Influence of bisphosphonates on alveolar bone density: a histomorphometric analysis

This study is a histomorphometrical analysis of the influence of the bisphosphonate alendronate on alveolar bone density. Eighteen male Wistar rats were randomly assigned to a control group (n = 9) that received no medication and an experimental group (n = 9) that received oral alendronate (1 mg/kg) from birth until euthanization at 3 months of age. Semi-serial 4-µm-thick transverse sections were obtained from the region between the roots of the left maxillary first molar, stained with hematoxylin and eosin, and examined with a Zeiss Axioskop II optical microscope for histomorphometric analysis. The images were captured with a digital camera coupled with the microscope and connected to a computer, and were analyzed using Image J 1.34s image-analysis software. A 1,200-point grid was positioned onto each digitized image. The number of intersection points of grid lines in the bone tissue was counted. The ratio between the number of points in the bone tissue and the total number of points of the grid (1,200) was used to determine the bone density of the analyzed tissue. Data from the control and experimental groups were compared and analyzed statistically by the Student's t-test (p = 0.05). There was no statistically significant difference (p = 0.3754) in the alveolar bone density between the control and alendronate-treated animals. It may be concluded that the bisphosphonate alendronate did not alter the morphology of the alveolar bone, maintaining its structural tissue characteristics in healthy animals.São Paulo State Research Foundation (FAPESP) and a research postgraduate scholarship granted by the Brazilian Government Research Funding Agency CAPES. The authors are indebted to the Department of Physiology of Ribeirão Preto Dental School, University of São Paulo, Brazil, and to the histotechnician MS. Fátima Aparecida Silveira from the Service Pathology of Bauru Dental School, University of São Paulo (USP), Brazi

Pixel classification through Mahalanobis distance for identification of grapevine canopy elements on RGB images

Vine vigour and fruit-cluster exposure to sunlight in a grapevine canopy fruiting zone has been shown to strongly correlate with key fruit composition and diseases incidence. In this framework, the use of automated image analysis for the identification of plant elements is an important issue to be addressed for vineyard assessment (Dunn and Martin, 2004). In addition, optimum segmentation method is strongly application dependent and thus needs to be tested for each particular case (Cheng et al., 2001). The objective of the present work is to propose and test a simple, rapid and practical method for the identification of two relevant elements of grapevines canopy: clusters and green leaves

Reprint of “Atlantic Multidecadal Oscillation (AMO) modulates dynamics of small pelagic fishes and ecosystem regime shifts in the eastern North and Central Atlantic”

Dynamics of abundance and migrations of populations of small pelagic clupeoid fish such as anchovy (Engraulis encrasicolus), sardine (Sardina pilchardus), sardinella (Sardinella aurita), sprat (Sprattus sprattus) and herring (Clupea harengus) in the eastern North and Central Atlantic between Senegal and Norway vary in synchrony with the warm and cool phases of the Atlantic Multidecadal Oscillation (AMO). This is shown by compiling retrospective data on fish catches and anecdotal observations, which in some cases date back to the mid-19th century. The AMO is defined as the de-trended mean of North Atlantic (0-60 degrees N) sea surface temperature anomalies. However, it is not primarily the temperature which drives the dynamics of the small pelagic fish populations. Instead, the AMO seems to be a proxy for complex processes in the coupled atmosphere-ocean system of the North Atlantic. This is manifested in large-scale changes in strength and direction of the current system that move water masses around the North Atlantic and likely involves the North Atlantic Oscillation (NAO), the Atlantic Meridional Overturning Circulation (AMOC), the Mediterranean Overflow Water (MOW) and the subpolar gyre (SPG). The contractions and expansions of the SPG apparently play a key role. This was particularly obvious in the mid-1990s, when the SPG abruptly contracted with the result that warm subtropical water masses moved to the north and east. Small pelagic fish populations in the eastern North and Central Atlantic, including those in the Mediterranean responded quickly by changing abundances and migrating northwards. It seems that the complex ocean-atmosphere changes in the mid-1990s, which are described in the text in detail, caused a regime shift in the ecosystems of the eastern North and Central Atlantic and the small pelagic clupeoid fish populations are the sentinels of this shift

