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Background: The partograph has been endorsed by World Health Organization (WHO) since 1994 which presents an algorithm for assessing maternal and foetal conditions and labor progression. Monitoring labour with a partograph can reduce adverse pregnancy outcomes such as prolonged labor, emergency C-sections, birth asphyxia and stillbirths. However, partograph use is still very low, particularly in low and middle income countries (LMICs). In Bangladesh the reported partograph user rate varies from 1.4% to 33.0%. Recently, an electronic version of the partograph, with the provision of online data entry and user aid for emergency clinical support, has been tested successfully in different settings. With this proven evidence, we conducted and operations research to test the feasibility and effectiveness of implementing an e-partograph, for the first time, in 2 public hospitals in Bangladesh Methods: We followed a prospective crossover design. Two secondary level referral hospitals, Jessore and Kushtia District Hospital (DH) were the study sites. All pregnant women who delivered in the study hospitals were the study participants. All nurse-midwives working in the labor ward of study hospitals were trained on appropriate use of both types of partograph along with standard labour management guidelines. Collected quantitative data was analyzed using SPSS 23 statistical software. Discrete variables were expressed as percentages and presented as frequency distribution and cross tabulations. Chi square tests were employed to test the association between exposure and outcome variables. Potential confounding factors were adjusted using multivariate binary logistic regression methods. Ethical approval was obtained from the institutional review board of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Findings: In total 2918 deliveries were conducted at Jessore DH and 2312 at Kushtia DH during one-year study period. Of them, 1012 (506 in each facility) deliveries were monitored using partograph (paper or electronic). The trends of facility based C-section rates was downwards in both the hospitals; 43% to 37% in Jessore and from 36% to 25% in Kushtia Hospital. There was a significant reduction of prolonged labour with e-partograph use. In Kushtia DH, the prolonged labour rate was 42% during phase 1 with the paper version which came down to 29% during phase-2 with the e-partograph use. The similar result was observed in Jessore DH where the prolonged labour rate reduced to 7% with paper partograph from the reported 30% prolonged labour with e-partograph. The e-partograph user rate was higher than the paper partograph during both phases (phase 1: 3.31, CI: 2.04–5.38, p < .001 and in phase 2: 15.20 CI: 6.36–36.33, p < .001) after adjusting for maternal age, parity, gestational age, religion, mother’s education, husband’s education, and fetal sex Conclusion: The partograph user rate has significantly improved with the e- partograph and was associated with an overall reduction in cesarean births. Use of the e-partograph was also associated with reduced rates of prolonged labour. This study has added to the growing body of evidence on the positive impact of e-partograph use. We recommend implementing e-partograph intervention at scale in both public and private hospitals in Bangladesh. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Introduction: Data collection using paper-based questionnaires can be time consuming and return errors affect data accuracy, completeness, and information quality in health surveys. We compared smartphone and paper-based data collection systems in the Burden of Obstructive Lung Disease (BOLD) study in rural Sudan. Methods: This exploratory pilot study was designed to run in parallel with the cross-sectional household survey. The Open Data Kit was used to programme questionnaires in Arabic into smartphones. We included 100 study participants (83% women; median age = 41.5 ± 16.4 years) from the BOLD study from 3 rural villages in East-Gezira and Kamleen localities of Gezira state, Sudan. Questionnaire data were collected using smartphone and paper-based technologies simultaneously. We used Kappa statistics and inter-rater class coefficient to test agreement between the two methods. Results: Symptoms reported included cough (24%), phlegm (15%), wheezing (17%), and shortness of breath (18%). One in five were or had been cigarette smokers. The two data collection methods varied between perfect to slight agreement across the 204 variables evaluated (Kappa varied between 1.00 and 0.02 and inter-rater coefficient between 1.00 and -0.12). Errors were most commonly seen with paper questionnaires (83% of errors seen) vs smartphones (17% of errors seen) administered questionnaires with questions with complex skip-patterns being a major source of errors in paper questionnaires. Automated checks and validations in smartphone-administered questionnaires avoided skip-pattern related errors. Incomplete and inconsistent records were more likely seen on paper questionnaires. Conclusion: Compared to paper-based data collection, smartphone technology worked well for data collection in the study, which was conducted in a challenging rural environment in Sudan. This approach provided timely, quality data with fewer errors and inconsistencies compared to paper-based data collection. We recommend this method for future BOLD studies and other population-based studies in similar settings. [ABSTRACT FROM AUTHOR]

Background: The use of filter paper as a simple, inexpensive tool for storage and transportation of blood, ‘Dried Blood Spots’ or Guthrie cards, for diagnostic assays is well-established. In contrast, there are a paucity of diagnostic evaluations of dried cerebrospinal fluid (CSF) spots. These have potential applications in low-resource settings, such as Laos, where laboratory facilities for central nervous system (CNS) diagnostics are only available in Vientiane. In Laos, a major cause of CNS infection is Japanese encephalitis virus (JEV). We aimed to develop a dried CSF spot protocol and to evaluate its diagnostic performance using the World Health Organisation recommended anti-JEV IgM antibody capture enzyme-linked immunosorbent assay (JEV MAC-ELISA). Methodology and Principal Findings: Sample volumes, spotting techniques and filter paper type were evaluated using a CSF-substitute of anti-JEV IgM positive serum diluted in Phosphate Buffer Solution (PBS) to end-limits of detection by JEV MAC-ELISA. A conventional protocol, involving eluting one paper punch in 200μl PBS, did not detect the end-dilution, nor did multiple punches utilising diverse spotting techniques. However, pre-cut filter paper enabled saturation with five times the volume of CSF-substitute, sufficiently improving sensitivity to detect the end-dilution. The diagnostic accuracy of this optimised protocol was compared with routine, neat CSF in a pilot, retrospective study of JEV MAC-ELISA on consecutive CSF samples, collected 2009–15, from three Lao hospitals. In comparison to neat CSF, 132 CSF samples stored as dried CSF spots for one month at 25–30°C showed 81.6% (65.7–92.3 95%CI) positive agreement, 96.8% (91.0–99.3 95%CI) negative agreement, with a kappa coefficient of 0.81 (0.70–0.92 95%CI). Conclusions/Significance: The novel design of pre-cut filter paper saturated with CSF could provide a useful tool for JEV diagnostics in settings with limited laboratory access. It has the potential to improve national JEV surveillance and inform vaccination policies. The saturation of filter paper has potential use in the wider context of pathogen detection, including dried spots for detecting other analytes in CSF, and other body fluids. [ABSTRACT FROM AUTHOR]

India has the highest burden of Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) worldwide. Innovative technology is the need of the hour to identify these cases that remain either undiagnosed or inadequately diagnosed due to the unavailability of appropriate tools at primary healthcare settings. We developed and evaluated 3 kits, namely ‘TB Detect’ (containing BioFM-Filter device), ‘TB Concentration and Transport’ (containing Trans-Filter device) and ‘TB DNA Extraction’ kits. These kits enable bio-safe equipment-free concentration of sputum on filters and improved fluorescence microscopy at primary healthcare centres, ambient temperature transport of dried inactivated sputum filters to central laboratories and molecular detection of drug resistance by PCR and DNA sequencing (Mol-DST). In a 2-site evaluation (n = 1190 sputum specimens) on presumptive TB patients, BioFM-Filter smear exhibited a significant increase in positivity of 7% and 4% over ZN smear and LED-FM smear (p<0.05), respectively and an increment in smear grade status (1+ or 2+ to 3+) of 16% over ZN smear and 20% over LED-FM smear. The sensitivity of Mol-DST in presumptive MDR-TB and XDR-TB cases (n = 148) was 90% for Rifampicin (95% confidence interval [CI], 78–96%), 84% for Isoniazid (95% CI, 72–92%), 83% for Fluoroquinolones (95% CI, 66–93%) and 75% for Aminoglycosides (95% CI, 35–97%), using phenotypic DST as the reference standard. Test specificity was 88–93% and concordance was ~89–92% (κ value 0.8–0.9). The patient-friendly kits described here address several of the existing challenges and are designed to provide ‘Universal Access’ to rapid TB diagnosis, including drug-resistant disease. Their utility was demonstrated by application to sputum at 2 sites in India. Our findings pave the way for larger studies in different point-of-care settings, including high-density urban areas and remote geographical locations. [ABSTRACT FROM AUTHOR]

