Assessment of the quality of oral biopsy procedure videos shared on YouTube.

OBJECTIVE: The aim of this study was to assess the quality of free-to-access videos on oral biopsy procedures on the YouTube platform. MATERIALS AND METHODS: We conducted a search on YouTube using the term "oral biopsy" and selected the first 100 videos in order of relevance. The following exclusion criteria were applied: language other than English, videos that did not cover oral biopsy techniques, videos on nonhuman specimens, postoperative instructions, personal experiences, exfoliative cytology, or "brush biopsy." Forty-seven selected videos were classified based on their duration, country of origin, date of upload to the system, author, information source and number of views, and likes and dislikes. Video quality was analyzed using DISCERN, the Global Quality Scale (GQS), and the Video Information and Quality Index (VIQI). RESULTS: The majority (78.7%) of analyzed videos were uploaded by dentists, originating from India (48.9%), with a mean duration of 11.8 min (SD, 20.4), with 104.5 likes (SD, 186.4) and 7.1 dislikes (SD, 10.55). The mean values for DISCERN, GQS, and VIQI were 1.3 (SD, 0.52), 2.1 (SD, 1.04), and 9.62 (SD, 1.69), respectively. CONCLUSION: The majority of videos on oral biopsy published on YouTube are of low quality.

Effect of Photo-polymerization Delay on the Bond Strength and Microhardness of Dual-polymerizing Resin Cements.

STATEMENT OF PROBLEM: To fully maximize the potential of dual-polymerizing resin cements, a thorough understanding of how the light- and chemical-polymerizing components interact in a resin system is required. Disorder in the polymerization process between the two components may hurt one of the components versus the other, affecting the overall properties and performance of the resin cements. PURPOSE: Evaluate photo-polymerization delay time on dentin shear-bond strength and Vickers microhardness of dual-polymerizing resin cements. METHODS AND MATERIALS: Shear bond strength (SBS) of self-adhesive (RelyX Unicem 2, 3M ESPE) and adhesive (RelyX Ultimate, 3M ESPE) dual-polymerizing resin cements were evaluated. Dentin specimens (n=80) were prepared for the SBS test according to ISO standard 29022:2013. Teeth were randomly allocated into eight groups based on the type of cement, and photo-polymerization delay times (0, 2, 5, and 10 minutes). Vickers microhardness test (HV) was performed following ASTM E384-17 (n=32) prepared based on cement type and photo-polymerization delay times; specimens were tested after 24 hours of storage. Statistical analysis was performed using two-way ANOVA to determine the individual and combined effects of resin cement type and photo-polymerization delay time on SBS and HV. RESULTS: Resin cement and photo-polymerization delay times for the adhesive cement at 0- and 2-minute pairings had significantly higher SBS means than all other combinations (p<0.0001). Resin cement type was also statistically significant (p<0.0001). Resin cement type and photo-polymerization delay times were not significant (p=0.3550) for HV. CONCLUSIONS: Photo-polymerization delay time affected dentin SBS with higher bond strength when photo-polymerization delay time was performed between 2 and 5 minutes with a self-adhesive resin cement, and between 0 and 2 minutes with an adhesive resin cement. Delaying photo-polymerization time to 10 minutes led to inferior dentin SBS and HV for both self-adhesive and adhesive dual-polymerizing resin cements.

Estimating the impact of stimulant use on initiation of buprenorphine and extended-release naltrexone in two clinical trials and real-world populations.

