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• Moxifloxacin daily doses of 2400 mg were tolerated over several months. • M. tuberculosis drug resistance could be overcome by a high-dose treatment regimen. • No occurrence of cardiac AEs despite high doses of QTc interval prolonging drugs. • No eradication of M. tuberculosis despite longstanding culture conversion. • Development of pretomanid resistance on an insufficient treatment regimen. [ABSTRACT FROM AUTHOR]

The placenta is an organ that forms the bridge between mother and fetus during pregnancy. Changes in the intrauterine environment directly impact the fetus' health, with maternal nutrition determining its development. This study analyzed the effects of different diets and probiotic supplementation during pregnancy on the biochemical parameters of maternal serum and placental morphology, oxidative stress, and cytokine levels in mice. Female mice were fed standard (CONT), restrictive (RD), or high-fat (HFD) diets before and during pregnancy. During pregnancy, the CONT and HFD groups were divided into two groups that received the Lactobacillus rhamnosus LB1.5 three times per week (CONT + PROB and HFD + PROB). The RD, CONT, or HFD groups received vehicle control. Maternal serum biochemical parameters (glucose, cholesterol, and triglycerides) were evaluated. The morphology, redox profile (thiobarbituric acid reactive substances, sulfhydryls, catalase, and superoxide dismutase enzyme activity), and inflammatory cytokines (interleukins 1α, 1β, IL-6, and tumor necrosis factor-alpha) were evaluated in the placenta. The serum biochemical parameters presented no differences between the groups. Regarding placental morphology, the HFD group showed an increased thickness of the labyrinth zone compared to the CONT + PROB group. However, no significant difference was found in the analysis of the placental redox profile and cytokine levels. RD and HFD, for 16 weeks before and during pregnancy, as well as probiotic supplementation during pregnancy, caused no change in serum biochemical parameters nor the gestational viability rate, placental redox state, and cytokine levels. However, HFD increased the thickness of the placental labyrinth zone. • High-fat diet increases the thickness of the labyrinth zone in the placenta. • Increased thickness of the placenta may alter transport between mother and fetus. • High-fat and restrictive diets during pregnancy did not alter the placental cytokines. • Gestational viability was not affected by high-fat or restrictive diets. • High-fat and restrictive diets did not alter the redox state in the placenta. [ABSTRACT FROM AUTHOR]

The bacterial composition of and the circulation of antimicrobial resistance genes (ARGs) in waste from Brazilian swine farms are still poorly understood. Considering that antimicrobial resistance (AMR) is one of the main threats to human, animal, and environmental health, the need to accurately assess the load of ARGs released into the environment is urgent. Therefore, this study aimed to characterize the microbiota in a swine farm in southern Brazil and the resistome in swine farm wastewater treated in a series of waste stabilization ponds (WSPs). Samples were collected from farm facilities and the surrounding environment, representing all levels of swine manure within the treatment system. Total metagenomic sequencing was performed on samples from WSPs, and 16S-rDNA sequencing was performed on all the collected samples. The results showed increased bacterial diversity in WSPs, characterized by the presence of Caldatribacteriota , Cloacimonadota , Desulfobacterota , Spirochaetota , Synergistota , and Verrucomicrobiota. Furthermore, resistance genes to tetracyclines, lincosamides, macrolides, rifamycin, phenicol, and genes conferring multidrug resistance were detected in WSPs samples. Interestingly, the most abundant ARG was linG , which confers resistance to the lincosamides. Notably, genes conferring macrolide (mphG and mefC) and rifamycin (rpoB_RIF) resistance appeared in greater numbers in the late WSPs. These drugs are among the high-priority antibiotic classes for human health. Moreover, certain mobile genetic elements (MGEs) were identified in the samples, notably tnpA , which was found in high abundance. These elements are of particular concern due to their potential to facilitate the dissemination of ARGs among bacteria. In summary, the results indicate that, in the studied farm, the swine manure treatment system could not eliminate ARGs and MGEs. Our results validate concerns about Brazil's swine production system. The misuse and overuse of antimicrobials during animal production must be avoided to mitigate AMR. [Display omitted] • The treatment of swine manure increased the bacterial diversity. • Macrolide and rifamycin resistance genes were found in swine manure after treatment. • Waste stabilization ponds failed to eliminate antimicrobial resistance genes. [ABSTRACT FROM AUTHOR]