New decision rules under strict uncertainty and a general distance-based approach

Strict uncertainty implies a complete lack of knowledge about the probabilities of possible future states of the world. However, there is complete information about the set of alternatives under consideration, the set of future states, and the scalar evaluation of choosing every alternative if a given state occurs. The principle of insufficient reason by Laplace, the maximin rule by Wald, the Hurwicz criterion, or the minimax regret criterion by Savage are examples of decision rules under strict uncertainty. Within the context of strict uncertainty, moderate pessimism implies the existence of a decision-maker who cautiously assumes that the most favorable state will not occur when the action has been taken with no conjecture being made about the other states. The criterion of moderate pessimism proposed by Ballestero implies the use of the inverse of the range of evaluation for each state as a weight system. In this paper, we extend the notion of moderate pessimism under strict uncertainty to solve some of its limitations. First, we propose a new domination analysis that avoids removing dominated alternatives that are still relevant in the final ranking of alternatives. Second, we propose additional score functions using the inverse of the standard deviation and the mean absolute deviation instead of the range of evaluations for each future state to reduce the impact of the possible existence of outliers in the decision table. This partial result is later generalized through the concept of average deviation of a given order. Finally, we show that all the mentioned decision rules are special cases of a general ranking method based on the Minkowski distance function. We illustrate the use of distance-based decision rules through an application in the context of portfolio selection

The patient, diagnostic, and treatment intervals in adult patients with cancer from high- and lower-income countries: A systematic review and meta-analysis

Background: Longer time intervals to diagnosis and treatment are associated with worse survival for various types of cancer. The patient, diagnostic, and treatment intervals are considered core indicators for early diagnosis and treatment. This review estimated the median duration of these intervals for various types of cancer and compared it across high- and lower-income countries. Methods and findings: We conducted a systematic review with meta-analysis (prospectively registered protocol CRD42020200752). Three databases (MEDLINE, Embase, and Web of Science) and information sources including grey literature (Google Scholar, OpenGrey, EThOS, ProQuest Dissertations & Theses) were searched. Eligible articles were published during 2009 to 2022 and reported the duration of the following intervals in adult patients diagnosed with primary symptomatic cancer: patient interval (from the onset of symptoms to first presentation to a healthcare professional), diagnostic interval (from first presentation to diagnosis), and treatment interval (from diagnosis to treatment start). Interval duration was recorded in days and study medians were combined in a pooled estimate with 95% confidence intervals (CIs). The methodological quality of studies was assessed using the Aarhus checklist. A total of 410 articles representing 68 countries and reporting on 5,537,594 patients were included. The majority of articles reported data from high-income countries (n = 294, 72%), with 116 (28%) reporting data from lower-income countries. Pooled meta-analytic estimates were possible for 38 types of cancer. The majority of studies were conducted on patients with breast, lung, colorectal, and head and neck cancer. In studies from high-income countries, pooled median patient intervals generally did not exceed a month for most cancers. However, in studies from lower-income countries, patient intervals were consistently 1.5 to 4 times longer for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries. Across both high- and lower-income countries, the longest diagnostic intervals were observed for hematological (71 days [95% CI 52 to 85], e.g., myelomas (83 days [47 to 145])), genitourinary (58 days [50 to 77], e.g., prostate (85 days [57 to 112])), and digestive/gastrointestinal (57 days [45 to 67], e.g., colorectal (63 days [48 to 78])) cancers. Similarly, the longest treatment intervals were observed for genitourinary (57 days [45 to 66], e.g., prostate (75 days [61 to 87])) and gynecological (46 days [38 to 54], e.g., cervical (69 days [45 to 108]) cancers. In studies from high-income countries, the implementation of cancer-directed policies was associated with shorter patient and diagnostic intervals for several cancers. This review included a large number of studies conducted worldwide but is limited by survivor bias and the inherent complexity and many possible biases in the measurement of time points and intervals in the cancer treatment pathway. In addition, the subintervals that compose the diagnostic interval (e.g., primary care interval, referral to diagnosis interval) were not considered. Conclusions: These results identify the cancers where diagnosis and treatment initiation may take the longest and reveal the extent of global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries. Estimates for the diagnostic and treatment intervals came mostly from high-income countries that have powerful health information systems in place to record such information.This work was supported by the Spanish Association against Cancer (Asociación Española contra el Cáncer, PROYE20023SANC “High resolution study of social inequalities in cancer (HiReSIC)” to MJS), the Cancer Epidemiological Surveillance Subprogram of the CIBER of Epidemiology and Public Health and the Health Institute Carlos III (VICA to MJS), and the Health Institute Carlos III (PI18/01593 “Multilevel population-based study of socioeconomic inequalities in the geographical distribution of cancer incidence, mortality and net survival” to DP). DP is supported by a Juan de la Cierva Fellowship from the Ministry of Science and the National Research Agency of Spain (MCIN/AEI, JC2019-039691-I, http://doi.org/10.13039/501100011033, Accessed 4 October 2021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Who with suspected prostate cancer can benefit from Proclarix after multiparametric magnetic resonance imaging?

