by invasive measurement of LV+dP/dt_max at an invasively optimized AV-interval in random order. Optimal (worst) LVPCs per patient were identified as those with maximal (minimal) %change in LV+dP/dt_max (%ΔLV+dP/dt_max) as compared to a preceding baseline. LV+dP/dt_max significantly increased in all 145 LVPCs (p<0.0001 compared to baseline) with significant intraindividual differences between LVPCs (p<0.0001). Overall, CRT acutely augmented %ΔLV+dP/dt_max by 31.3% (95% CI 24%–39%) in the optimal, by 21.3% (95% CI: 15%–27%) in the worst and by 28.2% (95% CI: 21%–36%) in a default distal LVPC. This resulted in an absolute additional acute increase in %ΔLV+dP/dt_max of 10.0% (95% CI: 7%–13%) of the optimal when compared to the worst (p<0.0001), and of 3.1% (95% CI: 1%–5%) of the optimal when compared to the default distal LVPC (p<0.001). Optimal LVPCs were not programmable with a standard bipolar lead in 44% (7/16) of patients.

Conclusion

The pacing configuration of a quadripolar LV lead determinates acute hemodynamic response. Pacing in the individually optimized configuration gives rise to an additional absolute 10% increase in %ΔLV+dP/dt_max when comparing optimal and worst vectors.     

Road Traffic Deaths and Injuries Are Under-Reported in Ethiopia: A Capture-Recapture Method

In low and middle income countries road traffic injuries are commonly under-reported. This problem is significantly higher among those less severely injured road users. The objective of this study was to determine the incidence and the level of ascertainment of road traffic injuries and deaths by traffic police and hospital registry. In this study two-sample capture-recapture method was applied using data from traffic police and hospital injury surveillance, through June 2012 to May 2013. The study was conducted on one of the busiest highways in Ethiopia, the Addis Ababa – Hawassa highway. Primary data were collected by accident investigators and hospital emergency nurses using a structured checklist. Four matching variables; name of the victim, sex, place and time of the accidents was used to get the matched cases. During the study period the police independently reported 224 deaths and 446 injuries/billion vehicle kilometer while hospitals reported 123 deaths and 1,046 injuries/billion vehicle kilometer. Both sources in common captured 73 deaths and 248 injuries/billion vehicle kilometer. Taking the two data sources into consideration, the capture-recapture model estimated the incidence of deaths and injuries ranged 368–390 and 1,869–1,895 per billion vehicle kilometer, respectively. The police source captured 57.4%–60.9% of deaths and 23.5%–23.9% of injuries while the hospital sources captured 31.5%–33.4% of deaths and 55.2%–56% of injuries. Deaths and injuries among females, younger age victims, cyclists/motorcyclists and pedestrians were under-reported by traffic police. In conclusion neither of the two sources independently provided accurate coverage of road traffic incident related deaths and injuries. Strengthening both systems is necessary to obtain accurate information on road accidents and human causalities.     

Different impacts of resources on opposite sex ratings of physical attractiveness by males and females

Parental investment hypotheses regarding mate selection suggest that human males should seek partners featured by youth and high fertility. However, females should be more sensitive to resources that can be invested on themselves and their offspring. Previous studies indicate that economic status is indeed important in male attractiveness. However, no previous study has quantified and compared the impact of equivalent resources on male and female attractiveness. Annual salary is a direct way to evaluate economic status. Here, we combined images of male and female body shape with information on annual salary to elucidate the influence of economic status on the attractiveness ratings by opposite sex raters in American, Chinese and European populations. We found that ratings of attractiveness were around 1000 times more sensitive to salary for females rating males, compared to males rating females. These results indicate that higher economic status can offset lower physical attractiveness in men much more easily than in women. Neither raters' BMI nor age influenced this effect for females rating male attractiveness. This difference explains many features of human mating behavior and may pose a barrier for male engagement in low-consumption lifestyles.     

Chromosome abnormalities and spontaneous fetal death following amniocentesis: Further data and associations with maternal age

The pooled results are presented of two North American surveys concerning spontaneous fetal deaths of conceptuses with cytogenetic abnormalities diagnosed prenatally whose mothers had declined elective abortion. The rate of fetal death of those with nonmosaic genotypes associated with Down syndrome was 30.1% (95% confidence interval of 19.0%–42.0%), which is almost identical with the difference of 30% previously estimated between rates observed at amniocentesis and in live births. The fetal death rate for (nonmosaic) 47,+18 was 68.0% (95% confidence interval of 46.5%–85.1%), close to the estimated difference of 75% between rates at amniocentesis and in live births for this genotype. For other nonmosaic genotypes, the rates (and 95% confidence intervals) were: 47,+13, 42.9% (9.9%–81.6%); 47,XXX, 0% (0%–9.0%); 47,XXY, 8.1% (0.8%–11.0%); 47,XYY, 3.0% (.08%–15.8%); for balanced translocations and inversions, 2.8% (0.3%–9.8%); and for markers, variants, and fragments, 0% (0%–12.8%). For 45,X, the rate was 75.0% (42.8%–94.5%), in contrast to the rate for 46,XX/45,X of 10.5% (1.3%–33.1%) and for structural X abnormalities associated with Turner syndrome of 0% (0%–60.2%). The rate for nonmosaic 45,X is significantly different from that for either of the other two categories associated with Turner syndrome. The maternal age of nonmosaic 47,+21 fetuses that survived to live birth was 39.1 ± 6.2, not significantly different from the rate for fetal deaths: 39.5 ± 3.8. The observations provide no support for opposing hypotheses by other groups that maternal age is positively or negatively associated with fetal death of 47,+21 conceptuses. For other chromosome abnormalities, maternal ages of fetal deaths are slightly lower than for live births, but none of the differences are significant. The rates of spontaneous fetal deaths derived here are likely to be pertinent to genetic counseling. Their use in adjusting the rates of abnormalities diagnosed at amniocentesis will enable derivation of predicted contemporary live-birth prevalence rates of abnormalities that would be observed in absence of selective abortion.