The BMP signaling pathway plays a key role during dorsoventral pattern formation of vertebrate embryos. In zebrafish, all cloned mutants affecting this process are deficient in members of the BMP pathway. In a search for factors differentially expressed in swirl/bmp2b mutants compared with wild type, we isolated zebrafish Sizzled, a member of the secreted Frizzled-related protein family and putative Wnt inhibitor. The knockdown of sizzled using antisense morpholino phenocopied the ventralized mutant ogon (formerly also known as mercedes and short tail). By sequencing and rescue experiments, we demonstrate that ogon encodes sizzled. Overexpression of sizzled, resulting in strongly dorsalized phenotypes, and the expression domains of sizzled in wild type embryos, localized in the ventral side during gastrulation and restricted to the posterior end during segmentation stages, correlate with its role in dorsoventral patterning. The expanded expression domain of sizzled in ogon and chordino together with its downregulation in swirl suggests a BMP2b-dependent negative autoregulation of sizzled. Indicating a novel role for a secreted Frizzled-related protein, we show that, in addition to the BMP pathway, a component of the Wnt signaling pathway is required for dorsoventral pattern formation in zebrafish. Keywords: ogon; sizzled; Zebrafish; Dorsoventral patterning; Secreted Frizzled-related protein

The expression patterns of region-specific neuroectodermal genes and fate-map analyses in zebrafish gastrulae suggest that posterior neural development is initiated by nonaxial signals, distinct from organizer-derived secreted bone morphogenetic protein (BMP) antagonists. This notion is further supported by the misexpression of a constitutively active form of zebrafish BMP type IA receptor (CA-BRIA) in the zebrafish embryos. It effectively suppressed the anterior neural marker, otx2, but not the posterior marker, hoxb1b. Furthermore, we demonstrated that the cells in the presumptive posterior neural region lose their neural fate only when CA-BRIA and Xenopus dominant-negative fibroblast growth factor (FGF) receptors (XFD) are coexpressed. The indications are that FGF signaling is involved in the formation of the posterior neural region, counteracting the BMP signaling pathway within the target cells. We then examined the functions of Fgf3 in posterior neural development. Zebrafish fgf3 is expressed in the correct place (dorsolateral margin) and at the correct time (late blastula to early gastrula stages), the same point that the most precocious posterior neural marker, hoxb1b, is first activated. Unlike other members of the FGF family, Fgf3 had little mesoderm-inducing activity. When ectopically expressed, Fgf3 expands the neural region with suppression of anterior neural fate. However, this effect was mediated by Chordino (zebrafish Chordin), because Fgf3 induces chordino expression in the epiblast and Fgf3-induced neural expansion was substantially suppressed in dino mutants with mutated chordino genes. The results obtained in the present study reveal multiple actions of the FGF signal on neural development: it antagonizes BMP signaling within posterior neural cells, induces the expression of secreted BMP antagonists, and suppresses anterior neural fate. Key Words: FGF; neural induction; organizer; marginal mesoderm; chordin; BMP.