Cathepsin D; Magnetic resonance imaging; ProclarixCatepsina D; Imatges per ressonància magnètica; ProclarixCatepsina D; Imágenes por resonancia magnética; ProclarixProclarix is a new blood-based test to assess the likelihood of clinically significant prostate cancer (csPCa) defined as >2 grade group. In this study, we analyzed whether Proclarix and PSA density (PSAD) could improve the selection of candidates for prostate biopsy after multiparametric magnetic resonance imaging (mpMRI). Proclarix and PSAD were assessed in 567 consecutive men with suspected PCa in whom pre-biopsy 3 Tesla mpMRI, scoring with Prostate Imaging-Report and Data System (PI-RADS) v.2, and guided and/or systematic biopsies were performed. Proclarix and PSAD thresholds having csPCa sensitivity over 90% were found at 10% and 0.07 ng/(mL*cm3), respectively. Among 100 men with negative mpMRI (PI-RADS <3), csPCa was detected in 6 cases, which would have been undetected if systematic biopsies were avoided. However, Proclarix suggested performing a biopsy on 70% of men with negative mpMRI. In contrast, PSAD only detected 50% of csPCa and required 71% of prostate biopsies. In 169 men with PI-RADS 3, Proclarix avoided 21.3% of prostate biopsies and detected all 25 cases of csPCa, while PSAD avoided 26.3% of biopsies, but missed 16% of csPCa. In 190 men with PI-RADS 4 and 108 with PI-RADS 5, Proclarix avoided 12.1% and 5.6% of prostate biopsies, but missed 4.8% and 1% of csPCa, respectively. PSAD avoided 18.4% and 9.3% of biopsies, but missed 11.4% and 4.2% csPCa, respectively. We conclude that Proclarix outperformed PSAD in the selection of candidates for prostate biopsy, especially in men with PI-RADS <3.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Instituto de Salud Carlos III, (grant number PI20/01666)

The Efficacy of Proclarix to Select Appropriate Candidates for Magnetic Resonance Imaging and Derived Prostate Biopsies in Men with Suspected Prostate Cancer

