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ABSTRACT: Objectives: Antimicrobial-resistant non-typhoidal Salmonella (NTS) infections are associated with worse health outcomes compared to antimicrobial-susceptible infections. Misuse of antimicrobials in food animals can amplify the emergence of antimicrobial resistance.The objective of this study was to examine the association between fluoroquinolone sales in food animals and the prevalence of quinolone-resistant NTS isolated from retail meats. Methods: We reviewed data for 4318 NTS isolates from retail meat samples collected from 2009 to 2018 through the FDA National Antimicrobial Resistance Monitoring System programs. The Pearson's correlation was used to examine the correlation between the prevalence of quinolone-resistant NTS and standardised fluoroquinolone sales. Results: After adjusting for the increase in beef and pork production, fluoroquinolone sales increased by 41.67% from 2013 to 2018. The prevalence of quinolone-resistant NTS from retail ground beef increased from 5% in 2014 to 11% in 2018. The increase of quinolone-resistant isolates in retail meats since 2016 was mostly related to Salmonella Infantis and Salmonella enteritidis. Conclusion: One Health integrated surveillance for NTS isolates from food of animal origin and human sources is necessary to elucidate trends in resistance to critical drugs. The study also underscores the need for judicious use of antimicrobials in agricultural settings.

Cytotoxic bile acids, such as deoxycholic acid (DCA), are responsible for hepatocyte cell death during intrahepatic cholestasis. The mechanisms responsible for this effect are unclear, and recent studies conflict, pointing to either a modulation of plasma membrane structure or mitochondrial-mediated toxicity through perturbation of mitochondrial outer membrane (MOM) properties. We conducted a comprehensive comparative study of the impact of cytotoxic and cytoprotective bile acids on the membrane structure of different cellular compartments. We show that DCA increases the plasma membrane fluidity of hepatocytes to a minor extent, and that this effect is not correlated with the incidence of apoptosis. Additionally, plasma membrane fluidity recovers to normal values over time suggesting the presence of cellular compensatory mechanisms for this perturbation. Colocalization experiments in living cells confirmed the presence of bile acids within mitochondrial membranes. Experiments with active isolated mitochondria revealed that physiologically active concentrations of DCA change MOM order in a concentration- and time-dependent manner, and that these changes preceded the mitochondrial permeability transition. Importantly, these effects are not observed on liposomes mimicking MOM lipid composition, suggesting that DCA apoptotic activity depends on features of mitochondrial membranes that are absent in protein-free mimetic liposomes, such as the double-membrane structure, lipid asymmetry, or mitochondrial protein environment. In contrast, the mechanism of action of cytoprotective bile acids is likely not associated with changes in cellular membrane structure.

Ceramide (Cer) is involved in the regulation of several cellular processes by mechanisms that depend on Cer-induced changes on membrane biophysical properties. Accumulating evidence shows that Cers with different N-acyl chain composition differentially impact cell physiology, which may in part be due to specific alterations in membrane biophysical properties. We now address how the sphingolipid (SL) N-acyl chain affects membrane properties in cultured human embryonic kidney cells by overexpressing different Cer synthases (CerSs). Our results show an increase in the order of cellular membranes in CerS2-transfected cells caused by the enrichment in very long acyl chain SLs. Formation of Cer upon treatment of cells with bacterial sphingomyelinase promoted sequential changes in the properties of the membranes: after an initial increase in the order of the fluid plasma membrane, reorganization into domains with gel-like properties whose characteristics are dependent on the acyl chain structure of the Cer was observed. Moreover, the extent of alterations of membrane properties correlates with the amount of Cer formed. These data reinforce the significance of Cer-induced changes on membrane biophysical properties as a likely molecular mechanism by which different acyl chain Cers exert their specific biological actions.

The unique features of the X chromosome can be crucial to complement autosomal profiling or to disentangle complex kinship problems, providing in some cases a similar or even greater power than autosomes in paternity/maternity investigations. While theoretical and informatics approaches for pairwise X-linked kinship analyses are well established for euploid individuals, these are still lacking for individuals with an X chromosome aneuploidy. To trigger the fulfilment of this gap, this research presents a mathematical framework that enables the quantification of DNA evidence in pairwise kinship analyses, involving two non-inbred individuals, one of whom with a non-mosaic X chromosome aneuploidy: Trisomy X (47, XXX), Klinefelter (47, XXY) or Turner (45, X0) syndrome. As previously developed for a regular number of chromosomes, this approach relies on the probability of related individuals sharing identical-by-descent (IBD) alleles at one specific locus and it can be applied to any set of independently transmitted markers, with no gametic association in the population. The kinship hypotheses mostly considered in forensic casework are specifically addressed in this work, but the reasoning and procedure can be applied to virtually any pairwise kinship problem under the referred assumptions. Algebraic formulae for joint genotypic probabilities cover all the possible genotypic configurations and pedigrees. Compared with the analyses assuming individuals with a regular number of chromosomes, complicating factors rely on the different possibilities for both the parental origin of the error (either maternal or paternal), and the type of error occurred (either meiotic or post-zygotic mitotic). These imply that a non-inbred female with Triple X or a male with Klinefelter syndrome may carry two IBD alleles at the same locus. Thus, and contrarily to what occurs for the standard case, IBD partitions depend not only on the kinship hypothesis under analysis but also on the genotypic configuration of the analyzed individuals. For some cases, parameters of interest can be inferred, while for others recommended values based on the available literature are provided. This work is the starting point to analyze X-chromosomal data under the scope of kinship problems, involving individuals with aneuploidies, as it will enhance the quantification of the DNA evidence not only in forensics but also in the medical genetics field. We hope it will trigger the development of approaches including other complicating factors, as a greater number of individuals, possibility of the occurrence of mutations and/or silent alleles, as well as the analysis of linked markers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This study aimed to identify whether patients with impacted maxillary canines take longer to treat than orthodontic patients without an impacted canine. We also sought to identify factors that are predictive of increased treatment duration in patients with impacted maxillary canines and treated by surgical exposure., Methods: A retrospective investigation of 37 patients with an impacted maxillary canine, treated by surgical exposure and fixed appliance therapy, was undertaken. In addition, an age- and sex-matched control group of 39 patients (without impacted canines) was also collected. Patient age, sex, and total treatment duration were recorded. For patients with an impacted canine, patient records and pretreatment cone-beam computed tomography datasets were assessed. Point coordinates identifying relevant landmarks were recorded, and a geometric method was used to calculate variables describing canine location, orientation, and apical morphology., Results: Controlling for age and sex, linear regression identified a statistically significant increase in treatment duration of 46.7 and 41.5 weeks for palatal and labial/midalveolar impacted canines, respectively, vs controls (P <0.002). Age and sex of patients with impacted canines collectively affected treatment duration (P = 0.04), with females of increased age being treated faster than younger males. Rotation of the impacted canine crown had a highly significant effect on treatment duration, with every degree of rotation increasing treatment duration by 0.32 weeks (P <0.001). There was a significant degree of multicollinearity between the other radiographic variables. Collectively, radiographic variables describing canine displacement significantly prolonged treatment duration (P <0.001) and explained 29.8% of the variability in total treatment time. The apical morphology of impacted maxillary canines was significantly associated with increased treatment duration (P = 0.01) and explained 11.3% of the overall treatment variability (P = 0.01)., Conclusions: Increased total treatment duration of surgically exposed