Publications by authors named "Ricardo Martinez"

89 Publications

Ear and Hearing Care Workforce: Current Status and its Implications.

Ear Hear 2021 Jan 21;42(2):249-257. Epub 2021 Jan 21.

Department of Noncommunicable Diseases, World Health Organization, Geneva, Switzerland.

Objective: This study aimed to provide comprehensive global evidence on the availability of ear and hearing care (EHC) professionals and real-life examples that showcase the impact of workforce shortages on the workload faced by existing professionals.

Methods: Six sources of data were used to estimate availability of EHC workforce: a scoping literature review, World Health Organization (WHO) National Health Workforce Accounts platform, WHO Member States survey and regional consultations, hearing care organizations survey, and official government statistics. EHC professionals' workload undertaking common interventions was estimated through the WHO workload indicators of staffing need human resource management tool.

Results: With data on otolaryngologists from 138, audiologists from 102, speech and language therapists from 124, and teachers of the deaf from 86 countries, this study revealed large gaps in availability of EHC cadres. The majority of countries in the African region had less than one professional in each cadre per million in comparison with most European countries having up to 50 times higher densities. Workload indicators of staffing need calculations revealed the challenging workload faced by existing EHC professionals, with ratios between existing and required staff of 0.01-0.86.

Conclusion: There is an enormous shortage of EHC professionals and urgent actions are needed to ensure sufficient and equitable access to services. Task sharing, a novel approach for improving access to hearing care alongside the development of new cadres, can be a vital strategy in overcoming the shortage of highly qualified providers in many settings, even in well-resourced health systems, to facilitate equitable access to required EHC services.
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http://dx.doi.org/10.1097/AUD.0000000000001007DOI Listing
January 2021

[Map of ethics conflicts in chronic patient's hospitalization].

Cuad Bioet 2020 Sep-Dec;31(103):367-375

Unidad de Hospitalización. Hospital Bernal. Calle del Dr. Robles sin número, Caravaca de la Cruz, Murcia, España.

The identification, priorization and anticipation of the ethics conflicts, allow the Healthcare Ethics Committees (HEC) a better approach to them, as well as the adoption of measures to prevent its appearance and/or its mitigation. For this purpose, we set ourselves the objective of knowing what they are in the present, how important they are, and what would be the future scenario to face. An qualitative structure research was made whit two focal groups whit the participation of nurses, nurse auxiliary and doctors from the hospitalization area, they also answer a future ethics conflicts Decalogue. The results were tested after by their importance level (Relevance-Frequency-Consistency). The medium age of the participants was 34,7 +- 15,4, whit a medium experience at work of 11,7 +- 15,4 years. A total of 40 ethics conflicts was identify grouped in 5 risk areas: professional, assistance, social, organizational and legal. From there 21 results the more important, between them we find patient abandonment, inexistence of internal performance protocols, patient and relatives false expectations waiting for non-assistance care, unnecessary care at the end of the life, lack of rules for family / caregivers, and ignorance of legality. The more important ethical dilemmas for the future identified by the personal will be patients in abandonment, the lack of sociohealth resources, conflicts with family / caregivers situation and lack of information for decision making at the end of the life. The ethical conflicts between the personal from a chronic patients hospital and the relatives/caregivers was identifying, the most important were prioritized, and futures were anticipated. In these scenarios, we highlight abandonment as the most important. A map of ethics conflicts is a good tool to identify risk areas for ethics conflicts, we see the difference between the ethics conflicts found in other kind of hospitals. The map of ethics conflicts need to be update periodically to keep the validity.
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http://dx.doi.org/10.30444/CB.76DOI Listing
February 2019

The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor-Positive Metastatic Breast Cancer.

Cancer Discov 2020 Aug 13;10(8):1174-1193. Epub 2020 May 13.

Center for Cancer Precision Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts.

Mechanisms driving resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor-positive (HR) breast cancer have not been clearly defined. Whole-exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate resistance mechanisms including loss, activating alterations in , and , and loss of estrogen receptor expression. experiments confirmed that these alterations conferred CDK4/6i resistance. Cancer cells cultured to resistance with CDK4/6i also acquired , or alterations, which conferred sensitivity to AURKA, ERK, or CHEK1 inhibition. Three of these activating alterations-in , and -have not, to our knowledge, been previously demonstrated as mechanisms of resistance to CDK4/6i in breast cancer preclinically or in patient samples. Together, these eight mechanisms were present in 66% of resistant tumors profiled and may define therapeutic opportunities in patients. SIGNIFICANCE: We identified eight distinct mechanisms of resistance to CDK4/6i present in 66% of resistant tumors profiled. Most of these have a therapeutic strategy to overcome or prevent resistance in these tumors. Taken together, these findings have critical implications related to the potential utility of precision-based approaches to overcome resistance in many patients with HR metastatic breast cancer..
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http://dx.doi.org/10.1158/2159-8290.CD-19-1390DOI Listing
August 2020

Understanding Participation in Genetic Research Among Patients With Multiple Sclerosis: The Influences of Ethnicity, Gender, Education, and Age.

Front Genet 2020 13;11:120. Epub 2020 Mar 13.

John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, United States.

This study examined reasons for participation in a genetic study of risk for multiple sclerosis (MS). Our sample consisted of 101 patients diagnosed with MS who were approached about enrolling in the Multiple Sclerosis Genetic Susceptibility Study. Participants were predominantly Hispanic (80%), female (80%), and well educated (71%), having at least some level of college education. Of these 101 individuals who were approached, 95 agreed to participate and are the focus of this report. Among enrollees, the most frequently cited reasons for participation were to find a cure for MS (56%), having MS (46%), and helping future generations (37%). Regression models comparing ethnic groups, Hispanics endorsed having MS as a reason to participate significantly more frequently than non-Hispanics (HI 52%, non-HI 19%, p = 0.015) while non-Hispanics endorsed finding new and better treatments significantly more frequently than Hispanics (Hispanic 17%, non-Hispanic 50%, p = 0.003). Among our three age groups, younger individuals endorsed finding a cure for MS significantly more frequently (74% of 18-35-year olds vs. 56% of 36-55 year olds vs. 39% of >55 year olds). Our results suggest that motivations for participation in genetic research vary by ethnicity, and that these influences need to be considered in developing more inclusive programs of disease-related genetic research. Future efforts should focus on development of standard methods for understanding participation in genetic and genomic research, especially among underrepresented groups as a catalyst for engaging all populations.
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http://dx.doi.org/10.3389/fgene.2020.00120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082924PMC
March 2020

Mania as Debut of Cushing's Syndrome.