Background: The integration of large language models (LLMs) like ChatGPT in diagnostic medicine, with a focus on digital pathology, has garnered significant attention. However, understanding the challenges and barriers associated with the use of LLMs in this context is crucial for their successful implementation. Methods: A scoping review was conducted to explore the challenges and barriers of using LLMs, in diagnostic medicine with a focus on digital pathology. A comprehensive search was conducted using electronic databases, including PubMed and Google Scholar, for relevant articles published within the past four years. The selected articles were critically analyzed to identify and summarize the challenges and barriers reported in the literature. Results: The scoping review identified several challenges and barriers associated with the use of LLMs in diagnostic medicine. These included limitations in contextual understanding and interpretability, biases in training data, ethical considerations, impact on healthcare professionals, and regulatory concerns. Contextual understanding and interpretability challenges arise due to the lack of true understanding of medical concepts and lack of these models being explicitly trained on medical records selected by trained professionals, and the black-box nature of LLMs. Biases in training data pose a risk of perpetuating disparities and inaccuracies in diagnoses. Ethical considerations include patient privacy, data security, and responsible AI use. The integration of LLMs may impact healthcare professionals' autonomy and decision-making abilities. Regulatory concerns surround the need for guidelines and frameworks to ensure safe and ethical implementation. Conclusion: The scoping review highlights the challenges and barriers of using LLMs in diagnostic medicine with a focus on digital pathology. Understanding these challenges is essential for addressing the limitations and developing strategies to overcome barriers. It is critical for health professionals to be involved in the selection of data and fine tuning of the models. Further research, validation, and collaboration between AI developers, healthcare professionals, and regulatory bodies are necessary to ensure the responsible and effective integration of LLMs in diagnostic medicine. [ABSTRACT FROM AUTHOR]

Background: Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT). Methods: We quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose. Results: In the validation study, mean intra-assay coefficients of variation (n = 162) were 15%, 13% and 10% for ‘low’ (6.78 µg/ml), ‘medium’ (18.18 µg/ml) and 'high’ (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n = 40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3–133%. Bloodspot adiponectin was stable for at least 30 months at −80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose. Conclusions: Bloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies. [ABSTRACT FROM AUTHOR]

Background: The psychometric properties of an online test are not necessarily identical to its paper and pencil original. The aim of this study is to test whether the factor structure of the Community Assessment of Psychic Experiences (CAPE) is measurement invariant with respect to online vs. paper and pencil assessment. Method: The factor structure of CAPE items assessed by paper and pencil (N = 796) was compared with the factor structure of CAPE items assessed by the Internet (N = 21,590) using formal tests for Measurement Invariance (MI). The effect size was calculated by estimating the Signed Item Difference in the Sample (SIDS) index and the Signed Test Difference in the Sample (STDS) for a hypothetical subject who scores 2 standard deviations above average on the latent dimensions. Results: The more restricted Metric Invariance model showed a significantly worse fit compared to the less restricted Configural Invariance model (χ2(23) = 152.75, p<0.001). However, the SIDS indices appear to be small, with an average of −0.11. A STDS of −4.80 indicates that Internet sample members who score 2 standard deviations above average would be expected to score 4.80 points lower on the CAPE total scale (ranging from 42 to 114 points) than would members of the Paper sample with the same latent trait score. Conclusions: Our findings did not support measurement invariance with respect to assessment method. Because of the small effect sizes, the measurement differences between the online assessed CAPE and its paper and pencil original can be neglected without major consequences for research purposes. However, a person with a high vulnerability for psychotic symptoms would score 4.80 points lower on the total scale if the CAPE is assessed online compared to paper and pencil assessment. Therefore, for clinical purposes, one should be cautious with online assessment of the CAPE. [ABSTRACT FROM AUTHOR]

Background: Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials.Methods and Findings: We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that "all adverse events were recorded." For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student's t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs.Conclusions: In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles. [ABSTRACT FROM AUTHOR]

Background: With an estimated 27 million annual incidents of maternal morbidity globally, how they are manifested or experienced is diverse and shaped by societal, cultural and personal influences. Using qualitative research to examine a woman's perception of her pregnancy, its complications, and potential long-term impact on her life can inform public health approaches and complement and inform biomedical classifications of maternal morbidities, historically considered a neglected dimension of safe motherhood. As part of the WHO’s Maternal Morbidity Working Group’s efforts to define and measure maternal morbidity, we carried out a thematic analysis of the qualitative literature published between 1998 and 2017 on how women experience maternal morbidity in low and lower-middle income countries. Results and conclusions: Analysis of the 71 papers included in this study shows that women’s status, their marital relationships, cultural attitudes towards fertility and social responses to infertility and pregnancy trauma are fundamental to determining how they will experience morbidity in the pregnancy and postpartum periods. We explore the physical, economic, psychological and social repercussions pregnancy can produce for women, and how resource disadvantage (systemic, financial and contextual) can exacerbate these problems. In addition to an analysis of ten themes that emerged across the different contexts, this paper presents which morbidities have received attention in different regions and the trends in researching morbidities over time. We observed an increase in qualitative research on this topic, generally undertaken through interviews and focus groups. Our analysis calls for the pursuit of high quality qualitative research that includes repeat interviews, participant observation and triangulation of sources to inform and fuel critical advocacy and programmatic work on maternal morbidities that addresses their prevention and management, as well as the underlying systemic problems for women’s status in society. [ABSTRACT FROM AUTHOR]

Background: Loop mediated isothermal amplification (LAMP) provides an opportunity for improved, field-friendly detection of malaria infections in endemic areas. However data on the diagnostic accuracy of LAMP for active case detection, particularly low-density parasitaemias, are lacking. We therefore evaluated the performance of a new LAMP kit compared with PCR using DNA from filter paper blood spots. Methods and Findings: Samples from 865 fever patients and 465 asymptomatic individuals collected in Zanzibar were analysed for Pan (all species) and Pf (P. falciparum) DNA with the Loopamp MALARIA Pan/Pf kit. Samples were amplified at 65°C for 40 minutes in a real-time turbidimeter and results were compared with nested PCR. Samples with discordant results between LAMP and nested PCR were analysed with real-time PCR. The real-time PCR corrected nested PCR result was defined as gold standard. Among the 117 (13.5%) PCR detected P. falciparum infections from fever patients (mean parasite density 7491/µL, range 6–782,400) 115, 115 and 111 were positive by Pan-LAMP, Pf-LAMP and nested PCR, respectively. The sensitivities were 98.3% (95%CI 94–99.8) for both Pan and Pf-LAMP. Among the 54 (11.6%) PCR positive samples from asymptomatic individuals (mean parasite density 10/µL, range 0–4972) Pf-LAMP had a sensitivity of 92.7% (95%CI 80.1–98.5) for detection of the 41 P. falciparum infections. Pan-LAMP had sensitivities of 97% (95%CI 84.2–99.9) and 76.9% (95%CI 46.2–95) for detection of P. falciparum and P. malariae, respectively. The specificities for both Pan and Pf-LAMP were 100% (95%CI 99.1–100) in both study groups. Conclusion: Both components of the Loopamp MALARIA Pan/Pf detection kit revealed high diagnostic accuracy for parasite detection among fever patients and importantly also among asymptomatic individuals of low parasite densities from minute blood volumes preserved on filter paper. These data support LAMPs potential role for improved detection of low-density malaria infections in pre-elimination settings. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) incidence in South Africa is among the highest globally. Initial loss to follow-up (ILFU), defined as not starting on TB treatment within 28 days of testing positive, is undermining control efforts. We assessed the feasibility, acceptability, and potential of a mHealth application to reduce ILFU. Methods: An mHealth application was developed to capture patients TB investigation data, provide results and monitor treatment initiation. This was implemented in two primary health clinics (PHC) in inner-city Johannesburg. Feasibility was assessed by comparing documentation of personal details, specimen results for same individuals during implementation period (paper register and Mhealth application). Effectiveness was assessed by comparing proportion of patients with results within 48 hours, and proportion started on treatment within 28 days of testing TB positive during pre- implementation (paper register) and implementation (mHealth application) periods. In-depth interviews with patients and providers were conducted to assess acceptability of application. Results: Pre-implementation, 457 patients were recorded in paper registers [195 (42.7%) male, median age 34 years (interquartile range IQR (28–40), 45 (10.5%) sputum Xpert positive]. During implementation, 319 patients were recorded in paper register and the mHealth application [131 (41.1%) male, median age 32 years (IQR 27–38), 33 (10.3%) sputum Xpert positive]. The proportion with complete personal details: [mHealth 95.0% versus paper register 94.0%, (p = 0.54)] and proportion with documented results: [mHealth 97.4% versus paper register 97.8%, (p = 0.79)] were not different in the two methods. The proportion of results available within 48 hours: [mHealth 96.8% versus paper register 68.6%), (p <0.001)], and the proportion on treatment within 28 days [mHealth 28/33 (84.8%) versus paper register 30/44 (68.2%), (p = 0.08)] increased during implementation but was not statistically significant. In-depth interviews showed that providers easily integrated the mHealth application into routine TB investigation and patients positively received the delivery of results via text message. Time from sputum collection to TB treatment initiation decreased from 4 days (pre-implementation) to 3 days but was not statistically significant. Conclusions: We demonstrated that implementation of the mHealth application was feasible, acceptable to health care providers and patients, and has potential to reduce the time to TB treatment initiation and ILFU in PHC settings. [ABSTRACT FROM AUTHOR]