BACKGROUND: Co-use of stimulants and opioids is rapidly increasing. Randomized clinical trials (RCTs) have established the efficacy of medications for opioid use disorder (MOUD), but stimulant use may decrease the likelihood of initiating MOUD treatment. Furthermore, trial participants may not represent "real-world" populations who would benefit from treatment. METHODS: We conducted a two-stage analysis. First, associations between stimulant use (time-varying urine drug screens for cocaine, methamphetamine, or amphetamines) and initiation of buprenorphine or extended-release naltrexone (XR-NTX) were estimated across two RCTs (CTN-0051 X:BOT and CTN-0067 CHOICES) using adjusted Cox regression models. Second, results were generalized to three target populations who would benefit from MOUD: Housed adults identifying the need for OUD treatment, as characterized by the National Survey on Drug Use and Health (NSDUH); adults entering OUD treatment, as characterized by Treatment Episodes Dataset (TEDS); and adults living in rural regions of the U.S. with high rates of injection drug use, as characterized by the Rural Opioids Initiative (ROI). Generalizability analyses adjusted for differences in demographic characteristics, substance use, housing status, and depression between RCT and target populations using inverse probability of selection weighting. RESULTS: Analyses included 673 clinical trial participants, 139 NSDUH respondents (weighted to represent 661,650 people), 71,751 TEDS treatment episodes, and 1,933 ROI participants. The majority were aged 30-49 years, male, and non-Hispanic White. In RCTs, stimulant use reduced the likelihood of MOUD initiation by 32% (adjusted HR [aHR] = 0.68, 95% CI 0.49-0.94, p = 0.019). Stimulant use associations were slightly attenuated and non-significant among housed adults needing treatment (25% reduction, aHR = 0.75, 0.48-1.18, p = 0.215) and adults entering OUD treatment (28% reduction, aHR = 0.72, 0.51-1.01, p = 0.061). The association was more pronounced, but still non-significant among rural people injecting drugs (39% reduction, aHR = 0.61, 0.35-1.06, p = 0.081). Stimulant use had a larger negative impact on XR-NTX initiation compared to buprenorphine, especially in the rural population (76% reduction, aHR = 0.24, 0.08-0.69, p = 0.008). CONCLUSIONS: Stimulant use is a barrier to buprenorphine or XR-NTX initiation in clinical trials and real-world populations that would benefit from OUD treatment. Interventions to address stimulant use among patients with OUD are urgently needed, especially among rural people injecting drugs, who already suffer from limited access to MOUD.

Qualitative fit test outcomes for N95 filtering facepiece respirators in health care workers.

BACKGROUND: We analyzed the qualitative fit test results of the filtering facepiece respirators (FFRs) used at our institution to determine their performance and utility. METHODS: We retrospectively analyzed 12,582 qualitative fit testing results for several FFR models among 8,809 health care workers (HCWs). RESULTS: The overall failure rate for HCWs was 15.2%. Nearly one-third (2933/8809, 33.3%) had multiple FFRs fit tested. HCW sex was a statistically significant indicator of fit testing failure (χ2 = 29.9, df = 1, P < .001), with women having a 44% higher likelihood (OR, 1.4; 95% CI: 1.27-1.65) than men. There were statistically significant differences in the failure rate across FFRs (Fig 4, F[5, 12475] = 8.4, P < .001). Fluidshield 46867S had a significantly higher failure rate (49%) than the 3M 1860 (P = .012), 3M 1860S (P < .001), 3M 8210 (P < .001), and Safelife (P < .001) FFRs. CONCLUSIONS: There was a large degree of variation in fit testing results for the FFRs tested. Although we were unable to find an FFR that fit more than 95% of the HCWs successfully, we identified poorly functioning FFRs that can help our institution with decision-making and budgeting for acquisition and stocking appropriate FFRs.

Real-Time Optical Vascular Imaging, a new method for the diagnosis and monitoring of oral diseases.

INTRODUCTION: Real-Time Optical Vascular Imaging (RTOVI) is a technology developed in the Centre for Oral Clinical & Translational Sciences, within the Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, that allows rapid and preparation free, in vivo imaging of the microvascular anatomy of the human oral cavity. Microvascular changes are known to be related to disease subtypes, in particular cancer. This makes in vivo microvascular examination clinically valuable. However, at present there is lack of any analytical method able to objectively assess microvascular morphology images. DISCUSSION: The assessment of microvascular morphology based on a subjective evaluation was proven to be unreliable. There was a need to develop a software-based analysis for in vivo microvascular images to support the validation of RTOVI. This paper reviews the authors work to develop and test an automated microvascular analysis method for RTOVI based on ImageJ, an open-source software. This allowed to determined which parameters offered a more robust mathematical representation of the microvascular anatomy of the gingival margin, such as the mean area per capillary and mean aspect ratio. However, in vivo microvascular images from elsewhere within the oral cavity posed a bigger challenge to the analysis procedure due to the microvascular architectural complexity and poorer contrast. Angiogenesis Analyzer, a well-known ImageJ plugin used for the quantification of in vitro microvascular images, is under development in collaboration with the University of Paris Est Créteil. The aim of this work is to obtain an automated analysis method for in vivo microvascular images able to offer a solid foundation for the diagnostic potential of RTOVI and subsequent clinical integration of this technology. CONCLUSION: An automated analysis method for in vivo microvascular images is paramount before any attempt to clinically validate RTOVI. Our initial work of testing a software-based analysis demonstrated the effectiveness of some parameters, which is valuable for future work, and led us to move into a more sophisticated method involving customising the Angiogenesis Analyzer plugin. This is an essential step, aiming to extend the potential of in vivo microscopy with the clinical integration of RTOVI. LAY DESCRIPTION: This article summarises the initial research work done in the field on in vivo microvascular imaging aiming to develop a technique for the diagnosis of oral diseases based on the shape of small blood vessels found just below the surface of the "skin" inside the mouth. This offers the potential to examine lesions without the need to take a sample (biopsy/cutting tissue) to observe it microscopically. This ultimately offers a potential to accelerate diagnostic decision making, avoid unpleasant and often deterrent surgical procedures and reducing diagnostic laboratory time and cost burdens. However, in order to assess images of small blood vessels obtained in clinic, we needed to develop and test a software-based analysis to avoid the subjective human interpretation, known not to work. This article describes the authors journey to achieve an automated and sophisticated analysis method unique in the world for in vivo microvascular images derived from real-time optical vascular imaging.