impacted maxillary canines is associated with increasing mesiopalatal canine crown rotation, worsening displacement, and hooked apical morphology., (Copyright © 2024 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objective: This systematic review aimed to evaluate if event-related potentials (ERPs) can be a relevant tool for cognitive dysfunction diagnosis in Multiple Sclerosis (MS)., Methods: Four databases were consulted (PubMed, Embase, Scielo, and Web of Science). The included studies should include adults with clear MS diagnoses, independently of having cognitive complaints, and all should have been submitted to ERPs (P300, N400 or mismatch negativity (MMN)). The main outcomes evaluated were ERPs' amplitude and/or latency., Results: 425 studies were obtained initially from all databases, with 26 studies fulfilling the eligibility criteria. P300 was the most used ERP (25 studies), showing a reduced amplitude or an increased latency in 84% of those. N400 was evaluated in one study, showing also abnormal results. MMN was addressed in two studies with inconsistent findings. Some studies further suggest that ERPs may show earlier abnormal results compared with neuropsychological tests., Conclusions: Most MS patient groups revealed ERP abnormalities, suggesting that these neurophysiological tests may be a relevant and appropriate diagnostic aid method for cognitive impairment in MS., Significance: The use of ERPs in MS patients seems able to demonstrate cognitive impairment and its use should be considered as part of the regular patient evaluation., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Children undergoing cardiac surgical procedures may require postoperative surgical or catheter-based reintervention before discharge. We examined racial/ethnic variations in reintervention and associated in-hospital death., Methods: Children undergoing cardiac surgical procedures from 2004 to 2015 were identified in the Pediatric Health Information Systems (PHIS) database. Regression analysis measured associations between race/ethnicity, in-hospital death, and postoperative cardiac surgical or catheter-based reintervention (surgical/catheter reintervention)., Results: Of 124,263 patients, 8265 (6.7%) had a surgical/catheter reintervention. Black patients had fewer reinterventions (5.9% vs 6.7%) and higher in-hospital mortality (3.9% vs 2.7%, P < .01) than White patients. After adjusting for sociodemographic and illness severity indicators, Black patients remained less likely to receive surgical/catheter reintervention (adjusted hazard ratio [aHR], 0.89; 95% CI, 0.82-0.98) despite having similar risk of death after reintervention (adjusted odds ratio, 1.17; 95% CI, 0.98-1.41) compared with White patients. The risk of death without surgical/catheter reintervention was also higher for Black (aHR, 1.26; 95% CI, 1.08-1.47) and other race/ethnicity (aHR, 1.33; 95% CI, 1.13-1.57) patients than for White patients. Similar trends were demonstrated when mechanical circulatory support and cardiac transplantation were included as reinterventions., Conclusions: Patients of Black and other race/ethnicity undergoing pediatric cardiac surgical procedures are more likely to die without postoperative cardiac reintervention than White patients. Black patients are also less likely to receive reintervention despite no significant difference in mortality with reintervention. Further studies should evaluate etiologies and methods of addressing these disparities., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Edwardsiella tarda (Et) is a zoonotic gram-negative pathogen with a diverse host range, including fish. However, the in-depth molecular mechanisms underlying the response of Labeo rohita (rohu) kidney to Et are poorly understood. A proteomic and histopathological analysis was performed for the rohu kidney after Et infection. The histopathology of the infected rohu kidney showed vacuolation and necrosis. After LC-MS/MS analysis, ~1240 proteins were identified with ≥2 unique peptides. A total of 96 differentially abundant proteins (DAPs) were observed between the control and Et infected group (ET). Metascape and STRING analysis were used for the gene ontology (GO), and protein-protein interaction network (PPI) for the significant pathways of DAPs. In PPI, low-abundant proteins were mapped to metabolic pathways and oxidative phosphorylation (cox5ab, uqcrfs1). High-abundance proteins were mapped to ribosomes (rplp2), protein process in the ER (hspa8), and immune system (ptgdsb.1, muc2). Our label-free proteomic approach in the rohu kidney revealed abundant enriched proteins involved in vesicle coat (ehd4), complement activation (c3a.1, c9, c7a), phagosome (thbs4, mapk1), metabolic reprogramming (hao1, glud1a), wound healing (vim, alox5), and the immune system (psap) after Et infection. A targeted proteomics approach of multiple reaction monitoring (MRM) validated the DAPs (nprl3, ambp, vmo1a, hspg2, muc2, hao1 and glud1a) between control and ET. Overall, the current analysis of histology and proteome in the rohu kidney provides comprehensive data on pathogenicity and the potential immune proteins against Et., Competing Interests: Declaration of competing interest The authors wish to declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

The Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) organized a collaborative study on mutations of Y-chromosomal short tandem repeats (Y-STRs). New data from 2225 father-son duos and data from 44 previously published reports, corresponding to 25,729 duos, were collected and analyzed. Marker-specific mutation rates were estimated for 33 Y-STRs. Although highly dependent on the analyzed marker, mutations compatible with the gain or loss of a single repeat were 23.2 times more likely than those involving a greater number of repeats. Longer alleles (relatively to the modal one) showed to be nearly twice more mutable than the shorter ones. Within the subset of longer alleles, the loss of repeats showed to be nearly twice more likely than the gain. Conversely, shorter alleles showed a symmetrical trend, with repeat gains being twofold more frequent than reductions. A positive correlation between the paternal age and the mutation rate was observed, strengthening previous findings. The results of a machine learning approach, via logistic regression analyses, allowed the establishment of algebraic formulas for estimating the probability of mutation depending on paternal age and allele length for DYS389I, DYS393 and DYS627. Algebraic formulas could also be established considering only the allele length as predictor for DYS19, DYS389I, DYS389II-I, DYS390, DYS391, DYS393, DYS437, DYS439, DYS449, DYS456, DYS458, DYS460, DYS481, DYS518, DYS533, DYS576, DYS626 and DYS627 loci. For the remaining Y-STRs, a lack of statistical significance was observed, probably as a consequence of the small effective size of the subsets available, a common difficulty in the modeling of rare events as is the case of mutations. The amount of data used in the different analyses varied widely, depending on how the data were reported in the publications analyzed. This shows a regrettable waste of produced data, due to inadequate communication of the results, supporting an urgent need of publication guidelines for mutation studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: We record the experiences of staff in a labour, delivery, and obstetric services (LD-OBS) unit in Alberta's largest quaternary medical centre-the Foothills Medical Centre (FMC)-as they navigated hospital policies during the COVID-19 pandemic. We examine how unit leadership applied these policies to better align with care delivery realities while staying true to the interprofessional nature of the unit., Methods: A total of 12 semi-structured qualitative interviews were conducted with LD-OBS unit staff. Snowball and purposive sampling strategies were used to capture experiences from key informants. Interview transcripts underwent inductive coding. The themes identified through this process were discussed with members of the authorial team until a consensus was reached., Results: FMC LD-OBS team members used 'interprofessional' as a value through which to interpret, adapt, and implement centrally developed COVID-19 policies. These were applied at 3 key moments: reconfiguring the unit, triaging, and rerouting patients, and contesting central personal protective equipment policies. LD-OBS leaders championed the importance of interprofessional collaboration and teamwork in the unit and worked to uphold it as a practice and value., Conclusion: The COVID-19 pandemic experience of the FMC LD-OBS unit illustrates the importance of considering interprofessionalism as a core value as policy was developed and implemented. Health authorities, hospitals, and other LD-OBS units may wish to consider how interprofessional work affects policy interpretation among health care teams, and how this may be leveraged to successfully adapt policies to local units, under both pandemic and 'normal' conditions., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Image 1., Competing Interests: The authors declare no conflict of interest., (© 2023 Published by Elsevier B.V. on behalf of Craniofacial Research Foundation.)