Medical multi-category diagnostic problems may involve discrete biomarkers. Many traditional accuracy measures are based on the assumption that all biomarkers follow continuous distributions and consequently may underestimate the true discrimination ability of the discrete markers. In particular, we focus on Hypervolume Under ROC Manifold (HUM) in this paper and propose an extension of the familiar continuous version of HUM to incorporate discrete biomarkers with ties. Statistical estimation and inference procedures are proposed along with asymptotic properties. We carry out simulation studies to examine the performance of our proposed estimators for the new HUM measure. A real medical example is analysed to illustrate our methodology. [ABSTRACT FROM AUTHOR]

Our study aimed to evaluate the trends of post retraction citations of articles reporting a radiology-imaging diagnostic method and to find if a different pattern exists between manuscripts reporting an ultrasound method and those reporting other radiology diagnostic methods. This study reviewed retractions stored in PubMed on the subject of radiology-imaging diagnosis to identify the motivation, time from publication to retraction, and citations before and after retraction. The PubMed database was searched on June 2017 to retrieve the retracted articles, and the Scopus database was screened to identify the post-retraction citations. The full text was screened to see the type of post-retraction citation (positive/negative) and whether the cited article appears or not as retracted. One hundred and two retractions were identified, representing 3.5% of the retracted articles indexed by PubMed, out of which 54 were included in the analysis. Half of the articles were retracted in the first 24 months after publication, and the number of post retraction citations was higher than the number of citations before retraction in 30 out of 54 cases (US methods: 9/20, other diagnostic methods 21/34, P-value = 0.2312). The plagiarism was the most common reason for retraction (31%), followed by repetitive publication (26%), and errors in data/manuscript (24%). In less than 2% of cases, the retracted articles appear as retracted in the text or reference list, while the negative citation is observed in 4.84% among manuscripts reporting an US diagnostic method and 0.32% among manuscripts reporting a diagnostic method other than US (P-value = 0.0004). No significant differences were observed when post retraction weighted citation index (WCI, no. of citations weighted by citation window) was compared to WCI prior retraction (P-value = 0.5972). In light of the reported results, we enumerated some recommendations that could potentially minimize the referral to retracted studies as valid. [ABSTRACT FROM AUTHOR]

Analysis of functional magnetic resonance imaging (fMRI) data has revealed that brain regions can be grouped into functional brain networks (fBNs) or communities. A community in fMRI analysis signifies a group of brain regions coupled functionally with one another. In neuroimaging, functional connectivity (FC) measure can be utilized to quantify such functionally connected regions for disease diagnosis and hence, signifies the need of devising novel FC estimation methods. In this paper, we propose a novel method of learning FC by constraining its rank and the sum of non-zero coefficients. The underlying idea is that fBNs are sparse and can be embedded in a relatively lower dimension space. In addition, we propose to extract overlapping networks. In many instances, communities are characterized as combinations of disjoint brain regions, although recent studies indicate that brain regions may participate in more than one community. In this paper, large-scale overlapping fBNs are identified on resting state fMRI data by employing non-negative matrix factorization. Our findings support the existence of overlapping brain networks. [ABSTRACT FROM AUTHOR]

Nicola Low and colleagues announce a call for research papers on sexually transmitted infections, to accompany a Collection on the topic. [ABSTRACT FROM AUTHOR]

Background: \Anticoagulation is used for stroke prophylaxis in non-valvular atrial fibrillation, amongst other by use of the vitamin K antagonist, warfarin. Quality in warfarin therapy is often summarized by the time patients spend within the therapeutic range (percent time in therapeutic range, TTR). The correlation between TTR and the occurrence of complications during warfarin therapy has been established, but the influence of patient characteristics in that respect remains undetermined. The objective of the present papers was to examine the association between mean TTR and complication rates with adjustment for differences in relevant patient cohort characteristics. Methods: A systematic literature search was conducted in MEDLINE and Embase (2005–2015) to identify eligible studies reporting on use of warfarin therapy by patients with non-valvular atrial fibrillation and the occurrence of hemorrhage and thromboembolism. Both randomized controlled trials and observational cohort studies were included. The association between the reported mean TTR and major bleeding and stroke/systemic embolism was analyzed by random-effects meta-regression with and without adjustment for relevant clinical cohort characteristics. In the adjusted meta-regressions, the impact of mean TTR on the occurrence of hemorrhage was adjusted for the mean age and the proportion of populations with prior stroke or transient ischemic attack. In the adjusted analyses on thromboembolism, the proportion of females was, furthermore, included. Results: Of 2169 papers, 35 papers met pre-specified inclusion criteria, holding relevant information on 31 patient cohorts. In univariable meta-regression, increasing mean TTR was significantly associated with a decreased rate of both major bleeding and stroke/systemic embolism. However, after adjustment mean TTR was no longer significantly associated with stroke/systemic embolism. The proportion of residual variance composed by between-study heterogeneity was substantial for all analyses. Conclusions: Although higher mean TTR in warfarin therapy was associated with lower complication rates in atrial fibrillation, the strength of the association was decreased when adjusting for differences in relevant clinical characteristics of the patient cohorts. This study suggests that mainly the safety of warfarin therapy increases with higher mean TTR, whereas effectiveness appears not to be substantially improved. Due to the limitations immanent in the meta-regression methods, the results of the present study should be interpreted with caution. Further research on the association between the quality of warfarin therapy and risk of complications is warranted with adjustment for clinically relevant characteristics. [ABSTRACT FROM AUTHOR]

We comment here on a recent paper in this journal, on a non-monotone transformation of biomarkers aimed at improving diagnostic accuracy. We highlight that, in a binary classification problem, the proposed transformation finds its motivation in the Neyman-Pearson lemma, so that the underlying approach is very general and it is applicable to many parametric families, other than the normal one. [ABSTRACT FROM AUTHOR]

This paper proposes SAR imaging algorithm with largest coherence based on the existing SAR imaging algorithm. The basic idea of SAR imaging algorithm in imaging processing is that output signal can have maximum signal-to-noise ratio (SNR) by using the optimal imaging parameters. Traditional imaging algorithm can acquire the best focusing effect, but would bring the decoherence phenomenon in subsequent interference process. Algorithm proposed in this paper is that SAR echo adopts consistent imaging parameters in focusing processing. Although the SNR of the output signal is reduced slightly, their coherence is ensured greatly, and finally the interferogram with high quality is obtained. In this paper, two scenes of Envisat ASAR data in Zhangbei are employed to conduct experiment for this algorithm. Compared with the interferogram from the traditional algorithm, the results show that this algorithm is more suitable for SAR interferometry (InSAR) research and application. [ABSTRACT FROM AUTHOR]

Recently, there has been a growing emphasis on basic number processing competencies (such as the ability to judge which of two numbers is larger) and their role in predicting individual differences in school-relevant math achievement. Children’s ability to compare both symbolic (e.g. Arabic numerals) and nonsymbolic (e.g. dot arrays) magnitudes has been found to correlate with their math achievement. The available evidence, however, has focused on computerized paradigms, which may not always be suitable for universal, quick application in the classroom. Furthermore, it is currently unclear whether both symbolic and nonsymbolic magnitude comparison are related to children’s performance on tests of arithmetic competence and whether either of these factors relate to arithmetic achievement over and above other factors such as working memory and reading ability. In order to address these outstanding issues, we designed a quick (2 minute) paper-and-pencil tool to assess children’s ability to compare symbolic and nonsymbolic numerical magnitudes and assessed the degree to which performance on this measure explains individual differences in achievement. Children were required to cross out the larger of two, single-digit numerical magnitudes under time constraints. Results from a group of 160 children from grades 1–3 revealed that both symbolic and nonsymbolic number comparison accuracy were related to individual differences in arithmetic achievement. However, only symbolic number comparison performance accounted for unique variance in arithmetic achievement. The theoretical and practical implications of these findings are discussed which include the use of this measure as a possible tool for identifying students at risk for future difficulties in mathematics. [ABSTRACT FROM AUTHOR]