We have analyzed the role of the zebrafish yolk cell in the processes of mesoderm induction and establishment of the organizer. By recombining blastomere-free yolk cells and animal cap tissue we have shown that the yolk cell itself can induce mesoderm in neighboring blastomeres. We further demonstrate the competence of all blastomeres to form mesoderm, suggesting the endogenous mesoderm inducing signal to be locally restricted. Ablation of the vegetal third of the yolk cell during the first 20 min of development does not interfere with mesoderm formation in general, but results in completely ventralized embryos. These embryos lack the notochord, neuroectoderm, and the anterior-most 14-15 somites, demonstrating that the ablation affects the formation of the trunk-, but not the tail region of the embryo. This suggests the presence of a trunk organizer in fish. The dorsalized mutant swirl (zbmp-2b) shows expanded dorsal structures and missing ventral structures. In contrast to the phenotypes obtained upon the ablation treatment in wild-type embryos, removal of the vegetal-most yolk in swirl mutants results in embryos which do form neuroectoderm and anterior trunk somites. However, both wild-type and swirl mutants lack a notochord upon vegetal yolk removal. These ablation experiments in wild-type and swirl mutant embryos demonstrate that in zebrafish dorsal determining factors originate from the vegetal part of the yolk cell. These factors set up two independent activities: one induces the notochord and the other is involved in the formation of the neuroectoderm and the trunk region by counteracting the function of swirl. In addition, these experiments show that the establishment of the anteroposterior axis is independent of the dorsoventral axis. Key Words: zebrafish; mesoderm induction; dorsal determinant; dorsoventral polarity; neuroectoderm; trunk organizer; organizer; maternal; anteroposterior axis; yolk cell.

Dissociative identity disorder (DID) is a psychobiological syndrome associated with a history of exposure to childhood abuse and neglect. The consequences of these traumatic events often include a profound impact on the way individuals inhabit and experience their bodies. Despite this, there is a paucity of empirical research on the subject. The aim of this study was to systematically document the occurrence of distorted body perceptions in DID and examine childhood maltreatment, posttraumatic stress disorder (PTSD) symptom severity, and posttraumatic cognitions as predictors of distorted body perceptions in DID. Participants were adult women with histories of childhood abuse and neglect and a current DID diagnosis receiving treatment at a psychiatric care facility. Data were obtained through a battery of self-report measures, including the Body Uneasiness Test, Childhood Trauma Questionnaire, PTSD Checklist for DMS-5, and Posttraumatic Cognitions Inventory. A series of unpaired t-tests documented elevated levels of weight phobia, body image concerns, body avoidance, compulsive self-monitoring, and depersonalization in DID compared to published non-clinical data on the Body Uneasiness Test. A series of multiple regression models including measures of childhood trauma, PTSD symptoms, and posttraumatic cognitions demonstrated that over and above childhood trauma and PTSD symptom severity, posttraumatic cognitions significantly predicted distorted body perceptions. In a treatment-seeking sample of women with DID, distorted body perceptions were elevated. Furthermore, posttraumatic cognitive distortions significantly predicted distorted body perceptions when controlling for childhood maltreatment and PTSD symptom severity. This suggests that distorted cognitions are a key target for therapeutic intervention. • First systematic, empirical exploration of body perceptions in DID • Individuals with DID presented with elevated levels of distorted body perceptions compared to published non-clinical data • Posttraumatic negative cognitions significantly predicted distorted body perceptions [ABSTRACT FROM AUTHOR]

Trauma and symptoms of posttraumatic stress disorder (PTSD) have repeatedly been linked to impaired cardiovascular functioning. Poor fear extinction is a well-established biomarker of PTSD that may provide insight into mechanisms underlying cardiovascular risk. The current study probed the cardiovascular response to extinction in a sample of trauma-exposed individuals. Participants were 51 trauma-exposed women who underwent a fear conditioning paradigm. Heart rate (HR) during extinction was examined in response to a conditioned stimulus that was previously paired with an aversive unconditioned stimulus (CS+) and one that was never paired (CS-). Heart rate variability (HRV) was calculated at baseline and during the extinction session. Consistent with fear bradycardia, initial HR deceleration (.5-2s) after CS + onset occurred during early extinction and appeared to extinguish over time. Higher baseline HRV was significantly associated with greater fear bradycardia during early extinction. This is the first study to demonstrate a pattern of fear bradycardia in early extinction, which was associated with higher HRV levels and decreased over the course of the extinction phase. These results suggest that increased fear bradycardia may be indicative of greater vagal control (i.e., HRV), both of which are psychophysiological biomarkers that may influence cardiovascular and autonomic disease risk in trauma-exposed individuals. [ABSTRACT FROM AUTHOR]