Aeromonas hydrophila (Ah) is a Gram-negative bacterium and a serious global pathogen causing Motile Aeromonas Septicaemia (MAS) in fish leading to global loss in aquaculture. Investigation of the molecular alterations of host tissues such as liver could be a powerful approach to identify mechanistic and diagnostic immune signatures of disease pathogenesis. We performed a proteomic analysis of Labeo rohita liver tissue to examine the protein dynamics in the host cells during Ah infection. The proteomic data was acquired using two strategies; discovery and targeted proteomics. Label-free quantification was performed between Control and challenged group (AH) to identify the differentially expressed proteins (DEPs). A total of 2525 proteins were identified and 157 were DEPs. DEPs include metabolic enzymes (CS, SUCLG2), antioxidative proteins, cytoskeletal proteins and immune related proteins (TLR3, CLEC4E). Pathways like lysosome pathway, apoptosis, metabolism of xenobiotics by cytochrome P450 were enriched by downregulated proteins. However, upregulated proteins majorly mapped to innate immune system, signaling of B cell receptor, proteosome pathway, ribosome, carbon metabolism and protein processing in ER. Our study would help in exploring the role of Toll-like receptors, C-type lectins and, metabolic intermediates like citrate and succinate in Ah pathogenesis to understand the Ah infection in fish. SIGNIFICANCE: Bacterial diseases such as motile aeromonas septicaemia (MAS) are among the most serious problems in aquaculture industry. Small molecules that target the metabolism of the host have recently emerged as potential treatment possibilities in infectious diseases. However, the ability to develop new therapies is hampered due to lack of knowledge about pathogenesis mechanisms and host-pathogen interactions. We examined alterations in the host proteome during MAS caused by Aeromonas hydrophila (Ah) infection, in Labeo rohita liver tissue to find cellular proteins and processes affected by Ah infection. Upregulated proteins belong to innate immune system, signaling of B cell receptor, proteosome pathway, ribosome, carbon metabolism and protein processing. Our work is an important step towards leveraging host metabolism in targeting the disease by providing a bigger picture on proteome pathology correlation during Ah infection., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Following a prostate cancer diagnosis, disease and treatment-related symptoms may result in diminished quality of life (QoL). Whether exercise improves QoL in men with metastatic castrate-resistant prostate cancer (mCRPC) is not fully understood., Methods: We conducted a 3-arm pilot randomized controlled trial to assess the feasibility, acceptability, safety, and efficacy of a 12-week remotely monitored exercise program among men with mCRPC. Here we report qualitative changes in QoL, consistent with the guidelines for pilot trials. Men were randomized to control, aerobic exercise, or resistance exercise. Exercise prescriptions were based on baseline cardiorespiratory and strength assessments. QoL outcomes were evaluated using self-reported questionnaires (e.g., QLQ-C30, PROMIS Fatigue, Pittsburgh Sleep Quality Index (PSQI), EPIC-26) collected at baseline and 12 weeks., Results: A total of 25 men were randomized (10 control, 8 aerobic, 7 resistance). Men were predominately white (76%) with a median age of 71 years (range: 51-84) and 10.5 years (range: 0.9-26.3) post prostate cancer diagnosis. The men reported poor sleep quality and high levels of fatigue at enrollment. Other baseline QoL metrics were relatively high. Compared to the controls at 12 weeks, the resistance arm reported some improvements in social function and urinary irritative/obstruction symptoms while the aerobic arm reported some improvements in social function and urinary incontinence, yet worsening nausea/vomiting. Compared to the resistance arm, the aerobic arm reported worse urinary irritative/obstruction symptoms and self-rated QoL, yet some improvements in emotional function, insomnia, and diarrhea., Conclusions: The 3-month exercise intervention pilot appeared to have modest effects on QoL among mCRPC survivors on ADT. Given the feasibility, acceptability, and safety demonstrated in prior analyses, evaluation of the effect of the intervention on QoL in a larger sample and for extended duration may still be warranted., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: The purpose of this study was to evaluate the impact of gender and peripheral blood parameters on the characteristics of Leucocyte-and Platelet-Rich Fibrin (L-PRF) membranes and to describe histologically three different zones of L-PRF membranes., Methods: Blood was collected from twenty healthy donors (10 men and 10 women). Peripheral blood parameters including leucocyte and platelet counts, and fibrinogen levels were recorded. L-PRF membranes were prepared to quantify the release of growth factors (PDGF, VEGF, BMP-2, and BMP-9) at 1, 2, 3 and 7 days and for histological examination. Three zones within each L-PRF membrane (face, body, and tail) were analysed separately, quantifying the area of leucocytes, platelets, and fibrin in percentage. The Young's modulus of the membranes was also considered (during tensile and compression tests)., Results: Women had significantly higher fibrinogen levels in their peripheral blood, and a higher release of BMP-9, whereas men showed a significantly higher Young's modulus in compression tests. The histology revealed significant differences in cellular content and fibrin concentration between the 3 areas, with the face being biologically the richest., Conclusion: Several factors influenced the final characteristics of L-PRF membranes. These need to be taken into consideration when interpreting the results of research, but especially in clinical practice., Competing Interests: The Department of Periodontology and the Department of Prosthetic Dentistry at KU Leuven are holders of a research chair from Intra-Lock International, devoted to optimizing osseointegration. The authors have stated explicitly that there are no conflicts of interest with this article., (© 2022 Published by Elsevier B.V. on behalf of Craniofacial Research Foundation.)

