Determining the potential for malignant transformation of oral lichen planus (OLP) is complicated by difficulties in diagnosis, differentiation from oral lichenoid lesions (OLLs) and the phenomenon ...of premalignant lesions' exhibiting lichenoid characteristics. The authors of this systematic review evaluated evidence regarding malignant transformation of OLP and characterized transformation prevalence, clinical characteristics of OLP lesions developing into squamous cell carcinoma (SCC) and time to transformation.
The authors searched PubMed, Embase and Thomson Reuters Web of Science in a systematic approach. They evaluated observational English-language studies involving human participants published in peer-reviewed journals. Inclusion required patients to have the diagnosis of OLP or OLL as confirmed with biopsy results on initial enrollment. They excluded all patients who had dysplasia on initial biopsy of OLP or OLL lesions.
Sixteen studies were eligible. Among 7,806 patients with OLP, 85 developed SCC. Among 125 patients with OLL, four developed SCC. The rate of transformation in individual studies ranged from 0 to 3.5 percent. The overall rate of transformation was 1.09 percent for OLP; in the solitary study in which investigators evaluated OLL, the rate of transformation was 3.2 percent. Patients' average age at onset of SCC was 60.8 years. The authors noted a slight predominance of female patients among those who experienced malignant transformation. The most common subsite of malignant transformation was the tongue. The average time from diagnosis of OLP or OLL to transformation was 51.4 months.
A small subset of patients with a diagnosis of OLP eventually developed SCC. The most common demographic characteristics of patients in this subset were similar to the most common demographic characteristics associated with OLP in general (that is, being female, being older and being affected in areas common to this condition). It is prudent for clinicians to pursue continued regular observation and follow-up in patients with these conditions, even in patients who do not fit a traditional high-risk category for oral SCC.
In recent years, serious concerns have arisen about reproducibility in science. Estimates of the cost of irreproducible preclinical studies range from 28 billion USD per year in the USA alone ...(Freedman et al. in PLoS Biol 13(6):e1002165,
2015
) to over 200 billion USD per year worldwide (Chalmers and Glasziou in Lancet 374:86–89,
2009
). The situation in the social sciences is not very different: Reproducibility in psychological research, for example, has been estimated to be below 50% as well (Open Science Collaboration in Science 349:6251,
2015
). Less well studied is the issue of reproducibility of simulation research. A few replication studies of agent-based models, however, suggest the problem for computational modeling may be more severe than for laboratory experiments (Willensky and Rand in JASSS 10(4):2,
2007
; Donkin et al. in Environ Model Softw 92:142–151,
2017
; Bajracharya and Duboz in: Proceedings of the symposium on theory of modeling and simulation—DEVS integrative M&S symposium, pp 6–11,
2013
). In this perspective, we discuss problems of reproducibility in agent-based simulations of life and social science problems, drawing on best practices research in computer science and in wet-lab experiment design and execution to suggest some ways to improve simulation research practice.
In recent years, concern has grown about the inappropriate application and interpretation of P values, especially the use of P<0.05 to denote "statistical significance" and the practice of P-hacking ...to produce results below this threshold and selectively reporting these in publications. Such behavior is said to be a major contributor to the large number of false and non-reproducible discoveries found in academic journals. In response, it has been proposed that the threshold for statistical significance be changed from 0.05 to 0.005. The aim of the current study was to use an evolutionary agent-based model comprised of researchers who test hypotheses and strive to increase their publication rates in order to explore the impact of a 0.005 P value threshold on P-hacking and published false positive rates. Three scenarios were examined, one in which researchers tested a single hypothesis, one in which they tested multiple hypotheses using a P<0.05 threshold, and one in which they tested multiple hypotheses using a P<0.005 threshold. Effects sizes were varied across models and output assessed in terms of researcher effort, number of hypotheses tested and number of publications, and the published false positive rate. The results supported the view that a more stringent P value threshold can serve to reduce the rate of published false positive results. Researchers still engaged in P-hacking with the new threshold, but the effort they expended increased substantially and their overall productivity was reduced, resulting in a decline in the published false positive rate. Compared to other proposed interventions to improve the academic publishing system, changing the P value threshold has the advantage of being relatively easy to implement and could be monitored and enforced with minimal effort by journal editors and peer reviewers.