• Compared with donor lymphocyte infusion (DLI), T cell dose was significantly increased with cytokine-induced killer (CIK) cell therapy. • T cell recovery was significantly improved after CIK cell therapy (P <.0001). • CIK cells are endowed with a reduced propensity to cause GVHD. • Compared with DLI, CIK cell therapy showed a significantly reduced 6-month calculated cumulative incidence of relapse. • CIK cell therapy may be a promising alternative to classic DLI when leukemia burden is low. Well-established donor lymphocyte infusion (DLI) and novel cytokine-induced killer (CIK) cell therapy for the treatment of relapsing hematologic malignancies after allogeneic hematopoietic stem cell transplantation (HSCT) were compared with respect to feasibility, safety, and efficacy. Altogether, a total of 221 infusions were given to 91 patients (DLI, n = 55; CIK, n = 36). T cell recovery was significantly improved after CIK cell therapy (P <.0001). Although patients with CIK cell treatment showed a significantly worse prognosis at the time of HSCT (risk score, 1.7 versus 2.1; P <.0001), DLI and CIK cell therapy induced complete remission (CR) in 29% and 53% patients, respectively, whereas relapse occurred in 71% and 47%. In both groups, all patients with overt hematologic relapse at the time of immunotherapy (DLI, n = 11; CIK, n = 8) succumbed to their disease, while 36% and 68% patients with DLI or CIK cell therapy applied due to molecular relapse or active disease at the time of transplantation achieved CR. The 6-month overall survival rate in the latter patients was 57% and 77%, respectively, with a median follow-up of 27.9 months (range,.9 to 149.2 months). The 6-month cumulative incidence of relapse was 55% and 22% in patients who received DLI and CIK cell therapy, respectively (P =.012). Acute graft-versus-host disease developed in 35% of the patients who received DLI and in 25% of those who received CIK. No transfusion-related deaths occurred. These data, while underscoring the therapeutic value of conventional DLI, suggest the improved safety and to a certain extent efficacy of CIK cell therapy for patients at high risk for post-transplantation relapse of various hematologic malignancies. [ABSTRACT FROM AUTHOR]

Coordinated group displays featuring precise entrainment of rhythmic behavior between neighbors occur not only in human music, dance and drill, but in the acoustic or optical signaling of a number of species of arthropods and anurans. In this review we describe the mechanisms of phase resetting and phase and tempo adjustments that allow the periodic output of signaling individuals to be aligned in synchronized rhythmic group displays. These mechanisms are well described in some of the synchronizing arthropod species, in which conspecific signals reset an individual's endogenous output oscillators in such a way that the joint rhythmic signals are locked in phase. Some of these species are capable of mutually adjusting both the phase and tempo of their rhythmic signaling, thereby achieving what is called perfect synchrony, a capacity which otherwise is found only in humans. We discuss this disjoint phylogenetic distribution of inter-individual rhythmic entrainment in the context of the functions such entrainment might perform in the various species concerned, and the adaptive circumstances in which it might evolve. • Precise entrainment of behavioral rhythm is prominent in arthropods and anurans, and also in humans. • Entrainment relies on rhythm isochrony and is generally expressed as group synchrony or alternation. • Rhythmic synchrony and alternation are often cooperative adaptations, but some cases are emergent phenomena. • In humans, precise rhythmic entrainment is a basic sensorimotor component of music, dance, and drill. • Precise rhythmic entrainment in humans evolved de novo within the hominid lineage. [ABSTRACT FROM AUTHOR]