Introduction: Non-medical prescribing was introduced into the United Kingdom (UK) to improve patient care, through extending healthcare professionals’ roles. More recent government health service policy focuses on the increased demand and the need for efficiency. This systematic policy review aimed to describe any changes in government policy position and the role that non-medical prescribing plays in healthcare provision. Method: The systematic policy review included policy and consultation documents that describe independent non-medical prescribing. A pre-defined protocol was registered with PROSPERO (CRD42015019786). Professional body websites, other relevant websites and the following databases were searched to identify relevant documents: HMIC, Lexis Nexis, UK Government Web Archive, UKOP, UK Parliamentary Papers and Web of Science. Documents published between 2006 and February 2018 were included. Results and discussion: Following exclusions, 45 documents were selected for review; 23 relating to policy or strategy and 22 to consultations. Of the former, 13/23 were published 2006–2010 and the remainder since 2013. Two main themes were identified: chronological aspects and healthcare provision. In the former, a publication gap for policy documents resulted from a change in government and associated major healthcare service reorganisation. In the later, the role of non-medical prescribing was found to have evolved to support efficient service delivery, and cost reduction. For many professions, prescribing appears embedded into practice; however, the pharmacy profession continues to produce policy documents, suggesting that prescribing is not yet perceived as normal practice. Conclusion: Prescribing appears to be more easily adopted into practice where it can form part of the overall care of the patient. Where new roles are required to be established, then prescribing takes longer to be universally adopted. While this review concerns policy and practice in the UK, the aspect of role adoption has wider potential implications. [ABSTRACT FROM AUTHOR]

Background: Detection of pulmonary nodules is an important aspect of an automatic detection system. Incomputer-aided diagnosis (CAD) systems, the ability to detect pulmonary nodules is highly important, which plays an important role in the diagnosis and early treatment of lung cancer. Currently, the detection of pulmonary nodules depends mainly on doctor experience, which varies. This paper aims to address the challenge of pulmonary nodule detection more effectively. Methods: A method for detecting pulmonary nodules based on an improved neural network is presented in this paper. Nodules are clusters of tissue with a diameter of 3 mm to 30 mm in the pulmonary parenchyma. Because pulmonary nodules are similar to other lung structures and have a low density, false positive nodules often occur. Thus, our team proposed an improved convolutional neural network (CNN) framework to detect nodules. First, a nonsharpening mask is used to enhance the nodules in computed tomography (CT) images; then, CT images of 512×512 pixels are segmented into smaller images of 96×96 pixels. Second, in the 96×96 pixel images which contain or exclude pulmonary nodules, the plaques corresponding to positive and negative samples are segmented. Third, CT images segmented into 96×96 pixels are down-sampled to 64×64 and 32×32 size respectively. Fourth, an improved fusion neural network structure is constructed that consists of three three-dimensional convolutional neural networks, designated as CNN-1, CNN-2, and CNN-3, to detect false positive pulmonary nodules. The networks’ input sizes are 32×32×32, 64×64×64, and 96×96×96 and include 5, 7, and 9 layers, respectively. Finally, we use the AdaBoost classifier to fuse the results of CNN-1, CNN-2, and CNN-3. We call this new neural network framework the Amalgamated-Convolutional Neural Network (A-CNN) and use it to detect pulmonary nodules. Findings: Our team trained A-CNN using the LUNA16 and Ali Tianchi datasets and evaluated its performance using the LUNA16 dataset. We discarded nodules less than 5mm in diameter. When the average number of false positives per scan was 0.125 and 0.25, the sensitivity of A-CNN reached as high as 81.7% and 85.1%, respectively. [ABSTRACT FROM AUTHOR]

Lower back pain is a major public health problem. Despite claims that lumbar belts change spinal posture due to applied pressure on the trunk, no mechanical model has yet been published to prove this treatment. This paper describes a first model for belt design, based on the one hand on the mechanical properties of the fabrics and the belt geometry, and on the other hand on the trunk geometrical and mechanical description. The model provides the estimation of the pressure applied to the trunk, and a unique indicator of the belt mechanical efficiency is proposed: pressure is integrated into a bending moment characterizing the belt delordosing action on the spine. A first in-silico clinical study of belt efficiency for 15 patients with 2 different belts was conducted. Results are very dependent on the body shape: in the case of high BMI patients, the belt effect is significantly decreased, and can be even inverted, increasing the lordosis. The belt stiffness proportionally increases the pressure applied to the trunk, but the influence of the design itself on the bending moment is clearly outlined. Moreover, the belt/trunk interaction, modeled as sticking contact and the specific way patients lock their belts, dramatically modifies the belt action. Finally, even if further developments and tests are still necessary, the model presented in this paper seems suitable for in-silico pre-clinical trials on real body shapes at a design stage. [ABSTRACT FROM AUTHOR]

Background: The concept 'vulnerability' is prevalent in the public domain, health care, social institutions and multidisciplinary research. Conceptual heterogeneity is present, hampering the creation of a common evidence-base of research achievements and successful policies. Recently an international expert group combined a specific literature review with a 2-stage Delphi procedure, arriving at a seemingly universal concept of vulnerability for the elderly with applications for research instruments. We replicated and extended this study, to generalize this result to health in general, and perinatal health in particular. Methods: Two independent expert panels (general health, perinatal health) repeated the Delphi-procedure, using an extended and updated literature review to derive statements on the concept and defining pathways of vulnerability. Additional views were collected on research tools. Consensus-by-design was explicitly avoided. Data collection and processing was independent. Results: Both panels showed surprising convergence on the pathways of vulnerability to health/ill-health, and their interaction. The agreed conceptual model describes a dynamic relation between health and ill-health and vulnerability. The 2 key pathways that link to vulnerability, are complementary, but not symmetrical as biological processes of maintaining health or obtaining better health are not reciprocal to recovery, so also not in terms of vulnerability impacts. An individual's degree of vulnerability is the net balance of risk effects and protective and healing factors (socially, biologically and in terms of health literacy and health care access). These factors can for measurement purposes (according to the panels: interview for exploration, checklists for population research) be grouped into ‘material resources’, ‘taking responsibility for one’s own health’, ‘risky activities and behaviors’, and ‘social support’. Supportive and transforming action can thus be undertaken. Conclusion: A universal concept of vulnerability in the context of health was successfully derived after careful replication and extension of an international Delphi study on vulnerability among the elderly. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this cross-sectional observational study was to compare the prevalence of different oral Candida spp. in patients with Type 2 Diabetes and chronic periodontitis in two oral sites: dorsal surface of the tongue and subgingival area. In order to determine subgingival areas as potential reservoirs of yeasts, this study aimed to find differences in the yeasts’ detection between the dorsum of the tongue, as the oral site most commonly inhabited with microorganisms, and subgingival samples. Additionally, potential predictors for the yeasts prevalence were determined. Material and methods: Subjects (N = 146) were divided into four groups: group A- healthy individuals without periodontitis, group B- healthy individuals with chronic periodontitis, group C- Type 2 Diabetes patients with good glycoregulation and Chronic periodontitis and group D- Type 2 Diabetes patients with poor glycoregulation and Chronic periodontitis. Samples were obtained from the tongue by swabbing. Subgingival plaque samples were taken by paper points and periodontal curette. Isolation and identification of different Candida spp. was done using ChromAgar medium. In addition, germ-tube production and carbohydrate assimilation tests were performed. Results: The prevalence of Candida spp. was higher in diabetics with poor glycoregulation. The most frequently isolated species was Candida albicans followed by Candida glabrata and Candida tropicalis. In 15.6% of cases, Candida spp. was present in the subgingival area while absent on the tongue. Multivariate regression model showed that HbA1c was Candida spp. predictor for both locations. Conclusions: Our results confirmed that there are Candida spp. carriers among subjects with clinically healthy oral mucosa. Also, this study identified subgingival areas as potential reservoirs of these pathogenic species. Glycoregulation has been recognized as a positive predictor factor of Candida spp. [ABSTRACT FROM AUTHOR]