To overcome the multifactorial complexity associated with the analysis and interpretation of the capillary electrophoresis results of forensic mixture samples, probabilistic genotyping methods have been developed and implemented as software, based on either qualitative or quantitative models. The former considers the electropherograms' qualitative information (detected alleles), whilst the latter also takes into account the associated quantitative information (height of allele peaks). Both models then quantify the genetic evidence through the computation of a likelihood ratio (LR), comparing the probabilities of the observations given two alternative and mutually exclusive hypotheses. In this study, the results obtained through the qualitative software LRmix Studio (v.2.1.3), and the quantitative ones: STRmix™ (v.2.7) and EuroForMix (v.3.4.0), were compared considering real casework samples. A set of 156 irreversibly anonymized sample pairs (GeneMapper files), obtained under the scope of former cases of the Portuguese Scientific Police Laboratory, Judiciary Police (LPC-PJ), were independently analyzed using each software. Sample pairs were composed by (i) a mixture profile with either two or three estimated contributors, and (ii) a single contributor profile associated. In most cases, information on 21 short tandem repeat (STR) autosomal markers were considered, and the majority of the single-source samples could not be a priori excluded as belonging to a contributor to the paired mixture sample. This inter-software analysis shows the differences between the probative values obtained through different qualitative and quantitative tools, for the same input samples. LR values computed in this work by quantitative tools showed to be generally higher than those obtained by the qualitative. Although the differences between the LR values computed by both quantitative software showed to be much smaller, STRmix™ generated LRs are generally higher than those from EuroForMix. As expected, mixtures with three estimated contributors showed generally lower LR values than those obtained for mixtures with two estimated contributors. Different software products are based on different approaches and mathematical or statistical models, which necessarily result in the computation of different LR values. The understanding by the forensic experts of the models and their differences among available software is therefore crucial. The better the expert understands the methodology, the better he/she will be able to support and/or explain the results in court or any other area of scrutiny., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background & Aims: Interpretation of blood micronutrient levels requires age-appropriate reference intervals. This study developed age-dependent micronutrient centiles for healthy children (HC) and explored their utility in sick children., Methods: 244 blood samples were collected from normal HC who underwent tests for acute illness. Age-dependent, centile charts were fitted for zinc, copper, magnesium and selenium in plasma and erythrocytes (RBC), and for vitamins B1, B2 and B6 in RBC. For 34 children with Crohn's disease (CrD) and 55 with coeliac disease (CoeD), Z-scores for the levels of these micronutrients were computed, using the new charts. Associations were explored between plasma and RBC micronutrient Z-scores, and in CrD with CRP and serum albumin., Results: In HC, plasma zinc and selenium increased and plasma copper, magnesium and RBC vitamins B1, B2 and B6 decreased with age. In HC and in CrD, plasma and RBC Z-scores for copper, selenium and magnesium (all p < 0.001) were positively correlated, but not for zinc. In CrD, albumin was related with plasma zinc (rho = 0.62; p < 0.001) and selenium Z-scores (rho = 0.65; p < 0.001) and plasma copper Z-score with CRP (rho = 0.45; p = 0.02). A higher proportion of CrD children had low levels for B2 (21% vs 0%; p = 0.01) and B6 (18% vs 0%; p = 0.02) using the new centile charts than the local laboratory references., Conclusion: Age-dependent micronutrient centile charts enable tracking of micronutrient status, Z-score calculation and may prevent misdiagnosis and inappropriate treatment of deficiencies. In systemic inflammatory conditions, RBC measurements of certain micronutrients may be more reliable to use than measurements in plasma., Competing Interests: Conflict of Interest Prof K Gerasimidis received research grants or speakers fees from Nestle, Nutricia, Abbott, Baxter, Servier, Janssen, Mead Johnson, Mylan and Dr Falk. The rest of the authors have no conflicts of interests to disclose., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Current clinical treatment strategies for the bypassing of small diameter (<6 mm) blood vessels in the management of cardiovascular disease frequently fail due to a lack of suitable autologous grafts, as well as infection, thrombosis, and intimal hyperplasia associated with synthetic grafts. The rapid advancement of 3D printing and regenerative medicine technologies enabling the manufacture of biological, tissue-engineered vascular grafts (TEVGs) with the ability to integrate, remodel, and repair in vivo, promises a paradigm shift in cardiovascular disease management. This review comprehensively covers current state-of-the-art biofabrication technologies for the development of biomimetic TEVGs. Various scaffold based additive manufacturing methods used in vascular tissue engineering, including 3D printing, bioprinting, electrospinning and melt electrowriting, are discussed and assessed against the biomechanical and functional requirements of human vasculature, while the efficacy of decellularization protocols currently applied to engineered and native vessels are evaluated. Further, we provide interdisciplinary insight into the outlook of regenerative medicine for the development of vascular grafts, exploring key considerations and perspectives for the successful clinical integration of evolving technologies. It is expected that continued advancements in microscale additive manufacturing, biofabrication, tissue engineering and decellularization will culminate in the development of clinically viable, off-the-shelf TEVGs for small diameter applications in the near future. STATEMENT OF SIGNIFICANCE: Current clinical strategies for the management of cardiovascular disease using small diameter vessel bypassing procedures are inadequate, with up to 75% of synthetic grafts failing within 3 years of implantation. It is this critically important clinical problem that researchers in the field of vascular tissue engineering and regenerative medicine aim to alleviate using biofabrication methods combining additive manufacturing, biomaterials science and advanced cellular biology. While many approaches facilitate the development of bioengineered constructs which mimic the structure and function of native blood vessels, several challenges must still be overcome for clinical translation of the next generation of tissue-engineered vascular grafts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: To present a structured approach for assessing stakeholder perceptions and implementing the approach in guideline development., Methods: This work was carried out by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Equity and Stakeholder Engagement Project Groups through brainstorming and iterative frameworks, stakeholder engagement, pilot testing, refinement of ideas, using input from workshops, and discussions at GRADE Working Group meetings to produce this document, which constitutes a GRADE conceptual article on implementation., Results: We introduce the FACE implementation criteria, feasibility, acceptability, cost, and equity; priority; and "intent to implement" criterion. We outline the implementation importance of networks and approaches to patient and other stakeholder engagement. Implementation is often highly contextual and can benefit from stakeholder engagement and other assessments. Our FACE approach provides stakeholder questions and language to inform guideline implementation and tools., Conclusion: The FACE criteria propose a series of knowledge translation questions to guide the assessment of implementation for evidence-based guidelines. It