Case Rep Psychiatry 2020 4;2020:9127632. Epub 2020 Mar 4.

Department of Psychiatry, Vigo Health Area, Hospital Álvaro Cunqueiro, Spain.

This is a case of a patient affected by Cushing syndrome that was admitted at the hospital due to hormonal problems. He had presented psychiatric symptoms that were mistakenly considered not directly connected to the pathology causing the clinical condition, but a mere psychological reaction to it.
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http://dx.doi.org/10.1155/2020/9127632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073507PMC
March 2020

A pan-cancer transcriptome analysis identifies replication fork and innate immunity genes as modifiers of response to the CHK1 inhibitor prexasertib.

Oncotarget 2020 Jan 21;11(3):216-236. Epub 2020 Jan 21.

Eli Lilly and Company, Indianapolis, IN, USA.

The combined influence of oncogenic drivers, genomic instability, and/or DNA damage repair deficiencies increases replication stress in cancer. Cells with high replication stress rely on the upregulation of checkpoints like those governed by CHK1 for survival. Previous studies of the CHK1 inhibitor prexasertib demonstrated activity across multiple cancer types. Therefore, we sought to (1) identify markers of prexasertib sensitivity and (2) define the molecular mechanism(s) of intrinsic and acquired resistance using preclinical models representing multiple tumor types. Our findings indicate that while cyclin E dysregulation is a driving mechanism of prexasertib response, biomarkers associated with this aberration lack sufficient predictive power to render them clinically actionable for patient selection. Transcriptome analysis of a pan-cancer cell line panel and models revealed an association between expression of E2F target genes and prexasertib sensitivity and identified innate immunity genes associated with prexasertib resistance. Functional RNAi studies supported a causal role of replication fork components as modulators of prexasertib response. Mechanisms that protect cells from oncogene-induced replication stress may safeguard tumors from such stress induced by a CHK1 inhibitor, resulting in acquired drug resistance. Furthermore, resistance to prexasertib may be shaped by innate immunity.
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http://dx.doi.org/10.18632/oncotarget.27400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980627PMC
January 2020

Regimens of vitamin D supplementation for women during pregnancy.

Cochrane Database Syst Rev 2019 Oct 3;10:CD013446. Epub 2019 Oct 3.

Department of Dietetics and Nutrition, Robert Stempel College of Public Health and Social Work, Florida International University, 11200 SW 8th Street, AHC 5 - 323, Miami, Florida, USA, 33199.

Background: Vitamin D deficiency during pregnancy increases the risk of pre-eclampsia, gestational diabetes, preterm birth, and low birthweight. In a previous Cochrane Review we found that supplementing pregnant women with vitamin D alone compared to no vitamin D supplementation may reduce the risk of pre-eclampsia, gestational diabetes, and low birthweight and may increase the risk of preterm births if it is combined with calcium. However the effects of different vitamin D regimens are not yet clear.

Objectives: To assess the effects and safety of different regimens of vitamin D supplementation alone or in combination with calcium or other vitamins, minerals or nutrients during pregnancy, specifically doses of 601 international units per day (IU/d) or more versus 600 IU/d or less; and 4000 IU/d or more versus 3999 IU/d or less.

Search Methods: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (12 July 2018), and the reference lists of retrieved studies.

Selection Criteria: Randomised trials evaluating the effect of different vitamin D regimens (dose, frequency, duration, and time of commencement of supplementation during pregnancy), alone or in combination with other nutrients on pregnancy and neonatal health outcomes. We only included trials that compared 601 IU/d or more versus 600 IU/d or less and 4000 IU/d or more versus 3999 IU/d or less. We did not include in the analysis groups that received no vitamin D, as that comparison is assessed in another Cochrane Review.

Data Collection And Analysis: Two review authors independently: i) assessed the eligibility of studies against the inclusion criteria; ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Our primary maternal outcomes were: pre-eclampsia, gestational diabetes, and any adverse effects; our primary infant outcomes were preterm birth and low birthweight. Data were checked for accuracy. The certainty of the evidence was assessed using the GRADE approach.

Main Results: In this review, we included data from 30 trials involving 7289 women. We excluded 11 trials, identified 16 ongoing/unpublished trials and two trials are awaiting classification. Overall risk of bias for the trials was mixed.Comparison 1. 601 IU/d or more versus 600 IU/d or less of vitamin D alone or with any other nutrient (19 trials; 5214 participants)Supplementation with 601 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of pre-eclampsia (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.42); 5 trials; 1553 participants,low-certainty evidence), may reduce the risk of gestational diabetes (RR 0.54, 95% CI 0.34 to 0.86; 5 trials; 1846 participants; moderate-certainty evidence), may make little or no difference to the risk of preterm birth (RR 1.25, 95% CI 0.92 to 1.69; 4 trials; 2294 participants; low-certainty evidence); and may make little or no difference to the risk of low birthweight (RR 0.90, 95% CI 0.66 to 1.24; 4 trials; 1550 participants; very low-certainty evidence) compared to women receiving 600 IU/d or less.Comparison 2. 4000 IU or more versus 3999 IU or less of vitamin D alone (15 trials; 4763 participants)Supplementation with 4000 IU/d or more of vitamin D during pregnancy may make little or no difference to the risk of: pre-eclampsia (RR 0.87, 95% CI 0.62 to 1.22; 4 trials, 1903 participants, low-certainty evidence); gestational diabetes (RR 0.89, 95% CI 0.56 to 1.42; 5 trials, 2276 participants; low-certainty evidence); preterm birth (RR 0.85, 95% CI 0.64 to 1.12; 6 trials, 2948 participants, low-certainty evidence); and low birthweight (RR 0.92, 95% CI 0.49 to 1.70; 2 trials; 1099 participants; low-certainty evidence) compared to women receiving 3999 IU/d or less.Adverse events (such as hypercalcaemia, hypocalcaemia, hypercalciuria, and hypovitaminosis D) were reported differently in most trials; however, in general, there was little to no side effects reported or similar cases between groups.