We present the first Fermi Space Telescope Gamma Ray Burst Monitor (GBM) catalog of 4,144 terrestrial gamma ray flashes (TGFs), detected since launch in 11 July 2008 through 31 July 2016. We discuss ...the updates and improvements to the triggered data and off‐line search algorithms, comparing this improved detection rate of ∼800 TGFs per year with event rates from previously published TGF catalogs from other missions. A Bayesian block algorithm calculated the temporal and spectral properties of the TGFs, revealing a delay between the hard (>300 keV) and soft (≤300 keV) photons of around 27 μs. Detector count rates of “low‐fluence” events were found to have average rates exceeding 150 kHz. Searching the World‐Wide Lightning Location Network data for radio sferics within ±5 min of each TGF revealed a clean sample of 1,314 World‐Wide Lightning Location Network locations, which were used to to accurately locate TGF‐producing storms. It also revealed lightning and storm activity for specific regions, as well as seasonal and daily variations of global lightning patterns. Correcting for the orbit of Fermi, we quantitatively find a marginal excess of TGFs being produced from storms over land near oceans (i.e., narrow isthmuses and small islands). No difference was observed between the duration of TGFs over the ocean and land. The distribution of TGFs at a given local solar time for predefined American, Asian, and African regions were confirmed to correlate well with known regional lightning rates.
Key Points
This catalog contains the largest released samples of TGFs and associated radio data
This study shows quantitatively that TGFs preferentially occur over land near coastlines
A Bayesian block algorithm was used to extract the spectral and temporal properties of each TGF
Ulcerated lesions of the oral cavity have many underlying etiologic factors, most commonly infection, immune related, traumatic, or neoplastic. A detailed patient history is critical in assessing ...ulcerative oral lesions and should include a complete medical and medication history; whether an inciting or triggering trauma, condition, or medication can be identified; the length of time the lesion has been present; the frequency of episodes in recurrent cases; the presence or absence of pain; and the growth of the lesion over time. For multiple or recurrent lesions the presence or history of ulcers on the skin, genital areas, or eyes should be evaluated along with any accompanying systemic symptoms such as fever, arthritis, or other signs of underlying systemic disease. Biopsy may be indicated in many ulcerative lesions of the oral cavity although some are more suitable for clinical diagnosis. Neoplastic ulcerated lesions are notorious in the oral cavity for their ability to mimic benign ulcerative lesions, highlighting the essential nature of biopsy to establish a diagnosis in cases that are not clinically identifiable or do not respond as expected to treatment. Adjunctive tests may be required for final diagnosis of some ulcerated lesions especially autoimmune lesions. Laboratory tests or evaluation to rule out systemic disease may be also required for recurrent or severe ulcerations especially when accompanied by other symptoms. This discussion will describe the clinical and histopathologic characteristics of a variety of ulcerated lesions found in the oral cavity.
Background
Uncontrolled hemorrhage is responsible for ∼80% of the potentially survivable deaths in combat and over 40% of early mortality in the under 65 age group in the United States. Providing an ...easily used infusible hemostatic agent to first responders could significantly reduce these fatalities. We report on an infusible lyophilized platelet‐derived hemostatic agent stabilized with trehalose and polysucrose prior to and during lyophilization.
Study Design and Methods
Characterization included determining the particle population size range, surface marker expression GPIb, GPIIbIIIa, and Annexin V binding. Function was assessed by aggregation, thromboelastography, and thrombin generation. Pharmacokinetics, biodistribution, and immunogenicity established using Indium111 labeled Thrombosomes in healthy New Zealand white rabbits (NZWRs), efficacy in thrombocytopenic NZWR, and safety in NZWRs, canines, and nonhuman primates.
Results
Thrombosomes retained GPIIbIIIa expression (98.71% ± 0.18 of the rehydrated particles), a reduced expression of GPIb (47.77% ± 6.65), and Annexin V binding (86.05% ± 2.65). Aggregation to all agonists except thrombin in buffer (78.15% ± 2.5) was <50%. Thrombin generation and thromboelastography results demonstrated a concentration gradient that was consistent from lot to lot. There were no observed adverse events in any safety study and blood loss was reduced by >80% in the thrombocytopenic ear bleed model.
Conclusion
Our in vitro characterization studies in conjunction with preclinical animal safety and efficacy studies demonstrated lot consistency in manufacturing, maintenance of hemostatic functions of Thrombosomes, safety at high dose concentrations, and the potential to provide an effective hemostatic agent at the site of injury.