A tornado hit the northeastern suburbs of Hamburg, Germany, on 7 June 2016. It had an estimated strength of upper end F1 on the Fujita scale and was short-lived with an approximate duration of only 13 min and a path length of just about 1.3 km. We demonstrate that such a small-scale, extreme event can be observed and forecasted accurately by a low-cost radar and by an atmospheric model with low computational costs, respectively. Observations from a low-cost single polarized X-band radar covering the urban area of Hamburg with 60 m spatial and 30 s temporal resolution are analyzed with respect to their ability to capture the development as well as the track of the tornado. In contrast to the national C-band radar network, the X-band radar is capable of capturing the hook echo of the tornado as well as the circular pattern in rain rates, because of its higher resolution in space and time. High-resolution forecasts of the tornado event are conducted with the computational efficient Conformal Cubic Atmosphere Model (CCAM) in order to test the capability of predicting the tornado with a lead time of a few hours. A three step downscaling method is used to obtain a spatial resolution of 1 km with initial conditions taken from the NCEP analysis. Calculated severe weather indices clearly indicate a potential for a tornado. CCAM cannot explicitly resolve small scale tornadic features but the model simulates a strong convective cell only a few kilometers apart from the tornadic thunderstorm observed by the radar. [ABSTRACT FROM AUTHOR]

Background: The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan.Methods: On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control.Findings: Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.Interpretation: Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto.Funding: The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG). [ABSTRACT FROM AUTHOR]

The spine is a segmented axial structure made of alternating vertebral bodies (centra) and intervertebral discs (IVDs) assembled around the notochord. Here, we show that, prior to centra formation, the outer epithelial cell layer of the zebrafish notochord, the sheath, segments into alternating domains corresponding to the prospective centra and IVD areas. This process occurs sequentially in an anteroposterior direction via the activation of Notch signaling in alternating segments of the sheath, which transition from cartilaginous to mineralizing domains. Subsequently, osteoblasts are recruited to the mineralized domains of the notochord sheath to form mature centra. Tissue-specific manipulation of Notch signaling in sheath cells produces notochord segmentation defects that are mirrored in the spine. Together, our findings demonstrate that notochord sheath segmentation provides a template for vertebral patterning in the zebrafish spine. [ABSTRACT FROM AUTHOR]

• S. pseudintermedius ST71 was the sequence type most frequent in our analyses. • MSSP and MRSP strains shared siet, lukS, and lukF virulence markers. • MSSP had a highly virulent profile, with cytotoxins, exfoliative toxin, and enterotoxins genes. • All MRSP strains and 77% of MSSP strains were classified as multidrug resistant (MDR). • All investigated S. pseudintermedius strains showed strong biofilm ability. Staphylococcus pseudintermedius is a zoonotic pathogen responsible for several infectious diseases in pet animals, yet its pathogenic potential is not fully understood. Thus, this study aims to unravel the virulence profile of S. pseudintermedius from canine origin. Methicillin-resistant (MRSP) and methicillin-susceptible (MSSP) strains were isolated from different infection sites and their genotypic and phenotypic features were compared to determine the clinical implications of MRSP and MSSP strains. Bacterial identification was performed using MALDI-TOF and 16S-rDNA sequencing. In addition, we used multilocus sequence typing (MLST) for strains' sequence type (ST) determination and phylogenetic relationship. The strains were screened for toxin genes, including cytotoxins (lukS, lukF), exfoliative toxin (siet), enterotoxins (sea, seb, sec, sec Canine, sel, sem, and seq) and toxic shock syndrome toxin (tst-1). In vitro phenotypic analyses assessing antimicrobial susceptibility profile, biofilm formation ability, and expression of extracellular matrix components were performed. The investigated S. pseudintermedius strains belong to 17 unique ST, most of which were classified as ST71. MSSP and MRSP strains shared siet, lukS, and lukF virulence markers. Our findings showed that some MSSP strains also harbored sel, seq, and sem enterotoxin genes, suggesting a more diverse virulence profile. All MRSP strains and 77% of MSSP strains were classified as multidrug resistant (MDR). Moreover, all investigated S. pseudintermedius strains showed strong biofilm formation ability. In summary, our findings highlight the wide spread of highly virulent and drug-resistant zoonotic S. pseudintermedius strains, being a potential concern for One Health issues. [ABSTRACT FROM AUTHOR]