is desirable for guideline developers to use a conceptual approach, such as FACE, to tailor implementation and inform end of guideline dissemination and knowledge translation activities., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Quantify the effect of the osseodensification Densah® protocol on the insertion torque, ISQ, and the removal torque of conical BioHorizons® implants., Materials and Methods: An ex vivo model over fresh pig tibia bone was used. Test group (TG) included 50 osteotomies using Densah® osseodensification protocol, and the control group (CG), 50 osteotomies using BioHorizons®'s recommended procedure. Conical BioHorizons® implants (3.8 × 10.5 mm) were implanted, verifying the insertion torque with a manual torque meter. ISQ values were registered with Ostell® device. Finally, implants were removed with manual reverse torque registering the values. Results were analyzed and compared with the Mann-Whitney test and t-test., Results: Median and interquartile range per group were as follows: insertion torque, CG: 26 (12) Ncm; TG: 42 (26) Ncm, removal torque, CG: 25 (20) Ncm; TG: 40 (28) Ncm, ISQ value, CG: 69.25 (5.5); TG: 71.5 (4). All variables were significantly higher (p ≤ 0.05) in the osseodensification group., Conclusions: The Osseodensification technique may improve primary stability in the clinical scenario on tapered implants. Further human RCTs are necessary to validate this., Competing Interests: There is no conflict of interest in this publication. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (© 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved.)

Objectives: Lesbian, gay, bisexual, trans and intersex (LGBTI) people experience health inequalities and barriers to accessing healthcare at a greater rate than the general population. This paper aims to present the Health4LGBTI training course for healthcare workers and the results of its pilot implementation., Methods: Funded by the European Parliament, the training course was developed by a multidisciplinary team including LGBTI organisations as part of the Health4LGBTI Project. 110 healthcare professionals from diverse medical fields attended the pilot training in six European Member States. Knowledge and attitudes were compared on the basis of a pre-post evaluation design utilising an ad hoc questionnaire., Results: Knowledge scores increased after the training, irrespective of age and sexual orientation of participants. Attitudes scores generally improved, particularly in terms of inclusivity and a greater acknowledgement of LGBTI health needs and self-competence., Conclusion: The Health4LGBTI training course is both feasible and effective in training healthcare professionals and support staff to improve cultural competence and thereby promoting inclusive healthcare practice., Practice Implications: The Health4LGBTI training course can be implemented in different healthcare contexts. Piloting of the course provided an opportunity for healthcare professionals and for support staff to improve their knowledge of, and attitudes towards, LGBTI people., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

The GHEP-ISFG organized a collaborative study to estimate mutation rates for the markers included in the Investigator Argus X-12 QS kit Qiagen. A total of 16 laboratories gathered data from 1,612 father/mother/daughter trios, which were used to estimate both maternal and paternal mutation rates, when pooled together with other already published data. Data on fathers and mothers' age at the time of birth of the daughter were also available for ∼93 % of the cases. Population analyses were computed considering the genetic information of a subset of 1,327 unrelated daughters, corresponding to 2,654 haplotypes from residents in several regions of five countries: Argentina, Brazil, Ecuador, Portugal and Spain. Genetic differentiation analyses between the population samples from the same country did not reveal signs of significant stratification, although results from Hardy-Weinberg and linkage disequilibrium tests indicated the need of larger studies for Ecuador and Brazilian populations. The high genetic diversity of the markers resulted in a large number of haplotype combinations, showing the need of huge databases for reliable estimates of their frequencies. It should also be noted the high number of new alleles found, many of them not included in the allelic ladders provided with the kit, as very diverse populations were analyzed. The overall estimates for locus specific average mutation rates varied between 7.5E-04 (for DXS7423) and 1.1E-02 (for DXS10135), the latter being a troublesome figure for kinship analyses. Most of the found mutations (∼92 %) are compatible with the gain or loss of a single repeat. Paternal mutation rates showed to be 5.2 times higher than maternal ones. We also found that older fathers were more prone to transmit mutated alleles, having this trend not been observed in the case of the mothers., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Thermally activated delayed fluorescence (TADF) has revolutionized the field of organic light emitting diodes owing to the possibility of harvesting non-emissive triplet states and converting them in emissive singlet states. This mechanism generates a long-lived delayed fluorescence component which can also be used in sensing oxygen concentration, measuring local temperature, or on imaging. Despite this strong potential, only recently TADF has emerged as a powerful tool to develop metal-free long-lived luminescent probes for imaging and sensing. The application of TADF molecules in aqueous and/or biological media requires specific structural features that allow complexation with biomolecules or enable emission in the aggregated state, in order to retain the delayed fluorescence that is characteristic of these compounds. Herein we demonstrate a facile method that maintains the optical properties of solvated dyes by dispersing TADF molecules in nanoparticles. TADF dye-doped silica nanoparticles are prepared using a modified fluorescein fluorophore. However, the strategy can be used with many other TADF dyes. The covalent grafting of the TADF emitter into the inorganic matrix effectively preserves and transfers the optical properties of the free dye into the luminescent nanomaterials. Importantly, the silica matrix is efficient in shielding the dye from solvent polarity effects and increases delayed fluorescence lifetime. The prepared nanoparticles are effectively internalized by human cells, even at low incubation concentrations, localizing primarily in the cytosol, enabling fluorescence microscopy imaging at low dye concentrations., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Pediatric Intensive Care Unit (PICU) teams provide care for critically ill children with diverse and often complex medical and surgical conditions. Researchers often lack guidance on an approach to select the best outcomes when evaluating this critically ill population. Studies would be enhanced by incorporating multi-stakeholder preferences to better evaluate clinical care. This manuscript outlines the methodology currently being used to develop a PICU Core Outcome Set (COS). This PICU COS utilizes mixed methods, an inclusive stakeholder approach, and a modified Delphi consensus process that will serve as a resource for PICU research programs., Methods: A Scoping Review of the PICU literature evaluating outcomes after pediatric critical illness, a qualitative study interviewing PICU survivors and their parents, and other relevant literature will serve to inform a modified, international Delphi consensus process. The Delphi process will derive a set of minimum domains for evaluation of outcomes of critically ill children and their families. Delphi respondents include researchers, multidisciplinary clinicians, families and former patients, research funding agencies, payors, and advocates. Consensus meetings will refine and finalize the domains of the COS, outline a battery instruments for use in future studies, and prepare for extensive dissemination for broad implementation., Discussion: The PICU COS will be a guideline resource for investigators to assure that outcomes most important to all stakeholders are