This paper presents the histological characterisation of a selection of worked bone artefacts from Middle Stone Age layers at Sibudu cave, South Africa. Histographic rendering is achieved using high-resolution Computed Tomography, which is non-destructive and facilitates three-dimensional histologic analysis. Excellent congruency in image quality was achieved with previous studies using this method. The results show that most of the artefact fragments contain mostly primary lamellar tissue, which is the bone tissue best adapted to withstand impact stresses. This indicates that bone with greater elastic properties was chosen. Histological characterisation allows the identification of animal taxa. Based on the sample analysed in this paper, Perissodactyla bone was used predominantly in the older layers at the site. Artiodactyla are represented throughout but appear far more frequently in the later (post-Howiesons Poort onwards) layers. Some of the Artiodactyla specimens have high proportions of Haversian tissue, reducing elasticity. The higher percentages of Haversian tissue in the post-Howiesons Poort artefacts relative to Holocene examples from southern Africa suggests that people may have started experimenting with bone from different animal taxa at this time and had not yet learned to eliminate the mechanically weaker secondary tissue. Apart from mechanical considerations, possible cultural constraints governing raw material selection is also explored. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a disease which is widely diagnosed using (colour fundus) images. Efficiency and accuracy are critical in diagnosing DR as lack of timely intervention can lead to irreversible visual impairment. In this paper, we examine strategies for scrutinizing images which affect diagnostic performance of medical practitioners via an eye-tracking study. A total of 56 subjects with 0 to 18 years of experience participated in the study. Every subject was asked to detect DR from 40 images. The findings indicate that practitioners use mainly two types of strategies characterized by either higher dwell duration or longer track length. The main findings of the study are that higher dwell-based strategy led to higher average accuracy (> 85%) in diagnosis, irrespective of the expertise of practitioner; whereas, the average obtained accuracy with a long-track length-based strategy was dependent on the expertise of the practitioner. In the second part of the paper, we use the experimental findings to recommend a scanning strategy for fast and accurate diagnosis of DR that can be potentially used by image readers. This is derived by combining the eye-tracking gaze maps of medical experts in a novel manner based on a set of rules. This strategy requires scrutiny of images in a manner which is consistent with spatial preferences found in human perception in general and in the domain of fundus images in particular. The Levenshtein distance-based assessment of gaze patterns also establish the effectiveness of the derived scanning pattern and is thus recommended for image readers. [ABSTRACT FROM AUTHOR]

In this paper we investigate the changes in the functional connectivity intensity, and some related properties, in healthy people, across the life span and at resting state. For the explicit computation of the functional connectivity we exploit a recently proposed model, that bases not only on the correlations data provided by the acquisition equipment, but also on different parameters, such as the anatomical distances between nodes and their degrees. The leading purpose of the paper is to show that the proposed approach is able to recover the main aspects of resting state condition known from the available literature, as well as to suggest new insights, perspectives and speculations from a neurobiological point of view. Our study involves 133 subjects, both males and females of different ages, with no evidence of neurological diseases or systemic disorders. First, we show how the model applies to the sample, where the subjects are grouped into 28 different groups (14 of males and 14 of females), according to their age. This leads to the construction of two graphs (one for males and one for females), that can be realistically interpreted as representative of the neural network during the resting state. Second, following the idea that the brain network is better understood by focusing on specific nodes having a kind of centrality, we refine the two output graphs by introducing a new metric that favours the selection of nodes having higher degrees. As a third step, we extensively comment and discuss the obtained results. In particular, it is remarkable that, despite a great overlapping exists between the outcomes concerning males and females, some intriguing differences appear. This motivates a deeper local investigation, which represents the fourth part of the paper, carried out through a thorough statistical analysis. As a result, we are enabled to support that, for two special age groups, a few links contribute in differentiating the behaviour of males and females. In addition, we performed an average-based comparison between the proposed model and the traditional statistical correlation-based approach, then discussing and commenting the main outlined discrepancies. [ABSTRACT FROM AUTHOR]

This paper describes and presents a stable and reliable set of stereo-photogrammetric normative data for global and spino-pelvic sagittal alignment, as a proven reference system for evaluating/measuring a fully unconstrained natural upright neutral standing attitude in a young healthy adult population. The methodological features described in this article will enable future studies to replicate and/or directly compare a wide range of different postural tests and/or sagittal alignment assessment procedures including the study of sagittal spine shape variations occurring during gait performance. To date, the quantitative evaluation of adult spinal deformity (ASD) has been mainly confined to the X-ray imaging approach and, more recently, to 3D X-ray reconstruction. Within the existing evaluation framework an opportunity exists for an additional approach: a quantitative evaluation procedure which is easy, accurate, relatively speedy and non-ionising, in order to monitor and track the progress of patients in the areas of both surgical and non-surgical treatment. The resources and methodology described in this paper have been proven to meet all these criteria. They have enabled full 3D posture (including 3D spine shape and sagittal alignment of the skeleton) to be consistently and successfully measured in adult volunteers. All the measurement/evaluation procedures and outcomes carried out were based entirely on the new non-ionising 3D opto-electronic stereo-photogrammetric approach described in this article. The protocol for this methodology was based on a standard set of 27 pre-selected anatomical “landmarks” on the human body, providing standard reference points for observation and measurement. A total of 124 healthy subjects were successfully assessed and, for each subject, 27 individual markers were applied to the corresponding locations on his/her body. Statistical tests to investigate gender differences were also carried out. Descriptive statistics are provided for all 15 of the spino-pelvic parameters under consideration. Results indicated significant differences between genders in five sets of parameters: Kyphosis tilt, Head tilt, Pelvic tilt, Spino-pelvic angle and T1-pelvic angle. The data also demonstrate a high degree of congruity with results obtained using the X-ray method, as evidenced by the existing literature in the field. In summary, the current study presents a new stereo-photogrammetric opto-electronic technology which can be used successfully for ASD evaluation and introduces a comprehensive set of normative data analogous to those proposed in X-ray analysis for sagittal spino-pelvic and total body alignment. [ABSTRACT FROM AUTHOR]

This paper extends the observations presented in the previously published work on the afterhyperpolarization (AHP) duration changes in motoneurones (MNs) on the paretic (more affected) side of 11 post-stroke patients by the same analysis on the non-paretic (less-affected) side. The estimated AHP duration for patients’ MNs supplying more-affected muscles was significantly longer than control values and the elongation decreased with patient age and disorder duration. For MNs supplying less-affected muscles, dependency of AHP duration on age was closer to the control data, but the scatter was substantially bigger. However, the AHP duration estimate of less-affected MNs tended to be longer than that of controls in the short time elapsed since the stroke, and shorter than controls in the long time. Our results thus suggest that the spinal MNs on both sides respond to the cerebral stroke rapidly with prolongation of AHP duration, which tends to normalize with time, in line with functional recovery. This suggestion is in concert with the published research on post-stroke changes in brain hemispheres. To our knowledge, these dependencies have never been investigated before. Since the number of our data was limited, the observed trends should be verified in a larger sample of patients and such a verification could take into account the suggestions for data analysis that we provide in this paper. Our data are in line with the earlier published research on MN firing characteristics post-stroke and support the conclusion that the MUs of the muscles at the non-paretic side are also affected and cannot be considered a suitable control for the MUs on the paretic side. [ABSTRACT FROM AUTHOR]

Statistical learning methods are widely used in medical literature for the purpose of diagnosis or prediction. Conventional accuracy assessment via sensitivity, specificity, and ROC curves does not fully account for clinical utility of a specific model. Decision curve analysis (DCA) becomes a novel complement as it incorporates a clinical judgment of the relative value of benefits (treating a true positive case) and harms (treating a false positive case) associated with prediction models. The preference of a patient or a policy-maker is formulated statistically as the underlying threshold probability, above which the patient would choose to be treated. Net benefit is then calculated for possible threshold probability, which places benefits and harms on the same scale. We consider the inference problems for DCA in this paper. Interval estimation procedure and inference methodology are provided after we derive the relevant asymptotic properties. Our formulation can accommodate the classification problems with multiple categories. We carry out numerical studies to assess the performance of the proposed methods. An eye disease dataset is analyzed to illustrate our proposals. [ABSTRACT FROM AUTHOR]