Longitudinal assessment of nonavalent vaccine HPV types in a sample of sexually active African American women from ten U.S. Cities.

BACKGROUND: Chronic infection with high-risk human papillomavirus is a necessary cause for cervical carcinogenesis. This study examined prevalence of nonavalent vaccine preventable HPV types over four months among sexually active women in the United States. METHODS: This sub-study obtained meta-data for 80 of the 1,365 women (18-25 years), enrolled in the BRAVO study, a randomized, open-label trial of home screening and treatment of asymptomatic bacterial vaginosis at high-risk for sexually transmitted infections conducted between 2008 and 2013. Participants were randomized to treatment or standard-of-care, and followed every 2-months for 12 months. Stored vaginal swabs from the first three visits were tested for the nine vaccine preventable HPV types using quantitative PCR. Prevalence and associated 95% confidence intervals for the HPV types were assessed using R (version 3.6.1). RESULTS: The average age of the participants was 21.5 (SD ± 2.11) years, with 60% having ever been pregnant and all were African-American. Majority (71%) reported ≥ two sex partners in the prior year with 89% having unprotected vaginal sex and 45% having a new sex partner in the prior year. About 30% had ≥ one of the nine nonavalent vaccine HPV types at all three time points over a period of four months, 15% at two of any three visits, 19% at one of the three visits and 36% were negative for all nine vaccine HPV types at all time points. The most frequently detected HPV vaccine types were 52, 58, 16, and 18. The prevalence of any vaccine HPV types, and high-risk HPV types was 63.8% and 58.8%, respectively. CONCLUSIONS: Our findings suggest that HPV vaccination which is currently recommended for all unvaccinated persons through age 26 years, is likely to be more beneficial than previously thought as nonavalent HPV vaccine was not available during the time these data were collected.

A hepatitis C elimination model in healthcare for the homeless organization: A novel reflexive laboratory algorithm and equity assessment.

BACKGROUND: Reaching World Health Organization hepatitis C (HCV) elimination targets requires diagnosis and treatment of people who use drugs (PWUD) with direct acting antivirals (DAAs). PWUD experience challenges engaging in HCV treatment, including needing multiple provider and laboratory appointments. Women, minoritized racial communities, and homeless individuals are less likely to complete treatment. METHODS: We implemented a streamlined opt-out HCV screening and linkage-to-care program in two healthcare for the homeless clinics and a medically supported withdrawal center. Front-line staff initiated a single-order reflex laboratory bundle combining screening, confirmation, and pre-treatment laboratory evaluation from a single blood draw. Multinomial logistic regression models identified characteristics influencing movement through each stage of the HCV treatment cascade. Multiple logistic regression models identified patient characteristics associated with HCV care cascade progression and Cox proportional hazards models assessed time to initiation of DAAs. RESULTS: Of 11,035 clients engaged in services between May 2017 and March 2020, 3,607 (32.7%) were screened. Of those screened, 1,020 (28.3%) were HCV PCR positive. Of those with detectable RNA, 712 (69.8%) initiated treatment and 670 (94.1%) completed treatment. Of those initiating treatment, 407 (57.2%) achieved SVR12. There were eight treatment failures and six reinfections. In the unadjusted model, the bundle intervention was associated with increased care cascade progression, and in the survival analysis, decreased time to initiation; these differences were attenuated in the adjusted model. Women were less likely to complete treatment and SVR12 labs than men. Homelessness increased likelihood of screening and diagnosis but was negatively associated with completing SVR12 labs. Presence of opioid and stimulant use disorder diagnoses predicted increased care cascade progression. CONCLUSIONS: The laboratory bundle and referral pathways improved treatment initiation, time to initiation, and movement across the cascade. Despite overall population improvements, women and homeless individuals experienced important gaps across the HCV care cascade.