considered in PICU clinical research in addition to those deemed most important to individual scientists., Trial Registration: COMET database (http://www.comet-initiative.org/, Record ID 1131, 01/01/18)., Competing Interests: Declaration of Competing Interest The authors declare not competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Spleen tyrosine kinase (SYK) is a promoter of cell survival in a variety of cell types, including normal and cancerous epithelial cells. We hypothesized that SYK would an important therapeutic target to inhibit for the treatment of HNSCC., Materials and Methods: SYK protein abundance in patient tumours was evaluated. SYK protein and mRNA abundance was used to examine patient survival and human papillomavirus (HPV) status. Small-interfering RNAs and gene editing with CRISPR/Cas9 were used to evaluate SYK expression on proliferation in HNSCC cell lines. The potency of SYK inhibitor ER27319 maleate on cellular proliferation was tested using a panel of 28 HNSCC cell lines and in vivo in HNSCC patient-derived xenograft (PDX) models., Results: Moderate to high protein expression of SYK was observed in 24% of patient tumors and high SYK expression was exclusively observed in HPV-positive samples (p < 0.001). SYK inhibition with RNA interference, gene editing or a SYK inhibitor (ER27319) decreased cell proliferation and migration. Treatment of PDXs with ER27319 maleate was observed to reduce tumour burden in vivo in two of three models., Conclusions: HPV-positive HNSCC harbours high SYK protein levels. We demonstrate that proliferation, migration and overall burden of these tumours can be reduced by genetic or pharmacologic inhibition of SYK. Taken together, these data establish SYK as a therapeutic target for HNSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: This TBS sham-controlled study aimed to evaluate the effects of intermittent TBS (iTBS) and continuous TBS (cTBS) upon ipsilateral hearing thresholds after stimulation on the left auditory cortex., Methods: Sixty healthy adults, aged between 19 and 32 years (median of 23 years), were randomly distributed into three groups and underwent iTBS, cTBS or sham stimulation. Each double-blind experimental session comprised two pure tone audiometric evaluations per subject, before and after stimulation. To assess volunteer safety, a follow-up of at least 48 hours was implemented., Results: The iTBS group mean thresholds displayed a tendency to decrease after stimulation, predominantly in the 500 Hz-6000 Hz interval and group comparisons revealed significant differences between the iTBS and sham groups for 500 Hz (p = 0.041) and between the iTBS and cTBS groups for 4000 Hz (p = 0.038). Neither relevant side effects nor any significant hearing threshold impairment after active or sham stimulation were found., Conclusions: A single stimulation session led to an effective neuromodulation of the auditory cortex, reflected in lower thresholds when using iTBS., Significance: These encouraging results with this safe noninvasive tool suggest that iTBS may have the potential to positively influence hearing thresholds., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The analysis of X-chromosome STRs is useful in certain kinship cases for which autosomal markers provide insufficient statistical power. Particularly, powerful results are achieved in paternity cases with a daughter, when the alleged father is not accessible for analysis, contrarily to his unquestioned mother or daughter. However, representative haplotype frequencies for this type of markers are not available for some populations, as is the case of Argentina, which prevents the quantification of the proof in routine forensic analyses. In this work we present haplotype frequencies for the 12 X-chromosome STRs included in the Investigator Argus X-12 kit, as well as segregation data, obtained from the analysis of the genetic profiles of 457 father-daughter duos, which gave us information on 914 (unrelated) haplotypes from residents of all Argentinian provinces., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In kinship testing powerful statistical results are usually obtained when genetic information is required to be shared between a set of individuals, under the assumption of one of the hypotheses. This is the case when the hypotheses parenthood or identity are compared with the hypothesis of no relatedness, even when only a pair of individuals is analyzed. In this work we will consider kinship problems where the sharing of genetic information is not required when a pair of individuals is analyzed, such as is the case of the hypotheses full-siblings or avuncular. Statistical evaluation was computed through the quantification of likelihood ratios, assuming the genotypic configuration of 100,000 simulated families, for each of the kinship problems analyzed: full-siblings vs. unrelated, full-siblings vs. half-siblings, half-siblings vs. unrelated, avuncular vs. unrelated, first cousins vs. unrelated, and half-first cousins vs. unrelated. For each of the six studied cases we have obtained results allowing us to weight the informative power impact of increasing the number of markers and of the addition of an extra individual, considering (a.) the use of different sets of STRs (from 8 to 35), and (b.) the introduction of a third undoubted relative. Based on these results we were able to provide recommendations for each case both on the minimal number of STRs to be used and on the third relative whose genetic analysis should be privileged., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The potential and difficulties of the application of genome wide data in forensics are analyzed. We argue that, besides statistical, computational, ethical, economic and technical validation problems, the state of the art of population genetics theory is insufficient to deal with the forensic use of this type of data. In order to keep the current standards of quantifying and reporting genetic evidence, namely in kinship analyses and identification, substantial improvement in the theoretical framework should be reached, since to obtain genome-wide results is to provide the experts with data that they cannot quantify the corresponding evidentiary value. Therefore, while a satisfactory, generalized theoretical and biostatistical modelling is not achieved, it may well be wiser to improve the already established approaches to a limited, pre-defined number of validated genetic markers, amenable to a consensual handling and reporting. Whole genome population analyses will prove extremely useful in selecting the best suited and most efficient of those markers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The PI3K/AKT/mTOR pathway is frequently altered in head and neck squamous cell cancer (HNSCC), making this pathway a logical therapeutic target. However, PI3K targeting is not universally effective. Biomarkers of response are needed to stratify patients likely to derive benefit and exclude those unlikely to respond., Materials and Methods: We examined the sensitivity of cell lines with constitutively-active (G12V mutant) HRAS and wild-type HRAS to PI3K inhibition using flow cytometry and cell viability assays. We then overexpressed and silenced HRAS and measured sensitivity to the PI3K inhibitor BYL719. Immunoblotting was used to determine activation of the PI3K pathway. MEK and mTOR inhibitors were then tested in HRAS mutant cells to determine their efficacy., Results: HRAS mutant cell lines were non-responsive to PI3K inhibition. Overexpression of HRAS led to reduced susceptibility to PI3K inhibition, while knockdown improved sensitivity. Immunoblotting revealed suppressed AKT phosphorylation upon PI3K inhibition in both wild-type and HRAS mutant cell lines, however mutant lines maintained phosphorylation of S6, downstream of mTOR. Targeting mTOR effectively reduced viability of HRAS mutant cells and we subsequently examined the ERK-TSC2-mTOR cascade as a mediator of resistance to PI3K inhibition., Conclusions: HRAS mutant cells are resistant to PI3K inhibition and our findings suggest the involvement of a signalling intersection of the MAPK and PI3K pathways at the level of ERK-TSC2, leading to persistent mTOR activity. mTOR