Background: Posterior tibial tendon dysfunction (PTTD) and adult acquired flatfoot deformity (AAFD) are used interchangeably, although both suggest quite different pathological processes. Objective: To investigate key differences in selection criteria used for inclusion into research studies. Methods: An electronic database search was performed from inception to June 2016. All primary research articles with clear inclusion/diagnostic criteria for PTTD or AAFD were included in the review. All criteria were extracted and synthesised into one aggregate list. Frequencies of recurring criteria were calculated and reported for each stage of the conditions. Results: Of the potentially eligible papers, 148 (65%) did not specify inclusion/selection criteria for PTTD or AAFD and were excluded. Eligibility criteria were reported 82 times in the 80 included papers, with 69 descriptions for PTTD and 13 for AAFD. After synthesis of criteria from all papers, there were 18 key signs and symptoms. Signs and symptoms were considered to be those relating to tendon pathology and those relating to structural deformity. The total number of individual inclusion/diagnostic criteria ranged from 2 to 9. The majority of articles required signs of both tendon dysfunction and structural deformity (84% for AAFD and 81% for PTTD). Across both groups, the most frequently reported criteria were abduction of the forefoot (11.5% of total criteria used), the presence of a flexible deformity (10.2%) and difficulty performing a single leg heel raise (10.0%). This was largely the case for the PTTD articles, whereas the AAFD articles were more focused on postural issues such as forefoot abduction, medial arch collapse, and hindfoot valgus (each 16.7%). Conclusion: As well as synthesising the available literature and providing reporting recommendations, this review has identified that many papers investigating PTTD/AAFD do not state condition-specific selection criteria and that this limits their clinical applicability. Key signs and symptoms of PTTD and AAFD appear similar, except in early PTTD where no structural deformity is present. We recommend that PTTD is the preferred terminology for the condition associated with signs of local tendon dysfunction with pain and/or swelling along the tendon and difficulty with inversion and/or single leg heel raise characterising stage I and difficulty with single leg heel raise and a flexible flatfoot deformity characterizing stage II PTTD. While AAFD may be useful as an umbrella term for acquired flatfoot deformities, the specific associated aetiology should be reported in studies to aid consolidation and implementation of research into practice. Trial registration: Prospero ID: [ABSTRACT FROM AUTHOR]

Background: Alzheimer’s disease neuroimaging initiative (ADNI) is a landmark imaging and omics study in AD. ADNI research literature has increased substantially over the past decade, which poses challenges for effectively communicating information about the results and impact of ADNI-related studies. In this work, we employed advanced information visualization techniques to perform a comprehensive and systematic mapping of the ADNI scientific growth and impact over a period of 12 years. Methods: Citation information of ADNI-related publications from 01/01/2003 to 05/12/2015 were downloaded from the Scopus database. Five fields, including authors, years, affiliations, sources (journals), and keywords, were extracted and preprocessed. Statistical analyses were performed on basic publication data as well as journal and citations information. Science mapping workflows were conducted using the Science of Science (Sci2) Tool to generate geospatial, topical, and collaboration visualizations at the micro (individual) to macro (global) levels such as geospatial layouts of institutional collaboration networks, keyword co-occurrence networks, and author collaboration networks evolving over time. Results: During the studied period, 996 ADNI manuscripts were published across 233 journals and conference proceedings. The number of publications grew linearly from 2008 to 2015, so did the number of involved institutions. ADNI publications received much more citations than typical papers from the same set of journals. Collaborations were visualized at multiple levels, including authors, institutions, and research areas. The evolution of key ADNI research topics was also plotted over the studied period. Conclusions: Both statistical and visualization results demonstrate the increasing attention of ADNI research, strong citation impact of ADNI publications, the expanding collaboration networks among researchers, institutions and ADNI core areas, and the dynamic evolution of ADNI research topics. The visualizations presented here can help improve daily decision making based on a deep understanding of existing patterns and trends using proven and replicable data analysis and visualization methods. They have great potential to provide new insights and actionable knowledge for helping translational research in AD. [ABSTRACT FROM AUTHOR]

It is often necessary to differentiate subjects from multiple categories using medical tests. We may then adopt statistical measures to characterize the performance of these tests. The three-way ROC analysis has been proposed to evaluate the diagnostic accuracy of medical tests with three categories, reflecting the correct classification probabilities across all possible decision thresholds. The geometry of the ROC surface is carefully studied, leading to numerical summary measures such as the volume under the surface. This paper generalizes the global volume under the surface of three-way ROC analysis to the weighted volume under the surface (WVUS) by introducing a weight function emphasizing particular regions of correct classification probabilities. This generalization practically allows researchers to calculate the diagnostic accuracy for a medical or clinical biomarker while satisfactorily high probabilities of correct classification for one or two classes are conditionally ensured. We provide the asymptotic properties of the proposed nonparametric and parametric estimators of WVUS, which could easily lend support to statistical inferences. Some simulations have been conducted to assess the proposed estimators and also to demonstrate the necessity of WVUS. A real data analysis about liver cancer illustrates our methodology. [ABSTRACT FROM AUTHOR]

Introduction: The Swedish Register of Palliative Care (SRPC) is a national quality register that collects data about end-of-life care from healthcare providers that care for dying patients. Data are used for quality control and research. Data are mainly collected with an end-of-life questionnaire (ELQ), which is completed by healthcare staff after the death of a patient. A previous validity assessment of the ELQ showed insufficient validity in some items including symptom relief. The aim of this study was to examine the validity of the revised ELQ. Materials and methods: Data from 100 consecutive patients’ medical records at two specialised palliative care units were used to complete new ELQs, which were then compared to the ELQ registrations from the SRPC for the same patients. The level of agreement was calculated for each ELQ item. To account for the possibility of the agreement occurring by chance, Cohen’s kappa was calculated for suitable items. To examine the extent of registration mistakes when transferring the paper form to the web, the original paper versions of the ELQ filled out at the units were compared to data from the ELQs reported to the SRPC. Results: Level of agreement between ELQ registrations from the SRPC and the new ELQs based on the medical records varied between 0.55 and 1.00, where 24 items showed level of agreement above 0.80 and 9 items showed level of agreement below 0.80. Cohen’s kappa with 95% confidence intervals was calculated for 24 items. The kappa values showed that two items had poor agreement, four fair agreement, 11 moderate agreement, five good agreement and two very good agreement. The level of agreement varied between 0.93 and 1.00 when comparing the ELQ registrations in the SRPC and the paper forms. Conclusion: The revised ELQ contains more items with high levels of agreement between registrations in the SRPC and notes in the patients’ medical records when compared to the previous version. Validating issues around symptom assessment remains a challenge in our model of quality assessment. [ABSTRACT FROM AUTHOR]

Aims: The aim of this systematic review and meta-analysis is to synthesize the available evidence in scientific papers of smokefree legislation effects on respiratory diseases and sensory and respiratory symptoms (cough, phlegm, red eyes, runny nose) among all populations. Materials and methods: Systematic review and meta-analysis were carried out. A search between January 1995 and February 2015 was performed in PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and Google Scholar databases. Inclusion criteria were: 1) original scientific studies about smokefree legislation, 2) Data before and after legislation were collected, and 3) Impact on respiratory and sensory outcomes were assessed. Paired reviewers independently carried out the screening of titles and abstracts, data extraction from full-text articles, and methodological quality assessment. Results: A total number of 1606 papers were identified. 50 papers were selected, 26 were related to symptoms (23 concerned workers). Most outcomes presented significant decreases in the percentage of people suffering from them, especially in locations with comprehensive measures and during the immediate post-ban period (within the first six months). Four (50%) of the papers concerning pulmonary function reported some significant improvement in expiratory parameters. Significant decreases were described in 13 of the 17 papers evaluating asthma hospital admissions, and there were fewer significant reductions in chronic obstructive pulmonary disease admissions (range 1–36%) than for asthma (5–31%). Six studies regarding different respiratory diseases showed discrepant results, and four papers about mortality reported significant declines in subgroups. Low bias risk was present in 23 (46%) of the studies. Conclusions: Smokefree legislation appears to improve respiratory and sensory symptoms at short term in workers (the overall effect being greater in comprehensive smokefree legislation in sensory symptoms) and, to a lesser degree, rates of hospitalization for asthma. [ABSTRACT FROM AUTHOR]

Background: Many classification methods have been proposed based on magnetic resonance images. Most methods rely on measures such as volume, the cerebral cortical thickness and grey matter density. These measures are susceptible to the performance of registration and limited in representation of anatomical structure. This paper proposes a two-stage local feature fusion method, in which deformable registration is not desired and anatomical information is represented from moderate scale. Methods: Keypoints are firstly extracted from scale-space to represent anatomical structure. Then, two kinds of local features are calculated around the keypoints, one for correspondence and the other for representation. Scores are assigned for keypoints to quantify their effect in classification. The sum of scores for all effective keypoints is used to determine which group the test subject belongs to. Results: We apply this method to magnetic resonance images of Alzheimer's disease and Parkinson's disease. The advantage of local feature in correspondence and representation contributes to the final classification. With the help of local feature (Scale Invariant Feature Transform, SIFT) in correspondence, the performance becomes better. Local feature (Histogram of Oriented Gradient, HOG) extracted from 16×16 cell block obtains better results compared with 4×4 and 8×8 cell block. Discussion: This paper presents a method which combines the effect of SIFT descriptor in correspondence and the representation ability of HOG descriptor in anatomical structure. This method has the potential in distinguishing patients with brain disease from controls. [ABSTRACT FROM AUTHOR]