Controlling hemorrhage has been a focus of survival since man recognized that the loss of blood led to death. Papyri from 1600 BCE describe methods for hemorrhage control including; direct pressure, ...ligature and the use of sutures. Multiple studies have demonstrated the survival advantage of early transfusion of whole blood or red cells and plasma. The added survival impact of early transfusion of platelets was recently reported in a substudy of the prospective Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. Early transfusion of platelets demonstrated a statistically significant survival benefit at 24 h and 30 days post-injury. 1 Platelet availability is limited due to the short shelf life (5–7 days) and storage requirements (room temperature with constant agitation). Providing platelets or platelet derived products for prehospital treatment and to rural and some urban hospitals is an unmet medical need. The interest in novel and alternative platelet products has grown over the past decade and the status of novel platelet products is presented herein. Development, approval, and distribution of hemostatically effective approved platelet products for prehospital use and routine stockage in rural and urban centers could significantly increase survival rates in bleeding patients.
Significance Evolutionary methods are increasingly being applied to investigating linguistic change. But does language change conform to the predictions of evolutionary theory? Here, we use data from ...closely related pairs of languages to show that a key prediction of evolutionary theory is met: rates of gain of new words are higher in larger populations whereas rates of word loss are greater in small populations. Our analysis provides, to our knowledge, the first statistically robust evidence of an influence of population size on rate of language change. These results demonstrate the potential for demographic factors to influence language evolution.
The effect of population size on patterns and rates of language evolution is controversial. Do languages with larger speaker populations change faster due to a greater capacity for innovation, or do smaller populations change faster due to more efficient diffusion of innovations? Do smaller populations suffer greater loss of language elements through founder effects or drift, or do languages with more speakers lose features due to a process of simplification? Revealing the influence of population size on the tempo and mode of language evolution not only will clarify underlying mechanisms of language change but also has practical implications for the way that language data are used to reconstruct the history of human cultures. Here, we provide, to our knowledge, the first empirical, statistically robust test of the influence of population size on rates of language evolution, controlling for the evolutionary history of the populations and formally comparing the fit of different models of language evolution. We compare rates of gain and loss of cognate words for basic vocabulary in Polynesian languages, an ideal test case with a well-defined history. We demonstrate that larger populations have higher rates of gain of new words whereas smaller populations have higher rates of word loss. These results show that demographic factors can influence rates of language evolution and that rates of gain and loss are affected differently. These findings are strikingly consistent with general predictions of evolutionary models.
We report on the spectral analysis of individual terrestrial gamma‐ray flashes (TGFs) observed with the Fermi Gamma‐ray Burst Monitor (GBM). The large GBM TGF sample provides 46 events suitable for ...individual spectral analysis: sufficiently bright, localized by ground‐based radio, and with the gamma rays reaching a detector unobstructed. These TGFs exhibit diverse spectral characteristics that are hidden when using summed analysis methods. We account for the low counts in individual TGFs by using Poisson likelihood, and we also consider instrumental effects. The data are fit with models obtained from Monte Carlo simulations of the large‐scale Relativistic Runaway Electron Avalanche (RREA) model, including propagation through the atmosphere. Source altitudes ranging from 11.6 to 20.2 km are simulated. Two beaming geometries were considered: In one, the photons retain the intrinsic distribution from scattering (narrow), and in the other, the photons are smeared into a wider beam (wide). Several TGFs are well fit only by narrow‐beam models, while others favor wide‐beam models. Large‐scale RREA models can accommodate both narrow and wide beams, with narrow beams suggest large‐scale RREA in organized electric fields while wide beams may imply converging or diverging electric fields. Wide beams are also consistent with acceleration in the electric fields of lightning leaders, but the TGFs that favor narrow‐beam models appear inconsistent with some lightning leader models.
Key Points
Spectral analysis of individual TGFs is done
Individual TGFs exhibit spectral diversity
Constraints on TGF source properties are obtained
Abstract Objectives Periodontal disease has long been linked to many systemic diseases, and recently a link between periodontal disease and cancer has been established. The purpose of this paper is ...to review the literature to explore the evidence to date of a relationship between periodontal disease and cancer. In addition, the main hypotheses for the association are discussed along with challenges in evaluating the evidence. Data/sources/study selection In this review, English-language papers studying the relationship between periodontal disease or tooth loss in humans and increased risk of several types of cancers along with overall cancer risk between 1990 and April 2009 were reviewed. Conclusions The most consistent increased risk was noted in studies of oral and esophageal cancers and periodontal disease. Gastric and pancreatic cancers had an association in most but not all studies. Lung, prostate, hematologic and other cancers were less consistently associated or did not have sufficient studies to determine a predictable pattern. Studies to date indicate a positive correlation between several forms of cancer and periodontal disease.
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