Our vasculature plays diverse and critical roles in homeostasis and disease. In recent decades, the use of zebrafish has driven our understanding of vascular development into new areas, identifying new genes and mechanisms controlling vessel formation and allowing unprecedented observation of the cellular and molecular events that shape the developing vasculature. Here, we highlight key mechanisms controlling formation of the zebrafish vasculature and investigate how knowledge from this highly tractable model system has informed our understanding of vascular disease in humans. [ABSTRACT FROM AUTHOR]

Whole genome sequencing (WGS) can help to relate Mycobacterium tuberculosis genomes to one another to assess genetic relatedness and infer the likelihood of transmission between cases. The same sequence data are now increasingly being used to predict drug resistance and susceptibility. Controlling the spread of tuberculosis and providing patients with the correct treatment are central to the World Health Organization's target to ‘End TB’ by 2035, for which the global prevalence of drug-resistant tuberculosis remains one of the main obstacles to success. So far, WGS has been applied largely to drug-susceptible strains for the purposes of understanding transmission, leaving a number of analytical considerations before transferring what has been learnt from drug-susceptible disease to drug-resistant tuberculosis. We discuss these potential problems here, alongside some of the challenges to characterizing the Mycobacterium tuberculosis ‘resistome’—the optimal knowledge-base required for WGS-based assays to successfully direct individualized treatment regimens through the prediction of drug resistance and susceptibility in the future. [ABSTRACT FROM AUTHOR]

Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) after transplantation. Patients with ALL who consecutively underwent transplantation in Frankfurt/Main, Germany between January 1, 2005 and July 1, 2014 were included in this retrospective study. Chimerism monitoring was performed in all, and MRD assessment was performed in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC). The 3-year probabilities of event-free survival (EFS) were .69 ± .06 for the cohort without IT and .69 ± .10 for IT patients. Incidences of relapse (CIR) and treatment-related mortality (CITRM) were equally distributed between both cohorts (without IT: 3-year CIR, .21 ± .05, 3-year CITRM, .10 ± .04; IT patients: 3-year CIR, .18 ± .09, 3-year CITRM .13 ± .07). Accordingly, 3-year EFS and 3-year CIR were similar in CC and MC patients with IT, whereas MC patients without IT experienced relapse. IT was neither associated with an enhanced immune recovery nor an increased risk for acute graft-versus-host disease. Relapse prevention by IT in patients at risk may lead to the same favorable outcome as found in CC and MRD-negative-patients. This underlines the importance of excellent MRD and chimerism monitoring after transplantation as the basis for IT to improve survival in childhood ALL. [ABSTRACT FROM AUTHOR]

We present here new isotopic data (δ 13 C, δ 15 N, δ 18 O, δ 2 H, and δ 34 S) from pulverised ivory powder, measured by continuous flow isotope ratio mass spectrometry from an unprecedented large dataset of 507 ivory samples, derived from twenty-eight African and six Asian elephant range states. The aim of this study is to assess the accuracy of isotopic fingerprinting and to evaluate its forensic potential and limitations to predict the provenance of ivory of unknown origin. We constructed a nominal assignment framework for the African reference samples, consisting of 208 different sites and applied the weighted k -Nearest Neighbor Classifier with reference site as classifier and inferred the accuracy of the assignments of samples from the African elephant species to their correct provenance. Our results show that isotopic profiling of African elephant ivory works on regional scales and we were able to assign 50% of all samples within 381 km, and the majority of the remaining samples within 1154 km. Source area determination is hampered by the fact that within-site and within-individual variation in ivory is immense because elephants as ecological generalists use a wide diversity of plant resources. We propose that forest elephant diets differ more between individuals (i.e. dietary niche partitioning is more significant) than in savanna elephants where individual diets overlap more. Increasing sampling effort in order to decrease median distance of the nominal assignment framework and to better understand within-site variance of the studied isotopic systems are imperative to establish isotopic profiling in the context of law enforcement and wildlife forensics. [ABSTRACT FROM AUTHOR]