inhibition alone or in combination with MAPK pathway inhibition may be a promising therapeutic strategy for this subset of HNSCC tumors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In Brazil, meat inspection occurs in a decentralized manner and consists of three types: (i) federal inspection (SIF), (ii) state inspection (SISP), and (iii) municipal inspection (SIM). The objective of this work was to discuss the three current inspection systems through the apparent prevalence of bovine brucellosis, a zoonosis that has an eradication program implemented by the Brazilian government. Nine abattoirs from federal, state, and municipal inspection systems were assessed and 1,490 animals were sampled. Serology for brucellosis was determined by the rose bengal test and the complement fixation test. The overall apparent prevalence (and 95% confidence interval) of brucellosis was 2.2% (1.5 to 2.9%). Apparent prevalence stratified by inspection system for SIF, SISP, and SIM was 0.4% (0.0 to 0.9%), 2.0% (0.8 to 3.2%), and 4.3% (2.5 to 6.1%), respectively. Multivariable logistic regression analysis revealed the odds ratio for finding an animal positive for brucellosis among inspection systems. A statistical difference ( P < 0.0015) was observed among surveillance systems, with SISP × SIF, SIM × SISP, and SIM × SIF having an odds ratio of 4,996, 2,304, and 11,494, respectively. Hence, the need for increasing official surveillance in state and municipal inspection systems seems to be necessary and could assist in the surveillance of bovine brucellosis and other diseases of interest to the federation. In addition, an increase in official presence would help to improve the selection of slaughtered cattle during ante- and postmortem inspection, with consequent impact on food safety and public health.

Regenerative endodontic procedures (REPs) associated with apical surgery could represent an alternative treatment strategy for patients whose teeth present incomplete root formation and extensive apical lesions. Leukocyte platelet-rich fibrin (L-PRF) has potential benefits in REPs; it could promote apical root formation and optimal bone healing. The aim of this case report was to describe innovative regenerative endodontic therapy using L-PRF in the root canal and an extensive apical lesion in an immature tooth with dens invaginatus and asymptomatic apical periodontitis. A healthy 20-year-old woman was referred to the dental clinic of the Universidad de Los Andes, Santiago, Chile, for endodontic treatment in tooth # 22 with incomplete root development and an extensive apical lesion. The diagnosis was asymptomatic apical periodontitis associated with dens invaginatus type II. The patient was treated with an innovative approach using L-PRF in REPs associated with apical surgery. Follow-ups were performed at 6 months and 1 year later. They included periapical radiographs, cone-beam computed tomographic imaging, sensitivity, and vitality tests. The clinical evaluations performed at 6 months and 1 year revealed an absence of symptoms. The radiographic evaluations showed that the apical lesion was resolved. The cone-beam images indicated that the root length increased and the walls had thickened. The sensitivity tests were positive, and the laser Doppler flowmetry showed positive blood flow after 1 year. The success of the results in this case report indicate that L-PRF can be used as a complement in apical surgery and REPs and could provide an innovative alternative treatment strategy for complex clinical cases like these., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

The "tracer patient" audit is an evaluation method introduced by the French health authority in the V2014 certification. This is not mandatory in private radiotherapy centres. In our continuous quality improvement approach and in order to improve the management of patient care, the management of our radiation therapy centre has decided to use this method to evaluate our medical practice and to engage healthcare professionals at the core of this approach., (Copyright © 2017. Published by Elsevier SAS.)

Some practical and theoretical aspects of evaluation of evidence based on the likelihood ratio (LR) in kinship cases are discussed. If relationships are complex or if complicating factors like mutation, correction for population structure or silent alleles need to be accounted for, available software may fail. We present an explicit general formula for non-inbred pairwise cases. Equipped with this formula it is possible to evaluate, say, how strongly a shared rare allele, points towards a specific relationship. Moreover, a general expression as the one presented, adds to the understanding of models and the underlying biological mechanisms. It is also useful for checking software and defining the limitations of programs. Some ideas for improving software may also be generated by the derivation of exact expressions. We argue that a proportional mutation model is well suited from a pragmatic point of view and derive some theoretical properties of this model. Several examples based on the general pairwise formula and its implementation in the freely available R package mut are presented., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The existence of pedigrees belonging to the same kinship class (i.e. indistinguishable through independent markers) is well known in the forensic community, and theoretical frameworks for autosomal and X-chromosomal markers were already developed for a pair of individuals. Nevertheless, studies for the cases where a greater number of individuals is available for testing are still lacking. With this work, we intend to pave the way for a theoretical and general framework, identifying the individuals/relatives that should be chosen to distinguish autosomal analyses between such pedigrees. In this work we identify the individuals/relatives that are non-informative for calculations (the pedigrees under discussion remaining indistinguishable independently of their genetic profile), as well as those that will likely be very informative, influencing the statistical outcome. For example, given the respective genotypes, to compare the likelihoods of the father of the individual B to be: (a.) the father, or (b.) a full-brother, of the individual A, the hypotheses H 1 : "The individual A is paternal half-sibling of the individual B", and H 0 : "The individual A is paternal uncle/aunt of the individual B" are considered. It is proved that considering just individuals A and B the hypotheses are equally likely. In this work we show that the same is also true for the case where the mother of B is available for testing, notwithstanding the hypotheses being differently weighted if the mother of A is considered. Similar considerations are done for other kinship hypotheses and/or individuals/relatives. Irrelevance of the genetic profile of some specific relatives are mathematically demonstrated, and data obtained from 20,000 simulated families are presented for the other cases., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In routine practice, intensive care physicians rarely have to manage children under 18years of age, particularly those under 15. This study's objectives were to assess the quality of training in pediatrics of adult intensive care teams, to document the workload generated by care of pediatric patients, and to identify the difficulties encountered in managing minors as patients. A survey was administered in Lower Normandy from 4 April 2012 to 1 September 2012. Physicians, residents, nurses, and nurses' aides practicing in one of the nine intensive care units of Lower Normandy were asked to complete an electronic or paper format questionnaire. This questionnaire assessed their level of pediatric training, the workload management of pediatric patients entailed, and the challenges posed by these patients. One hundred and nine questionnaires were returned (by 26 attending physicians, 18 residents, 38 nurses, and 27 nurses' aides). Eighty-three of the respondents (76%) had no experience in a pediatric unit of any kind. Forty-two percent thought that the pediatric age range lies between 3months and 15years of age. However, more than 50% of respondents would like