Neuronal inclusions resembling Negri bodies in the thalamus of a red kangaroo (Macropus rufus).

Eosinophilic intracytoplasmic neuronal inclusions resembling Negri bodies, but not associated with lyssaviral infection, were detected in the ventrolateral thalamus of a young-adult, male red kangaroo (Macropus rufus). Similar neuronal inclusions, also with a regional distribution in the brain, have been reported as an incidental, possibly age-related finding in other animal species.

The role of transcranial magnetic stimulation in understanding attention-related networks in single subjects.

Attention is a cognitive mechanism that has been studied through several methodological viewpoints, including animal models, MRI in stroke patients, and fMRI in healthy subjects. Activation-based fMRI research has also pointed to specific networks that activate during attention tasks. Most recently, network neuroscience has been used to study the functional connectivity of large-scale networks for attention to reveal how strongly correlated networks are to each other when engaged in specific behaviors. While neuroimaging has revealed important information about the neural correlates of attention, it is crucial to better understand how these processes are organized and executed in the brain in single subjects to guide theories and treatments for attention. Noninvasive brain stimulation is an effective tool to causally manipulate neural activity to detect the causal roles of circuits in behavior. We describe how combining transcranial magnetic stimulation (TMS) with modern precision network analysis in single-subject neuroimaging could test the roles of regions, circuits, and networks in regulating attention as a pathway to improve treatment effect magnitudes and specificity.

Hypofractionated adjuvant surgical cavity radiotherapy following resection of limited brain metastasis.

BACKGROUND: Following surgical resection of oligometastatic disease to the brain there is a high rate of local relapse which is reduced by the addition of focal radiation therapy, often delivered as single fraction stereotactic radiosurgery (SRS) to the surgical cavity. This study audited the outcomes of an alternative approach using hypofractionated radiation therapy (HFRT) to the surgical resection cavity. METHODS AND MATERIALS: Seventy-nine patients who received surgical resection and focal radiation therapy to the surgical cavity using HFRT with intensity modulated radiation therapy with or without stereotactic radiotherapy were identified. Doses were delivered in five fractions every second day for 10 days. Follow-up involved MRI surveillance with three-monthly MRI scans post resection. The major endpoints were local control at the surgical cavity site, and presence of radiation necrosis at the treated site. RESULTS: Seventy-nine patients were included for the analysis with a median follow-up of 10.8 months. Of the cohort, 56% experienced intracranial progression, with all patients progressing distant to the resection cavity, and 7% progressing locally in addition. The one-year local control rate was 89.8%. The median progression-free survival was 10.0 months and median overall survival was 14.3 months. There was one CTCAE grade 3 toxicity of symptomatic radiation necrosis with no grade 4-5 toxicities seen. CONCLUSIONS: The rate of local relapse following HFRT to the surgical cavity is low with minimal risk of radiation necrosis. HFRT can be considered as an alternative to SRS for focal radiotherapy after brain metastasis resection.

Encephalomyocarditis virus infection in alpacas.

Encephalomyocarditis virus (EMCV) infection was detected by real-time reverse transcription PCR (qRT-PCR) in four adult alpacas (Vicugna pacos) from two properties on the Far North Coast of New South Wales (NSW) in April and May 2018 and in two adult alpacas from a third property on the Central Coast of NSW in October 2018. Viral RNA was detected in a range of samples, including blood, fresh body organs and mucosal swabs. EMCV was isolated from the blood and body organs of five of these alpacas. These animals displayed a range of clinical signs, including inappetence, colic, recumbency and death. Necropsy findings included multifocal to coalescing areas of myocardial pallor, pulmonary congestion and oedema, hepatic congestion and serosal effusion. Histopathological changes comprised acute, multifocal myocardial degeneration and necrosis, with mild, neutrophilic and lymphocytic inflammation (5/5 hearts) and mild, perivascular neutrophilic meningoencephalitis (1/3 brains). This is the first report of disease due to EMCV in alpacas under farm conditions, and it identifies EMCV infection as a differential diagnosis for acute disease and death in this camelid species. In addition to the samples traditionally preferred for EMCV isolation (fresh heart, brain and spleen), blood samples are also appropriate for EMCV detection by qRT-PCR assay.