Objective: The Hospital Anxiety and Depression Scale (HADS) is widely used to screen for anxiety and depression. A large literature is citable in support of its validity, but difficulties are increasingly being identified, such as inexplicably discrepant optimal cutpoints and inconsistent factor-structures. This article examines whether these problems could be due to the construction of the HADS that poses difficulties for translation and cross-cultural use. Methods: Authors’ awareness of difficulties translating the HADS were identified by examining 20% of studies using the HADS, obtained by a systematic literature search in Pubmed and PsycINFO in May 2012. Reports of use of translations and validation studies were recorded for papers from non-English speaking countries. Narrative and systematic reviews were examined for how authors dealt with different translations. Results: Of 417 papers from non-English speaking countries, only 45% indicated whether a translation was used. Studies validating translations were cited in 54%. Seventeen reviews, incorporating data from diverse translated versions, were examined. Only seven mentioned issues of language and culture, and none indicated insurmountable problems in integrating results from different translations. Conclusion: Initial decisions concerning item content and response options likely leave the HADS difficult to translate, but we failed to find an acknowledgment of problems in articles involving its translation and cross-cultural use. Investigators’ lack of awareness of these issues can lead to anomalous results and difficulties in interpretation and integration of these results. Reviews tend to overlook these issues and most reviews indiscriminately integrate results from studies performed in different countries. Cross-culturally valid, but literally translated versions of the HADS may not be attainable, and specific cutpoints may not be valid across cultures and language. Claims about rates of anxiety and depression based on integrating cross-cultural data or using the same cutpoint across languages and culture should be subject to critical scrutiny. [ABSTRACT FROM AUTHOR]

Type 2 diabetes leads to premature death and reduced quality of life for 8% of Americans. Nutrition management is critical to maintaining glycemic control, yet it is difficult to achieve due to the high individual differences in glycemic response to nutrition. Anticipating glycemic impact of different meals can be challenging not only for individuals with diabetes, but also for expert diabetes educators. Personalized computational models that can accurately forecast an impact of a given meal on an individual’s blood glucose levels can serve as the engine for a new generation of decision support tools for individuals with diabetes. However, to be useful in practice, these computational engines need to generate accurate forecasts based on limited datasets consistent with typical self-monitoring practices of individuals with type 2 diabetes. This paper uses three forecasting machines: (i) data assimilation, a technique borrowed from atmospheric physics and engineering that uses Bayesian modeling to infuse data with human knowledge represented in a mechanistic model, to generate real-time, personalized, adaptable glucose forecasts; (ii) model averaging of data assimilation output; and (iii) dynamical Gaussian process model regression. The proposed data assimilation machine, the primary focus of the paper, uses a modified dual unscented Kalman filter to estimate states and parameters, personalizing the mechanistic models. Model selection is used to make a personalized model selection for the individual and their measurement characteristics. The data assimilation forecasts are empirically evaluated against actual postprandial glucose measurements captured by individuals with type 2 diabetes, and against predictions generated by experienced diabetes educators after reviewing a set of historical nutritional records and glucose measurements for the same individual. The evaluation suggests that the data assimilation forecasts compare well with specific glucose measurements and match or exceed in accuracy expert forecasts. We conclude by examining ways to present predictions as forecast-derived range quantities and evaluate the comparative advantages of these ranges. [ABSTRACT FROM AUTHOR]

Human fingers are 3D objects. More information will be provided if three dimensional (3D) fingerprints are available compared with two dimensional (2D) fingerprints. Thus, this paper firstly collected 3D finger point cloud data by Structured-light Illumination method. Additional features from 3D fingerprint images are then studied and extracted. The applications of these features are finally discussed. A series of experiments are conducted to demonstrate the helpfulness of 3D information to fingerprint recognition. Results show that a quick alignment can be easily implemented under the guidance of 3D finger shape feature even though this feature does not work for fingerprint recognition directly. The newly defined distinctive 3D shape ridge feature can be used for personal authentication with Equal Error Rate (EER) of ~8.3%. Also, it is helpful to remove false core point. Furthermore, a promising of EER ~1.3% is realized by combining this feature with 2D features for fingerprint recognition which indicates the prospect of 3D fingerprint recognition. [ABSTRACT FROM AUTHOR]

Objectives: Recently, improvements have been made to diagnostics for gambiense sleeping sickness control but their performance remains poorly documented and may depend on specimen processing prior to examination. In a prospective study in the Democratic Republic of the Congo, we compared the diagnostic performance of several parasite detection techniques, immune trypanolysis and of m18S PCR on whole blood stored in a stabilisation buffer or dried on filter paper. Methods: Individuals with CATT whole blood (WB) titer ≥1∶4 or with clinical signs indicative for sleeping sickness were examined for presence of trypanosomes in lymph node aspirate (LNA) and/or in blood. Blood was examined with Capillary Centrifugation Technique (CTC), mini-Anion Exchange Centrifugation Technique (mAECT) and mAECT on buffy coat (BC). PCR was performed on whole blood (i) stored in guanidine hydrochloride EDTA (GE) stabilisation buffer and (ii) dried on filter paper, and repeatability and reproducibility were assessed. Immune trypanolysis (TL) was performed on plasma. Results: A total of 237 persons were included. Among 143 parasitologically confirmed cases, 85.3% had a CATT-WB titre of ≥1/8, 39.2% were positive in LNA, 47.5% in CTC, 80.4% in mAECT-WB, 90.9% in mAECT-BC, 95.1% in TL and up to 89.5% in PCR on GE-stabilised blood. PCR on GE-stabilised blood showed highest repeatability (87.8%) and inter-laboratory reproducibility (86.9%). Of the 94 non-confirmed suspects, respectively 39.4% and 23.4% were TL or PCR positive. Suboptimal specificity of PCR and TL was also suggested by latent class analysis. Conclusion: The combination of LNA examination with mAECT-BC offered excellent diagnostic sensitivity. For PCR, storage of blood in stabilisation buffer is to be preferred over filter paper. TL as well as PCR are useful for remote diagnosis but are not more sensitive than mAECT-BC. For TL and PCR, the specificity, and thus usefulness for management of non-confirmed suspects remain to be determined. [ABSTRACT FROM AUTHOR]

In this paper the possibility of classification of X-ray images of the cervical vertebrae is studied. The images should be classified into one of the following classes—the images of healthy vertebrae and the images of vertebrae with syndesmophytes. The vertebra contours, described unambiguously by using the generalized shape language, are the basis of the analysis. As a result, the contour is represented as a chain of sinquads that determine switches. The found switches are the characteristic points of the analyzed contour. In these points additional features of the contour are determined. On the basis of these features two aforementioned classes of images are defined as fuzzy sets. Such an approach allows us to create a hierarchical algorithm of classification based on the syntactic and fuzzy description of the contour. [ABSTRACT FROM AUTHOR]

Polytomous discrimination index is a novel and important diagnostic accuracy measure for multi-category classification. After reconstructing its probabilistic definition, we propose a nonparametric approach to the estimation of polytomous discrimination index based on an empirical sample of biomarker values. In this paper, we provide the finite-sample and asymptotic properties of the proposed estimators and such analytic results may facilitate the statistical inference. Simulation studies are performed to examine the performance of the nonparametric estimators. Two real data examples are analysed to illustrate our methodology. [ABSTRACT FROM AUTHOR]

Accurate estimation of motion field in respiration-correlated 4DCT images, is a precondition for the analysis of patient-specific breathing dynamics and subsequent image-supported treatment planning. However, the lung motion estimation often suffers from the sliding motion. In this paper, a novel lung motion method based on the non-rigid registration of point clouds is proposed, and the tangent-plane distance is used to represent the distance term, which describes the difference between two point clouds. Local affine transformation model is used to express the non-rigid deformation of the lung motion. The final objective function is expressed in the Frobenius norm formation, and matrix optimization scheme is carried out to find out the optimal transformation parameters that minimize the objective function. A key advantage of our proposed method is that it alleviates the requirement that the source point cloud and the reference point cloud should be in one-to-one corresponding relationship, and the requirement is difficult to be satisfied in practical application. Furthermore, the proposed method takes the sliding motion of the lung into consideration and improves the registration accuracy by reducing the constraint of the motion along the tangent direction. Non-rigid registration experiments are carried out to validate the performance of the proposed method using popi-model data. The results demonstrate that the proposed method outperforms the traditional method with about 20% accuracy increase. [ABSTRACT FROM AUTHOR]