Authors' Conclusions: Supplementing pregnant women with more than the current vitamin D recommendation may reduce the risk of gestational diabetes; however, it may make little or no difference to the risk of pre-eclampsia, preterm birth and low birthweight. Supplementing pregnant women with more than the current upper limit for vitamin D seems not to increase the risk of the outcomes evaluated. In general, the GRADE was considered low certainty for most of the primary outcomes due to serious risk of bias and imprecision of results. With respect to safety, it appears that vitamin D supplementation is a safe intervention during pregnancy, although the parameters used to determine this were either not reported or not consistent between trials. Future trials should be consistent in their reports of adverse events. There are 16 ongoing trials that when published, will increase the body of knowledge.
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http://dx.doi.org/10.1002/14651858.CD013446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776191PMC
October 2019

Aurora A-Selective Inhibitor LY3295668 Leads to Dominant Mitotic Arrest, Apoptosis in Cancer Cells, and Shows Potent Preclinical Antitumor Efficacy.

Mol Cancer Ther 2019 12 17;18(12):2207-2219. Epub 2019 Sep 17.

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.

Although Aurora A, B, and C kinases share high sequence similarity, especially within the kinase domain, they function distinctly in cell-cycle progression. Aurora A depletion primarily leads to mitotic spindle formation defects and consequently prometaphase arrest, whereas Aurora B/C inactivation primarily induces polyploidy from cytokinesis failure. Aurora B/C inactivation phenotypes are also epistatic to those of Aurora A, such that the concomitant inactivation of Aurora A and B, or all Aurora isoforms by nonisoform-selective Aurora inhibitors, demonstrates the Aurora B/C-dominant cytokinesis failure and polyploidy phenotypes. Several Aurora inhibitors are in clinical trials for T/B-cell lymphoma, multiple myeloma, leukemia, lung, and breast cancers. Here, we describe an Aurora A-selective inhibitor, LY3295668, which potently inhibits Aurora autophosphorylation and its kinase activity and , persistently arrests cancer cells in mitosis, and induces more profound apoptosis than Aurora B or Aurora A/B dual inhibitors without Aurora B inhibition-associated cytokinesis failure and aneuploidy. LY3295668 inhibits the growth of a broad panel of cancer cell lines, including small-cell lung and breast cancer cells. It demonstrates significant efficacy in small-cell lung cancer xenograft and patient-derived tumor preclinical models as a single agent and in combination with standard-of-care agents. LY3295668, as a highly Aurora A-selective inhibitor, may represent a preferred approach to the current pan-Aurora inhibitors as a cancer therapeutic agent.
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http://dx.doi.org/10.1158/1535-7163.MCT-18-0529DOI Listing
December 2019

Diabetes and Its Effect on Abdominal Aortic Aneurysm Growth Rate in Hispanic Patients.

Ann Vasc Surg 2019 Nov 5;61:254-260. Epub 2019 Aug 5.

Research Institute, Doctors Hospital at Renaissance Health System, Edinburg, TX; Department of Surgery, University of Texas Rio Grande Valley School of Medicine, Edinburg, TX.

Background: The growth rate of abdominal aortic aneurysms (AAA) can vary depending on age, baseline diameter, blood pressure, race, and history of smoking. Paradoxically, previous studies show evidence of a protective effect of diabetes on the rate of AAA expansion despite its well-established role in the morbidity and mortality of cardiovascular disease. This study aims to investigate the impact diabetes plays on AAA growth within a Hispanic population.

Methods: Data were collected from patients who were predominantly Mexican-American at a single hospital site. Baseline and follow-up measures for AAA diameter were obtained from serial imaging studies. Demographics, medical history, the presence of type 2 diabetes, and medication use were extracted from hospital records. Linear mixed-effects growth models were used to calculate the overall AAA growth rate and to assess the difference in AAA growth rate between demographics, comorbidities, and medication use.

Results: The study comprised 201 patients (70.4% male) with a mean baseline age of 79.1 years, of whom 43.2% were diabetic. The average monthly AAA growth rate across all study participants was 0.15 mm (SE = 0.02 mm). Independently, the average AAA expansion rate for the diabetic and nondiabetic groups was 0.07 mm (SE = 0.04 mm) and 0.21 mm (SE = 0.03 mm) per month, respectively. This demonstrates a 65% lower linear AAA expansion rate per month in patients with diabetes.

Conclusions: This study confirms a difference of AAA physiology between diabetics and nondiabetics in the Hispanic community. The observed significant difference in AAA growth rate may be a combination of factors associated with race/ethnicity, prevalence of diabetes mellitus, and low compliance with diabetic control exhibited in the Mexican-American population.
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http://dx.doi.org/10.1016/j.avsg.2019.06.004DOI Listing
November 2019

First record of a basal mammaliamorph from the early Late Triassic Ischigualasto Formation of Argentina.

PLoS One 2019 7;14(8):e0218791. Epub 2019 Aug 7.

Jackson School of Geosciences, The University of Texas at Austin, Austin, Texas, United States of America.