Declining levels of serum chemokine (C-X-C motif) ligand 10 over time are associated with new onset of psoriatic arthritis in patients with psoriasis: a new biomarker?

BACKGROUND: We previously found that serum levels of chemokine (C-X-C motif) ligand 10 (CXCL10) decreased after the onset of psoriatic arthritis (PsA). OBJECTIVES: We measured CXCL10 levels over time in patients with psoriasis who developed PsA to determine whether the drop in CXCL10 was specific to these patients and further assess its association with PsA development. METHODS: Prospectively followed patients with psoriasis without arthritis [cutaneous psoriasis (PsC)] were assessed yearly by rheumatologists for the presence of PsA. Patients with PsC who developed PsA (converters) were matched to those that did not develop PsA (nonconverters) based on psoriasis duration and the interval between follow-up visits. The duration between baseline and the first visit postconversion in converters was used to assign a pseudoconversion date in nonconverters. Linear mixed-effects models were used to model the expression of CXCL10 over time. RESULTS: CXCL10 significantly declined over time in converters prior to PsA development with a significant difference in the trend over time between converters (n = 29) and nonconverters (n = 52; P < 0·001). CXCL10 continued to decline after PsA onset in a subset of converters. There was a significant difference in the trend of CXCL10 levels between converters (n = 24) and nonconverters (n = 16; P = 0·01) preconversion/pseudoconversion. This difference remained postconversion (P = 0·006) and was not different from the preconversion period (P = 0·75). CONCLUSIONS: A large difference in CXCL10 was identified in patients with PsC that are destined to develop PsA over time. This exploratory analysis supports the association of CXCL10 with PsA development in patients with PsC and warrants further study of the predictive ability of this chemokine. What is already known about this topic? Chemokine (C-X-C motif) ligand 10 (CXCL10) is elevated in psoriatic affected tissues and serum and/or plasma. Patients with psoriasis that develop psoriatic arthritis (PsA) have elevated CXCL10 levels at baseline and these levels drop after arthritis onset. What does this study add? By monitoring levels of CXCL10 in serum over multiple visits in patients with psoriasis that develop PsA as well as those that do not develop PsA, an association was identified between CXCL10 and PsA development. What is the translational message? CXCL10 is a strong candidate for use by physicians for the detection of patients with psoriasis that are at risk of developing PsA. Linked Comment: Kirby and Fitzgerald. Br J Dermatol 2020; 183:805-806.

Molecular Characterization of the Major Open Reading Frames (ORFs) and Enhancer Elements From Four Geographically Distinct North American Equine Infectious Anemia Virus (EIAV) Isolates.

Although the equine lentivirus (equine infectious anemia virus [EIAV]) poses a major threat to equid populations throughout most regions of the world, detailed knowledge concerning its molecular epidemiology is still in its infancy. Such information is important because the few studies conducted to date suggest there is extensive genetic variation between viral isolates that if confirmed has significant implications for future vaccine design and development of newer diagnostic procedures. Here, we avoid potential assembly artifacts inherent in composite sequencing techniques by using long-range PCR in conjunction with next-generation sequencing for the rapid molecular characterization of all major open reading frames (ORFs) and known transcription factor binding motifs within the long terminal repeats (LTRs) of four North American EIAV isolates from Pennsylvania (EIAVPA), Tennessee (EIAVTN), North Carolina (EIAVNC), and Florida (EIAVFL). These were compared with complete published EIAV field strain genomic sequences from Asia (EIAVLIA, EIAVMIY), Europe (EIAVIRE), and North America (EIAVWY) plus EIAVUK a laboratory variant of EIAVWY. Phylogenetic analysis using the long-range PCR products suggested all the New World EIAV isolates comprised a single monophyletic group associated with EIAVIRE. This is distinct from the Asian isolates and so consistent with known historical details concerning the reintroduction of equids into North America by European settlers. Nonetheless nucleotide sequence identity for example between EIAVPA and EIAVTN, EIAVNC, EIAVFL, EIAVWY, EIAVUK plus EIAVIRE was limited to 84.6%, 81.0%, 82.1%, 80.4%, 80.1%, and 77.6%, respectively, with some of these values being not too dissimilar to those between EIAVPA and EIAVLIA or EIAVMIY at 78.0% and 75.4%, respectively. Overall, these results suggest substantial genetic diversity exists even within North American EIAV isolates. Comparative alignment of predicted amino acid sequences from all strains provides increased understanding concerning the extent of permitted substitutions in each viral ORF and known transcriptional LTR control elements.