Diagnosis; Proclarix; Prostate cancerDiagnóstico; Proclarix; Cáncer de próstataDiagnòstic; Proclarix; Càncer de pròstataPurpose To analyze how Proclarix is valuable to appropriately select candidates for multiparametric magnetic resonance imaging (mpMRI) and derived biopsies, among men with suspected prostate cancer (PCa). Proclarix is a new marker computing the clinically significant PCa (csPCa) risk, based on serum thosmbospondin-1, cathepsin D, prostate-specific antigen (PSA) and percent free PSA, in addition to age, that has been developed in men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and normal digital rectal examination (DRE). Materials and Methods Proclarix score (0%–100%) is analyzed in a prospective frozen serum collection of 517 correlative men scheduled for guided and/or systematic biopsies after mpMRI. Outcome variables were csPCa detection (grade group ≥2), insignificant PCa (iPCa) overdetection and avoided mpMRIs. Results The area under the curve of Proclarix was 0.701 (95% CI 0.637–0.765) among 281 men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and -normal DRE, and 0.754 (95% CI 0.701–0.807) in the others, p=0.038. Net benefit of Proclarix existed in all men. After selecting 10% threshold, Proclarix was integrated in an algorithm which also used the serum PSA level and DRE. A reduction of 25.4% of mpMRIs request was observed and 17.7% of prostate biopsies. Overdetection of iPCa was reduced in 18.2% and 2.6% of csPCa were misdiagnosed. Conclusions Proclarix is valuable in all men with suspected PCa. An algorithm integrating Proclarix score, serum PSA, and DRE can avoid mpMRI requests, unnecessary prostate biopsies and iPCa overdetection, with minimal loss of csPCa detection

Improving the Early Detection of Clinically Significant Prostate Cancer in Men in the Challenging Prostate Imaging-Reporting and Data System 3 Category

Clinically significant prostate cancer; Prostate Cancer predictive model; Multiparametric magnetic resonance imagingCáncer de próstata clínicamente significativo; Modelo predictivo de cáncer de próstata; Resonancia magnética multiparamétricaCàncer de pròstata clínicament significatiu; Model predictiu del càncer de pròstata; Imatge de ressonància magnètica multiparamètricaBackground Prostate Imaging-Reporting and Data System (PI-RADS) category 3 is a challenging scenario for detection of clinically significant prostate cancer (csPCa) and some tools can improve the selection of appropriate candidates for prostate biopsy. Objective To assess the performance of the European Randomized Study of Screening for Prostate Cancer (ERSPC) magnetic resonance imaging (MRI) model, the new Proclarix test, and prostate-specific antigen density (PSAD) in selecting candidates for prostate biopsy among men in the PI-RADS 3 category. Design, setting, and participants We conducted a head-to-head prospective analysis of 567 men suspected of having PCa for whom guided and systematic biopsies were scheduled between January 2018 and March 2020 in a single academic institution. A PI-RADS v.2 category 3 lesion was identified in 169 men (29.8%). Outcome measurement and statistical analysis csPCa, insignificant PCa (iPCa), and unnecessary biopsy rates were analysed. csPCa was defined as grade group ≥2. Receiver operating characteristic (ROC) curves, decision curve analysis curves, and clinical utility curves were plotted. Results and limitations PCa was detected in 53/169 men (31.4%) with a PI-RADS 3 lesion, identified as csPCa in 25 (14.8%) and iPCa in 28 (16.6%). The area under the ROC curve for csPCa detection was 0.703 (95% confidence interval [CI] 0.621–0.768) for Proclarix, 0.657 (95% CI 0.547–0.766) for the ERSPC MRI model, and 0.612 (95% CI 0.497–0.727) for PSAD (p = 0.027). The threshold with the highest sensitivity was 10% for Proclarix, 1.5% for the ERSPC MRI model, and 0.07 ng/ml/cm3 for PSAD, which yielded sensitivity of 100%, 91%, and 84%, respectively. Some 21.3%, 26.2%, and 7.1% of biopsies would be avoided with Proclarix, PSAD, and the ERSPC MRI model, respectively. Proclarix showed a net benefit over PSAD and the ERSPC MRI model. Both Proclarix and PSAD reduced iPCa overdetection from 16.6% to 11.3%, while the ERSPC MRI model reduced iPCa overdetection to 15.4%. Conclusions Proclarix was more accurate in selecting appropriate candidates for prostate biopsy among men in the PI-RADS 3 category when compared to PSAD and the ERSPC MRI model. Proclarix detected 100% of csPCa cases and would reduce prostate biopsies by 21.3% and iPCa overdetection by 5.3%