We describe a new probainognathian cynodont, Pseudotherium argentinus, from the early Late Triassic Ischigualasto Formation of Argentina. Pseudotherium adds to a growing assemblage of small Triassic cynodonts that offers new insight into events leading up to the origin of crown Mammalia and the successively more inclusive Mammaliaformes and Mammaliamorpha. Using high-resolution X-ray computed tomography, we illustrate and describe the holotype and only known specimen, which consists of a well-preserved isolated skull. It preserves apomorphic features of the orbit and braincase. Prefrontal and vestigial postorbital bones are present, despite the absence of an ossified postorbital bar. As in Brasilitherium riograndensis, thin turbinal-like bones are present in the nasopharyngeal passage, and we discuss impediments to establishing their identity and function. Compared to more basal cynodonts, the cochlea is elongated but uncoiled and in this and other features it resembles basal mammaliamorphs. Our analysis found weak support for Pseudotherium as the sister taxon of Tritylodontidae. However, a broader assessment of its relationships in light of additional character data from the literature and unpublished computed tomography data suggest that it may be more realistic to view the relationships of Pseudotherium as an unresolved polytomy with tritylodontids, and the taxa referred to as tritheledontids and brasilodontids (groups of variable membership and questionable monophyly). Thus, Pseudotherium may lie just inside or just outside of Mammaliamorpha, and there is also weak character support for its sister taxon relationship with Brasilitherium. Our results amplify previous conclusions that phylogenetic relationships in this adaptive radiation of small cynodonts will remain somewhat uncertain until more complete specimens are recovered, and until high-resolution CT scans of existing specimens become available to the larger community. Toward that goal, we make the CT dataset for the holotype of Pseudotherium argentinus publically available under a Creative Commons license at www.DigiMorph.org.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218791PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685608PMC
February 2020

Resection of Cavity Shave Margins in Stage 0-III Breast Cancer Patients Undergoing Breast Conserving Surgery: A Prospective Multicenter Randomized Controlled Trial.

Ann Surg 2019 Jul 8. Epub 2019 Jul 8.

Yale University, New Haven, CT.

Objective: Single-center studies have demonstrated that resection of cavity shave margins (CSM) halves the rate of positive margins and re-excision in breast cancer patients undergoing partial mastectomy (PM). We sought to determine if these findings were externally generalizable across practice settings.

Methods: In this multicenter randomized controlled trial occurring in 9 centers across the United States, stage 0-III breast cancer patients undergoing PM were randomly assigned to either have resection of CSM ("shave" group) or not ("no shave" group). Randomization occurred intraoperatively, after the surgeon had completed their standard PM. Primary outcome measures were positive margin and re-excision rates.

Results: Between July 28, 2016 and April 13, 2018, 400 patients were enrolled in this trial. Four patients (2 in each arm) did not meet inclusion criteria after randomization, leaving 396 patients for analysis: 196 in the "shave" group and 200 to the "no shave" group. Median patient age was 65 years (range; 29-94). Groups were well matched at baseline for demographic and clinicopathologic factors. Prior to randomization, positive margin rates were similar in the "shave" and "no shave" groups (76/196 (38.8%) vs. 72/200 (36.0%), respectively, P = 0.604). After randomization, those in the "shave" group were significantly less likely than those in the "no shave" group to have positive margins (19/196 (9.7%) vs. 72/200 (36.0%), P < 0.001), and to require re-excision or mastectomy for margin clearance (17/196 (8.7%) vs. 47/200 (23.5%), P < 0.001).

Conclusion: Resection of CSM significantly reduces positive margin and re-excision rates in patients undergoing PM.
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http://dx.doi.org/10.1097/SLA.0000000000003449DOI Listing
July 2019

Assessment of leadership behavior in occupational health and safety.

Work 2019 ;63(3):405-413

Universidad Autónoma de Occidente, Cali, Colombia.

Background: Improving Occupational Health and Safety performance has become a challenge for industry, because investing in technology, equipment, or robust management systems has not been enough to prevent accidents in the workplace. With the expansion of commercial relations and the intensification of competitiveness in the global market, leadership is essential to prevention.

Objective: Evaluate leadership in occupational safety through a case study.

Methods: The leadership training methodology "The seven steps of leadership and worker involvement" was adapted and applied. Data collection was conducted through the application of diagnosis, training, and monitoring of the evolution of the leadership performance in the management of occupational safety via structured interviews, monitoring of accidents and statistical analysis of the data.

Results: Research has shown that assertive leadership behavior positively influences performance in the management of occupational safety and the results of this case study showed a reduction in accidents with injuries of more than 50%.

Conclusions: Evidence shows that there is a correlation between safety leadership behavior and the reduction in the occurrence of accidents.
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http://dx.doi.org/10.3233/WOR-192946DOI Listing
September 2019

Are Current Serum and Plasma Ferritin Cut-offs for Iron Deficiency and Overload Accurate and Reflecting Iron Status? A Systematic Review.

Arch Med Res 2018 08 17;49(6):405-417. Epub 2018 Dec 17.

Evidence and Programme Guidance, Department of Nutrition for Health and Development, World Health Organization, Geneva, Switzerland.

Background: Serum or plasma ferritin concentration is recommended by WHO as a biomarker to assess iron status in individuals and populations.

Methods: A systematic review was undertaken to summarise the evidence for ferritin reflecting iron status and to assess the cut-off points in different populations. Electronic databases were searched for studies evaluating ferritin concentrations compared against bone marrow aspirates for iron deficiency and to liver biopsies for risk of iron overload.

Results: From 18822 records, 298 studies were assessed in full-text, including 72 studies on iron deficiency and 36 on iron overload in the quantitative analysis. All studies were observational. For iron deficiency, the mean ferritin concentration in healthy individuals was 15.1 μg/L (9 studies, 390 participants) when bone marrow iron content was 0, and 70.4 μg/L (3 studies, 151 participants) when bone marrow iron was 1+ or higher. In non-healthy populations, mean ferritin concentrations were 82.43 μg/L for iron depletion (38 studies, 1023 participants) and 381.61 μg/L for iron sufficiency (38 studies, 1549 participants) with wide variations depending on the pathology. For iron overload the results point out to a cut-off close to 500 μg/L although the data was very limited.