Combined effects of HIV and obesity on the gastrointestinal microbiome of young men who have sex with men.

OBJECTIVES: The prevalence of obesity is rising among people living with HIV, which may synergistically increase inflammation and the risk of associated diseases. Disruption of gut bacterial communities may be one of the key drivers of this inflammation; however, the combined effects of HIV and obesity on the microbiome have not been explored. METHODS: This study included 381 men who have sex with men. Thirty-nine were HIV-positive and obese (H+O+), 143 were HIV-positive and nonobese, 64 were HIV-negative and obese, and 135 were HIV-negative and nonobese. Microbiome composition was assessed by targeted sequencing of the V4 region of the 16S ribosomal RNA (rRNA) gene using rectal swab samples. Inverse probability of treatment-weighted marginal structural models were used to investigate differences in microbial composition between groups while controlling for numerous clinical and behavioural confounders. RESULTS: Significant variability in microbial composition was explained by the combination of HIV and obesity, over and above each condition alone (R2 for the marginal contribution of the H+/O+ group = 0.008; P = 0.001). H+O+ participants had the highest ratios of Prevotella to Bacteroides, a pro-inflammatory enterotype that has been described in HIV infection and obesity independently. H+O+ participants had lower levels of Bacteroides and Veillonella than all other groups, suggesting a synergistic effect of HIV and obesity on these genera. CONCLUSIONS: Our findings support the hypothesis that HIV and obesity act together to disrupt gut microbial communities, which may help explain higher levels of generalized inflammation among people living with both HIV and obesity.

Real-time optical vascular imaging: a method to assess the microvascular circulation of myofascial free flaps used in the head and neck region.

Microvascular free flaps are considered the gold standard in head and neck reconstructive surgery. Myofascial flaps, in particular, are useful in certain oral and maxillofacial reconstruction cases, where mucosal regeneration over the transplanted tissue is planned. Despite high success rates, 1-6% of free flaps fail. A plethora of methods are available to assess transplanted tissue viability after reconstruction, including clinical observational monitoring, surface Doppler, implantable Doppler probe, colour Doppler sonography, laser Doppler flowmeter, surface temperature and indocyanine green angiography. However, no method has demonstrated adequate reliability or has proven to be cost-effective. The authors tested a technique called real-time optical vascular imaging to evaluate the microvascular circulation of myofascial free flaps. This technique was develop at Guy's Hospital, London to observe the microvascular anatomy of the oral cavity in vivo, non-invasively and without the need for patient preparation, with the aim of detecting and monitoring oral diseases. This technology detects the red blood cells flowing inside the microvasculature at a depth of approximately 2mm, allowing the microvascular architecture and blood flow to be determined. This study showed that RTOVI may prove to be beneficial for the early detection of vascular compromise due to its immediacy and the feasibility of assessing multiple graft tissue regions.