Glioma detection and segmentation is a challenging task for radiologists and clinicians. The research reported in this paper seeks to develop a better clinical decision support algorithm for clinicians diagnosis. This paper presents a probabilistic method for detection and segmentation between abnormal tissue regions and brain tumour (tumour core and edema) portions from Magnetic Resonance Imaging (MRI). A framework is constructed to learn structure of undirected graphical models that can represent the spatial relationships among variables and apply it to glioma segmentation. Compared with the pixel of image, the superpixel is more consistent with human visual cognition and contains less redundancy, thus, the superpixels are considered as the basic unit of structure learning and glioma segmentation scheme. ℓ1-regularization techniques are applied to learn the appropriate structure for modeling graphical models. Conditional Random Fields (CRF) are used to model the spatial interactions among image superpixel regions and their measurements. A number of features including statistics features, the combined features from the local binary pattern as well as gray level run length, curve features, and fractal features were extracted from each superpixel. The features are then passed by ℓ1-regularization to ensure a robust classification. The proposed method is compared with support vector machine and Fuzzy c-means to classify each superpixel into normal and abnormal tissue. The proposed system is tested for the presence of low grade as well as high grade glioma tumors on images collected from BRATS2013, BRATS2015 data set and Henan Provincial People’s Hospital (HNPPH) data set. The experiments performed provides similarity between segmented and truth image up to 91.5% by correlation method. [ABSTRACT FROM AUTHOR]

Background: Complementary and alternative medicine (CAM) is very popular with patients frequently combining it with orthodox health care. The high prevalence of CAM use and satisfaction with CAM reported by patients directly challenges an orthodox system that can only approve such use if it results from the application of biomedical concepts and science. Studies highlighting this as a cultural, sociological and historical phenomenon emphasise the value of choice for consumers of health care. Musculoskeletal conditions typify common problems for which the effectiveness of orthodox care is often unclear. We postulated that the reasons people give for using or not using CAM for musculoskeletal conditions, would therefore indicate the full range of expectations that people have of health care. Furthermore, these reasons would indicate how much people feel orthodox health care is or is not meeting their expectations. Therefore, this study aims to investigate people’s reasons for choosing or avoiding CAM for non-traumatic musculoskeletal conditions. Methods: A systematic search and narrative synthesis was conducted of published qualitative and quantitative studies related to CAM and non-traumatic musculoskeletal conditions. Results: We identified 169 relevant papers detailing 152 separate studies, from which 1486 justifications were extracted concerning CAM use. Content analysis resulted in 11 distinct categories across four themes: practical aspects of care, clinical effectiveness, non-clinical outcomes of care, and a person’s philosophy of illness and care. People provided similar rationales for both using and avoiding CAM, emphasising that, whilst CAM is perceived by many patients with musculoskeletal conditions to fill gaps in care (such as practitioner time or quality of the therapeutic relationship), orthodox care also seeks to deliver these aspects of care. However, people who used CAM also highlighted its alignment with their general philosophy and ideas about illness and health care, and often emphasised CAM’s capacity to give them control over their condition and its treatment. Conclusion: Currently, CAM appears to have a significant role for patients with common painful long-term conditions in providing choices to enable individual needs to be met. [ABSTRACT FROM AUTHOR]

We present a finite difference time domain (FDTD) model for computation of A line scans in time domain optical coherence tomography (OCT). The OCT output signal is created using two different simulations for the reference and sample arms, with a successive computation of the interference signal with external software. In this paper we present the model applied to two different samples: a glass rod filled with water-sucrose solution at different concentrations and a peripheral nerve. This work aims to understand to what extent time domain OCT can be used for non-invasive, direct optical monitoring of peripheral nerve activity. [ABSTRACT FROM AUTHOR]

Background: Forensic odontology (FO) is regarded in the literature as one of the most reliable and economical scientific methods for victim identification in mass disasters (MDs). The present paper systematically reviews the role of forensic odontologists in various global MDs. Method: A comprehensive search of the literature databases (PubMed, Medline, SCOPUS, Web of Science and Google Scholar), along with cross-referencing published peer-reviewed articles, was conducted. The search included full texts, abstracts or titles, had no inclusion year limit (searched until September 2017) and was limited to the English language. Keywords included a combination of ‘Forensic odontology’, ‘Dental records’, ‘Victim identification’, ‘Natural mass disaster’, ‘Criminal mass disaster’, ‘Accidental mass disaster’ and ‘Victim disaster’. Results: Of the included disasters (20), 12 (57.14%) were accidental, 5 (23.80%) natural and 3 (19.04%) were criminal. The maximum number of victims was associated with the Japan tsunami (15892), followed by the Thailand tsunami (4280) and the Estonia ferry disaster (852). A total of 23654 victims were reported, of which 20569 (86.96%) were positively identified. Reports from 17 MDs included the use of FO in victim identification [3025 (14.70%) cases]. In addition, 1094 victims (5.31%; from 7 papers) were identified using FO in combination with other methodologies. The highest percentage of victims was identified using FO following the Kentucky air crash (47; 100%), followed by the Newark air crash (38; 76%), the Nepal air crash (10; 71.42%), the France air crash (56; 65.88%), the Australian bushfire (14; 63.63%), and the Estonia ferry disaster (57; 60.63%). Conclusion: FO has played a significant role in victim identification in several MDs around the world. The success of FO-based identification is heavily dependent on the availability of ante-mortem records from general dental practitioners. Hence, adequate knowledge about FO and appropriate dental record keeping among general dental practitioners are critical. [ABSTRACT FROM AUTHOR]

The human pulmonary valve, one of the key cardiac structures, plays an important role in circulatory system. However, there are few mathematical models to accurately simulate it. In this paper, we establish a geometric model of the normal human pulmonary valve from a mathematical perspective in the fully opening case. Based on the statistical data of the human pulmonary valves, we assume that the motions of the three cusps are symmetrical in the cardiac cycle. Thus, we first propose that each cusp is a part of the cylindrical shell according to its structure and physiological feature. The parameters for the pulmonary valve cusps in three-dimensional space are obtained by the fitting functions. We verify the accuracy of our results by comparing the areas of the pulmonary valve and pulmonary valve flap. [ABSTRACT FROM AUTHOR]

Objective: Gestural interfaces allow accessing and manipulating Electronic Medical Records (EMR) in hospitals while keeping a complete sterile environment. Particularly, in the Operating Room (OR), these interfaces enable surgeons to browse Picture Archiving and Communication System (PACS) without the need of delegating functions to the surgical staff. Existing gesture based medical interfaces rely on a suboptimal and an arbitrary small set of gestures that are mapped to a few commands available in PACS software. The objective of this work is to discuss a method to determine the most suitable set of gestures based on surgeon’s acceptability. To achieve this goal, the paper introduces two key innovations: (a) a novel methodology to incorporate gestures’ semantic properties into the agreement analysis, and (b) a new agreement metric to determine the most suitable gesture set for a PACS. Materials and methods: Three neurosurgical diagnostic tasks were conducted by nine neurosurgeons. The set of commands and gesture lexicons were determined using a Wizard of Oz paradigm. The gestures were decomposed into a set of 55 semantic properties based on the motion trajectory, orientation and pose of the surgeons’ hands and their ground truth values were manually annotated. Finally, a new agreement metric was developed, using the known Jaccard similarity to measure consensus between users over a gesture set. Results: A set of 34 PACS commands were found to be a sufficient number of actions for PACS manipulation. In addition, it was found that there is a level of agreement of 0.29 among the surgeons over the gestures found. Two statistical tests including paired t-test and Mann Whitney Wilcoxon test were conducted between the proposed metric and the traditional agreement metric. It was found that the agreement values computed using the former metric are significantly higher (p < 0.001) for both tests. Conclusions: This study reveals that the level of agreement among surgeons over the best gestures for PACS operation is higher than the previously reported metric (0.29 vs 0.13). This observation is based on the fact that the agreement focuses on main features of the gestures rather than the gestures themselves. The level of agreement is not very high, yet indicates a majority preference, and is better than using gestures based on authoritarian or arbitrary approaches. The methods described in this paper provide a guiding framework for the design of future gesture based PACS systems for the OR. [ABSTRACT FROM AUTHOR]