Conclusion: Ferritin concentration is low in iron deficient individuals and high in iron-loaded individuals, regardless of confounding clinical conditions. Current WHO thresholds for healthy populations appear valid but the data is limited for different age groups or physiological conditions. For iron overload, ferritin concentration would only help in the presumptive diagnosis and guide the need for further assessment.
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http://dx.doi.org/10.1016/j.arcmed.2018.12.005DOI Listing
August 2018

The effect of Hispanic ethnicity on surgical outcomes: An analysis of the NSQIP database.

Am J Surg 2019 04 10;217(4):618-633. Epub 2018 Oct 10.

Research Institute, Doctors Hospital at Renaissance Health System, Edinburg, TX, USA; Department of Surgery, University of Texas Rio Grande Valley School of Medicine, Edinburg, TX, USA.

Background: Existing literature has shown racial/ethnic disparities between white and black surgical populations, however, surgical outcomes for Hispanic patients are limited in both scope and quantity.

Methods: Data from the American College of Surgeons National Surgical Quality Improvement Program from 2007 to 2015 was used to analyze surgical outcomes in approximately 3.5 million patients.

Results: Overall, Hispanics experienced lower odds of mortality compared to non-Hispanic White, non-Hispanic Black, and non-Hispanic American Indian or Alaska Native patients (all P < 0.0001). No difference was found in mortality odds between Hispanics and non-Hispanic Asian or Native Hawaiian patients. Hispanics experienced minimal disparities in complications as compared to non-Hispanic White and non-Hispanic Black but had a higher rate of select complications when compared to Non-Hispanic Asian, Native Hawaiian, or Pacific Islander.

Conclusion: Hispanics, in general, had lower odds of 30-day postoperative mortality and major morbidity compared to most of the races/ethnicities included in the ACS NSQIP database.
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http://dx.doi.org/10.1016/j.amjsurg.2018.10.004DOI Listing
April 2019

Skull anatomy and phylogenetic assessment of a large specimen of Ecteniniidae (Eucynodontia: Probainognathia) from the Upper Triassic of southern Brazil.

Zootaxa 2018 Aug 9;4457(3):351-378. Epub 2018 Aug 9.

Programa de Pós-Graduação em Biodiversidade Animal, Universidade Federal de Santa Maria, 97105-120 Santa Maria, RS, Brazil..

Ecteniniidae comprises an endemic radiation of carnivore probainognathian cynodonts from the Late Triassic of South America. Three taxa have been included in this clade: Ecteninion lunensis Martínez et al., 1996 and Diegocanis elegans Martínez et al., 2013 from Argentina, and Trucidocynodon riograndensis Oliveira et al., 2010 from Brazil. Herein, a new specimen (skull and mandible) assigned to T. riograndensis from the Carnian of the Candelária Sequence (Southern Brazil) is described. A phylogenetic analysis recovered the new specimen as the sister taxon of the holotype of T. riograndensis, and both in a trichotomy with E. lunensis and D. elegans, all supporting the monophyly of Ecteniniidae. The new specimen of T. riograndensis is almost 20% larger than its holotype. Therefore, it represents one of the largest specimens of a carnivorous probainognathian from the Late Triassic known to date and contributes to knowledge of size variation in ecteniniids.
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http://dx.doi.org/10.11646/zootaxa.4457.3.1DOI Listing
August 2018

Micromachining of Polyurethane Membranes for Tissue Engineering Applications.

ACS Biomater Sci Eng 2018 Oct 5;4(10):3522-3533. Epub 2018 Sep 5.

Bioscience Division, Los Alamos National Laboratory, P.O. Box 1663 MS M888, Los Alamos, New Mexico 87545, United States.

Engineered tissue barrier models offer alternatives in toxicology and disease research. To mimic barrier-tissue microenvironment, a porous membrane that can approach the stiffness of physiological basement membranes is required. While several biocompatible membranes with micrometer range thickness (10 μm) and a stiffness less than polystyrene (3 GPa) or polyethylene (PET, 2 GPa), have been developed, there has been little effort to optimize the process to enable rapid and reproducible pore production in these membranes. Here, we investigate the use of laser irradiation with femtosecond (fs) pulses because the combination of high-precision and cold-ablation causes minimal damage to polymeric membranes. This process enables automated, high-throughput and reproducible fabrication of thin, microporous membranes that can be utilized to culture cells at air-liquid interface (ALI), a unique culture technique that simulates the tissue-barrier microenvironment. We show the optimization of laser parameters on a thin polyurethane membrane and patterned pores with an average diameter of 5 μm. Tissue was cultured at ALI for 28 days to demonstrate the membrane's utility in constructing a tissue barrier model. These results confirm the utilization of fs laser machining as a viable method for creating a porous barrier substrate in tissue engineering platforms.
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http://dx.doi.org/10.1021/acsbiomaterials.8b00578DOI Listing
October 2018

An early trend towards gigantism in Triassic sauropodomorph dinosaurs.

Nat Ecol Evol 2018 08 9;2(8):1227-1232. Epub 2018 Jul 9.

Instituto y Museo de Ciencias Naturales, Centro de Investigaciones de la Geósfera y la Biósfera (CIGEOBIO), Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de San Juan, San Juan, Argentina.