Validation of an Oral Disease Severity Score (ODSS) tool for use in oral mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease predominantly affecting the oral mucosa. Optimal management relies upon thorough clinical assessment and documentation at each visit. OBJECTIVES: The primary aim of this study was to validate the Oral Disease Severity Score (ODSS) for the assessment of oral involvement in MMP. We also compared its inter- and intraobserver reliability with those of the oral parts of the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Physician's Global Assessment (PGA). METHODS: Fifteen patients with mild-to-moderately severe oral MMP were scored for disease severity by 10 oral medicine clinicians from four U.K. centres using the ODSS, the oral sections of MMPDAI and ABSIS, and PGA. Two clinicians rescored all patients after 2 h. RESULTS: In terms of reliability, the interobserver ODSS total score intraclass correlation coefficient (ICC) was 0·97, MMPDAI activity 0·59 and damage 0·15, ABSIS total 0·84, and PGA 0·72. The intraobserver ICCs (two observers) for ODSS total were 0·97 and 0·93; for MMPDAI activity 0·93 and 0·70 and damage 0·93 and 0·79; for ABSIS total 0·99 and 0·94; and for PGA 0·92 and 0·94. Convergent validity between ODSS and MMPDAI was good (correlation coefficient 0·88). The mean ± SD time for completion of ODSS was 93 ± 31 s, with MMPDAI 102 ± 24 s and ABSIS involvement 71 ± 18 s. The PGA took < 5 s. CONCLUSIONS: This study has validated the ODSS for the assessment of oral MMP. It has shown superior interobserver agreement over MMPDAI, ABSIS and PGA, and superior intraobserver reliability to MMPDAI. It is quick and easy to perform. What's already known about this topic? There are no validated scoring methodologies for oral mucous membrane pemphigoid (MMP). Proposed disease activity scoring tools for MMP include the Mucous Membrane Disease Area Index (MMPDAI) and the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). The Oral Disease Severity Score (ODSS) has been validated for use in oral pemphigus vulgaris (PV). It has been shown to be reliable and sensitive in both lichen planus (LP) and MMP. What does this study add? The ODSS has been shown to be a thorough, sensitive and reproducible, yet quick scoring tool for the assessment of oral involvement in MMP. Its versatility for use in oral PV, MMP and LP is an added advantage over other scoring methodologies. What are the clinical implications of this work? We propose that the ODSS be used as a clinical scoring tool for monitoring activity in oral MMP in clinical practice as well as for use in multicentre studies.

Effect of Preheating and Fatiguing on Mechanical Properties of Bulk-fill and Conventional Composite Resin.

CLINICAL RELEVANCE: Bulk-fill composite resins may have comparable mechanical properties to conventional composite resin. Preheating does not reduce the mechanical properties of composite resins.

Material Flaw Populations and Component Strength Distributions in the Context of the Weibull Function.

A clear relationship between the population of brittle-fracture controlling flaws generated in a manufactured material and the distribution of strengths in a group of selected components is established. Assumptions regarding the strength-flaw size relationship, the volume of the components, and the number in the group, are clarified and the contracting effects of component volume and truncating effects of group number on component strength empirical distribution functions highlighted. A simple analytical example is used to demonstrate the forward prediction of population → distribution and the more important reverse procedure of empirical strength distribution → underlying flaw population. Three experimental examples are given of the application of the relationships to state-of-the-art micro- and nano-scale strength distributions to experimentally determine flaw populations: two on etched microelectromechanical systems (MEMS) structures and one on native and oxidized silicon nanowires. In all examples, the minimum threshold strength and conjugate maximum flaw size are very well estimated and the complete flaw population, including the minimum flaw size, are very poorly estimated, although etching, bimodal, and oxidation effects were clearly discernible. The results suggest that the best use of strength distribution information for MEMS manufacturers and designers might be in estimation of the strength threshold.

Goftte: A R package for assessing goodness-of-fit in proportional (sub) distributions hazards regression models.

BACKGROUND AND OBJECTIVE: In this paper, we introduce a new R package goftte for goodness-of-fit assessment based on cumulative sums of model residuals useful for checking key assumptions in the Cox regression and Fine and Gray regression models. METHODS: Monte-Carlo methods are used to approximate the null distribution of cumulative sums of model residuals. To limit the computational burden, the main routines used to approximate the null distributions are implemented in a parallel C++ programming environment. Numerical studies are carried out to evaluate the empirical type I error rates of the different testing procedures. The package and the documentation are available to users from CRAN R repositories. RESULTS: Results from simulation studies suggested that all statistical tests implemented in goftte yielded excellent control of the type I error rate even with modest sample sizes with high censoring rates. CONCLUSIONS: As compared to other R packages goftte provides new useful method for testing functionals, such as Anderson-Darling type test statistics for checking assumptions about proportional (sub-) distribution hazards. Approximations for the null distributions of test statistics have been validated through simulation experiments. Future releases will provide similar tools for checking model assumptions in multiplicative intensity models for recurrent data. The package may help to spread the use of recent advocated goodness-of-fit techniques in semiparametric regression for time-to-event data.