the upper limit to be 16years or even older. Ninety-three respondents (85%) estimated having some exposure to pediatric patients in their routine practice, but this activity remained quite low. Seventy-three (67%) reported difficulties with the management of these young patients. This survey provides current information regarding the level of training of adult intensive care unit professionals and their concerns about managing patients under 18years of age, both in terms of workload and specific challenges., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Communicating and interpreting genetic evidence in the administration of justice is currently a matter of great concern, due to the theoretical and technical complexity of the evaluative reporting and large difference in expertise between forensic experts and law professionals. A large number of initiatives have been taken trying to bridge this gap, contributing to the education of both parties. Results however have not been very encouraging, as most of these initiatives try to cope globally with the problem, addressing simultaneously theoretical and technical approaches which are in a quite heterogeneous state of development and validation. In consequence, the extension and complexity of the resulting documents disheartens their study by professionals (both jurists and geneticists) and makes a consensus very hard to reach even among the genetic experts' community. Here we propose a 'back-to-basics', example-driven approach, in which a model report for the two most common situations faced by forensic laboratories is presented. We do hope that this strategy will provide a solid basis for a stepwise generalisation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The use of biostatistical software programs to assist in data interpretation and calculate likelihood ratios is essential to forensic geneticists and part of the daily case work flow for both kinship and DNA identification laboratories. Previous recommendations issued by the DNA Commission of the International Society for Forensic Genetics (ISFG) covered the application of bio-statistical evaluations for STR typing results in identification and kinship cases, and this is now being expanded to provide best practices regarding validation and verification of the software required for these calculations. With larger multiplexes, more complex mixtures, and increasing requests for extended family testing, laboratories are relying more than ever on specific software solutions and sufficient validation, training and extensive documentation are of upmost importance. Here, we present recommendations for the minimum requirements to validate bio-statistical software to be used in forensic genetics. We distinguish between developmental validation and the responsibilities of the software developer or provider, and the internal validation studies to be performed by the end user. Recommendations for the software provider address, for example, the documentation of the underlying models used by the software, validation data expectations, version control, implementation and training support, as well as continuity and user notifications. For the internal validations the recommendations include: creating a validation plan, requirements for the range of samples to be tested, Standard Operating Procedure development, and internal laboratory training and education. To ensure that all laboratories have access to a wide range of samples for validation and training purposes the ISFG DNA commission encourages collaborative studies and public repositories of STR typing results., (Published by Elsevier Ireland Ltd.)

Objectives: This clinical trial explored the clinical and radiographic dimensional changes of the alveolar ridge in the first 4 months after tooth extraction in combination with the application of Leukocyte- and Platelet Rich Fibrin (L-PRF)., Methods: Eighteen single rooted maxillary and mandibular sockets were filled with L-PRF without soft tissue closure. Clinical measurements (bone sounding) were performed using a customized acrylic stent and radiographic measurements were accomplished using Cone Beam Computed Tomography (CBCT), immediately after tooth extraction and after 4 months., Results: The clinical observations indicated a mean horizontal resorption of 1.18±2.4mm (p=0.8) at the crest, 1.25±2.0mm (p=0.57) and 0.83±2.0mm (p=0.78) at 2mm and 4mm apical to the crest, respectively. The buccal plate demonstrated a mean vertical loss of 0.44±3.5mm (p=0.9), the centre of the socket had a significant filling of 5.72±3.6mm (p=0.0001) and the oral cortical plate had a mean vertical gain of 0.09mm±1.57mm (p=0.9). The radiographic analysis demonstrated a mean vertical bone loss of 0.27±2.5mm (p=0.9) on the buccal and of 0.03±1.6mm (p=0.9) at the oral crest. The width of the alveolar ridge had a mean loss of 1.33mm±1.43mm., Conclusions: Within the limitations of this pilot study, it can be concluded that L-PRF might show clinical benefits for ridge preservation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Mutation is a topic of intense research and raises important problems in forensics. Since the markers of choice in current forensic genetics analyses are microsatellites or Short Tandem Repeat Polymorphisms (STRs), mutation is sufficiently common to cause difficulties in evaluating DNA evidence in a significant proportion of cases but at the same time rare enough to turn the estimation of the corresponding probability of occurrence into a hard task. We address these issues using the simplest model of transmission: the Y chromosome specific STRs. Within this model, and under an explicit set of definitions and involved assumptions, we developed the theoretical framework required for the study of allelic transitions in gametogenesis, identifying the required parameters and associated probabilities and finally we discuss the estimation of these parameters and their application in forensics. We conclude that (i) for forensic casework the relevant parameter for incorporation in a likelihood ratio is biallelic specific (i.e. the mutation rate estimate corresponds to the probability of the specific allelic transition observed) and (ii) for these estimates as well as in order to provide data for testing mutation models the absolute frequency of mutated and non-mutated transmissions per allele, along with the description of the observed mutations should be reported., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

This paper is motivated by power considerations in connection with relationship testing. Given the true relationship between a set of individuals, a claimed relationship between the same individuals, and a set of genetic markers, we compute the power of exclusion, i.e., the probability that the genotypes will be incompatible with the claimed relationship. If exclusion is impossible, as will be the case if it is required for instance to distinguish between sibs and half sibs, we rather obtain the distribution of the likelihood ratio. The problem we are addressing can also be seen as a standard way of measuring the ability of a battery of tests to resolve claimed family relationships. In particular, simple exclusion probabilities are regularly calculated worldwide as a part of designing forensic marker sets. Our approach to these problems is guided by a natural way of calculating exclusion probabilities on a computer. We present a user friendly implementation for this as part of the R package paramlink, originally designed by one of the authors (MDV) for pedigree manipulations and likelihood computations. By doing so we are able to handle problems more challenging than we have seen in the literature. Specifically, we deal with complex pedigrees with arbitrary inbreeding and conditioning. We present examples for autosomal as well as X-linked markers and some formulae to validate the results. The examples indicate a wide range of applications. Details are presented for an immigration case where previously reported calculations are extended to account for possible inbreeding and known genotypes. The supplementary material includes a tutorial on how to perform these calculations in paramlink., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)