Dinosaurs dominated the terrestrial ecosystems for more than 140 Myr during the Mesozoic era, and among them were sauropodomorphs, the largest land animals recorded in the history of life. Early sauropodomorphs were small bipeds, and it was long believed that acquisition of giant body size in this clade (over 10 tonnes) occurred during the Jurassic and was linked to numerous skeletal modifications present in Eusauropoda. Although the origin of gigantism in sauropodomorphs was a pivotal stage in the history of dinosaurs, an incomplete fossil record obscures details of this crucial evolutionary change. Here, we describe a new sauropodomorph from the Late Triassic of Argentina nested within a clade of other non-eusauropods from southwest Pangaea. Members of this clade attained large body size while maintaining a plesiomorphic cyclical growth pattern, displaying many features of the body plan of basal sauropodomorphs and lacking most anatomical traits previously regarded as adaptations to gigantism. This novel strategy highlights a highly accelerated growth rate, an improved avian-style respiratory system, and modifications of the vertebral epaxial musculature and hindlimbs as critical to the evolution of gigantism. This reveals that the first pulse towards gigantism in dinosaurs occurred over 30 Myr before the appearance of the first eusauropods.
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http://dx.doi.org/10.1038/s41559-018-0599-yDOI Listing
August 2018

Fellatio-associated erythema of the soft palate: an incidental finding during a routine dental evaluation.

BMJ Case Rep 2018 Jun 11;2018. Epub 2018 Jun 11.

Department of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania, USA.

Oral lesions can have widely variable aetiology, hence, the importance of a comprehensive history and oral examination. We describe the case of a 47-year-old man who presented with an incidental erythematous lesion of the soft palate. The diagnosis was established during a routine dental examination. We found the lesion to be associated with the practice of fellatio. Oral sex is a very common sexual practice, and as clinicians we should consider it as a potential cause of palatal lesions in our differential diagnosis. This should also raise our suspicion for sexually transmitted diseases in high-risk patients.
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http://dx.doi.org/10.1136/bcr-2017-221901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6011465PMC
June 2018

Performance and comparability of laboratory methods for measuring ferritin concentrations in human serum or plasma: A systematic review and meta-analysis.

PLoS One 2018 3;13(5):e0196576. Epub 2018 May 3.

Evidence and Programme Guidance, Department of Nutrition for Health and Development, World Health Organization, Geneva, Switzerland.

Background: Different laboratory methods are used to quantify ferritin concentrations as a marker of iron status. A systematic review was undertaken to assess the accuracy and comparability of the most used methods for ferritin detection.

Methods And Findings: National and regional databases were searched for prospective, retrospective, sectional, longitudinal and case-control studies containing the characteristics and performance of at least one method for serum/plasma ferritin determinations in humans published to date. The analysis included the comparison between at least 2 methods detailing: sensitivity, precision, accuracy, predictive values, inter-methods adjustment, and use of international reference materials. Pooled method performance was analyzed for each method and across methods.

Outcomes: Search strategy identified 11893 records. After de-duplication and screening 252 studies were assessed, including 187 studies in the qualitative analysis and 148 in the meta-analysis. The most used methods included radiometric, nonradiometric and agglutination assays. The overall within-run imprecision for the most reported ferritin methods was 6.2±3.4% (CI 5.69-6.70%; n = 171), between-run imprecision 8.9±8.7% (CI 7.44-10.35%; n = 136), and recovery rate 95.6% (CI 91.5-99.7%; n = 94). The pooled regression coefficient was 0.985 among all methods analyzed, and 0.984 when comparing nonradiometric and radiometric methods, without statistical differences in ferritin concentration ranging from 2.3 to 1454 μμg/L.

Conclusion: The laboratory methods most used to determine ferritin concentrations have comparable accuracy and performance. Registered in PROSPERO CRD42016036222.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196576PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933730PMC
August 2018

Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma.

Clin Cancer Res 2018 07 11;24(14):3263-3272. Epub 2018 Apr 11.

Sarah Cannon Research Institute, Nashville, Tennessee.

Prexasertib, a checkpoint kinase 1 inhibitor, demonstrated single-agent activity in patients with advanced squamous cell carcinoma (SCC) in the dose-escalation portion of a phase I study (NCT01115790). Monotherapy prexasertib was further evaluated in patients with advanced SCC. Patients were given prexasertib 105 mg/m as a 1-hour infusion on day 1 of a 14-day cycle. Expansion cohorts were defined by tumor and treatment line. Safety, tolerability, efficacy, and exploratory biomarkers were analyzed. Prexasertib was given to 101 patients, including 26 with SCC of the anus, 57 with SCC of the head and neck (SCCHN), and 16 with squamous cell non-small cell lung cancer (sqNSCLC). Patients were heavily pretreated (49% ≥3 prior regimens). The most common treatment-related adverse event was grade 4 neutropenia (71%); 12% of patients had febrile neutropenia. Median progression-free survival was 2.8 months [90% confidence interval (CI), 1.9-4.2] for SCC of the anus, 1.6 months (90% CI, 1.4-2.8) for SCCHN, and 3.0 months (90% CI, 1.4-3.9) for sqNSCLC. The clinical benefit rate at 3 months (complete response + partial response + stable disease) across tumors was 29% (23% SCC of the anus, 28% SCCHN, 44% sqNSCLC). Four patients with SCC of the anus had partial or complete response [overall response rate (ORR) = 15%], and three patients with SCCHN had partial response (ORR = 5%). Biomarker analyses focused on genes that altered DNA damage response or increased replication stress. Prexasertib demonstrated an acceptable safety profile and single-agent activity in patients with advanced SCC. The prexasertib maximum-tolerated dose of 105 mg/m was confirmed as the recommended phase II dose. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-3347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050086PMC
July 2018

A First-in-Human Phase 1 Study of LY3023414, an Oral PI3K/mTOR Dual Inhibitor, in Patients with Advanced Cancer.

Clin Cancer Res 2018 07 10;24(14):3253-3262. Epub 2018 Apr 10.

Stephenson Oklahoma Cancer Center/Sarah Cannon Research Institute, Oklahoma City, Oklahoma.

The PI3K/mTOR pathway is frequently aberrated in cancer. LY3023414 is a potent and selective ATP-competitive inhibitor of class I PI3K isoforms, mTOR, and DNA-PK. Here we report the dose-escalation results of the first-in-human phase I study of LY3023414. A 3+3 dose escalation for once-daily and twice-daily oral dosing of LY3023414 was followed by an expansion cohort for CYP3A4 drug-drug interaction (DDI) assessment. The primary objective was to determine the recommended phase 2 dose (RP2D). Additional objectives included safety, pharmacokinetics/pharmacodynamics, and antitumor activity. Forty-seven patients with solid tumors received LY3023414 at once-daily (20-450 mg) or twice-daily dosing (150-250 mg). Dose-limiting toxicities were observed at 450 mg once-daily (thrombocytopenia, hypotension, hyperkalemia) in three of three patients, 250-mg twice-daily dosing (hypophosphatemia, fatigue, mucositis) in three of four patients, and in one of 15 patients at 200 mg twice-daily (nausea). Common related AEs included nausea (38%), fatigue (34%), and vomiting (32%) and were mostly mild or moderate. LY3023414 pharmacokinetics demonstrated dose-dependent increase in exposure with ≥ 90% target inhibition at doses ≥150 mg. DDI analysis demonstrated LY3023414 to be a weak inhibitor of CYP3A4. Durable partial response was observed in a patient with endometrial cancer harboring PIK3R1 and PTEN truncating mutations, and 13 additional patients (28%) had a decrease in their target lesions by up to 30%. LY3023414 has a tolerable safety profile and single-agent activity in patients with advanced cancers. The RP2D of LY3023414 monotherapy is 200 mg twice daily based on safety, tolerability, and pharmacokinetic/pharmacodynamic data. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-3421DOI Listing
July 2018

First results of a highly granulated 3D CdTe detector module for PET.

Phys Med Biol 2018 01 17;63(2):025032. Epub 2018 Jan 17.

Institut de Física d'Altes Energies (IFAE), The Barcelona Institute of Science and Technology, Campus UAB, E-08193 Bellaterra (Barcelona), Spain.

We present the performance of a highly granulated 3D detector module for PET, consisting of a stack of pixelated CdTe detectors. Each detector module has 2 cm  ×  2 cm  ×  2 cm of CdTe material, subdivided into 4000 voxels, where each voxel has size 1 mm  ×  1 mm  ×  2 mm and is connected to its own read-out electronics via a BiSn solder ball. Each read-out channel consists of a preamp, a discriminator, a shaper, a peak-and-hold circuit and a 10 bits SAR ADC. The preamp has variable gain where at the maximum gain the ADC resolution is equivalent to 0.7 keV. Each ASIC chip reads 100 CdTe pixel channels and has one TDC to measure the time stamp of the triggered events, with a time resolution of less than 1 ns. With the bias voltage set at  -250 V mm and for 17838 working channels out of a total of 20 000, we have obtained an average energy resolution of 2.2% FWHM for 511 keV photons. For 511 keV photons that have undergone Compton scattering, we measured an energy resolution of 3.2% FWHM. A timing resolution for PET coincidence events of 60 ns FWHM was found.
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http://dx.doi.org/10.1088/1361-6560/aaa44cDOI Listing
January 2018

Acute kidney injury in Latin America in "big data" era.

Nefrologia 2017 Sep - Oct;37(5):461-464

Servicio de Nefrología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

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http://dx.doi.org/10.1016/j.nefro.2017.03.010DOI Listing
October 2018

Fingolimod induces neuronal-specific gene expression with potential neuroprotective outcomes in maturing neuronal progenitor cells exposed to HIV.

J Neurovirol 2017 Dec 14;23(6):808-824. Epub 2017 Sep 14.

Research Service, Bruce W. Carter Veterans Affairs Medical Center, 1201 NW 16th Street, Miami, FL, 33125, USA.

Fingolimod (FTY720), a structural analogue of sphingosine, targets sphingosine-1-phosphate receptor signaling and is currently an immunomodulatory therapy for multiple sclerosis. Fingolimod accesses the central nervous system (CNS) where its active metabolite, fingolimod phosphate (FTY720-P), has pleotropic neuroprotective effects in an inflammatory microenvironment. To investigate potential neuronal-specific mechanisms of fingolimod neuroprotection, we cultured the human neuronal progenitor cell line, hNP1, in differentiation medium supplemented with HIV- or Mock-infected supernatants, with or without FTY720-P. Gene expression was investigated using microarray and functional genomics. FTY720-P treatment increased differentially expressed (DE) neuronal genes by 33% in HIV-exposed and 40% in Mock-exposed cultures. FTY720-P treatment broadened the functional profile of DE genes in HIV-exposed versus Mock-exposed neurons, including not only immune responses but also transcriptional regulation and cell differentiation, among others. FTY720-P treatment downregulated the gene for follistatin, the antagonist of activin signaling, in all culture conditions. FTY720-P treatment differentially affected both glycolysis-related and immune response genes in Mock- or HIV-exposed cultures, significantly upregulating 11 glycolysis-related genes in HIV-exposed neurons. FTY720-P treatment also differentially upregulated genes related to innate immune responses and antigen presentation in Mock-exposed and more so in HIV-exposed neurons. However, in HIV-exposed neurons, FTY720-P depressed the magnitude of differential expression in almost half the genes, suggesting an anti-inflammatory potential. Moreover, in HIV-exposed neurons, FTY720-P reduced expression of the amyloid precursor protein (APP) gene, resulting in reduced expression of the APP protein. This study provides new evidence that fingolimod alters neuronal gene expression in inflammatory, viral-infected microenvironments, with the potential for neuroprotective effects.
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http://dx.doi.org/10.1007/s13365-017-0571-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725524PMC
December 2017

Novel insight into the origin of the growth dynamics of sauropod dinosaurs.

PLoS One 2017 27;12(6):e0179707. Epub 2017 Jun 27.

IMCN-Instituto y Museo de Ciencias Naturales, Universidad Nacional de San Juan, San Juan, Argentina.

Sauropod dinosaurs include the largest terrestrial animals and are considered to have uninterrupted rapid rates of growth, which differs from their more basal relatives, which have a slower cyclical growth. Here we examine the bone microstructure of several sauropodomorph dinosaurs, including basal taxa, as well as the more derived sauropods. Although our results agree that the plesiomorphic condition for Sauropodomorpha is cyclical growth dynamics, we found that the hypothesized dichotomy between the growth patterns of basal and more derived sauropodomorphs is not supported. Here, we show that sauropod-like growth dynamics of uninterrupted rapid growth also occurred in some basal sauropodomorphs, and that some basal sauropods retained the plesiomorphic cyclical growth patterns. Among the sauropodomorpha it appears that the basal taxa exploited different growth strategies, but the more derived Eusauropoda successfully utilized rapid, uninterrupted growth strategies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179707PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5487048PMC
September 2017

Ulcerated Lesion of the Tongue as Manifestation of Systemic Coccidioidomycosis.

Case Rep Med 2017 13;2017:1489501. Epub 2017 Mar 13.

Department of Oral Pathology, University of Campinas, Piracicaba, SP, Brazil.

Systemic mycoses and their oral manifestations are very rare. We present a case of a 60-year-old man with an ulcerated lesion on the lateral border of the tongue. Histologic studies revealed a granulomatous fungal infection by . After pharmacological treatment, the lesion resolved. Recently, northern Mexico has been reported to be an endemic zone of . infections; therefore it should be considered in the differential diagnosis of mouth lesions. A comprehensive clinical history, physical exploration, and complementary studies are essential for an accurate diagnosis.
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http://dx.doi.org/10.1155/2017/1489501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5366790PMC
March 2017

Hospital Emergency Care as a Public Good and Community Health Benefit.

Ann Emerg Med 2017 Aug 27;70(2):229-232. Epub 2017 Mar 27.

Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA. Electronic address:

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http://dx.doi.org/10.1016/j.annemergmed.2017.01.032DOI Listing
August 2017

Apolipoprotein E4 Suppresses Neuronal-Specific Gene Expression in Maturing Neuronal Progenitor Cells Exposed to HIV.

J Neuroimmune Pharmacol 2017 09 20;12(3):462-483. Epub 2017 Mar 20.

Bruce W. Carter Veterans Affairs Medical Center, 1201 NW 16th Street, Miami, FL, 33125, USA.

The apolipoprotein ε4 gene allele and the apolipoprotein E4 protein (ApoE4) are important host susceptibility factors linked to neurocognitive disorders associated with HIV infection or Alzheimer's disease. Our previous studies showed differential effects of the two most common human ApoE genotypes, APOE3/3 and APOE3/4, on gene expression by differentiating human neuroepithelial progenitor cells continuously exposed to HIV. To investigate the effects of ApoE3 versus ApoE4 isoforms specifically on maturing neurons, we adapted a human neuronal progenitor cell line, hNP1, with ApoE genotype APOE3/3. Differentiating hNP1 cells were exposed for 16 days to HIV- or mock-infected supernatants and to added recombinant ApoE isoforms rApoE3 or rApoE4 to modulate the ApoE phenotype of the cells. Gene expression was investigated using microarray and functional genomics analyses. Added rApoE3 differentially affected 36 genes. Added rApoE4 differentially affected 85 genes; 41 of which were differentially expressed only in HIV or mock-supernatant treated cells, and 80% of which were downregulated. Genes differentially downregulated only by rApoE4 represented multiple neuronal functions related to neurogenesis. Approximately five times more genes were differentially enriched by rApoE4 versus rApoE3 in the Gene Ontology (GO) cellular process analysis, with 4 orders of magnitude greater significance. Half of the top 10 GO processes affected by rApoE4 treatment were neurogenesis-related. The largest differences in gene expression between the two isoforms were observed within the HIV-exposed cultures, suggesting that HIV exposure magnifies ApoE4's suppressive effect on neuronal gene expression. This study provides evidence for neuronal-specific responses to ApoE4 that could affect neurogenesis and neuronal survival.
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http://dx.doi.org/10.1007/s11481-017-9734-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527073PMC
September 2017

Meeting Our Patients Where They Are.

Authors:
Ricardo Martinez

Ann Emerg Med 2017 04 16;69(4):393-394. Epub 2016 Nov 16.

Emory School of Medicine, Atlanta, GA; Adeptus Health, Lewisville, TX. Electronic address:

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http://dx.doi.org/10.1016/j.annemergmed.2016.10.009DOI Listing
April 2017

The Influence of Age and Sexual Drive on the Predictive Validity of the Juvenile Sex Offender Assessment Protocol-Revised.

Int J Offender Ther Comp Criminol 2018 Jan 1;62(1):150-169. Epub 2016 Jun 1.

1 Fordham University, Bronx, NY, USA.

The Juvenile Sex Offender Assessment Protocol-Revised (J-SOAP-II) is the most commonly used measure in the assessment of recidivism risk among juveniles who have committed sexual offenses (JSOs), but mixed support exists for its predictive validity. This study compared the predictive validity of the J-SOAP-II across two offender characteristics, age and sexual drive, in a sample of 156 JSOs who had been discharged from a correctional facility or a residential treatment program. The J-SOAP-II appeared to be a better predictor of sexual recidivism for younger JSOs (14-16 years old) than for older ones (17-19 years old), with significant differences found for the Dynamic Summary Scale and Scale III (Intervention). In addition, several of the measure's scales significantly predicted sexual recidivism for JSOs with a clear pattern of sexualized behavior but not for those without such a pattern, indicating that the J-SOAP-II may have greater clinical utility for JSOs with heightened sexual drive. The implications of these findings are discussed.
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http://dx.doi.org/10.1177/0306624X16650681DOI Listing
January 2018